Mechanistic regulation of planarian shape during growth and degrowth.

Adult planarians can grow when fed and degrow (shrink) when starved while maintaining their whole-body shape. It is unknown how the morphogens patterning the planarian axes are coordinated during feeding and starvation or how they modulate the necessary differential tissue growth or degrowth. Here, we investigate the dynamics of planarian shape together with a theoretical study of the mechanisms regulating whole-body proportions and shape. We found that the planarian body proportions scale isometrically following similar linear rates during growth and degrowth, but that fed worms are significantly wider than starved worms. By combining a descriptive model of planarian shape and size with a mechanistic model of anterior-posterior and medio-lateral signaling calibrated with a novel parameter optimization methodology, we theoretically demonstrate that the feedback loop between these positional information signals and the shape they control can regulate the planarian whole-body shape during growth. Furthermore, the computational model produced the correct shape and size dynamics during degrowth as a result of a predicted increase in apoptosis rate and pole signal during starvation. These results offer mechanistic insights into the dynamic regulation of whole-body morphologies.

Regenerative Peripheral Nerve Interface: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain.

Surgical procedures, including nerve reconstruction and end-organ muscle reinnervation, have become more prominent in the prosthetic field over the past decade. Primarily developed to increase the functionality of prosthetic limbs, these surgical procedures have also been found to reduce postamputation neuropathic pain. Today, some of these procedures are performed more frequently for the management and prevention of postamputation pain than for prosthetic fitting, indicating a significant need for effective solutions to postamputation pain. One notable emerging procedure in this context is the Regenerative Peripheral Nerve Interface (RPNI). RPNI surgery involves an operative approach that entails splitting the nerve end longitudinally into its main fascicles and implanting these fascicles within free denervated and devascularized muscle grafts. The RPNI procedure takes a proactive stance in addressing freshly cut nerve endings, facilitating painful neuroma prevention and treatment by enabling the nerve to regenerate and innervate an end organ, i.e., the free muscle graft. Retrospective studies have shown RPNI's effectiveness in alleviating postamputation pain and preventing the formation of painful neuromas. The increasing frequency of utilization of this approach has also given rise to variations in the technique. This article aims to provide a step-by-step description of the RPNI procedure, which will serve as the standardized procedure employed in an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394). In this trial, RPNI is compared to two other surgical procedures for postamputation pain management, specifically, Targeted Muscle Reinnervation (TMR) and neuroma excision coupled with intra-muscular transposition and burying.

Management of Superficial and Deep Peroneal Nerve Neuromas with Targeted Muscle Reinnervation in Nonamputees: Operative Technique and Early Outcomes.

Background: Targeted muscle reinnervation (TMR), a surgical technique developed by the senior authors that coapts proximal ends of nerves to distal motor nerves of adjacent muscles, has demonstrated efficacy in the treatment and prevention of neuroma pain. The objective of this study is to describe the surgical technique for TMR of the superficial peroneal nerve (SPN) and deep peroneal nerve (DPN) in nonamputee patients and provide data on postoperative functional outcomes. Methods: A single-institution retrospective chart review was performed between March 2018 and April 2021. Patients were de-identified and included if they were nonamputees receiving TMR for pain in the peroneal nerve distribution. Data extracted included demographic information, symptoms before operation, relevant nerve coaptation, peri-, and postoperative complications, and long-term functional outcomes. Results: Of the 19 patients reviewed, 11 patients underwent TMR of the SPN alone: eight had complete resolution of their symptoms; two indicated partial improvement in pain; and one patient had no improvement. Four patients underwent TMR of the DPN alone: two patients had complete resolution of their pain, and two patients had partial improvement with pain. Four patients underwent TMR of both the SPN/DPN: two patients had complete resolution of their symptoms, and two patients were noted to have significant improvement but had persistent pain from prior foot operations. Average follow-up time was 260 days. Conclusions: TMR is a successful technique in the management of SPN and DPN neuroma pain. Our technique revealed excellent clinical outcomes, no procedure-specific complications, and improved subjective pain reports.

Thin and Thinned Anterolateral Thigh Flaps for Upper Extremity Reconstruction.

