bluuebunny/crossref_metadata_2025 huggingface dataset:
“It’s like building a new person”: lived experience perspectives on eating disorder recovery processes
Authors: LaMarre Andrea , Hellner Megan , Silverstein Scout , Baker Jessica H. , Urban Bek , Yourell Jacqlyn , Wolfe Hannah , Perry Taylor , Steinberg Dori
Published: July 2024

Background

Deeply engaging with the expertise of those who have experienced or supported someone with an eating disorder can add to a growing body of knowledge about recovery processes. In this qualitative study, we sought to explore and generate nuanced understandings of recovery experiences of people with a lived ED experience (first hand or as a caregiver) who were working as mentors in the field. To do this, we focused on changes that occur in personality, traits, and interests over the course of an eating disorder and into recovery.

Method

We conducted semi-structured interviews with 27 people with an eating disorder history, either through personal lived experience (n = 14) or as a caregiver of a loved one with an eating disorder (n = 13). We undertook a reflexive thematic analysis of the data through a critical realist lens.

Results

We developed three themes, which illustrate the nonlinearity, relationality, and systemically linked nature of changes across experiences of having and recovering from an eating disorder. The first theme focuses on expansion; participants described how their worlds got bigger as they explored who they were becoming and discovered new ways of living in line with their values. The second theme emphasizes the balance between support and autonomy participants described as important for enabling change to occur across the recovery process. The last theme highlights the ways in which changes throughout the recovery process entwined with systemic factors, including actively pushing back against diet culture and weight stigma.

Conclusions

Participants’ stories highlight interactions between individual, relational, and societal shifts that occur throughout the course of an ED and into recovery. They support ongoing calls to orient to ED recovery as situated within a broader social milieu, which invites us to build supportive environments to enable expansion and flourishing.
Relationship between childhood trauma and non-suicidal self-injury in high school students: the mediating role of the stress perception and the moderating role of teacher-student relationship
Authors: Liu Yilin , Fang Yuan , Chen Yuanling , Qin Fuyi , Li Xinrui , Feng Ruibin , Luo Xinyu , Wen Jia , Chen Yatang , Teng Zhaowei , Zeng Yong
Published: July 2024

This study delves into the correlation between childhood trauma and non-suicidal self-injury (NSSI) behaviors among high school students. Additionally, it examines the mediating role of stress perception and the moderating role of the teacher-student relationship in this association. A questionnaire survey was administered to 1,329 high school students in Yunnan Province to assess childhood trauma, NSSI behaviors, and stress perception. Firstly, the survey revealed a 12% prevalence of NSSI, with girls exhibiting a higher occurrence compared to boys (OR = 0.413, 95% CI: 0.280–0.609). Secondly, childhood trauma emerged as a significant predictor of NSSI behavior, irrespective of gender or whether the individual was an only child (r = 0.17, P < 0.01). Thirdly, stress perception functioned as a mediator in the relationship between childhood trauma and NSSI among high school students (t = 4.65, P < 0.01). The mediation effect occupies 26.56% of the total effect. Furthermore, the teacher-student relationship moderated the mediating effect of stress perception on the link between childhood trauma and NSSI (β = 0.0736, P < 0.01). Notably, individuals with strong teacher-student relationships exhibited a significant elevation in stress perception upon exposure to childhood trauma. The findings of this study support a moderated mediation model in the association between childhood trauma and NSSI, suggesting profound implications for the development of targeted interventions and prevention strategies among high school students.
Pharmacokinetics of piperaquine and its association with intermittent malaria preventive therapy outcomes during pregnancy
Authors: Mlugu Eulambius M. , Minzi Omary M.S. , Johansson Mats , Kamuhabwa Appolinary A. R. , Aklillu Eleni
Published: July 2024

Background

Dihydroartemisinin-piperaquine (DHP) recently showed superior effectiveness over sulfadoxine-pyrimethamine for malaria intermittent preventive treatment in pregnancy (IPTp). We investigated day 7 piperaquine pharmacokinetics and its therapeutic efficacy in preventing malaria during pregnancy.

Methods

Malaria-free (mRDT) pregnant women (n = 400) who received monthly IPTp-DHP were enrolled and followed till delivery. Day 7 Plasma piperaquine concentrations were determined after each IPTp dose using UPLC/MS/MS. IPTp outcomes (symptomatic malaria and parasitemia during pregnancy, placental malaria, and maternal malaria at delivery) were monitored. Linear mixed model and Cox regression were used to assess predictors of day 7 piperaquine concentration and treatment outcome, respectively.

Results

The incidences of symptomatic malaria and parasitemia during pregnancy per 100 person-year at risk were 2 and 33, respectively. The prevalence of histopathologically confirmed placental malaria and maternal malaria at delivery were 3% and 9.8%, respectively. Repeated monthly IPTp-DHP resulted in significantly increased day 7 plasma piperaquine concentration (p < 0.001). Following the 1st, 2nd, and 3rd monthly IPTp-DHP doses, the proportions of women with day 7 piperaquine concentration below the therapeutic threshold (< 30 ng/mL) were 6.1%, 4.1% and 3.6%, respectively. Factors such as maternal age, body weight and trimester were not significant predictors of day 7 piperaquine concentration. However, having a low day 7 piperaquine plasma concentration (< 30 ng/mL) was significantly associated with a higher risk of parasitemia during pregnancy (p = 0.004).

Conclusion

Lower day 7 piperaquine plasma concentration is a risk factor for parasitemia during pregnancy. Single plasma sampling at day 7 can be used to monitor piperaquine effectiveness during IPTp-DHP.

Trial registration

Registered 09/12/2016, PACTR201612001901313.
Impact of tracheostomy tube modalities on ventilatory mechanics: a bench study
Authors: Combret Yann , Machefert Margaux , Prieur Guillaume , Fresnel Emeline , Artaud-Macari Elise , Lamia Bouchra , Lebret Marius , Medrinal Clément
Published: July 2024

Purpose

Tracheostomized patients often present with muscle weakness, altered consciousness, or swallowing difficulties. Hence, the literature is scarce regarding the challenging management of tracheostomy weaning. There is a need to strengthen the understanding of respiratory mechanisms with the different tracheostomy tube modalities that compose this weaning pathway. We aimed to evaluate the impact of these modalities on the work of breathing (WOB), total positive end-expiratory pressure (PEEPtot), and tidal volume (VT).

