Partial Denervation of the Thumb Carpometacarpal Joint: A New Technique.

BACKGROUND: To report the clinical outcomes of partial denervation for the treatment of basilar thumb joint arthritis. METHODS: Patients who underwent partial denervation of the basilar thumb joint for osteoarthritis from a single center between 2019 and 2021 were recruited into the study. This involved a technique that involved cauterization of the joint capsule and its innervation through the branches of the superficial radial, palmar cutaneous branch of the median, lateral antebrachial, and ulnar nerves. Patients were followed up postoperatively to record clinical (grip strength, thumb apposition and opposition pinch grip strength, Kapandji score) and patient-reported outcomes (visual analogue scale [VAS], Quick Disabilities of the Arm, Shoulder and Hand [QuickDASH], Patient-reported Wrist Evaluation [PRWE]). RESULTS: Twelve patients (15 carpometacarpal joints; 9 female and 3 male patients) underwent a partial denervation of the thumb (Eaton stage 3-4). The mean age at the time of surgery was 63 ± 5 years (range 56-72). The mean clinical follow-up duration was 23 ± 11 months (range 9-42 months), and functional score follow-up duration was 27 ± 7 months (range 14-42 months). At the latest clinical follow, VAS score, Kapandji score, grip strength, and thumb apposition/opposition pinch strength all improved significantly (P < .05). The mean QuickDASH score was 30 ± 16, and PRWE score was 32 ± 17. Patients who had unilateral partial thumb denervation demonstrated greater improvement in grip strength than patients who had bilateral partial thumb denervation procedures (P = .01). CONCLUSION: In this clinical case series, our method of basilar thumb joint partial denervation has been effective in improving clinical outcomes and reducing pain due to osteoarthritis. LEVEL OF EVIDENCE: IV, case series.

Dorsal Subluxation of The Proximal Carpal Row with the Use of a Bridge Plate.

Background Spanning bridge plates were first popularized for fixation of complex distal radius fractures. However, indications for their use have expanded including the surgical treatment algorithm for treating conditions such as Kienböck's disease. Traditionally, initial surgical treatment of Lichtman Stages II to III Kienböck's disease included lunate decompression, unloading, and revascularization procedures. The addition of a dorsal spanning bridge plate further facilitates lunate offloading and may improve bone revascularization. Case Description We report a complication of proximal carpal row dorsal subluxation secondary to dorsal spanning plate fixation in a patient with Stage IIIb Kienböck's disease. The patient had undergone wrist arthroscopy, lunate forage, radius core decompression, and spanning plate fixation. At 6 weeks after surgery, radiographic imaging demonstrated dorsal subluxation of the proximal carpal row that was corrected upon bridge plate removal. Serial radiographs during follow-up showed no further carpal subluxation without Kienböck's disease progression at 12 months postremoval of hardware. Patient remains pain free and has returned to elite level sport. Literature Review To our knowledge no previous cases of proximal carpal row subluxation with the use of dorsal bridge plate has been reported in the literature. Clinical Relevance Proximal row carpal subluxation can occur with dorsal bridge plate fixation.

Clinical Outcomes of Arthroscopic-Assisted Volar Scapholunate Capsulodesis: A Case Series.

Purpose We have previously described arthroscopic-assisted volar scapholunate (SL) capsulodesis as an alternative technique for addressing volar SL interosseous ligament (SLIL) injuries. In this article, we report the outcomes of this procedure in a cohort of patients. Methods Postoperative outcomes including range of motion, grip strength, visual analog scale (VAS) pain score, Quick Disabilities of the Arm, Shoulder and Hand (QuickDASH), and Mayo Wrist Score were assessed through a prospective review of six patients in a single center who underwent this procedure. Results Six patients (four male and two female) with a mean age of 43 ± 14 years were evaluated in the study. The mean duration of follow-up was 41 ± 17 weeks. Postoperative outcomes noted a reduction in VAS pain score from 8 before surgery to 0.7 postoperatively ( p = 0.00004) and improvement in Mayo Wrist Score (42 preoperatively to 80 postoperatively; p = 0.001), grip strength (86% of contralateral side; p = 0.20), and flexion arc (81% of contralateral side; p = 0.08). QuickDASH was 20 ± 8 and Patient-Rated Wrist Evaluation score was 13 ± 2 at the last clinical follow-up. There was an improvement in SL gap ( p = 0.03), SL angle ( p = 0.11), and radiolunate angle ( p = 0.15) measurements postoperatively. Conclusions The described arthroscopic-assisted volar SL capsulodesis in this study presents an alternative method to address volar SLIL pathology with positive short-term clinical outcomes. Clinical Relevance Arthroscopic-assisted volar SL capsulodesis may be considered in the treatment algorithm for volar SLIL injuries.

