bluuebunny/crossref_metadata_2025 huggingface dataset:
748. CAUSES, TREATMENT AND OUTCOMES OF CONDUIT NECROSIS FOLLOWING OESOPHAGECTOMY: A SINGLE CENTRE RETROSPECTIVE STUDY
Authors: Tankel James , Amin Samir , Katz Amit , Dehghani Mehrnoush , Sakalla Ms Rawan , Cools-Lartigue Jonathan , Spicer Jonathan , Najmeh Sara , Mueller Carmen , Ferri Lorenzo
Published: September 2024

Background

Conduit necrosis (CN) following esophagectomy is a poorly described entity associated with high morbidity and mortality. Identifying factors associated with CN would help stratify patients at risk of this devastating complication. Furthermore, describing the outcomes of various treatment options may aid in personalising treatment to maximise the chance of recovery. The aim of this study was to describe the causes, treatment and outcomes of CN following esophagectomy.

Methodology

Between 01/2006 and 12/2023, a single centre retrospective review of a prospectively maintained comprehensive oesophageal cancer surgical database was performed. Complications data from the online Canadian Thoracic Surgery Quality Improvement Program was also utilized. All patients with oesophageal and junctional cancer who underwent transthoracic en bloc surgical resection were included. Defined as circumferential ischaemia of the neo-esophageal conduit identified on postoperative endoscopy, patients with CN were identified. Clinical and demographic data of these patients was compared to those with no documented history of conduit complications. The treatment and outcomes of CN were also recorded.

Results

Anastomotic leak occurred in 146/1043 patients (14.0%), CN in 39 (3.7%) and tracheo-oesophageal fistula in 7 (0.7%). Compared to the 853 patients without conduit complications, CN was associated with BMI >34.5kg/m2 (3/39 vs 15/853,p = 0.03), proximal lesions (5/39,12.9% vs 23/853,2.7%, p = 0.002) and McKeown oesophagogastrectomy (13/39,33.3% vs 125/853,14.7%, p=<0.001). Initially, endoscopic treatment, anastomotic refashioning, taking down the conduit and oesophagostomy was used in 14, 13, 8 and 4 patients (35.9%,33.3%,20.5% and 10.3%) with success rates of 7/14(50.0%), 6/13(46.2%), 4/8(50.0%), and 3/4(75.0%) respectively. The 90-day mortality of CN was 10.9% and associated with a prolonged hospital admission (median 46 vs 12 days, p=<0.001)

Conclusion

CN is an uncommon entity but associated with high morbidity, mortality and prolonged postoperative length of stay. Treatment decisions remain complex and whilst endoscopic management seems feasible, re-intervention is often required. Further understanding of how to improve salvage treatment in this unique cohort of patients is required.
770. CLOSURE OF OESOPHAGEAL DEFECTS USING THE VACSTENT DEVICE: INITIAL INSIGHTS FROM THE LARGEST UK CASE SERIES
Authors: Aslam Nasar , Gertner Julian , Maguire Joshua , Duku Margaret , Thorpe Sally , Mohammadi Borzoueh , Dawas Khaled , Ahmed Omer , Banks Matthew , Graham David , Qureshi Yassar , Sweis Rami , Sehgal Vinay
Published: September 2024

Introduction

Oesophageal defects are associated with poor morbidity and mortality and often require prolonged hospitalisation and artificial nutrition. Existing endoscopic treatment modalities exhibit limitations. Covered stents are associated with a migration rate of up to 50% and closure with endoscopic clips is limited to simple defects. Vacuum therapy is a well understood and established surgical therapy to promote wound healing. Endoscopic Vacuum Therapy (EVT) utilises these principles in the management of transmural oesophageal defects. The VACstent GITM (MicroTech) is a novel device which synergistically incorporates the advantages of a fully covered oesophageal stent while concurrently employing EVT. This approach seals the defect while mitigating against stent migration through the vacuum effect. Luminal patency is also maintained which helps to preserve nutritional independence. Accelerated healing and enhanced nutrition are thought to help reduce morbidity and enhance patient quality of life.

Methods

This single-centre prospective case series describes outcomes for patients with transmural oesophageal defects treated with the VACstent GITM device.

All procedures were performed with propofol sedation and fluoroscopic guidance. The VACstent GITM was exchanged every 5-7 days until endoscopic closure. A contrast study was used to confirm closure after which oral nutrition was restarted.

The primary outcome was clinical success, defined as the endoscopic and radiological evidence of defect closure. Secondary outcomes included number of stent exchanges, technical success, and the adverse event (AE) rate.

Results

The VACstent GITM device was used for seven patients between October 2023 and February 2024. Four patients had anastomotic leaks with three having iatrogenic perforations. The mean patient age was 60 (± 19.3) years with 57% of the patient cohort being male. The clinical success rate was 86% with a technical success rate of 100% and a median defect closure time of 13 (± 6.6) days. A median number of 1 stent exchanges was required. The median defect size was 8mm (± 6.2). There were no reported AEs. All patients were able to successfully come of artificial nutrition.

