Myocardial infarction resulting in irreversible loss of cardiomyocytes (CMs) remains a leading cause of heart failure. Although cell transplantation has modestly improved cardiac function, major challenges including increasing cell survival, engraftment, and functional integration with host tissue, remain. Embryonic stem cells (ESCs), which can be differentiated into cardiac progenitors (CPs) and CMs, represent a candidate cell source for cardiac cell therapy. However, it is not known what specific cell type or condition is the most appropriate for transplantation. This problem is exasperated by the lack of efficient and predictive strategies to screen the large numbers of parameters that may impact cell transplantation. We used a cardiac tissue model, engineered heart tissue (EHT), and quantitative molecular and electrophysiological analyses, to test transplantation conditions and specific cell populations for their potential to functionally integrate with the host tissue. In this study, we validated our analytical platform using contractile mouse neonatal CMs (nCMs) and noncontractile cardiac fibroblasts (cFBs), and screened for the integration potential of ESC-derived CMs and CPs (ESC-CMs and -CPs). Consistent with previous in vivo studies, cFB injection interfered with electrical signal propagation, whereas injected nCMs improved tissue function. Purified bioreactor-generated ESC-CMs exhibited a diminished capacity for electrophysiological integration; a result correlated with lower (compared with nCMs) connexin 43 expression. ESC-CPs, however, appeared able to appropriately mature and integrate into EHT, enhancing the amplitude of tissue contraction. Our results support the use of EHT as a model system to accelerate development of cardiac cell therapy strategies.

Background: The supercharge end-to-side anterior interosseous nerve–to–ulnar motor nerve transfer offers a viable option to enhance recovery of intrinsic function following ulnar nerve injury. However, in the setting of chronic ulnar nerve compression where the timing of onset of axonal loss is unclear, there is a deficit in the literature on outcomes after supercharge end-to-side anterior interosseous nerve–to–ulnar motor nerve transfer. Methods: A retrospective study of patients who underwent supercharge end-to-side anterior interosseous nerve–to–ulnar motor nerve transfer for severe cubital tunnel syndrome over a 5-year period was performed. The primary outcomes were improvement in first dorsal interosseous Medical Research Council grade at final follow-up and time to reinnervation. Change in key pinch strength; grip strength; and Disabilities of the Arm, Shoulder and Hand questionnaire scores were also evaluated using paired t tests and Wilcoxon signed rank tests. Results: Forty-two patients with severe cubital tunnel syndrome were included in this study. Other than age, there were no significant clinical or diagnostic variables that were predictive of failure. There was no threshold of compound muscle action potential amplitude below which supercharge end-to-side anterior interosseous nerve–to–ulnar motor nerve transfer was unsuccessful. Conclusions: This study provides the first cohort of outcomes following supercharge end-to-side anterior interosseous nerve–to–ulnar motor nerve transfer in chronic ulnar compression neuropathy alone and underscores the importance of appropriate patient selection. Prospective cohort studies and randomized controlled trials with standardized outcome measures are required. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Background Traumatic peripheral nerve injuries cause chronic pain, disability, and long-term reductions in quality of life. However, their incidence after extremity trauma remains poorly understood. Methods The Truven MarketScan Commercial Claims and Encounters database from 2010 to 2015 was used to identify patients aged 18 to 64 who presented to emergency departments for upper and/or lower extremity traumas. Cumulative incidences were calculated for nerve injuries diagnosed within 2 years of trauma. Cox regression models were developed to evaluate the associations between upper extremity nerve injury and chronic pain, disability, and use of physical therapy or occupational therapy. Results The final cohort consisted of 1 230 362 patients with employer-sponsored health plans. Nerve injuries were diagnosed in 2.6% of upper extremity trauma patients and 1.2% of lower extremity trauma patients. Only 9% and 38% of nerve injuries were diagnosed by the time of emergency department and hospital discharge, respectively. Patients with nerve injuries were more likely to be diagnosed with chronic pain (hazard ratio [HR]: 5.9, 95% confidence interval [CI], 4.3-8.2), use physical therapy services (HR: 10.7, 95% CI, 8.8-13.1), and use occupational therapy services (HR: 19.2, 95% CI, 15.4-24.0) more than 90 days after injury. Conclusions The incidence of nerve injury in this national cohort was higher than previously reported. A minority of injuries were diagnosed by emergency department or hospital discharge. These findings may improve practitioner awareness and inform public health interventions for injury prevention.

