Lumican, a Multifunctional Cell Instructive Biomarker Proteoglycan Has Novel Roles as a Marker of the Hypercoagulative State of Long Covid Disease.

This study has reviewed the many roles of lumican as a biomarker of tissue pathology in health and disease. Lumican is a structure regulatory proteoglycan of collagen-rich tissues, with cell instructive properties through interactions with a number of cell surface receptors in tissue repair, thereby regulating cell proliferation, differentiation, inflammation and the innate and humoral immune systems to combat infection. The exponential increase in publications in the last decade dealing with lumican testify to its role as a pleiotropic biomarker regulatory protein. Recent findings show lumican has novel roles as a biomarker of the hypercoagulative state that occurs in SARS CoV-2 infections; thus, it may also prove useful in the delineation of the complex tissue changes that characterize COVID-19 disease. Lumican may be useful as a prognostic and diagnostic biomarker of long COVID disease and its sequelae.

Mid-Term Follow Up of the Nexel Total Elbow Arthroplasty.

INTRODUCTION: Aseptic loosening is one of the most common complications of total elbow arthroplasty (TEA). Modern implants, such as the Nexel, have been designed in an attempt to decrease loosening. The present study aims to report implant survivorship, radiographic assessment of loosening and lucency, and patient-reported outcome measures (PROMs) in patients treated with the Nexel TEA at mid-term follow-up. METHODS: Consecutive series of adult patients underwent TEA using the Nexel by a single surgeon via standardized technique. Patients with minimum 3 year follow-up with radiographic and PROM data were included. Survivorship was defined by the absence of revision. Loosening was assessed via Wrightington method by three independent fellowship-trained shoulder and elbow surgeons. Lucency was analyzed across individual radiographic zones on orthogonal radiographs. PROMs included the Quick Dash (QDASH), Patient Rated Elbow Evaluation (PREE), and EuroQoL (EQ5D). RESULTS: 38 consecutive patients (22 female, 16 male) with mean age of 67 underwent TEA via triceps-sparing isolated medial window approach. Mean follow-up was 5.5 years (range 3-9). Primary diagnoses were: 19 osteoarthritis (OA), 9 rheumatoid arthritis (RA), 9 post-traumatic arthritis (PA), 1 conversion of elbow arthrodesis. Overall survivorship was 97.4%, with one patient undergoing revision for infection. Loosening was found in 5.3% of elbows, averaged across three observers. Lucency was most pronounced at the level of the humeral condyles. PROMs demonstrated significant and clinically meaningful improvements in 76%, 92%, and 73% of patients for QDASH, PREE, and EQ5D, respectively. No significant correlations were found between patient age, gender, loosening, lucency, and PROMs. CONCLUSION: At mid-term follow-up, the Nexel TEA demonstrated excellent overall survivorship and low rate of implant loosening. The single failure requiring revision for infection was conversion of a prior elbow arthrodesis. PROMs overall exhibited marked and consistent improvement from preop to final postop follow-up. Although promising, these results should be interpreted with some caution as long term data regarding this prosthesis are still lacking.

Accidental Gunshot Wound Fatalities Related to Dropped Firearms.

ABSTRACT: A death resulting from the accidental discharge of a firearm represents a rare but oftentimes preventable tragedy. Such deaths may occur in a variety of settings. One such setting involves the discharge of a loaded firearm, which occurs when it is accidentally dropped, thrown, or falls to the ground. We report on 3 cases in which a loaded firearm discharged when it was dropped, resulting in the deaths of 3 individuals. In 2 cases, the person carrying the dropped firearm was killed, whereas in the third case, a child standing near the person who dropped the weapon was killed. We discuss the risk factors involved in these tragic incidents and present preventive strategies.

Pentosan Polysulfate Affords Pleotropic Protection to Multiple Cells and Tissues.

