tbuckley/cabot-search huggingface dataset:
Association between primary hypothyroidism and metabolic dysfunction-associated steatotic liver disease: an updated meta-analysis
Authors: Alessandro Mantovani, Alessandro Csermely, Josh Bilson, Niccolò Borella, Scoccia Enrico, Barbara Pecoraro, Emigela Shtembari, Riccardo Morandin, Stergios A Polyzos, Luca Valenti, Herbert Tilg, Christopher D Byrne, Giovanni Targher
Journal: Gut (2024)

Objective Epidemiological studies have reported an association between primary hypothyroidism and metabolic dysfunction-associated steatotic liver disease (MASLD). However, the magnitude of the risk and whether this risk changes with the severity of MASLD remains uncertain. We performed a meta-analysis of observational studies to quantify the magnitude of the association between primary hypothyroidism and the risk of MASLD. Design We systematically searched PubMed, Scopus and Web of Science from database inception to 31 January 2024, using predefined keywords to identify observational studies in which MASLD was diagnosed by liver biopsy, imaging or International Classification of Diseases codes. A meta-analysis was performed using random-effects modelling. Results We identified 24 cross-sectional and 4 longitudinal studies with aggregate data on ~76.5 million individuals. Primary hypothyroidism (defined as levothyroxine replacement treatment, subclinical hypothyroidism or overt hypothyroidism) was associated with an increased risk of prevalent MASLD (n=24 studies; random-effects OR 1.43, 95% CI 1.23 to 1.66; I 2 =89%). Hypothyroidism was also associated with a substantially higher risk of metabolic dysfunction-associated steatohepatitis or advanced fibrosis (n=5 studies; random-effects OR 2.84, 95% CI 2.07 to 3.90; I 2 =0%). Meta-analysis of data from four longitudinal studies showed that there was a marginally non-significant association between hypothyroidism and risk of developing MASLD over a median 4.5-year follow-up (random-effects HR 1.39, 95% CI 0.98 to 1.97; I 2 =85%). Sensitivity analyses did not modify these findings. The funnel plot did not reveal any significant publication bias. Conclusion This large and updated meta-analysis provides evidence that primary hypothyroidism is significantly associated with both an increased presence of and histological severity of MASLD.
Perioperative outcomes and safety of valveless insufflation system in minimally invasive urological surgery: A systematic review and meta-analysis
Authors: Youyi Lu, Qingsong Zou, Bo Jiang, Qi Li
Journal: International Journal of Surgery (2024)

Background: With the rapid development of laparoscopic and robot-assisted surgery, many technological innovations and improvements have emerged to optimize minimally invasive surgery and ensure minimal patient risk. Although AirSeal has been widely reported in the field of urology, its perioperative outcomes and safety in minimally invasive urological surgery remain unclear because of inconsistent levels of evidence. Objectives: The authors performed this meta-analysis to evaluate the perioperative outcomes and safety of the valveless insufflation system (VIS) in minimally invasive urological surgery compared with the conventional insufflation system (CIS). Methods: The authors comprehensively searched PubMed, Web of Science, Cochrane Library, and Embase databases to identify eligible studies published up to January 2024. Review Manager software (version 5.3.0) was used for the statistical analysis. Eligible studies were randomized controlled trials (RCTs) or non-RCTs of minimally invasive urological surgery with VIS vs CIS. The study outcomes included perioperative outcomes and safety. The authors excluded publication types, including letters, reviews, case reports, and animal and pediatric studies. Results: The authors finally identified five RCTs and eight non-RCTs in this meta-analysis. The meta- analysis indicated that the operative time was comparable between the groups ( P =0.57, I 2 =91%). However, a VIS may increase blood loss ( P =0.0004, I 2 =45%) and shorten hospital stays ( P &lt;0.00001, I 2 =90%). Due to the high heterogeneity of the results, the authors carefully evaluated all included studies and discovered that the studies by Bucur and Ferroni may be the sources of heterogeneity. When these two studies were excluded, heterogeneity was significantly reduced, and the operative time for VIS was significantly shorter than that for CIS ( P =0.0002). Adjusted blood loss showed no difference between the VIS and CIS groups ( P =0.10). In terms of safety, the pooled results revealed that the incidence of Clavien–Dindo III–IV complications in the VIS group was significantly lower than that in the CIS group ( P =0.02, I 2 =0%). Moreover, VIS significantly reduced general pain ( P =0.02, I 2 =15%) and shoulder pain ( P =0.001, I 2 =0%) 12–24 h postoperatively. No significant differences were observed in total complications ( P =0.06, I 2 =0%), blood transfusion ( P =0.14, I 2 =0%), and subcutaneous emphysema ( P =0.96, I 2 =63%) between the two groups. Conclusions: Our meta-analysis revealed additional perioperative advantages of the VIS in minimally invasive urological surgery. Moreover, VIS is superior to CIS owing to less severe complication rates, general pain, and shoulder pain.
A commentary on “Early plasma proteomic biomarkers and prediction model of acute respiratory distress syndrome after cardiopulmonary bypass: a prospective nested cohort study”
Authors: Xin Zhu, Peng Liu
Journal: International Journal of Surgery (2024)

