A brief review of complex regional pain syndrome and current management.

Complex regional pain syndrome (CRPS) is a debilitating chronic pain condition that, although exceedingly rare, carries a significant burden for the affected patient population. The complex and ambiguous pathophysiology of this condition further complicates clinical management and therapeutic interventions. Furthermore, being a diagnosis of exclusion requires a diligent workup to ensure an accurate diagnosis and subsequent targeted management. The development of the Budapest diagnostic criteria helped to consolidate existing definitions of CRPS but extensive work remains in identifying the underlying pathways. Currently, two distinct types are identified by the presence (CRPS type 1) or absence (CRPS type 2) of neuronal injury. Current management directed at this disease is broad and growing, ranging from non-invasive modalities such as physical and psychological therapy to more invasive techniques such as dorsal root ganglion stimulation and potentially amputation. Ideal therapeutic interventions are multimodal in nature to address the likely multifactorial pathological development of CRPS. Regardless, a significant need remains for continued studies to elucidate the pathways involved in developing CRPS as well as more robust clinical trials for various treatment modalities.

Complex regional pain syndrome (CRPS) is a debilitating and complex condition that places a significant physical, psychological and emotional burden upon afflicted patients necessitating multi-modal approaches to treatment.The development of the Budapest criteria provided a robust and well-tested set of diagnostic criteria to aid clinicians in the diagnosis of CRPS.The pathophysiology of CRPS has been challenging to elucidate with numerous proposed mechanisms, altogether suggesting a multi-factorial process is involved in the development of this condition.Non-invasive treatments for CRPS are essential in addressing the physical limitations this disease can cause as well as addressing the significant psychological burden that involves increased incidence of depression and suicidal ideation.Invasive treatments offer promising results, especially when considering dorsal root ganglion stimulation; however, the need for more robust clinical trials remains, especially when considering a small portion of patients who have refractory CRPS resort to amputation to control their pain symptoms.

Left hemothorax resulting from delayed right ventricular apical pacing lead perforation without hemopericardium, a case report.

INTRODUCTION AND IMPORTANCE: Right ventricular pacemaker lead perforation is a rare but well documented complication of pacemaker implantation. Lead perforation can cause an array of symptoms ranging from none to hemodynamic instability and tamponade. In previously reported cases, lead perforation has always been able to be confirmed by imaging, with computed tomography (CT) scan considered to be the gold standard diagnostic imaging modality. CASE PRESENTATION: An 80-year-old male underwent uncomplicated implantation of a dual chamber pacemaker for sick sinus syndrome as an outpatient. Thirty-nine days later, the patient presented to the emergency department complaining of new-onset, left-sided, pleuritic chest pain. He was found to have unilateral hemothorax and abnormal pacemaker lead interrogation. Pacemaker lead perforation was suspected but not confirmed with imaging. Lead perforation was only identified after surgical exploration. CLINICAL DISCUSSION: This patient had multiple risk factors for pacemaker lead perforation. However, imaging, including CT scan was unable to confirm perforation. The presence of an otherwise unexplained left hemothorax strongly suggested that surgical intervention was indicated. The lead perforation was subsequently confirmed with subxiphoid exploration of the pericardial space. The mechanism of lead perforation resulting in hemothorax in this case is not straight forward, as no direct communication between the pericardial and pleural spaces was identified. However, previously described visceral pericardial self-sealing may contribute to the small pericardial accumulation described herein. CONCLUSION: This patient's presentation and clinical course underscore the importance of maintaining a high index of suspicion for pacemaker lead perforation despite a lack of confirmation with imaging.

Amniotic mesenchymal stem cells mitigate osteoarthritis progression in a synovial macrophage-mediated in vitro explant coculture model.

