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result(s) for
"Surgery, Experimental"
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CXCR1/2 inhibition enhances pancreatic islet survival after transplantation
by
Ruffini, Pier Adelchi
,
Bonifacio, Ezio
,
Sordi, Valeria
in
Adult
,
Allosteric proteins
,
Animals
2012
Although long considered a promising treatment option for type 1 diabetes, pancreatic islet cell transformation has been hindered by immune system rejection of engrafted tissue. The identification of pathways that regulate post-transplant detrimental inflammatory events would improve management and outcome of transplanted patients. Here, we found that CXCR1/2 chemokine receptors and their ligands are crucial negative determinants for islet survival after transplantation. Pancreatic islets released abundant CXCR1/2 ligands (CXCL1 and CXCL8). Accordingly, intrahepatic CXCL1 and circulating CXCL1 and CXCL8 were strongly induced shortly after islet infusion. Genetic and pharmacological blockade of the CXCL1-CXCR1/2 axis in mice improved intrahepatic islet engraftment and reduced intrahepatic recruitment of polymorphonuclear leukocytes and NKT cells after islet infusion. In humans, the CXCR1/2 allosteric inhibitor reparixin improved outcome in a phase 2 randomized, open-label pilot study with a single infusion of allogeneic islets. These findings indicate that the CXCR1/2-mediated pathway is a regulator of islet damage and should be a target for intervention to improve the efficacy of transplantation.
Journal Article
How Strong Can We Pull? Critical Thresholds for Traction Forces on the Aortic Annulus: Measurements on Fresh Porcine Hearts
by
Hartrumpf, Martin
,
Sterner, Josephine
,
Ostovar, Roya
in
Animal experimentation
,
aortic valve
,
Endocarditis
2022
Background and Objectives: Friable or infected tissue remains a challenge in surgical aortic valve replacement. We recently described the “Caput medusae” method, in which circumferential tourniquets temporarily secure the prosthesis and are then gently knotted. Tourniquets have been shown to develop significantly less force than knots. The current study investigates the critical threshold forces for tissue damage to the aortic annulus. Materials and Methods: In 14 fresh porcine hearts, the aortic valve leaflets were removed and several pledgeted sutures were placed along the annulus at defined locations. The hearts were mounted in a self-constructed device. Incremental traction force was applied to every suture and continuously recorded. The movement of each Teflon pledget was filmed with a high-speed camera. Forces at the moment of pledget “cut-in” as well as complete “tear-out” were determined from the recordings. Results: The average threshold force was determined 9.31 ± 6.04 N for cut-in and 20.41 ± 10.02 N for tear-out. Detailed analysis showed that the right coronary region had lower threshold forces than the other regions (4.77 ± 3.28 N (range, 1.67–12.75 N) vs. 10.67 ± 6.04 N (1.62–26.00 N) for cut-in and 10.67 ± 4.04 N (5.40–18.64 N) vs. 23.33 ± 9.42 N (9.22–51.23 N) for tear-out). The findings are discussed in conjunction with the knot and tourniquet forces from our previous study. Conclusions: Even in healthy tissue, moderate forces can reach a critical level at which a Teflon pledget will cut into the annulus, while a complete tear-out is unlikely. The right coronary portion is more susceptible to damage than the remaining regions. When compared to previous data, forces during manual knotting may exceed the critical cut-in level, while rubber tourniquets may provide a higher safety margin against tissue rupture.
Journal Article
Establishing a global orthopedic surgery training program
by
Willms, Scott
,
Nesbitt, Colleen
,
Rees, Huw
in
International aspects
,
Orthopedic surgery
,
Surgery, Experimental
2025
Background: We established a 1-year fellowship training program in global orthopedic surgery at the University of Saskatchewan in 2023. Methods: The program is an ongoing, fully funded program directed toward orthopedic surgeons from low- and middle-income countries. These surgeons would typically have been denied access to a Canadian fellowship training position due to economic and licensing obstacles. The challenges associated with creating and maintaining a funded global surgical training program at a Canadian health care institution will be discussed and we will provide a step-by-step guide to establish a similar program in any subspecialty area at any training program in Canada. There will also be a discussion of the advantages and disadvantages of establishing a funded global training model versus shortterm medical missions. Results: pending. Conclusion: pending.
Journal Article
A general strategy towards personalized nanovaccines based on fluoropolymers for post-surgical cancer immunotherapy
2020
Cancer metastases and recurrence after surgical resection remain an important cause of treatment failure. Here we demonstrate a general strategy to fabricate personalized nanovaccines based on a cationic fluoropolymer for post-surgical cancer immunotherapy. Nanoparticles formed by mixing the fluoropolymer with a model antigen ovalbumin, induce dendritic cell maturation via the Toll-like receptor 4 (TLR4)-mediated signalling pathway, and promote antigen transportation into the cytosol of dendritic cells, which leads to an effective antigen cross-presentation. Such a nanovaccine inhibits established ovalbumin-expressing B16-OVA melanoma. More importantly, a mix of the fluoropolymer with cell membranes from resected autologous primary tumours synergizes with checkpoint blockade therapy to inhibit post-surgical tumour recurrence and metastases in two subcutaneous tumour models and an orthotopic breast cancer tumour. Furthermore, in the orthotopic tumour model, we observed a strong immune memory against tumour rechallenge. Our work offers a simple and general strategy for the preparation of personalized cancer vaccines to prevent post-operative cancer recurrence and metastasis.A fluoropolymer-based cancer nanovaccine that delivers antigens directly to the cytosol of dendritic cells and elicits strong antitumour immune responses inhibiting tumour growth in animal models can be used to produce personalized treatment for post-surgical immunotherapy.
