bluuebunny/crossref_metadata_2025 huggingface dataset:
Social and Cognitive Skills (SCOPE)—a generic model for multi-professional work and education in healthcare
Authors: Dieckmann Peter , Bruun Birgitte , Mundt Sofie , Holgaard Ragnhild , Østergaard Doris
Published: July 2024

In this article, we present a generic model for social and cognitive skills that can be used in work and (simulation-based) education in healthcare. We combined existing non-technical skills tools into a tool that we call SCOPE. SCOPE is a model that comprises the three social categories of “teamwork”, “leading”, and “task management” as well as the two cognitive categories of “situation awareness” and “decision making”. Each category comprises between three and six elements. We formulated guiding questions for each category in an attempt to emphasize its core meaning. We developed a dynamic graphical representation of the categories that emphasize the constant changes in the relative importance of the categories over the course of a clinical or educational situation. Anecdotal evidence supports the value of the model for aligning language around social and cognitive skills across specialties and professions.
A prospective cohort study in depression and anxiety among Vietnamese migrants in Japan during the early to mid-COVID-19 pandemic
Authors: Yamashita Tadashi , Quy Pham Nguyen , Yamada Chika , Nogami Emi , Kato Kenji
Published: July 2024

Introduction

The enduring COVID-19 pandemic has had persistent, intermittent socioeconomic impacts on migrants. This raises the concern that many Vietnamese migrants in Japan may have developed mental health issues due to the socioeconomic impact. The study aimed to examine changes in the socio-economic and mental health status of Vietnamese migrants in Japan and factors affecting mental health status during the early to mid-COVID-19 period.

Methods

We conducted a prospective cohort study among Vietnamese migrants in Japan from September to October 2021 (baseline) and from May to June 2022 (follow-up) using an online questionnaire. Multiple linear regression analyses were conducted to examine the association between changes in socioeconomic status and alterations in symptoms of depression and anxiety within this demographic.

Results

The mean age of the 159 participants was 26.1 ± 4.9 years, with a mean length of residency in Japan of 4.0 ± 4.1 years. The mean PHQ-9 score exhibited a significant decrease from 7.89 (SD = 6.34) to 6.62 (SD = 5.87) (p = 0.01). Variables associated with changes in depression and anxiety included subjective socioeconomic status (unstandardized partial regression coefficient (UPRC): 1.901, 95% confidence interval (CI) 0.30 to 3.50, p = 0.02) and (UPRC: 2.060, 95% CI 0.80 to 3.32, p = 0.002), as well as changes in having someone with whom to discuss one’s health (UPRC: 2.689, 95% CI 0.89 to 4.49, p = 0.004) and (UPRC: 1.955, 95% CI 0.54 to 3.38, p = 0.007).

Conclusions

In this prospective cohort study of depression and anxiety, depressive symptoms among Vietnamese migrants decreased from 2021 to 2022. Key findings underscore the importance of socioeconomic status improvement and having someone to discuss to about their health as protective factors against mental health challenges. Employment and social support have emerged as crucial determinants of mental health among Vietnamese migrants in Japan, emphasizing the necessity for comprehensive support strategies addressing both economic vulnerabilities and social connectedness.
Reflective practice is a prerequisite for One Health development
Authors: Stephen Craig , Berezowski John
Published: July 2024

One Health is being promoted as a transformative approach in health, conservation, and environmental sustainability. The polycrisis of climate change, pandemics, food insecurity, biodiversity loss, pollution and inequity is creating an urgency to evolve the epistemology and methods of One Health. However, the amount of effort placed into critical and systematic reflection on One Health is outweighed by advocacy for its use, or for expanding its scope of practice. This paper advocates for reflective One Health practice to foster new ways of knowing and doing that are helpful in the face of a rapidly narrowing window of opportunity to preserve the social and environmental factors that secure health and resilience for all species and generations. We propose six areas for reflection; (1) how to moderate conformity so that One Health does not become its own silo; (2) finding the moral purpose of One Health to align actions with desired outcomes; (3) coping with the problem of too many interacting problems; (4) the strategic trajectory of growth to accelerate action on root causes and ensure One Health is future-ready; (5) how to identify priorities across a vast array of problems, values, and needs and (6) how to know if we are making the world healthier and safer and for whom. Reflective practice requires investment in ongoing conversation to guard against over-confidence that we have captured the “one right way” to meet changing expectations and circumstances in a fair and effective way. Our intention is to stimulate thinking and discussion within the One Health community to ensure that “doing is shaped by knowing”. We hope One Health will continue to be an emergent and highly variable set of ever more effective practices that constantly changes in response to the complex, interconnected and changing problems facing the health of people, animals, and the environment.
On-demand engineered double-network gelatin/silicate composited hydrogels with enhanced wet adhesion and stable release of bioactive ion for promoting wound healing
Authors: Luo Xiaomin , Ji Lufeng , Ao Fen , Yang Chen , Chang Jiang , Yin Changyu , Ren Huijun , Teng Ming , Li Liuying , Liu Xinhua
Published: July 2024

