bluuebunny/crossref_metadata_2025 huggingface dataset:
351. INVESTIGATING THE IMPACT OF INDUCTION CHEMOTHERAPY FOR ESOPHAGEAL ADENOCARCINOMA ON THE GUT MICROBIOME
Authors: Aiyar Niharikaa , Allen Jonathan , Akhter Akhi , Rispoli Thiaine , Kulikova Maria , Shathasivam Premalatha , Wilson Gavin , Darling Gail , Coburn Bryan , Yeung Jonathan
Published: August 2023

Background

Esophageal adenocarcinoma (EAC) is a highly heterogeneous cancer with a current five-year survival rate of ~18%. To improve outcomes, understanding factors impacting treatment response is imperative. Gut microbiome signatures are one such factor and have been associated with response to immunotherapy and survival in several solid cancers. Thus, we aim to identify variations in gut microbiome signatures at different stages of treatment and elucidate the link of these signatures to treatment responses and patient outcomes.

Methods

Fecal samples were collected from 50 patients prior to induction and 18 during or post induction and stored at −20 ̊C before extracting DNA using the QIAamp DNA Mini Kit. Extracted DNA was quantified and 16S gene expression was confirmed by qPCR using primers targeting the V3-V4 region of the 16S gene, following which 16S rRNA sequencing was performed.

FastQC, MultiQC and Cut Adapt were used for quality control of sequence data before assembly with vsearch. The resulting data was processed following the deblur pipeline. Taxonomy was assigned using Qiime2 classift-hybrid-vsearch-sklean function. Statistical comparison of diversity was conducted in R.

Results

Species diversity within individual samples, the alpha diversity, showed no significant difference between baseline and post-induction samples. Likewise, the comparison of diversity between samples, the beta diversity, showed no significant clustering on baseline compared to post-induction.

On the genus level, there was no significant statistical difference between the normalized counts of individual genera shared between baseline and post-induction samples.

Conclusion

These preliminary results suggest that induction therapy has minimal impact upon species richness of the gut microbiome when compared to baseline as measured by fecal microbiome. Future directions of this project include examining the gut microbiome at further stages of treatment and investigating the microbiome of the tumour itself.
364. A CASE OF SEVERE REFRACTORY MASSIVE MASTOID ASCITES AFTER THORACIC DUCT LIGATION FOR POSTOPERATIVE MASTOIDECTOMY
Authors: Ken Ito , Takashi Kamei , Motohisa Hagiwara , Masahiro Chin , Yasuyuki Hara , Eiji Hashizume
Published: August 2023

The patient, a male in his 70s, was referred to our hospital after an upper gastrointestinal endoscopy revealed esophageal cancer. After a close examination, he was diagnosed with esophageal squamous cell carcinoma T3, N2, M0, Stage III. After preoperative chemotherapy, he underwent thoracoscopic esophagectomy and gastric tube reconstruction. Intraoperatively, the thoracic duct was injured on the cranial side of the aortic arch and was ligated with a clip. When tube feeding was started postoperatively, a pleural effusion was observed, and the patient was treated with central venous nutrition. The effusion did not improve, so thoracoscopic surgery was performed on the postoperative day 12, and the thoracic duct was ligated just above the diaphragm. Postoperatively, the patient developed ascites in addition to pleural effusion, and continued to totally drain 3000 mL of thoracoabdominal fluid every day. Lymphangiography showed that lymphatic flow was interrupted at the site of thoracic duct ligation, but the site of leakage was unknown. Based on previous reports, octreotide 300 μg and etilefrine 100 mg was administered continuously, and pleural drainage decreased, and ascites drainage increased. Ascites volume exceeded 3000 mL in three days and was treated with a single puncture, but no improvement was observed. Tolvaptan 3.75 mg was started, and ascites decreased gradually. Patient’s general condition improved with nutrition and rehabilitation, and he was discharged on the day 189. We report a very rare case of refractory massive ascites following thoracic duct ligation for postoperative chylothorax, along with a discussion of the relevant literature.
380. INTEGRATIVE TRANSCRIPTOMIC AND FUNCTIONAL ANALYSIS OF CHEMOTHERAPY RESISTANCE IN ESOPHAGEAL ADENOCARCINOMA
Authors: Kong Mingyang (Iris) , Pal Sanjima , Qian Qiu , Tai Kulsum , Osman Nathan , Berube Julie , Bourdeau France , Zeng Wotan , Giannias Betty , Huang Sui , Bailey Swneke , Sangwan Veena , Bertos Nick , Ferri Lorenzo
Published: August 2023

Background

Gastroesophageal Adenocarcinoma (GEA) is one of the most lethal malignancies in North America with a 5-year survival of <20%. Currently, the standard-of-care treatment for GEA patients is docetaxel-based triplet chemotherapy. However, around 40% of patients are innately resistant to chemotherapy, and half of the initial responders develop acquired resistance during treatment. There is an urgent need to understand the molecular mechanisms driving chemotherapy resistance and identify alternative therapeutic options.

Methods

Primary tumor tissue was collected from 29 GEA patients to generate patient-derived organoids (PDOs). PDOs were treated with chemotherapy, and the cell viability was measured using Cell Titer Glo. A 3200-compound library was screened at a single concentration (1uM) on three chemo-resistant PDOs. Compounds that showed efficacy in all three lines were then tested in combination with chemotherapy to evaluate their synergistic effects. Single-cell RNA sequencing (scRNA) was performed for 8 chemo-sensitive and 16 chemo-resistant patients. We conducted a transcriptomic analysis to identify markers that are differentially expressed in the two groups. Pathway analysis was performed using Gene Set Enrichment Analysis.