Upper extremity reconstruction remains challenging due to the high functional and esthetic demands of this location. The anterolateral thigh (ALT) flap is a workhorse flap for microsurgical reconstruction of the upper extremity and can be elevated in various planes depending on desired thickness of the flap. Microsurgical reconstruction of the upper extremity often benefits from a thin flap that can resurface the extremity, which can provide improved functional and esthetic outcomes. This article reviews the anatomy, preoperative planning, and operative technique, as well as presents 4 cases to illustrate the outcomes and benefits of thin and thinned ALT flaps.

Targeted Muscle Reinnervation: Surgical Protocol for a Randomized Controlled Trial in Postamputation Pain.

Over the past decade, the field of prosthetics has witnessed significant progress, particularly in the development of surgical techniques to enhance the functionality of prosthetic limbs. Notably, novel surgical interventions have had an additional positive outcome, as individuals with amputations have reported neuropathic pain relief after undergoing such procedures. Subsequently, surgical techniques have gained increased prominence in the treatment of postamputation pain, including one such surgical advancement - targeted muscle reinnervation (TMR). TMR involves a surgical approach that reroutes severed nerves as a type of nerve transfer to "target" motor nerves and their accompanying motor end plates within nearby muscles. This technique originally aimed to create new myoelectric sites for amplified electromyography (EMG) signals to enhance prosthetic intuitive control. Subsequent work showed that TMR also could prevent the formation of painful neuromas as well as reduce postamputation neuropathic pain (e.g., Residual and Phantom Limb Pain). Indeed, multiple studies have demonstrated TMR's effectiveness in mitigating postamputation pain as well as improving prosthetic functional outcomes. However, technical variations in the procedure have been identified as it is adopted by clinics worldwide. The purpose of this article is to provide a detailed step-by-step description of the TMR procedure, serving as the foundation for an international, randomized controlled trial (ClinicalTrials.gov, NCT05009394), including nine clinics in seven countries. In this trial, TMR and two other surgical techniques for managing postamputation pain will be evaluated.

Preference Signaling and the Integrated Plastic Surgery Match: A National Survey Study.

OBJECTIVE: Rooted in economics market strategies, preference signaling was introduced to the Plastic Surgery Common Application (PSCA) in 2022 for integrated plastic surgery residency applicants. This study surveyed program and applicant experience with preference signaling and assessed how preference signals influenced likelihood of interview invitations. DESIGN: Two online surveys were designed and distributed to all program directors and 2022-2023 applicants to integrated plastic surgery. Opinions regarding the utility of preference signaling were solicited, and the influence of preference signals on likelihood of interview offers was assessed. SETTING: All integrated plastic surgery programs. PARTICIPANTS: All 88 program directors and 2022-2023 applicants to integrated plastic surgery. RESULTS: A total of 45 programs and 99 applicants completed the survey (response rates, 54.2% and 34.2%, respectively). Overall, 79.6% of applicants and 68.9% of programs reported that preference signals were a useful addition to the application cycle. Programs reported that 41.4% of students who sent preference signals received interview offers, compared to 84.6% of home students, 64.8% of away rotators, and 7.1% of other applicants; overall, students who signaled were 5.8 times more likely to receive an interview offer compared to students who were not home students and did not rotate or signal. After multivariable adjustment, programs with higher Doximity rankings, numbers of away rotators, and numbers of integrated residents per year received more preference signals (all p < 0.05). CONCLUSIONS: Applicants and programs report that preference signaling was a useful addition to the integrated plastic surgery application cycle. Sending preference signals resulted in a higher likelihood of interview offers among nonrotators. Preference signaling may be a useful tool to reduce congestion in the integrated plastic surgery application cycle.

A Retrospective Study Analyzing Opioid Prescription Practices in Hand Surgery from 2013 to 2019.