Silicate bioceramics have demonstrated great potential in hydrogel dressings for wound healing due to their special origins of promoting endothelial cell angiogenesis and inhibiting apoptosis of cardiomyocyte. However, there are still some deficiencies, such as insufficient biological activity, instability of silicate ion release, and lower wet adhesion on wounds with tissue exudate, limiting their further clinical applications. Herein, inspired by mussels, a multifunctional double-network hydrogel (FS/PAM-Gel-PDA) wound dressing composited gelatin with silicate ceramic powder with satisfactory wet adhesion, stable release of bioactive ions, hemostasis, and the ability of promoting vascular regeneration was engineered through specifically grafting dopamine to gelatin and introducing ferrous silicate ceramic powder into the hydrogel. The comprehensive experimental results substantiate that the FS/PAM-Gel-PDA has wet-adhesion strength of up to 21.78 kPa, and remains stably adherent to porcine myocardial tissues intuitively after bending, twisting, soaking in water, and stretching. The test results of ion release behavior in vitro show that the oxidation and agglomeration of ferrous silicate ceramic powder can be effectively inhibited by using dopamine to form an antioxidant layer on the surface of ceramic powder, and thus, the stable release of Fe2+ and SiO44− effective ions can be realized. The animal experiment exhibits that FS/PAM-Gel-PDA can achieve rapid hemostasis in the lethal liver defect model. Meanwhile, the FS/PAM-Gel-PDA reveals the remarkable ability to promote wound healing in a full-thickness skin injury model, which can obviously accelerate skin re-epithelialization. To sum up, the FS/PAM-Gel-PDA has excellent wet adhesion and stable release of active ions to accelerate angiogenesis, which shows great potential in promoting wound healing.

Graphical Abstract
Preliminary study: nutrigenomics analysis results of COVID-19 survivors
Authors: Veterini Anna Surgean , Semedi Bambang Pujo , Airlangga Prananda Surya , Firdaus Khildan Miftahul , Uhud Akhyar Nur , Kriswidyatomo Prihatma , Sumara Rauzan
Published: July 2024

Background

Numerous attempts have been made at both prevention and treatment of COVID-19. Specific genotypes carry a risk of causing clinical symptoms that can be beneficial or detrimental. We performed nutrigenomics testing on COVID-19 survivors who were on ventilators during their treatment and mild COVID-19 survivors who did not require ventilators to determine the risk of genetic variation through nutrigenomic testing regarding COVID-19 incidence. DNA was isolated from saliva and genotyped for genetic markers using a commercially available nutrigenomics test. We compared genotype frequencies between those with severe symptoms (cases) and those with mild symptoms (controls).

Result

Sequencing results showed that the distribution from pattern of the Sankey diagram included an ultra risk category in the control group, but not in the case group. None of the subjects in the case group were in the ultra risk category for resilience. A descriptive pattern of risk-level distribution was observed in both the control and case groups. One subject in the ultra risk category was in the control group, indicating a lower risk factor for severe COVID-19.

Conclusion

From this study, a uniqueness begins to emerge, revealing the discovery of ultra-category patterns in the endurance of the control group. The vitamin E risk deficiency is significantly higher in the severe COVID-19 group compared to the mild group, categorized as "typical."
A scientometric analysis of career anchor/orientation research from 1975 to 2023
Authors: Woldeamanuel Asegid Getachew
Published: July 2024

Career has traditionally been associated with its external dimension. However, the emergence of the concept of career anchor/orientation broadened its scope to include an internal component that encompasses the subjective desire, values and talents of individuals. The current scientometric review focused on analyzing career anchor/orientation research over the last five decades (1975–2023). The articles/documents used for analysis were searched and located from a purposely selected highly recognized databases. A total of 111 documents (articles, books, book chapters, conference proceedings) were selected for analysis. The result showed that the conceptualization of career anchor/orientation has remained stable with only some changes and emergence of few rival models. While the existing literature has provided valuable insights into the concept of career anchors, there are several gaps that need to be addressed. Future research should strive to expand the current understanding of career anchors by exploring additional career anchors, investigating their organizational implications, examining their interaction with other individual and contextual factors, and studying their manifestation in non-traditional work settings. The research in the area has shown a swinging trend with lots of ups and downs. Career anchor/orientation publications were spread over more than 24 countries. The US is ranked 1st with 28% of the total publication and is followed by the Asia continent and the UK. Africa, only represented by two countries (South Africa and Nigeria), is ranked fourth. Most of the empirical research have mainly focused on assessing the distribution of the dimensions of career anchor/orientation with few relating it with job settings and outcomes. It is recommended that career anchor/orientation scientometric analysis should be done by searching articles from more databases. More to this, as national contexts and cultural differences play a critical role in shaping career anchor/orientation of individuals it is suggested that more research needs to be done across a number of countries.
An open-label, multicenter, phase I study of ATG-022 in patients with advanced/metastatic solid tumors (CLINCH).
Authors: Bishnoi Sarwan , Cao Dan , Mendis Shehara Ramyalini , Coward Jim , Zhao Jun , Xie Hui , Zheng Li
Published: July 2024

