Bioengineering approaches for nerve graft revascularization: Current concepts and future directions.

Peripheral nerve injury (PNI) is the most common neurological injury in civilian and military injuries, with over 360,000 PNI procedures performed in the US yearly. Segmental loss of nerve tissue results in a nerve gap precluding a tension-free primary repair, and in these cases, interpositional autologous or acellular nerve allografts are used to bridge the gap. Graft ischemia time is a critical factor in achieving satisfactory nerve regeneration. Rapid nerve graft revascularization is essential in order to sustain Schwann cell growth which in turn is crucial for axonal regeneration. Currently, nerve autografts are considered the gold standard for segmental nerve gaps but are associated with several disadvantages such as limited supply of expendable donor tissue, increased operative time, and donor site morbidity. Hence, readily available, off-the-shelf nerve allografts or scaffolds are being investigated since they provide advantages such as a virtually limitless sourcing, a wide variety of sizes to match recipient nerves, and no donor site morbidity. New, exciting advances in tissue engineering to augment revascularization of nerve allografts or conduits have been investigated. Strategies include pro-angiogenic mesenchymal stem cells, extracellular vesicles, functionalized scaffolds, bioactive peptides, and three-dimensional bioprinting. This article discusses these bioengineering advances and future strategies aimed at enhancing nerve graft and scaffold revascularization. This article is categorized under: Neurological Diseases > Biomedical Engineering Neurological Diseases > Molecular and Cellular Physiology.

Modified Frailty Index Identifies Increased Risk of Postoperative Complications in Geriatric Patients After Open Reduction Internal Fixation for Distal Radius and Ulna Fractures: Analysis of 5654 Geriatric Patients, From the 2005 to 2017 the National Surgical Quality Improvement Project Database.

BACKGROUND: Open reduction internal fixation (ORIF) of distal radius and ulnar fractures (DRUFs) is one of the most common fracture surgeries for hand surgeons. Few studies have evaluated how frailty contributes to outcomes in geriatric hand surgery patients. This study hypothesizes that geriatric patients scoring higher on the modified Frailty Index 5 (mFI-5) are at greater risk of postoperative complications following DRUF fixation. METHODS: The American College of Surgeons National Surgical Quality Improvement Project database was reviewed for ORIF for DRUFs from 2005 to 2017. Statistically significant differences for demographics, comorbidities, mFI-5, and postoperative complications between geriatric and nongeriatric patients were evaluated with multivariate logistic regression analysis. RESULTS: A total of 17,097 ORIF for DRUFs were collected by the National Surgical Quality Improvement Project 2005-2017, with 5654 patients older than 64 years (33.2%). Average age for geriatric patients undergoing ORIF for DRUFs was 73.7 years. Within geriatric patients, an mFI-5 score >2 confers 1.6-times increased risk of returning to the operating room following ORIF for DRUF (adjusted odds ratio, 1.6; P = 0.02), whereas an increase in mFI-5 score >2 confers a 3.2-times increased risk of deep vein thrombosis among geriatrics (adjusted odds ratio, 3.2 P < 048). CONCLUSION: Frailty among geriatric patients confers increased risk of deep vein thrombosis postoperatively. Geriatric patients with higher frailty scores carry a significantly increased risk of returning to the operating room within 30 days. Hand surgeons can use the mFI-5 to screen geriatric patients with DRUF patients to guide perioperative decision-making.

Molecular Basis of Surgical Coaptation Techniques in Peripheral Nerve Injuries.

Peripheral nerve injuries requiring surgical repair affect over 100,000 individuals in the US annually. Three accepted methods of peripheral repair include end-to-end, end-to-side, and side-to-side neurorrhaphy, each with its own set of indications. While it remains important to understand the specific circumstances in which each method is employed, a deeper understanding of the molecular mechanisms underlying the repair can add to the surgeon's decision-making algorithm when considering each technique, as well as help decide nuances in technique such as the need for making epineurial versus perineurial windows, length and dept of the nerve window, and distance from target muscle. In addition, a thorough knowledge of individual factors that are active in a particular repair can help guide research into adjunct therapies. This paper serves to summarize the similarities and divergences of the three commonly used nerve repair strategies and the scope of molecular mechanisms and signal transduction pathways in nerve regeneration as well as to identify the gaps in knowledge that should be addressed if we are to improve clinical outcomes in our patients.

Final 24-hour Drain Output and Postoperative Day Are Poor Indicators for Appropriate Drain Removal.

