Transcriptional Profiling of Synovial Macrophages using Minimally Invasive Ultrasound-Guided Synovial Biopsies in Rheumatoid Arthritis [dataset1]
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ABSTRACT:
ORGANISM(S): Homo sapiens
PROVIDER: GSE314078 | GEO | 2025/12/22
REPOSITORIES: GEO
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Project description:Pilot study of the feasibility and clinical significance of whole tissue and cell-type-specific transcriptional profiling of cells from synovial biopsy in Rheumatoid Arthritis (RA)
2025-12-18 | GSE314080 | GEO
Project description:ObjectiveCurrently, there are no reliable biomarkers for predicting therapeutic response in patients with rheumatoid arthritis (RA). The synovium may unlock critical information for determining efficacy, since a reduction in the numbers of sublining synovial macrophages remains the most reproducible biomarker. Thus, a clinically actionable method for the collection of synovial tissue, which can be analyzed using high-throughput strategies, must become a reality. This study was undertaken to assess the feasibility of utilizing synovial biopsies as a precision medicine-based approach for patients with RA.MethodsRheumatologists at 6 US academic sites were trained in minimally invasive ultrasound-guided synovial tissue biopsy. Biopsy specimens obtained from patients with RA and synovial tissue from patients with osteoarthritis (OA) were subjected to histologic analysis, fluorescence-activated cell sorting, and RNA sequencing (RNA-seq). An optimized protocol for digesting synovial tissue was developed to generate high-quality RNA-seq libraries from isolated macrophage populations. Associations were determined between macrophage transcriptional profiles and clinical parameters in RA patients.ResultsPatients with RA reported minimal adverse effects in response to synovial biopsy. Comparable RNA quality was observed from synovial tissue and isolated macrophages between patients with RA and patients with OA. Whole tissue samples from patients with RA demonstrated a high degree of transcriptional heterogeneity. In contrast, the transcriptional profile of isolated RA synovial macrophages highlighted different subpopulations of patients and identified 6 novel transcriptional modules that were associated with disease activity and therapy.ConclusionPerformance of synovial tissue biopsies by rheumatologists in the US is feasible and generates high-quality samples for research. Through the use of cutting-edge technologies to analyze synovial biopsy specimens in conjunction with corresponding clinical information, a precision medicine-based approach for patients with RA is attainable.
| S-EPMC5984677 | biostudies-literature
Project description:Transcriptional Profiling of Synovial Macrophages using Minimally Invasive Ultrasound-Guided Synovial Biopsies in Rheumatoid Arthritis [dataset2]
| PRJNA1390053 | ENA
Project description:IntroductionTo improve patient outcomes (eg, reducing blood loss and infection), practitioners have gravitated toward noninvasive and minimally invasive surgeries (MIS), which demand specialized toolkits. Focused ultrasound, for example, facilitates thermal ablation from a distance, thereby reducing injury to surrounding tissue. Focused ultrasound can often be performed noninvasively; however, it is more difficult to carry out in neuro-oncological tumors, as ultrasound is dramatically attenuated while propagating through the skull. This shortcoming has prompted exploration of MIS options for intracranial placement of focused ultrasound probes, such as within the BrainPath™ (NICO Corporation, Indianapolis, IN). Herein, we present the design, development, and in vitro testing of an image-guided, focused ultrasound prototype designed for use in MIS procedures. This probe can ablate neuro-oncological lesions despite its small size.Materials & methodsPreliminary prototypes were iteratively designed, built, and tested. The final prototype consisted of three 8-mm-diameter therapeutic elements guided by an imaging probe. Probe functionality was validated on a series of tissue-mimicking phantoms.ResultsLesions were created in tissue-mimicking phantoms with average dimensions of 2.5 × 1.2 × 6.5 mm and 3.4 × 3.25 × 9.36 mm after 10- and 30-second sonification, respectively. 30 s sonification with 118 W power at 50% duty cycle generated a peak temperature of 68 °C. Each ablation was visualized in real time by the built-in imaging probe.ConclusionWe developed and validated an ultrasound-guided focused ultrasound probe for use in MIS procedures. The dimensional constraints of the prototype were designed to reflect those of BrainPath trocars, which are MIS tools used to create atraumatic access to deep-seated brain pathologies.