Pentosan polysulfate (PPS), a small semi-synthetic highly sulfated heparan sulfate (HS)-like molecule, shares many of the interactive properties of HS. The aim of this review was to outline the potential of PPS as an interventional therapeutic protective agent in physiological processes affecting pathological tissues. PPS is a multifunctional molecule with diverse therapeutic actions against many disease processes. PPS has been used for decades in the treatment of interstitial cystitis and painful bowel disease, it has tissue-protective properties as a protease inhibitor in cartilage, tendon and IVD, and it has been used as a cell-directive component in bioscaffolds in tissue engineering applications. PPS regulates complement activation, coagulation, fibrinolysis and thrombocytopenia, and it promotes the synthesis of hyaluronan. Nerve growth factor production in osteocytes is inhibited by PPS, reducing bone pain in osteoarthritis and rheumatoid arthritis (OA/RA). PPS also removes fatty compounds from lipid-engorged subchondral blood vessels in OA/RA cartilage, reducing joint pain. PPS regulates cytokine and inflammatory mediator production and is also an anti-tumor agent that promotes the proliferation and differentiation of mesenchymal stem cells and the development of progenitor cell lineages that have proven to be useful in strategies designed to effect repair of the degenerate intervertebral disc (IVD) and OA cartilage. PPS stimulates proteoglycan synthesis by chondrocytes in the presence or absence of interleukin (IL)-1, and stimulates hyaluronan production by synoviocytes. PPS is thus a multifunctional tissue-protective molecule of potential therapeutic application for a diverse range of disease processes.

Natural and Semi-Synthetic Flavonoid Anti-SARS-CoV-2 Agents for the Treatment of Long COVID-19 Disease and Neurodegenerative Disorders of Cognitive Decline.

The aim of this review is to highlight the beneficial attributes of flavonoids, a diverse family of widely-distributed polyphenolic phytochemicals that have beneficial cell and tissue protective properties. Phytochemicals are widely distributed in plants, herbs and shrubs used in traditional complimentary medical formulations for centuries. The bioactive components that convey beneficial medicinal effects in these complex herbal preparations are now being identified using network pharmacology and molecular docking procedures that identify their molecular targets. Flavonoids have anti-oxidant, anti-inflammatory, antiviral, antibacterial and anti-cancer properties that have inspired the development of potent multifunctional derivatised flavonoids of improved efficacy. The antiviral properties of flavonoids and the emergence of the severe acute respiratory syndrome (SARS-CoV-2) pandemic has resulted in a resurgence of interest in phytochemicals in the search for efficacious compounds that can prevent viral infection or replication, with many promising plant compounds identified. Promising semi-synthetic flavonoid derivatives have also been developed that inhibit multiple pathological neurodegenerative processes; these offer considerable promise in the treatment of diseases of cognitive decline. Clinical trials are currently being undertaken to evaluate the efficacy of dietary supplements rich in flavonoids for the treatment of virally-mediated diseases. Such trials are expected to identify flavonoids with cell and tissue protective properties that can be harnessed in biomedical applications that may serve as supportive adjunctive procedures to conventional anti-viral drug therapies against diseases such as COVID-19.

Xylan Prebiotics and the Gut Microbiome Promote Health and Wellbeing: Potential Novel Roles for Pentosan Polysulfate.

This narrative review highlights the complexities of the gut microbiome and health-promoting properties of prebiotic xylans metabolized by the gut microbiome. In animal husbandry, prebiotic xylans aid in the maintenance of a healthy gut microbiome. This prevents the colonization of the gut by pathogenic organisms obviating the need for dietary antibiotic supplementation, a practice which has been used to maintain animal productivity but which has led to the emergence of antibiotic resistant bacteria that are passed up the food chain to humans. Seaweed xylan-based animal foodstuffs have been developed to eliminate ruminant green-house gas emissions by gut methanogens in ruminant animals, contributing to atmospheric pollution. Biotransformation of pentosan polysulfate by the gut microbiome converts this semi-synthetic sulfated disease-modifying anti-osteoarthritic heparinoid drug to a prebiotic metabolite that promotes gut health, further extending the therapeutic profile and utility of this therapeutic molecule. Xylans are prominent dietary cereal components of the human diet which travel through the gastrointestinal tract as non-digested dietary fibre since the human genome does not contain xylanolytic enzymes. The gut microbiota however digest xylans as a food source. Xylo-oligosaccharides generated in this digestive process have prebiotic health-promoting properties. Engineered commensal probiotic bacteria also have been developed which have been engineered to produce growth factors and other bioactive factors. A xylan protein induction system controls the secretion of these compounds by the commensal bacteria which can promote gut health or, if these prebiotic compounds are transported by the vagal nervous system, may also regulate the health of linked organ systems via the gut-brain, gut-lung and gut-stomach axes. Dietary xylans are thus emerging therapeutic compounds warranting further study in novel disease prevention protocols.

Pentosan Polysulfate, a Semisynthetic Heparinoid Disease-Modifying Osteoarthritic Drug with Roles in Intervertebral Disc Repair Biology Emulating the Stem Cell Instructive and Tissue Reparative Properties of Heparan Sulfate.

