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.

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.

Small-Molecule-Directed Endogenous Regeneration of Visual Function in a Mammalian Retinal Degeneration Model.

Degenerative retinal diseases associated with photoreceptor loss are a leading cause of visual impairment worldwide, with limited treatment options. Phenotypic profiling coupled with medicinal chemistry were used to develop a small molecule with proliferative effects on retinal stem/progenitor cells, as assessed in vitro in a neurosphere assay and in vivo by measuring Msx1-positive ciliary body cell proliferation. The compound was identified as having kinase inhibitory activity and was subjected to cellular pathway analysis in non-retinal human primary cell systems. When tested in a disease-relevant murine model of adult retinal degeneration (MNU-induced retinal degeneration), we observed that four repeat intravitreal injections of the compound improved the thickness of the outer nuclear layer along with the regeneration of the visual function, as measured with ERG, visual acuity, and contrast sensitivity tests. This serves as a proof of concept for the use of a small molecule to promote endogenous regeneration in the eye.

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%).

Landscape-scale benefits of protected areas for tropical biodiversity.

The United Nations recently agreed to major expansions of global protected areas (PAs) to slow biodiversity declines1. However, although reserves often reduce habitat loss, their efficacy at preserving animal diversity and their influence on biodiversity in surrounding unprotected areas remain unclear2-5. Unregulated hunting can empty PAs of large animals6, illegal tree felling can degrade habitat quality7, and parks can simply displace disturbances such as logging and hunting to unprotected areas of the landscape8 (a phenomenon called leakage). Alternatively, well-functioning PAs could enhance animal diversity within reserves as well as in nearby unprotected sites9 (an effect called spillover). Here we test whether PAs across mega-diverse Southeast Asia contribute to vertebrate conservation inside and outside their boundaries. Reserves increased all facets of bird diversity. Large reserves were also associated with substantially enhanced mammal diversity in the adjacent unprotected landscape. Rather than PAs generating leakage that deteriorated ecological conditions elsewhere, our results are consistent with PAs inducing spillover that benefits biodiversity in surrounding areas. These findings support the United Nations goal of achieving 30% PA coverage by 2030 by demonstrating that PAs are associated with higher vertebrate diversity both inside their boundaries and in the broader landscape.

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.

Prostaglandin F2α regulates mitochondrial dynamics and mitophagy in the bovine corpus luteum.

Prostaglandins are arachidonic acid-derived lipid mediators involved in numerous physiological and pathological processes. PGF2α analogues are therapeutically used for regulating mammalian reproductive cycles and blood pressure, inducing term labor, and treating ocular disorders. PGF2α exerts effects via activation of calcium and PKC signaling, however, little is known about the cellular events imposed by PGF2α signaling. Here, we explored the early effects of PGF2α on mitochondrial dynamics and mitophagy in the bovine corpus luteum employing relevant and well characterized in vivo and in vitro approaches. We identified PKC/ERK and AMPK as critical protein kinases essential for activation of mitochondrial fission proteins, DRP1 and MFF. Furthermore, we report that PGF2α elicits increased intracellular reactive oxygen species and promotes receptor-mediated activation of PINK-Parkin mitophagy. These findings place the mitochondrium as a novel target in response to luteolytic mediator, PGF2α. Understanding intracellular processes occurring during early luteolysis may serve as a target for improving fertility.

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.

Humid tropical vertebrates are at lower risk of extinction and population decline in forests with higher structural integrity.

Reducing deforestation underpins global biodiversity conservation efforts. However, this focus on retaining forest cover overlooks the multitude of anthropogenic pressures that can degrade forest quality and imperil biodiversity. We use remotely sensed indices of tropical rainforest structural condition and associated human pressures to quantify the relative importance of forest cover, structural condition and integrity (the cumulative effect of condition and pressures) on vertebrate species extinction risk and population trends across the global humid tropics. We found that tropical rainforests of high integrity (structurally intact and under low pressures) were associated with lower likelihood of species being threatened and having declining populations, compared with forest cover alone (without consideration of condition and pressures). Further, species were more likely to be threatened or have declining populations if their geographic ranges contained high proportions of degraded forest than if their ranges contained lower proportions of forest cover but of high quality. Our work suggests that biodiversity conservation policies to preserve forest integrity are now urgently required alongside ongoing efforts to halt deforestation in the hyperdiverse humid tropics.

