Long-Term Mortality After Charcot Reconstruction.

Charcot neuroarthropathy is a complicated phenomenon with the potential to cause significant deformity, morbidity, and mortality. Costs associated with Charcot-related complications are substantial, with thousands of amputations occurring annually. The purpose of this study was to retrospectively review a single surgeon's experience and record the 10-year mortality rate among patients after Charcot reconstruction at a single institution between 2007 and 2013. Lower-extremity limb salvage is crucial to reduce the burden of Charcot neuroarthropathy. This article provides an example of the potential long-term success of reconstruction surgery for this condition.

Rate and Location of Reulceration and Reamputation After Partial First-Ray Amputation versus Hallux Amputation in Diabetic and Nondiabetic Populations.

BACKGROUND: We sought to determine the rates of reulceration and reamputation in individuals who underwent partial first-ray amputations versus hallux amputations in diabetic and nondiabetic populations. METHODS: Eighty-four amputations were reviewed in a retrospective fashion. A retrospective medical record review was performed to determine patients who underwent a hallux amputation, both partial and complete, and patients who underwent a partial first-ray amputation. Only patients from 2007 to 2019 were reviewed. The reulceration rate of hallux amputations was 61% compared with a partial first-ray amputation reulceration rate of 74%. RESULTS: The reamputation rate of hallux amputation versus partial first-ray amputation was 43% versus 51%. At final follow-up, it was statistically significant that patients who underwent hallux amputation were more likely to be healed than those who underwent partial first-ray amputation, regardless of reulceration or reamputation. In addition, patients who underwent hallux amputation went on to digital amputation, and those who underwent partial first-ray amputation went on to transmetatarsal amputation. CONCLUSIONS: Comparing partial first-ray amputation to hallux amputation, hallux amputation patients are more prone to subsequent digital ulceration. Patients who initially undergo hallux amputation have variable subsequent amputations, often digital. Reulceration primarily occurs at the incision site for partial first-ray amputations, with a higher likelihood of subsequent transmetatarsal amputation. Patients with a medical history of diabetes and staged procedures are more likely to receive partial first-ray amputations. However, hallux amputation patients have a lower risk of reulceration and reamputation, regardless of subsequent events. These findings underscore the importance of discussing risks and preventive measures with patients undergoing such amputations, emphasizing postoperative examinations for specific areas of concern. Hallux amputation appears to offer greater protection against reulceration and reamputation for both diabetic and nondiabetic populations.

Morbidity Associated With Distal Tibial Autograft Harvest.

Distal tibial autograft harvesting has been studied in the past, but morbidity at the level of the donor site is unclear. The purpose of this retrospective review is to assess morbidity in distal tibial autograft harvesting associated with foot and ankle arthrodesis procedures. A retrospective analysis was performed utilizing patients treated in the last 13 years at a large, multicenter, academic, tertiary referral, research institution. Included patients were between the ages of 18 and 80 years old. One-hundred and seven patients (39 male; 68 female) underwent ipsilateral distal tibial bone graft (n = 110) harvesting to augment the index procedure. Patients were followed for an average of 11.2 months after surgery (Range: 1-73 months). The incidence rate of distal tibial stress fractures was 4.5%, with an overall postoperative complication rate of 8.2%. Overall, low complication rates associated with distal tibial autograft harvesting were found, supporting the use of the distal tibia as an appropriate site for autograft harvesting in foot and ankle surgery.

The Vagus Nerve Regulates Immunometabolic Homeostasis in the Ovine Fetus near Term: The Impact on Terminal Ileum.