Conclusion

This case series illustrates the safety and efficacy of the VACstent for the treatment of a heterogenous group of oesophageal defects. To our knowledge this represents the largest series in a cohort of patients from the United Kingdom. Larger scale comparative studies incorporating a more diverse patient cohort will further clarify the potential of the VACstent device in reducing the necessity for major surgical interventions in this complex and challenging patient population. It will also help to refine future treatment algorithms for oesophageal defect management.
771. EVOLUTION OF THE SURGICAL MANAGEMENT OF OESOPHAGEAL PERFORATION
Authors: Johnson Mary Ann , Read Matthew
Published: September 2024

Background

Oesophageal perforations historically have been managed with open trans-thoracic operations. With the increasing experience of minimally invasive procedures, we have performed a case series of trans-hiatal repairs for oesophageal perforations. Our unit has maintained a prospective database of oesophageal perforations since 2014.

Methods

Retrospective review of outcomes of open trans-thoracic operation to laparoscopic trans-hiatal oesophageal perforation repairs.

Results

From 80 patients, our database demonstrates an evolution in the treatment of oesophageal perforations from open thoracotomy to either endoscopic intervention (20) or trans-hiatal repair (12).

Conclusion

Laparoscopic Trans-hiatal oesophageal Repair is comparable and feasible in carefully selected patients (a video recording of the repair will be part of the presentation)
793. MODIFIED HELLER DOR FOR ACHALASIA
Authors: Lisboa Fernando , Ferreira Luis Fernando , Diniz Gabriel
Published: September 2024

Introduction

Achalasia is an esophageal disorder that involves a failure in the relaxation of the lower esophageal sphincter, which leads to dysphagia and other symptoms. The objective of the present study is to report the surgical technique performed in a patient with achalasia, in which the Heller myotomy technique was performed together with Dor fundoplication.

Method

The technique performed was a modified Heller-Dor with long myotomy Surgical intervention began with the introduction of the trocars plus pneumoperitoneum, a narrow of distal esohagus and enlargement of the diaphragmatic crura, mas found. Continuing with dissection of the esophageal hiatus with ultrasonic forceps, release of phreno-esophageal membrane. The esophagus was elongated in the mediastinum and brought 7 centimeters to the abdomen. After that, there was approximation of the diaphragmatic crura with 1 point of Ethibond 2-0. Following the dissection of the eophagogastric junction and identification of the posterior and anterior vagus nerve, releasing the “fat pad” for correct identification of the esophagogastric junction. So, the myotomy in the esophagus 6 centimeters above the cardia and 3 centimeters below, was performed. Follow, the gastric fundus was sutured to the anterior border of the esophagus and left diaphragmatic pillar with 2-0 Ethibond, until the esophagus gastric junction in running suture. The anterior suture, covering the myotomy the edge of the muscular layer of the esophagus as the same way.

Conclusion

Finally, with regard to the treatment of achalasia, Heller cardiomyotomy plus Dor fundoplication, has been shown to be efficient for improvement of dysphagia symptoms and to avoid symptoms related to emergence of reflux after myotomy.

https://drive.google.com/file/d/176L7Jo0tFMylWvhsgtscESHHFbOONl4A/view?usp=sharing
795. REVIEW OF CLINICAL CHARACTERISTICS AND PROGNOSIS OF MULTIPLE PRIMARY ESOPHAGEAL SQUAMOUS CELL CARCINOMA
Authors: Wenyi Liu , Yu Zhentao
Published: September 2024

Background

Multiple Primary Esophageal Squamous Cell Carcinoma (MPESCC) is a rare and highly aggressive type of tumor, classified into Synchronous Multiple Primary Esophageal Squamous Cell Carcinoma (S-MPESCC) and Metachronous Multiple Primary Esophageal Squamous Cell Carcinoma (M-MPESCC). MPESCC has garnered increasing attention in recent years due to its complex pathogenesis, poor prognosis, and unclear treatment protocols. Compared to solitary esophageal squamous cell carcinoma (SESCC), patients with MPESCC typically show higher rates of lymph node and distant metastasis, leading to a poorer prognosis. This review aims to summarize the clinical characteristics, common treatment methods, and prognosis of MPESCC by analyzing existing literature, providing references for clinical practice.

Methods

The clinical characteristics of MPESCC patients differ significantly from those of SESCC patients, relevant literature was collected for meta-analysis of the following data of the patients: Gender and Age, Medical History, Pathological Features, Lymph Node and Distant Metastasis, Tumor Distribution. Treatment Methods include Surgical Treatment, Radiotherapy and Chemotherapy. Postoperative recurrence and metastasis are also included in the statistics.

Results

Tumors in MPESCC patients exhibit significant differences in pathological staging and grading, which makes treatment more challenging. Patients with MPESCC have significantly higher rates of lymph node and distant metastasis compared to those with SESCC. MPESCC tumors can appear in multiple locations within the esophagus, with pathological characteristics that may vary between sites. Surgery remains the primary treatment method for MPESCC. Due to the high risk of recurrence and metastasis in MPESCC patients, regular endoscopic and imaging examinations are necessary postoperatively to detect and address any recurrent or new tumors early.

Conclusion

MPESCC is a complex type of esophageal cancer with a poor prognosis. It’s clinical characteristics and treatment strategies differ significantly from those of SESCC. Multidisciplinary comprehensive treatment and close postoperative follow-up are crucial for improving the prognosis of patients with MPESCC. Further research is needed to optimize treatment protocols and enhance patient survival rates.
805. BOCHDALEK HERNIA - CASE REPORT
Authors: Lisboa Fernando , Ferreira Luis Fernando , Diniz Gabriel , Alves Emerson
Published: September 2024

Introduction

Bochdalek hernia is a rare type of diaphragmatic hernia congenital and is quite uncommon in adulthood, representing only 0.17-6% of all diaphragmatic hernias.

