A Modular Communicative Leadless Pacing-Defibrillator System.

BACKGROUND: The subcutaneous implantable cardioverter-defibrillator (ICD) is associated with fewer lead-related complications than a transvenous ICD; however, the subcutaneous ICD cannot provide bradycardia and antitachycardia pacing. Whether a modular pacing-defibrillator system comprising a leadless pacemaker in wireless communication with a subcutaneous ICD to provide antitachycardia and bradycardia pacing is safe remains unknown. METHODS: We conducted a multinational, single-group study that enrolled patients at risk for sudden death from ventricular arrhythmias and followed them for 6 months after implantation of a modular pacemaker-defibrillator system. The safety end point was freedom from leadless pacemaker-related major complications, evaluated against a performance goal of 86%. The two primary performance end points were successful communication between the pacemaker and the ICD (performance goal, 88%) and a pacing threshold of up to 2.0 V at a 0.4-msec pulse width (performance goal, 80%). RESULTS: We enrolled 293 patients, 162 of whom were in the 6-month end-point cohort and 151 of whom completed the 6-month follow-up period. The mean age of the patients was 60 years, 16.7% were women, and the mean (±SD) left ventricular ejection fraction was 33.1±12.6%. The percentage of patients who were free from leadless pacemaker-related major complications was 97.5%, which exceeded the prespecified performance goal. Wireless-device communication was successful in 98.8% of communication tests, which exceeded the prespecified goal. Of 151 patients, 147 (97.4%) had pacing thresholds of 2.0 V or less, which exceeded the prespecified goal. The percentage of episodes of arrhythmia that were successfully terminated by antitachycardia pacing was 61.3%, and there were no episodes for which antitachycardia pacing was not delivered owing to communication failure. Of 162 patients, 8 died (4.9%); none of the deaths were deemed to be related to arrhythmias or the implantation procedure. CONCLUSIONS: The leadless pacemaker in wireless communication with a subcutaneous ICD exceeded performance goals for freedom from major complications related to the leadless pacemaker, for communication between the leadless pacemaker and subcutaneous ICD, and for the percentage of patients with a pacing threshold up to 2.0 V at a 0.4-msec pulse width at 6 months. (Funded by Boston Scientific; MODULAR ATP ClinicalTrials.gov NCT04798768.).

Promoting Nerve Regeneration: Electrical Stimulation, Gene Therapy, and Beyond.

Peripheral nerve injuries often result in life-altering functional deficits even with optimal management. Unlike the central nervous system, peripheral nerves have the ability to regenerate lost axons after injury; however, axonal regeneration does not equate to full restoration of function. To overcome this physiological shortcoming, advances in nerve regeneration and repair are paramount, including electrical stimulation, gene therapy, and surgical technique advancements.

Nerve transfers to restore femoral nerve function following oncologic nerve resection.

INTRODUCTION: Advances in the care of soft-tissue tumors, including imaging capabilities and adjuvant radiation therapy, have broadened the indications and opportunities to pursue surgical limb salvage. However, peripheral nerve involvement and femoral nerve resection can still result in devastating functional outcomes. Nerve transfers offer a versatile solution to restore nerve function following tumor resection. METHODS: Two cases were identified by retrospective review. Patient and disease characteristics were gathered. Preoperative and postoperative motor function were assessed using the Medical Research Council Muscle Scale. Patient-reported pain levels were assessed using the numeric rating scale. RESULTS: Nerve transfers from the obturator and sciatic nerve were employed to restore knee extension. Follow up for Case 1 was 24 months, 8 months for Case 2. In both patients, knee extension and stabilization of gait without bracing was restored. Patient also demonstrated 0/10 pain (an average improvement of 5 points) with decreased neuromodulator and pain medication use. CONCLUSION: Nerve transfers can restore function and provide pain control benefits and ideally are performed at the time of tumor extirpation. This collaboration between oncologic and nerve surgeons will ultimately result in improved functional recovery and patient outcomes.

Targeted Muscle Reinnervation at the Time of Upper-Extremity Amputation for the Treatment of Pain Severity and Symptoms.