aDepartment of Anesthesiology, The First Affiliation hospital of Dalian Medical University, Liaoning Province, Dalian, 116001, China bDepartment of Heart Intensive Care Unit, The First Affiliation hospital of Dalian Medical University, Liaoning Province, Dalian, 116001, China Co-authors: Xin Zhu and Peng Liu equally contributed to the article. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. Published online ■ ■ *Corresponding author. Address: Peng Liu, Address: Department of Heart Intensive Care Unit, The First Affiliation hospital of Dalian Medical University, Liaoning Province, Dalian, 116001, China. E-mail address: [email protected] This is an open access article distributed under the Creative Commons Attribution-ShareAlike License 4.0, which allows others to remix, tweak, and build upon the work, even for commercial purposes, as long as the author is credited and the new creations are licensed under the identical terms. http://creativecommons.org/licenses/by-sa/4.0/
Sleep patterns, genetic susceptibility, and digestive diseases: A large-scale longitudinal cohort study
Authors: Yuying Ma, Shiyi Yu, Qinming Li, Haifeng Zhang, Ruijie Zeng, Ruibang Luo, Qizhou Lian, Felix W. Leung, Chongyang Duan, Weihong Sha, Hao Chen
Journal: International Journal of Surgery (2024)

Background: Sleep problems are prevalent. However, the impact of sleep patterns on digestive diseases remains uncertain. Moreover, the interaction between sleep patterns and genetic predisposition with digestive diseases has not been comprehensively explored. Methods: Four hundred ten thousand five hundred eighty-six participants from UK Biobank with complete sleep information were included in the analysis. Sleep patterns were measured by sleep scores as the primary exposure, based on five healthy sleep behaviors. Individual sleep behaviors were secondary exposures. Genetic risk of the digestive diseases was characterized by polygenic risk score. Primary outcome was incidence of 16 digestive diseases. Results: Healthy sleep scores showed dose-response associations with reduced risks of digestive diseases. Compared to participants scoring 0–1, those scoring 5 showed a 28% reduced risk of any digestive disease, including a 50% decrease in irritable bowel syndrome, 37% in non-alcoholic fatty liver disease, 35% in peptic ulcer, 34% in dyspepsia, 32% in gastroesophageal reflux disease, 28% in constipation, 25% in diverticulosis, 24% in severe liver disease, and 18% in gallbladder disease, whereas no correlation was observed with inflammatory bowel disease and pancreatic disease. Participants with poor sleep and high genetic risk exhibited approximately a 60% increase in the risk of digestive diseases. A healthy sleep pattern is linked to lower digestive disease risk in participants of all genetic risk levels. Conclusions: In this large population-based cohort, a healthy sleep pattern was associated with a reduced risk of digestive diseases, regardless of genetic susceptibility. The authors’ findings underscore the potential impact of healthy sleep traits in mitigating the risk of digestive diseases.
Enhancing IgA-mediated neutrophil cytotoxicity against neuroblastoma by CD47 blockade
Authors: Chilam Chan, Marjolein Stip, Maaike Nederend, Marco Jansen, Elsemieke Passchier, Femke van den Ham, Judith Wienke, Geert van Tetering, Jeanette Leusen
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Approximately half of the neuroblastoma patients develop high-risk neuroblastoma. Current treatment involves a multimodal strategy, including immunotherapy with dinutuximab (IgG ch14.18) targeting GD2. Despite achieving promising results, the recurrence rate remains high and poor survival persists. The therapeutic efficacy of dinutuximab is compromised by suboptimal activation of neutrophils and severe neuropathic pain, partially induced by complement activation. Methods To enhance neutrophil cytotoxicity, IgG ch14.18 was converted to the IgA isotype, resulting in potent neutrophil-mediated antibody-dependent cell-mediated cytotoxicity (ADCC), without complement activation. However, myeloid checkpoint molecules hamper neutrophil cytotoxicity, for example through CD47 that is overexpressed on neuroblastomas and orchestrates an immunosuppressive environment upon ligation to signal regulatory protein alpha (SIRPα) expressed on neutrophils. In this study, we combined IgA