This review highlights the attributes of pentosan polysulfate (PPS) in the promotion of intervertebral disc (IVD) repair processes. PPS has been classified as a disease-modifying osteoarthritic drug (DMOAD) and many studies have demonstrated its positive attributes in the countering of degenerative changes occurring in cartilaginous tissues during the development of osteoarthritis (OA). Degenerative changes in the IVD also involve inflammatory cytokines, degradative proteases, and cell signaling pathways similar to those operative in the development of OA in articular cartilage. PPS acts as a heparan sulfate (HS) mimetic to effect its beneficial effects in cartilage. The IVD contains small cell membrane HS proteoglycans (HSPGs) such as syndecan, and glypican and a large multifunctional HS/chondroitin sulfate (CS) hybrid proteoglycan (HSPG2/perlecan), that have important matrix-stabilizing properties and sequester, control, and present growth factors from the FGF, VEGF, PDGF, and BMP families to cellular receptors to promote cell proliferation, differentiation, and matrix synthesis. HSPG2 also has chondrogenic properties and stimulates the synthesis of extracellular matrix (ECM) components and expansion of cartilaginous rudiments, and has roles in matrix stabilization and repair. Perlecan is a perinuclear and nuclear proteoglycan (PG) in IVD cells with roles in chromatin organization and control of transcription factor activity, immunolocalizes to stem cell niches in cartilage, promotes escape of stem cells from quiescent recycling, differentiation and attainment of pluripotency and migratory properties. These participate in tissue development and morphogenesis, ECM remodeling and repair. PPS also localizes in the nucleus of stromal stem cells, promotes development of chondroprogenitor cell lineages, ECM synthesis and repair and discal repair by resident disc cells. The availability of recombinant perlecan and PPS offers new opportunities in repair biology. These multifunctional agents offer welcome new developments in repair strategies for the IVD.

Implication of bone morphology in degenerative rotator cuff lesions: A prospective comparative study between greater tuberosity angle and critical shoulder angle.

BACKGROUND: Degenerative rotator cuff tear is a frequent and multifactorial pathology. The role of bone morphology of the greater tuberosity and lateral acromion has been validated, and can be measured with two plain radiographic markers on true anteroposterior views: the greater tuberosity angle (GTA) and the critical shoulder angle (CSA). However, the interdependence of both markers remains unknown, as well as their relationship with the level of professional and sports activities involving the shoulder. The aim of this prospective comparative study was to describe the correlation between the GTA and CSA in patients with degenerative rotator cuff tears. HYPOTHESIS: GTA and CSA are independent factors from one another and from demographic factors, such as age, dominance, sports, or professional activities. PATIENT AND METHODS: All patients presenting to a shoulder specialized clinic were assigned to two groups. The first consisted of patients with a symptomatic degenerative rotator cuff tear visible on MRI and the control group consisted of patients with any other shoulder complaints and no history or visible imaging of any rotator cuff lesion. RESULTS: There were 51 shoulders in 49 patients in the rotator cuff tear group (RCT) and 53 shoulders in 50 patients in the control group. Patient demographics were similar in both groups. Mean GTA was 72.1°±3.7 (71.0-73.1) in the RCT group and 64.0°±3.3 (63.1-64.9) in the control group (p<0.001). Mean CSA was 36.7°±3.7 (35.7-37.8) in the RCT group, and 32.1°±3.7 (31.1-33.1) in the control group (p<0.001). A summation of GTA and CSA values over 103° increased the odds of having a rotator cuff tear by 97-fold (p<0.001). There was no correlation between GTA and CSA, nor between GTA or CSA and age, sex, tear size, or dominance. Patients with different levels of professional and sports activities did not have significantly different GTA or CSA values. CONCLUSION: GTA and CSA are independent radiologic markers that can reliably predict the presence of a degenerative rotator cuff tear. A sum of both values over 103° increases the odds of having a rotator cuff tear by 97-fold. These markers are not correlated with patient demographic or environmental factors, suggesting that the variability of the native acromion and greater tuberosity morphology may be individual risk factors for rotator cuff tear. LEVEL OF EVIDENCE: II; diagnostic study.

A single dose of tranexamic acid reduces blood loss after reverse and anatomic shoulder arthroplasty: a randomized controlled trial.