Results

Cell viability of the PDOs obtained from chemo-resistant patients was significantly higher than that of chemo-sensitive patients. High-throughput (HTP) screening revealed 21 drugs that showed efficacy in all three PDOs, including inhibitors for ribosomes, oxidative phosphorylation (OXPHOS) pathway, and NFkB pathway. Correspondingly, scRNA analysis indicated that chemo-resistant patients have up-regulated ribosome biosynthesis and OXPHOS pathways, as well as increased expression of CCND1, which is a downstream target of the NFkB pathway. Furthermore, the IGF1R inhibitor Ceritinib demonstrated a significant synergistic effect when combined with chemotherapy, with a synergy score of 19.9.

Conclusions

GEA organoids recapitulate the chemotherapy response of patients, making them an ideal model for ex-vivo drug testing. Integrative analysis of the HTP functional screening and scRNA sequencing data revealed ribosome biogenesis, OXPHOS pathway and IGF-1R as potential therapeutic targets to overcome chemoresistance in GEA.
385. HOSPITAL COSTS OF POSTOPERATIVE ADVERSE EVENTS FOLLOWING ESOPHAGECTOMY: RESULTS FROM 10 CANADIAN INSTITUTIONS
Authors: Jones Daniel , Anstee Caitlin , Gingrich Molly , Yasufuku Kazuhiro , Malthaner Richard , Safieddine Najib , Finley Christian , Kidane Biniam , French Danny , Ferri Lorenzo , Graham Andrew , Seely Andrew
Published: August 2023

Background

Surgical resection plays a central role in the multimodal curative intent management of esophageal cancer. Despite advances in peri-operative care, 60% of patients undergoing esophagectomy experience postoperative adverse events (AEs), if AEs are prospectively collected by surgeons. We recently performed a systematic review documenting the published index hospital costs of AEs, yet the overall costs of AEs in Canadian esophageal centres remains unknown.

Methods

Between 2017–2021, prospectively collected data from 10 Canadian esophageal centres were included. Volumes of esophagectomy, incidence of postoperative AEs (anastomotic leak (AL), pneumonia, respiratory failure), graded using the Ottawa TM&M system [ottawatmm.org], and obtained from 2 Canadian Association of Thoracic Surgeons (CATS) National Positive Deviance Seminars were included. Using literature-derived index hospitalization costs of AEs, estimates of annual costs were obtained (2023 Cdn$).

Results

Data from 795 esophagectomies performed in Canada between 2017–2019 revealed an average AL rate of 15% (8.7–22%). This led to an estimated yearly hospital cost of $6.63 M. Additional data from 863 esophagectomies performed between 2018–2021 revealed an average yearly pneumonia rate of 10.2% (2.4–20.3%)., with an estimated cost of $1.44 M, and respiratory failure (requiring ICU admission) of 7.8% (0–13.8%), with an estimated cost of $1.83 M. When all 10 centres are combined, these 3 AEs equate to over $9.9 M in hospital expenditures/year. A 1% reduction/year in the 3 AEs would lead to a cost-savings of $816,738.

Conclusion

Our analysis of only 3 post-operative AEs highlights the staggering costs to hospitals across Canada individually, and collectively, and emphasizes the need to support value-based QI research. Direct financial support from hospitals to support value-based QI in esophageal surgery has the potential to simultaneously improve care and provide valuable cost savings.
428. PHARYNGEAL SQUAMOUS CELL CARCINOMA AND RISK OF LATER ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Elbe Peter , Ekheden Isabella , Vujasinovic Miroslav , Maret-Ouda John , Marsk Elin , Thuresson Marcus , Roelstraete Björn , Ye Weimin , Ludvigsson Jonas F
Published: August 2023

Introduction

Pharyngeal squamous cell carcinoma is a known risk factor for later squamous cell carcinoma of the esophagus. We investigated whether the risk of esophageal carcinoma is high enough to justify routine gastroscopy surveillance in a northern European population. If the risk among patients with pharyngeal carcinoma corresponds to the risk among patients with Barretts esophagus of developing adenocarcinoma, it could justify surveillance.

Method

Histopathology data from pharyngeal and esophageal biopsies obtained 1980–2016 in Sweden’s 28 pathology departments were linked to national population-based healthcare registers. We calculated a subdistribution hazard ratio (HR) comparing the risk of esophageal cancer and death in patients with pharyngeal carcinoma to a matched general population.

Result

In total 1399 patients with pharyngeal cancer were identified. 344 were excluded due to age under 18 years, previous esophageal cancer, death or cancer within 6 months of diagnosis. Thus, 1055 patients remained. Median follow up time was 5,1 years. 78% were men and median age at diagnosis of pharyngeal cancer was 64 years. Four (0.38%) patients developed esophageal squamous cell carcinoma during follow-up, equal to 1 in 263 patients (HR = 14,32; 95%CI = 1,55-132,30). 855 of the patients (81%) died during follow-up (HR = 7,65; 95% = 6,82-8,59).

Discussion

The yearly risk of developing esophageal squamous cell carcinoma was 0,07%, which is lower than the risk among patients with Barretts esophagus. Therefore, we find no support for long-term endoscopic surveillance among patients with pharyngeal cancer.
475. CROSS X FLOT: WHICH ONE HAS LESS COMPLICATIONS?
Authors: Bianchi Edno Tales , Galleti Ricardo , Lucas Phellipe Fabbrini Santos , Reginaldo Tales Barione , Tustumi Francisco , Souza Jorge , Namur Guilherme , Azevedo Beatriz , Kruger Jaime
Published: August 2023

Background

Today there are 2 main neoadjuvant schemes for the treatment of esophageal tumors: CROSS and FLOT. There are still no data in the literature to categorically state which one is associated with greater complications and mortality and whether there is an impact on the quality of the lymphadenectomy.