Methods

With a three-dimensional (3D) printed head mimicking human upper airways, we added a tracheal extension, and pierced to allow insertion of a size 7.0 tracheostomy cannula. The whole was connected to an artificial lung. Three lung mechanics were simulated (normal, obstructive and restrictive). We compared five different tracheostomy tube modalities to a control scenario in which the tube was capped and the cuff was deflated.

Results

A marginal difference was observed on the WOB within conditions with a slight increase + 0.004 [95% CI (0.003–0.004); p < 0.001] when the cuff was inflated in the normal and restrictive models and a slight decrease in the obstructive model. The highest PEEPtot that was reached was + 1 cmH2O [95% CI (1–1.1); p < 0.001] with high-flow therapy (HFT) with the cuff inflated in the obstructive model. We observed a statistically significant reduction in VT [up to − 57 mL 95% CI (− 60 to − 54); p < 0.001] when the cuff was inflated, in both the normal and obstructive models.

Conclusions

Our results support the use of conditions that involve cuff deflation. Intermediate modalities with the cuff deflated produced similar results than cannula capping.
Crustal thickness variations beneath Egypt through gravity inversion and forward modeling: linking surface thermal anomalies and Moho topography
Authors: Bekhit Ahmed Mohamed , Sobh Mohamed , Abdel Zaher Mohamed , Abdel Fattah Tharwat , Diab Ahmed I.
Published: July 2024

This study aims to quantify the topography of the Moho boundary, the lower crust and uppermost mantle contact of Egypt, in order to estimate the crustal thickness variation and its link to the distribution of thermal anomalies under Egypt. This is accomplished by modeling satellite gravity, supported by the passive seismic constraints throughout Egypt. However, when estimating the thickness of the crust in Egypt using just seismic data, substantial uncertainty and deviation are produced due to the sparsely dispersed stations. Integrating seismic and gravity data minimizes uncertainty and improves estimate accuracy. The investigation is broken down into four stages, the first involving utilizing the Sentinel-3B satellite to create land surface temperature maps. The subsequent steps consist of gravity and seismic data adjustments, inversion and forward modeling. We used seismically restricted nonlinear inversion to look at Goco06s satellite gravity data to model the Moho’s topographic surface. The data gathered from deep seismic refraction and receiver functions adjusted the analyzed data. The inversion process relies on the adapted Bott's approach and Tikhonov regularization, using the assumption of the sphericity of the Earth planet. Reference values for depth of Moho and density contrast were set at 35 km and 500 kg/m3, respectively. The average statistical difference for Moho depth between gravity-based model and seismic data is − 0.10 km. Through forward gravity modeling, five gravity profiles were chosen and interpreted in 2.5D models. The results indicated that the Moho depth in the south varies from 35 to 39 km and decreases in the north and the Mediterranean. In upper Egypt, the highest Moho depth is 39 km. The depth varies beneath the Sinai Peninsula as it is about 35 km in its south, reaches 30 km in the northern portion, and ranges along the Red Sea’s Rift Margin from 29 to 32 km. Moreover, the final model shows the relation between Moho coincides with the surface temperature anomalies approved by satellite images and hot springs. The model reveals a correlation between Moho discontinuity and surface temperature anomalies, revealing the highest geothermal potential in a rectangular area in central Egypt, between latitudes 25°N and 30°N, based on satellite imagery and hot springs distribution.
Correlation between serum bilirubin, blood uric acid, and C-reactive protein and the severity of chronic obstructive pulmonary disease
Authors: Zhao Tingting , Lv Tian
Published: July 2024

Objective

To explore the correlation between serum bilirubin, blood uric acid, and C-reactive protein (CRP) and the severity of chronic obstructive pulmonary disease (COPD). Methods: Patients with COPD who were admitted to our hospital between March 2020 and March 2023 were retrospectively studied. Based on whether their condition progressed to the acute exacerbation stage, they were divided into an exacerbation group (100 cases) and a stability group (100 cases). The clinical data from both groups were analysed to assess the correlations between serum bilirubin, blood uric acid, CRP, and the severity of COPD. Results: Univariate analysis indicated significant differences in the neutrophil-to-lymphocyte ratio (t = 5.678, P < 0.05), α-hydroxybutyrate dehydrogenase (t = 5.862, P < 0.05), total bilirubin (t = 4.341, P < 0.05), direct bilirubin (t = 5.342, P < 0.05), indirect bilirubin (t = 5.452, P < 0.05), blood uric acid (t = 4.698, P < 0.05), and CRP (t = 4.892, P < 0.05) between the two groups. Multivariate analysis revealed that total bilirubin, blood uric acid, and CRP were positively correlated with exacerbations of COPD (regression coefficients were 0.413, 0.354, and 0.356, respectively; P < 0.05). The evaluation of predictive value showed that the combined predictive value of these three indicators was the highest, with an AUC of 0.823 (95% CI: 0.754–0.911). Conclusion: Serum bilirubin, blood uric acid, and CRP levels are elevated in patients with acute exacerbations of COPD (AECOPD), showing good consistency in predicting the occurrence of AECOPD. The combined diagnostic value of these three indicators is greater than that of any single indicator, providing a reference for the early clinical prediction of AECOPD.
Epidemiological characteristics of first-time SARS-CoV-2 Omicron infection among hospital staff in Chengdu, China
Authors: Tang Li , Wang Yeyuan , Li Xue , Yang Liu , Luo Yingjuan , Li Chunrong , He Yulei
Published: July 2024

Background

After China ended its ‘dynamic zero-COVID policy’ on 7 December 2022, a large-scale outbreak of SARS-CoV-2 Omicron infections emerged across the country. We conducted a hospital-wide prospective study to document the epidemiological characteristics of the outbreak among healthcare workers in a hospital of Chengdu, where no previous staff SARS-CoV-2 infections were detected.