PURPOSE: Targeted muscle reinnervation (TMR) is a technique for the management of peripheral nerves in amputation. Phantom limb pain (PLP) and residual limb pain (RLP) trouble many patients after amputation, and TMR has been shown to reduce this pain when performed after the initial amputation. We hypothesize that TMR at the time of amputation may improve pain for patients after major upper-extremity amputation. METHODS: We conducted a retrospective review of patients who underwent major upper-extremity amputation with TMR performed at the time of the index amputation (early TMR). Phantom limb pain and RLP intensity and associated symptoms were assessed using the numeric rating scale (NRS), the Patient-Reported Outcome Measurement Information System (PROMIS) Pain Intensity Short-Form 3a, the Pain Behavior Short-Form 7a, and the Pain Interference Short-Form 8a. The TMR cohort was compared with benchmarked data from a sample of upper-extremity amputees. RESULTS: Sixteen patients underwent early TMR and were compared with 55 benchmark patients. More than half of early TMR patients were without PLP (62%) compared with 24% of controls. Furthermore, half of all patients were free of RLP compared with 36% of controls. The median PROMIS PLP intensity score for the general sample was 47 versus 38 in the early TMR sample. Patients who underwent early TMR reported reduced pain behaviors and interference specific to PLP (50 vs 53 and 41 vs 50, respectively). The PROMIS RLP intensity score was lower in patients with early TMR (36 vs 47). CONCLUSIONS: This study demonstrates that early TMR is a promising strategy for treating pain and improving the quality of life in the upper-extremity amputee. Early TMR may preclude the need for additional surgery and represents an important technique for peripheral nerve surgery. TYPE OF STUDY/LEVEL OF EVIDENCE: Therapeutic IV.

Instillation negative pressure wound therapy: An effective approach for hardware salvage.

Wound infection involving hardware can be notoriously difficult to treat, often requiring the removal of the infected implant. The goal of this study was to determine the utility of instillation negative pressure wound therapy to help eradicate infection and allow for definitive wound closure in patients without removing the infected hardware. A retrospective review was performed on the outcomes of 28 patients who presented with open wounds with exposed or infected hardware and who were treated with a combination of surgical debridement and negative pressure wound therapy with instillation (NPWTi). Eleven patients were treated for infected spinal hardware, 12 for extremity, and 5 for sternal hardware. Twenty-five of 28 (89%) patients had successful retention or replacement of hardware, with clearance of infection and healed wounds. Original hardware was maintained in 17 of 28 (61%) patients. In 11 patients, original hardware was removed, with subsequent replacement in eight of those patients after a clean wound was achieved. Average time to definitive closure was 12.6 days. Average follow-up was 135 days. This series supports NPWTi as an effective adjunct therapy to help expeditiously eradicate hardware infection, allowing for hardware retention.

Targeted muscle reinnervation in oncologic amputees: Early experience of a novel institutional protocol.

BACKGROUND: We describe a multidisciplinary approach for comprehensive care of amputees with concurrent targeted muscle reinnervation (TMR) at the time of amputation. METHODS: Our TMR cohort was compared to a cross-sectional sample of unselected oncologic amputees not treated at our institution (N = 58). Patient-Reported Outcomes Measurement Information System (NRS, PROMIS) were used to assess postamputation pain. RESULTS: Thirty-one patients underwent amputation with concurrent TMR during the study; 27 patients completed pain surveys; 15 had greater than 1 year follow-up (mean follow-up 14.7 months). Neuroma symptoms occurred significantly less frequently and with less intensity among the TMR cohort. Mean differences for PROMIS pain intensity, behavior, and interference for phantom limb pain (PLP) were 5.855 (95%CI 1.159-10.55; P = .015), 5.896 (95%CI 0.492-11.30; P = .033), and 7.435 (95%CI 1.797-13.07; P = .011) respectively, with lower scores for TMR cohort. For residual limb pain, PROMIS pain intensity, behavior, and interference mean differences were 5.477 (95%CI 0.528-10.42; P = .031), 6.195 (95%CI 0.705-11.69; P = .028), and 6.816 (95%CI 1.438-12.2; P = .014), respectively. Fifty-six percent took opioids before amputation compared to 22% at 1 year postoperatively. CONCLUSIONS: Multidisciplinary care of amputees including concurrent amputation and TMR, multimodal postoperative pain management, amputee-centered rehabilitation, and peer support demonstrates reduced incidence and severity of neuroma and PLP.