Background: The potential for opioid prescription medication addiction and abuse has been a growing concern in healthcare. It is not uncommon for hand surgery patients to be overprescribed opioid medication for postoperative pain management. The objective of this study was to characterize changes in opioid prescription practices of hand surgeons treating Medicare Part D patients from 2013 to 2019. Methods: A retrospective analysis of Medicare Part D prescriber data from 2013 to 2019 was conducted. This database provides information on drugs paid for under the Medicare Part D Prescription Drug Program. For each prescriber and medication, the dataset includes the total number of prescriptions dispensed (original prescriptions and number of refills), and total medication cost. Results: In 2013, the 10 most common medications prescribed totaled 114,409 prescriptions, with 89,701 (78.4%) opioid prescriptions. In 2019, the 10 most common medications prescribed totaled 164,955 prescriptions, with 109,665 (66.5%) opioid prescriptions. Although total opioid prescriptions dropped, there was a 22% increase in the total number of prescriptions written. The two most common medications prescribed, hydrocodone-acetaminophen and oxycodone-acetaminophen, totaled 75,796 in 2013, compared with 76,518 in 2019. The overall number of prescriptions for nonsteroidal anti-inflammatory drugs increased by 157%, and the percentage of total opioids prescribed declined by 7.9%. Conclusions: The increase in total opioid prescriptions from 2013 to 2019 by hand surgeons in the Medicare Part D Prescription Drug Program lags behind the recommended shift to nonopioid pain management. The reasons for the overall rise in prescriptions deserve further exploration.

Immediate Plastic Surgery Intervention after Soft Tissue Sarcoma Resection: Examining Wound Healing, Readmission, and Reoperation.

Many orthopedic and surgical oncologists use a multidisciplinary approach to soft tissue sarcoma (STS) resection. This study assesses the role of immediate plastic surgeon involvement during index soft tissue sarcoma resection. Methods: Adult patients who underwent index STS resection between 2005 and 2018 were queried from an institutional database. Main outcomes analyzed were 90-day same-site reoperation, any-cause readmission, and wound healing complications. Univariate and multivariate logistic regression were used to identify risk factors. Additional evaluation was then performed for the following two cohorts: patients with and without plastic surgeon involvement. Results: In total, 228 cases were analyzed. Multivariate regression demonstrated the following predictors for 90-day wound-healing complications: plastic surgery intervention [OR = 0.321 (0.141-0.728), P = 0.007], operative time [OR = 1.003 (1.000-1.006), P = 0.039], and hospital length of stay [OR = 1.195 (1.004-1.367), P = 0.010]. For 90-day readmission, operative time [OR = 1.004 (1.001-1.007), P = 0.023] and tumor stage [OR = 1.966 (1.140-3.389), P = 0.015] emerged as multivariate predictors. Patients whose resection included a plastic surgeon experienced similar primary outcomes despite these patients having expectedly longer operative times (220 ± 182 versus 108 ± 67 minutes, P < 0.001) and hospital length of stay (3.99 ± 3.69 versus 1.36 ± 1.97 days, P < 0.001). Conclusions: Plastic surgeon involvement emerged as a significant protector against 90-day wound healing complications. Cases that included plastic surgeons achieved similar complication rates in all categories relative to cases without plastic surgery intervention, despite greater operative time, hospital length of stay, and medical complications.

A Consensus Approach for Targeted Muscle Reinnervation in Amputees.

Amputations have been performed with few modifications since the dawn of surgery. Blood vessels are ligated, bones are shortened, and nerves are cut. In a percentage of people, this can result in severe neuropathic, residual limb, and phantom limb pain. Targeted muscle reinnervation is a surgical procedure initially conceived to optimize function for myoelectric prostheses in amputees. Recently, it has been adopted more widely by surgeons for the prevention and treatment of neuropathic pain. Perhaps as a function of its relatively recent development, many authors perform this operation differently, and there has been no overall agreement regarding the principles, indications, technical specifics, and postoperative management guidelines. This article is written as a consensus statement by surgeons focused on the treatment of neuropathic pain and those with extensive experience performing targeted muscle reinnervation. It is designed to serve as a roadmap and template for extremity surgeons to consider when performing targeted muscle reinnervation.

Vascularized Bone Graft Reconstruction for Upper Extremity Defects: A Review.

Upper extremity reconstruction may pose clinical challenges for surgeons due to the often-critical, complex functional demands of the damaged and/or missing structures. The advent of vascularized bone grafts (VBGs) has aided in reconstruction of upper extremity (UE) defects due to their superior regenerative properties compared with nonvascularized bone grafts, ability to reconstruct large bony defects, and multiple donor site options. VBGs may be pedicled or free transfers and have the potential for composite tissue transfers when bone and soft tissue are needed. This article provides a comprehensive up-to-date review of VBGs, the commonly reported donor sites, and their indications for the treatment of specific UE defects.