We demonstrate our comparative data from each group undergoing curative treatment of esophageal tumor, along with associated complications and number of dissected lymph nodes at a single institution during the Covid-19 pandemic.

Methods

A retrospective analysis of 56 patients who underwent curative treatment of esophageal tumor by minimally invasive esophagectomy was carried out. The squamous cell carcinoma group (SCCG) were composed by 28 subjects and of these 23 underwent CROSS, denominated CROSS group (CG). 27 were in the adenocarcinoma of the esophagogastric junction group (AdG) and of these, 23 underwent FLOT, denominated FLOT group (FG).

Complications, in-hospital and 90-day mortality were analyzed, as well as the quality of lymphadenectomy and response to neoadjuvant treatment and compared between groups.

Results

Toxicity complication during preoperative treatment was 3 (10%) in the CG and 8 (28%) in the FG (p < 0.05).

Post-operatory complications was seen 11 in the SCCG (3 pulmonary, 5 fistulas—1 death) and 10 in the AdG (2 pulmonary, 4 fistulas—2 deaths). When analyzing the groups submitted to neoadjuvant therapy (23 FLOT x 23 CROSS), the same number of 8 (34%) were identified with no difference in Clavien-Dindo scale severity.(p > 0,05).

The mean of lymphonodes dissected were similar between 2 groups (27,01 ± 8). Complete response was 13% in FG and 21% in CG with 3 patients (13%) with ypt0n +.

Conclusion

The group submitted to CROSS had a greater tolerance during the preoperative treatment. There was no difference in the number of complications related to the neoadjuvant scheme, as well as the quality of the lymphadenectomy, suggesting that the treatment can be individualized for each patient.
480. ANTIREFLUX SURGERY’S LIFESPAN: 20 YEARS AFTER LAPAROSCOPIC FUNDOPLICATION
Authors: Vittori Arianna , Salvador Renato , Capovilla Giovanni , Riccio Federica , Nezi Giulia , Forattini Francesca , Provenzano Luca , Nicolett Loredana , Moletta Lucia , Costantini Andrea , Valmasoni Michele , Costantini Mario
Published: August 2023

Background

Laparoscopic Fundoplication (LF) is the surgical technique of choice for treating GERD, but only few studies report a follow-up beyond 15 years. The aim was to evaluate the results at least 20 years after laparoscopic fundoplication at a single national referral center for esophageal diseases.

Methods

We prospectively collected data on a cohort of consecutive patients who underwent LF between 1992–2001. Patients were divided into two groups: a GERD group (patients with pathological esophageal acid exposure and hiatal hernias <3 cm) and a large hiatal hernia (HH) group (patients having type I > 3 cm and types II-IV hiatal hernias). Patients were followed up for at least 20 years using endoscopy, barium-swallow, esophageal manometry, and pH monitoring. LF was defined failed in case of: GERD symptom recurrence (SS > 10); recurrence of esophagitis; HH recurrence or slipped-fundoplication; pathological pH-monitoring; BE progression or adenocarcinoma onset.

Results

The study population consisted of 142 patients: 112 in the GERD group and 30 in the HH group. The characteristics of patients are shown on Figure 1. Conversion to open surgery proved necessary in 8 patients (5.6%). At a median follow-up of 22 years, 80.4% of the GERD patients and 63.3% of the HH patients were failure-free. Revisional surgery was necessary in 14 (9.8%) patients (9 GERD and 5 HH patients); indications were dysphagia (5 cases), slipped fundoplication or hernia recurrence (6 cases), abnormal pH-monitoring or esophagitis resistant to medical therapy (2 cases), and telescoping (one case). Two decades after LARS, 87.6% of GERD patients and 76.7% of HH patients were satisfied with the procedure.

Conclusions

The present study concerns one of the largest populations of patients who had undergone LF to have been followed up for more than 20 years at a single center. The findings showed that laparoscopic antireflux surgery is effective and durable (for >20 years) in patients with uncomplicated GERD and, to a lesser extent, in those with a large hiatal hernia. The satisfaction rate more than 20 years after surgery almost reached 90% in the GERD group.
482. SECOND-LINE OF CAMRELIZUMAB PLUS NIMOTUZUMAB IN ADVANCED ESOPHAGEAL SQUAMOUS CELL CARCINOMA (ESCC): A SINGLE-ARM, OPEN-LABEL, PHASE 2 TRIAL
Authors: Xia Jin , Meng Xiangrui , Ji Yinghua , Yang Xiuli , Hong Yonggui , Wang Junsheng , Cui Donghai , Wang Feng
Published: August 2023

Background

Anti-PD-1 antibody camrelizumab monotherapy is recommended for the treatment of advanced second-line ESCC. However, the long-term survival is limited, and new effective treatments are needed. Epidermal growth factor receptor (EGFR) is usually over-expressed in more than 50% of ESCC patients(pts), and is a potential target for the treatment of ESCC. Our study aimed to assess the efficacy and safety of combination with camrelizumab and nimotuzumab (EGFR inhibitor) as second-line treatment for advanced ESCC.

Methods

This ongoing phase II trial in four sites in China enrolled pts aged 18–75 with unresectable locally advanced, locally recurrent, or metastatic ESCC that progressed or were intolerant after first-line treatment, and ECOG PS score of 0–1. Pts received 200 mg intravenous camrelizumab (Q2W) plus 400 mg intravenous nimotuzumab (QW) in 4-week cycles until disease progression, unacceptable adverse events (AEs) or withdrawal of consent. The primary endpoint was investigator-assessed objective response rate (ORR), overall survival (OS). Secondary endpoints included disease control rate (DCR), progression-free survival (PFS).