therapy with CD47 blockade. Results In vitro killing assays showed enhanced IgA-mediated ADCC by neutrophils targeting neuroblastoma cell lines and organoids in comparison to IgG. Notably, when combined with CD47 blockade, both IgG and IgA therapy were enhanced, though the combination with IgA resulted in the greatest improvement of ADCC. Furthermore, in a neuroblastoma xenograft model, we systemically blocked CD47 with a SIRPα fusion protein containing an ablated IgG1 Fc, and compared IgA therapy to IgG therapy. Only IgA therapy combined with CD47 blockade increased neutrophil influx to the tumor microenvironment. Moreover, the IgA combination strategy hampered tumor outgrowth most effectively and prolonged tumor-specific survival. Conclusion These promising results highlight the potential to enhance immunotherapy efficacy against high-risk neuroblastoma through improved neutrophil cytotoxicity by combining IgA therapy with CD47 blockade.
Dose escalation study of a personalized peptide-based neoantigen vaccine (EVX-01) in patients with metastatic melanoma
Authors: Sofie Kirial Mørk, Signe Koggersbøl Skadborg, Benedetta Albieri, Arianna Draghi, Kalijn Bol, Mohammad Kadivar, Marie Christine Wulff Westergaard, Joachim Stoltenborg Granhøj, Annie Borch, Nadia Viborg Petersen, Nikolas Thuesen, Ida Svahn Rasmussen, Lars Vibe Andreasen, Rebecca Bach Dohn, Christina Westmose Yde, Nis Noergaard, Torben Lorentzen, Anders Bundgaard Soerensen, Daniela Kleine-Kohlbrecher, Anders Jespersen, Dennis Christensen, Jens Kringelum, Marco Donia, Sine Reker Hadrup, Inge Marie Svane
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Neoantigens can serve as targets for T cell-mediated antitumor immunity via personalized neopeptide vaccines. Interim data from our clinical study NCT03715985 showed that the personalized peptide-based neoantigen vaccine EVX-01, formulated in the liposomal adjuvant, CAF09b, was safe and able to elicit EVX-01-specific T cell responses in patients with metastatic melanoma. Here, we present results from the dose-escalation part of the study, evaluating the feasibility, safety, efficacy, and immunogenicity of EVX-01 in addition to anti-PD-1 therapy. Methods Patients with metastatic melanoma on anti-PD-1 therapy were treated in three cohorts with increasing vaccine dosages (twofold and fourfold). Tumor-derived neoantigens were selected by the AI platform PIONEER and used in personalized therapeutic cancer peptide vaccines EVX-01. Vaccines were administered at 2-week intervals for a total of three intraperitoneal and three intramuscular injections. The study’s primary endpoint was safety and tolerability. Additional endpoints were immunological responses, survival, and objective response rates. Results Compared with the base dose level previously reported, no new vaccine-related serious adverse events were observed during dose escalation of EVX-01 in combination with an anti-PD-1 agent given according to local guidelines. Two patients at the third dose level (fourfold dose) developed grade 3 toxicity, most likely related to pembrolizumab. Overall, 8 out of the 12 patients had objective clinical responses (6 partial response (PR) and 2 CR), with all 4 patients at the highest dose level having a CR (1 CR, 3 PR). EVX-01 induced peptide-specific CD4+ and/or CD8+T cell responses in all treated patients, with CD4+T cells as the dominating responses. The magnitude of immune responses measured by IFN-γ ELISpot assay correlated with individual peptide doses. A significant correlation between the PIONEER quality score and induced T cell immunogenicity was detected, while better CRs correlated with both the number of immunogenic EVX-01 peptides and the PIONEER quality score. Conclusion Immunization with EVX-01-CAF09b in addition to anti-PD-1 therapy was shown to be safe and well tolerated and elicit vaccine neoantigen-specific CD4+and CD8+ T cell responses at all dose levels. In addition, objective tumor responses were observed in 67% of patients. The results encourage further assessment of the antitumor efficacy of EVX-01 in combination with anti-PD-1 therapy.
Remote‐Controlled Sensing and Drug Delivery via 3D‐Printed Hollow Microneedles
Authors: Mahmood Razzaghi, Joel Alexander Ninan, Mostafa Azimzadeh, Esfandyar Askari, Alireza Hassani Najafabadi, Ali Khademhosseini, Mohsen Akbari
Journal: Advanced Healthcare Materials (2024)