Comparing the hydrosurgery system to conventional debridement techniques for the treatment of delayed healing wounds: a prospective, randomised clinical trial to investigate clinical efficacy and cost-effectiveness.

In these uncertain times of high health care costs, clinicians are looking for cost-effective devices to employ in their everyday practices. In an effort to promote cost-effective and proper wound repair, the hydrosurgical device allows accurate debridement of only unwanted tissue while precisely conserving viable structures for eventual repair. This prospective, randomised study compared procedures using the hydrosurgery system (VERSAJET™) with conventional debridement in order to assess clinical efficacy and cost-effectiveness when treating subjects with chronic wounds. A total of 40 subjects were recruited. There was no difference in time to achieve stable wound closure between the treatment groups (P = 0·77). There were no significant differences between the two groups in terms of cost of the first operative procedure (P = 0·28), cost of surgical procedures during the study (P = 0·51), cost of study treatment (P = 0·29) or cost to achieve stable wound closure (P = 0·85). There were no differences in quantitative bacterial counts after debridement with either methods (P = 0·376). However, the time taken for the first excision procedure was significantly faster using the hydrosurgery system (VERSAJET) when compared with conventional debridement (P < 0·001). The total excision time for all procedures was significantly less for the Hydrosurgery group than for the conventional group (P = 0·005). Also, the Hydrosurgery group demonstrated significantly less intraoperative blood loss than conventional group for all procedures (P = 0·003). In this study, although there were no differences in time to stable wound closure or bacterial reduction between the two groups, the hydrosurgery system (VERSAJET) did offer advantages in terms of operative times and intraoperative blood loss and was cost-neutral, despite the handpiece cost.

Targeted Muscle Reinnervation at the Time of Amputation Decreases Recurrent Symptomatic Neuroma Formation.

BACKGROUND: Targeted muscle reinnervation (TMR) is an effective technique for the prevention and management of phantom limb pain (PLP) and residual limb pain (RLP) among amputees. The purpose of this study was to evaluate symptomatic neuroma recurrence and neuropathic pain outcomes between cohorts undergoing TMR at the time of amputation (ie, acute) versus TMR following symptomatic neuroma formation (ie, delayed). METHODS: A cross-sectional, retrospective chart review was conducted using patients undergoing TMR between 2015 and 2020. Symptomatic neuroma recurrence and surgical complications were collected. A subanalysis was conducted for patients who completed Patient-Reported Outcome Measurement Information System (PROMIS) pain intensity, interference, and behavior scales and an 11-point numeric rating scale (NRS) form. RESULTS: A total of 105 limbs from 103 patients were identified, with 73 acute TMR limbs and 32 delayed TMR limbs. Nineteen percent of the delayed TMR group had symptomatic neuromas recur in the distribution of original TMR compared with 1% of the acute TMR group ( P < 0.05). Pain surveys were completed at final follow-up by 85% of patients in the acute TMR group and 69% of patients in the delayed TMR group. Of this subanalysis, acute TMR patients reported significantly lower PLP PROMIS pain interference ( P < 0.05), RLP PROMIS pain intensity ( P < 0.05), and RLP PROMIS pain interference ( P < 0.05) scores in comparison to the delayed group. CONCLUSIONS: Patients who underwent acute TMR reported improved pain scores and a decreased rate of neuroma formation compared with TMR performed in a delayed fashion. These results highlight the promising role of TMR in the prevention of neuropathic pain and neuroma formation at the time of amputation. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.

Multiple Concurrent Decompressions for the Treatment of Upper Extremity Pain.