BMP2 and GDF5 for Compartmentalized Regeneration of the Scapholunate Ligament.

Background Chronic injuries to the scapholunate ligament (SLIL) alter carpal kinematics and may progress to early degenerative osteoarthritis. To date, there is no consensus for the best method for SLIL reconstruction. This study aims to assess the use of growth factors (bone morphogenetic protein [BMP]2 and growth and differentiation factor 5 [GDF5]) for compartmentalized regeneration of bone and ligament in this multiphasic scaffold in a rabbit knee model. Case Description A total of 100 µg of BMP2 and 30 µg of GDF5 were encapsulated into a heparinized gelatin-hyaluronic acid hydrogel and loaded into the appropriate compartment of the multiphasic scaffold. The multiphasic scaffold was implanted to replace the native rabbit medial collateral ligament ( n = 16). The rabbits were randomly assigned to two different treatment groups. The first group was immobilized postoperatively with the knee pinned in flexion with K-wires for 4 weeks ( n = 8) prior to sacrifice. The second group was immobilized for 4 weeks, had the K-wires removed followed by a further 4 weeks of mobilization prior to sample harvesting. Literature Review Heterotopic ossification as early as 4 weeks was noted on gross dissection and confirmed by microcomputed tomography and histological staining. This analysis revealed formation of a bony bridge located within and over the ligament compartment in the intra-articular region. Biomechanical testing showed increased ultimate force of the ligament compartment at 4 weeks postimplantation consistent with the presence of bone formation and higher numbers of scaffold failures at the bone-tendon junction. This study has demonstrated that the addition of BMP2 and GDF5 in the bone-ligament-bone (BLB) scaffold resulted in heterotopic bone formation and failure of the ligament compartment. Clinical Relevance The implantation of a three-dimensional-printed BLB scaffold alone demonstrated superior biomechanical and histological results, and further investigation is needed as a possible clinical reconstruction for the SLIL.

Impact of High Fat Diet and Sex in a Rabbit Model of Carpal Tunnel Syndrome.

Carpal tunnel syndrome (CTS) is a common musculoskeletal disorder, characterized by fibrosis of the subsynovial connective tissue (SSCT) mediated by transforming growth factor beta (TGF-ß). Risk factors for CTS include metabolic dysfunction and age. Additionally, the incidence of CTS is higher in women. In this study we hypothesized that a high-fat diet (HFD), a common driver of metabolic dysfunction, would promote SSCT fibrosis found in CTS and that this response would be sex dependent. To test this, we examined the effects of HFD and sex on SSCT fibrosis using our established rabbit model of CTS. Forty-eight (24 male, 24 female) adult rabbits were divided into four groups including HFD or standard diet with and without CTS induction. SSCT was collected for histological and gene expression analysis. HFD promoted SSCT thickening and upregulated profibrotic genes, including TGF-ß. Fibrotic genes were differentially expressed in males and females. Interestingly while the prevalence of CTS is greater in women than in men, the converse is observed in the presence of metabolic dysfunction. This work recapitulates this clinical observation and begins to elucidate the sex-based differences found in SSCT fibrosis. This knowledge should drive further research and may lead to metabolic and sex specific therapeutic strategies for the treatment of patients with CTS.

Biomechanical analysis of three techniques of suspensionplasty after trapeziectomy: a cadaveric study.

The aim of the present cadaveric study was to assess resistance to first metacarpal subsidence of three techniques of suspensionplasty after trapeziectomy. In total, 18 forearms (mean age 60 years [range 20-89]) were used with six specimens per surgical technique: palmar oblique ligament reconstruction with tendon interposition (LRTI), abductor pollicis longus (APL) suspensionplasty, or suture suspensionplasty. There was no significant difference in mean trapezial space height after trapeziectomy and suspensionplasty compared to the preoperative trapezial height. However, after simulation of physiological lateral pinch, there was a significant (p < 0.05) difference in mean trapezial space height between the APL suspensionplasty and the suture suspensionplasty compared to the LRTI group. After axial loading, there was significantly greater metacarpal subsidence in the LRTI group compared to the APL and suture suspensionplasty groups but no statistically significant difference between the suture suspensionplasty and the APL suspensionplasty groups.Level of evidence: V.