Remote health monitoring and treatment serve as critical drivers for advancing health equity, bridging geographical and socioeconomic disparities, ensuring equitable access to quality healthcare for those in underserved or remote regions. By democratizing healthcare, this approach offers timely interventions, continuous monitoring, and personalized care independent of one's location or socioeconomic status, thereby striving for an equitable distribution of health resources and outcomes. Meanwhile, microneedle arrays (MNAs), revolutionize painless and minimally invasive access to interstitial fluid for drug delivery and diagnostics. This paper introduces an integrated theranostic MNA system employing an array of colorimetric sensors to quantitatively measure -pH, glucose, and lactate, alongside a remotely-triggered system enabling on-demand drug delivery. Integration of an ultrasonic atomizer streamlines the drug delivery, facilitating rapid, pumpless, and point-of-care drug delivery, enhancing system portability while reducing complexities. An accompanying smartphone application interfaces the sensing and drug delivery components. Demonstrated capabilities include detecting pH (3 to 8), glucose (up to 16 mm), and lactate (up to 1.6 mm), showcasing on-demand drug delivery, and assessing delivery system performance via a scratch assay. This innovative approach confronts drug delivery challenges, particularly in managing chronic diseases requiring long-term treatment, while also offering avenues for non-invasive health monitoring through microneedle-based sensors.
The <i>Support-Pro</i> Online Training Platform: Increasing Health Care Professionals’ Confidence and Knowledge in Treating People Living With Type 1 Diabetes
Authors: Alexandra Katz, Amélie Roy-Fleming, Asmaa Housni, Meryem K. Talbo, Sarah Haag, Rémi Rabasa-Lhoret, Anne-Sophie Brazeau
Journal: Diabetes Care (2024)
From gut microbiota to brain: implications on binge eating disorders
Authors: Weiwei Guo, Wei Xiong
Journal: Gut Microbes (2024)

The prevalence of eating disorders has been increasing over the last 50 years. Binge eating disorder (BED) and bulimia nervosa (BN) are two typical disabling, costly and life-threatening eating disorders that substantially compromise the physical well-being of individuals while undermining their psychological functioning. The distressing and recurrent episodes of binge eating are commonly observed in both BED and BN; however, they diverge as BN often involves the adoption of inappropriate compensatory behaviors aimed at averting weight gain. Normal eating behavior is coordinated by a well-regulated trade-off between intestinal and central ingestive mechanism. Conversely, despite the fact that the etiology of BED and BN remains incompletely resolved, emerging evidence corroborates the notion that dysbiosis of gastrointestinal microbiome and its metabolites, alteration of gut-brain axis, as well as malfunctioning central circuitry regulating motivation, execution and reward all contribute to the pathology of binge eating. In this review, we aim to outline the current state of knowledge pertaining to the potential mechanisms through which each component of the gut-brain axis participates in binge eating behaviors, and provide insight for the development of microbiome-based therapeutic interventions that hold promise in ameliorating patients afflicted with binge eating disorders.
Prediction of the pathological subtypes by intraoperative frozen section for patients with cT1N0M0 invasive lung adenocarcinoma (ECTOP-1015): a prospective multi-center study
Authors: Zichen Fu, Xuxia Shen, Chaoqiang Deng, Hang Cao, Yan Jin, Qiang Zheng, Yongguo Yang, Bin Qian, Chunyan Yuan, Weihua Wang, Lei Zhang, Qingping Song, Shuying Zuo, Junjie Ma, Shuqing You, Senzhong Zheng, Qingli Gao, Guangli Su, Yang Zhang, Fangqiu Fu, Haiquan Chen, Yuan Li
Journal: International Journal of Surgery (2024)