3032

Background: Claudin 18.2 (CLDN 18.2) is a tumor associated antigen broadly expressed in gastric, pancreatic, and other solid tumors. ATG-022 is an antibody drug conjugate (ADC), consisting of a humanized monoclonal antibody that binds to CLDN 18.2 with high affinity of sub-nM grade and a conjugated linker-payload vc-MMAE. ATG-022 has displayed promising tumor growth inhibition activity both in vitro and in vivo. Methods: CLINCH is a phase I, multi-center, open-label, dose-finding study (NCT05718895) of ATG-022 in patients with advanced solid tumours. The study design includes a dose escalation phase, enrolling subjects with advanced/metastatic solid tumors, regardless of CLDN 18.2 expression, and a dose expansion phase which will enroll select advanced/metastatic solid tumors with CLDN 18.2-positive expression at the defined maximum tolerated dose and/or recommended Phase 2 dose to further evaluate the safety, tolerability, and efficacy of ATG-022. Other endpoints include pharmacokinetics (PK) and exploratory biomarkers of drug activity. In the dose escalation phase, ATG-022 is administered intravenously every 3 weeks (Q3W) at the starting dose of 0.3 mg/kg, followed by 0.9, 1.8, 2.4, 3.0, and 3.6 mg/kg Q3W using a modified 3+3 dose-escalation design. Efficacy assessments are evaluated per RECIST1.1 criteria. Results: As of 9 Oct 2023, 10 patients (pts) with advanced solid tumors have been enrolled to receive ATG-022 at a dose from 0.3 to 2.4 mg/kg. Median age was 59 years. Baseline ECOG scores were 0 (0 pts) and 1 (10 pts); 8 pts had stage IV disease. Three pts had received more than 3 prior lines of systemic therapy. Eight pts (80%) had ≥ 1 TRAEs; 1 pt (10%) had ≥ 1 Serious TRAEs; 3 (30%) pts had grade ≥ 3 TRAEs. The most common grade ≥ 3 TRAEs included nausea (30%), vomiting (30%) and decreased appetite (30%). No DLT was reported among the current dose levels. Among 7 pts with gastric cancer, 3 pts are confirmed to be CLDN 18.2 positive. One of these pts has maintained stable disease with tumor shrinkage for more than 6 months (treatment ongoing) at a dose of 0.9 mg/kg, demonstrating tolerability of ATG-022. One PR was observed in a gastric cancer pt (CLDN 18.2 expression to be determined) at the dosage of 1.8 mg/kg. It was noteworthy that a CR was seen in a gastric cancer pt dosed at 2.4 mg/kg, with negative CLDN 18.2 expression. PK analysis of ATG-022 from 0.3 to 2.4 mg/kg revealed that the exposure of total antibody, MMAE and ADC drug is increased as dose increased. No accumulation of ATG-022 was observed. Conclusions: ATG-022 demonstrated preliminary anti-tumor activity, tolerability, safety, as well as comparable PK properties at current dose levels. The high affinity of sub-nM grade of ATG-022 in pts with low CLDN 18.2 expression needs further investigation. The dose escalation is ongoing and updated data will be presented. Clinical trial information: NCT05718895 .
4CAST: A phase 1b dose exploration, open-label, single-center study evaluating the safety of INO-464 in combination with chemotherapy in patients with metastatic breast cancer.
Authors: Dear Rachel Fitz-Gerald , Liu Jia (Jenny) , Cosman Rasha , Walsh Natalie , Selga Mariz , Perez San Juan Beatriz , Purcell Carley , Chaffer Christine Louise
Published: July 2024

e13112

Background: Metastatic triple negative breast cancer (TNBC) has a poor prognosis and the development of new targeted therapies is an area of unmet need. The androgen receptor (AR) antagonist, INO-464, but not abiraterone or enzalutamide, blocks chemotherapy induced cell plasticity to inhibit and primary and metastatic breast cancer (MBC) growth. Single agent INO-464 at a dose of 450mg/d is well tolerated but has low efficacy. Laboratory data demonstrates suppression of metastatic TNBC and an increase in survival with the combination of INO-464 and taxane chemotherapy. Methods: We designed a Phase 1b open-label, single center dose exploration (Part 1) and dose expansion (Part 2) clinical trial of INO-464 450mg/d with docetaxel (IV 75mg/m2 q3wkly) or nab-paclitaxel (IV 100mg/m2 D1/8/15 q4wkly) in any subtype of MBC. The primary objective was to assess the safety and tolerability of INO-464 (450mg/d) and docetaxel or nab-paclitaxel utilizing a rolling 6 design, as well as to determine the maximum tolerated dose (MTD) and the recommended dose of INO-464 to be given with a taxane in the dose expansion study. Secondary objectives included anti-tumor activity and testosterone levels. Results: Recruitment began in August 2022. The cut-off date for this analysis was 19 January 2024. Eight patients have been treated to date and 6 patients were DLT evaluable. All were women with MBC with mean age of 56 (range 48-64) years. Patients had received a median of 5 (range 2 to 7) lines of chemotherapy for MBC. Patient 001 had G3 anaphylaxis due to docetaxel that resolved with adrenaline but came off study and was not DLT evaluable. The protocol was amended to give INO-464 with 1mg of dexamethasone. No DLTs were subsequently observed. Adverse events (AEs) were mostly low grade and chemotherapy related although G2 pneumonitis occurred beyond the DLT period in two patients, one of whom had prior sacituzimab govotecan-related pneumonitis. INO-464-related AEs were G1 fatigue/headache in 4/6 patients. Seven of seven patients had a best response (RECIST1.1) SD, and CA15.3 stability was seen in 4/7 patients. Baseline serum testosterone was detectable in 4/6 patients (range 0.5-1.3 nmol/L, lower limit of detection of <0.5), and remained undetectable or at the lower limit of detection throughout treatment. Conclusions: The MTD of INO-464 is 450mg daily with 0.5mg dexamethasone in combination with docetaxel or nab-paclitaxel chemotherapy. The combination is well tolerated with early efficacy signals. Dose expansion will test the combination in metastatic TNBC with nuclear AR positive breast cancer. Clinical trial information: NCT04947189 .
Outstanding safety and efficacy data of IMC002, an autologous CLDN18.2-targeting CAR-T, in CLDN18.2+ advanced solid tumors.
Authors: Luo Tianhang , Lu Zhengmao , Zheng Rui , Zhou Jun , Wang Suqiong , Hao Ruidong , Sun Minmin
Published: July 2024