BACKGROUND: Glucosensing elements are widely distributed throughout the body and relay information about circulating glucose levels to the brain via the vagus nerve. However, while anatomical wiring has been established, little is known about the physiological role of the vagus nerve in glucosensing. The contribution of the vagus nerve to inflammation in the fetus is poorly understood. Increased glucose levels and inflammation act synergistically when causing organ injury, but their interplay remains incompletely understood. We hypothesized that vagotomy (Vx) will trigger a rise in systemic glucose levels and this will be enhanced during systemic and organ-specific inflammation. Efferent vagus nerve stimulation (VNS) should reverse this phenotype. METHODS: Near-term fetal sheep (n = 57) were surgically prepared using vascular catheters and ECG electrodes as the control and treatment groups (lipopolysaccharide (LPS), Vx + LPS, Vx + LPS + selective efferent VNS). The experiment was started 72 h postoperatively to allow for post-surgical recovery. Inflammation was induced with LPS bolus intravenously (LPS group, 400 ng/fetus/day for 2 days; n = 23). For the Vx + LPS group (n = 11), a bilateral cervical vagotomy was performed during surgery; of these n = 5 received double the LPS dose, LPS800. The Vx + LPS + efferent VNS group (n = 8) received cervical VNS probes bilaterally distal from Vx in eight animals. Efferent VNS was administered for 20 min on days 1 and 2 +/10 min around the LPS bolus. Fetal arterial blood samples were drawn on each postoperative day of recovery (-72 h, -48 h, and -24 h) as well as at the baseline and seven selected time points (3-54 h) to profile inflammation (ELISA IL-6, pg/mL), insulin (ELISA), blood gas, and metabolism (glucose). At 54 h post-LPS, a necropsy was performed, and the terminal ileum macrophages' CD11c (M1 phenotype) immunofluorescence was quantified to detect inflammation. The results are reported for p < 0.05 and for Spearman R2 > 0.1. The results are presented as the median (IQR). RESULTS: Across the treatment groups, blood gas and cardiovascular changes indicated mild septicemia. At 3 h in the LPS group, IL-6 peaked. That peak was decreased in the Vx + LPS400 group and doubled in the Vx + LPS800 group. The efferent VNS sped up the reduction in the inflammatory response profile over 54 h. The M1 macrophage activity was increased in the LPS and Vx + LPS800 groups only. The glucose and insulin concentrations in the Vx + LPS group were, respectively, 1.3-fold (throughout the experiment) and 2.3-fold higher vs. control (at 3 h). The efferent VNS normalized the glucose concentrations. CONCLUSIONS: The complete withdrawal of vagal innervation resulted in a 72-h delayed onset of a sustained increase in glucose for at least 54 h and intermittent hyperinsulinemia. Under the conditions of moderate fetal inflammation, this was related to higher levels of gut inflammation. The efferent VNS reduced the systemic inflammatory response as well as restored both the concentrations of glucose and the degree of terminal ileum inflammation, but not the insulin concentrations. Supporting our hypothesis, these findings revealed a novel regulatory, hormetic, role of the vagus nerve in the immunometabolic response to endotoxin in near-term fetuses.

Prevalence of Ankle Charcot Neuroarthropathy Presenting in a Tertiary Care Center.

Charcot neuroarthropathy's (CN) anatomic classification was originally formulated by the Brodsky article and the Trepman et al modification, including midfoot (type 1), rearfoot (type 2), ankle (type 3a), calcaneus (type 3b), multiarticular (type 4), and forefoot (type 5). In these classic studies, ankle joint and multijoint CN are reported as 9% and 6% to 9%, respectively, but we believe ankle CN to be more common than that in a tertiary setting. We retrospectively reviewed patients presenting initially or as referral between 2004 and 2020. Initial presentation radiographs were reviewed and classified by 3 authors based on Brodsky's model with Trepman and colleagues' modification, and any discrepancies were reviewed by the fourth author. A total of 175 patients (205 feet) were assessed. This revealed 80 cases classified as type 1 (39.0%), 23 cases type 2 (11.2%), 17 cases type 3a (8.3%), 2 cases type 3b (1.0%), and 83 cases type 4 (40.5%). After subdividing type 4, total prevalence included 150 with type 1 anatomic location (73.2%), 103 type 2 (50.2%), 44 type 3a (21.5%), and still 2 type 3b (1.0%). This study revealed a similar prevalence of isolated ankle CN (8.5%) compared to the Trepman et al article (9%), however, in total, ankle CN (21.5%) occurred 2.4-times more than the original 9%. Our study also found there to be a higher prevalence of ankle CN in the setting of multiarticular CN, which has not been evaluated in past studies. The prevalence of multiarticular CN was found to be 4.5-fold greater than the Trepman article (6%-9%).

SIRT1 induction in the skeletal muscle of male mice partially preserves limb muscle mass but not contractile force in response to androgen deprivation.

