Foot Surgery Using Resorbable Magnesium Screws.

The use of bioabsorbable magnesium (Mg) screws is new in foot surgery. Their relative merit over conventional titanium screws has not yet been proven. This prospective case series study was conducted to compare the clinical and radiological outcomes of bioabsorbable Mg screws and titanium screws. A consecutive series of patients (n = 60; 11 men and 49 women) underwent corrective hallux valgus surgery. The minimum follow-up period was 1 year. The assessment was based on a patient questionnaire, including the American Orthopedic Foot and Ankle Society (AOFAS) hallux valgus score, visual analog scale, patient's global impression of change (PGIC), and fifth metatarsus circumference (IF5C). The radiographic assessment included the intermetatarsal and hallux valgus angles, as well as time to osteotomy union and hardware failure. At 1 year, similar results were obtained radiographically. The healing of the osteotomies was significantly faster in the Mg group. Hardware failure was common in the Mg group (5/26) than in the TI group (0/34) but hardware removal was more common in the TI group (6/34) versus the MG group (0/26). IF5C increased by 8 ± 2 mm in the Mg group. The AOFAS and PGIC scores at 6 months were similar. Validated foot scores and radiographic analysis indicated that there was no detectable difference between the groups. The fast achievement of osteotomy union compensates for a high rate of hardware failure, resulting in patient satisfaction and avoiding reoperation for hardware removal.

Bromelain-based enzymatic debridement of chronic wounds: Results of a multicentre randomized controlled trial.

Chronic wounds are estimated to affect over 6 million people annually in the United States with an estimated annual cost of $25 billion. Debridement represents a key step in their management and is considered a basic necessity to induce the functional process of tissue repair. However, there is an unmet need for an efficient rapid acting non-surgical debridement agent. Bromelain-based enzymatic debridement has been proven to provide an effective, selective and safe non-surgical debridement in deep burns. EscharEx (MediWound Ltd, Yavne, Israel), is a bromelain-based enzymatic debridement agent currently in development for chronic wounds. The aim of this study was to assess its safety and efficacy in chronic wounds. Seventy-three patients suffering from a lower extremity ulcer of diabetic/venous insufficiency/post-surgical/traumatic aetiology were enrolled in a multicentre, assessor blinded, randomized controlled trial. Patients were randomized to topical treatment by either EscharEx or its gel vehicle for up to 10 daily 4 hour applications, and then continued follow-up for up to 6 months. The EscharEx arm achieved a significantly higher incidence of complete debridement compared to the gel vehicle arm; 55 versus 29% (p = .047), thus meeting the primary endpoint of this study. The EscharEx and gel vehicle arms achieved similar reductions in wound area, non-viable tissue area and wound healing scores during the debridement period. There were no significant differences between the arms in the incidence of complete wound closure (41% in the EsxcharEx arm vs. 53% in the gel vehicle arm) and in the mean time to complete wound closure (70.0 ± 32.8 days in the EsxcharEx arm vs. 65.7 ± 38.4 days in gel vehicle arm). There were no significant safety issues and EscharEx demonstrated a favourable benefit to risk profile.

Treatment of hallux rigidus by a novel bi-phasic aragonite-based implant: results of a two year multi-centre clinical trial.

PURPOSE: The two year results of a multi-centre clinical trial were examined to evaluate surgical treatment of hallux rigidus using a novel, bi-phasic, biodegradable, and cell-free aragonite-based scaffold (Agili-C™, CartiHeal Ltd, Israel). METHODS: Twenty patients with moderate-to-severe hallux rigidus were recruited. After thorough metatarsophalangeal joint (MTPJ-1) debridement, the scaffolds were implanted into the defect centre. Eight patients received concomitant osteotomy. Treatment outcome was followed clinically (Pain VAS, FAAM-ADL, FAAM-Sport, AOFAS-HMIS, maximum active range of extension ROM-EXT, and flexion ROM-FLEX), and by medical imaging, at six month intervals for two years. Adverse events were recorded throughout the study follow-up period. RESULTS: Significant clinical improvement over time was observed in all evaluated parameters (screening to final evaluation averages: Pain VAS 59 to 26, FAAM-ADL 57 to 77, FAAM-Sport 39 to 66, AOFAS-HMIS 51 to 81, ROM-EXT 18° to 36°), except for ROM-FLEX. Radiographs showed stable MTPJ-1 width over the two years in 17/18 cases (94%). MRI demonstrated progressive implant biodegradation, coupled with articular cartilage and subchondral bone regeneration, with a repair tissue defect fill of 75-100% in 14/17 (82%) subjects at their final visit. Revision surgery with implant removal was performed in two patients. CONCLUSION: Bi-phasic, osteochondral, biodegradable, aragonite-based scaffold demonstrated positive clinical outcome and a good safety profile in the treatment of medium-to-advanced hallux rigidus. According to the medical imaging, this implant has the potential to restore the entire osteochondral unit of metatarsal head.