e16012

Background: Claudin 18.2 (CLDN18.2) is a promising therapeutic target for advanced solid tumors with CLDN18.2 expression. IMC002 is an autologous CLDN18.2-targeting CAR-T cell directed by a CLDN18.2-specific VHH, the specificity of which was confirmed by a membrane proteome array assay. Preclinical studies showed that IMC002 exhibited high tumor specificity, anti-tumor efficacy, and excellent safety profile in both cell and animal models. Methods: This is an open label first in human Phase 1 dose escalation study to evaluate the safety and efficacy of IMC002 in advanced solid tumors with CLDN18.2 expression which is defined as CLDN18.2 expression of ≥1+ membrane staining intensity in ≥10% tumor cells. Accelerated titration followed by Bayesian optimal interval design was adopted with a total of 4 dose levels planned at 1, 3, 5 and 7 million (mil) CAR-T cells/kg respectively. All patients (pts) were given a single dose of IMC002 infusion after lymphodepletion chemotherapy. Dose limiting toxicity (DLT) was evaluated during the 28-day period after IMC002 infusion. Safety, anti-tumor activity, pharmacokinetics and pharmacodynamics were explored in this study. Here, we present preliminary safety and efficacy data for the pts dosed with up to 3 mil CAR-T cells/kg. Results: As of January 17, 2024, 3 advanced unresectable gastric cancer pts received IMC002 infusion, 1 patient at 1 mil CAR-T cells/kg and 2 pts at 3 mil CAR-T cells/kg. No DLT or SAE was reported. Manageable CRS (grade 1) was reported in all 3 pts. Other adverse events related to cell therapy included grade 1-2 lipase increase (3/3), diarrhea (1/3), pruritis (1/3) and γ-GGT increase (1/3). All adverse events recovered quickly. Preliminary efficacy data showed that best overall response of the 3 pts was all stable disease as evaluated by RECIST 1.1. The two pts at the dose level of 3 mil CAR-T cells/kg underwent successful radical surgery at week (W) 11 and 44 after IMC002 infusion respectively. Pathological complete response (pCR) was achieved in the patient with surgery at W44. Distinct CAR-T cell expansion in peripheral blood was observed in all 3 pts, with the peak number of CAR+ cells reaching on day 7-11 in the peripheral blood after the infusion. Moreover, CAR-T cell infiltration was detected in the W11 and W44 surgical samples. Significant elevations of serum levels of IFN-γ, IL-10, IP-10, IL-2 and IL-6 were observed in the 3 pts. The trial is ongoing. Conclusions: IMC002 showed a favorable safety profile, encouraging anti-tumor activities with observed pCR and persistent expansion in the tumor tissue at the low dosage levels in pts with advanced CLDN18.2+ gastric cancer. In addition, our trial has successfully provided a surgical treatment opportunity after CAR-T therapy downstaging of unresectable gastric cancers. Clinical trial information: NCT05472857 .
Update results of anlotinib combined with penpulimab and nab-paclitaxel as first-line treatment for advanced esophageal squamous cell carcinoma (ESCC): A single-arm, open-label phase II clinical trial.
Authors: Chang Zhiwei , Liu Xiao-Lei , Yu Dan-Dan , Han Hui-Qiong , He Jian , Wang Rui-Rui , Jia Yong-Xu , Yan Jie , Qin Yanru
Published: July 2024

e16017

Background: Recently, PD-1 blockades combined with dual chemotherapy in first-line setting exhibited encouraging efficacy for patients with ESCC. However, the safety profile of conventional dual chemotherapy remained unsatisfactory. Therefore, PD-1 blockades combined with anti-angiogenic tyrosine kinase inhibitors (TKIs) and single chemotherapy regimen might be a promising strategy. Anlotinib, a novel multitarget TKI primarily targeting VEGFR1-3, demonstrated promising therapeutic activity as first-line combination therapy or second-line monotherapy for patients with ESCC in China clinically. Therefore, this study was designed to explore the efficacy and safety of anlotinib combined with penpulimab (PD-1 blockade) and nab-paclitaxel as first-line therapy in advanced ESCC. Preliminary results were presented at the 2024 ASCO-GI Symposium (Abs 340), the consecutively updated results were presented in this report. Methods: Patients with previously untreated metastatic or locally advanced ESCC were recruited and treated with anlotinib (12mg, po, d1~14, q3w) and penpulimab (200mg, iv, d1, q3w) plus nab-paclitaxel (220mg/m2, iv, d1, q3w) until disease progression or unacceptable toxicity. The tumor response was assessed according to RECIST 1.1 using CT scans every two cycles. Adverse events were recorded by severity in accordance with the NCI CTC AE Version 5.0. The predefined sample size was 30. Primary endpoint was PFS and secondary endpoints included safety, ORR, DCR and OS. Results: From Jul 2022 to Dec 2023, a total of 27 patients were enrolled, 25 patients who had received first tumor response were included in this analysis. The best overall response indicated that there were 1 CR (4.0%), 18 PR (72.0%), 3 SD (12.0%) and 3 NE (12.0%). Therefore, the preliminary ORR was 76.0% (95%CI: 54.9%-90.6%), DCR was 88.0% (95%CI: 68.8%-97.5%). Median PFS of the 25 patients was not yet reached. Additionally, safety profile exhibited that the regimen was tolerable. The most common treatment-emergent adverse events among the 27 patients with the incidence > 20% were anemia (40.7%), peripheral nerve toxicity (37.0) and white blood cell decreased (25.9%). Common grade ≥3 treatment-emergent adverse events were white blood cell decreased (7.4%), diarrhea (3.7%), glutamic-pyruvic transaminase was elevated (3.7%), glutamic oxalacetic transaminase increased (3.7%), hypertension (3.7%) and immune enteritis (3.7%). Conclusions: The combination of anlotinib plus penpulimab and nab-paclitaxel as first-line therapy for advanced ESCC demonstrated promising efficacy and manageable safety profile. And the conclusions needed to be confirmed in subsequent trials.
Effect of two enteral immunonutrition formulas on immune function in Chinese patients with gastrointestinal cancers undergoing surgery: A secondary analysis of a randomized clinical trial.
Authors: Xu Xuan , Liu Yan , Xiao Gang , Zhou Yanbing , Liang Bin , Wang Baogui , Kang Weiming , Ye Yingjiang , Liang Han , Lin Guole , Yu Jianchun , Chen Wei
Published: July 2024