Methods

All hospital staff members were invited to complete an online questionnaire on COVID-19 in January 2023, and SARS-CoV-2 infection cases were followed up by telephone in June 2023 to collect data on long COVID. Univariable and multivariable logistic regression analyses were performed to evaluate factors associated with SARS-CoV-2 infection.

Results

A total of 2,899 hospital staff (93.5%) completed the online questionnaire, and 86.4% were infected with SARS-CoV-2 Omicron. The clinical manifestations of these patients were characterized by a high incidence of systemic symptoms. Cough (83.4%), fatigue (79.8%) and fever (74.3%) were the most frequently reported symptoms. Multivariable logistic analysis revealed that females [adjusted odds ratio (aOR): 1.42, 95% confidence interval (CI): 1.07–1.88] and clinical practitioners (aOR: 10.32, 95% CI: 6.57–16.20) were associated with an increased risk of SARS-CoV-2 infection, whereas advanced age ≥ 60 years (aOR: 0.30, 95% CI: 0.19–0.49) and a three-dose COVID-19 vaccination with the most recent dose administered within 3 months before 7 December 2022 (aOR: 0.44, 95% CI: 0.23–0.87 for within 1 month; aOR: 0.46, 95% CI: 0.22–0.97 for within 1–3 months) were associated with reduced risk. Among the cases, 4.27% experienced long COVID of fatigue, brain fog or both, with the majority reporting minor symptoms.

Conclusion

Our findings provide a snapshot of the epidemiological situation of SARS-CoV-2 infection among healthcare workers in Chengdu after China’s deregulation of COVID-19 control. Data in the study can aid in the development and implementation of effective measures to protect healthcare workers and maintain the integrity of healthcare systems during challenging times such as a rapid and widespread Omicron outbreak.
Neoadjuvant chemo-immunotherapy following concurrent immuno-chemoradiotherapy and immune-maintenance therapy as primary treatment for locally advanced cervical cancer: A prospective, single-arm, phase 2 trial.
Authors: Chen Fo-Ping , Chen Kai , Huang Xiaodan , Huang Lin , Wu Hai-Ying , Ouyang Yi , Ye Weijun
Published: July 2024

5533

Background: Immunotherapy in combination with chemoradiotherapy has shown good efficacy in locally advanced cervical cancer (LACC). We report on the efficacy of neoadjuvant camrelizumab plus chemotherapy (TP) following concurrent immuno-chemoradiotherapy and maintenance immunotherapy for LACC. Methods: Eligible participants were adults with histologically confirmed squamous cell carcinoma, adenosquamous cell carcinoma, or adenocarcinoma of the cervix (FIGO 2018 stage IIB-IVA disease), ECOG PS score 0-2, and adequate bone marrow and organ function. All pts received 2 cycles neoadjuvant camrelizumab (200 mg d1 q3w) plus TP (albumin-bound Paclitaxel 260mg/m2 d1 q3w; cisplatin 75 mg/m2 d1-3 q3w) treatment, following 5-week external beam radiotherapy (EBRT) protocol (45-50 Gy/25 fractions with concurrent triweekly camrelizumab and cisplatin) to the whole pelvis plus brachytherapy every 3 weeks for 2 cycles, and then maintenance therapy of camrelizumab (200mg q3w, up to one year). The primary endpoint was progression-free survival (PFS) at 2 years. PFS was evaluated when at least 13 events were observed using a stratified log-rank test with an overall one-sided significance level of 0.05. Results: 67 pts provided informed consent and 12 were excluded for not meeting eligibility. 55 pts received the investigational agent and were evaluable for safety and efficacy analyses. The median age was 54 years [IQR 50 to 60]; 51 [92.7%] were squamous cell carcinoma, and 4 [7.3%] were adenocarcinoma; 9 [16.4%] were stage IIB, 2 [3.6%] were IIIA, 5 [9.1%] were IIIB, 30 [54.5%] were IIIC1r, 6 [10.9%] were IIIC2r, and 3 [5.5%] were IVA. As of data cutoff (Jan. 15, 2024), median follow-up was 9.5 (IQR 7.1 to 10.3) months. Of the 55 pts, 1 (1.8%) pt underwent hysterectomy after EBRT because of pelvic empyema, and was excluded from response evaluation. At three months after brachytherapy, the overall remission rate was 100% (53 [98.1%] complete remission and 1 [1.9%] partial remission). We identified 3 (5.5%) pts with treatment failure (2 [3.6] distant metastasis, and 1 [(1.8%] para-aortic lymph node relapse) during follow-up; 1-year PFS was 90.6% (85.4%-95.8%). The most common clinically significant grade 3-4 adverse events (AEs) were decreased neutrophils (18.2%), thrombocytopenia (9.1%) and anemia (27.3%). Serious AEs occurred in 7 (12.7%), most commonly due to infectious complications. There were no treatment-related deaths. Conclusions: The interim data support Camrelizumab plus TP neoadjuvant chemo-immunotherapy following immuno-chemoradiotherapy and Camrelizumab maintenance therapy as an active go-forward regimen in LACC. No new safety signals were observed, and most AEs were mild to moderate. Clinical trial information: ChiCTR2200061097.
Efficacy and safety of disitamab vedotin (RC48) combined with camrelizumab and S-1 for neoadjuvant therapy of locally advanced gastric cancer with HER2 overexpression: Preliminary results of a prospective, single-arm, phase II study.
Authors: Chai Jie , Wang Longgang , Liu Luguang , Liu Bing , Sun Dong
Published: July 2024