Background: Peripheral nerve injuries may result in pain, disability, and decreased quality of life (QoL). Pain is an incompletely understood experience and is associated with emotional and behavioral qualities. We hypothesized that pain following peripheral nerve surgery could be predicted by changes in emotions or QoL postoperatively. Methods: Using prospectively collected data, a retrospective study design was used to evaluate the relationships among pain, QoL, and psychosocial factors in patients who underwent peripheral nerve surgery. Patients completed questionnaires rating pain; impact of pain on QoL, sadness, depression, frustration, anger, and hopefulness before surgery; and each postoperative follow-up visit. Multilevel modeling was used to assess the concurrent and lagged relationships between pain and psychosocial factors. Results: Increased pain was concurrently associated with decreased hopefulness ( P = .001) and increased the impact on QoL, sadness, depression, and anger ( P < .001). In lagged analyses, the impact on QoL and anger prospectively predicted pain ( P < .001 and P = .02, respectively). Pain predicted subsequent scores of QoL, sadness, depression, anger, and hopefulness ( P < .01). Having an upper limb nerve injury and self-report of “no comment for childhood trauma” were predictors of postsurgical pain. Conclusion: Psychosocial measures and pain are reciprocally related among patients who underwent surgery for peripheral nerve injuries or compression. Our study provides evidence of the important relationships among psychosocial factors, pain, and outcome and identifies treatment targets following nerve surgery.

Intracranial translucency can be prospectively identified by trained sonographers in 96% of normal fetuses at 11 to 13 weeks. Measurements of brain stem and brain stem-occipital bone diameters are reproducible.

Peripheral nerve transfer (PNT) to improve upper limb function following cervical spinal cord injury (SCI) involves the transfer of supralesional donor nerves under voluntary control to intralesional or sublesional lower motor neurons not under voluntary control. Appropriate selection of donor and recipient nerves and surgical timing affect functional outcomes. Although the gold standard of nerve selection is intraoperative nerve stimulation, preoperative electrodiagnostic (EDX) evaluation may help guide surgical planning. Currently there is no standardized preoperative EDX protocol. This study reviews the EDX workup preceding PNT surgery in cervical SCI and proposes an informed EDX protocol to assist with surgical planning. The PICO (Population, Intervention, Comparison, Outcome) framework was used to formulate relevant Medical Subject Headings (MeSH) terms and identify published cases of PNT in cervical SCI in Medline, Embase, CINAHL, and Emcare databases in the last 10 years. The EDX techniques evaluating putative donor nerves, recipient nerve branches, time sensitivity of nerve transfer and other electrophysiological parameters were summarized to guide creation of a preoperative EDX protocol. Needle electromyography (EMG) was the most commonly used EDX technique to identify healthy donor nerves. Although needle EMG has also been used on recipient nerves, compound muscle action potential amplitudes may provide a more accurate determination of recipient nerve health and time sensitivity for nerve transfer. Although there has been progress in presurgical EDX evaluation, EMG and nerve conduction study approaches are variable, and each has limitations in their utility for preoperative planning. There is need for standardization in the EDX evaluation preceding PNT surgery to assist with donor and recipient nerve selection, surgical timing and to optimize outcomes. Based on results of this review, herein we propose the PreSCIse (PRotocol for Electrodiagnosis in SCI Surgery of the upper Extremity) preoperative EDX panel to achieve said goals through an interdisciplinary and patient‐centered approach.

Embryonic stem cell (ESC) derivatives are a promising cell source for cardiac cell therapy. Mechanistic studies upon cell injection in conventional animal models are limited by inefficient delivery and poor cell survival. As an alternative, we have used an engineered heart tissue (EHT) based on neonatal rat cardiomyocytes (CMs) cultivated with electrical field stimulation as an in vitro model to study cell injection. We injected (0.001, 0.01, and 0.1 million) and tracked (by qPCR and histology) undifferentiated yellow-fluorescent protein transgenic mouse ESCs and Flk1 + /PDGFRα+ cardiac progenitor (CPs) cells, to investigate the effect of the cardiac environment on cell differentiation, as well as to test whether our in vitro model system could recapitulate the formation of teratoma-like structures commonly observed upon in vivo ESC injection. By 8 days post-injection, ESCs were spatially segregated from the cardiac cell population; however, ESC injection increased survival of CMs. The presence of ESCs blocked electrical conduction through the tissue, resulting in a 46% increase in the excitation threshold. Expression of mouse cardiac troponin I, was markedly increased in CP injected constructs compared to ESC injected constructs at all time points and cell doses tested. As early as 2 weeks, epithelial and ganglion-like structures were observed in ESC injected constructs. By 4 weeks of ESC injection, teratoma-like structures containing neural, epithelial, and connective tissue were observed in the constructs. Non-cardiac structures were observed in the CP injected constructs only after extended culture (4 weeks) and only at high cell doses, suggesting that these cells require further enrichment or differentiation prior to transplantation. Our data indicate that the cardiac environment of host tissue and electrical field stimulation did not preferentially guide the differentiation of ESCs towards the cardiac lineage. In the same environment, injection of CP resulted in a more robust cardiac differentiation than injection of ESC. Our data demonstrate that the model-system developed herein can be used to study the functional effects of candidate stem cells on the host myocardium, as well as to measure the residual activity of undifferentiated cells present in the mixture.

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