e16019

Background: Immunomodulating nutrition is believed to reduce systemic inflammation and postoperative complications in surgical patients.This study aimed to evaluate the impact of two enteral immunonutrition formulas (immune-enhanced formula and immune-modulating formula) on the immune function of Chinese patients following gastrointestinal cancer surgery. Methods: We conducted a secondary analysis of immune function in perioperative enteral immunonutrition. Between October 2018 and September 2020, 308 patients undergoing resection and gastrointestinal reconstruction for gastrointestinal cancer received preoperative 5-day and postoperative 7-day feeding. They were randomly assigned in a double-blinded manner to either the immune-enhanced formula (intervention) or immune-modulating formula group (control). . The primary endpoints were the levels of CD4+ and CD8+ T cells and CD4+/CD8+ ratio. Secondary endpoints included inflammatory markers, such as C-reactive protein (CRP) and IL-6 levels. Results: Of the 308 patients included, 193 (62.7%) exhibited adequate compliance ( > 75%). Patients in the immune-enhanced formula group did not demonstrate significant differences in CD4+ T cells, CD8+ T cells, CRP, and IL-6 levels compared with the immune-modulating formula group. However, among patients with low prealbumin levels, the median difference in CD4+/CD8+ ratio on postoperative day 7 was 1.845 in the immune-enhanced formula group and 1.68 in the immune-modulating formula group ( P = 0·036). Conclusions: This study suggests that immunonutrition may significantly enhance immune function in patients with gastrointestinal tumors. In particular, our data indicate that immune-enhanced formula may be more effective in ameliorating immune responses in patients with compromised nutritional status, making them more responsive to immunonutrition. Clinical trial information: NCT03665714 .
Polymeric micellar paclitaxel plus cisplatin combined with tislelizumab as the first-line treatment of advanced unresectable esophageal squamous cell carcinoma: A phase II study.
Authors: Cao Guochun , Li Xiaoyou , Liu Delin , Zhu Jinghua
Published: July 2024

e16022

Background: Immunotherapy combined with chemotherapy has become the standard first-line treatment for advanced and metastatic esophageal squamous cell carcinoma (ESCC). However, the prophylactic use of hormones, a routine preconditioning regimen of paclitaxel, may weaken the immune response. Polymeric micellar paclitaxel is a new formulation of paclitaxel without polyoxyethylene castor oil solvent, which do not need for pretreatment with anti-allergy drugs before administration. We aimed to evaluate the efficacy and safety of polymeric micellar paclitaxel (pm-Pac) plus cisplatin combined with tislelizumab for unresectable advanced ESCC. Methods: This is a single-center, single-arm, prospective phase II clinical trial. Stage IV ESCC patients diagnosed histologically or cytologically without systemic treatment are eligible for this study. Polymeric micellar paclitaxel plus cisplatin combined with tislelizumab was treated for 2 cycles. After imaging evaluation, if there was no disease progression, an additional two cycles of treatment were completed, followed by maintenance treatment with tislelizumab for one year. At day 1 of each therapy cycle, patients were given pm-Pac 230 mg/m2 followed by cisplatin 70 mg/m2 combined with tislelizumab 200 mg via intravenous infusion, every three weeks. This trial planned to include 30 patients. The primary endpoint was objective response rate (ORR) determined by the independent review committee. And the secondary endpoints included overall survival, progression-free survival evaluated based on the Response Evaluation Criteria in Solid Tumors (version 1.1), as well as the incidence and severity of adverse events. Results: From September 2022 to January 2024, 31 patients were included in the trial. Median age was 65 years, 29 (93.5%) patients were male. Median follow-up was 13.1 months, 2 patient achieved complete response (CR), 19 of them showed partial response (PR), 8 stable disease (SD), illustrating an ORR of 67.7% and a DCR of 93.5%. Median PFS was 7.3 months. The most common AEs were neutropenia (90.3%), nausea(83.8%) and thrombocytopenia (25.8%). No grade 3 or higher immune-related AE was observed, and there were no treatment-related deaths. Conclusions: The pm-Pac plus cisplatin combined with tislelizumab as first-line treatment of unresectable advanced ESCC showed effective without new safety signal. This combination therapy may have great efficacy, but multi-center randomized trials with larger sample size are warranted in further.
Efficacy and safety of SOX regimen combined with inetetamab as first-line treatment for HER2-positive advanced gastric cancer.
Authors: Kong Ying , Dong Qi , Jin Peng , Li Yan Ming , Ma Li , Liu Yan Hai
Published: July 2024