Arthroscopic-Assisted Volar Scapholunate Capsulodesis: A New Technique.

Most current surgical techniques for scapholunate interosseous ligament injuries address the dorsal component only. Previously, volar capsulodesis has been described either as an open approach or an "all-inside" technique. In this article, we report an alternative arthroscopic technique to address volar scapholunate interosseous ligament injuries. Arthroscopic-assisted volar scapholunate capsulodesis may be considered in the treatment algorithm for volar scapholunate interosseous ligament injuries.

Deep Learning Estimation of Median Nerve Volume Using Ultrasound Imaging in a Human Cadaver Model.

Median nerve swelling is one of the features of carpal tunnel syndrome (CTS), and ultrasound measurement of maximum median nerve cross-sectional area is commonly used to diagnose CTS. We hypothesized that volume might be a more sensitive measure than cross-sectional area for CTS diagnosis. We therefore assessed the accuracy and reliability of 3-D volume measurements of the median nerve in human cadavers, comparing direct measurements with ultrasound images interpreted using deep learning algorithms. Ultrasound images of a 10-cm segment of the median nerve were used to train the U-Net model, which achieved an average volume similarity of 0.89 and area under the curve of 0.90 from the threefold cross-validation. Correlation coefficients were calculated using the areas measured by each method. The intraclass correlation coefficient was 0.86. Pearson's correlation coefficient R between the estimated volume from the manually measured cross-sectional area and the estimated volume of deep learning was 0.85. In this study using deep learning to segment the median nerve longitudinally, estimated volume had high reliability. We plan to assess its clinical usefulness in future clinical studies. The volume of the median nerve may provide useful additional information on disease severity, beyond maximum cross-sectional area.

Fibroblastic differentiation of mesenchymal stem/stromal cells (MSCs) is enhanced by hypoxia in 3D cultures treated with bone morphogenetic protein 6 (BMP6) and growth and differentiation factor 5 (GDF5).

INTRODUCTION: Culture conditions and differentiation cocktails may facilitate cell maturation and extracellular matrix (ECM) secretion and support the production of engineered fibroblastic tissues with applications in ligament regeneration. The objective of this study is to investigate the potential of two connective tissue-related ligands (i.e., BMP6 and GDF5) to mediate collagenous ECM synthesis and tissue maturation in vitro under normoxic and hypoxic conditions based on the hypothesis that BMP6 and GDF5 are components of normal paracrine signalling events that support connective tissue homeostasis. METHODS: Human adipose-derived MSCs were seeded on 3D-printed medical-grade polycaprolactone (PCL) scaffolds using a bioreactor and incubated in media containing GDF5 and/or BMP6 for 21 days in either normoxic (5% oxygen) or hypoxic (2% oxygen) conditions. Constructs were harvested on Day 3 and 21 for cell viability analysis by live/dead staining, structural analysis by scanning electron microscopy, mRNA levels by RTqPCR analysis, and in situ deposition of proteins by immunofluorescence microscopy. RESULTS: Pro-fibroblastic gene expression is enhanced by hypoxic culture conditions compared to normoxic conditions. Hypoxia renders cells more responsive to treatment with BMP6 as reflected by increased expression of ECM mRNA levels on Day 3 with sustained expression until Day 21. GDF5 was not particularly effective either in the absence or presence of BMP6. CONCLUSIONS: Fibroblastic differentiation of MSCs is selectively enhanced by BMP6 and not GDF5. Environmental factors (i.e., hypoxia) also influenced the responsiveness of cells to this morphogen.

Combination of BMP2 and EZH2 Inhibition to Stimulate Osteogenesis in a 3D Bone Reconstruction Model.