Purpose: Neuropathic pain can be life altering and difficult to treat. Nerves can be compressed along their path in the upper extremities, resulting in chronic neuropathic pain. This study was performed to evaluate the effectiveness and safety of multiple concomitant distal nerve decompressions for the treatment of upper extremity nerve pain. Methods: A retrospective review of patients from a single surgeon's academic practice was performed to identify those undergoing nerve decompressions for an indication of "pain" as the referring diagnosis between April 2020 and June 2021. The primary outcomes included patient-reported severity of pain using the Visual Analog Scale and quality-of-life measures, including level of frustration, depression, and impact on quality of life attributable to pain on a similar 0-10 Likert scale. Complications, if any, were also determined. Results: Eleven patients were identified to have undergone multiple concurrent nerve decompressions for the indication of upper extremity pain. All sites chosen for decompression were found to be provocative, ie, elicited increased pain on examination with compression. The median number of decompressions performed was 5 (interquartile range, 4-6), ranging from 3 to 7. The mean follow-up time was 5 months (SD, 3.43 months). The average pain over the last month and the average pain over the past week had significant improvement at the final follow-up, and there was a statistically significant decrease in the patient-reported mean impact of pain on quality of life following decompressions (preoperative, 5.8; postoperative, 3.6; P = .017; 95% confidence interval, 0.2-4.3). No complications were identified. Conclusions: Performing multiple concomitant nerve decompressions of the upper extremities is safe and effective in the treatment of chronic neuropathic pain following upper extremity trauma. Type of study/level of evidence: Therapeutic IV.

A National Survey of Perspectives of Physician Assistants in Academic Plastic and Reconstructive Surgery.

Physician assistants (PAs) are an essential part of the healthcare team who improve access and efficiencies in patient care. A better understanding of the impact and current utilization of PAs in plastic and reconstructive surgery is needed. The purpose of this national survey was to evaluate the role and scope of practice of PAs in academic plastic surgery, as well as characterize current trends of PA utilization, compensation, and perceived value from a PA perspective. Methods: A voluntary, anonymous 50-question survey was distributed via SurveyMonkey to practicing PAs at 98 academic plastic surgery programs. The survey included questions about employment characteristics, involvement in clinical research and academic work, structural organization, academic benefits, compensation, and position held. Results: Ninety-one PAs from 35 plastic surgery programs completed the survey and were included (overall program response rate = 36.8%, participants response rate = 30.4%). Practice environments included outpatient clinics, the operating room, and inpatient care. Most commonly, respondents supported multiple surgeons as opposed to one surgeon's practice. For 57% of respondents, compensation is based on a tiered system that accounts for specialty and experience. The reported mode base salary range corroborates national averages and most reported annual bonuses based on merit. The majority of respondents felt valued in their role. Conclusions: Through this national survey, we provide granularity as to how PAs are utilized and compensated in academic plastic surgery. We offer insight into the overall perceived value from a PA perspective that helps define the role and will ultimately help strengthen collaboration.

Design and rationale of the MODULAR ATP global clinical trial: A novel intercommunicative leadless pacing system and the subcutaneous implantable cardioverter-defibrillator.

Background: The subcutaneous implantable cardioverter-defibrillator (S-ICD) has demonstrated safety and efficacy for the treatment of malignant ventricular arrhythmias. However, a limitation of the S-ICD lies in the inability to either pace-terminate ventricular tachycardia or provide prolonged bradycardia pacing support. Objective: The rationale and design of a prospective, single-arm, multinational trial of an intercommunicative leadless pacing system integrated with the S-ICD will be presented. Methods: A technical description of the modular cardiac rhythm management (mCRM) system (EMPOWER leadless pacemaker and EMBLEM S-ICD) and the implantation procedure is provided. MODULAR ATP (Effectiveness of the EMPOWER™ Modular Pacing System and EMBLEM™ Subcutaneous ICD to Communicate Antitachycardia Pacing) is a multicenter, international trial enrolling up to 300 patients at risk of sudden cardiac death at up to 60 centers trial design. The safety endpoint of freedom from major complications related to the mCRM system or implantation procedure at 6 months and 2 years are significantly higher than 86% and 81%, respectively, and all-cause survival is significantly >85% at 2 years. Results: Efficacy endpoints are that at 6 months mCRM communication success is significantly higher than 88% and the percentage of subjects with low and stable thresholds is significantly higher than 80%. Substudies to evaluate rate-responsive features and performance of the pacing module are also described. Conclusion: The MODULAR ATP global clinical trial will prospectively test the safety and efficacy of the first intercommunicating leadless pacing system with the S-ICD. This trial will allow for robust validation of device-device communication, pacing performance, rate responsiveness, and system safety.

