Pedicled Pronator Quadratus Transposition for Functional Opponensplasty: A Cadaveric Anatomical Study for Feasibility.

BACKGROUND: Techniques on opponensplasty for chronic carpal tunnel syndrome have been described previously. A novel pronator quadratus (PQ) transposition for chronic carpal tunnel syndrome is described. In addition, the relationship of the distal perforating branch of the radial artery to the surrounding tissue is detailed to optimize further use of the PQ flap for clinical applications. METHODS: Ten cadaver hands underwent PQ dissection, and the perforating branch of the radial artery was identified. Measurements were taken from the radiocarpal joint and the radial styloid to the distal perforating branch. Finally, a proposed surgical technique of PQ transposition with proximal radius periosteum to the first metacarpophalangeal joint and anterior interosseous nerve transfer was performed. RESULTS: The average distance of the perforating branch from the radiocarpal joint was 10 ± 1.05 mm, and the average distance from the radial styloid was 17.1 ± 1.6 mm. Pronator quadratus transposed with a layer of radius periosteum demonstrated anatomical feasibility. CONCLUSIONS: The distal perforating branch of the radial artery predictably perfuses the PQ muscle, which may be used in the future as a means of opponensplasty for chronic carpal tunnel syndrome.

Tissue Expander-Based Breast Reconstruction at a Major Safety-Net Hospital: Managing the Outsized Risk of Infection.

Background: Immediate tissue expander (TE) breast reconstruction is reported to have the highest rate of postoperative infection among reconstructive modalities. The risk of infection is higher among patients treated at safety-net hospitals. Objectives: The goal of this study was to identify significant contributing factors to the elevated infection risk at our major safety-net institution. Methods: A retrospective chart review was conducted on all TE-based reconstruction patients with a diagnosis of postoperative infection between 2015 and 2019. Preoperative, perioperative, and postoperative risk factors for infection were determined and compared across patient and procedure demographics. Results: Two hundred forty-three patients, for a total of 412 breast reconstructions, were included in our study. Significant preoperative selection factors were identified to contribute to the elevated risk of infection, including the following: older age, higher BMI, and diabetes. Significant intraoperative and postoperative contributing factors included greater mastectomy weight, larger TE's and intraoperative fill volume, and longer drain duration. Doxycycline treatment for infected patients resulted in a significantly higher rate of resolution. Conclusions: Safety-net hospital population patients undergoing TE breast reconstruction are at higher risk for postoperative infection. Personal and procedural risk factors are identified. Balancing the benefits of immediate breast reconstruction with TEs with the elevated risk of postoperative infection remains challenging. Implementation of more stringent eligibility criteria may help mitigate the risk of infection.

Surgical Outcomes in Prepectoral Breast Reconstruction.

BACKGROUND: Prepectoral breast reconstruction has reemerged as a popular option for prosthetic-based breast reconstruction. Recent published literature highlights good outcomes; however, techniques are evolving and options exist for different technologies. The aim of this study is to evaluate short-term complication rates of prepectoral reconstructions using Cortiva acellular dermal matrix. METHODS: A multicenter retrospective study was conducted of all patients who underwent mastectomy with immediate direct-to-implant or 2-stage prepectoral breast reconstruction with Cortiva (RTI Surgical, Alachua, Fla.) between January 2016 and September 2018. The incidence of surgical complications was determined and studied against patient demographics and procedural details. RESULTS: One-hundred eighteen patients met the inclusion criteria for a total of 183 individual breasts reconstructed with prepectoral implant. Average length of follow-up was 9.26 months (range, 1.0 month to 2.5 years). Thirty-two breasts (17.49%) experienced 1 or more complications. Prepectoral reconstruction was successful 89.07% of the time. Infection was the most common cause of both reoperation and implant failure, with 7.65% of all breasts requiring washout and 5.46% failing prosthetic reconstruction secondary to infection. CONCLUSIONS: Surgical outcomes for prepectoral breast reconstruction using 2-stage and direct-to-implant are similar and comparable to the literature for dual-plane reconstruction, with infection being the main cause of failure.

