Purpose
Osteochondral implants are currently adopted for the treatment of symptomatic full-thickness chondral and osteochondral defects. Agili-C™ is a cell-free aragonite-based scaffold which aims to ...reproduce the original structure and function of the articular joint while directing the growth and regeneration of both cartilage and its underlying subchondral bone. The goal of the present study was to investigate the ex vivo mechanisms of action (MOA) of the Agili-C™ implant in the repair of full-thickness cartilage defects. In particular, we tested whether Agili-C™ implant has the potential to stimulate cartilage ingrowth through chondrocytes migration into the 3D interconnected porous structure of the scaffold, along with maintaining their viability and phenotype and the deposition of hyaline cartilage matrix.
Methods
Articular cartilage samples were collected through the Gift of Hope Organ and Tissue Donor Network (Itasca, IL) within 24 h from death. For this study, cartilage from a total of 14 donors was used. To model a chondral defect, donut-shaped cartilage explants were prepared from each tissue specimen. The chondral phase of the Agili-C™ implant was placed inside the tissue in full contact and press fit manner. Cartilage explants with the Agili-C™ implant inside were cultured for 60 days. As a control, the same donut-shaped cartilage explants were cultured without Agili-C™, under the same culture conditions.
Results
Using fresh human cadaveric articular cartilage tissue in a 60-day culture, it was demonstrated that chondrocytes were able to migrate into the Agili-C™ scaffold and contribute to the deposition of the extracellular matrix (ECM) rich in collagen type II and aggrecan, and lacking collagen type I. Additionally, we were able to show the formation of a layer populated by progenitor-like cells on the articular surface of the implant.
Conclusions
The analysis of samples taken from knee and ankle joints of human donors with a wide age range and both genders supports the potential of Agili-C™ scaffold to stimulate cartilage regeneration and repair. Based on these results, the present scaffold can be used in the clinical practice as a one-step procedure to treat full-thickness chondral defects.
Background
Although studied in a few randomized controlled trials, the efficacy of medical cannabis (MC) for chronic pain remains controversial. Using an alternative approach, this multicentre, ...questionnaire‐based prospective cohort was aimed to assess the long‐term effects of MC on chronic pain of various aetiologies and to identify predictors for MC treatment success.
Methods
Patients with chronic pain, licensed to use MC in Israel, reported weekly average pain intensity (primary outcome) and related symptoms before and at 1, 3, 6, 9 and 12 months following MC treatment initiation. A general linear model was used to assess outcomes and identify predictors for treatment success (≥30% reduction in pain intensity).
Results
A total of 1,045 patients completed the baseline questionnaires and initiated MC treatment, and 551 completed the 12‐month follow‐up. At 1 year, average pain intensity declined from baseline by 20% −1.97 points (95%CI = −2.13 to −1.81; p < 0.001). All other parameters improved by 10%–30% (p < 0.001). A significant decrease of 42% reduction of 27 mg; (95%CI = −34.89 to 18.56, p < 0.001) from baseline in morphine equivalent daily dosage of opioids was also observed. Reported adverse effects were common but mostly non‐serious. Presence of normal to long sleep duration, lower body mass index and lower depression score predicted relatively higher treatment success, whereas presence of neuropathic pain predicted the opposite.
Conclusions
This prospective study provides further evidence for the effects of MC on chronic pain and related symptoms, demonstrating an overall mild‐to‐modest long‐term improvement of the tested measures and identifying possible predictors for treatment success.
Background and Objective: Medical cannabis is becoming an acceptable treatment modality in medicine, especially for pain relief. Concurrently, cannabis use is becoming more prevalent worldwide, a ...public demand-driven trend despite the lack of established scientific basis. This observational open-label study sought to investigate the effectiveness of cannabis therapy for alleviating low back pain symptoms. Methods: Two types of cannabis treatment modalities were sequentially administered to chronic low back pain patients. After an initial 1-month washout period (WO1), the first modality was cannabidiol (CBD)-rich sublingual extract treatment administered for 10 months. Following another washout period, the second modality, Δ⁹-tetrahydrocannabinol (THC)-rich smoked inflorescence (whole dried cannabis flowers) was administered for 12 months. Results: Enrolled in the study were 24 patients whose advanced imaging studies (i.e. computerized tomography or magnetic resonance imaging of the lumbar spine) revealed disc herniation or spinal stenosis. Three patients dropped out of extract therapy treatment but resumed study participation to receive THC-rich smoking therapy. After a minimum of 2 years, cannabis therapy had reduced lower back pain symptoms, as assessed by Oswestry Disability Index, the SF-12 patient-reported outcome questionnaire, and the visual analogue scale. Pain reduction was not significant during the extract treatment part of the study; however, pain reduction was significant during the inhaled therapy part of the study. Conclusions: Our findings indicate that inhaled THC-rich therapy is more effective than CBD-rich sublingual extract therapy for treating low back pain and that cannabis therapy is safe and effective for chronic low back pain.