High concentrations of bone morphogenetic protein 2 (BMP2) in bone regeneration cause adverse events (e.g, heterotopic bone formation and acute inflammation). This study examines novel epigenetic strategies (i.e., EZH2 inhibition) for augmenting osteogenesis, thereby aiming to reduce the required BMP2 dose in vivo for bone regeneration and minimize these adverse effects. Human bone marrow-derived mesenchymal stem cells (BMSCs) were grown on three-dimensional (3D)-printed medical-grade polycaprolactone scaffolds and incubated in osteogenic media containing 50 ng/mL BMP2 and/or 5 µM GSK126 (EZH2 inhibitor) for 6 days (n = 3 per group and timepoint). Constructs were harvested for realtime quantitative polymerase chain reaction analysis at Day 10 and immunofluorescence (IF) microscopy at Day 21. After pretreating for 6 days and maintaining in osteogenic media for 4 days, BMSC-seeded scaffolds were also implanted in an immunocompromised subcutaneous murine model (n = 39; 3/group/donor and 3 control scaffolds) for histological analysis at 8 weeks. Pretreatment of BMSCs with BMP2 and BMP2/GSK126 costimulated expression of osteoblast-related genes (e.g., IBSP, SP7, RUNX2, and DLX5), as well as protein accumulation (e.g., collagen type 1/COL1A1 and osteocalcin/BGLAP) based on IF staining. While in vivo implantation for 8 weeks did not result in bone formation, increased angiogenesis was observed in BMP2 and BMP2/GSK126 groups. This study finds that BMP2 and GSK126 costimulate osteogenic differentiation of MSCs on 3D scaffolds in vitro and may contribute to enhanced vascularization when implanted in vivo to support bone formation. Thus, epigenetic priming with EZH2 inhibitors may have translational potential in bone healing by permitting a reduction of BMP2 dosing in vivo to mitigate its side effects. Impact statement While autografts are still the gold standard for bone reconstruction, tissue availability and donor morbidity are significant limitations. Previous attempts to use high concentrations of bone morphogenetic protein 2 (BMP2) have been shown to cause adverse events such as excessive bone formation and acute inflammation. Overall, the utilization of EZH2 inhibitors to modulate gene expression in favor of bone healing has been demonstrated in vitro in a tissue engineering strategy. Our study will pave the way to developing tissue engineering strategies involving GSK126 as an adjuvant to increase the effects of BMP2 for stimulating cells of interest on a three-dimensional scaffold for bone regeneration.

Multiphasic scaffold for scapholunate interosseous ligament reconstruction: A study in the rabbit knee.

Scapholunate interosseous ligament tears are a common wrist injury in young and active patients that can lead to suboptimal outcomes after repair. This research aims to assess a multiphasic scaffold using 3D-printing for reconstruction of the dorsal scapholunate interosseous ligament. The scaffold was surgically implanted in vivo in the position of the native rabbit medial collateral ligament. Two branches of treatment were implemented in the study. In the first group, the rabbits (n = 8) had the knee joint fixed in flexion for 4 weeks using 1.4 mm K-wires prior to sample harvesting. The second group (n = 8) had the rabbit knee joint immobilized for 4 weeks prior to K-wire removal and mobilization for an additional 4 weeks prior to sample harvesting. Overall, samples were harvested at 4 weeks post-surgery (immobilized group) and eight weeks post-surgery (mobilized group). Mechanical tensile testing (n = 5/group) and histology (n = 3/group) of the constructs were conducted. Tissue integration and maturation were observed resulting in increased mechanical strength of the operated joint at 8 weeks (P < .05). Bone and ligament tissues were regenerated in their respective compartments with structural and mechanical properties approaching those reported for the human dorsal SLIL ligament. Clinical Significance: This proof of concept study has demonstrated that the synthetic multiphasic scaffold was capable of regenerating both bone and ligament while also withstanding the physiological load once implanted in the rabbit knee. The artificial scaffold may provide an alternative to current techniques for reconstruction of scapholunate instability or other ligament injuries in the hand and wrist.

Additively Manufactured Multiphasic Bone-Ligament-Bone Scaffold for Scapholunate Interosseous Ligament Reconstruction.

