Kakar, Sanjeev

Background Radiocarpal dislocations are rare, high-energy injuries. High morbidity and poor functional outcomes are common. Currently, there is limited data on functional outcomes following treatment of this injury. Methods A retrospective review was conducted analyzing the radiographic and clinical outcome of patients treated for a radiocarpal dislocation from 1979 to 2010. Outcome assessments included wrist range of motion, grip strength, Mayo wrist score, patient-rated wrist evaluation (PRWE), and disabilities of the arm, shoulder and hand (DASH) score. Statistical analysis was performed with the Student's t test. Results Twenty-six patients (26 wrists) were treated for a radiocarpal dislocation during the study period; 23 wrists were treated acutely (within 4 weeks of injury), and 3 were treated after a delayed presentation (>4 weeks). Clinical follow-up of more than 6 months was available in 17 patients. Three patients (12 %) underwent primary fusion as initial treatment (two radioscapholunate fusion; one total wrist fusion). Four wrists (24 %) failed initial treatment and were salvaged with scapholunate ligament reconstruction (one wrist) or partial wrist fusion (three wrists). Seventeen patients completed PRWE and DASH questionnaires with a mean of 14.6 years following surgery (range 2–32 years). Subjective outcomes tended to be superior in those patients treated with ligament reconstruction versus partial or complete wrist fusion; however, comparisons were not statistically significant. Conclusion Radiocarpal dislocations result in significant osseous and ligamentous injury to the distal radius and carpus. Early recognition and treatment of radiocarpal dislocations with open reduction, internal fixation, and repair of ligaments may result in improved long-term functional outcomes when compared to acute partial or complete wrist arthrodesis.

The biological interface between an orthopedic implant and the surrounding host tissue may have a dramatic effect upon clinical outcome. Desired effects include bony ingrowth (osseointegration), stimulation of osteogenesis (osteoinduction), increased vascularization, and improved mechanical stability. Implant loosening, fibrous encapsulation, corrosion, infection, and inflammation, as well as physical mismatch may have deleterious clinical effects. This is particularly true of implants used in the reconstruction of load-bearing synovial joints such as the knee, hip, and the shoulder. The surfaces of orthopedic implants have evolved from solid-smooth to roughened-coarse and most recently, to porous in an effort to create a three-dimensional architecture for bone apposition and osseointegration. Total joint surgeries are increasingly performed in younger individuals with a longer life expectancy, and therefore, the postimplantation lifespan of devices must increase commensurately. This review discusses advancements in biomaterials science and cell-based therapies that may further improve orthopedic success rates. We focus on material and biological properties of orthopedic implants fabricated from porous metal and highlight some relevant developments in stem-cell research. We posit that the ideal primary and revision orthopedic load-bearing metal implants are highly porous and may be chemically modified to induce stem cell growth and osteogenic differentiation, while minimizing inflammation and infection. We conclude that integration of new biological, chemical, and mechanical methods is likely to yield more effective strategies to control and modify the implant–bone interface and thereby improve long-term clinical outcomes.

Human adipose‐derived mesenchymal stromal cells (AMSCs) grown in platelet lysate are promising agents for therapeutic tissue regeneration. Here, we investigated whether manipulation of epigenetic events by the clinically relevant histone deacetylase inhibitor suberoylanilide hydroxamic acid (SAHA) alters differentiation of AMSCs. The multipotency of AMSCs was validated by their ability to differentiate into osteogenic, chondrogenic, and adipogenic lineages. High‐throughput RNA sequencing and RT‐qPCR established that human histone deacetylases (HDAC1 to HDAC11, and SIRT1 to SIRT7) are differentially expressed in AMSCs. SAHA induces hyper‐acetylation of histone H3 and H4, stimulates protein expression of the HDAC‐responsive gene SLC9A3R1/NHERF1 and modulates the AKT/FOXO1 pathway. Biologically, SAHA interferes with osteogenic, chondrogenic and adipogenic lineage commitment of multipotent AMSCs. Mechanistically, SAHA‐induced loss of differentiation potential of uncommitted AMSCs correlates with multiple changes in the expression of principal transcription factors that control mesenchymal or pluripotent states. We propose that SAHA destabilizes the multi‐potent epigenetic state of uncommitted human AMSCs by hyper‐acetylation and perturbation of key transcription factor pathways. Furthermore, AMSCs grown in platelet lysate may provide a useful biological model for screening of new HDAC inhibitors that control the biological fate of human mesenchymal stromal cells. J. Cell. Physiol. 230: 52–62, 2015. © 2014 Wiley Periodicals, Inc.