e16100

Background: A combination of HER2-targeted therapy, immunotherapy and chemotherapy is being explored in the perioperative treatment of gastric/gastric junction (GC/GEJ) adenocarcinoma.Disitamab vedotin (RC48), a HER2-directed antibody-drug conjugate (ADC), demonstrated significant anti-tumor activity. Moreover, data suggest that the combination of RC48 with immunotherapy exhibits a synergistic effect. Therefore, we conducted the study to investigate the effects of combining RC48 with camrelizumab and S-1 in the neoadjuvant setting for locally advanced, resectable GC/GEJC with HER2 overexpression. Methods: In this prospective, phase II, single-arm study, we included patients with histologically confirmed, resectable gastric/gastric junction adenocarcinoma (GC/GEJ) staged as cT3-4aN1-3M0 according to the TNM 8th edition, and demonstrating HER2 overexpression (IHC 3+ or IHC 2+). Participants received three cycles of treatment on a three-weekly basis (Q3W). Surgical resection was scheduled to occur 3-4 weeks following the completion of neoadjuvant therapy. The primary endpoint was the pathological complete response (pCR) rate; the secondary endpoints included the major pathological response (MPR) rate, clinical downgrading rate, disease-free survival (DFS), overall survival (OS), and safety. Results: Between Sep 18, 2022 and Feb 2, 2024, a total of 23 patients were enrolled. Seven patients had not completed neoadjuvant treatment.Two patients refused surgery due to organ preservation. Two patients refused study therapy after 2 cycles of neoadjuvant treatment. 12 patients who experienced D2 resection, 6 (50%) achieved MPR, including 4 (33.3%) with pCR (ypT0N0M0).The R0 resection rate was 100%. Median DFS and OS have not been reached. The most common reported AEs (grade≥3) were decreased neutrophil count (10%), bowel obstruction (5%), ALT increased (5%) and AST increased (5%). There have been no treatment-related mortalities documented. Conclusions: The preliminary findings suggest that the neoadjuvant combination of RC48, camrelizumab and S-1 presents a promising and safe treatment option for locally advanced resectable GC/GEJ adenocarcinoma with HER2 overexpression. Clinical trial information: ChiCTR2300075446.
Neoadjuvant serplulimab in combination with concurrent chemoradiotherapy for locally advanced, resectable esophagogastric junction adenocarcinoma.
Authors: Ge Yuping , Zhao Lin , Kang Weiming , Yan Junfang , Wang Xiang , Li Ningning , Ye Xin , You Yan , Gao Xin
Published: July 2024

e16103

Background: Surgery combined with perioperative therapy was recommended as standard treatment for patients with locally advanced esophagogastric junction (EGJ) adenocarcinoma, but the survival rate was still poor. Immunotherapy has shown antitumor activity and an acceptable safety profile in advanced EGJ cancer. The aim of this study was to evaluate the efficacy and safety of neoadjuvant Serplulimab combined with concurrent chemoradiotherapy in previously untreated locally advanced resectable EGJ adenocarcinoma. Methods: Eligible patients with resectable EGJ(Siewert Type II and Type III, Siewert classification 2000)adenocarcinoma stage cT3-4 or N+ were enrolled. Patients received neoadjuvant Serplulimab (300mg on day 1) plus SOX(oxaliplatin at 130mg/㎡on day 1; TS1 40-60mg two times per day on D1-D14, Q3W) in first cycle, followed by Serplulimab (300mg on day 1) combined with concurrent chemoradiotherapy (Reduced SOX regimen: oxaliplatin at 100mg/㎡on day 1, TS1 40-60mg two times per day on D1-D14, Q3W; Radiotherapy dose:45Gy in 25f) in second and third cycle. The patient finished the preoperative treatment and rested for 6-8 weeks for surgery. The primary endpoint was pathological complete response (pCR) rate. Secondary endpoints were major pathological response(MPR) rate, R0 resection rate, objective response rate(ORR), disease-free survival(DFS), overall survival(OS), and toxicity. Results: From March 8, 2023 to January 31,2024,15 patients were enrolled. Nine patients completed neoadjuvant therapy. Eight of these patients underwent radical surgical resection. One out of nine achieved a confirmed pathological complete response (pCR) after three cycles of neoadjuvant treatment. Additionally, two out of nine patients achieved major pathological response(MPR). So, the pCR rate was 11.1%, and the MPR rate was 22.2%. The Tumor and Lymph Nodes downstaging rates are 62.5% and 87.5%, respectively. The median DFS and OS were not reached. In terms of safety, fifteen patients who received at least one cycle of neoadjuvant therapy were included. The most common treatment-related adverse events(TRAE) across all grades were nausea/vomiting(6/15), anorexia(5/15), thrombocytopenia(4/15), and fatigue(4/15). Four patients (26.7%) had grade≥3 adverse events during preoperative therapy, with thrombocytopenia(3/15) and hepatic veno-occlusive disease(1/15). Immune-related adverse reactions(irAE) included myositis(1/15) and rash(1/15), both were grade 1. No grade 4 or higher TRAEs were observed. Conclusions: Initial benefits were demonstrated when using Serplulimab with concurrent chemoradiotherapy for the treatment of locally advanced, resectable EGJ adenocarcinoma patients. The efficacy and safety of Serplulimab with chemoradiotherapy will be further investigated in this trial later. Clinical trial information: NCT05918419 .
Short term outcomes of robotic assisted minimally invasive oesophagectomy: A single institutional experience.
Authors: Chandramohan Raj Prakash , Sharma Ashwani , Dabas Surender Kumar , Mohan Sandeep Kumar , Mukharjee Sourabh
Published: July 2024