Targeted muscle reinnervation in above knee amputation: surgical technique.

In the United States, an estimated 185,000 individuals undergo amputation of their upper or lower limb. This results in residual limb pain in up to 85% of cases. Targeted muscle reinnervation (TMR) is a technique that has been shown to prevent symptomatic neuroma formation. In this video, the authors demonstrate their technique utilizing TMR at the time of above-the-knee amputation. Coaptations are made to provide motor targets for branches of the saphenous, tibial, and peroneal sensory nerves. At the featured patient's most recent follow-up visit 3 months postoperatively, she reported no stump pain or phantom limb pain. The video can be found here: https://stream.cadmore.media/r10.3171/2022.10.FOCVID2293.

Free Vascularized Fibular Flap with Bilateral Bipolar Latissimus Transfer for Upper Extremity Reconstruction: A Case Report.

CASE: A 19-year-old woman presented with bilateral mangled upper extremities after jumping in front of a moving train. After revascularization, osteocutaneous free vascularized fibula flap was performed to reconstruct the right humerus. The left forearm required transradial amputation with acute targeted muscle reinnervation. Finally, staged bilateral bipolar latissimus dorsi functional muscle flaps were performed to restore elbow flexion. CONCLUSION: Staged orthoplastic reconstruction of the upper extremities is an effective treatment approach for traumatic bone and soft-tissue defects. This patient's recovery demonstrates improved quality of life after severe upper extremity trauma.

Alternative Nerve Transfer for Shoulder Function: Thoracodorsal and Medial Triceps to Anterior Axillary Nerve.

We describe a reliable approach for double nerve transfer of the medial triceps branch and thoracodorsal nerve to the axillary nerve to increase axonal input. We present a review of outcomes for both end-to-end and reverse end-to-side nerve transfer. Methods: A retrospective review of patients who underwent nerve transfer for improvement of shoulder abduction at Harborview Medical Center and Northwestern Memorial Hospital between 2012 and 2021 was conducted. Patients were prospectively contacted to fill out a 30 item Disabilities of the Arm, Shoulder and Hand questionnaire, with an option to upload a video demonstrating active range of motion. Results: Twenty-one patients with 23 affected extremities were included in the final analysis. Fifteen patients completed the prospective arm of the study (71% response rate). Seventy-nine percent of patient limbs achieved a Medical Research Council Motor Scale (MRC-MS) of 4 or greater, and measured shoulder abduction active range of motion (AROM) was 139.2 degrees (range, 29-174 degrees) and 140.9 degrees (range, 60-180 degrees) (P = 0.95) for end-to-end and reverse end-to-side, respectively. Comparing end-to-end with reverse end-to-side neurorrhaphy, outcomes, including follow-up, mean postoperative MRC-MS, mean change in MRC-MS, Disabilities of the Arm, Shoulder and Hand, abduction AROM, and flexion AROM, were not statistically different. Conclusions: We showed improvements in shoulder abduction with the thoracodorsal nerve, in addition to the medial triceps branch, to increase axonal donation and power the axillary nerve without sacrificing the spinal accessory nerve. Furthermore, we demonstrated improvements with reverse end-to-side coaptation when intraoperative stimulation of the axillary nerve revealed residual function.

Vascularized Medial Femoral Condyle Periosteal Flaps With Allograft Bone for Distal Radius Giant Cell Tumors: A Case Report.

CASE: Distal radius reconstruction after giant cell tumor (GCT) resection is typically performed with free fibular flaps when a vascularized bone is needed. However, vascularized fibular flaps are contraindicated in patients with peroneal artery variants. We present 2 patients with GCTs of the radius and bilateral peronea arteria magna who underwent resection with wrist fusion using an allograft bone and vascularized free medial femoral condyle periosteal flaps. Both patients had excellent outcomes with minimal postoperative morbidity. CONCLUSION: Allograft bone with vascularized medial femoral condyle periosteal flaps is an effective option for reconstructing distal radius defects after GCT resection when conventional methods fail.