In males, the factors that decrease limb muscle mass and strength in response to androgen deprivation are largely unknown. Sirtuin1 (SIRT1) protein levels are lower in the limb muscle of male mice subjected to androgen deprivation. The present study aimed to assess whether SIRT1 induction preserved limb muscle mass and force production in response to androgen deprivation. Physically mature male mice containing an inducible muscle-specific SIRT1 transgene were subjected to a sham or castration surgery and compared to sham and castrated male mice where the SIRT1 transgene was not induced. SIRT1 induction partially preserved whole-body lean mass, tibialis anterior (TA) mass and triceps surae muscle mass in response to castration. Further analysis of the TA muscle showed that muscle-specific SIRT1 induction partially preserved limb muscle soluble protein content and fibre cross-sectional area. Unilateral AAV9-mediated SIRT1 induction in the TA muscle showed that SIRT1 partially preserved mass by acting directly in the muscle. Despite those positive outcomes to limb muscle morphology, muscle-specific SIRT1 induction did not preserve the force generating capacity of the TA or triceps surae muscles. Interestingly, SIRT1 induction in females did not alter limb muscle mass or limb muscle strength even though females have naturally low androgen levels. SIRT1 also did not alter the androgen-mediated increase in limb muscle mass or strength in females. In all, these data suggest that decreases in SIRT1 protein in the limb muscle of males may partially contribute to the loss of limb muscle mass in response to androgen deprivation. KEY POINTS: SIRT1 induction in skeletal muscle of male mice subjected to androgen deprivation partially preserved limb muscle mass and fibre cross-sectional area. SIRT1 induction in skeletal muscle of male mice subjected to androgen deprivation did not prevent preserve limb muscle force generating capacity. SIRT1 induction in skeletal muscle of females did not alter baseline limb muscle mass, nor did it affect the androgen-mediated increase in limb muscle mass.

Safety and Complication Rate of Ring External Fixation in the Foot and Ankle.

External fixation is a powerful tool for foot and ankle surgeons. Currently, there is no consensus on true complication rate. The purpose of this study was to report our institution's complication rate of ring external fixation performed by a single surgeon. We retrospectively evaluated electronic medical record of 224 patients with 238 circular frames between 2009 and 2021 at a single institution. Minor complications were defined as a frame managed without early frame removal or return to operating room. Major complications were defined as early return to operative room or early removal defined by our institution as less than 2 months. We recorded over 1642 Ilizarov wires and 278 half pins; 10% (n = 163) of wires and 7% (n = 19) of half pins had a complication. We recorded 44% (n = 104) minor complications and 9% (n = 22) major complications. Minor complications average (mean) onset was 4 weeks, 89% (n = 93) involved wires, and 73% resolved without additional care. Major complications average (mean) onset was 3.7 weeks. Of these, 32% (n = 7) went on to successful revision. This revealed a significant correlation between minor complications and history of osteomyelitis (p < .05). While minor complications do appear high, this was due to wire irritation and local erythema which resolved without additional intervention. To better assess complications with external fixation the authors believe that wire irritation and pin site erythema should be recognized as an expected outcome. A better understanding of ring external fixation in foot and ankle surgery is vital to appropriate perioperative management and patient care.

Double versus Triple Arthrodesis for Flatfoot Deformity: When, Why, and How?

Different types of arthrodesis for flatfoot deformity have a long history in foot and ankle surgery. Arthrodesis of the rearfoot can be a useful tool in helping correct deformity and maintaining that correction with good long-term results. Questions have risen recently however about the necessity of including the calcaneocuboid joint in the traditional rearfoot arthrodesis or triple arthrodesis. The double arthrodesis of the talonavicular and subtalar joints has grown in popularity and this review helps the reader choose with a review of the biomechanics, surgical approaches, fixation techniques and recent literature outcomes of both procedures.

Short- to Intermediate-Term Radiographic Outcomes Following Cotton Osteotomy.