To investigate the safety and regenerative potential of a hemicondylar aragonite–based scaffold in the reconstruction of large osteochondral lesions occupying an extensive portion of the medial ...femoral condyle in a goat model.
Eight Saanen goats were treated by the implantation of an aragonite-based scaffold (size: 19 × 8 × 8 mm) on a previously prepared hemicondylar osteochondral defect located in the right medial femoral condyle of the knee. Goats were euthanized after 12 months and the specimens underwent X-ray imaging, macroscopic, micro-computed tomography, histology, and immunohistochemistry evaluations to assess subchondral bone and cartilage regeneration.
In all 8 goats, no adverse event or persistent inflammation was observed. The evaluations performed showed integration of the scaffold, which almost completely resorbed at 12 months. In all animals, no signs of osteoarthritis progression were seen. Concurrent regeneration of the osteochondral unit was observed, with trabecular bone tissue replacing the implant and restoring the subchondral layer, and the formation of an overlying hyaline cartilage surface, well integrated within the surrounding native tissue, also was observed.
The use of the hemicondylar biphasic aragonite–based implant in the treatment of osteochondral defects in the goat model proved to be technically feasible and safe. The scaffold degraded and was replaced by regenerated tissue within the 12-month study period, restoring the osteochondral unit both at the level of the cartilaginous layer and the subchondral bone.
The present animal study describes a scaffold-based procedure for the treatment of large condylar defects, which often require massive allograft or unicompartmental replacement. The aragonite-based implant promoted a regeneration of both cartilage and subchondral bone, and its use as a “biologic” unicondylar prosthesis might be feasible also in the clinical setting.
Polyp segmentation is an important task in early identification of colon polyps for prevention of colorectal cancer. Numerous methods of machine learning have been utilized in an attempt to solve ...this task with varying levels of success. A successful polyp segmentation method which is both accurate and fast could make a huge impact on colonoscopy exams, aiding in real-time detection, as well as enabling faster and cheaper offline analysis. Thus, recent studies have worked to produce networks that are more accurate and faster than the previous generation of networks (e.g., NanoNet). Here, we propose ResPVT architecture for polyp segmentation. This platform uses transformers as a backbone and far surpasses all previous networks not only in accuracy but also with a much higher frame rate which may drastically reduce costs in both real time and offline analysis and enable the widespread application of this technology.
Chitosan hydrogels (CHs) have been considered as a potential implant material for replacement and repair of the Nucleus Pulposus (NP) within the intervertebral disk. The nonlinear mechanical behavior ...of a CH material is investigated experimentally and computationally in this study. A series of confined and unconfined compression tests are designed and conducted for this hydrogel. Hyperelastic strain energy density functions (SEDFs) are calibrated using the experimental data. A hyperelastic constitutive model is selected to best fit the multi-axial behavior of the hydrogel. Its general prediction ability is verified using finite element (FE) simulations of hydrogel indentation experiments conducted using a spherical tip indentor. In addition, digital image correlation (DIC) technique is also used in the indentation test in order to process the full-field surface strains where the indentor contacts the hydrogel. The DIC test results in the form of top-surface strains compared well with those predicted by the FE model. Results show repeatability for the examined specimens under the applied tests. Confined and unconfined test results are found to be sufficient to calibrate the SEDFs. The Ogden model was selected to represent the nonlinear behavior of the CH material which can be used in future biomechanical simulations of the spine.
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► Chitosan hydrogels as implant material within the intervertebral disk. ► Hydrogel nonlinear mechanical behavior is investigated experimentally and computationally. ► Best fit hyperelastic constitutive model selection under multi-axial loading. ► A digital image correlation technique to verify the chitosan constitutive model. ► Finite-element simulations for indentation tests of hydrogels.