e16028

Background: Patients with HER2-positive advanced gastric cancer have a poor prognosis. Trastuzumab combined with chemotherapy is the first-line standard treatment. Inetetamab is a novel anti-HER2 drug, and its efficacy and safety in gastric cancer have not been reported yet. Methods: Thirty-eight patients with HER2-positive advanced gastric cancer or gastroesophageal junction adenocarcinoma were randomly divided into two groups: one group received inetetamab combined with the SOX regimen, and the other group received trastuzumab combined with the SOX regimen. After 4-6 cycles, patients with stable disease received maintenance therapy. The primary endpoints were progression-free survival (PFS) and overall survival (OS), and the secondary endpoints were the objective response rate (ORR), disease control rate (DCR), and adverse events (AEs). Results: Thirty-seven patients completed the trial, with 18 patients in the inetetamab group and 19 patients in the trastuzumab group. In the inetetamab group, the median PFS was 8.5 months, compared to 7.3 months in the trastuzumab group (P = 0.046), indicating a significant difference. The median OS was 15.3 months vs. 14.3 months (P = 0.46), and the ORR was 50% vs. 42% (P = 0.63), with no significant differences between groups. Common AEs included leukopenia, thrombocytopenia, nausea, and vomiting. The incidence rates of grade ≥ 3 AEs were 56% in the inetetamab group and 47% in the trastuzumab group (P = 0.63), with no significant difference. Conclusions: In the first-line treatment of HER2-positive advanced gastric cancer, the efficacy of inetetamab and trastuzumab was comparable. The inetetamab group had superior PFS benefits, and both groups had good safety.
Early evidence of pancreatic enzyme insufficiency in patients with gastric neoplasia.
Authors: Shah Raj N , Zakhour Joud , Karam Wissam , Alqam Anas , Dean Tanner , Nabbout Nassim H.
Published: July 2024

e16037

Background: The incidence and association of Exocrine Pancreatic Insufficiency (EPI) in patients with gastric neoplasms has not been well reported. Malnutrition and cachexia occur commonly in patients with advanced gastric cancer (AGC), significantly affecting the quality of life and prognosis in these patients. EPI is one of the factors associated with malnutrition and can cause increased morbidity and mortality. ( [1] ) While an association between pancreatic tumors and EPI has been well established, such an association has not been well studied with gastric tumors. Methods: We queried the HERON database for the number of patients diagnosed with Malignant neoplasms of the stomach using International Classification of Disease (ICD) code C16 who then developed EPI, represented by ICD codes K87, K86.6, and K89.9. We conducted a comparative analysis involving individuals diagnosed with gastric neoplasia but lacking a preceding diagnosis of EPI. Specifically, we examined two distinct groups within this cohort: those individuals who were subsequently diagnosed with EPI and those who were not. Additionally, our study incorporated a comparison with the broader general population, utilizing the same database. We used CHI squared testing, odds ratio, and Cramer’s V for statistical analysis. Results: We identified ICD codes in the whole database of 1566102 patients from the database inception to Jan 1, 2024. Out of these, 1609 patients had the diagnosis of gastric neoplasms in the database. 21 patients had the diagnosis of PEI occurring following the diagnosis of gastric neoplasm. 3148 patients developed EPI without gastric neoplasms. The association was statistically significant with a p-value of < / = .001. The odds ratio reported was 6.58 (95% CI = 4.27-10.13). The Cramer’s V was 0.007. Conclusions: The findings reveal preliminary evidence within our cohort of a significant association between the diagnosis of gastric malignant neoplasm and subsequent development of EPI. However, the strength of this association, as indicated by Cramer’s V, is comparatively low. This could be attributed to various factors, including possible missed diagnosis related to limited physician awareness. To delve deeper into this early evidence, a prospective study should be initiated, and physician should pay special attention to this underreported condition. The study should also investigate subgroup variables such as the patient's age, gender, carcinoma stage at diagnosis, nutritional status before and after treatment, as well as the type and duration of treatment, including chemotherapy and radiotherapy. ( [2] ).
Analysis of factors affecting complete pathological remission after neoadjuvant immunocombination chemotherapy treatment for locally advanced esophageal squamous carcinoma.
Authors: Liao Ziyi , Ma Daiyuan
Published: July 2024

e16061

Background: Chemotherapy combined with immunotherapy for locally advanced esophageal squamous carcinoma has achieved a high rate of complete pathological remission, which is conducive to a better prognosis for patients; however, not all ESCC patients benefit from ICI therapy, so finding validated prognostic markers of efficacy will help us to screen for populations that are superior to neoadjuvant immunotherapy. Methods: Patients with locally advanced esophageal squamous carcinoma treated with neoadjuvant immune-combination chemotherapy followed by radical surgery from January 2019 to June 2023 at our institution were collected. The grouping was based on whether pathologic complete remission (pCR) was achieved after neoadjuvant therapy. Clinical and treatment-related data as well as hematologic, inflammatory, and nutritional indices within 1 week before neoadjuvant therapy and within 1 week after 2 cycles of neoadjuvant immune-combination chemotherapy treatment were collected from all patients, and univariate and multivariate analyses were performed to assess independent predictors of pCR. Results: Patients in both pCR and Non-pCR groups were more likely to obtain pCR if they had pre-treatment BMI > 21Kg/m2 vs BMI ≤21Kg/m2, number of neoadjuvant therapy cycles ≥3 cycles vs number of neoadjuvant therapy cycles = 2 cycles, and CYFRA21-1ng/ml < 3.28 vs ≥3.28 before neoadjuvant therapy (p < 0.05). Patients with albumin ≥40.10g/L vs albumin < 40.10g/L, NLR < 2.50 vs NLR ≥2.50, and NRI ≥98.06 vs NRI < 98.06 were more likely to achieve pCR before treatment in both groups (p < 0.05). SII ≥521.75 VS SII < 521.75 was more likely to achieve pCR after 2 cycles of treatment (p < 0.05). Univariate analysis of the comparison of dynamic changes in nutritional inflammatory indexes during treatment between the two groups of patients showed that pCR was more likely to be achieved in patients with persistently elevated eosinophil counts and NLR after 2 cycles of neoadjuvant immune-combination chemotherapy treatment (p < 0.05). The results of multifactorial analysis showed that pre-treatment BMI, SII after 2 cycles of treatment, and dynamic changes in eosinophils during neoadjuvant therapy were independent influences on complete pathological remission after neoadjuvant immune-combination chemotherapy treatment (p < 0.05). Conclusions: Complete pathological remission after neoadjuvant immune-combination chemotherapy treatment for esophageal squamous carcinoma was significantly correlated with the patient's pre-treatment BMI, Post-treatment SII, and eosinophil dynamics during treatment.
Influence of neoadjuvant regimen on the prognosis of locally advanced gastric and gastroesophageal junction cancer with HER2 overexpression.
Authors: Zhao Lingdi , Liu Xiao , Chen Guanglong , Ma Baozhen , Huang Jinxi , Jiang Zhiqiang , Hou Xinfang , Li Ning , Qin Peng , Zhang Yong , Wang Zibing , Li Zhi , Gao Quanli
Published: July 2024