The objective of the present study is to report the technique surgery performed on a patient with a bochdalek hernia.

Methods

The information was obtained through medical record review, interview with the patient and literature review.

Results/Discussion

A 49-year-old female patient was admitted to a hospital in Natal (RN- Brazil) with vomiting for seven months, average of 3-4 vomits daily after meals, associated with dysphagia, epigastric pain and weight loss of 26 kg during this period.

The physical examination, she was dehydrated, emaciated and with a flaccid abdomen and painless. Laboratory exams, she presented high levels of ureia and hypokalemia. CT scan of the chest and abdomen with contrast showed a hernia right posterolateral diaphragm with insinuation of the transverse colon and portion distal part of the stomach, in addition to significant gastric stasis, without signs of ischemia.

Vigorous hydration was carried out and fasting was maintained, in addition, was inserted nasogastric tube and began parenteral nutrition. After ten days of parenteral nutrition and correction of hydro electrolyte disorders, there was an improvement in symptoms with laboratory normalization. So, she undergo a surgical intervention by videolaparoscopy.

Surgical intervention took place with the pneumoperitoneum with Veress needle and trocars inserted (2 10-inch trocars). mm and 3 of 5 mm). Introduction of 30° optics. Cavity inventory identified massive right posterolateral diaphragmatic hernia, containing transverse colon and part of the stomach. Hepatic retractor was positioned to retracted the right hepatic lobe.

Completely reduced the hernia through the Bochdalek foramen, after undoing content adhesions with the diaphragm. Afterwards, the closing of the defect with 2-0 Ethibond thread and a biocompatible mesh placed over the suture (Phasix) 10x10 cm and fixed with the same thread in separate stitches. Left drain blake type number 24 Fr, was left in the right hemithorax. The procedure was done uneventful.

Conclusions

Bochdalek hernia is a structural defect in the diaphragm, which can cause the passage of practically any intra-abdominal organ to the chest. Surgical repair of the defect is the only existing treatment option.

In this case, we have a late presentation and in a complicated form.

We opted for clinical stabilization of the patient, with nutrition and timely videolaparoscopy on the tenth day of hospitalization. The correction of hernia laparoscopically allows wide access to the workplace and with good mobility for dissection of the hernial sac, in addition to unquestionable acceleration of postoperative recovery and reduction of surgical trauma and size of the incisions. This way, we have a shorter hospitalization time with early return to the patient's daily activities.
813. SELF-DILATATION FOR THE MANAGEMENT OF REFRACTORY BENIGN OESOPHAGEAL STRICTURES: OUTCOMES FROM THE LARGEST EUROPEAN TERTIARY CENTRE EXPERIENCE TO DATE
Authors: Ioannidis Giannis , Pilavaki Pampina , Basra Ruman , Gertner Julian , Aslam Nasar , Duku Margaret , Thorpe Sally , Haidry Rehan , Ahmad Omer , Sweis Rami , Graham David , Banks Matthew , Lovat Laurence , Sehgal Vinay
Published: September 2024

Background

Benign oesophageal strictures are commonly encountered in endoscopy and are often effectively managed with endoscopic dilatation. However, up to 40% of patients may develop refractory benign oesophageal strictures (RBES), necessitating frequent endoscopic interventions that are often challenging, pose a greater risk of complications, and negatively impact quality of life. Oesophageal self-dilatation (SD) offers an alternative treatment that potentially reduces the need for repeat hospital visits while allowing patients greater autonomy in managing their condition. We describe the efficacy and safety of oesophageal SD at a tertiary referral centre.

Methods

We retrospectively reviewed the electronic records of patients with RBES (n=43) who were referred for SD to our centre between 2013 and 2024. The primary outcomes were the endoscopic dilatation-free interval (EDFI; longest period of time patients did not require endoscopic dilatation) and the number of endoscopic procedures performed within 12 months of starting SD. Secondary outcomes included the technical success rate of learning SD, improvement in the Dakkak and Bennett dysphagia score, and complications. Results are reported as median (interquartile range).

Results

41/43 patients (median age 57 years) with various RBES aetiologies (32% peptic, 19.5% post-radiation, 12% post-surgical, 11.6% post-endoscopic resection, 24.9% other) and locations (24.4% proximal, 29.3% middle, 34.1% lower, 12.2% multi-segment) successfully learned SD. Median follow-up was 23.2 months. The EDFI increased from 68.5 (41-106) to 161 (121-279) days (P<0.001) while endoscopic interventions decreased from 7 (4.7-10) to 1 (0.75-3) (P<0.001) within 12 months before and after SD. The all-time EDFI was 405 days (130-705) and dysphagia score improved from 2 at baseline to 0 after SD. One patient experienced clinically significant haematemesis and one presumed SD-related oesophageal perforation.

Conclusion

To our knowledge, we have described the largest European case series of oesophageal SD that has been published to date. Oesophageal SD appears to be an effective, well-tolerated, and safe approach in managing often complex patients with RBES providing a viable alternative to conventional endoscopic interventions. However, the occurrence of adverse events highlights the importance of careful patient selection and ongoing monitoring. Further research is warranted to validate these findings and identify predictive factors for treatment success.
Surgical treatment of chronic aortic dissection with liver dysfunction due to constrictive pericarditis caused by IgG4-related disease: a case report
Authors: Shimada Akie , Yamamoto Taira , Dohi Shizuyuki , Endo Daisuke , Tabata Minoru
Published: September 2024

Background

Severe liver failure with ascites may be associated with cardiac disease and may be the primary manifestation of constrictive pericarditis or aortic dissection. We report a case of a patient with a chief complaint of ascites for whom close examination revealed that the liver injury was attributed to constrictive pericarditis and chronic aortic dissection, with immunoglobulin G4 (IgG4)-related disease (IgG4-RD) as the primary cause.