Results

From 2/2021 to 4/2023, 28 of the planned 42 pts with an average 63 years old had been enrolled, including 18 (64%) males and 21 (75%) patients with an ECOG PS score of 1. Nine pts had previously used anti-PD-1/PD-L1 antibody. Among the 21 evaluable pts, 8 pts achieved partial response (PR), 13 pts stable disease (SD), illustrating an ORR of 38.0% and a DCR of 100%. Median PFS was not reached. 82.1% pts experienced adverse event(AE), with 21.4% being grade ≥ 3. The most frequent AE were RCCEP (57.1%), neutrophil count decreased (17.8%), white blood cell decreased (14.2%).

Conclusions

Camrelizumab plus nimotuzumab demonstrated encouraging clinical efficacy and acceptable safety as second-line treatment, and might be a favorable option for pts with advanced ESCC. The study enrollment is ongoing, and further survival and safety data will be reported in the future. Clinical trial information: NCT03766178.
485. MATTHEW EFFECT OF NEOADJUVANT THERAPY IN ESOPHAGEAL CANCER
Authors: Liu Yixin , Yang Yushang , Chen Longqi
Published: August 2023

Carcinoma.

Background

Neoadjuvant therapy benefits long-term survival to patients with locally advanced Esophageal Squamous Cell Carcinoma (ESCC). If the survival benefit brought by neoadjuvant therapy is considered as a positive improvement for majority patients, outweighing the negative harms, it means that some patients will experience a reduction in survival due to the negative harms, just as the Matthew effect. This study focuses on these failures of Matthew effect who may not benefit from neoadjuvant therapy and explores the specific recurrent patterns.

Method

A total of 457 recurrent ESCC patients undergoing curative esophagectomy were enrolled, including 140 patients treated with neoadjuvant therapy. The median progression time (MPT) were 24.3 months. Tumor recurrences or metastases occurring before MPT were defined as treatment failure. We retrospectively investigated the patterns of recurrence and the prognosis in patients with neoadjuvant therapy.

Results

Among recurrent patients, locoregional recurrence, lung and bone metastases were the most common recurrence sites. The median progression time to the first recurrence was 24.3 months. The locoregional recurrence rate of neoadjuvant group was lower than that of none-adjuvant group (46% vs 60.2%), while the liver and brain metastasis rates was higher (16% vs 7.5% and 8.1% vs 3.3% respectively). Kaplan–Meier analysis showed unsatisfactory prognosis for neoadjuvant therapy failures than those without neoadjuvant therapy. Moreover, for non-neoadjuvant ESCC, shorter overall survival was found in distant recurrence failures than those with locoregional recurrence, while the different recurrence patterns shared similar prognosis for neoadjuvant therapy failures.

Conclusion

For treatment failure patients with early progression, neoadjuvant therapy has an advantage in controlling local recurrence, but this positive improvement does not transform into survival benefits, indicating Matthew effect of neoadjuvant therapy in ESCC.
491. VITAMIN B12 DEFICIENCY AFTER ONCOLOGICAL ESOPHAGECTOMY AND GASTRECTOMY
Authors: Sallakhi Aria , Baumgartl Isabella Alexandra , Andresen Julian Ramin , Khater Hagar , Gibas Georg , Medibach Amadea , Marolt Cordula , Radlspöck Wolfgang , Zacherl Johannes
Published: August 2023

Vitamin B12 deficiency is common in patients with resections of the upper digestive tract and must be expected during follow-up examinations. While esophagectomy with gastric pull-ups preserve the duodenal passage and a large part of the stomach, (sub)total gastrectomies result in significant losses of gastric tissue and the common Y-Roux reconstruction bypasses the duodenal passage.

This is a monocentric, retrospective, descriptive analysis of prospectively collected follow-up data. Between January 2015 and December 2019, 232 patients underwent an oncological (sub)total gastrectomy or esophagectomy.

After applying the exclusion criteria (patient below 18, primary bone marrow disease, hereditary forms of anemia, postoperative tumor recurrence, R1/R2 situation), 157 patients remained for analysis: 103 patients (=66%) with esophagectomy (ER) and 54 (=34%) with (sub)total gastrectomy (SGE). Vitamin B12 levels were analyzed three, six, twelve, 18, and 24 months after the surgery. Prophylactic intramuscular vitamin B12 substitution (Erycytol 1 mg depot) was routinely prescribed quarterly only in patients with a total gastrectomy.

After 3 postoperative months the incidence of vitamin B12 deficiency were 24% in the ER group vs. 5% (p = 0,064) in the SGE group; 17% vs. 10% (p = 0.4) after 6 months; 8% vs. 5% (p = 0.65) after 1 year; 10% vs. 10% (p = 0.83) after 18 months, and 12.5% vs. 39% (p = 0.022) after 2 years. The resulted incidence of hyperchromic macrocytic anemia is furtherly discussed in the abstract entitled ‘Types and incidence of postoperative anemia after oncological esophageal and gastric resections’. Comparing the total gastrectomy versus subtotal gastrectomy subgroups, patients with a subtotal gastrectomy have higher vitamin B12 deficiency incidences throughout the 24-month follow-up period.

The human body physiologically provide a sufficient vitamin B12 storage for minimum 6–9 months. The high incidence of vitamin B12 deficiency in the ER group in the first 6 postoperative months might be due to a pre-existing vitamin B12 deficiency.