Journal Article
High-precision tumor resection down to few-cell level guided by NIR-IIb molecular fluorescence imaging
2022
In vivo fluorescence/luminescence imaging in the near-infrared-IIb (NIR-IIb, 1,500 to 1,700 nm) window under <1,000 nm excitation can afford subcentimeter imaging depth without any tissue autofluorescence, promising high-precision intraoperative navigation in the clinic. Here, we developed a compact imager for concurrent visible photographic and NIR-II (1,000 to 3,000 nm) fluorescence imaging for preclinical image-guided surgery. Biocompatible erbium-based rare-earth nanoparticles (ErNPs) with bright down-conversion luminescence in the NIR-IIb window were conjugated to TRC105 antibody for molecular imaging of CD105 angiogenesis markers in 4T1 murine breast tumors. Under a ∼940 ± 38 nm light-emitting diode (LED) excitation, NIR-IIb imaging of 1,500- to 1,700-nm emission afforded noninvasive tumor–to–normal tissue (T/NT) signal ratios of ∼40 before surgery and an ultrahigh intraoperative tumor-to-muscle (T/M) ratio of ∼300, resolving tumor margin unambiguously without interfering background signal from surrounding healthy tissues. High-resolution imaging resolved small numbers of residual cancer cells during surgery, allowing thorough and nonexcessive tumor removal at the few-cell level. NIR-IIb molecular imaging afforded 10-times-higher and 100-times-higher T/NT and T/M ratios, respectively, than imaging with IRDye800CW-TRC105 in the ∼900- to 1,300-nm range. The vastly improved resolution of tumor margin and diminished background open a paradigm of molecular imaging-guided surgery.
Journal Article
Testing the proportional hazards assumption in cox regression and dealing with possible non-proportionality in total joint arthroplasty research: methodological perspectives and review
by
Kuitunen, Ilari
,
Ponkilainen, Ville T.
,
Reito, Aleksi
in
Arthroplasty
,
Complications
,
Epidemiology
2021
Background
Survival analysis and effect of covariates on survival time is a central research interest. Cox proportional hazards regression remains as a gold standard in the survival analysis. The Cox model relies on the assumption of proportional hazards (PH) across different covariates. PH assumptions should be assessed and handled if violated. Our aim was to investigate the reporting of the Cox regression model details and testing of the PH assumption in survival analysis in total joint arthroplasty (TJA) studies.
Methods
We conducted a review in the PubMed database on 28th August 2019. A total of 1154 studies were identified. The abstracts of these studies were screened for words “cox and “hazard*” and if either was found the abstract was read. The abstract had to fulfill the following criteria to be included in the full-text phase: topic was knee or hip TJA surgery; survival analysis was used, and hazard ratio reported. If all the presented criteria were met, the full-text version of the article was then read. The full-text was included if Cox method was used to analyze TJA survival. After accessing the full-texts 318 articles were included in final analysis.
Results
The PH assumption was mentioned in 114 of the included studies (36%). KM analysis was used in 281 (88%) studies and the KM curves were presented graphically in 243 of these (87%). In 110 (45%) studies, the KM survival curves crossed in at least one of the presented figures. The most common way to test the PH assumption was to inspect the log-minus-log plots (
n
= 59). The time-axis division method was the most used corrected model (
n
= 30) in cox analysis. Of the 318 included studies only 63 (20%) met the following criteria: PH assumption mentioned, PH assumption tested, testing method of the PH assumption named, the result of the testing mentioned, and the Cox regression model corrected, if required.
Conclusions
Reporting and testing of the PH assumption and dealing with non-proportionality in hip and knee TJA studies was limited. More awareness and education regarding the assumptions behind the used statistical models among researchers, reviewers and editors are needed to improve the quality of TJA research. This could be achieved by better collaboration with methodologists and statisticians and introducing more specific reporting guidelines for TJA studies. Neglecting obvious non-proportionality undermines the overall research efforts since causes of non-proportionality, such as possible underlying pathomechanisms, are not considered and discussed.
Journal Article
Clinical application of robotic orthopedic surgery: a bibliometric study
2021
Objectives
The present study aimed to evaluate the status and trends of robotic orthopedic surgery in a clinical setting using bibliometrics.
Methods
All relevant publications on the clinical use of robotic surgery in orthopedics were searched from the Web of Science database. Subsequently, data were analyzed using bibliometrics. Visualizing data of bibliographic coupling, co-citation, and co-occurrence analysis were performed using VOSviewer.
Results
In total, 224 clinical studies met the included standards between 2000 to 2019. Global publications presented an increasing annual trend, with the United States found to have the largest number of publications and robotic companies active in the field (
n
= 99), followed by China (
n
= 38), and the United Kingdom (
n
= 27). The institution with the most contributions was the Beijing Jishuitan Hospital in China (
n
= 15). The most productive scholars were Tian Wei and Mont Michael A, with 14 publications each. The top 30 most cited papers list showed 29 publications to be cited on more than 40 occassions. The journal with the most related and influential publications on robotic orthopedic surgery was the Journal of Arthroplasty. Fourteen types of robots were used, with the majority applied in knee and spinal surgery. MAKO was the most widely used robot in hip and knee surgery and Mazor in spinal surgery. Most studies were small sample populations of low-quality in this field. The top 20 most frequently used keywords were identified from 950 author keywords. Research on orthopedic robots were classified into two clusters by co-occurrence networks: spinal-related robotic surgery and joint-related robotic surgery.
Conclusions
The present bibliometric study summarizes the clinical research of orthopedic robots on study type, sample size, type of surgery, robot information, surgical site, most popular keywords, most cited papers, journals, authors, institutions, and countries. These findings may assist the scholars better understand the current status and research trends to guide future practice and directions.
Journal Article