The cotton osteotomy or the medial cuneiform opening wedge osteotomy has been a common adjunct procedure in flatfoot reconstruction to correct for forefoot varus or a dorsiflexed first ray. The main goal of the study is to retrospectively review outcomes specifically in the short-intermediate term for the cotton osteotomy. The medical records of a single foot and ankle surgeon (PRB) were reviewed for patients who met inclusion and exclusion criteria. The study period was from January 2006 to October 2018. The analysis was performed using information obtained from chart-review to examine union and complication rates, as well as changes in the cuneiform articular angle based on graft size and type. A total of 71 feet in 61 patients underwent cotton osteotomies for flatfoot reconstruction. Overall complication rate was 5.6% (4/71) with 2 nonunions (2/47) in those that had radiographic follow-up of greater than 9 months. Change in cuneiform articular angle (CAA) showed 0.91° of correction per 1-millimeter increase in graft wedge size from preoperative to 3 weeks. Change for anterior-posterior medial cuneiform bisection dorsal length (AP length) was 0.70 mm per 1 mm of graft used from preoperative to 3 weeks. 6 weeks to 10 weeks showed statistically significant changes in the CAA (p = .01) and the AP length (p = .002). The cotton osteotomy showed statistically significant radiographic loss of correction between the 6- and 10-week time points when patients were allowed to begin weightbearing. Metal grafts may provide maintenance of correction which warrants future studies on their efficacy.

Reulceration and Reoperation Incidence After Isolated Partial Fifth Ray Amputations: A Multicenter Study.

Ulceration or reulceration is a common complication following partial or total fifth ray amputations. The primary aim of this study was to evaluate the incidence of reulceration following partial fifth ray amputations. This was a multicenter review of 117 consecutive limbs that underwent partial fifth ray amputations at the University of Pittsburgh Medical Center and Wake Forest Baptist Medical Centers. Procedures were performed at various levels along the fifth metatarsal. Incidence of postoperative ulceration was evaluated on the ipsilateral foot. We hypothesized there would be an association between location of resection and development of reulceration. Seventy-one of 117 patients (60.7%) experienced repeat ulceration following a partial fifth ray amputation. Median follow-up time was 19 months. There was no statistical difference based on location of amputation (proximal, middle, distal, isolated base) with regards to reulceration (p = .166), further amputation (p = .271), transmetatarsal amputation (p = .160), or below knee amputation (p = .769). There was statistical significance in the follow up time between study sites (p = .013), fifth ray amputation reoperation rate between study sites (p = .001), and reulceration rates between study sites (p = .017). Partial fifth ray amputations can be a good initial salvage procedure to clear infection and prolong bipedal ambulatory status. The results of the present study put forward that there is not an association between location of amputations of the fifth ray and development of reulceration, transfer lesions or more proximal amputations.

Reoperation, reamputation, and new ulceration following complete or partial toe amputation among diabetic and non-diabetic patients.

AIMS: To compare the number of reoperations, reamputations, and new ulcers following toe amputation in diabetic and non-diabetic patients with sub-group analysis on index amputation level. METHODS: One-hundred sixteen patients with a complete (CTA) or partial (PTA) toe amputation and minimum of 12-month (12 M) follow-up were identified in electronic medical records. The number of reoperations and reamputations, number and location of new ulcers, and final amputation level of the ipsilateral extremity were compared between diabetic and non-diabetic patients and between those with CTA and PTA at 12 M and final follow-up (FFU). RESULTS: Diabetic patients had significantly more reoperations, reamputations, and new ulcers than non-diabetic patients at 12 M and FFU. There were no differences in reoperations, reamputations, or new ulcer location between CTA and PTA; however, patients with PTA developed more new ulcers at 12 M and FFU and were more likely to have a distal final amputation level compared to those with CTA. CONCLUSIONS: Diabetic patients required significantly more reoperations and reamputations following a toe amputation and developed more new ulcers than non-diabetic patients regardless of index amputation level. These high rates among diabetic patients highlight the complications encountered following toe amputation and emphasize the need for close, multi-disciplinary care.

Recording and manipulation of vagus nerve electrical activity in chronically instrumented unanesthetized near term fetal sheep.