After the 6th postoperative month there is an approximation between the Vitamin B12 deficiency incidences of ER and (S)GE patients. In the final 2-year follow-up, the incidence of vitamin B12 deficiency was significantly higher in the (S)GE group.
492. TYPES AND INCIDENCE OF POSTOPERATIVE ANEMIA AFTER ONCOLOGICAL ESOPHAGECTOMY AND GASTRECTOMY
Authors: Sallakhi Aria , Baumgartl Isabella Alexandra , Andresen Julian Ramin , Khater Hagar , Gibas Georg , Medibach Amadea , Marolt Cordula , Radlspöck Wolfgang , Zacherl Johannes
Published: August 2023

According to current literature, anemias that develop after oncological esophageal and gastric resections are classified as deficiency anemias. Due to the surgery-related changes in the mechanical and biochemical conditions of the upper gastrointestinal tract, there is an alteration in the processing and absorption of hematopoietic-relevant vitamins and trace elements like iron, vitamin B6, vitamin B12, folic acid, copper and essential amino acids in the postoperative phase.

Between January 2015 and December 2019, 232 patients underwent a (sub)total gastrectomy or esophagectomy at our center. In this monocentric retrospective analysis of prospectively collected follow-up data, 157 patients were included after applying the exclusion criteria: Age below 18, primary bone marrow disease, hereditary forms of anemia, postoperative tumor recurrence and R1/R2 situation. 103 patients (=66%) belonged to the esophagectomy group and 54 patients (=34%) to the (sub)total gastrectomy group. Preoperatively and three, six, twelve, 18, and 24 months postoperatively the following laboratory parameters were collected and descriptively analyzed: Hemoglobin, MCV, MCH, serum iron, ferritin, transferrin, and vitamin B12.

Two years after the oncological resection 28% of patients with esophagectomy, EE, and 48% of patients with (sub)total gastric resection, (S)GE, show anemia. Normocytic anemia was the dominant type. The MCV distribution of anemic patients in the EE group was as follows: 3% microcytic, 77% normocytic, and 20% macrocytic. The anemic patients in the (S)GE group show the following MCV distribution: 16% microcytic, 81% normocytic, and 3% macrocytic. The (S)GE collective has more anemic patients in percentage terms than the EE collective throughout the whole follow-up period. This difference is significant at the 12th (p = 0.032) and 18th-month (p = 0.023) postoperative follow-up.

A high percentage of patients with oncological resection of the upper gastrointestinal tract have a relevant postoperative anemia. The known postoperative iron and vitamin deficiencies, that would be associated with microcytic hypochromic and macrocytic hyperchromic anemia, are not the relevant causes for this anemia as it is predominantly a normocytic form. Normocytic anemia is an indication for an anemia of chronic disease. The reason for the predominance of normocytic anemia is not specifically known.
Efficacy and Safety of Approximately 3 Years of Continuous Ozanimod in Moderately to Severely Active Ulcerative Colitis: Interim Analysis of the True North Open-label Extension
Authors: Danese Silvio , Panaccione Remo , Abreu Maria T , Rubin David T , Ghosh Subrata , Dignass Axel , Afzali Anita , Wolf Douglas C , Chiorean Michael V , Vermeire Severine , Jain Anjali , Charles Lorna , Lawlor Garrett , Osterman Mark T , Wu Hsiuanlin , Canavan James B , Petersen AnnKatrin , Colombel Jean-Frederic , Regueiro Miguel
Published: August 2023

Backgrounds and Aims

This interim analysis from the True North open-label extension [OLE] study examines efficacy and safety of approximately 3 years of continuous ozanimod treatment in patients with moderately to severely active ulcerative colitis.

Methods

Clinical responders after 52 weeks of ozanimod during the phase 3 True North study, who continued treatment in the OLE, were evaluated. Efficacy, including endoscopic and histological endpoints, was assessed during the OLE for approximately 2 additional years through OLE Week 94, using observed case [OC] and nonresponder imputation [NRI] analyses. Adverse events were monitored from True North baseline through OLE data cutoff and expressed as exposure-adjusted incidence rates.

Results

This analysis included 131 patients; 54% had achieved corticosteroid-free remission at True North Week 52. In OC analyses, clinical response, clinical remission, and corticosteroid-free remission were achieved by 91.4%, 69.1%, and 67.9% of patients, respectively, at OLE Week 94 [146 weeks of total treatment]. Similarly, endoscopic improvement, histological remission, and mucosal healing were achieved by 73.3%, 67.3%, and 56.3% of patients, respectively, at OLE Week 94. Efficacy rates were lower using NRI analyses, but maintenance of efficacy was demonstrated through OLE Week 94. No new safety signals emerged from this analysis. Serious infections, malignancy, cardiovascular events, and hepatic events occurred infrequently.

Conclusions

Among patients who achieved clinical response after 1 year of ozanimod treatment during True North, a high percentage sustained clinical and mucosal efficacy over 2 additional years in the OLE. No new safety signals were observed with long-term ozanimod use.
Radial artery occlusion after coronary angiography with trans radial access: a nurse led study employing duplex ultrasonography and the reverse Barbeau test
Authors: Johansson Ulrika , Isaksen Kjetil , Dalen Ingvild , Larsen Alf Inge
Published: August 2023

Aims

Trans-radial access (TRA) is the recommended approach for coronary angiography and percutaneous coronary intervention (PCI). Radial artery occlusion (RAO) is the most common complication. We examined the incidence of RAO by means of duplex ultrasonography (DUSG) and the reverse Barbeau test (RBT), after TRA in a clinical setting using conventional pressure dressings to achieve haemostasis. All radial artery patency examinations were performed by one dedicated nurse after a brief training course, we assessed the feasibility and quality of this routine in regular clinical practice.