Case summary

A 72-year-old man presented to the emergency department with scrotal oedema and ascites. Initially, the patient was hospitalized in the Department of Hepatology. However, computed tomography (CT) revealed aortic dissection (DeBakey type II), pericardial thickening, and impaired right ventricular dilatation. Therefore, we performed an ascending aortic replacement. IgG4 staining of the aortic wall revealed an IgG4/IgG-positive cell ratio of 35%. Pathological examination did not confirm the diagnosis of IgG4-related aortitis; however, the patient was diagnosed with IgG4-RD because of decreased blood IgG4 levels in response to steroid medication and the presence of heterogeneous thickened lesions in the pericardium. The patient took prednisolone 5 mg/day for 1 month post-operatively. His IgG4 level decreased but re-elevated above the baseline value after discontinuation of oral medication.

Discussion

Liver cirrhosis was suspected given the ascites, although a CT scan on admission confirmed insufficiency of systemic circulation due to cardiac constrictive pericarditis with aortic dissection. Despite the complexity of various pathologies in this patient, collaborative efforts and effective communication within the medical team enabled successful aortic surgery, averting life-threatening complications.
Endometriosis and long-term cardiovascular risk: a nationwide Danish study
Authors: Havers-Borgersen Eva , Hartwell Dorthe , Ekelund Charlotte , Butt Jawad H , Østergaard Lauge , Holgersson Christine , Schou Morten , Køber Lars , Fosbøl Emil L
Published: September 2024

Background and Aims

Endometriosis, a systemic gynaecological disease affecting 10% of women in reproductive age, shares pathophysiological characteristics with cardiovascular disease. However, data on the relationship between endometriosis and cardiovascular outcomes are scarce, prompting this study to address the knowledge gap.

Methods

Using Danish nationwide registries, women diagnosed with endometriosis (1977–2021) were identified and matched with controls in a 1:4 ratio based on year of birth. The primary outcome was a composite of acute myocardial infarction and ischaemic stroke. The secondary outcomes were arrhythmias, heart failure, and mortality.

Results

In total, 60 508 women with endometriosis and 242 032 matched controls were included (median age 37.3 years). Women with endometriosis were more comorbid and used more medications than controls. The incidence rates of the composite outcomes were 3.2 [95% confidence interval (CI) 3.2–3.3] and 2.7 (95% CI 2.7–2.8) per 1000 person-years among women with and without endometriosis, respectively. Women with endometriosis had a significantly higher associated rate of the composite outcome compared with controls [unadjusted hazard ratio (HR) 1.18 (95% CI 1.14–1.23), adjusted HR 1.15 (95% CI 1.11–1.20)]. Likewise, women with endometriosis were also at significantly increased associated risk of arrhythmias [unadjusted HR 1.24 (95% CI 1.20–1.28) and adjusted HR 1.21 (95% CI 1.17–1.25)] and heart failure [unadjusted HR 1.16 (95% CI 1.09–1.22) and adjusted HR 1.11 (95% CI 1.05–1.18)] but at decreased risk of mortality [unadjusted HR 0.95 (95% CI 0.92–0.97) and adjusted HR 0.93 (95% CI 0.91–0.96)].

Conclusions

Women with endometriosis have a higher associated long-term risk of cardiovascular outcomes compared with controls. Despite subtle absolute risk differences, the high prevalence of endometriosis underscores the importance of these findings.
Confidence in diagnosing and managing care for cognitive impairment in primary care: a survey comparing barriers by primary care clinician type
Authors: JaKa Meghan M , Rossom Rebecca C , Borson Soo , O’Connor Patrick J , Zibley Laura J , von Sternberg Thomas L , Crain A Lauren , Ekstrom Heidi L , Crouse Bethany , Werner Ann M , Hanson Leah R
Published: September 2024

Background

As cognitive impairment (CI) prevalence rises and primary care screening becomes commonplace, it is critical to understand how to support clinicians. We describe clinician-reported barriers to diagnosing and managing care for patients with CI in a health system with standardized screening. We also explore whether barriers differ by clinician type-physician or advanced-practice clinician (APC).

Methods

Theory-informed surveys were administered to primary care clinicians in a large integrated health system. The survey assessed barriers, confidence in diagnosing CI and managing CI care, beliefs about the consequences of diagnosing CI, and usability of the electronic health record (EHR) to diagnose and manage CI care; it also included open-ended response items. Descriptive statistics and content analysis were used to describe perceived barriers. Differences by clinician type were compared using chi-square.

Results

Of the 408 eligible clinicians, 249 started the survey and 247 completed the primary outcomes (61% response rate). Many said they were only a little or not at all confident in diagnosing (70%) and managing care for (60%) CI, with specific gaps in confidence in distinguishing types of dementia and having CI-related conversations with patients or family/care partners. APCs reported lower confidence than physicians. Other barriers were lack of time, low usability of EHR, and lack of family/care partner availability. These did not differ by clinician type. Open-ended responses suggest clinicians would like more support for CI care.