Drains are used in plastic surgery to remove excess fluid while ameliorating complications. However, there is a paucity of evidence supporting guiding parameters on when to discontinue a drain. The aim of our study was to determine whether two of the most common parameters, drain volume 24 hours before removal or postoperative day, are valid indicators for drain removal. Methods: A retrospective chart review was conducted for surgical operations performed by our division between July 2014 and May 2019. Of the 1308 patients, 616 had a drain and a complete record. Demographics, medical history, operative time, antibiotic use, anatomic site, donor/recipient, and complication type were recorded. Complications were defined as events that deviated from expected postoperative course or required pharmacological/procedural intervention. T-test and Chi square were used to analyze data. Results: In total, 544 patients were in the no complication group, and 72 were in the complication group. The complication group patients had drains removed later than patients in the no complication group (15.7 days versus 12.5 days, P = 0.0003) and had similar final 24-hour drain volumes versus patients in the no complication group (16.7 mL versus 18.8 mL, P = 0.2548). The complication group had more operations on the pelvis (11% versus 2.1%; P = 0.000017) or thigh (8.5% versus 3.4%; P = 0.029). Conclusions: Our data suggest neither postoperative day nor 24-hour volume before drain removal are valid indicators for removal. Late removal correlates with more complications; however, persisting output leading to later removal may be predictive of an impending complication rather than delays in drain removal causing the complication.

Sensorimotor Outcomes of Upper Extremity End-to-Side Nerve Transfers: A Meta-analysis.

BACKGROUND: End-to-side nerve transfer (ETSNT) for treatment of peripheral nerve injuries is controversial given the myriad anatomic locations, injury types, and indications. Efficacy of ETSNT remains debated. We hypothesized differences in age, sex, transfer location, and time to surgery influence outcomes. METHODS: We performed a search of the PubMed database for ETSNT in the upper extremity from 1988 to 2018. Age, sex, transfer location, time to surgery, donor and recipient axons, and strength and sensation outcomes as measured by Medical Research Council scale were extracted from articles. Meaningful recovery was classified as Medical Research Council Grade 3 or greater. Association between meaningful recovery and younger (<25) and older (≥25) patients, injury mechanism, sex, transfer location, donor axons, and recipient axons were calculated using a χ 2 or Fisher exact test. A logistic mixed effect model was used with time to surgery, age (categorical), transfer location, and injury type as a fixed effect, and a random paper effect was included to account for correlation among patients from the same paper. RESULTS: One hundred fifteen patients from 11 studies were included. Neither age (continuous variable, P = 0.68) nor time to surgery ( P = 0.28) affected meaningful recovery. Injury mechanism, sex, and younger age (<25 vs ≥25 years) were not associated with meaningful recovery. Within the brachial plexus ETSNT demonstrated median M4 ± 1 postoperative strength, with trunks/cords as the primary axon donor ( P = 0.03). The musculocutaneous nerve demonstrated promising but variable results in 31 patients with median strength M3 ± 4. Digital nerves consistently demonstrated meaningful sensory recovery as both donor and recipient axons (15 of 15, 100%). Logistic regression analysis demonstrated that odds of meaningful recovery after ETSNT are significantly greater for transfers within the brachial plexus compared with the distal arm (odds ratio, 41.9; 95% CI, 1.1-1586.7, P = 0.04), but location does not significantly affect meaningful recovery ( P = 0.22). CONCLUSIONS: Patients undergoing ETSNT for digital nerve injury demonstrated meaningful recovery. End-to-side nerve transfer seems to be more efficacious when performed within the brachial plexus. This study did not find sex, injury mechanism, or time to surgery to significantly affect meaningful recovery. Additional study is needed to better evaluate the effectiveness of ETSNT in the upper extremity.

Optimal Irrigant in High Pressure Paint Injection Injuries of the Hand.

High pressure injection injury to the hand with paint leads to amputation rates near 48%. Historically, authors utilized saline irrigation alone, but have high reoperation rates. We conducted a cadaveric study to determine the ideal detergent for effective paint removal from the soft tissue. METHODS: Two cadaveric hands were amputated from the same cadaver. The left and right hand digits were injected with flat white latex-based paint and flat white oil-based paint, respectively. Each digit received a longitudinal incision and was scrubbed for 120 seconds with 50 mL of a randomly assigned detergent and no detergent (saline) as the control. After achieving a lather, each finger was cleansed with 50 mL saline before being evaluated by two blinded hand surgery faculty. Reviewers assessed the washouts as adequate or inadequate, in order to generate a Kappa statistic and measure inter-rater reliability prior to ranking each digit (1 through 5) (ie, 1 = most paint-free soft tissue). RESULTS: The two hand faculty had an inter-rater reliability of 0.70. Both reviewers ranked povidone-iodine 10% or Johnson & Johnson shampoo as the best irrigant for latex-based paint. In oil-based paint, povidone-iodine 10%, Johnson & Johnson, & Techni-care were ranked as top three. All reviewers reported detergents were better than saline alone. CONCLUSIONS: The addition of detergent created an irrigant that removed both latex- and oil-based paint better than normal saline alone. Based on these results, surgeons treating high-pressure injection injury should consider using Povidone-Iodine 10% or Johnson & Johnson baby shampoo for latex- or oil-based paint.