The scapholunate interosseous ligament (SLIL) is a frequently torn wrist ligament, and current surgical options for SLIL tears are suboptimal. This research aims to develop a novel multiphasic bone-ligament-bone scaffold (BLB) with a porous interface using 3D-printing and cell sheet technology for the reconstruction of the dorsal scapholunate interosseous ligament. The BLB comprises two bone compartments bridged by aligned polycaprolactone fibers mimicking the architecture of the native tissue. Mechanical testing of the BLBs shows their ability to withstand physiological forces. Combination of the BLB with human bone marrow mesenchymal stem cell sheet demonstrates that the harvesting did not compromise cell viability, while allowing homogeneous distribution in the ligament compartment. The BLBs are loaded with cell sheets and bone morphogenetic protein-2 in the ligament and bone compartment respectively prior to ectopic implantation into athymic rats. The histology demonstrates rapid tissue infiltration, high vascularization, and more importantly the maintenance of the compartmentalization as bone formation remains localized to the bone compartment despite the porous interface. The cells in the ligament compartment become preferentially aligned, and this proof-of-concept study demonstrates that the BLB can provide sufficient compartmentalization and fiber guiding properties necessary for the regeneration of the dorsal SLIL.

How myeloid cells contribute to the pathogenesis of prominent emerging zoonotic diseases.

Up to 75 % of emerging human diseases are zoonoses, spread from animals to humans. Although bacteria, fungi and parasites can be causative agents, the majority of zoonotic infections are caused by viral pathogens. During the past 20 years many factors have converged to cause a dramatic resurgence or emergence of zoonotic diseases. Some of these factors include demographics, social changes, urban sprawl, changes in agricultural practices and global climate changes. In the period between 2014-2017 zoonotic viruses including ebola virus (EBOV), chikungunya virus (CHIKV), dengue virus (DENV) and zika virus (ZIKV), caused prominent outbreaks resulting in significant public health and economic burdens, especially in developing areas where these diseases are most prevalent. When a viral pathogen invades a new human host, it is the innate immune system that serves as the first line of defence. Myeloid cells are especially important to help fight viral infections, including those of zoonotic origins. However, viruses such as EBOV, CHIKV, DENV and ZIKV have evolved mechanisms that allow circumvention of the host's innate immune response, avoiding eradication and leading to severe clinical disease. Herein, the importance of myeloid cells in host defence is discussed and the mechanisms by which these viruses exploit myeloid cells are highlighted. The insights provided in this review will be invaluable for future studies looking to identify potential therapeutic targets towards the treatment of these emerging diseases.

Chondrocytes Contribute to Alphaviral Disease Pathogenesis as a Source of Virus Replication and Soluble Factor Production.

Arthritogenic alphavirus infections often result in debilitating musculoskeletal disorders that affect the joints, muscle, and bone. In order to evaluate the infection profile of primary human skeletal muscle and chondrocyte cells to Ross River virus (RRV) in vitro, cells were infected at a multiplicity of infection (MOI) of 1 over a period of two days. Viral titers were determined by plaque assay and cytokine expression by Bio-Plex® assays using the supernatants harvested. Gene expression studies were conducted using total RNA isolated from cells. Firstly, we show that RRV RNA is detected in chondrocytes from infected mice in vivo. Both human primary skeletal muscle and chondrocyte cells are able to support productive RRV infection in vitro. We also report the production of soluble host factors including the upregulation of heparanase (HPSE) and inflammatory host factors such as interleukin-6 (IL-6), monocyte chemoattractant protein 1 (MCP-1), RANTES (regulated on activation, normal T cell expressed and secreted), interferon gamma (IFN-γ), and tumor necrosis factor alpha (TNF-α), which are also present during clinical disease in humans. Our study is the first to demonstrate that human chondrocyte cells are permissive to RRV infection, support the production of infectious virus, and produce soluble factors including HPSE, which may contribute to joint degradation and the pathogenesis of disease.

Tissue Engineering in Hand Surgery: A Technology Update.

The field of hand surgery is constantly evolving to meet the challenges of repairing intricate anatomical structures with limited availability of donor tissue. The past 10 years have seen an exponential growth in tissue engineering, which has broadened the perspectives of tackling these age-old problems. Various fabrication techniques such as melt electrospinning and fused deposition modelling have been employed to synthesize 3-dimensional bioscaffolds that can be used to replace lost tissue. These bioscaffolds with strategic biomimicry have been shown to allow for integrative and functional repair of tissue injuries. This review article summarizes the most current advances in tissue engineering and its applications in the field of hand surgery. It outlines the current tissue engineering techniques commonly used for tackling musculoskeletal problems and highlights the most promising approaches according to clinical evidence. In particular, the paper explores regenerative medicine concepts applied to specific tissues including nerve, bone, cartilage, tendon, ligament, and vessels. In the face of innovative and pioneering research, tissue engineering will undoubtedly play a key role in reconstructive hand surgery in the not too distant future.