BACKGROUND: The chronically instrumented pregnant sheep has been used as a model of human fetal development and responses to pathophysiologic stimuli. This is due to the unique amenability of the unanesthetized fetal sheep to the surgical placement and maintenance of catheters and electrodes, allowing repetitive blood sampling, substance injection, recording of bioelectrical activity, application of electric stimulation, and in vivo organ imaging. Recently, there has been growing interest in the pleiotropic effects of vagus nerve stimulation (VNS) on various organ systems such as innate immunity and inflammation, and metabolism. There is no approach to study this in utero and corresponding physiological understanding is scarce. NEW METHOD: Based on our previous presentation of a stable chronically instrumented unanesthetized fetal sheep model, here we describe the surgical instrumentation procedure allowing successful implantation of a cervical uni- or bilateral VNS probe with or without vagotomy. RESULTS: In a cohort of 68 animals, we present the changes in blood gas, metabolic, and inflammatory markers during the postoperative period. We detail the design of a VNS probe which also allows recording from the fetal nerve. We also present an example of fetal vagus electroneurogram (VENG) recorded from the VNS probe and an analytical approach to the data. COMPARISON WITH EXISTING METHODS: This method represents the first implementation of fetal VENG/VNS in a large pregnant mammalian organism. CONCLUSIONS: This study describes a new surgical procedure allowing to record and manipulate chronically fetal vagus nerve activity in an animal model of human pregnancy.

Common Pitfalls in Subtalar Joint Preparation for Arthrodesis via Sinus Tarsi Approach.

This cadaveric study assessed factors that could lead to nonunions in subtalar joint arthrodesis. The purpose of this study was to assist surgeons in achieving sufficient joint preparation in hopes to achieve more frequent arthrodesis of the subtalar joint. We evaluated the influence of experience in regard to cartilage preparation of the joint. We also assessed which quadrants of the subtalar joint were more likely to have unprepared cartilage. The subtalar joints in 17 cadaveric limbs were prepared by 17 participants with differing levels of experience. After the cartilage was denuded, the percentage of unprepared cartilage in each subtalar joint was calculated. The medial quadrants were more likely to have unprepared surfaces. There was also a learning curve present with subtalar joint preparation, as seen by the significantly larger percentage of unprepared cartilage in cadavers prepared by first year residents.

Surgical Treatment and Management for Chronic Dislocated Subtalar Joint.

Lateral dislocation of the subtalar joint is a relatively uncommon pathology. It has previously been described in the literature secondary to acute trauma. This form of dislocation can also be acquired and seen in severe long-standing cases of flatfoot and Charcot neuroarthropathy. This study aims to describe this "sidecar" deformity, etiologies of the deformity, and the surgical options for correction. This study was performed by reviewing medical records of a single foot and ankle surgeon for patients who met inclusion criteria and underwent surgical correction. The study period was from October 2010 to July 2017. Statistical analysis was performed using chart-review information to examine variables affecting selected outcome measures. The outcome measures evaluated were minor and major complications, as well as functional limb status. A total of 16 patients were included in the study. Etiology included 10 severe flatfoot deformities and 6 Charcot deformities. Seven patients underwent staged reconstruction, and 9 underwent a single-stage reconstruction. Seven patients (44%) had complications; all were major and required unplanned reoperation. In all 16 patients (100%), limb salvage and a functional limb resulted. We conclude that patients with a limb-threatening sidecar deformity can be successfully treated with reconstruction. This is challenging and associated with a high complication rate. Patients with a history of infection should be counseled on the possibility of requiring a staged reconstruction with multiple surgeries as well as the possibility of amputation.

Outcomes and Management of Infected Intramedullary Nails After Tibiotalocalcaneal Arthrodesis in Limb Salvage: A Retrospective Case Series.

Retrograde intramedullary nails are often used for tibiotalocalcaneal arthrodesis to correct severe hindfoot deformities in high-risk patient populations. The purposes of the current study are to report outcomes of patients undergoing staged management of infection after intramedullary nail fixation for tibiotalocalcaneal arthrodesis and to review the surgical approach to management of this limb-threatening complication. The authors reviewed patients who underwent hindfoot intramedullary nailing with subsequent revision for infection between January 2006 and December 2016. Staged protocol with antibiotic nail for the management of deep infection was used in 19 patients. The mean follow-up was 115.87 ± 92.80 (range 2.29 to 341.86) weeks. Twelve of the patients had diabetes, 10 had Charcot neuroarthropathy, and 7 had arthrodesis for equinovarus deformity. Sixteen had peripheral neuropathy and 13 had history of ulceration on the operated extremity. Limb salvage with the use of this protocol was achieved in 14 (73.68%) of 19 patients. Five (26.32%) patients had proximal amputation with 3 (15.79%) deaths within the follow-up period. Amputation was more likely in the nonsmoking (p = .01) and insulin-dependent (odds ratio = 22, p = .02) patient cohorts, whereas death was associated only with higher body mass index (p = .03). Time to revision was greater in patients with external bracing postoperatively as well (p = .004). Outcomes, including total number of procedures and retained antibiotic rods, were not associated with any of the preoperative variables or indications. In high-risk patient populations, the presented staged management of infected intramedullary hindfoot nails showed promising outcomes for limb preservation.