Mutation of p107 exacerbates the consequences of Rb loss in embryonic tissues and causes cardiac and blood vessel defects.

The retinoblastoma tumor-suppressor protein, pRb, is a member of the pocket protein family that includes p107 and p130. These proteins have well-defined roles in regulating entry into and exit from the cell cycle and also have cell cycle-independent roles in facilitating differentiation. Here we investigate the overlap between pocket protein's function during embryonic development by using conditional mutant alleles to generate Rb;p107 double-mutant embryos (DKOs) that develop in the absence of placental defects. These DKOs die between e13.5 and e14.5, much earlier than either the conditional Rb or the germline p107 single mutants, which survive to birth or are largely viable, respectively. Analyses of the e13.5 DKOs shows that p107 mutation exacerbates the phenotypes resulting from pRb loss in the central nervous system and lens, but not in the peripheral nervous system. In addition, these embryos exhibit novel phenotypes, including increased proliferation of blood vessel endothelial cells, and heart defects, including double-outlet right ventricle (DORV). The DORV is caused, at least in part, by a defect in blood vessel endothelial cells and/or heart mesenchymal cells. These findings demonstrate novel, overlapping functions for pRb and p107 in numerous murine tissues.

Longitudinal Durability of Patient-Reported Pain Outcomes after Targeted Muscle Reinnervation at the Time of Major Limb Amputation.

BACKGROUND: Phantom limb pain (PLP) and residual limb pain (RLP) are debilitating sequelae of major limb amputation. Targeted muscle reinnervation (TMR), when performed at the time of amputation, has been shown to be effective for management of this pain; however, its long-term effects and the longitudinal trend of patient-reported outcomes is unknown. The purpose of this study was to characterize the longitudinal patient-reported outcomes of pain and quality of life following TMR at the time of initial amputation. STUDY DESIGN: A prospective case series of patients undergoing major limb amputation with TMR performed at the time of amputation were followed from October 2015 to December 2020 with outcomes measured 3, 6, 12, and 18 months or longer after amputation and TMR. Outcomes included patient-reported severity of PLP and RLP as measured by the numeric rating scale (NRS). Secondary outcomes included the Patient-Reported Outcomes Measurement Information System (PROMIS) Pain Interference and Pain Behavior Questionnaires. RESULTS: Eighty-one patients with 83 treated limbs were included in the study, and 23 patients completed surveys at 18 months or later, with an average follow-up time of 2.4 years. By 3 months after operation, all patient-reported outcomes for PLP and RLP were consistent with previously reported data that demonstrated superiority to non-TMR amputees. Mixed-model linear regression analysis showed that PLP NRS severity scores continued to improve over the study period (p = 0.022). The remaining outcomes for RLP severity and PROMIS quality-of-life measures demonstrated that these scores remained stable over the study period (p > 0.05). CONCLUSION: TMR is an effective surgical procedure that improves the chances of having reduced RLP and PLP when performed at the time of amputation, and our study demonstrates the long-term durability of its efficacy.

Evaluating hip disarticulation outcomes in a 51-patient series.