| S-EPMC8895244 | biostudies-literature
Project description:ObjectivesTo develop an EULAR training model for education in synovial tissue biopsy (STB) under ultrasound guidance (UG) following a stepwise approach: (1) development of educational material on UGSTB in large and small joints; (2) assessment of the validity, reliability and feasibility of the UGSTB educational procedure on cadaveric specimens; (3) validation of this procedure in live patients.MethodsUsing a nominal group (NG) and a DELPHI consensus methodology, educational audio-visual (AV) material and minimal requirements for education in UGSTB were developed by an expert panel. Then the experts performed an UGSTB on cadaveric joints using the developed approach. The samples retrieved from the cadaveric joints were confirmed histologically and the procedure was then tested by a group of ultrasonographers with different expertise for feasibility and face validity. The AV material and the practical procedures' phases were subsequently ranked by the experts to finalise the training model for performing UGSTB in patients. The ST retrieved in patients was assessed for tissue quality.ResultsBased on NG and DELPHI processes, educational material and a stepwise standardised cadaver-based training model were developed. The knee was the cadaveric joint with the highest yield of histologically good quality of ST. 90% of the UGSTB from patients showed synovial membrane and 77% intact lining layer.ConclusionsThis EULAR endeavour provided a consensus-based comprehensive educational material and a practical cadaver-based model for training in UGSTB, which has shown feasibility and validity in tissue acquisition in specimens and patients.
| S-EPMC11749067 | biostudies-literature
Project description:BackgroundMinimally invasive autopsies, also known as minimally invasive tissue sampling (MITS), have proven to be an alternative to complete diagnostic autopsies (CDAs) in places or situations where this procedure cannot be performed. During the coronavirus disease 2019 (COVID-19) pandemic, CDAs were suspended by March 2020 in Brazil to reduce biohazard. To contribute to the understanding of COVID-19 pathology, we have conducted ultrasound (US)-guided MITS as a strategy.MethodsThis case series study includes 80 autopsies performed in patients with COVID-19 confirmed by laboratorial tests. Different organs were sampled using a standardized MITS protocol. Tissues were submitted to histopathological analysis as well as immunohistochemical and molecular analysis and electron microscopy in selected cases.ResultsUS-guided MITS proved to be a safe and highly accurate procedure; none of the personnel were infected, and accuracy ranged from 69.1% for kidney, up to 90.1% for lungs, and reaching 98.7% and 97.5% for liver and heart, respectively. US-guided MITS provided a systemic view of the disease, describing the most common pathological findings and identifying viral and other infectious agents using ancillary techniques, and also allowed COVID-19 diagnosis confirmation in 5% of the cases that were negative in premortem and postmortem nasopharyngeal/oropharyngeal swab real-time reverse-transcription polymerase chain reaction.ConclusionsOur data showed that US-guided MITS has the capacity similar to CDA not only to identify but also to characterize emergent diseases.