Conclusion

Low levels of confidence among other barriers suggest an urgent need to develop and implement effective multifaceted strategies to improve CI care.
Dissecting the Pandora’s box: preliminary phylogenomic insights into the internal and external relationships of stink bugs (Hemiptera: Pentatomidae)
Authors: Genevcius Bruno C
Published: September 2024

Stink bugs are invaluable models for macroevolutionary investigations owing to their astonishing ecological and morphological diversity. Nevertheless, such studies have been hampered by the absence of a solid phylogenetic hypothesis. Morphological and molecular studies based on Sanger data have found no consensus for the position of Pentatomidae, and the deep relationships within the family have been poorly resolved. These persistent uncertainties have cast the systematics of stink bugs into the metaphorical realm of a Pandora’s Box. Here, I conduct the first phylogenomic study focusing on pentatomids. Using public data, I aimed at testing the power of genome-scale data to resolve phylogenetic relationships within the family and to address the controversial position of the family within Pentatomoidea. Based on a dataset of 40 taxa and over 1,900 proteins, my results indicate the Pentatomidae as the sister group of all remaining families of Pentatomoidea, with an uncertainty of whether Plataspididae is included in this clade. Within Pentatomidae, my analyses confirm some previous findings, such as the monophyly of Asopinae and the relationship between Nezarini and Antestiini. On the other hand, most of the deep relationships within the family were strikingly different from previous works, for example, the Podopinae as the sister group of the Paleartic Carpocorini. My analyses confirm that the addition of massive amounts of data to phylogenetic studies may help achieve better supported trees for the stink bugs and allies. I argue that a solid and stable phylogeny-based classification will only be achieved with increased employment of -omics data.
China, the IMF, and Sovereign Debt Crises
Authors: Ferry Lauren L , Zeitz Alexandra O
Published: September 2024

The rise of China as a major bilateral lender has transformed the financial landscape for developing countries and, consequently, the process of resolving debt crises. We examine how China’s loans impact the response of the International Monetary Fund (IMF) to countries in debt distress. We argue that China’s lending approach and its absence from creditor forums, notably the Paris Club, can complicate the IMF’s efforts in managing debt crises. When China is a major lender, the IMF cannot rely on the Paris Club to coordinate bilateral creditors, and concerns about coordination, free-riding, and borrowers’ outside options can make it more difficult to agree on an IMF program. Therefore, we expect that countries that have borrowed more from China will undergo more protracted negotiations with the IMF in a debt crisis. We test our argument using data on the number of negotiating trips by IMF staff to borrowing countries to prepare IMF loans from 2000 to 2019. We find that countries with higher levels of outstanding debt to China require a greater number of IMF negotiating trips if they are in debt distress at the time. Our findings highlight the impact of Chinese lending on the sovereign debt regime and contribute to debates about China’s engagement with multilateralism.
When Is Digital Censorship Permissible? A Conversation Norms Account
Authors: Kim Tami
Published: September 2024

How do people decide what should—and should not—be censored? Seven studies investigate the psychology of digital censorship regarding user-generated content. Study 1 is inductive, identifying three dimensions—content, intent, and outcomes—along which consumers believe censorship decisions regarding user-generated content should be made. Despite the prevailing practice of content-based digital-censorship decisions—that is, censorship based on whether the focal content includes negative, concrete attributes such as obscene language and violence—people’s acceptance of censorship decisions is determined, in part, by the degree to which the creator’s intent is considered (an “intent-sensitivity hypothesis”; studies 2A–D) even when failing to censor would engender negative consequences. The current research contends that this effect stems from people’s belief that when online platforms make censorship decisions regarding user-generated content, they should abide by conversation norms. Thus, people demonstrate less intent sensitivity in contexts in which doing so is not as conversationally normative—for instance, when platforms are used for professional, rather than social, purposes (study 3). Furthermore, people do not expect the platform to exhibit intent sensitivity in less conversationally intimate contexts (study 4).
Phase III randomized trial comparing neoadjuvant paclitaxel plus platinum with 5-fluorouracil plus platinum in esophageal or gastroesophageal junction squamous cell carcinoma
Authors: Noronha Vanita , Patil Vijay Maruti , Menon Nandini , Joshi Amit , Shah Minit Jalan , Singh Ajaykumar , Goud Supriya , Shah Srushti , More Sucheta , Nawale Kavita , Nakti Dipti , Yadav Akanksha , Jogdhankar Shweta , Kaushal Rajiv Kumar , Tiwari Virendra Kumar , Niyogi Devayani , Purandare Nilendu , Janu Amit , Chakrabarty Nivedita , Mahajan Abhishek , Tibdewal Anil , Agarwal Jaiprakash , Pawar Akash , Chowdhury Oindrila Roy , Sharma Vibhor , Kapu Venkatesh , Trikha Mehak , Kumar Srigadha Vivek , Kolkur Manali , Bhagyavant Priyanka , Peelay Zoya , Khedkar Rutvij , Jain Medha , Badwe Rajendra Achyut , Prabhash Kumar
Published: September 2024

Background

Standard neoadjuvant chemotherapy for locally advanced esophageal or gastroesophageal junction squamous cancer, 5-fluorouracil plus platinum, is toxic and logistically challenging; alternative regimens are needed.

Methods

This was a phase III randomized open-label noninferiority trial at Tata Memorial Center, India, in resectable locally advanced esophageal or gastroesophageal junction squamous cancer. Patients were randomly assigned 1:1 to 3 cycles of 3-weekly platinum (cisplatin 75 mg/m2 or carboplatin area under the curve 6) with paclitaxel 175 mg/m2 (day 1) or 5-fluorouracil 1000 mg/m2 continuous infusion (days 1-4), followed by surgery.