Plantar Approach for Midfoot Wedge Resection to Reconstruct the Rocker Bottom Foot.

Chronic deformity of the foot can lead to ulceration, infection, and amputation. Midfoot wedge osteotomy for deformity correction has been described in the literature; however, most reports are case review or small series. Wedge osteotomy can be performed from a medial or plantar approach, but there are limited data on outcomes regarding these relatively uncommon procedures. This study aims to review a population of patients with a rocker bottom foot deformity that underwent a midfoot wedge resection performed from the plantar surface for deformity correction, wound healing, and limb salvage. A review of medical records from a single foot and ankle surgeon was undertaken. Patients who had a midfoot wedge performed from the plantar surface to address rocker bottom deformity resulting from Charcot neuroarthropathy or severe flatfoot were included. Thirty patients met inclusion criteria. The outcome measures evaluated were minor and major complications, wound healing, and functional limb status. Statistical analysis was performed to evaluate factors that influenced outcomes. At time of final follow up, 17 of 20 (85%) preoperative wounds had healed. Mean preoperative talo-first metatarsal angle was -25° and improved to -5° postoperatively. An 87% limb salvage rate (26/30) was demonstrated. Body mass index was the only statistically significant factor that influenced functional limb status. Maintaining a functional limb can have profound effects on a patient's quality of life. Generally, patients with this severe rocker bottom foot deformity have multiple comorbidities and are at an increased risk of major amputation and early death. The current study has shown that patients with a rocker bottom foot deformity can benefit from midfoot wedge resection from a plantar approach to achieve a plantigrade foot.

Vagal contributions to fetal heart rate variability: an omics approach.

OBJECTIVE: Fetal heart rate variability (fHRV) is an important indicator of health and disease, yet its physiological origins, neural contributions, in particular, are not well understood. We aimed to develop novel experimental and data analytical approaches to identify fHRV measures reflecting the vagus nerve contributions to fHRV. APPROACH: In near-term ovine fetuses, a comprehensive set of 46 fHRV measures was computed from fetal pre-cordial electrocardiogram recorded during surgery and 72 h later without (n = 24) and with intra-surgical bilateral cervical vagotomy (n = 15). MAIN RESULTS: The fetal heart rate did not change due to vagotomy. We identify fHRV measures specific to the vagal modulation of fHRV: multiscale time irreversibility asymmetry index (AsymI), detrended fluctuation analysis (DFA) α 1, Kullback-Leibler permutation entropy (KLPE) and scale-dependent Lyapunov exponent slope (SDLE α). SIGNIFICANCE: We provide a systematic delineation of vagal contributions to fHRV across signal-analytical domains which should be relevant for the emerging field of bioelectronic medicine and the deciphering of the 'vagus code'. Our findings also have clinical significance for in utero monitoring of fetal health during surgery. Key points •Fetal surgery causes a complex pattern of changes in heart rate variability measures with an overall reduction of complexity or variability. •At 72 h after surgery, many of the HRV measures recover and this recovery is delayed by an intrasurgical cervical bilateral vagotomy. •We identify HRV pattern representing complete vagal withdrawal that can be understood as part of 'HRV code', rather than any single HRV measure. •We identify HRV biomarkers of recovery from fetal surgery and discuss the effect of anticholinergic medication on this recovery.

ANESTHESIA OF AQUARIUM-HOUSED WALRUS ( ODOBENUS ROSMARUS): A CASE SERIES.