e16112

Background: With the aim to decrease the rate of pulmonary complications associated with thoracotomy, minimally invasive esophagectomy (MIE) was introduced. Our purpose is to see the feasibility, safety and short-term outcomes of Robot-Assisted MIE (RAMIE). Methods: Seventy-three patients of carcinoma oesophagus who underwent Robotic Esophagectomy from May 2018 to March 2023 were included. Demographic profiles, neoadjuvant therapy, and operative and postoperative outcomes were evaluated. Results: Fifty-three patients were male while 29 were female, with median age of 60 years. Four patients had a previous history of surgery for cancer, 2 had carcinoma colon, one had carcinoma breast and another had carcinoma thyroid. 71% of patients had clinical stage 3 disease and the most common location of the tumour was the middle third (62.7%). 85.3% of patients received neoadjuvant therapy. Eighty percent of our patients underwent Robotic Mc Keown’s Esophagectomy while 20% had Robotic Ivor-Lewis Operation. The thoracic part in 1 patient was converted to open due to extensive adhesions in the right hemithorax. Mean abdominal console time was 146 min (+ 32 min) and thoracic console time was 120 min (+ 39 min); with a total operative time of 314 min (+ 44 min). Intraoperative blood loss was 300 ml (+ 86 ml). Post-operative and short-term outcomes: Out of 75 patients, 74.7% patients recovered well without any major complications. The most common complications were pulmonary (16%). Anastomotic leakage was found in 8 patients of whom 4 patients were managed conservatively, 1 required oesophageal stenting, other 2 had bedside opening of neck wound and 1 required pectoralis major muscle flap cover. Clinically recurrent laryngeal nerve palsy was found in 2 patients while Chylothorax was found in 2 patients. The median ICU stay was 3 days (range 1-28 days), whereas the median hospital stay was 8 days (range 6-38 days). Our 30-day mortality was 1.3% and this patient died on POD8 due to sepsis and respiratory failure, while 90 day mortality was 4%. Oncological Outcomes: Pathological complete response was seen in 21.3% of patients and median lymph nodal yield was 21 nodes (range 9-68). There was one microscopic margin positivity. Conclusions: RAMIE is a technically feasible and safe procedure with good lymph node yield and R0 resections. Postoperative complications and short-term oncologic results are comparable to other high-volume centres.
Neoadjuvant chemoradiotherapy (nCRT) combined with sequential tislelizumab for resectable esophageal squamous cell carcinoma (ESCC): Preliminary results of a single-arm, open-label phase Ib trial (CRIS).
Authors: Jiang Youhua , Qiu Guoqin , Li Jianqiang , Wang Jiangfeng , Wang Changchun , Wu Jie , Cheng Lei , Zheng Yuanda , Ruan Rongwei , Song Ge , Ye Xuemei
Published: July 2024

e16116

Background: Neoajuvant chemoradiation is the standard treatment for resectable locally advanced esophageal squamous cell carcinoma (ESCC). Immune checkpoint inhibitors (ICIs) have shown a survival benefit for advanced ESCC and showed promising efficacy in neoadjuvant treatment for several cancers. This study aimed to evaluate the safety and efficacy of neoadjuvant chemoradiotherapy (nCRT) combined with sequential tislelizumab followed by surgery for resectable ESCC. Methods: This is a single-arm, phase Ib study. Eligibility criteria include histologically confirmed ESCC and clinical T3-4aN0M0 or T2-4aN+M0 (AJCC/UICC 8th). Patients received neoadjuvant radiotherapy (41.4Gy in 23 fractions) with concurrent chemotherapy (paclitaxel, 50 mg/m2, carboplatin area under the curve of 2mg/mL/min, QW*5). Then followed by two cycles of tislelizumab (200mg, Q3W). The primary endpoint was the pathological complete response (pCR) rate and safety. Results: From Feb 2022 to Jan 2024, 35 patients had been enrolled, of whom the median age was (65.5 (95%CI, 59-67), including 31 (88.6%) males. 12 patients were still undergoing chemoradiotherapy and 2 patients did not receive immunotherapy due to pneumonia and myocarditis after chemoradiotherapy. 16 patients completed all 2 cycles tislelizumab preoperatively and 5 patients completed 1 cycle tislelizumab because of AEs. Two patients refused surgery after achieved complete clinical response under radiology and were still alive, the other 19 patients underwent resection. The R0 resection rate was 94.7% (18/19). The pCR rate was 63.2% (12/19) and the MPR rate was 78.9% (15/19). During neoadjuvant treatment, 8 patients had a grade 3 or worse adverse event including leukopenia (33.3%, 7/21, Grade 3), esophagitis (4.8%, 1/21, Grade 3) and anemia (4.8%, 1/20, Grade 4). One patient developed grade 4 postoperative complication (5.3%, 1/19, pneumonia) and died within 90 days of surgery due to COVID-19. Grade 1-2 postoperative complications occurred in 21.1% (4/19) patients, including anastomotic fistula (21.1%, 4/19), chylothorax (5.3%, 1/19) and pneumonia (10.5%, 2/19). Conclusions: Preliminary results showed that neoadjuvant chemoradiotherapy (nCRT) combined with sequential tislelizumab showed promising outcomes and well tolerated for resectable ESCC patients. Further larger prospective studies are needed to confirm such findings.
A comparative study of double track anastomosis and tubular esophagogastric anastomosis in laparoscopic radical proximal gastrectomy for upper gastric carcinoma.
Authors: Wei Meng , Yu Wenbin , Yan Zepeng
Published: July 2024