| S-EPMC8672862 | biostudies-literature
Project description:BackgroundContraceptive arm implants, such as Implanon NXT®/Nexplanon®, are reversible methods of birth control that have gained global popularity, with over 20 million worldwide users. While palpable implants can be easily removed, deep or non-palpable implants pose complications during extraction, often requiring open surgery. This ultrasound-guided removal technique offers a minimally invasive, safe, and effective alternative, providing real-time control over the implant and neurovascular structures. Our study aims to evaluate the effectiveness and challenges of this implant removal method.MethodsIn this retrospective observational study, all cases referred to our institution for ultrasound-guided removal of contraceptive implants, from June 2022 to December 2023, were reviewed. Our facility serves as a referral center for handling challenging implants. Twenty-nine women with contraceptive implants were referred for implant removal in this period of time. Thirty implants were sent for removal in total (one patient had a double implant). Data specific to the patients were collected: age and body mass index (BMI). Data specific to the implant were also collected: time since implant insertion (months), history of a previous removal attempt, type of implant (single or double rod), implant palpability, laterality of the implant, supra or subfascial location, success or failure of the ultrasound-guided removal procedure and presence of complications in the post-procedure. Statistical analysis was conducted to determine the relationship between the procedure success rate and these variables, and also between these variables and the supra or subfascial location of the implant.ResultsTwenty-six of the 30 implants (86.67%) were successfully removed with this fully ultrasound-guided technique. In cases where the implant could not be removed, there was a higher rate of subfascial implant location (75%), while in cases where the removal was successful, the rate of subfascial implant location was significantly lower at 19.23% (P=0.048). Patients whose implants could be removed had a median BMI of 23.71 kg/m2, which was higher than the BMI of patients whose implants could not be removed (20.82 kg/m2), with a P=0.022. No complications were registered.ConclusionsPercutaneous real-time ultrasound-guided implant removal is effective, safe and offers a minimally-invasive alternative to open surgery. The removal of subfascial implants is also feasible but more challenging, leading to a reduction of success rate in this group. These positive outcomes suggest its potential as a standard initial approach for deep contraceptive implant removal.
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Project description:ObjectivesTo determine the feasibility and safety of ultrasound-guided minimally invasive autopsy in COVID-19 patients.Methods60 patients who expired between 04/22/2020-05/06/2020 due to COVID-19 were considered for inclusion in the study, based on availability of study staff. Minimally invasive ultrasound-guided autopsy was performed with 14G core biopsies through a 13G coaxial needle. The protocol required 20 cores of the liver, 30 of lung, 12 of spleen, 20 of heart, 20 of kidney, 4 of breast, 4 of testis, 2 of skeletal muscle, and 4 of fat with total of 112 cores per patient. Quality of the samples was evaluated by number, size, histology, immunohistochemistry, and in situ hybridization for COVID-19 and PCR-measured viral loads for SARS-CoV-2.ResultsFive (5/60, 8%) patients were included. All approached families gave their consent for the minimally invasive autopsy. All organs for biopsy were successfully targeted with ultrasound guidance obtaining all required samples, apart from 2 patients where renal samples were not obtained due to atrophic kidneys. The number, size, and weight of the tissue cores met expectation of the research group and tissue histology quality was excellent. Pathology findings were concordant with previously reported autopsy findings for COVID-19. Highest SARS-CoV-2 viral load was detected in the lung, liver, and spleen that had small to moderate amount, and low viral load in was detected in the heart in 2/5 (40%). No virus was detected in the kidney (0/3, 0%).ConclusionsUltrasound-guided percutaneous post-mortem core biopsies can safely provide adequate tissue. Highest SARS-CoV-2 viral load was seen in the lung, followed by liver and spleen with small amount in the myocardium.
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Project description:Organ-directed gene transfer remains an attractive method for both gaining a better understanding of heart disease and for cardiac therapy. However, virally mediated transfer of gene products into cardiac cells requires prolonged exposure of the myocardium to the viral substrate. Pericardial injection of viral vectors has been proposed and used with some success to achieve myocardial transfection and may be a suitable approach for transfection of atrial myocardium. Indeed, such an organ-specific method would be particularly useful to reverse phenotypes in young and adult genetically altered murine models of cardiac disease. We therefore sought to develop a minimally invasive technique for pericardial injection of substances in mice. Pericardial access in anaesthetised, spontaneously breathing mice was achieved using continuous high-resolution ultrasound guidance. We could demonstrate adequate delivery of injected substances into the murine pericardium. Atrial epicardial and myocardial cells were transfected in approximately one third of mice injected with enhanced green fluorescent protein-expressing adenovirus. Cellular expression rates within individual murine atria were limited to a maximum of 20 %; therefore, expression efficiency needs to be further improved. Minimally invasive, ultrasound-guided injection of viral material appears a technically challenging yet feasible method for selective transfection of atrial epi- and myocardium. This pericardial injection method may be useful in the evaluation of potential genetic interventions aimed at rescuing atrial phenotypes in transgenic mouse models.
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