Imaging Utilization in Children With Headaches: Current Status and Opportunities for Improvement.

BACKGROUND: Despite a variety of evidence-based guidelines documents, imaging is anecdotally commonly used in the setting of children with headaches, but the frequency of such imaging is unknown. We assessed the use of and estimated costs of imaging utilization in children with headaches at a pediatric hospital. MATERIALS AND METHODS: Retrospectively reviewing charts of all relevant imaging examinations in 2015, we focused on radiology reports with indications containing the terms "headache" or "migraine" and excluded patients who fulfilled evidence-based criteria in support of obtaining imaging. All radiology results were recorded and categorized as normal, likely causative, possibly causative, or unlikely causative of headache. Societal costs were estimated using allowable Medicare fees, and losses of total facility time were estimated using scheduled examination slots. RESULTS: In 2015, 4,257 imaging studies were performed for indications of headache or migraine. Of these, 3,098 (73%) met our exclusion criteria, meaning they had appropriate indications, and 1,159 (27%) were presumably imaged outside of guideline recommendations. Overall, 19.8% (230 of 1,159) had diagnoses that were likely or potentially causative of headaches, and 71.2% (825 of 1,159) were normal. The remainder had findings unlikely to cause headaches. The total estimated societal cost of imaging studies for presumed primary headache imaging at our institution in 2015 was $322,422. The loss of imaging time was 845.3 hours. CONCLUSION: Given the large number of normal examinations and the inappropriate use of radiography, imaging utilization in children with headaches can likely be improved. In addition to reducing ionizing radiation and the need for sedation, reductions in unnecessary imaging would result in societal cost savings and increase imaging capacity for other patients.

Peripheral blood detection of systemic graft-specific xeno-antibodies following transplantation of human neural progenitor cells into the porcine spinal cord.

Extensive pre-clinical and clinical studies have searched for therapeutic efficacy of cell-based therapeutics in diseases of the Central Nervous System (CNS) with no other viable options. Allogeneic cells represent the primary source of these therapies and immunosuppressive regimens have been empirically employed based on experience with solid organ transplantation, attempting to avoid immune mediated graft rejection. In this study, we aimed to 1) characterize the host immune response to stem cells transplanted into the CNS and 2) develop a non-invasive method for detecting immune response to transplanted cell grafts. Human neural progenitor cells were transplanted into the spinal cord of 10 Göttingen minipigs, of which 5 received no immunosuppression and 5 received Tacrolimus. Peripheral blood samples were collected longitudinally for flow cytometry cross match studies. Necropsy was performed at day 21 and spinal cord tissue analysis. We observed a transient increase in xeno-reactive antibodies was detected on post-operative day 7 and 14 in pigs that did not receive immunosuppression. This response was not detected in pigs that received Tacrolimus immunosuppression. No difference in graft survival was observed between the groups. Infiltration of numerous immune mediators including granulocytes, T lymphocytes, and activated microglia, and complement deposition were detected. In summary, a systemic immunologic response to stem cell grafts was detected for two weeks after transplantation using peripheral blood. This could be used as a non-invasive biomarker by investigators for detection of immunologic rejection. However, the absence of a detectable response in peripheral blood does not rule out a parenchymal immune response.

Ferumoxytol Labeling of Human Neural Progenitor Cells for Diagnostic Cellular Tracking in the Porcine Spinal Cord with Magnetic Resonance Imaging.