Methods and results

In total 97 patients undergoing first-time coronary angiograph and in some cases, PCI via TRA completed the study. Conventional pressure dressing as means of haemostasis was used. Radial artery patency was examined by DUSG and by RBT, before and at follow-up 1 month after the procedure. An inter- and intra-observer validation of the ultrasound measurements was performed before inclusion. Two cases of RAO (2.1%) were discovered following TRA. All RAO cases were detected by both DUSG and the RBT. Results from the inter-observer validation showed no statistically significant discrepancy between an experienced physician and a newly trained nurse operator (P = 0.403). An intraclass correlation coefficient (ICC) was calculated at 0.89 indicating excellent reproducibility.

Conclusion

In a high-volume TRA centre, we found a low incidence of RAO using conventional pressure dressing as means of haemostasis. The easy-to-use RBT detected all cases of RAO. Following a short course of training, a nurse from the cardiac catheterization laboratory was able to perform high quality DUSG examinations of the radial artery to assess patency.
Genetic and transcriptomic dissection of host defense to Goss's bacterial wilt and leaf blight of maize
Authors: Hao Yangfan , Hu Ying , Jaqueth Jennifer , Lin Jinguang , He Cheng , Lin Guifang , Zhao Mingxia , Ren Jie , Tamang Tej Man , Park Sunghun , Robertson Alison E , White Frank F , Fu Junjie , Li Bailin , Liu Sanzhen
Published: August 2023

Goss's wilt, caused by the Gram-positive actinobacterium Clavibacter nebraskensis, is an important bacterial disease of maize. The molecular and genetic mechanisms of resistance to the bacterium, or, in general, Gram-positive bacteria causing plant diseases, remain poorly understood. Here, we examined the genetic basis of Goss's wilt through differential gene expression, standard genome-wide association mapping (GWAS), extreme phenotype (XP) GWAS using highly resistant (R) and highly susceptible (S) lines, and quantitative trait locus (QTL) mapping using 3 bi-parental populations, identifying 11 disease association loci. Three loci were validated using near-isogenic lines or recombinant inbred lines. Our analysis indicates that Goss's wilt resistance is highly complex and major resistance genes are not commonly present. RNA sequencing of samples separately pooled from R and S lines with or without bacterial inoculation was performed, enabling identification of common and differential gene responses in R and S lines. Based on expression, in both R and S lines, the photosynthesis pathway was silenced upon infection, while stress-responsive pathways and phytohormone pathways, namely, abscisic acid, auxin, ethylene, jasmonate, and gibberellin, were markedly activated. In addition, 65 genes showed differential responses (up- or down-regulated) to infection in R and S lines. Combining genetic mapping and transcriptional data, individual candidate genes conferring Goss's wilt resistance were identified. Collectively, aspects of the genetic architecture of Goss's wilt resistance were revealed, providing foundational data for mechanistic studies.
Essential Cases: Land Law
Authors: Nair Aruna
Published: August 2023

Essential Cases: Land Law provides a bridge between course textbooks and key case judgments. Essential Cases provides you with succinct summaries of some of the landmark and most influential cases in land law. Each summary begins with a review of the main case facts and decisions. The summary is then concluded with expert commentary on the case from the author, Aruna Nair, including her assessment of the wider questions raised by the decision.
Jones & Sufrin's EU Competition Law
Authors: Sufrin Brenda , Dunne Niamh , Jones Alison
Published: August 2023

EU Competition Law: Text, Cases, and Materials provides a complete guide to European competition law in a single authoritative volume. Carefully selected extracts from key cases, academic articles, and statutory materials are accompanied by in-depth author commentary from three experienced academics in the field. Thorough footnoting and referencing give a tour of the available literature, making this an ideal text and stand-alone resource for undergraduate and postgraduate students, as well as for competition law scholars engaged in specialised study. This eighth edition has been fully updated with detailed coverage and commentary on recent developments. These include contemporary concerns about the objectives, interpretation, and application of competition law in the light of sustainability imperatives including the EU’s Green Deal, worldwide economic and political upheaval stemming in particular from the Covid-19 pandemic and the war in Ukraine, and continuing developments in the digital economy; the EU Courts’ judgments on Articles 101, 102, and mergers including Intel (RENV), Google and Alphabet, Google (Android), Slovak Telekom, Generics, Lundbeck, and CK Telecoms; cases on the Commission’s enforcement powers and judicial review, including Sped-Pro and Slovak Telekom; new legislation, guidelines, and notices (in final form or draft) on vertical agreements, horizontal agreements, and market definition; Commission actions in the pharmaceutical, energy, and financial sectors, including interaction with regulatory rules, liberalisation programmes, and intellectual property law; private litigation in the wake of the directive on damages, including the Court’s judgments in Sumal and Paccar; and thorough discussion of ongoing developments in competition law such as the Commission’s enforcement policy against cartels, the appraisal of mergers, the use of commitments decisions, the use of comfort letters during Covid-19 and the Commission’s revised notice on informal guidance, and the increasing activity by national competition authorities. The eighth edition contains an entirely new chapter on the digital economy, including detailed coverage of the Digital Markets Act.
1. Introduction to Competition Law
Authors: Jones Alison , Sufrin Brenda , Dunne Niamh
Published: August 2023