Osteoarthritis (OA) is a disease of the synovial joint marked by chronic, low-grade inflammation leading to cartilage destruction. Regenerative medicine strategies for mitigating OA progression and/or promoting cartilage regeneration must be assessed using models that mimic the hallmarks of OA. More specifically, these models should maintain synovial macrophage phenotype in their native micro-environment. Herein, an in vitro coculture model of patient-matched human OA cartilage and synovium was assessed for viability, macrophage phenotype, and progressive cartilage destruction in the presence of an inflammatory milieu. Additionally, the influence of synovial macrophages and their polarization within the model was defined using depletion studies. Finally, the model was used to compare the ability of human amniotic stem cells (hAMSCs) and human adipose stem cells (hADSCs) to mitigate OA progression. OA cocultures demonstrated progressive and significant reductions in chondrocyte viability and cartilage glycosaminoglycan content within a proinflammatory environment. Selective depletion of synovial macrophages resulted in significant decreases in M1:M2 percentage ratio yielding significant reductions in concentrations of interleukin-1 beta, matrix metalloproteinase-13 and attenuation of cartilage damage. Finally, hAMSCs were found to be more chondroprotective versus hADSCs as indicated by significantly improved OA chondrocyte viability (89.8 ± 2.4% vs. 58.4 ± 2.4%) and cartilage glycosaminoglycan content (499.0 ± 101.9 µg/mg dry weight vs. 155.0 ± 26.3 µg/mg dry weight) and were more effective at shifting OA synovial macrophage M1:M2 ratio (1.3:1 vs. 5:1), respectively. Taken together, the coculture model mimics salient features of OA, including macrophage-mediated cartilage destruction that was effectively abrogated by hAMSCs but not hADSCs.

Amniotic Mesenchymal Stromal Cells Exhibit Preferential Osteogenic and Chondrogenic Differentiation and Enhanced Matrix Production Compared With Adipose Mesenchymal Stromal Cells.

BACKGROUND: Therapeutic efficacy of various mesenchymal stromal cell (MSC) types for orthopaedic applications is currently being investigated. While the concept of MSC therapy is well grounded in the basic science of healing and regeneration, little is known about individual MSC populations in terms of their propensity to promote the repair and/or regeneration of specific musculoskeletal tissues. Two promising MSC sources, adipose and amnion, have each demonstrated differentiation and extracellular matrix (ECM) production in the setting of musculoskeletal tissue regeneration. However, no study to date has directly compared the differentiation potential of these 2 MSC populations. PURPOSE: To compare the ability of human adipose- and amnion-derived MSCs to undergo osteogenic and chondrogenic differentiation. STUDY DESIGN: Controlled laboratory study. METHODS: MSC populations from the human term amnion were quantified and characterized via cell counting, histologic assessment, and flow cytometry. Differentiation of these cells in comparison to commercially purchased human adipose-derived mesenchymal stromal cells (hADSCs) in the presence and absence of differentiation media was evaluated via reverse transcription polymerase chain reaction (PCR) for bone and cartilage gene transcript markers and histology/immunohistochemistry to examine ECM production. Analysis of variance and paired t tests were performed to compare results across all cell groups investigated. RESULTS: The authors confirmed that the human term amnion contains 2 primary cell types demonstrating MSC characteristics-(1) human amniotic epithelial cells (hAECs) and (2) human amniotic mesenchymal stromal cells (hAMSCs)-and each exhibited more than 90% staining for MSC surface markers (CD90, CD105, CD73). Average viable hAEC and hAMSC yields at harvest were 2.3 × 106 ± 3.7 × 105 and 1.6 × 106 ± 4.7 × 105 per milliliter of amnion, respectively. As well, hAECs and hAMSCs demonstrated significantly greater osteocalcin ( P = .025), aggrecan ( P < .0001), and collagen type 2 ( P = .044) gene expression compared with hADSCs, respectively, after culture in differentiation medium. Moreover, both hAECs and hAMSCs produced significantly greater quantities of mineralized ( P < .0001) and cartilaginous ( P = .0004) matrix at earlier time points compared with hADSCs when cultured under identical osteogenic and chondrogenic differentiation conditions, respectively. CONCLUSION: Amnion-derived MSCs demonstrate a greater differentiation potential toward bone and cartilage compared with hADSCs. CLINICAL RELEVANCE: Amniotic MSCs may be the source of choice in the regenerative treatment of bone or osteochondral musculoskeletal disease. They show significantly higher yields and better differentiation toward these tissues than MSCs derived from adipose.

Tissues reborn: fetal membrane-derived matrices and stem cells in orthopedic regenerative medicine.

The amniotic and chorionic membranes, as well as the stem cell populations contained within them, represent a widely available, versatile, and promising resource for use in numerous regenerative medicine applications. The primary focus of this review is to examine the use of the fetal membranes and/or their resident stem cell populations for regenerating orthopedic tissues. This discussion is prefaced by a brief synopsis of the structure, function, and biological properties of the extracellular matrix; embryological development; and a brief description of the distinct stem cell populations residing within the amniotic and chorionic membranes. Commercially available perinatal tissue allograft products available in the United States are reviewed, and a concise summary regarding the US Food and Drug Administration's current viewpoint on these technologies is provided. Concluding remarks regarding suggested future research directives for evaluating these tissues and stem cell sources in relation to orthopedic regenerative medicine applications also are presented.