e16117

Background: For the upper gastric cancer, especially adenocarcinoma at the esophagogastric junction, the optimal surgical method is still controversial. The purpose of the study is to evaluate the safety and clinical effect of double track (DT) anastomosis in laparoscopic radical proximal gastrectomy (LRPG). Methods: A retrospective analysis was conducted involving 243 patients who underwent LRPG in the Department of Gastrointestinal Surgery, Qilu Hospital of Shandong University from Jan. 2017 to Dec. 2020. Patients were divided into tubular esophagogastric (TG) anastomosis group and double track (DT) anastomosis group, according to the digestive tract reconstruction. Their intraoperative conditions, perioperative recovery and postoperative follow-up were compared. Patients were divided into ≥60 and < 60 groups according to age, to analysis the pros and cons of the two surgical methods in different age groups. According to whether or not indocyanine green (ICG) tracer technology was used during the operation, DT group was also divided into ICG group and non-ICG group. Results: Compared with the TG group, the DT group had less volume of gastric tube drainage, shorter gastric tube drainage time and proton pump inhibitors application time, and lower reuse rate of proton pump inhibitors. However, the DT group had more total operation time and lymph node dissection time. The median follow-up time of the patients was 36.0 months. At the end of study, the 1-year OS rate and DFS rate were 94.2% and 92.6% in the TG group and 95.8% and 93.7% in the DT group. The 3-year OS rate and DFS rate were 90.2% and 85.2% in the TG group and 91.9% and 87.7% in the DT group. And there was no significant difference in survival outcomes between the two groups. The DT group had a lower anastomotic stenosis at 3rd month after surgery. Moreover, the incidence of reflux esophagitis and Gerd Q score in the DT group were lower compared with the TG group at 3rd month, 1st year and 3rd year after surgery. In addition, elderly patients had a higher incidence of short-term complications in DT group compared with TG group. In the ICG analysis, the ICG DT group had significantly shorter total operation time and lymph node dissection time, less intraoperative blood loss and more lymph nodes obtained compared with the non-ICG DT group. Conclusions: DT anastomosis is a safe and effective way in LRPG for upper gastric carcinoma. Although the operation time of it is longer than that of TG anastomosis, it has a better anti-reflux effect and reduces the incidence of dysphagia and anastomotic stenosis. In elderly patients, it is important to minimize operative time and better to use TG anastomosis. The application of ICG tracer technique in LRPG has positive significance.
LncRNA EGOT and tumorigenesis via Hedgehog pathway in gastric cancer.
Authors: Ji Wenlong , Yang Zhaolong , Zhao Kun , Feng Jifeng , He Xia , Zhou Guoren , Peng Wei
Published: July 2024

e16130

Background: Gastric cancer (GC) is one of the mostly terminal malignancies with poor prognosis. Long noncoding RNA EGOT (EGOT) acts as a crucial regulator in the breast cancer. However, the function of EGOT in GC remains unknown. Methods: This work was to explore the clinical value and biological significance of EGOT in GC. EGOT levels in GC tissue and cell were analyzed by qRT–PCR. After knockdown of EGOT, GC cell growth and cycle progression were detected. Results: The expression of EGOTwas observably elevated in GC. Upregulation of EGOT was related with lymphatic metastasis and TNM stage. In addition, knockdown of EGOT by siRNA could significantly inhibit GC cell proliferation and arrest cycle progression in G1 phase. Moreover, EGOT mediated cyclin D1 expression in GC cells which was regulated by Hedgehog pathway. Further, loss of EGOT downregulated Hedgehog signaling pathway in GC cells. Conclusions: EGOT functions as an oncogene in GC, and may be useful as a conceivable diagnostic and prognostic biomarker for GC tumorigenesis.
Efficacy and safety of donafenib combined with anti-PD-1 antibodies for initially unresectable hepatocellular carcinoma (HCC): A retrospective real-world study.
Authors: Liu Sulai , Zhou Shuyi , Song Yinghui , Liu Jianming , Guo Chao , Yang Pingzhou , Li Ou , Yi Weimin , Peng Chuang
Published: July 2024

e16131

Background: Given its clear efficacy and high safety demonstrated in the phase 3 ZGDH3 study, donafenib has been recommended by the Chinese guidelines for the first-line treatment of unresectable hepatocellular carcinoma (uHCC). Recently, combination therapies have shown favorable results. However, the clinical experience of donafenib combined with anti-PD-1 therapy for uHCC has not yet been investigated. Thus, we aimed to investigate the efficacy and safety of donafenib combined with anti-PD-1 antibody in the treatment of uHCC. Methods: A single-center, retrospective study was performed based on the medical records of consecutive patients diagnosed with HCC who were not suitable for curative surgery at Hunan Provincial People's Hospital from July 2021 to September 2023. Patient with ≥18 years, no prior systemic therapy, having at least one measurable lesion (per mRECIST) were enrolled. Patients were treated with donafenib and anti-PD-1 antibodies until disease progression or unacceptable toxicity, local treatment such as TACE, HAIC or ablation were allowed. The primary endpoint was progression-free survival (PFS) by mRecist criteria, and secondary endpoints included overall survival (OS), objective response rate (ORR) and disease control rate (DCR) by mRecist criteria, and safety. The last follow-up time was December 15, 2023. Results: In total, 48 patients were enrolled: 87.5% males, median age 59.5 years (range, 32.0-78.0), 95.8% ECOG of 0, 68.8% HBV positive, 14.6% BCLC stage B, 75.0% BCLC stage C, 47.9% baseline AFP≥400 ng/mL, 70.8% with macrovascular invasion. Among them, 9 patients (18.8%) received donafenib combined with anti-PD-1 antibody as first-line treatment, 37 (77.1%) with concurrent TACE(n = 25) or HAIC(n = 6) or both as treatment(n = 6), 2 (4.2%) received ablation treatment. At the time of data cut-off, the median follow-up time was 10.0 months (95% CI, 6.37-12.2). Considering efficacy, 9 pts (18.7%) achieved complete response, 20 (41.7%) achieved partial response, 17 (35.4%) had stable disease, and 2(4.2%) had progressive disease. The ORR and DCR were 60.4% and 95.8% by mRecist, respectively. Median progression-free survival was 15.8 months (95% CI, 8.9-NA). Median overall survival was not reached, 12-month OS rate were 90.7% (95% CI:73.7%-96.9%). In terms of safety, 44 pts (91.7%) had TRAEs. The incidence of ≥grade 3 TRAEs was 33.3% (16/48). Common TRAEs included elevated AST(45.8%), hand-foot syndrome (39.6%), decreased platelet count(35.4%),elevated ALT(31.2%), rash (25.0%) and decreased white blood cell count (14.6%). Grade 3/4 TRAEs included elevated AST(10.4%), elevated ALT(8.3%), rash(8.3%) and hand-foot syndrome (8.3%). No grade 5 TRAEs were observed. Conclusions: Donafenib combined with anti-PD-1 antibodies shows promising efficacy and manageable toxicity in patients with initially uHCC.
Hepatocellular carcinoma etiology drives survival outcomes: A population-based analysis.
Authors: Cranford Hannah M. , Jones Patricia Denise , Liu Qinran , Koru-Sengul Tulay , Reis Isildinha M. , Pinheiro Paulo S.
Published: July 2024