BACKGROUND: Hematoma formation and the need for blood transfusions are commonly reported complications after shoulder arthroplasty. Tranexamic acid (TXA) has been widely used in hip and knee arthroplasty to decrease perioperative blood loss. The role of TXA is still being established in shoulder arthroplasty. MATERIALS AND METHODS: We conducted a double-blind randomized controlled trial comparing intravenous TXA vs. placebo in 60 patients undergoing primary anatomic or reverse shoulder arthroplasty. Of these patients, 29 received a placebo whereas 31 received a single dose of 2 g of intravenous TXA. Patient demographic characteristics, as well as drain tube output, blood loss, hematoma formation, transfusion requirement, length of hospital stay, and pain score, were recorded. Patients were followed up for 12 weeks to assess for complications. RESULTS: Patients who received TXA had a lower drain tube output at all time points: 41 mL vs. 133 mL at 6 hours, 75 mL vs. 179 mL at 12 hours, and 94 mL vs. 226 mL at 24 hours (P < .001 for all). They also had a higher postoperative hemoglobin (Hb) level (12.3 g/dL vs. 11.4 g/dL, P = .009), lower change in Hb level (1.7 g/dL vs. 2.3 g/dL, P = .011), lower total Hb loss (0.078 g vs. 0.103 g, P = .042), lower blood volume loss (0.55 L vs. 0.74 L, P = .021), higher postoperative hematocrit level (36.7% vs. 34.6%, P = .020), and lower hematocrit change (5.4% vs. 7.6%, P = .022). There was no significant difference in pain score or length of hospital stay, and no patients required a transfusion. CONCLUSION: A single dose of 2 g of intravenous TXA decreases blood loss and drain tube output in primary anatomic and reverse arthroplasty of the shoulder. No differences were detected in the occurrence of complications, need for transfusion, pain score, or length of hospital stay. With the mounting evidence now available, patients undergoing elective primary shoulder arthroplasty should be given intravenous TXA to decrease perioperative blood loss.

Accuracy of arthroscopic fluid pump systems in shoulder surgery: a comparison of 3 different pump systems.

BACKGROUND: Extra-articular fluid extravasation is a known complication during shoulder arthroscopy. The risk and amount of extravasation to a large degree is dependent on the fluid pressure delivered to the surgical site. Accurate measurement, knowledge, and control of the pressure delivered is thus important to surgeons, anesthetists, and the patient. The purpose of this study was to compare the pressure measurement accuracy of 3 arthroscopic fluid pumps, with 2 of them having 2 different settings. METHODS: Twenty-five patients (n = 5 per group) undergoing shoulder arthroscopy were selected. Three different arthroscopic fluid pumps (ConMed 24K, Stryker Crossflow, Arthrex Dual Wave) were tested in 5 different operational settings (Stryker, standard and dynamic mode; ConMed, with and without TIPS; Arthrex Dual Wave). In each operation, the set pump pressures and the subsequently delivered intra-articular surgical site fluid pressures were measured by a spinal needle connected to an anesthetic standard pressure transducer attached to the anesthetic machine. Independent measures of the surgical site pressures were obtained before multiple portals were created or extravasation had occurred. Measurements were taken at the beginning of surgery. RESULTS: Measurements of the mean intra-articular pressure were found to not be significantly different from the set pressure for the ConMed 24K with TIPS (0.98 ± 0.02-fold) and Stryker Crossflow in standard mode (0.98 ± 0.02-fold). However, actual pressure was significantly greater than the set pressure for the ConMed 24K without TIPS (by 1.30 ± 0.13-fold), Stryker Crossflow in dynamic mode (by 1.82 ± 0.08-fold), and Arthrex Dual Wave (by 2.19 ± 0.06-fold). CONCLUSION: Independently measured intra-articular pressure can be more than double the set pressure for some arthroscopic pumps. Measuring intra-articular pressure can thus aid in adjusting the set pressure. This could minimize the risk of intraoperative complications.

The relationship between synovial inflammation, structural pathology, and pain in post-traumatic osteoarthritis: differential effect of stem cell and hyaluronan treatment.