This chapter provides an introduction to, and basis for, the material discussed in the subsequent chapters and sets competition law in its economic and political context. It introduces some relevant concepts of microeconomics including demand curves, consumer and producer surplus, elasticity of demand, and economies of scale and scope. It discusses the model of perfect competition and the concepts of allocative, productive, and dynamic efficiency; the problems in competition terms of monopoly and oligopoly; and the concept of welfare, particularly consumer welfare. It considers various schools of competition analysis and theories and concepts relevant to competition law. It discusses the possible objectives of competition law, and particularly considers the objectives of EU competition law. The chapter also looks at US antitrust law; competition law and regulation; and outlines the law on State aid. It introduces the problem of the application of EU competition law to the digital economy (dealt with in full in Chapter 16).
2. The Competition Law and Institutions of the European Union
Authors: Jones Alison , Sufrin Brenda , Dunne Niamh
Published: August 2023

This chapter sketches the history and functions of the EU and its institutions in order to set the EU competition rules in context. It then describes the competition provisions themselves and outlines the way in which the rules are applied and enforced, including the public enforcement of Articles 101 and 102 under Regulation 1/2003, the control of mergers with a European dimension under Regulation 139/2004, public enforcement by the national competition authorities of the Member States, and the role of private enforcement. It discusses the position and powers of the European Commission, particularly the role of the Competition Directorate General (DG Comp); the powers of the EU Courts; the significance of fundamental rights and the general principles of EU law in competition cases; the application of competition rules to particular sectors of the economy; and the application of the EU rules to the EEA.
16. EU Competition Law and Policy in the Digital Economy
Authors: Jones Alison , Sufrin Brenda , Dunne Niamh
Published: August 2023

This chapter considers the application of the EU competition rules specifically within the digital economy. It considers: the competition dynamics that typically arise in digital markets; examples of competition enforcement in digital markets at EU level to date; and some of the enforcement challenges that arise, including the limited scope of application of the EU competition rules, the prevalence of novel or controversial theories of harm, and the speed of intervention and effectiveness of remedies that can be imposed. The chapter also explores efforts to augment the ordinary competition law framework in the digital context. In particular, it considers the provisions and implications of the Digital Markets Act, which imposes a series of prescriptive ex ante obligations on large digital gatekeepers.
Poole's Textbook on Contract Law
Authors: Merkin KC Robert , Saintier Séverine
Published: August 2023

Course-focused and comprehensive, Poole’s Textbook on Contract Law provides an accessible overview of the key areas on the law curriculum. This book has been guiding students through contract law for many years. It places the law of contract clearly within its wider context, including the growing distinction between commercial and consumer contracting, before proceeding to provide detailed yet accessible treatment of all the key areas encountered when studying contract law. Part 1 considers formation, looking in detail at agreement, certainty and agreement mistakes, the enforceability of promises and the intention to be legally bound. Part 2 looks at content, interpretation, exemption clauses and unfair terms, performance, and breach. Part 3 considers the enforcement of contractual obligations, including remedies, detailed treatment of damages for breach of contract, privity and third party rights, and discharge by frustration. Part 4 looks at methods of policing the making of a contract, such as non-agreement mistakes which render the contract void, misrepresentation, duress, undue influence, unconscionable bargains, and illegality. The book also includes references to relevant EU consumer legislation and introduces students to the various attempts (international and European) to produce a harmonized set of contract principles.
Smith, Hogan and Ormerod's Essentials of Criminal Law
Authors: Child John , Ormerod David
Published: August 2023

Smith, Hogan, and Ormerod’s Essentials of Criminal Law presents a clear and authoritative discussion of the criminal law, combining authority with supportive learning features. The book engages with all the key topics of criminal law on the typical LLB syllabus, whilst encouraging the development of analytical and assessment skills. Particular attention is paid to student assessment, with end-of-chapter sections offering advice on how to approach essay and problem questions. Short learning and assessment tips are provided throughout the chapters. Key cases are highlighted across chapters which include brief summaries of the main facts and judgment. Each chapter includes a section on reform, introducing important academic criticism of the law.
Mayson, French, and Ryan on Company Law
Authors: French Derek
Published: August 2023

Mayson, French & Ryan on Company Law looks at all aspects of current UK company law. The 38th edition continues the tradition of providing accurate technical detail, examination of theory, and quotations from key cases. The volume starts with an overview of the topic. Next it looks at the establishment of companies. It moves on to consider finance which includes an examination of shares, accounts, loans, market abuse, capital and borrowing. The next part of the text considers governance. It looks at shareholders, directors, duties of directors, company secretaries and auditors, remedies and acting for a company. The last part of the text examines insolvency and liquidation.
Company Law Concentrate
Authors: Roach Lee
Published: August 2023

Each Concentrate revision guide is packed with essential information, key cases, revision tips, exam Q&As, and more. Concentrates show you what to expect in a law exam, what examiners are looking for, and how to achieve extra marks. Company Law Concentrate helps readers to consolidate knowledge in this area of law. This seventh edition has been fully updated and includes coverage of the Economic Crime and Corporate Transparency Bill/Act 2023, the Law Commission’s review of corporate criminal liability, and the Corporate Insolvency and Governance Act 2023. Case law updates include BTI 2014 LLV v Sequana SA [2022], Okpabi v Royal Dutch Shell plc [2021], Sevilleja v Marex Financial Ltd [2020], and WM Morrison Supermarkets plc v Various Claimants [2020]. Chapters examine business structures, incorporation, the constitution of the company, directors, members, corporate governance, capital and capital maintenance issues, members’ remedies, and corporate rescue and liquidation.
Examining Strategies among Veterans Affairs Outpatient Social Workers to Facilitate Job Retention and Emotional Well-Being during the COVID-19 Pandemic
Authors: Kranke Derrick , Solorzano Emily , Weber Stephani , Gioia Debbie , Dobalian Aram
Published: August 2023