A systematic review of nerve grafting, end-to-end repair, and nerve transfer for obturator nerve injuries.

OBJECTIVE: Obturator nerve injury can occur as a complication of gynecologic surgeries, occurring most frequently in patients with endometriosis and genitourinary malignancies. The resulting injury causes paresthesia and major weakness in adduction and atrophy of the adductor group of lower extremity muscles. The objective of this study was to conduct a systematic review and meta-analysis of the effectiveness of end-to-end repair, nerve grafting, and nerve transfer in improving motor function in patients with obturator nerve injury. METHODS: PubMed, Cochrane, Medline, and Embase libraries were searched from May 1994 to August 2020 according to the PRISMA guidelines for articles that present functional outcomes after obturator nerve injury in patients treated with nerve grafting, end-to-end repair, or nerve transfer. RESULTS: A total of 25 patients from 22 studies were included in the study, 15 of whom were treated with end-to-end repair (60%), nine with nerve grafting (36%), and one with nerve transfer (4%). Of the 15 patients with transection data, two had incomplete (13%) and 13 had complete (87%) nerve transections. The patients underwent pelvic lymphadenectomy (n=24) and radical cystectomy (n=1) operations. The mean Medical Research Council (MRC) score was 2.95±1.7 immediately after treatment and 4.77±0.6 at the final follow-up. All patients achieved good outcomes (MRC ≥3) at the final follow-up. The mean MRC score for end-to-end repair (n=15), nerve grafting (n=9), and nerve transfer (n=1) was 4.8±0.6, 4.7±0.8, and 5, respectively. Patients with end-to-end repair had higher immediate post-operative strength than those treated with nerve grafting (p=0.03) and tended to achieve full functional recovery after shorter periods of time (rho=-0.65, p=0.049). Other parameters did not correlate with MRC. CONCLUSION: End-to-end repair, nerve grafting, and nerve transfer are equally effective in restoring function in patients with obturator nerve injury. However, patients treated with end-to-end repair had higher immediate post-operative strength than those treated with nerve grafting.

Computational Systems Biology of Morphogenesis.

Extracting mechanistic knowledge from the spatial and temporal phenotypes of morphogenesis is a current challenge due to the complexity of biological regulation and their feedback loops. Furthermore, these regulatory interactions are also linked to the biophysical forces that shape a developing tissue, creating complex interactions responsible for emergent patterns and forms. Here we show how a computational systems biology approach can aid in the understanding of morphogenesis from a mechanistic perspective. This methodology integrates the modeling of tissues and whole-embryos with dynamical systems, the reverse engineering of parameters or even whole equations with machine learning, and the generation of precise computational predictions that can be tested at the bench. To implement and perform the computational steps in the methodology, we present user-friendly tools, computer code, and guidelines. The principles of this methodology are general and can be adapted to other model organisms to extract mechanistic knowledge of their morphogenesis.

An In Vivo Comparison: Novel Mesh Suture Versus Traditional Suture-Based Repair in a Rabbit Tendon Model.

Purpose: Despite advancements in surgical techniques, suture pull-though and rupture continue to limit the early range of motion and functional rehabilitation after flexor tendon repairs. The aim of this study was to evaluate a suturable mesh compared with a commonly used braided suture in an in vivo rabbit intrasynovial tendon model. Methods: Twenty-four New Zealand female rabbits (3-4 kg) were injected with 2 units/kg botulinum toxin evenly distributed into 4 sites in the left calf. After 1 week, the animals underwent surgical tenotomy of the flexor digitorum tendon and were randomized to repair with either 2-0 Duramesh suturable mesh or to 2-0 Fiberwire using a 2-strand modified Kessler and 6-0 polypropylene running epitendinous suture. Rabbits were killed at 2, 4, and 9 weeks after surgery. Results: Grouping across time points, 58.3% (7 of 12) of Duramesh repairs were found to be intact for the explant compared with 16.7% (2 of 12) of Fiberwire repairs (P = .09). At 2 weeks, the mean Duramesh repairs were significantly stronger than the Fiberwire repairs with a mean failure load of 50.7 ± 12.7 N compared to 14.8 ± 18.3 N (P = .02). The load supported by the Duramesh repairs at 2 weeks (mean 50.7 ± 12.7 N) was similar to the load supported by both Fiberwire (52.2 ± 13.6 N) and Duramesh (57.6 ± 22.3 N) at 4 weeks. The strength of repair between Fiberwire and Duramesh at 4 weeks and 9 weeks was not significantly different. Conclusions: The 2-strand tendon repair with suturable mesh achieved significantly greater strength at 2 weeks than the conventional suture material. Future studies should evaluate the strength of repair prior to 2 weeks to determine the strength curve for this novel suture material. Clinical Relevance: This study evaluates the utility of a novel suturable mesh for flexor tendon repair in an in vivo rabbit model compared with conventional suture material.

