Search

The Society of Cardiovascular Anesthesiologists (SCA) is committed to improving the quality, safety, and value that cardiothoracic anesthesiologists bring to patient care. To fulfill this mission, the SCA supports the creation of peer-reviewed manuscripts that establish standards, produce guidelines, critically analyze the literature, interpret preexisting guidelines, and allow experts to engage in consensus opinion. The aim of this report, commissioned by the SCA President, is to summarize the distinctions among these publications and describe a novel SCA-supported framework that provides guidance to SCA members for the creation of these publications. The ultimate goal is that through a standardized and transparent process, the SCA will facilitate up-to-date education and implementation of best practices by cardiovascular and thoracic anesthesiologists to improve patient safety, quality of care, and outcomes.

A bluish green chalcedony (a micro to crypto polycrystalline form of silica) from Africa has been marketed with the trademark AQUAPRASETM. A multimethodological approach, combining gemological analyses, thin section examination, scanning electron microscopy, X-ray powder diffraction, Raman spectroscopy, and trace elements chemical analyses by LA–ICP–MS, was carried out to characterize this material from a gemological and mineralogical point of view. The chalcedony samples consist of a mixture of quartz and moganite, as shown by the X-ray powder diffraction analysis and Raman spectroscopy. “Aquaprase” showed a strong microstructural zoning in terms of grain size, from macrocrystalline to micro and crypto, and morphology. Trace element variations correlated well with the different colored areas of the samples. In particular, the main chromophore ion present in the bluish green areas of the “aquaprase” chalcedony was chromium, followed by iron and nickel, so this chalcedony could be included in the group of chromium-bearing chalcedony. Rayleigh light scattering contributed to the blue hue of the gems.

Introduction/Purpose: Minimally invasive dorsal cheilectomy (MIDC) has become a popular alternative to an open approach for treating Hallux Rigidus, although the current literature is divided on its effectiveness regarding complications and patient reported outcomes. To combat a portion of the complications related to the MIDC approach, a first metatarsophalangeal (MTP) joint arthroscopy can often be added to the procedure. The combined procedure has been demonstrated to be effective at improving patient reported outcomes without increasing the complication rate relative to an open procedure. This study looks to examine the effectiveness of the MIDC with first MTP arthroscopy procedure in patients with hallux rigidus with minimum 1 year follow up. Methods: This was a multicenter retrospective review was conducted for adult patients treated with MIDC and first MTP arthroscopy between 3/1/2020 and 8/1/2022, with at least one year of postoperative follow-up data. Patient charts were reviewed for demographic information, operative time, pre and postoperative first MTP range of motion (ROM), visual analog scale (VAS), Manchester-Oxford Foot Questionnaire (MOXFQ), and EQ5DLD scores. Continuous data was expressed as a mean and standard deviation, categorical data was expressed as a percentage. Wilcoxon Rank Sum test was used to compare continuous variables. All P < 0.05 was considered significant. Results: A total of 31 patients were included in the study with an average follow-up time of 16.5 months (range: 12 to 26.2). There was 1 (3.2%) complication of an underservice EHL tendon tear, 2 (6.5%) patients were converted to a MTP fusion, and 1 (3.2%) patient underwent revision cheilectomy and capsular release for MTP joint contracture. There was a significant improvement in patient’s ROM in dorsiflexion (50 vs 89.6 degrees, P=0.002), but not in plantarflexion (11.3 vs 18.6 degrees, P=0.07). There was a significant improvement in patient’s postoperative VAS pain scores (6.4 vs 2.1, P< 0.001), MOXFQ pain scores (58.1 vs 30.7, P=0.001), MOXFQ Walking/Standing scores (56.6 vs 20.6, P=0.001), MOXFQ Social Interaction scores (47.3 vs 19.36, P=0.002), and MOXFQ Index scores (54.7 vs 22.4, P< 0.001). Conclusion: We found that MIDC with first MTP arthroscopy was effective at improving patient reported outcomes, specifically patient’s pain scores, at one year with low complication and revision rates. These results demonstrate MIDC and first MTP arthroscopy’s is an effective treatment for early-stage hallux rigidus and may be considered as an alternative to an open approach.