Results

Between August 2014 and June 2022, we enrolled 420 patients; 210 to each arm. Statistically significantly more patients on paclitaxel plus platinum (n =194, 92.3%) received all 3 chemotherapy cycles than on 5-fluorouracil with platinum (n = 170, 85.9%; P = .009). 5-fluorouracil plus platinum caused more grade 3 or higher toxicities (n = 124, 69.7%) than paclitaxel plus platinum (n = 97, 51.9%; P = .001). Surgery was performed in 131 (62.4%) patients on 5-fluorouracil plus platinum vs 139 (66.2%) on paclitaxel plus platinum (P = .415). Paclitaxel plus platinum resulted in higher pathologic primary tumor clearance (n = 33, 25.8%, vs n = 17, 15%; P = .04) and pathologic complete responses in 21.9% compared with 12.4% from 5-fluorouracil plus platinum (P = .053). Median overall survival was 27.5 months (95% confidence interval [CI] = 18.6 to 43.5 months) from paclitaxel plus platinum, which was noninferior to 27.1 months (95% CI = 18.8 to 40.7 months) from 5-fluorouracil plus platinum (hazard ratio [HR] = 0.89, 95% CI = 0.72 to 1.09; P = .346).

Conclusion

Neoadjuvant paclitaxel plus platinum chemotherapy is safer and results in similar R0 resections, higher pathologic tumor clearance and noninferior survival compared with 5-fluorouracil plus platinum. Paclitaxel plus platinum should replace 5-fluorouracil plus platinum as neoadjuvant chemotherapy for resectable locally advanced esophagealor gastroesophageal junction squamous cancer.

Clinical Trials Registry India Number

CTRI/2014/04/004516.
Non-parametric Bayesian approach to multiple treatment comparisons in network meta-analysis with application to comparisons of anti-depressants
Authors: Barrientos Andrés F , Page Garritt L , Lin Lifeng
Published: September 2024

Network meta-analysis is a powerful tool to synthesize evidence from independent studies and compare multiple treatments simultaneously. A critical task of performing a network meta-analysis is to offer ranks of all available treatment options for a specific disease outcome. Frequently, the estimated treatment rankings are accompanied by a large amount of uncertainty, suffer from multiplicity issues, and rarely permit possible ties of treatments with similar performance. These issues make interpreting rankings problematic as they are often treated as absolute metrics. To address these shortcomings, we formulate a ranking strategy that adapts to scenarios with high-order uncertainty by producing more conservative results. This improves the interpretability while simultaneously accounting for multiple comparisons. To admit ties between treatment effects in cases where differences between treatment effects are negligible, we also develop a Bayesian non-parametric approach for network meta-analysis. The approach capitalizes on the induced clustering mechanism of Bayesian non-parametric methods, producing a positive probability that two treatment effects are equal. We demonstrate the utility of the procedure through numerical experiments and a network meta-analysis designed to study antidepressant treatments.
Promoters Constrain Evolution of Expression Levels of Essential Genes in Escherichia coli
Authors: Tsuru Saburo , Hatanaka Naoki , Furusawa Chikara
Published: September 2024

Variability in expression levels in response to random genomic mutations varies among genes, influencing both the facilitation and constraint of phenotypic evolution in organisms. Despite its importance, both the underlying mechanisms and evolutionary origins of this variability remain largely unknown due to the mixed contributions of cis- and trans-acting elements. To address this issue, we focused on the mutational variability of cis-acting elements, that is, promoter regions, in Escherichia coli. Random mutations were introduced into the natural and synthetic promoters to generate mutant promoter libraries. By comparing the variance in promoter activity of these mutant libraries, we found no significant difference in mutational variability in promoter activity between promoter groups, suggesting the absence of a signature of natural selection for mutational robustness. In contrast, the promoters controlling essential genes exhibited a remarkable bias in mutational variability, with mutants displaying higher activities than the wild types being relatively rare compared to those with lower activities. Our evolutionary simulation on a rugged fitness landscape provided a rationale for this vulnerability. These findings suggest that past selection created nonuniform mutational variability in promoters biased toward lower activities of random mutants, which now constrains the future evolution of downstream essential genes toward higher expression levels.
SIADH and mixed delirium following the abrupt cessation of long-acting benzodiazepines: a case report
Authors: Alenezi Ahmad F , Alnuaimi Ahmed , Liberman Dan
Published: September 2024

Benzodiazepines (BZDs) are among the most commonly used medications due to their efficacy and rapid onset of action. Although they offer significant therapeutic benefits in treating various psychiatric and neurological conditions, their clinical utility is limited by substantial risks, including dependency and withdrawal symptoms. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) has been linked to BZD withdrawal. In this case report, we examine the case of an elderly female presented with a mixed delirium and SIADH following the abrupt cessation of long-term clonazepam therapy. To our knowledge, this is the second case that documents a link between SIADH and BZD withdrawal.
Can mass media campaigns increase demand for renewable energy? Experimental evidence from Senegal
Authors: Coville Aidan , Orozco-Olvera Victor , Reichert Arndt
Published: September 2024