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.

The effects of cueing episodic future thinking on delay discounting in children, adolescents, and adults.

Discounting the value of delayed rewards such that even a relatively small, immediately available reward is preferred to a larger delayed reward is a commonly observed human trait. Children are particularly steep discounters of delayed rewards as evidenced by delay of gratification studies. In recent years, however, a growing literature indicates that cueing individuals to imagine personal future events attenuates their discounting of delayed rewards. The present studies extend this literature by examining whether cueing future thinking promotes patient choices in children and adolescents. In Experiment 1 we found that cueing future thinking had no effect on 8-11-year-olds' (n = 177) delay discounting of either real or hypothetical rewards. In Experiment 2 we found that cueing adolescents (12-14-year-olds, n = 126) and adults (n = 122) to think about personal future events decreased their discounting of delayed rewards relative to three other conditions: a no cue control, an episodic memory condition and a novel 'future other' condition in which individuals imagine future events that might happen to a significant other person in their life. Cueing adults and adolescents to think about personal future events did not however affect how connected they felt to their future selves or their subjective sense of how close future time points felt to them - two constructs that have previously been shown to be related to delay discounting.

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.

Factors Determining the Success of the Chronically Instrumented Non-anesthetized Fetal Sheep Model of Human Development: A Retrospective Cohort Study.

Background The chronically instrumented non-anesthetized fetal sheep (CINAFS) model has been a mainstay of human fetal development research for the past 60 years. As a large "two for one" animal model, involving the instrumentation of the ewe and her fetus, the model poses challenges to implement de novo and maintain overtime at the highest standards of operating procedures to ensure ongoing performance. A common yet conventionally underreported issue researchers face is a high rate of animal loss. Here, we investigate what determines the success of the CINAFS model of human development. Methods We conducted a retrospective cohort analysis consisting of 82 experiments spanning the course of six years. Our team identified 10 variables that we anticipated were likely to influence the experimental outcome, such as the time of year, animal size, and surgical complexity. To evaluate the role of each variable in contributing to the success of the model, a binary logit regression analysis with a Fisher scoring optimization was fit to the data (SAS, V9 engine, release 3.8, SAS Institute, Cary, NC, USA). A higher predictive probability indicates a larger impact by the given variable on the outcome of the experiment. A Wald chi-squared analysis was run on the data to control for confounders and determine significance. Results The single variable identified in this study as determining the success of experiment outcomes using the CINAFS model is the experience level of the team. Conclusion The CINAFS model offers enormous potential to further our understanding of human fetal development and create interventional technologies related to fetal health. However, to improve experimental outcomes using the CINAFS model, stronger communication and training are needed. We discuss the implications of our findings for the successful implementation of this challenging yet scientifically advantageous animal model of human physiology.

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.

The effect of episodic future thinking on young children's future-oriented decision making.

We investigated whether the developmental emergence of episodic future thinking (EFT) is associated with performance on a type of delay of gratification task: a delay choice task that involved choosing between a small reward now or a larger reward the next day. In Study 1, 4- to 5-year-olds' (N = 99) EFT as measured by a tool saving task was significantly associated with performance on the delay choice task, but this was not the case for other EFT measures. Study 2 compared the performance of 4- to 5-year-olds (N = 130) on the delay choice task when cued to think about either a future, past, or habitual event versus a no-cue baseline. Overall, cuing impaired performance on the delay choice task. Although EFT does show a relation to performance in a delay choice task in preschoolers, deliberately engaging in thought about future events may be too taxing in young children to reliably enhance the ability to make future-oriented decisions. (PsycInfo Database Record (c) 2021 APA, all rights reserved).