BACKGROUND: Synovitis is implicated in the severity and progression of pain and structural pathology of osteoarthritis (OA). Increases in inflammatory or immune cell subpopulations including macrophages and lymphocytes have been reported in OA synovium, but how the particular subpopulations influence symptomatic or structural OA disease progression is unclear. Two therapies, hyaluronan (HA) and mesenchymal stem cells (MSCs), have demonstrated efficacy in some clinical settings: HA acting as device to improve joint function and provide pain relief, while MSCs may have immunomodulatory and disease-modifying effects. We used these agents to investigate whether changes in pain sensitization or structural damage were linked to modulation of the synovial inflammatory response in post-traumatic OA. METHODS: Skeletally mature C57BL6 male mice underwent medial-meniscal destabilisation (DMM) surgery followed by intra-articular injection of saline, a hyaluronan hexadecylamide derivative (Hymovis), bone marrow-derived stem cells (MSCs), or MSC + Hymovis. We quantified the progression of OA-related cartilage, subchondral bone and synovial histopathology, and associated pain sensitization (tactile allodynia). Synovial lymphocytes, monocyte/macrophages and their subpopulations were quantified by fluorescent-activated cell sorting (FACS), and the expression of key inflammatory mediators and catabolic enzyme genes quantified by real-time polymerase chain reaction (PCR). RESULTS: MSC but not Hymovis significantly reduced late-stage (12-week post-DMM) cartilage proteoglycan loss and structural damage. Allodynia was initially reduced by both treatments but significantly better at 8 and 12 weeks by Hymovis. Chondroprotection by MSCs was not associated with specific changes in synovial inflammatory cell populations but rather regulation of post-injury synovial Adamts4, Adamts5, Mmp3, and Mmp9 expression. Reduced acute post-injury allodynia with all treatments coincided with decreased synovial macrophage and T cell numbers, while longer-term effect on pain sensitization with Hymovis was associated with increased M2c macrophages. CONCLUSIONS: This therapeutic study in mice demonstrated a poor correlation between cartilage, bone or synovium (histo)pathology, and pain sensitization. Changes in the specific synovial inflammatory cell subpopulations may be associated with chronic OA pain sensitization, and a novel target for symptomatic treatment.

A Biomechanical Comparison of Different Suture Materials Used for Arthroscopic Shoulder Procedures.

PURPOSE: To evaluate the viscoelastic properties of 4 commercially available cord-like sutures and 2 commercially available suture tapes when subjected to physiological loads, as well as to compare them with each other and to identify the clinically most desirable combination of suture material properties. METHODS: Six suture materials (Ethibond, FiberWire, FiberTape, Orthocord, Ultrabraid, and Ultratape) underwent creep testing (n = 7, 60 N, 10 minutes) to determine specimen stiffness, initial elongation at 60 N of load, static creep (during 10 minutes of loading), and relaxed elongation (material recovery 3 minutes after removal of load). Furthermore, cyclic testing (n = 7, 10-45 N, 0.5 Hz, 500 cycles) was carried out to determine dynamic creep, peak-to-peak displacement, and relaxed elongation. Mechanical testing was conducted on a material testing machine in 37°C phosphate-buffered saline solution. RESULTS: FiberTape showed the greatest stiffness (23.9 ± 3.2 N/mm, P < .001), the smallest amounts of static (0.38 ± 0.10 mm, P < .001) and dynamic (0.16 ± 0.09 mm, P = .003) creep, and the smallest peak-to-peak displacement (0.20 ± 0.02 mm, P < .001). FiberTape and FiberWire showed the smallest initial elongation (1.17 ± 0.17 mm and 1.63 ± 0.25 mm, respectively; P < .001). Ultrabraid showed the greatest relaxed elongation, both statically (4.73 ± 0.73 mm, P < .001) and dynamically (4.18 ± 0.83 mm, P = .002). CONCLUSIONS: FiberTape consistently displayed less creep, greater stiffness, and less extensibility than the other suture types. Ultrabraid showed the largest amount of relaxed elongation on both static and dynamic testing. CLINICAL RELEVANCE: When considering high stiffness in combination with low initial extension and low static creep to be ideal parameters to achieve optimal initial construct stability and considering low dynamic creep in combination with low peak-to-peak displacement to be ideal conditions for the repetitive loading of the construct during the healing process, tapes seem to be superior to cord-like sutures for performing rotator cuff repair.

Functionally distinct tendons have different biomechanical, biochemical and histological responses to in vitro unloading.

Tendons with different in vivo functions are known to have different baseline biomechanics, biochemistry and ultrastructure, and these can be affected by changes in loading. However it is not know whether different tendon types respond in the same, or different ways, to changes in loading. This study performed in vitro un-loading (stress deprivation) in culture on ovine medial extensor tendons (MET, a positional tendon), and superficial and deep digital flexor tendons (SDFTs and DDFTs, with energy-storing and intermediate functions respectively), for 21 days (n = 14 each). Tensile strength and elastic modulus were then measured, followed by biochemical assays for sulphated glycosaminoglycan (sGAG) and hydroxyproline content. Histological inspection for cell morphology, cell density and collagen alignment was also performed. The positional tendon (MET) had a significant reduction (∼50%) in modulus and strength (P < 0.001) after in vitro stress-deprivation, however there were no significant effects on the energy-storing tendons (SDFT and DDFT). In contrast, sGAG was not affected in the MET, but was reduced in the SDFT and DDFT (P < 0.001). All tendons lost compactness and collagen organisation, and had reduced cell density, but these were more rapid in the MET than the SDFT and DDFT. These results suggest that different tendon types respond to identical stimuli in different ways, thus; (i) the results from an experiment in one tendon type may not be as applicable to other tendon types as previously thought, (ii) positional tendons may be particularly vulnerable to clinical stress-deprivation, and (iii) graft tendon source may affect the biological response to loading in ligament and tendon reconstruction.