e16142

Background: Previous studies on survival differences according to etiology of hepatocellular carcinoma (HCC) (5-year observed survival of 23%) are limited to hospital-based series and restricted cohorts. We performed a population-based survival analysis by major HCC etiologies, inclusive of hepatitis-C virus (HCV), hepatitis-B virus (HBV), alcohol-related liver disease (ALD), and non-alcoholic fatty liver disease (NAFLD) as singular causes, in addition to unexplored dual etiological groups, (HCV&HBV, HCV&ALD, and HBV&ALD), and accounting for age at diagnosis, tumor characteristics, and socio-demographics. Methods: All 19,956 cases of HCC diagnosed in Florida during 2005–2018 from the Florida cancer registry were linked for HCC etiology using Agency for Healthcare Administration and Florida Department of Health viral hepatitis data. Survival analysis was performed for the 15,759 linked HCC cases, comparing HCC etiologic groups (4 single and 3 dual). Results included age-adjusted 5-year survival, Kaplan-Meier curves, and adjusted hazard ratios from Cox regression models. Results: The leading single etiology was ‘HCV only’ (n=4,983; 31.6%); the leading dual etiology was ‘HCV&ALD’ (n=2,694; 17.1%). The age-adjusted 5-year survival was low (<22%) across all HCC etiologies; however, non-ALD causes showed higher survival [‘HCV only’ (21.5%; 95%CI:20.2%–22.8%), ‘HBV only’ (20.2%; 95%CI:16.6%–23.9%), ‘NAFLD only’ (19.9%; 95%CI:18.7%–21.2%)] than ALD-related etiologies [‘ALD only’ (14.4%; 95%CI:12.7%–16.0%), ‘HCV&ALD’ (10.4%; 95%CI:9.0%–11.9%), ‘HBV&ALD’ (8.1%; 95%CI:2.2%–14.1%)]. Compared to the reference category ‘HCV only,’ age-adjusted hazard ratios were 1.69 (95%CI: 1.41–2.03; p-value<0.0001) for ‘HBV&ALD,’ 1.33 (95%CI:1.26–1.40; p-value<0.0001) for ‘HCV&ALD,’ and 1.35 (95%CI:1.28–1.43; p-value<0.0001) for ‘ALD only.’ Multivariable analysis including additional factors showed minimal variation from these results. Conclusions: Significant differences in survival based on HCC etiology are important for prevention, surveillance, and targeted treatments based on etiologic-specific biomarkers. Specific pathophysiological mechanisms for ALD in addition to viral hepatitis could be responsible for poorer outcomes for dual etiologies involving alcohol use, compared to viral etiology alone. To increase overall survival, improved screening is needed for patients with multiple HCC risk factors. [Table: see text]
Comparing the efficacy and safety of TACE combined with donafenib or lenvatinib in the treatment of unresectable hepatocellular carcinoma.
Authors: Wei Ning , Lu Dong , Zhou Chunze , Cheng Delei , Zhang Zhengfeng , Zhang Xingming , Xiao Jingkun , Lv Weifu
Published: July 2024

e16153

Background: For unresectable Intermediate/Advanced-Stage Hepatocellular Carcinoma (uHCC), the efficacy of TACE monotherapy has been unsatisfactory. Studies have shown that TACE combined with molecular targeted drugs exhibits potential synergistic effects, which can prolong the overall survival (OS) of uHCC patients (pts). Donafenib and lenvatinib are small molecule targeted drugs approved as first-line treatments for HCC. The aim of this study is to evaluate the efficacy and safety of TACE combined with donafenib or lenvatinib in the treatment of uHCC. Methods: A retrospective analysis was conducted on the clinical data of uHCC pts treated with donafenib combined with TACE (Dona-TACE) or lenvatinib combined with TACE (Lenva-TACE) at The First Affiliated Hospital of USTC from January 2018 to October 2022. The OS, progression free survival (PFS), objective response rate (ORR), and disease control rate (DCR) of two groups of pts were evaluated according to the mRECIST, and the incidence of adverse events (AEs) was evaluated using CTCAE 5.0. Pts with complete baseline information and at least one follow-up evaluation were incorporated in the final analysis. Results: A total of 105 pts treated with donafenib and 59 pts treated with lenvatinib met the study criteria. After matching with a 1:1 propensity score, 35 pts in the Dona-TACE group and 35 pts in the Lenva-TACE group were included in this study. The baseline characteristics of the two groups are similar (males, 85.7% vs. 85.7%; ECOG PS of 1, 74.3% vs. 71.4%; Exceeding up-to-seven criteria, 74.3% vs. 62.9%; BCLC stage C, 42.9% vs. 40.0%; Combination immunotherapy, 62.9% vs. 54.3%). There was no significant difference in median OS (29.0 vs. 27.3m, P = 0.748) and median PFS (10.5 vs. 10.3m, P = 0.869) in the Dona-TACE and Lenva-TACE groups. The ORR (85.7% vs. 74.3%, P = 0.969) and DCR (94.3% vs. 97.1%, P = 0.280) of the Dona-TACE and Lenva-TACE group were equivalent. Compared with the Lenva-TACE group, pts in the Dona-TACE group had a lower incidence of grade 3-4 adverse events (any grade, 94.3% vs. 91.4%; grade 3 or 4, 34.3% vs. 57.1%, P < 0.05). Among them, pts in the Dona-TACE group had a lower incidence of proteinuria (any grade, 22.9% vs 42.9%; grade 3 or 4, 0 vs17.1%, P < 0.05) and hypertension (any grade, 42.9% vs 71.4%; grade 3 or 4, 2.9% vs 25.7%, P < 0.05) than those in the Lenva-TACE group. Multivariate analysis showed that ECOG PS score, up-to-seven criteria, and tumor blood supply were independent prognostic factors affecting OS (HR, 3.470, 3.619, 3.067; P < 0.05). Conclusions: The efficacy of donafenib and lenvatinib combined with TACE in the treatment of uHCC is equivalent. Furthermore, compared to lenvatinib combined with TACE, donafenib combined with TACE has higher safety.
Changing treatment patterns for hepatocellular carcinoma: A SEER-Medicare study.
Authors: Iheanacho Franklin , Tramontano Angela , Abrams Thomas Adam , Manz Christopher
Published: July 2024