Complex Osteochondral Lesions of the Talus Treated With a Novel Bi-Phasic Aragonite-based Implant.

To present initial results of a novel, bi-phasic, porous, biodegrade, and cell-free aragonite-based scaffold for treating complex osteochondral lesions of the talus (OLT). Four subjects (2 males and 2 females; 34-61 years old) were operated on their ankles due to chronic and deep OLT-Hepple grades 4 or 5 (1.8-2.2 cm2). Three subjects had OLT on the medial central trochlea, and 1 had a combined medial and lateral lesions. OLT were exposed through medial malleolus osteotomy, with an additional lateral arthrotomy in the combined lesions. Bi-phasic porous osteochondral scaffolds (single implant or 2 implants) were implanted in a press-fit manner using a designated surgical toolset. Treatment outcome was followed clinically (Foot and Ankle Outcome Score, EQ-5D 3L, Tegner activity scale) and by medical imaging (radiographs, magnetic resonance imaging) from 18 to 32 months. All Foot and Ankle Outcome Score values increased from preoperative to final follow-up values (Symptoms 62 to 71, Pain 53 to 84, ADL 60 to 89, Sport 19 to 65, and QoL 18 to 47). EQ-5D 3L increased from 0.59 to 0.76, and Tegner activity values increased from 1.5 to 3. Kellgren-Lawrence ankle radiographic scores remained stable (2 to 2). Postoperative MR evaluation demonstrated cartilage defect fill of 75% to 100% respect to the native cartilage in 3 subjects (4 OLTs), while 1 lesion was filled 25% to 50%. No graft related serious adverse events or graft failures were reported. The use of a bi-phasic osteochondral biodegradable aragonite-based scaffold in the treatment of complex OLT during the reported period presented positive and promising clinical and radiologic outcome, without serious adverse events or graft failures.

Osteogenic differentiation of human bone marrow-derived mesenchymal stem cells is enhanced by an aragonite scaffold.

Bone graft substitutes and bone void fillers are predominantly used to treat bone defects and bone fusion in orthopaedic surgery. Some aragonite-based scaffolds of coralline exoskeleton origin exhibit osteoconductive properties and are described as useful bone repair scaffolds. The purpose of this study was to evaluate the in vitro osteogenic potential of the bone phase of a novel aragonite-based bi-phasic osteochondral scaffold (Agili-C™, CartiHeal Ltd.) using adult human bone marrow-derived mesenchymal stem cells (MSCs). Analyses were performed at several time intervals: 3, 7, 14, 21, 28 and 42 days post-seeding. Osteogenic differentiation was assessed by morphological characterisation using light microscopy after Alizarin red and von Kossa staining, and scanning electron microscopy. The transcript levels of alkaline phosphatase (ALP), runt-related transcription factor 2 (RUNX2), bone gamma-carboxyglutamate (BGLAP), osteonectin (SPARC) and osteopontin (SPP1) were determined by quantitative PCR. Proliferation was assessed by a thymidine incorporation assay and proliferating cell nuclear antigen (PCNA) immunocytochemistry. Our results demonstrate that the bone phase of the bi-phasic aragonite-based scaffold supports osteogenic differentiation and enhanced proliferation of bone marrow-derived MSCs at both the molecular and histological levels. The scaffold was colonized by differentiating MSCs, suggesting its suitability for incorporation into bone voids to accelerate bone healing, remodelling and regeneration. The mechanism of osteogenic differentiation involves scaffold surface modification with de novo production of calcium phosphate deposits, as revealed by energy dispersive spectroscopy (EDS) analyses. This novel coral-based scaffold may promote the rapid formation of high quality bone during the repair of osteochondral lesions.