AbstractImproving the effectiveness of adipose‐tissue derived human mesenchymal stromal/stem cells (AMSCs) for skeletal therapies requires a detailed characterization of mechanisms supporting cell proliferation and multi‐potency. We investigated the molecular phenotype of AMSCs that were either actively proliferating in platelet lysate or in a basal non‐proliferative state. Flow cytometry combined with high‐throughput RNA sequencing (RNASeq) and RT‐qPCR analyses validate that AMSCs express classic mesenchymal cell surface markers (e.g., CD44, CD73/NT5E, CD90/THY1, and CD105/ENG). Expression of CD90 is selectively elevated at confluence. Self‐renewing AMSCs express a standard cell cycle program that successively mediates DNA replication, chromatin packaging, cyto‐architectural enlargement, and mitotic division. Confluent AMSCs preferentially express genes involved in extracellular matrix (ECM) formation and cellular communication. For example, cell cycle‐related biomarkers (e.g., cyclins E2 and B2, transcription factor E2F1) and histone‐related genes (e.g., H4, HINFP, NPAT) are elevated in proliferating AMSCs, while ECM genes are strongly upregulated (>10‐fold) in quiescent AMSCs. AMSCs also express pluripotency genes (e.g., POU5F1, NANOG, KLF4) and early mesenchymal markers (e.g., NES, ACTA2) consistent with their multipotent phenotype. Strikingly, AMSCs modulate expression of WNT signaling components and switch production of WNT ligands (from WNT5A/WNT5B/WNT7B to WNT2/WNT2B), while upregulating WNT‐related genes (WISP2, SFRP2, and SFRP4). Furthermore, post‐proliferative AMSCs spontaneously express fibroblastic, osteogenic, chondrogenic, and adipogenic biomarkers when maintained in confluent cultures. Our findings validate the biological properties of self‐renewing and multi‐potent AMSCs by providing high‐resolution quality control data that support their clinical versatility. J. Cell. Biochem. 115: 1816–1828, 2014. © 2014 Wiley Periodicals, Inc.

A 63‐year‐old right‐handed office worker presented with acute right wrist pain after lifting a heavy file at work. Results of a clinical examination suggested flexor carpi radialis tendinopathy. Diagnostic ultrasound (US) not only detected a complete flexor carpi radialis tear but also revealed the presence of a concomitant flexor carpi radialis brevis (FCRB) tendon with associated tenosynovitis. The ability of US to correctly identify the FCRB has not been previously reported. Furthermore, the US appearance of FCRB tendinopathy and tenosynovitis has not been described. High‐resolution US can identify the FCRB muscle‐tendon in the wrist region. Sonologists and sonographers should be aware of the US appearance of the FCRB as well as the potential for the FCRB to contribute to radial wrist pain syndromes.

Painful radioulnar convergence following resection of the distal ulna can produce substantial disability and prove a challenging surgical problem, particularly in the revision setting. The purpose of this study was to evaluate the outcome of a series of patients with chronic distal radioulnar joint instability or multiple prior procedures treated with linked distal radioulnar joint arthroplasty with the APTIS prosthesis. A series of ten patients were identified with a mean follow up of 4.0 years. At final follow-up nine of ten implants survived free from revision or removal, with patients experiencing good pain relief and functional outcomes, with reasonable overall satisfaction in all seven patients who returned the questionnaires. Despite the medium-term follow-up and small number of patients, our results suggest the linked distal radioulnar joint arthroplasty may be a viable option for treating painful radioulnar convergence following multiple failed procedures at the distal radioulnar joint.