Effects of tendon injury on uninjured regional tendons in the distal limb: An in-vivo study using an ovine tendinopathy model.

Following injury to a tendon little is known about potential for pathology to develop in other regional tendons from overloading or altered function. The aim of this study was to investigate the gene expression and histopathological changes that occur 1) within the deep digital flexor tendon (DDFT) after injury to the superficial digital flexor tendon (SDFT) and 2) within the flexor tendons (SDFT and DDFT) after injury to the extensor tendons. Merino wethers [Ovis aries] (n = 18) were divided into three equal groups and underwent either partial transection of the SDFT, complete transection of the extensor tendons or were left as non-operated controls. Tendons were harvested and sampled regionally for gene expression (real time PCR) and histologic analysis eight weeks after surgery. Transection of the SDFT resulted in increased expression of collagen III, versican, biglycan, lumican and MMP1 (P<0.026 for all genes) within the DDFT. There was no effect of transecting the extensor tendons on the expression of any gene tested in either the SDFT or the DDFT. The DDFT had elevated histopathology scores induced by transection of the SDFT, eight weeks previously. There were minimal histological differences in either the SDFT or DDFT after transection of the extensor tendons. Transection of the SDFT results in a mild, subclinical tendinopathy within the DDFT with potential implications on treatment and rehabilitation of SDFT injuries. Injury to the extensor tendons has minimal measured effect on the SDFT or DDFT.

Morbidity and mortality in cervical spine injuries in the elderly.

BACKGROUND: The aim of our study was to identify the demographics and complications in elderly cervical spine injuries and predictive factors for surgery, complications and mortality. We hypothesized younger healthier patients were more likely to undergo surgical intervention. METHODS: A retrospective review of 225 consecutive patients aged 65 years and over with cervical spine injuries was carried out over a 3-year period. RESULTS: There were 113 males and 112 females with an average of 79.7 years (range 65-98). The most common fracture was C2 peg type (21.8%). Five patients had complete spinal cord injury (2.2%), 25 had incomplete spinal cord injury (11.1%) and 84% were neurologically intact. Fifty-four patients were managed operatively (24%), while 171 patients were managed non-operatively (76%). The operative group had higher rates of pneumonia (odds ratio (OR) 5.3, 95% confidence interval (CI) 2.6-10.7, P < 0.01), cardiac arrhythmia (OR 4.1, 95% CI 1.5-11.2, P < 0.01) and respiratory failure (OR 2.6, 95% CI 1.2-5.5, P < 0.05). There was no difference in mortality between the operative and non-operative group (18.5% and 12.9%, P = 0.3). Patients with complete spinal cord injury had 100% mortality. Significant predictive factors for complications and death were neurological deficits, comorbidities and the presence of other injuries (P < 0.05). Surgery was not predictive for death and the operative group was younger than the non-operative group (P < 0.05). CONCLUSIONS: In the setting of a high complication rate, consideration should be given to palliation in elderly patients with complete spinal cord injury and there must be good rational for surgery.

Achilles and tail tendons of perlecan exon 3 null heparan sulphate deficient mice display surprising improvement in tendon tensile properties and altered collagen fibril organisation compared to C57BL/6 wild type mice.