Reconstruction of Large Osteochondral Defects Using a Hemicondylar Aragonite-Based Implant in a Caprine Model.

PURPOSE: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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. CLINICAL RELEVANCE: 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.

Percutaneous surgery of the forefoot compared with open technique - Functional results, complications and patient satisfaction.

BACKGROUND: The use of percutaneous surgery is currently very common in foot and ankle surgery. The following prospective open-label patient-preference based study compares the traditional open technique versus the percutaneous surgery technique. METHODS: The current study describes the results of 287 patients operated due to forefoot deformities either by open surgery or percutaneously. 96 of them underwent hallux valgus corrective surgery. The rest had lesser toe deformities. They were followed for a period of up to 24 months, to assess the surgery related pain, complications, and patient satisfaction. 112 patients were operated using a conventional open technique were compared to 175 patients treated using a percutaneous technique. Technique choice was left to the patient preference, though older patients with disturbed blood flow, were advised to undergo percutaneous surgery. RESULTS: There is less pain using the percutaneous techniques relative to the open technique during the first 6 post-operative weeks. The 6, and 24 months FAOS score is similar in both groups. Complications are rare in any of the groups, with a significantly higher ASEPSIS score in the open surgery group. CONDCLUSIONS: Percutaneous forefoot surgery appears safe and efficacious, demonstrating equal radiographic (in a 96 strong cohort of hallux valgus patients) and clinical results at six and 24 months. Due to less post-operative pain, and less infection risk it appears that percutaneous techniques are superior to open technique in some respects of treatment and indeed the PGIC of patients was significantly higher in this group.

Effect of adding medical cannabis to analgesic treatment in patients with low back pain related to fibromyalgia: an observational cross-over single centre study.

OBJECTIVES: Low back pain (LBP) occurs in many patients with fibromyalgia (FM). The current study aimed to assess the possible pain and function amelioration associated with medical cannabis therapy (MCT) in this setting. METHODS: 31 patients were involved in an observational cross-over study. The patients were screened, treated with 3 months of standardised analgesic therapy (SAT): 5 mg of oxycodone hydrochloride equivalent to 4.5 mg oxycodone and 2.5 mg naloxone hydrochloride twice a day and duloxetine 30 mg once a day. Following 3 months of this therapy, the patients could opt for MCT and were treated for a minimum of 6 months. Patient reported outcomes (PRO's) included: FIQR, VAS, ODI and SF-12 and lumbar range of motion (ROM) was recorded using the modified Schober test. RESULTS: While SAT led to minor improvement as compared with baseline status, the addition of MCT allowed a significantly higher improvement in all PRO's at 3 months after initiation of MCT and the improvement was maintained at 6 months. ROM improved after 3 months of MCT and continued to improve at 6 months. CONCLUSIONS: This observational cross-over study demonstrates an advantage of MCT in FM patients with LBP as compared with SAT. Further randomised clinical trial studies should assess whether these results can be generalised to the FM population at large.

Agili-C implant promotes the regenerative capacity of articular cartilage defects in an ex vivo model.

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.

[PERCUTANEOUS CORRECTION OF FOREFOOT DEFORMITIES IN DIABETIC PATIENTS IN ORDER TO PREVENT PRESSURE SORES - TECHNIQUE AND RESULTS IN 20 CONSECUTIVE PATIENTS].