e16082

Background: The relative high recurrence rate in locally advanced gastric or gastroesophageal junction (G/GEJ) cancer with Her2 overexpression after surgery, along with the absence of a standard neoadjuvant treatment protocol, necessitates exploration of novel approaches for this patient population. Methods: In this study, we conducted a retrospective analysis of clinical characteristics, postoperative pathological results, and survival data for patients who underwent neoadjuvant treatment and subsequent surgery at our center from September 2020 to December 31, 2022. The inclusion criteria were as follows: 1) pathologically confirmed adenocarcinoma of the G/GEJ; 2) diagnosed as cT3-4 or N+ by enhanced CT and endoscopic ultrasound; 3) Her2 immunohistochemistry 3+ or 2+ with Fish positive in biopsy specimens; 4) discussed in a multidisciplinary team for the need for neoadjuvant treatment; 5) received 2-4 cycles of neoadjuvant therapy; 6) underwent radical D2 surgery; 7) had complete follow-up data. Results: Seventy-three patients met the inclusion criteria, with 19 receiving chemotherapy + anti-PD-1, 10 receiving chemotherapy + anti-Her2, and 44 receiving chemotherapy alone. Their pCR rates were 31.6%, 10%, and 2.3%, respectively (P = 0.003); MPR rates were 42.1%, 30%, and 11.4% (P = 0.022). As of the last follow-up on December 31, 2023, the median DFS for the chemotherapy group was 18.1 months (95% confidence interval 14.9-21.3); median DFS for the other two groups had not been reached. DFS analysis revealed differences in median DFS among different neoadjuvant treatment regimens (P = 0.025); further pairwise comparisons indicated that this difference mainly stemmed from the chemotherapy + anti-Her2 group compared to the chemotherapy group. Conclusions: In locally advanced gastric and gastroesophageal junction cancer with Her2 overexpression, neoadjuvant chemotherapy combined with anti-Her2 treatment improves the pCR rate and prolongs DFS compared to neoadjuvant chemotherapy alone.
Correlation of plasma GDF15 with aging, organ disfunction, sarcopenia, and postoperative infectious complication in patients with esophageal cancer.
Authors: Ozawa Yohei , Okamoto Hiroshi , Taniyama Yusuke , Sato Chiaki , Ishida Hirotaka , Abe Takaaki , Kamei Takashi
Published: July 2024

e16088

Background: The age of cancer incidence is increasing every year. Along with it, cancer patients getting has more comorbidity and decreasing muscle strength which may lead to increase postoperative complications. Especially, since esophageal cancer (EC) patients have heavy drinking and smoking history and high age of morbidity, they usually have multiple comorbidities and so that they particularly have high incidence of cachexia. A novel inflammatory marker known as growth differentiation factor 15 (GDF15) has been recently reported relation with cancer cachexia. This study conducted to evaluate correlation between clinical data which suggested cachexia of EC patients and plasma GDF15. Methods: Eighty-one esophageal cancer patients who first visited our outpatient ward from July 2021 to March 2023 were enrolled in this study. After obtaining consent for the study, plasma samples collected before starting any treatment for the cancer. The quantification of GDF15 was performed by ELISA. Clinical information was collected from clinical record including age, comorbidities, biochemical data, Controlling Nutritional Status (CONUT) score, and Skeletal Mass Index (SMI). GDF15 was then evaluated for clinical impact by comparison with postoperative results. Mann-Whitney U test, student-t test, ANOVA were used appropriately to analyze the relationship between the GDF-15 and patient characteristics and post operative complications. Multivariate analysis ware used logistic regression analysis. P-values < 0.05 were considered statistically significant for all statistical analyses. Results: Mean age was 68.3-year-old and 80.3% of these were male. Malnutrition patients diagnosed by using CONUT were 24 (29.6%) and sarcopenia patients diagnosed by using SMI were 21 (25.9%). The median value of GDF15 was 1165 pg/mL with its range were from 298 to 9100 pg/mL. Plasma GDF15 was statistically correlated with age ( P< 0.001), performance status ( P= 0.046), prevalence of hypertension ( P= 0.045) and/or diabetes ( P= 0.018), serum level of aspartate aminotransferase (AST) ( P< 0.001)/ γ-glutamyltransferase (γ-GTP) ( P< 0.001)/ creatinine ( P= 0.004)/ blood sugar ( P= 0.028), and SMI ( P= 0.003). Seventy-two patients underwent curative surgery, and no perioperative death was observed. The patients who occurred anastomotic leakage and infectious complication observed statistically higher GDF15 than those without (P = 0.030, P = 0.016). Optimal cut-off value was detected as 940 ng/mL for detecting infectious complication by ROC-curve with AUC value of 0.68. Conclusions: This study showed GDF15 is potentially suggesting deterioration of general condition, which came from aging, organ disfunction, and decreasing muscle mass, which may lead to cachexia in EC patients. In addition, higher GDF15 patients have risk of postoperative infectious complication.
Outcomes of R-MPV followed by ara-c in primary central nervous system lymphoma: A single-center retrospective analysis.
Authors: Khurshid Aatif , Paranji Sreshta , Kapur Rohan , Weber Alec , Cohen Michelle , Vegunta Rathnamitreyee , Seiter Karen , Liu Delong , Ahmed Tauseef , Sweeney Richard , Steinberg Amir S.
Published: July 2024