Background: This study aims to assess the diagnostic accuracy of the intraoperative frozen section (FS) in determining the pathological subtypes among patients diagnosed with cT1N0M0 invasive lung adenocarcinoma. Materials and methods: This was a prospective, multicenter (seven centers in China) clinical trial of Eastern Cooperative Thoracic Oncology Projects (ECTOP-1015). Patients with cT1N0M0 invasive lung adenocarcinoma were enrolled in the study. Pathological images obtained from FS and final pathology (FP) were reviewed by at least two pathologists. The primary endpoint was the concordance between FS and FP diagnoses. The interobserver agreement for identifying pathological subtypes on FS was evaluated among three pathologists. Results: A total of 935 patients were enrolled. The best sensitivity of diagnosing the predominant subtype was 78.2% in the evaluation of the acinar pattern. The presence of an acinar pattern diagnosed by FS was an independent factor for the concordance between FS and FP ( P =0.007, 95% confidence interval: 2.332–4.736). Patients with tumor size &gt;2 cm measured by pathology showed a better concordance rate for the predominant subtype (81.6% vs. 74.6%, P =0.023). The presence of radiological ground glass opacity component did not affect the diagnosis accuracy of FS for the predominant subtype (concordance rate: 76.4% vs. 75.2%, P =0.687). Patients with ground glass opacity component showed better accuracy of the identification in the presence of lepidic pattern-predominant adenocarcinoma (82.1% vs. 71.0%, P =0.026). Substantial agreement between the FS diagnosis from three pathologists for the predominant pathological pattern was revealed with κ=0.846. Conclusions: This is the largest prospective trial evaluating FS diagnosing pathological subtype in cT1N0M0 invasive lung adenocarcinoma. A favorable concordance in the assessment of the pathological subtypes between FS and FP was observed, indicating the feasibility of utilizing accurate intraoperative pathological diagnoses from FS in guiding surgical strategies. A combination of radiology could improve the precision of FS.
Exosomal circPOLQ promotes macrophage M2 polarization via activating IL-10/STAT3 axis in a colorectal cancer model
Authors: Zhenqiang Sun, Yanxin Xu, Bo Shao, Pengyuan Dang, Shengyun Hu, Haifeng Sun, Chen Chen, Chaoguan Wang, Jinbo Liu, Yang Liu, Junhong Hu
Journal: Journal for ImmunoTherapy of Cancer (2024)

Background Accumulating evidence demonstrates that an increased tumor-associated macrophage abundance is often associated with poor prognosis in colorectal cancer (CRC). The mechanism underlying the effect of tumor-derived exosomes on M2 macrophage polarization remains elusive. Results The novel circular RNA circPOLQ exhibited significantly higher expression in CRC tissues than in paired normal tissues. Higher circPOLQ expression was associated with poorer prognosis in patients with CRC. In vitro and in vivo experiments showed that tumor-derived exosomal circPOLQ did not directly regulate CRC cell development but promoted CRC metastatic nodule formation by enhancing M2 macrophage polarization. circPOLQ activated the interleukin-10/signal transducer and activator of transcription 3 axis by targeting miR-379–3 p to promote M2 macrophage polarization. Conclusion circPOLQ can enter macrophages via CRC cell-derived exosomes and promote CRC metastatic nodule formation by enhancing M2 macrophage polarization. These findings reveal a tumor-derived exosome-mediated tumor–macrophage interaction potentially affecting CRC metastatic nodule formation.
The independent predictive role of platelet to white blood cell ratio on all-cause mortality: A 7-year nationwide follow-up study in China
Authors: Xinyi Lyu, Yang Xiong, Lisha Jiang, Feng Qin
Journal: International Journal of Surgery (2024)

aDepartment of Urology, Institute of Urology, West China Hospital, Sichuan University, Sichuan Province 610041, China bDepartment of Urology and Andrology Laboratory, West China Hospital, Sichuan University, Sichuan Province 610041, China cDay Surgery Center, West China Hospital, Sichuan University, Sichuan Province 610041, China Notes: Xinyi Lyu and Yang Xiong contributed equally to this work. Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article. *Corresponding Author Address: Department of Urology and Andrology Laboratory, West China Hospital, Sichuan University, 37 Guoxue Alley, Chengdu, Sichuan Province 610041, China. E-mail address: [email protected] (F. Qin). *Corresponding Author Address: Day Surgery Center, West China Hospital, Sichuan University, Sichuan Province 610041, China. E-mail address: [email protected] (L. Jiang). Supplemental Digital Content is available for this article. Direct URL citations are provided in the HTML and PDF versions of this article on the journal's website, www.lww.com/international-journal-of-surgery. Published online ■ ■ This is an open access article distributed under the Creative Commons Attribution License 4.0 (CCBY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. http://creativecommons.org/licenses/by/4.0/