Background: Hip disarticulations are proximal lower extremity amputations with high postoperative complication and mortality rates. The purpose of the study was to evaluate hip disarticulation outcomes at our institution. Targeted Muscle Reinnervation (TMR) is an effective surgical technique shown to reduce pain in amputees. A secondary goal of the study was to evaluate the impact of implementing TMR on this patient population. Methods: A retrospective review was performed for patients who underwent hip disarticulation with and without TMR between 2009 and 2020. Information on one-year mortality, thirty-day complication rates, operation times, surgical charges, and pain scores was collected. Results: Fifty-one patients underwent hip disarticulation, eight of which had TMR performed at the time of their hip disarticulation. The one-year mortality rate was 37% with 30-day infection, readmission, reoperation, and rates of 37%, 39%, and 27% respectively. The thirty-day major complication rate was 47% overall but not statistically significantly different between groups. There were no differences between groups with regard to 30-day readmission, reoperation, and infection rates. Conclusions: Our results represent one of the largest series of hip disarticulation outcomes. Performing TMR at the time of hip disarticulation did not negatively affect outcomes and may be a beneficial adjunct to improve pain. Further research is warranted.

Increasing the vegetable intake dose is associated with a rise in plasma carotenoids without modifying oxidative stress or inflammation in overweight or obese postmenopausal women.

The optimal amount of vegetable consumption required to reduce chronic disease risk is widely debated. Intervention trials evaluating biological activity of vegetables at various doses are limited. We conducted a 3-dose, crossover feeding trial to test the hypothesis that vegetable intake is associated in a dose-dependent manner with increased plasma carotenoids and subsequently reduced oxidative stress and inflammation in 49 overweight, postmenopausal women. Participants were assigned in random order to 2 (130 g), 5 (287 g), and 10 (614 g) daily servings of fresh, greenhouse-grown vegetables for 3-wk intervals with a 4-wk washout period between treatments. Plasma total carotenoids significantly increased from 1.63 to 2.07 µmol/L with a dose of 2 vegetable servings, from 1.49 to 2.84 µmol/L with a dose of 5 vegetable servings, and from 1.40 to 4.42 µmol/L with a dose of 10 vegetable servings (pre-post paired ttests, all P < 0.001). The change during each feeding period increased with each dose level (P < 0.001). Urine concentrations of 8-isoprostane F2α, hexanoyl lysine, and serum high sensitivity C-reactive protein were not affected by any administered vegetable dose. In this variable-dose vegetable study, a dose-response for plasma carotenoids was demonstrated without significant change in oxidative stress and inflammation in overweight, postmenopausal women.

Metastatic osteosarcoma induced by inactivation of Rb and p53 in the osteoblast lineage.

Mutation of the RB-1 and p53 tumor suppressors is associated with the development of human osteosarcoma. With the goal of generating a mouse model of this disease, we used conditional and transgenic mouse strains to inactivate Rb and/or p53 specifically in osteoblast precursors. The resulting Rb;p53 double mutant (DKO) animals are viable but develop early onset osteosarcomas with complete penetrance. These tumors display many of the characteristics of human osteosarcomas, including being highly metastatic. We established cell lines from the DKO osteosarcomas to further investigate their properties. These immortalized cell lines are highly proliferative and they retain their tumorigenic potential, as judged by their ability to form metastatic tumors in immunocompromised mice. Moreover, they can be induced to differentiate and, depending on the inductive signal, will adopt either the osteogenic or adipogenic fate. Consistent with this multipotency, a significant portion of these tumor cells express Sca-1, a marker that is typically associated with stem cells/uncommitted progenitors. By assaying sorted cells in transplant assays, we demonstrate that the tumorigenicity of the osteosarcoma cell lines correlates with the presence of the Sca-1 marker. Finally, we show that loss of Rb and p53 in Sca-1-positive mesenchymal stem/progenitor cells is sufficient to yield transformed cells that can initiate osteosarcoma formation in vivo.

Surgical Innovations to Restore Function in Pediatric Peripheral Nerve Conditions.

Peripheral nerve injuries in children can result in devastating lifelong deficits. Because of the time-sensitive nature of muscle viability and the limited speed of nerve regeneration, early recognition and treatment of nerve injuries are essential to restore function. Innovative surgical techniques have been developed to combat the regenerative length and speed; these include nerve transfers. Nerve transfers involve transferring a healthy, expendable donor nerve to an injured nerve to restore movement and sensation. Nerve transfers are frequently used to treat children affected by conditions, including UE trauma, brachial plexus birth injury, and acute flaccid myelitis. Pediatricians play an important role in the outcomes of children with these conditions through early diagnosis and timely referrals. With this review, we aim to provide awareness of state-of-the-art surgical treatment options that significantly improve the function of children with traumatic nerve injuries, brachial plexus birth injury, and acute flaccid myelitis.