The social work profession is dealing with an increased rate of turnover, due largely in part to the pandemic. A recent study showed that U.S. Department of Veterans Affairs (VA) inpatient social workers utilized strategies of “emotional preparedness” to retain their job during the pandemic. The aim of this current study is to explore if outpatient social workers utilized similar strategies for their own job retention. There may be differences in the strategies utilized because outpatient and inpatient social workers tend to work in different environments. In this qualitative study, authors conducted interviews with (N = 13) outpatient social workers from a VA site in the Southwestern region of the United States. Findings were analyzed thematically. Authors conducted open coding and applied a priori themes/strategies from extant research among VA inpatient social workers. Most of the a priori themes/strategies were prevalent among outpatient social workers, and two emerging themes were (1) acknowledging shared trauma and (2) human connection to overcome isolation. Strategies of emotional preparedness should be implemented on a grander scale to facilitate job retention since there is an expected deficit in the social work workforce until at least 2030.
Statistical characterization of the chordal product determinant of Grassmannian codes
Authors: Álvarez-Vizoso Javier , Beltrán Carlos , Cuevas Diego , Santamaría Ignacio , Tuček Vít , Peters Gunnar
Published: August 2023

We consider the chordal product determinant, a measure of the distance between two subspaces of the same dimension. In information theory, collections of elements in the complex Grassmannian are searched with the property that their pairwise chordal products are as large as possible. We characterize this function from an statistical perspective, which allows us to obtain bounds for the minimal chordal product and related energy of such collections.
Asphericity of Cubical Presentations: The 2-Dimensional Case
Authors: Arenas Macarena
Published: August 2023

We show that under suitable hypotheses, the second homotopy group of the coned-off space associated to a $C(9)$ cubical presentation is trivial, and use this to provide classifying spaces for proper actions for the fundamental groups of many quotients of square complexes admitting such cubical presentations. When the cubical presentations satisfy a condition analogous to requiring that the relators in a group presentation are not proper powers, we conclude that the corresponding coned-off space is aspherical.
Assessing the effectiveness of imidacloprid and thiamethoxam via root irrigation against Megalurothrips usitatus (Thysanoptera: Thripidae) and its residual effects on cowpea
Authors: Yu Xiao-Rui , Tariq Talha , Guo Ling-Hang , Wu Sheng-Yong , Tang Liang-De , Zang Lian-Sheng
Published: August 2023

Systemic neonicotinoid insecticides (NEOs) applied by seed-treatment or root application have emerged as a prevalent strategy for early-season insect pest management. This research investigated the effectiveness of imidacloprid and thiamethoxam, administered through root irrigation, in managing thrips in cowpea [Vigna unguiculata (Linn.) Walp.], and the residual properties of both insecticides in cowpea and soil. The results show that thrips density depends on the application rate of insecticides. At the maximum application rate (1,500 µg/ml, active ingredient), imidacloprid and thiamethoxam controlled thrips densities below the economic injury level (EIL, the EIL of thrips on cowpea was 7/flower) for 20 days and 25 days with the density of 6.90 and 6.93/flower at the end of the periods, respectively. Imidacloprid and thiamethoxam residues decreased gradually over time and decreased sharply after 15 days after treatment (DAT), the 2 insecticides were not detected (<0.001 mg/kg) at 45 DAT. According to our findings, the application of imidacloprid and thiamethoxam via root irrigation proved residual control lasting up to 20–25 days for controlling thrips damage at experimental rates, with a strong association to their residual presence in cowpea (0.6223 < R2 < 0.9545). Considering the persistence of the imidacloprid and thiamethoxam, the maximum tested application rate (1,500 µg/ml) was recommended. As the residues of imidacloprid and thiamethoxam were undetectable in cowpea pods at all tested rates, it may be suggested that the use of each insecticide is safe for consumers and effective against thrips, and could be considered for integrated thrips management in the cowpea ecosystem.
Molecular mechanism of Enterococcus faecalis-induced phosphine sensitivity in Tribolium castaneum (Coleoptera: Tenebrionidae)
Authors: Wang Zhengyan , Hu Haisheng , Chang Zhenzhen , Zhang Shan , Lu Yujie
Published: August 2023

Tribolium castaneum (Herbst) (Coleoptera: Tenebrionidae) has developed extensive resistance to the fumigant phosphine. Knowledge of the resistance mechanisms offers insight into resistance management. Although several studies have highlighted the positive or negative impacts of symbiotic microbiota on host pesticide resistance, little is known about the association between gut symbionts and host phosphine resistance. To reveal the effect of the gut bacterium, Enterococcus faecalis (Andrewes & Horder) (Lactobacillales: Enterococcaceae), on host phosphine resistance and its underlying mechanism, we investigated mortality, fitness, redox responses, and immune responses of adult T. castaneum when challenged with E. faecalis inoculation and/or phosphine exposure. When T. castaneum was exposed to phosphine, E. faecalis inoculation decreased its survival and female fecundity and aggravated its oxidative stress. Furthermore, E. faecalis inoculation suppressed the expression and activity of superoxide dismutase, catalase, and peroxidase in phosphine-exposed T. castaneum. Enterococcus faecalis inoculation also triggered excessive host immune responses, including the immune deficiency signaling pathway and the dual oxidase-reactive oxygen species system. These findings suggest that E. faecalis likely modulates host phosphine resistance by interfering with the redox system. This provides information for examining the symbiotic function in the insect-microorganism relationship and new avenues for pesticide resistance management.