This paper examines public investment in mass media campaigns aimed at stimulating market-led growth within the renewable energy sector in a developing country setting. We run a randomized field experiment to estimate the impact of a large-scale information campaign on the adoption of renewable energy technology, which includes clips broadcasted on national radio and print materials distributed in rural villages in Senegal. While the radio campaign primarily influences the number of renewable energy products owned by existing users (intensive margin), the combination of radio and print significantly increases the number of new adopters (extensive margin). However, when scaled nationally, we calculate a meaningful advantage of the radio clips over the print materials in terms of the cost per additional sales of solar lamps. The study further introduces an innovative methodological approach for examining nationally broadcasted information campaigns, offering valuable insights for future research and policy evaluations.
Impacts of stellar wind and supernovae on star cluster formation: Origins of extremely high N/O ratios and multiple stellar populations
Authors: Fukushima Hajime , Yajima Hidenobu
Published: September 2024

We study metal enrichment originating from stellar wind and supernovae in low-metallicity clouds by performing three-dimensional radiation hydrodynamics simulations. We find that metals ejected from stellar wind are accumulated, leading to subsequent star formation in the nitrogen-enriched gas. During this early phase, the ${\rm N/O}$ ratios are similar to observed nitrogen-enriched galaxies (${\rm [N/O]}\gtrsim 0.5$). Then, once supernovae occur, the ${\rm N/O}$ ratios decrease significantly. If the duration of star formation is comparable to the time-scale of supernovae, the mass fraction of nitrogen-enriched stars reaches half the mass of star clusters. We suggest that the mass of the star cluster needs to exceed $\sim \!10^6$ M$_{\odot }$ to have multiple populations due to stellar wind, considering the condition for massive star cluster formation and the timescales of stellar evolution.
CPK10 regulates low light–induced tomato flower drop downstream of IDL6 in a calcium-dependent manner
Authors: Fu Xin , Li Ruizhen , Liu Xianfeng , Cheng Lina , Ge Siqi , Wang Sai , Cai Yue , Zhang Tong , Shi Chun-Lin , Meng Sida , Tan Changhua , Jiang Cai-Zhong , Li Tianlai , Qi Mingfang , Xu Tao
Published: September 2024

Flower drop is a major cause for yield loss in many crops. Previously, we found that the tomato (Solanum lycopersicum) INFLORESCENCE DEFICIENT IN ABSCISSION-Like (SlIDL6) gene contributes to flower drop induced by low light. However, the molecular mechanisms by which SlIDL6 acts as a signal to regulate low light–induced abscission remain unclear. In this study, SlIDL6 was found to elevate cytosolic Ca2+ concentrations ([Ca2+]cyt) in the abscission zone (AZ), which was required for SlIDL6-induced flower drop under low light. We further identified that 1 calcium-dependent protein kinase gene, SlCPK10, was highly expressed in the AZ and upregulated by SlIDL6-triggered [Ca2+]cyt. Overexpression and knockout of SlCPK10 in tomato resulted in accelerated and delayed abscission, respectively. Genetic evidence further indicated that knockout of SlCPK10 significantly impaired the function of SlIDL6 in accelerating abscission. Furthermore, Ser-371 phosphorylation in SlCPK10 dependent on SlIDL6 was necessary and sufficient for its function in regulating flower drop, probably by stabilizing the SlCPK10 proteins. Taken together, our findings reveal that SlCPK10, as a downstream component of the IDL6 signaling pathway, regulates flower drop in tomato under low-light stress.
In situ deposition of nanobodies by an engineered commensal microbe promotes survival in a mouse model of enterohemorrhagic E. coli
Authors: Srivastava Rajkamal , González-Prieto Coral , Lynch Jason P , Muscolo Michele E , Lin Catherine Y , Brown Markus A , Lemos Luisa , Shrestha Anishma , Osburne Marcia S , Leong John M , Lesser Cammie F
Published: September 2024

Engineered smart microbes that deliver therapeutic payloads are emerging as treatment modalities, particularly for diseases with links to the gastrointestinal tract. Enterohemorrhagic Escherichia coli (EHEC) is a causative agent of potentially lethal hemolytic uremic syndrome. Given concerns that antibiotic treatment increases EHEC production of Shiga toxin (Stx), which is responsible for systemic disease, novel remedies are needed. EHEC encodes a type III secretion system (T3SS) that injects Tir into enterocytes. Tir inserts into the host cell membrane, exposing an extracellular domain that subsequently binds intimin, one of its outer membrane proteins, triggering the formation of attaching and effacing (A/E) lesions that promote EHEC mucosal colonization. Citrobacter rodentium (Cr), a natural A/E mouse pathogen, similarly requires Tir and intimin for its pathogenesis. Mice infected with Cr(ΦStx2dact), a variant lysogenized with an EHEC-derived phage that produces Stx2dact, develop intestinal A/E lesions and toxin-dependent disease. Stx2a is more closely associated with human disease. By developing an efficient approach to seamlessly modify the C. rodentium genome, we generated Cr_Tir-MEHEC(ΦStx2a), a variant that expresses Stx2a and the EHEC extracellular Tir domain. We found that mouse precolonization with HS-PROT3EcT-TD4, a human commensal E. coli strain (E. coli HS) engineered to efficiently secrete an anti-EHEC Tir nanobody, delayed bacterial colonization and improved survival after challenge with Cr_Tir-MEHEC(ΦStx2a). This study suggests that commensal E. coli engineered to deliver payloads that block essential virulence determinants can be developed as a new means to prevent and potentially treat infections including those due to antibiotic resistant microbes.
Combined associations of obesity and physical activity with pain, fatigue, stiffness and anxiety in adults with spondyloarthropathies: UK Biobank study
Authors: Roberts Matthew J , Johnson William , Qooja Sepehr , Moorthy Arumugam , Bishop Nicolette C
Published: September 2024

Objective

Inflammatory spondyloarthropathies are associated with pain, fatigue, stiffness and anxiety. The National Institute for Health and Care Excellence and the EULAR provide limited lifestyle guidance for managing symptoms with inflammatory spondyloarthropathies. We investigated the combined associations of obesity and physical activity with symptom severity in inflammatory spondyloarthropathies.