INTRODUCTION: Diabetes mellitus is a 21st century pandemic. Due to life-span prolongation combined with the increased rate of diabetes, a growing population of patients is afflicted with neuropathic foot deformities. Traditional operative repair of these deformities is associated with a high complication rate and relatively common infection incidence. In recent years, in order to prevent these complications, percutaneous deformity correction methods were developed. OBJECTIVES: Description of experience accumulated in treating 20 consecutive patients with diabetic neuropathic foot deformities treated in a percutaneous fashion. METHODS: A consecutive series of patients treated at our institute for neuropathic foot deformity was assessed according to a standard protocol using the AOFAS forefoot score and the LUMT score performed at baseline as well as at 6 months and 12 months. Treatment related complications were monitored. RESULTS: All procedures were performed in an ambulatory setting using local anesthesia. A total of 12 patients had soft tissue corrections, and 8 had a combined soft tissue and bone correction. Baseline AOFAS score was 48±7 and improved to 73±9 at six months and 75±7 at one year. LUMT score in 11 patients with a chronic wound decreased from 22±4 to 2±1 at one year post-op. One patient required hospitalization due to post-op bleeding. CONCLUSIONS: Percutaneous techniques allow deformity correction of diabetic feet, including those with open wounds in an ambulatory setting with a low complication rate.

All-polyethylene tibial components are not inferior to metal-backed tibial components in long-term follow-up of knee arthroplasties.

BACKGROUND: All-polyethylene tibias (APT) are under-utilized in most of the Western countries, due to a shift from the original all-polyethylene design to metal-backed tibia (MBT) components. Only few total knee prostheses allow direct comparison between APT and MBT components, due to different geometric designs in many systems. The Depuy PFC Sigma prostheses have a similar geometric design in both the MBT and the APT, and with the same corresponding femoral component, thus allowing an assessment and comparison between APT and MBT components. METHODS: This is a retrospective analysis of a consecutive series of osteoarthritic patients who underwent total knee arthroplasties with at least 10-year follow-up comparing a modern congruent APT component to a modular MBT component of the same design. RESULTS: Seventy-three patients (81 knees, mean age 73 years) were available for assessment. Among the cohort, three patients had revision surgery (one from the APT group). In total, 73 patients were available for follow-up (59 MBT prostheses and 22 APT prostheses). There were no differences in knee function (Knee Society score, range of motion, stability) or radiographic parameters between the groups. Of the three revisions due to tibial tray loosening, only one was performed in the APT group and two were performed in the MBT group; another revision in the MBT group was due to loosening of both components; none of the revisions were due to septic complications. Ten-year survivorship of both designs was 92 %. CONCLUSIONS: While function of both designs appears similar, the APT design shows a trend toward requiring fewer revisions and is more cost-effective.

Assessment of the normal and pathological alignment of the elbow in children using the trochleocapitellar index.

BACKGROUND: The current research is a retrospective study that involves the description of a new trochleocapitellar index (TCI), on basis of anteroposterior (AP) radiographs of normal and fractured paediatric elbows. This index may be useful in assessing the alignment of the elbow with a supracondylar fracture. METHODS: The index was evaluated to define its normal and pathological range in children between the ages of 1-13 years. A total of 212 elbows in 141 children were radiographically evaluated. 70 children without fracture elbows were evaluated by radiographs taken at the time of trauma. 35 children with unilateral fractures that healed in a normal alignment were compared to 33 patients that had a mal-union and three patients with bilateral elbow fractures. The patients were radiographically assessed at the time of fracture as well as after fracture healing as part of a routine clinical assessment. Treatment included observation, cast or internal fixation as needed. RESULTS: The current study establishes that the normal range of the TCI was 0.25-0.8. The average TCI is 0.45. The lower range correlates with a valgus alignment of the elbow while the higher range indicates a neutral alignment. The TCI in fractured elbows that have healed in a clinically normal alignment is different than the contra-lateral elbow's TCI. This might indicate a sub-clinical remaining deformity. CONCLUSIONS: In current practice, paediatric patients with elbow trauma, often undergo bilateral radiographs during emergency room visits. The TCI has high negative and positive predictive values and might be superior to direct angle measurement that is currently in use. The use of the TCI measurement is expected to reduce exposure to irradiation in elbow trauma patients as bilateral comparative films appear to be superfluous when this measurement is used.

Chronic posttraumatic cartilage lesion of the knee treated with an acellular osteochondral-regenerating implant: case history with rehabilitation guidelines.

