Mid-Term Outcomes of Combined Hip Arthroscopy and Limited Open Capsular Plication in the Non-Dysplastic Hip.

BACKGROUND: Hip microinstability remains poorly-defined but increasingly diagnosed in the setting of borderline dysplasia (LCEA 20-25°), soft tissue laxity, or following unrepaired arthroscopic capsulotomy. While hip microinstability is com-monly treated with arthroscopic capsular plication with short-term outcomes reported, this procedure has been performed open for some time. The purpose of current study was to assess the durability of outcomes of combined arthroscopy and open capsular plication in treating symptomatic hip microinstability at mid-term follow-up. METHODS: We retrospectively identified hips that underwent combined hip arthroscopy and open capsular plication for symptomatic microinstability between 2008 and 2013. Hips with excessive femoral anteversion (femoral version >35°) or classic acetabular dysplasia (LCEA <20°) were treated with bony reorientation and were not included in the current study. Patient reported outcomes scores were collected preoperatively and at a minimum five year follow-up. Hips that required reoperation or did not meet criteria for minimally clinically important difference (MCID, ≥8 increase in mHHS) or patient acceptable symptom scores (PASS, mHHS) were considered failures. RESULTS: A total of 27 hips met criteria for inclusion and follow-up was obtained for 22 hips (81.5%) at a mean of 7.1 years. All patients were female with a mean age of 25.9 years and 7 (32%) hips had previous surgery. Patients undergoing the combined procedure improved from a mean baseline mHHS of 55.3±13 to a mean follow-up mHHS of 74.5±20.9 (p<0.001). At midterm follow-up, 54.5% of hips met criteria for PASS and 68.2% of hips met criteria for MCID, with 72.7% of hips meeting criteria for either MCID or PASS. Overall, 10 hips (45%) were considered failures with 6 hips (27%) requiring reoperation and an additional 4 hips (18%) with clinical failure. Hips without previous surgery had a failure rate of 33.3% (5/15) while 71.4% (5/7) of those with previous surgery failed (P=.09). CONCLUSION: Our study demonstrates a high (45%) rate of reoperations and persistent symptoms in hips with microinstability treated with combined arthroscopy and open capsular plication. Further mid- and long-term studies evaluating soft tissue plication are needed, as well as comparisons with bony procedures in the setting of microinstability are needed.Level of Evidence: III.

Circulating exosomes derived from transplanted progenitor cells aid the functional recovery of ischemic myocardium.

The stem cell field is hindered by its inability to noninvasively monitor transplanted cells within the target organ in a repeatable, time-sensitive, and condition-specific manner. We hypothesized that quantifying and characterizing transplanted cell-derived exosomes in the recipient plasma would enable reliable, noninvasive surveillance of the conditional activity of the transplanted cells. To test this hypothesis, we used a human-into-rat xenogeneic myocardial infarction model comparing two well-studied progenitor cell types: cardiosphere-derived cells (CDCs) and c-kit+ cardiac progenitor cells (CPCs), both derived from the right atrial appendage of adults undergoing cardiopulmonary bypass. CPCs outperformed the CDCs in cell-based and in vivo regenerative assays. To noninvasively monitor the activity of transplanted CDCs or CPCs in vivo, we purified progenitor cell-specific exosomes from recipient total plasma exosomes. Seven days after transplantation, the concentration of plasma CPC-specific exosomes increased about twofold compared to CDC-specific exosomes. Computational pathway analysis failed to link CPC or CDC cellular messenger RNA (mRNA) with observed myocardial recovery, although recovery was linked to the microRNA (miRNA) cargo of CPC exosomes purified from recipient plasma. We further identified mechanistic pathways governing specific outcomes related to myocardial recovery associated with transplanted CPCs. Collectively, these findings demonstrate the potential of circulating progenitor cell-specific exosomes as a liquid biopsy that provides a noninvasive window into the conditional state of the transplanted cells. These data implicate the surveillance potential of cell-specific exosomes for allogeneic cell therapies.

Stem Cell Therapy for Hypoplastic Left Heart Syndrome: Mechanism, Clinical Application, and Future Directions.

Hypoplastic left heart syndrome is a type of congenital heart disease characterized by underdevelopment of the left ventricle, outflow tract, and aorta. The condition is fatal if aggressive palliative operations are not undertaken, but even after the complete 3-staged surgical palliation, there is significant morbidity because of progressive and ultimately intractable right ventricular failure. For this reason, there is interest in developing novel therapies for the management of right ventricular dysfunction in patients with hypoplastic left heart syndrome. Stem cell therapy may represent one such innovative approach. The field has identified numerous stem cell populations from different tissues (cardiac or bone marrow or umbilical cord blood), different age groups (adult versus neonate-derived), and different donors (autologous versus allogeneic), with preclinical and clinical experience demonstrating the potential utility of each cell type. Preclinical trials in small and large animal models have elucidated several mechanisms by which stem cells affect the injured myocardium. Our current understanding of stem cell activity is undergoing a shift from a paradigm based on cellular engraftment and differentiation to one recognizing a primarily paracrine effect. Recent studies have comprehensively evaluated the individual components of the stem cells' secretomes, shedding new light on the intracellular and extracellular pathways at the center of their therapeutic effects. This research has laid the groundwork for clinical application, and there are now several trials of stem cell therapies in pediatric populations that will provide important insights into the value of this therapeutic strategy in the management of hypoplastic left heart syndrome and other forms of congenital heart disease. This article reviews the many stem cell types applied to congenital heart disease, their preclinical investigation and the mechanisms by which they might affect right ventricular dysfunction in patients with hypoplastic left heart syndrome, and finally, the completed and ongoing clinical trials of stem cell therapy in patients with congenital heart disease.

Regenerative medicine therapy for single ventricle congenital heart disease.

One of the most complex forms of congenital heart disease (CHD) involving single ventricle physiology is hypoplastic left heart syndrome (HLHS), characterized by underdevelopment of the left ventricle (LV), mitral and aortic valves, and narrowing of the ascending aorta. The underdeveloped LV is incapable of providing long-term systemic flow, and if left untreated, the condition is fatal. Current treatment for this condition consists of three consecutive staged palliative operations: the first is conducted within the first few weeks of birth, the second between 4 to 6 months, and the third and final surgery within the first 4 years. At the conclusion of the third surgery, systemic perfusion is provided by the right ventricle (RV), and deoxygenated blood flows passively to the pulmonary vasculature. Despite these palliative interventions, the RV, which is ill suited to provide long-term systemic perfusion, is prone to eventual failure. In the absence of satisfying curative treatments, stem cell therapy may represent one innovative approach to the management of RV dysfunction in HLHS patients. Several stem cell populations from different tissues (cardiac and non-cardiac), different age groups (adult- vs. neonate-derived), and different donors (autologous vs. allogeneic), are under active investigation. Preclinical trials in small and large animal models have elucidated several mechanisms by which these stem cells affect the injured myocardium, and are driving the shift from a paradigm based upon cellular engraftment and differentiation to one based primarily on paracrine effects. Recent studies have comprehensively evaluated the individual components of the stem cells' secretomes, shedding new light on the intracellular and extracellular pathways at the center of their therapeutic effects. This research has laid the groundwork for clinical application, and there are now several trials of stem cell therapies in pediatric populations that will provide important insights into the value of this therapeutic strategy in the management of HLHS and other forms of CHD. This article reviews the many stem cell types applied to CHD, their preclinical investigation and the mechanisms by which they might affect RV dysfunction in HLHS patients, and finally, the completed and ongoing clinical trials of stem cell therapy in patients with CHD.