Walruses are a challenging species to anesthetize as a result of their large mass, limited access for drug delivery, unique physiology, and small number of reports describing anesthetic procedures. Three aquarium-housed walruses ( Odobenus rosmarus) ranging in age from 3 to 11 yr old (344-1,000 kg) were anesthetized for dental or ophthalmic surgical procedures, with one animal anesthetized twice and one anesthetized three times. Preanesthetic medication was with intramuscular midazolam (0.1-0.2 mg/kg) and meperidine (2-3 mg/kg). A catheter was placed in the extradural intravertebral vein, and anesthesia was induced with propofol to effect. Orotracheal intubation was performed and anesthesia maintained with isoflurane in oxygen using a circle breathing system connected to a ventilator. Intermittent positive pressure ventilation was used in all procedures. For the ophthalmic surgery, the neuromuscular blocking agent, cisatracurium, was given intravenously to provide a central eye and optimal surgical conditions. The neuromuscular block was antagonized with edrophonium. Total anesthesia times ranged from 1.5 to 6 hr. Midazolam and meperidine were antagonized with flumazenil and naltrexone, respectively, in five of six cases. Nonsteroidal anti-inflammatory agents were provided for analgesia. Recoveries were calm and uneventful. The described anesthetic protocols and case management were successful under the conditions encountered.

Sculpting the Sculptors: Methods for Studying the Fetal Cholinergic Signaling on Systems and Cellular Scales.

The non-neuronal, immunological effects of the cholinergic signaling are exerted on the system's scale of observation via the vagus nerve and on the cellular scale via α7 nicotinic acetylcholine receptor (nAChR) signaling in myeloid cells of the periphery or brain's microglia and astrocytes. The developmental effects of such multi-scale signaling can be conceived of as an example of psychoneuroimmunological (PNI) homeokinesis and, while reported in the literature, are not yet systematically well studied. To be better understood, the intricacy of the multi-scale interactions requires relevant preclinical animal models. Chronically instrumented non-anesthetized fetal sheep model comes with a strong track record of bench-to-bed translation and a large body of evidence for its strong resemblance to and relevance for human physiology on various scales of organization. Recently, there has been growing interest in pleiotropic effects of vagus nerve stimulation (VNS) on various organ systems such as innate immunity, metabolism, and emotion with implications for programming of PNI phenotype. Here we describe the procedures required to record and manipulate the vagus nerve activity in this large pregnant mammalian organism. Extending this in vivo model to in vitro, on the cellular scale, we present the method to manipulate the cholinergic signaling in ovine fetal microglia and astrocytes and analyze their responses on protein and RNA levels. Together these models can provide multi-scale-level mechanistic insights into the effects of cholinergic signaling on PNI phenotype.

Prognostic Scoring System for Patients Undergoing Reconstructive Foot and Ankle Surgery for Charcot Neuroarthropathy: The Charcot Reconstruction Preoperative Prognostic Score.

Charcot neuroarthropathy is a destructive process that occurs in patients with peripheral neuropathy, often due to poorly controlled diabetes mellitus. Surgical reconstruction can be necessary to provide a plantigrade foot that is wound free. A risk of major amputation exists after a Charcot event and after attempted reconstruction. We retrospectively reviewed the data from 34 patients (36 reconstructions) who had undergone reconstructive surgery for Charcot neuroarthropathy. The mean patient age was 56.44 years. The mean follow-up period was 56 months. We collected patient age, body mass index, presence of wound or osteomyelitis, anatomic location, activity of disease, and hemoglobin A1c. Using these data, each patient was given a score using our novel prognostic scoring system, the Charcot Reconstruction Preoperative Prognostic Score (CRPPS). Our primary outcome measure was no wound and no major amputation at the final follow-up visit. The limb salvage rate was 89% (32 of 36), and 78% (28 of 36) had no wound at the final follow-up examination. For patients without a wound or major amputation at the final follow-up visit, the mean CRPPS was 2.96 ± 1.23. The mean CRPPS for those with a wound or major amputation at the final follow-up visit was 4.33 ± 1.07 (p = .0024). Univariate logistic regression revealed 2 statistically significant predictors of wound and/or amputation: anatomic location (odds ratio [OR] 5.0, 95% confidence interval [CI] 1.051 to 23.789; p = .043) and CRPPS (OR 2.724, 95% CI 1.274 to 5.823, p = .01). A CRPPS of ≥4 was also predictive of a negative outcome (OR 7.286, 95% CI 1.508 to 35.211; p = .013). This scoring system, with a sensitivity of 75%, specificity of 71%, and negative predictive value of 85%, is a potential starting point when educating patients and making treatment decisions in this exceptionally challenging group.