Osteochondral defects are often symptomatic and lead to deranged joint function. The spontaneous healing capacity of osteochondral defects is limited. In this case study, use of an acellular scaffold capable of induction of mesenchymal stem-cell migration is described. This scaffold was used on an Outerbridge grade IV medical condylar defect measuring ~2 cm2. At 24 mo follow-up, the articular surface appeared restored by MRI, and the patient returned to sports.

Cannabis oil extracts for chronic pain: what else can be learned from another structured prospective cohort?

Introduction: The use of medicinal cannabis for managing pain expands, although its efficacy and safety have not been fully established through randomized controlled trials. Objectives: This structured, prospective questionnaire-based cohort was aimed to assess long-term effectiveness and safety of cannabis oil extracts in patients with chronic pain. Methods: 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. Results: 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 (F(3,450) = 26.22, P < 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. Conclusion: 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.

Segmentation of polyps based on pyramid vision transformers and residual block for real-time endoscopy imaging.

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.

Aragonite-Based Scaffold Versus Microfracture and Debridement for the Treatment of Knee Chondral and Osteochondral Lesions: Results of a Multicenter Randomized Controlled Trial.

BACKGROUND: Lesions of the articular cartilage, with or without involvement of the subchondral bone, are a common cause of pain and dysfunction in the knee. Although several treatment options have been developed, the majority of previous clinical trials examined patients with isolated or focal midsized defects, which rarely represent the condition found in the general population. Rather, cartilage lesions are often associated with the presence of mild to moderate osteoarthritic changes. PURPOSE: The present multicenter randomized controlled trial compared the clinical and radiographic outcomes of an aragonite-based osteochondral implant with a control group (arthroscopic debridement/microfractures) in patients affected by joint surface lesions of the knee, including those with concurrent mild to moderate osteoarthritis. STUDY DESIGN: Randomized controlled trial; Level of evidence, 1. METHODS: A total of 251 patients were enrolled in 26 medical centers according to the following criteria: age 21 to 75 years, up to 3 cartilage defects of International Cartilage Regeneration & Joint Preservation Society grade 3a or above located on the femoral condyles and/or trochlea, total treatable area from 1 to 7 cm2, bony defect depth ≤8 mm, and knee osteoarthritis grade 0 to 3 according to Kellgren-Lawrence score. Patients were randomized to the aragonite-based implant or debridement/microfracture control arm in a 2:1 ratio. Evaluation was performed at 6, 12, 18, and 24 months based on overall Knee injury and Osteoarthritis Outcome Score (KOOS) as the primary endpoint, and the KOOS subscales (Pain, Quality of Life, Activities of Daily Living), percentage of responders, and International Knee Documentation Committee (IKDC) subjective score as the secondary endpoints. Patients also underwent magnetic resonance imaging evaluation at 12 and 24 months to assess defect fill grade. Failures (ie, need for any secondary treatment) and adverse events were also recorded. RESULTS: The implant group showed a statistically superior outcome in the primary endpoint and all secondary endpoints at each follow-up. The magnitude of improvement in the implant group was twice as large as that in the control group in terms of mean KOOS improvement at 2 years. Responder rate (defined as at least a 30-point improvement in overall KOOS) was 77.8% in the implant group as opposed to 33.6% in the control (P < .0001). Statistically superior results were seen in the IKDC score as well. At 24 months, 88.5% of the implanted group had at least 75% defect fill on magnetic resonance imaging as compared with 30.9% of controls (P < .0001). The failure rate was 7.2% for the implant group versus 21.4% for control. CONCLUSION: This aragonite-based scaffold was safe and effective in the treatment of chondral and osteochondral lesions in the knee, including patients with mild to moderate osteoarthritis, and provided superior outcomes as compared with the control group. REGISTRATION: NCT03299959 (ClinicalTrials.gov identifier).

ß-D-xylosides stimulate GAG synthesis in chondrocyte cultures due to elevation of the extracellular GAG domains, accompanied by the depletion of the intra-pericellular GAG pools, with alterations in the GAG profiles.