In Vitro, In Vivo and Ex Vivo Models for Peripheral Nerve Injury and Regeneration.

Peripheral Nerve Injuries (PNI) frequently occur secondary to traumatic injuries. Recovery from these injuries can be expectedly poor, especially in proximal injuries. In order to study and improve peripheral nerve regeneration, scientists rely on peripheral nerve models to identify and test therapeutic interventions. In this review, we discuss the best described and most commonly used peripheral nerve models that scientists have and continue to use to study peripheral nerve physiology and function.

Substance Addiction and the Hand Surgery Patient: A Comprehensive Review.

Substance abuse is pervasive in the American society, with 10% of the United States population using marijuana, up to 17% of patients undergoing upper-extremity surgery reporting chronic opioid use, and up to 20% of acute hand infections occurring secondary to intravenous drug use. It is common, therefore, for a hand surgeon to take care of a patient under the influence of nonprescription drugs. The range of abused substances is diverse, and the implications are profound. As such, it is important for hand surgeons to understand the potential implications of drug use to best guide patient care and surgical decision-making. The abuse of opioids, amphetamines, marijuana, and other substances has an impact on treatment timing, adherence to postoperative hand therapy, and/or clinic follow ups. The physiologic effects of these drugs affect surgical risk, wound healing, and bone healing. Social factors associated with drug abuse can complicate the management of these patients. Collectively, all these factors substantially affect surgical outcomes. In this review, we provide an overview of commonly abused illicit and prescription drugs seen in hand surgery practice, tips to identify substance abuse, the drugs' implications for surgical risks, outcomes, and some recommendations for management.

Preventing Unnecessary Intubations: A 5-Year Regional Burn Center Experience Using Flexible Fiberoptic Laryngoscopy for Airway Evaluation in Patients With Suspected Inhalation or Airway Injury.

The decision to intubate acute burn patients is often based on the presence of classic clinical exam findings. However, these findings may have poor correlation with airway injury and result in unnecessary intubation. We investigated flexible fiberoptic laryngoscopy (FFL) as a means to diagnose upper airway thermal and inhalation injury and guide airway management. A retrospective chart review of all burn patients who underwent FFL from 2013 to 2017 was performed. Their charts were reviewed to determine the indications for FFL including the historical data and physical exam findings that indicated airway injury as well as patient age, TBSA, type and depth of burn injury, carboxyhemoglobin level, and clinical course. Fifty-one patients underwent FFL, with an average TBSA of 6.5% (range 0.5-38.0%) and carboxyhemoglobin level of 3.5%. Burn mechanism was flame (35.3%) or flash (51.0%), with 50% occurring in enclosed spaces. In all cases, the decision to perform FFL was based on physical exam findings meeting criteria for intubation, including facial burns, singed nasal hairs, nasal soot, voice change, throat pain or abnormal sensation, shortness of breath, carbonaceous sputum, wheezing, or stridor. Based on FFL, 9 patients (17.7%) were treated with steroids, 28 patients (54.9%) received supportive care, and 6 patients (11.8%) had repeat FFL for monitoring. One patient was intubated after repeat FFL examination. All patients who underwent FFL met traditional criteria for intubation based on exam, however 98% were monitored without issues based on FFL findings. FFL is a valuable tool that can lead to fewer intubations in acute burn patients with a stable respiratory status for whom history and physical exam suggest upper airway injury.

Subungual Tumors: An Algorithmic Approach.

The presentation of benign and malignant subungual tumors often follows a final common pathway of nonspecific nail deformity; as such, delays in diagnosis are common. Therefore, it is imperative to have a high degree of suspicion for malignant lesions and an organized approach to subungual tumors. To that end, we present a diagnostic algorithm encompassing the most common benign and malignant subungual tumors, along with a summary of the presentation, imaging, and treatment of these lesions.

Optimizing Collagen Scaffolds for Bone Engineering: Effects of Cross-linking and Mineral Content on Structural Contraction and Osteogenesis.