The aim of this study was to determine the role of the perlecan (Hspg2) heparan sulphate (HS) side chains on cell and matrix homeostasis in tail and Achilles tendons in 3 and 12 week old Hspg2 exon 3 null HS deficient (Hspg2Δ3 - ∕Δ3 -) and C57 BL/6 Wild Type (WT) mice. Perlecan has important cell regulatory and matrix organizational properties through HS mediated interactions with a range of growth factors and morphogens and with structural extracellular matrix glycoproteins which define tissue function and allow the resident cells to regulate tissue homeostasis. It was expected that ablation of the HS chains on perlecan would severely disrupt normal tendon organization and functional properties and it was envisaged that this study would better define the role of HS in normal tendon function and in tendon repair processes. Tail and Achilles tendons from each genotype were biomechanically tested (ultimate tensile stress (UTS), tensile modulus (TM)) and glycosaminoglycan (GAG) and collagen (hydroxyproline) compositional analyses were undertaken. Tenocytes were isolated from tail tendons from each mouse genotype and grown in monolayer culture. These cultures were undertaken in the presence of FGF-2 to assess the cell signaling properties of each genotype. Total RNA was isolated from 3-12 week old tail and Achilles tendons and qRT-PCR was undertaken to assess the expression of the following genes Vcan, Bgn, Dcn, Lum, Hspg2, Ltbp1, Ltbp2, Eln and Fbn1. Type VI collagen and perlecan were immunolocalised in tail tendon and collagen fibrils were imaged using transmission electron microscopy (TEM). FGF-2 stimulated tenocyte monolayers displayed elevated Adamts4, Mmp2, 3, 13 mRNA levels compared to WT mice. Non-stimulated tendon Col1A1, Vcan, Bgn, Dcn, Lum, Hspg2, Ltbp1, Ltbp2, Eln and Fbn1 mRNA levels showed no major differences between the two genotypes other than a decline with ageing while LTBP2 expression increased. Eln expression also declined to a greater extent in the perlecan exon 3 null mice (P < 0.05). Type VI collagen and perlecan were immunolocalised in tail tendon and collagen fibrils imaged using transmission electron microscopy (TEM). This indicated a more compact form of collagen localization in the perlecan exon 3 null mice. Collagen fibrils were also smaller by TEM, which may facilitate a more condensed fibril packing accounting for the superior UTS displayed by the perlecan exon 3 null mice. The amplified catabolic phenotype of Hspg2Δ3 - ∕Δ3 - mice may account for the age-dependent decline in GAG observed in tail tendon over 3 to 12 weeks. After Achilles tenotomy Hspg2Δ3 - ∕Δ3 - and WT mice had similar rates of recovery of UTS and TM over 12 weeks post operatively indicating that a deficiency of HS was not detrimental to tendon repair.

Comparative analysis of 2 glenoid version measurement methods in variable axial slices on 3-dimensionally reconstructed computed tomography scans.

BACKGROUND: Most glenoid version measurement methods have been validated on 3-dimensionally corrected axial computed tomography (CT) slices at the mid glenoid. Variability of the vault according to slice height and angulation has not yet been studied and is crucial for proper surgical implant positioning. The aim of this study was to analyze the variation of the glenoid vault compared with the Friedman angle according to different CT slice heights and angulations. The hypothesis was that the Friedman angle would show less variability. MATERIALS AND METHODS: Sixty shoulder CT scans were retrieved from a hospital imaging database and were reconstructed in the plane of the scapula. Seven axial slices of different heights and coronal angulations were selected, and measurements were carried out by 3 observers. RESULTS: Mid-glenoid mean version was -8.0° (±4.9°; range, -19.6° to +7.0°) and -2.1° (±4.7°; range, -13.0° to +10.3°) using the vault method and Friedman angle, respectively. For both methods, decreasing slice height or angulation did not significantly alter version. Increasing slice height or angulation significantly increased anteversion for the vault method (P < .001). Both interobserver reliability and intraobserver reliability were significantly higher using the Friedman angle. CONCLUSION: Version at the mid and lower glenoid is similar using either method. The vault method shows less reliability and more variability according to slice height or angulation. Yet, as it significantly differs from the Friedman angle, it should still be used in situations where maximum bone purchase is sought with glenoid implants. For any other situation, the Friedman angle remains the method of choice.

The greater tuberosity angle: a new predictor for rotator cuff tear.

BACKGROUND: The implication of scapular morphology in rotator cuff tears has been extensively studied. However, the role of the greater tuberosity (GT) should be of equal importance. The aim of this study was to propose a new radiographic marker, the GT angle (GTA), which measures the position of the GT in relation to the center of rotation of the humeral head. The hypothesis was that a higher angle value would be associated with a higher likelihood in detecting a rotator cuff tear. METHODS: During 1 year, patients were prospectively recruited from a single institution specialized shoulder clinic in 2 different groups. The patient group consisted of individuals with a degenerative rotator cuff tear involving at least the supraspinatus. The control group consisted of individuals with no rotator cuff pathology. Individuals in both groups with congenital, post-traumatic, or degenerative alterations of the proximal humerus were excluded. The GTA was measured on an anteroposterior shoulder x-ray image with the arm in neutral rotation by 3 observers at 2 different times. RESULTS: The study recruited 71 patients (33 patients, 38 controls). Mean GTA value was 72.5° (range, 67.6°-79.2°) in patients and 65.2° (range, 55.8°-70.5°) for controls (P <.001). A value above 70° resulted in 93-fold higher odds of detecting a rotator cuff tear (P <.001). Interobserver and intraobserver reliability were high. CONCLUSIONS: GT morphology is implicated in rotator cuff tears. The GTA is a reliable radiographic marker, with more than 70° being highly predictive in detecting such lesions.