e16166

Background: Sorafenib was the first systemic therapy approved in 2005 for hepatocellular carcinoma (HCC), then 9 new therapies were approved between 2017-2022. No studies have evaluated treatment patterns of systemic therapy since these therapies became available. Methods: This retrospective cohort study used SEER-Medicare data to identify patients with a new diagnosis of HCC between 2014-2019 and associated comorbidity and treatment claims through 2020. Patients had continuous coverage with Medicare Parts A/B/D from 3 months before diagnosis to the earlier of 3 years, death or censoring. We excluded deaths reported by death certificate or autopsy. We used claims to identify receipt of local therapies (ablation, transplant, resection, transarterial bland/chemo/radioembolization, external/stereotactic radiation, brachytherapy) and all FDA-approved systemic therapies for HCC. We described cohort characteristics, treatment patterns, and overall survival (OS) and used Chi-squared statistics to compare treatment patterns and OS for patients diagnosed between 2014-17 vs 2018-19. Results: 11,799 patients were included (69.2% male, 76.9% White, median age: 71 years, 36.2% NAFLD, 44.1% Hepatitis C, 10.6% Hepatitis B, 28.1% alcoholic liver disease). Within one year of diagnosis, 76.3% of all patients received any local or systemic treatment, which did not change over time (2014-17: 76.1%, 2018-19: 76.6%, p=0.60). Receipt of local therapy within 1 year was unchanged (2014-17: 73%, 2018-19: 73.2%, p=0.77) and there were no clinically significant changes in treatment rates for specific local therapies. Receipt of systemic therapy in the first year decreased slightly (2014-17: 16.97%, 2018-19: 15.2%, p=0.012). First line systemic treatment changed drastically: 83.7% of patients diagnosed in 2014-17 received first-line sorafenib vs only 40.1% of those diagnosed 2018-19 (Table). Median overall survival for patients receiving no treatment, systemic therapies first or local therapies first was 1.9, 11 and 16.3 months, respectively. Among patients receiving systemic therapy first, survival from initiation of first line treatment increased from 9.1 to 11.2 months for patients diagnosed in 2014-17 vs 2018-19 (p= <.0001). Conclusions: While overall local and systemic treatment rates have not changed substantially, more recent patients with HCC are more likely to receive first-line novel therapies over first-line sorafenib and associated survival has modestly increased. [Table: see text]
The safety of atezolizumab plus bevacizumab (atezo/bev) treatment in Chinese patients (pts) with hepatocellular carcinoma (HCC) with active hepatitis B virus (HBV) infection: Results from the TALENTop study.
Authors: Zhu Xiao-Dong , Sun Hui-Chuan , Shen Feng , Bai Xueli , Chen Minshan , Huang Zhiyong , Song Tianqiang , Zeng Yongyi , Kuang Ming , Xiang Bangde , Liu Lianxin , Li Deyu , Wen Tianfu , Chen Yongjun , Peng Tao , Li Xiangcheng , Zhou Jian , Fan Jia
Published: July 2024

e16168

Background: HCC pts with active HBV infection were excluded from most clinical trials involving immune checkpoint inhibitors because of safety concerns. We are aiming to evaluate the treatment safety of atezo/bev treatment in the TALENTop study (NCT04649489) which enrolled a large number of pts with active HBV infection. Methods: The TALENTop study is to clarify whether liver resection may provide additional benefits in Chinese HCC pts with macrovascular invasion who responded to conversion therapy with atezo/bev. After two versions of protocol modification, pts with active HBV infection were allowed. This study is ongoing, and the primary analysis is expected later. The current analysis is to evaluate treatment safety in pts with active HBV infection in the induction phase when pts received 3 cycles of atezo/bev and 1 cycle of atezo monotherapy. We compared the adverse events (AEs) between pts with active (baseline serum HBV-DNA ≥500 IU/mL) or inactive HBV infection (HBV-DNA < 500 IU/mL). All pts with detectable HBV-DNA or positive hepatitis B surface antigen received oral antiviral therapy throughout the study. Results: From Apr 2021 to Sep 2023, 296 pts were enrolled and completed induction phase therapy of atezo/bev. 274 pts (92.6%) had HBV-related HCC, and 133 pts (44.9%) had active HBV infection. The baseline characteristics were mainly balanced between groups, except pts with active HBV infection were younger (52 vs 56 years, P = 0.024), had larger tumor size (the diameter of target lesion 88.3 vs 78.1 mm, P = 0.007), and had higher album-bilirubin score (-2.62 vs -2.80, P < 0.001). In the induction phase, the AEs of any grade were higher in pts with active HBV infection (88.0% vs 73.6%, P = 0.002). However, the grade ≥3 AEs (20.3% vs 17.8%, P = 0.584), grade ≥3 treatment-related AEs (12.0% vs 12.3%, P = 0.950) and serious AEs (15.0% vs 13.5%, P = 0.706) were comparable between pts with active and inactive HBV infection. Additionally, the incidence of liver-related AEs was also comparable, including increased AST (17.3% vs 16.0%), increased ALT (17.3% vs 14.7%), and increased bilirubin (10.5% vs 12.9%). AEs leading to treatment withdrawal were also comparable (6.0% vs 6.1%, P = 0.966). In pts with active HBV infection, 20.8% remained serum HBV-DNA ≥500 IU/mL at the end of cycle 4. Conclusions: Active HBV infection did not compromise the safety of atezo/bev therapy. These findings could support that, with concurrent use of oral antiviral therapy, pts with active HBV infection should be not excluded from clinical trials or delayed for immunotherapy. Clinical trial information: NCT04649489 .