e19046

Background: Primary central nervous system lymphoma (PCNSL) lymphoma is a rare non-Hodgkin’s Lymphoma. Currently, there is no uniform consensus in the optimal management of PCNSL. In patients that can tolerate systemic therapy, induction therapy is typically done with a high-dose methotrexate-based regimen, due to evidence of better penetration of the blood brain barrier. One such regimens is high dose methotrexate combined with rituximab, procarbazine, and vincristine (R-MPV). Options for consolidation therapy include high-dose systemic therapy with stem cell rescue (ASCT), whole brain radio therapy (WBRT) and high-dose cytarabine (ara-c) with or without etoposide (EA). At our institution we utilize an R-MPV induction approach with some form of ara-c consolidation without etoposide. We aimed to execute a retrospective cohort study to analyze outcomes of this approach. Methods: All the patients diagnosed with PCNSL who received an induction regimen of R-MPV from 10/01/2020 to 06/01/2023 were included. Data was then gathered by chart review of the electronic medical record. Treatment outcomes were evaluated based on imaging with brain MRIs and PET scans. Central findings such as complete response (CR) rate, progression free survival (PFS) and overall survival (OS) were ascertained. Results: 10 charts were reviewed. 9 out of the 10 patients had a histological presentation consistent with diffuse large B-cell lymphoma; 1 patient had a diagnosis of B-cell lymphoma. In terms of demographics, the patients ages ranged from 54 to 83 years, with a median of 74 years. Complete response was achieved in 5 out of the 10 patients (CR rate of 50%), and no relapse was noted in any of these patients. 2 out of the 10 patients progressed on treatment, with 1 dying from progression of the disease. The median follow-up for patients who were still alive was 24 months. 2-year PFS was 80%, and 2-year OS was 90%. Median PFS and OS were not reached. Mean PFS and OS were 28 months and 30.5 months respectively. Conclusions: Based on our study results, the CR rate we observed for R-MPV appears consistent with existing literature on this regimen and other methotrexate-based induction regimens. Our results for R-MPV with ara-c consolidation provides similar outcomes to existing studies on treatment with different methotrexate-based induction and consolidation with ASCT, particularly the 80% PFS we observed. This percent PFS also appears similar to studies of consolidation with ara-c and EA, and superior to PFS with WBRT. Overall, these results are reassuring as in a specific set of older patients who might not be candidates for ASCT, our specific nonmyeloablative approach could be worthwhile. However, our study does have the limitation of being a single center retrospective perspective. [Table: see text]
Combination therapy with the oncolytic virus CF33-CD19 and blinatumomab for the treatment of advanced solid tumors.
Authors: Li Daneng , Seiz Amanda , Fein Seymour H. , Byon John Chong Han , Wilkinson Grey A , Woodard Paul Paul
Published: July 2024

TPS2687

Background: CF33-CD19 is a novel chimeric vaccinia virus that selectively replicates in tumor cells and can provoke anti-tumor immunity. CF33-CD19 expresses a truncated and non-signaling CD19 protein on the surface of infected tumor cells before virus-mediated tumor lysis, labeling them for CD19-targeted therapies. Preclinical studies with CF33-CD19 have shown that combination therapy with CD19 targeting chimeric antigen receptor T cells is more effective than either monotherapy in murine xenograft and syngeneic models [1]. Likewise, combination therapy with bispecific T-cell engagers (BiTE)s that bind CD3-positive T cells and infected solid tumor cells that express de novo CD19, showed pronounced recruitment of T cells to the tumor microenvironment, resulting in tumor growth inhibition in mouse models. CD19xCD3 targeting BiTEs such as blinatumomab may offer an off-the-shelf alternative to adoptive cell therapies. This phase I study, called OASIS, dose escalates CF33-CD19 administered intravenously (IV) or intratumorally (IT) combined with blinatumomab in adults with advanced or metastatic solid tumors. Methods: The OASIS study (NCT06063317) is enrolling patients with advanced or metastatic solid tumors with ≥ 2 prior lines of therapy. Patients who have received prior treatment with a poxvirus based oncolytic virus or a bispecific CD19-directed CD3 T-cell engager are excluded. A safety run-in will evaluate the safety of CF33-CD19 monotherapy administered IT or IV before initiating the combination therapy regimen. Combination therapy will be administered in 28-day cycles with CF33-CD19 on days 1 and 15. Following viral transduction to promote de novo CD19 expression, blinatumomab is given on days 2-9 and 16-23 via a 7-day continuous infusion. Patients > 45 kg will receive 9 mcg of blinatumomab during the first week of cycle 1, then 28 mcg during the third week of cycle 1 and subsequent cycles. The study consists of two parts. Part 1 follows a 3+3 dose escalation scheme independently of each route of CF33-CD19 administration (IT and IV) with dose levels of CF33-CD19 ranging from 1.0x107 to 3.0x109 PFU. Part 2 is a cohort expansion in select indications at the optimal dose. The co-primary endpoints are safety and identification of the recommended phase 2 dose. Secondary endpoints include objective response rate according to RECIST v1.1 and iRECIST. Enrollment began in October 2023. 1. Park et al. Sci Transl Med. 2020 Sep 2;12(559):eaaz1863. doi: 10.1126/scitranslmed.aaz1863. PMID: 32878978. Clinical trial information: NCT06063317 .