Methods

The relationship between BMI, physical activity and symptom severity (spinal and general pain, fatigue, anxiety, mobility) was examined in people with ISpAs (n = 1577). BMI categories were normal weight (18.5–24.9 kg/m2), overweight (25.0–29.9 kg/m2) and obese (≥30 kg/m2). Physical activity was assessed via the International Physical Activity Questionnaire (low < 600 metabolic equivalent of task (MET)-min/week, moderate ≥ 600 METs, high ≥ 3000 METs). Statistical models adjusted for confounders, including medication, estimated the likelihood (odds ratios, OR) of higher symptom severity across BMI and physical activity categories.

Results

Overweight and obesity, compared with normal weight, were linked to higher severity of all symptoms, with stronger associations for obesity (OR ≥ 2.34, P < 0.001) than overweight (OR ≥ 1.37, P ≤ 0.032). Moderate activity, compared with low, was associated with lower severity of all symptoms (OR ≤ 0.77, P ≤ 0.032). High activity, compared with low, was associated with lower severity of fatigue, anxiety and mobility issues (OR ≤ 0.74, P ≤ 0.029), but associations with spinal and general pain were not significant (OR ≤ 0.80, P ≥ 0.056). No BMI-by-physical activity combinations were detected, indicating physical activity benefits all BMI groups to a similar extent.

Conclusion

National Institute for Health and Care Excellence and EULAR guidance for inflammatory spondyloarthropathies should emphasize maintaining a normal weight. Moderate physical activity is optimal for reducing symptom severity and should be promoted in lifestyle guidance.
Cross-linking manipulation of waterborne biodegradable polyurethane for constructing mechanically adaptable tissue engineering scaffolds
Authors: Sheng Nan , Lin Weiwei , Lin Jingjing , Feng Yuan , Wang Yanchao , He Xueling , He Yuanyuan , Liang Ruichao , Li Zhen , Li Jiehua , Luo Feng , Tan Hong
Published: September 2024

Mechanical adaptation of tissue engineering scaffolds is critically important since natural tissue regeneration is highly regulated by mechanical signals. Herein, we report a facile and convenient strategy to tune the modulus of waterborne biodegradable polyurethanes (WBPU) via cross-linking manipulation of phase separation and water infiltration for constructing mechanically adaptable tissue engineering scaffolds. Amorphous aliphatic polycarbonate and trifunctional trimethylolpropane were introduced to polycaprolactone-based WBPUs to interrupt interchain hydrogen bonds in the polymer segments and suppress microphase separation, inhibiting the crystallization process and enhancing covalent cross-linking. Intriguingly, as the crosslinking density of WBPU increases and the extent of microphase separation decreases, the material exhibits a surprisingly soft modulus and enhanced water infiltration. Based on this strategy, we constructed WBPU scaffolds with a tunable modulus to adapt various cells for tissue regeneration and regulate the immune response. As a representative application of brain tissue regeneration model in vivo, it was demonstrated that the mechanically adaptable WBPU scaffolds can guide the migration and differentiation of endogenous neural progenitor cells into mature neurons and neuronal neurites and regulate immunostimulation with low inflammation. Therefore, the proposed strategy of tuning the modulus of WBPU can inspire the development of novel mechanically adaptable biomaterials, which has very broad application value.
An objective diagnosis of gout and calcium pyrophosphate deposition disease with machine learning of Raman spectra acquired in a point-of-care setting
Authors: Niessink Tom , Jansen Tim L , Coumans Frank A W , Welting Tim J M , Janssen Matthijs , Otto Cees
Published: September 2024

Objective

Raman spectroscopy is proposed as a next-generation method for the identification of monosodium urate (MSU) and calcium pyrophosphate (CPP) crystals in synovial fluid. As the interpretation of Raman spectra requires specific expertise, the method is not directly applicable for clinicians. We developed an approach to demonstrate that the identification process can be automated with the use of machine learning techniques. The developed system is tested in a point-of-care-setting at our outpatient rheumatology department.

Methods

We collected synovial fluid samples from 446 patients with various rheumatic diseases from three centres. We analysed all samples with our Raman spectroscope and used 246 samples for training and 200 samples for validation. Trained observers classified every Raman spectrum as MSU, CPP or other. We designed two one-against-all classifiers, one for MSU and one for CPP. These classifiers consisted of a principal component analysis model followed by a support vector machine.

Results

The accuracy for classification of CPP using the 2023 ACR/EULAR CPPD classification criteria was 96.0% (95% CI: 92.3, 98.3), while the accuracy for classification of MSU using the 2015 ACR/EULAR gout classification criteria was 92.5% (95% CI: 87.9, 95.7). Overall, the accuracy for classification of pathological crystals was 88.0% (95% CI: 82.7, 92.2). The model was able to discriminate between pathological crystals, artifacts and other particles such as microplastics.

Conclusion

We here demonstrate that potentially complex Raman spectra from clinical patient samples can be successfully classified by a machine learning approach, resulting in an objective diagnosis independent of the opinion of the medical examiner.