Hyaluronan oligosaccharides stimulate matrix metalloproteinase and anabolic gene expression in vitro by intervertebral disc cells and annular repair in vivo.

The role of hyaluronan (HA) oligosaccharides in disc cell-mediated matrix metalloproteinase (MMP) and anabolic gene expression in vitro and annular repair in vivo were examined. Monolayer and alginate bead cultures of ovine intervertebral disc cells were stimulated with 10-12 mer hyaluronan oligosaccharides (HA-oligos). Annulus fibrosus (AF) monolayers were poorly responsive to the HA-oligos, proMMP-2 levels were marginally elevated and levels were MMP-9 unaffected. ProMMP-2 displayed a strong dose-dependent increase in the nucleus pulposus (NP) monolayers. In AF alginate bead cultures, proMMP-2 and active MMP-9 increased up to day 10, in NP cultures proMMP-2 was progressively converted to active MMP-2 over days 7-10 and active MMP-9 levels were elevated on day 10. A steady decline in MMP-2 and MMP-9 activity was evident over days 2-10 in the non-stimulated NP cultures. Disc cell viabilities were ≥92 ± 5% in all cultures indicating that the HA-oligo was not cytotoxic. Reverse-transcription polymerase chain reaction demonstrated an upregulation in MMP1, MMP113 and ADAMTS1 and the anabolic matrix repair genes ACAN, COL1A1 and COL2A1 in the NP by HA-oligos, whereas AF MMP13, ADAMTS1, ADAMTS4 and ADAMTS5, ACAN and COL2A1 were down-regulated; this differential regulation is expected to promote clearance of granulation/scar tissue from AF defects and matrix replenishment. The AF defect sites contained enlarged annular lamellae in vivo in response to the HA oligos, which is consistent with an active repair response. Masson trichrome and PicroSirius red histology and immunolocalization of type I collagen supported active remodelling in the outer lesion zone by the HA-oligo treatment but not the inner lesion. Copyright © 2016 John Wiley & Sons, Ltd.

Efficacy of administered mesenchymal stem cells in the initiation and co-ordination of repair processes by resident disc cells in an ovine (Ovis aries) large destabilizing lesion model of experimental disc degeneration.

BACKGROUND: Forty percent of low back pain cases are due to intervertebral disc degeneration (IVDD), with mesenchymal stem cells (MSCs) a reported treatment. We utilized an ovine IVDD model and intradiscal heterologous MSCs to determine therapeutic efficacy at different stages of IVDD. METHODOLOGY: Three nonoperated control (NOC) sheep were used for MSC isolation. In 36 sheep, 6 × 20 mm annular lesions were made at three spinal levels using customized blades/scalpel handles, and IVDD was allowed to develop for 4 weeks in the Early (EA) and late Acute (LA) groups, or 12 weeks in the chronic (EST) group. Lesion IVDs received injections of 10 × 106 MSCs or PBS, and after 8 (EA), 22 (LA) or 14 (EST) weeks recuperation the sheep were sacrificed. Longitudinal lateral radiographs were used to determine disc heights. IVD glycosaminoglycan (GAG) and hydroxyproline contents were quantified using established methods. An Instron materials testing machine and customized jigs analyzed IVD (range of motion, neutral zone [NZ] and stiffness) in flexion/extension, lateral bending and axial rotation. qRTPCR gene profiles of key anabolic and catabolic matrix molecules were undertaken. Toluidine blue and hematoxylin and eosin stained IVD sections were histopathologically scoring by two blinded observers. RESULTS: IVDD significantly reduced disc heights. MSC treatment restored 95% to 100% of disc height, maximally improved NZ and stiffness in flexion/extension and lateral bending in the EST group, restoring GAG levels. With IVDD qRTPCR demonstrated elevated catabolic gene expression (MMP2/3/9/13, ADAMTS4/5) in the PBS IVDs and expession normalization in MSC-treated IVDs. Histopathology degeneracy scores were close to levels of NOC IVDs in MSC IVDs but IVDD developed in PBS injected IVDs. DISCUSSION: Administered MSCs produced recovery in degenerate IVDs, restored disc height, composition, biomechanical properties, down regulated MMPs and fibrosis, strongly supporting the efficacy of MSCs for disc repair.