We report on the diagnostic capability of magnetic resonance imaging (MRI)-based tracking of ferumoxytol-labeled human neural progenitor cells (hNPCs) transplanted into the porcine spinal cord. hNPCs prelabeled with two doses of ferumoxytol nanoparticles (hNPC-FLow and hNPC-FHigh ) were injected into the ventral horn of the spinal cord in healthy minipigs. Ferumoxytol-labeled grafts were tracked in vivo up to 105 days after transplantation with MRI. Injection accuracy was assessed in vivo at day 14 and was predictive of "on" or "off" target cell graft location assessed by histology. No difference in long-term cell survival, assessed by quantitative stereology, was observed among hNPC-FLow , hNPC-FHigh , or control grafts. Histological iron colocalized with MRI signal and engrafted human nuclei. Furthermore, the ferumoxytol-labeled cells retained nanoparticles and function in vivo. This approach represents an important leap forward toward facilitating translation of cell-tracking technologies to clinical trials by providing a method of assessing transplantation accuracy, delivered dose, and potentially cell survival. Stem Cells Translational Medicine 2017;6:139-150.

Magnetic Resonance Imaging-Guided Transplantation of Neural Stem Cells into the Porcine Spinal Cord.

BACKGROUND: Cell-based therapies are a promising treatment option for traumatic, tumorigenic and degenerative diseases of the spinal cord. Transplantation into the spinal cord is achieved with intravascular, intrathecal, or direct intraparenchymal injection. The current standard for direct injection is limited by surgical invasiveness, difficulty in reinjection, and the inability to directly target anatomical or pathological landmarks. The objective of this study was to present the proof of principle for minimally invasive, percutaneous transplantation of stem cells into the spinal cord parenchyma of live minipigs under MR guidance. METHODS: An MR-compatible spine injection platform was developed to work with the ClearPoint SmartFrame system (MRI Interventions Inc.). The system was attached to the spine of 2 live minipigs, a percutaneous injection cannula was advanced into the spinal cord under MR guidance, and cells were delivered to the cord. RESULTS: A graft of 2.5 × 106 human (n = 1) or porcine (n = 1) neural stem cells labeled with ferumoxytol nanoparticles was transplanted into the ventral horn of the spinal cord with MR guidance in 2 animals. Graft delivery was visualized with postprocedure MRI, and characteristic iron precipitates were identified in the spinal cord by Prussian blue histochemistry. Grafted stem cells were observed in the spinal cord of the pig injected with porcine neural stem cells. No postoperative morbidity was observed in either animal. CONCLUSION: This report supports the proof of principle for transplantation and visualization of pharmacological or biological agents into the spinal cord of a large animal under the guidance of MRI.

Preclinical Validation of Multilevel Intraparenchymal Stem Cell Therapy in the Porcine Spinal Cord.

BACKGROUND: Although multiple clinical trials are currently testing different stem cell therapies as treatment alternatives for many neurodegenerative diseases and spinal cord injury, the optimal injection parameters have not yet been defined. OBJECTIVE: To test the spinal cord's tolerance to increasing volumes and numbers of stem cell injections in the pig. METHODS: Twenty-seven female Göttingen minipigs received human neural progenitor cell injections using a stereotactic platform device. Cell transplantation in groups 1 to 5 (5-7 pigs in each) was undertaken with the intent of assessing the safety of an injection volume escalation (10, 25, and 50 µL) and an injection number escalation (20, 30, and 40 injections). Motor function and general morbidity were assessed for 21 days. Full necropsy was performed; spinal cords were analyzed for graft survival and microscopic tissue damage. RESULTS: No mortality or permanent surgical complications were observed during the 21-day study period. All animals returned to preoperative baseline within 14 days, showing complete motor function recovery. The histological analysis showed that there was no significant decrease in neuronal density between groups, and cell engraftment ranged from 12% to 31% depending on the injection paradigm. However, tissue damage was identified when injecting large volumes into the spinal cord (50 µL). CONCLUSION: This series supports the functional safety of various injection volumes and numbers in the spinal cord and gives critical insight into important safety thresholds. These results are relevant to all translational programs delivering cell therapeutics to the spinal cord.