Thoracolumbar facet orientations were measured and analyzed.
To establish a comprehensive database for facet orientation in the thoracolumbar vertebrae and to determine the normal human condition.
...Most studies on facet orientation have based their conclusions on two-dimensional measurements, in small samples or isolated vertebrae. The amount of normal asymmetry in facet orientation is poorly addressed.
Transverse and longitudinal facet angles were measured directly from 240 human vertebral columns (males/females, blacks/whites). The specimens' osteologic material is part of the Hamann-Todd Osteological Collection housed at the Cleveland Museum of Natural History (Cleveland, OH). A total of 4,080 vertebrae (T1-L5) from the vertebral columns of individuals 20 to 80 years of age were measured, using a Microscribe three-dimensional apparatus (Immersion Co., San Jose, CA). Data were recorded directly on computer software. Statistical analysis included paired t tests and analysis of variance. RESULTS.: Facet orientation is independent of gender, age, and ethnic group. Asymmetry in facet orientation is found in the thorax. All thoracolumbar facets are positioned in an oblique plane. In the transverse plane, all facets from T1 to T11 are positioned with an anterior inclination of approximately 25 degrees to 30 degrees from the frontal plane. The facets of T12-L2 are oriented closer to the midsagittal plane of the vertebral body (mean range, 25.89 degrees-33.87 degrees), while the facets of L3-L5 are oriented away from that plane (mean range, 40.40 degrees-56.30 degrees). Facet transverse orientation at the thoracolumbar junction is highly variable (approximately 80% with approximately 101 degrees and approximately 20% with 35 degrees). All facets are oriented more vertically from T1 (approximately 150 degrees) to L5 (approximately 170 degrees). The facet sagittal orientations of the lumbar zygoapophyseal joints are not equivalent. CONCLUSIONS.: Asymmetry in facet orientation is a normal characteristic in the thorax.
The use of medicinal cannabis for managing pain expands, although its efficacy and safety have not been fully established through randomized controlled trials.
This structured, prospective ...questionnaire-based cohort was aimed to assess long-term effectiveness and safety of cannabis oil extracts in patients with chronic pain.
Adult Israeli patients licensed to use cannabis oil extracts for chronic pain were followed prospectively for 6 months. The primary outcome measure was change from baseline in average weekly pain intensity, and secondary outcomes were changes in related symptoms and quality of life, recorded before treatment initiation and 1, 3, and 6 months thereafter. Generalized linear mixed model was used to analyze changes over time. In addition, "responders" (≥30% reduction in weekly pain at any time point) were identified.
The study included 218 patients at baseline, and 188, 154, and 131 at 1, 3, and 6 months, respectively. At 6 months, the mean daily doses of cannabidiol and Δ9-tetrahydrocannabinol were 22.4 ± 24.0 mg and 20.8 ± 30.1 mg, respectively. Pain decreased from 7.9 ± 1.7 at baseline to 6.6 ± 2.2 at 6 months (
(3,450) = 26.22,
< 0.0001). Most secondary parameters also significantly improved. Of the 218 participants, 24% were "responders" but could not be identified by baseline parameters. "Responders" exhibited higher improvement in secondary outcomes. Adverse events were common but mostly nonserious.
This prospective cohort demonstrated a modest overall long-term improvement in chronic pain and related symptoms and a reasonable safety profile with the use of relatively low doses of individually titrated Δ9-tetrahydrocannabinol and cannabidiol.
Arabs are a large minority group in the Israeli society. With the increasing use of medical cannabis throughout Israel due to changing governmental policies, the interactions of the Arab society with ...medical cannabis becomes of scientific and medical relevance. Recreational cannabis use is considered haram (forbidden) in Islam. However, most religious scholars agree that medical cannabis usage might be justified as zarurat (emergency and life-saving, therefore allowed) use. Obstacles to medical cannabis use within the Arabic population may relate to language barrier and/or cultural barriers. There are few Arabic-speaking web-based medical-cannabis support groups, and little official information about it is available in the Arabic language. In order for the full benefits of medical cannabis to reach the entire Israeli population, a government-sponsored web-based educational program is necessary in Hebrew and Arabic, both of which are among the nation's official languages, thereby contributing to the equalization of health resource accessibility.
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