The familial disease of hereditary multiple exostoses is characterized by abnormal skeletal deformities requiring extensive surgical procedures. In hereditary multiple exostoses patients there is a shortage in the pericellular glycosaminoglycan (GAG) of heparan sulfate (HS), related to defective activity of HS glycosyltransferases, mainly in the pericellular regions of chondrocytes. This study searched for a novel approach employing xylosides with different aglycone groups priming a variety of GAG chains, in attempting to alter the GAG compositional profile. Cell cultures of patients with osteochondroma responded to p-nitrophenyl ß-D-xyloside by a significant increase in total GAG synthesis, expressed mainly in the extracellular domains, limited to chondroitin sulfate). The different ß-D-xylosides, in addition to increasing the synthesis of extracellular GAGs, led to a significant depletion of the intracellular GAG domains. In mouse chondrocyte cultures, ß-D-xylosides with different aglycones created a unique distribution of the GAG pools. Of special interest was the finding that the naphthalene methanol ß-D-xyloside showed the highest absolute levels of HS-GAGs in both extracellular and intra-pericellular moieties compared with other ß-D-xylosides and with controls without xyloside. In summary, ß-D-xylosides can be utilized in chondrocyte cultures to modify the distribution of GAGs between the extracellular and intracellular compartments. In addition, xylosides may alter the profile of specific GAG chains in each moiety.

Comparing Sublingual and Inhaled Cannabis Therapies for Low Back Pain: An Observational Open-Label Study.

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.

Aragonite-Based Scaffold for the Treatment of Joint Surface Lesions in Mild to Moderate Osteoarthritic Knees: Results of a 2-Year Multicenter Prospective Study.

BACKGROUND: Osteoarthritis (OA) is considered a contraindication to most cartilage repair techniques. Several regenerative approaches have been attempted with the aim of delaying or preventing joint replacement, with controversial results. Currently, there is a paucity of data on the use of single-step techniques, such as cell-free biomimetic scaffolds, for the treatment of joint surface lesions (JSLs) in OA knees. PURPOSE: To present the 2-year follow-up clinical and radiological outcomes after implantation of a novel, cell-free aragonite-based scaffold for the treatment of JSLs in patients with mild to moderate knee OA in a multicenter prospective study. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: A total of 86 patients, 60 male and 26 female, with a mean age of 37.4 ± 10.0 years, mild to moderate knee OA, and a mean defect size of 3.0 ± 1.7 cm2, were recruited at 8 medical centers according to the following criteria: radiographic mild to moderate knee OA (Kellgren-Lawrence grade 2 or 3); up to 3 treatable chondral/osteochondral defects (International Cartilage Repair Society grades 3 and 4) on the femoral condyles or trochlea; a total defect size ≤7 cm2; and no concurrent knee instability, severe axial malalignment, or systemic arthropathy. All patients were evaluated at baseline and at 6, 12, 18, and 24 months after implantation using the Knee injury and Osteoarthritis Outcome Score (KOOS) and International Knee Documentation Committee (IKDC) subjective score. Additionally, magnetic resonance imaging (MRI) was performed to assess the amount of cartilage defect filling at the repaired site. RESULTS: Significant improvement on all KOOS subscales was recorded from baseline (Pain: 49.6 ± 13.1; Activities of Daily Living [ADL]: 56.1 ± 18.4; Sport: 22.8 ± 18.8; Quality of Life [QoL]: 23.5 ± 16.5; Symptoms: 55.4 ± 19.9) to the 24 months' follow-up (Pain: 79.5 ± 21.1 [P < .001]; ADL: 84.1 ± 21.4 [P < .001]; Sport: 60.8 ± 31.9 [P < .001]; QoL: 54.9 ± 30.4 [P < .001]; Symptoms: 77.7 ± 21.2 [P < .001]). The IKDC subjective score showed a similar trend and improved from 37.8 ± 14.7 at baseline to 65.8 ± 23.5 at 24 months (P < .001). MRI showed a significant increase in defect filling over time: up to 78.7% ± 25.3% of surface coverage after 24 months. Treatment failure requiring revision surgery occurred in 8 patients (9.3%). CONCLUSION: The use of an aragonite-based osteochondral scaffold in patients with JSLs and mild to moderate knee OA provided significant clinical improvement at the 24-month follow-up, as reported by the patients. These findings were associated with good cartilage defect filling, as observed on MRI.