Routes to Residency: A National Survey Demonstrating the Pathways to Become a Plastic Surgeon.

Plastic and reconstructive surgery (PRS) residency training can be completed through multiple pathways. Current residents' experiences regarding these different routes have not been previously described. The objective of the present study was to describe the educational pathways taken by current PRS residents in the United States. We hypothesized that there would be a small cohort of current PRS residents who were initially unsuccessful in matching into an integrated residency. METHODS: An online survey was sent to PRS residents across all training years from October 2020 to January 2021. The survey collected information about residents' match history, experience after not matching, and narrative comments on their route to residency. Public match data from the past 20 years (2001-2021) were also summarized with descriptive statistics. RESULTS: One hundred seventy-four residents responded (response rate 15%; 174/1158). Of these, 133 applied to integrated programs as senior medical students, and 15 (11%) did not match after applying as a senior medical student. Unmatched applicants took multiple different routes to PRS, including participating in the Supplemental Offer and Acceptance Program, reapplying, transferring after some general surgery training, and completing an independent PRS residency. Three-fourths (76%) of independent program residents did not originally apply to the integrated match. CONCLUSIONS: An initial unsuccessful match result does not portend that one will not be able to train for a career in PRS. Our findings illustrate the potential routes to successful completion of PRS residency training, both for unmatched applicants and residents who develop later interest in PRS.

Biologic Augmentation of Tibiotalocalcaneal Arthrodesis With Allogeneic Bone Block Is Associated With High Rates of Fusion.

BACKGROUND: The orthopaedic conditions and systemic comorbidities that occur in patients who require bone block tibiotalocalcaneal (TTC) arthrodesis have made this procedure associated with a higher-than-normal risk of nonunion, graft collapse, hardware failure, and amputation. Here, we present a novel approach to bone block TTC arthrodesis using adjunctive osteoinductive agents and a prolonged course of protected weightbearing to assess if we could improve on historical outcomes. We also evaluated the efficacy of a vascularized medial femoral condyle (MFC) free flap to augment TTC arthrodesis. METHODS: Fourteen adult patients underwent bone block TTC arthrodesis biologically augmented with fresh-frozen femoral head allograft, bone marrow aspirate concentrate, and demineralized bone matrix cortical fibers. Three patients with soft tissue defects underwent vascularized reconstruction with an MFC free flap. Radiographic union, the Foot Function Index (FFI), and PROMIS pain interference (PI), and physical function (PF) scores were assessed at follow-up. RESULTS: TTC fusion was documented on plain radiograph in 13 of 14 patients (92.9%) and CT in 10 of 11 patients (90.9%). Mean time to fusion was 183.2 ± 83.2 days. One patient (7.1%) experienced nonunion and persistent infection requiring amputation. Patients who underwent vascularized bone grafting had significantly shorter time to fusion (112.3 ± 31.7 days vs 204.4 ± 82.7 days, P = .05). Patient-reported outcomes revealed mild to moderate pain and dysfunction after 1 year (mean FFI = 41.0% ± 23.1%, PROMIS PI = 58.3 ± 1.8, PROMIS PF = 39.0 ± 2.2). CONCLUSION: In this relatively small series, the biologic augmentation of bone block TTC arthrodesis with osteoinductive agents and protective weightbearing resulted in excellent rates of fusion, modest pain, and preserved function of the lower extremity in almost all those treated. Osseous healing appears to be enhanced and accelerated with application of an MFC flap. We believe that this approach offers a viable salvage option for these challenging clinical problems. LEVEL OF EVIDENCE: Level IV, case series.