INTRODUCTION: Osseous defects of the craniofacial skeleton occur frequently in congenital, posttraumatic, and postoncologic deformities. The field of scaffold-based bone engineering emerged to address the limitations of using autologous bone for reconstruction of such circumstances. In this work, the authors evaluate 2 modifications of three-dimensional collagen-glycosaminoglycan scaffolds in an effort to optimize structural integrity and osteogenic induction. METHODS: Human mesenchymal stem cells (hMSCs) were cultured in osteogenic media on nonmineralized collagen-glycosaminoglycan (C-GAG) and nanoparticulate mineralized collagen-glycosaminoglycan (MC-GAG) type I scaffolds, in the absence and presence of cross-linking. At 1, 7, and 14 days, mRNA expression was analyzed using quantitative real-time -reverse-transcriptase polymerase chain reaction for osteocalcin (OCN) and bone sialoprotein (BSP). Structural contraction was measured by the ability of the scaffolds to maintain their original dimensions. Mineralization was detected by microcomputed tomographic (micro-CT) imaging at 8 weeks. Statistical analyses were performed with Student t-test. RESULTS: Nanoparticulate mineralization of collagen-glycosaminoglycan scaffolds increased expression of both OCN and BSP. Cross-linking of both C-GAG and MC-GAG resulted in decreased osteogenic gene expression; however, structural contraction was significantly decreased after cross-linking. Human mesenchymal stem cells-directed mineralization, detected by micro-CT, was increased in nanoparticulate mineralized scaffolds, although the density of mineralization was decreased in the presence of cross-linking. CONCLUSIONS: Optimization of scaffold material is an essential component of moving toward clinically translatable engineered bone. Our current study demonstrates that the combination of nanoparticulate mineralization and chemical cross-linking of C-GAG scaffolds generates a highly osteogenic and structurally stable scaffold.

Computed tomography image guidance for more accurate repair of anterior table frontal sinus fractures.

BACKGROUND: Anterior table frontal sinus fractures accompanied by nasofrontal duct injury require surgical correction. Extracranial approaches for anterior table osteotomies have traditionally used plain radiograph templates or a "cut-as-you-go" technique. We compared these methods with a newer technique utilizing computed tomography (CT)-guided imaging. METHODS: Data of patients with acute, traumatic anterior table frontal sinus fractures and nasofrontal duct injury between 2009 and 2013 were reviewed (n = 29). Treatment groups compared were as follows: (1) CT image guidance, (2) plain radiograph template, and (3) cut-as-you-go. Frontal sinus obliteration was performed in all cases. Demographics, operative times, length of stay, complications, and osteotomy accuracy were recorded. RESULTS: Similar demographics, concomitant injuries, operative times, and length of stay among groups were noted. No patients in the CT-guided group had perioperative complications including intraoperative injury of the dura, cerebrum, or orbital structures. In the plain radiograph template group, 25% of patients had inadvertent dural exposure, and 12.5% required take-back to the operating room for cranial bone graft donor site hematoma. In the cut-as-you-go group, 11% required hardware removal for exposure. There were no cases of cerebrospinal fluid leak, meningitis, or mucocele in any group (follow-up, 29.2 months). The CT image guidance group had the most accuracy of the osteotomies (95%) compared with plain radiograph template (85%) and the cut-as-you-go group (72.5%). CONCLUSIONS: A new technique using CT image guidance for traumatic frontal sinus fractures repair offers more accurate osteotomy and elevation of the anterior table without increased operative times or untoward sequelae.

Absorption and chemopreventive targets of sulforaphane in humans following consumption of broccoli sprouts or a myrosinase-treated broccoli sprout extract.

SCOPE: Sulforaphane (SFN), an isothiocyanate derived from crucifers, has numerous health benefits. SFN bioavailability from dietary sources is a critical determinant of its efficacy in humans. A key factor in SFN absorption is the release of SFN from its glucosinolate precursor, glucoraphanin, by myrosinase. Dietary supplements are used in clinical trials to deliver consistent SFN doses, but myrosinase is often inactivated in available supplements. We evaluated SFN absorption from a myrosinase-treated broccoli sprout extract (BSE) and are the first to report effects of twice daily, oral dosing on SFN exposure in healthy adults. METHODS AND RESULTS: Subjects consumed fresh broccoli sprouts or the BSE, each providing 200 µmol SFN daily, as a single dose and as two 100-µmol doses taken 12 h apart. Using HPLC-MS/MS, we detected ∼3 x higher SFN metabolite levels in plasma and urine of sprout consumers, indicating enhanced SFN absorption from sprouts. Twelve-hour dosing retained higher plasma SFN metabolite levels at later time points than 24-hour dosing. No dose responses were observed for molecular targets of SFN (i.e. heme oxygenase-1, histone deacetylase activity, p21). CONCLUSION: We conclude that the dietary form and dosing schedule of SFN may impact SFN absorption and efficacy in human trials.