Lower Extremity Nerve Transfers in Acute Flaccid Myelitis Patients: A Case Series.

Acute flaccid myelitis (AFM) is characterized by flaccid paralysis following prodromal symptoms. Complete recovery is rare, and patients typically have residual extremity weakness. This study aimed to describe the technique and outcomes of lower extremity nerve transfers for children with AFM. METHODS: A retrospective review of eight children who developed AFM in 2016 and had lower extremity nerve transfers was performed. Principles of nerve transfer were applied to develop novel nerve transfer procedures to restore function for this patient population. Pre- and postoperative muscle strength grades were reviewed, and qualitative improvements in function were recorded. RESULTS: A variety of nerve transfers were utilized in eight patients with average time to surgery from AFM diagnosis of 15.7 months. Restoration of gluteal, femoral, hamstring, and gastrocnemius function was attempted. Variable MRC grade improvement was achieved (range MRC grade 0-4). All patients reported subjective improvements in function. Four of five patients with follow-up who underwent nerve transfers for restoration of gluteal function transitioned from wheelchair use to walking with assistive devices as their primary modes of ambulation. No donor site complications occurred. CONCLUSIONS: The unique needs of this patient population and variable patterns of residual weakness require meticulous assessment and development of individualized surgical plans. With appropriate goals and expectations in mind, functional improvement may be achieved, including return to ambulation.

Targeted Muscle Reinnervation in Partial Hand Amputations.

Targeted muscle reinnervation (TMR) surgery has been shown to aid in prevention and treatment of neuropathic pain. Technical and anatomical descriptions of TMR surgery for upper extremity amputees (including transradial, transhumeral, and forequarter amputations) have been reported, yet such descriptions of TMR surgery for partial hand amputations are currently lacking. Herein we outline the technique of different types of partial hand amputation TMR surgeries to serve as a reference and guide. A retrospective review was performed by our multi-institutional team to identify clinical cases where partial hand TMR surgeries were performed. Patient demographics, characteristics, amputation subtype, nerve transfer, pain score, pain outcome, and functional outcome data were collected and analyzed. From January 2018 to September 2019, 13 patients underwent partial hand TMR procedures. Eight cases resulted from trauma, and 6 were secondary to oncologic procedures. The amputations consisted of 8 ray, 2 trans-metacarpal, 2 radial-sided hand, and 1 index finger amputation with recurrent painful neuromas. Twelve patients were weaned off narcotics completely and only 3 remained on a neuromodulator for ongoing pain control. Technical considerations for partial hand TMR surgery have been outlined, with early pilot data showing beneficial pain control outcomes.

E2F4 cooperates with pRB in the development of extra-embryonic tissues.

The retinoblastoma gene, RB-1, was the first identified tumor suppressor. Rb(-/-) mice die in mid-gestation with defects in proliferation, differentiation and apoptosis. The activating E2F transcription factors, E2F1-3, contribute to these embryonic defects, indicating that they are key downstream targets of the retinoblastoma protein, pRB. E2F4 is the major pRB-associated E2F in vivo, yet its role in Rb(-/-) embryos is unknown. Here we establish that E2f4 deficiency reduced the lifespan of Rb(-/-) embryos by exacerbating the Rb mutant placental defect. We further show that this reflects the accumulation of trophectoderm-like cells in both Rb and Rb;E2f4 mutant placentas. Thus, Rb and E2f4 play cooperative roles in placental development. We used a conditional mouse model to allow Rb(-/-);E2f4(-/-) embryos to develop in the presence of Rb wild-type placentas. Under these conditions, Rb(-/-);E2f4(-/-) mutants survived to birth. These Rb(-/-);E2f4(-/-) embryos exhibited all of the defects characteristic of the Rb and E2f4 single mutants and had no novel defects. Taken together, our data show that pRB and E2F4 cooperate in placental development, but play largely non-overlapping roles in the development of many embryonic tissues.