Introduction/Purpose: Minimally invasive surgical (MIS) treatment of hallux valgus (HV) deformity is increasing in popularity. A 2mm-diameter burr is used to create a distal first metatarsal osteotomy prior to capital fragment translation and fixation. The metatarsal will shorten by the burr’s diameter (2mm). Plantar or dorsal capital fragment displacement may also cause load transference and possibly transfer metatarsalgia. In this study, we examine the effect of MIS HV on forefoot loading mechanics with respect to metatarsal shortening and sagittal plane displacement. Methods: Four lower-limb cadaveric specimens were studied. A pedobarography pressure-sensing mat was used to record forefoot plantar pressure in a controlled weightbearing stance position.10 Control and post-osteotomy measurements were obtained with the capital fragment fixated in 3 possible positions: 0mm, 5mm dorsal, and 5mm plantar displacement. Pedobarography data yielded pressure data within measurable graphical depictions. Raw mean contact pressure measurements were taken under the first and fifth metatarsal heads to establish medial and lateral forefoot loading pressure ratios. A priori power analysis was performed based on previous peer-reviewed pedobarographic data and our study was adequately powered. Results: 40 measurements were recorded and ratios of medial-to-lateral forefoot loading were constructed. Medial forefoot pressure change control versus 0mm displacement, and control versus dorsal displacement was not found to be statistically significant (p=0.525, p=0.55 respectively). Significant medial pressure increase was identified comparing control versus plantar displacement (p=0.006). Lateral pressure increased significantly with dorsal displacement of the osteotomy (p=0.013). Conclusion: MIS hallux valgus correction does not appear to cause increase in lateral forefoot pressure loading when sagittal plane displacements are controlled. Plantar displacement increases medial loading, and dorsal displacement increases lateral loading. The clinician must consider metatarsal head position post-osteotomy, as decrease in medial loading and subsequent increase in lateral loading may lead to lateral forefoot pain and transfer metatarsalgia.

Introduction/Purpose: Many patients use the internet as a source for medical information regarding their medical condition. However, the accuracy and reliability of the information is variable. The recent release of general population facing artificial intelligence (AI) chatbot programs has created a potential alternative medical information source for patients. Our study examined the accuracy of the information provided by ChatGPT for total ankle arthroplasty (TAA), as determined by four fellowship-trained foot and ankle orthopedic surgeons. Methods: GPT-4, the latest ChatGPT model, was asked the 12 of the most common questions patients have regarding TAA. Its responses were recorded and evaluated by four fellowship-trained foot and ankle orthopedic surgeons on a scale of 1 – 4, with 1 representing an excellent response not requiring clarification and 4 representing an unsatisfactory response requiring significant clarification. Averages of scores for each question were recorded and an average of every score was used to develop an overall accuracy score. Results: The overall accuracy score of GPT-4 was 1.35. The responses by GPT-4 received a score of 1 for 32 of 48 (66.7%) responses. There was found to be no significant difference in scores for any of GPT-4’s responses. Conclusion: Our study found that GPT-4 performed well in providing accurate and near complete information to commonly questions asked to physicians by patients regarding TAA. Our results suggest that AI models, like GPT-4, may be an effective alternative source of medical information for patients. Further study with subsequent AI models and direct patient interaction may shed further light on the utility of this potential patient education modality. ChatGPT Response Accuracy Score Accuracy scores for ChatGPT, as determined by four foot and ankle fellowship-trained orthopedic surgeons

Background: Percutaneous Zadek osteotomy (ZO) has emerged as a surgical treatment of insertional Achilles tendinopathy (IAT) over the last decade. Existing literature is limited regarding the comparison of this approach with the more established, open ZO technique. This systematic review aims to evaluate and compare the current data on open vs percutaneous ZO approaches to help set evidence-based guidelines. Methods: A systematic literature search was performed using the keywords (Zadek osteotomy) OR (Keck and Kelly osteotomy) OR (dorsal closing wedge calcaneal osteotomy) OR (Haglund Deformity) OR (Haglund Syndrome) OR (Insertional Achilles Tendinopathy) and MeSH terms Osteotomy , Calcaneus , Syndrome , Insertional , Achilles tendon , and Tendinopathy . Our search included the following databases: PubMed, Embase, and the Cochrane Library. The PRISMA protocol and the Cochrane Handbook guidelines were followed. All studies included were published from 2009 to 2024 and included the use of open or percutaneous approaches of ZO for the treatment of IAT with at least a 12-month follow-up. The MINORS score criteria were used to evaluate the strength and quality of studies. Results: A total of 17 studies were reviewed, including 611 subjects and 625 ZO procedures. Of these procedures, 81 (11%) subjects had a percutaneous and 544 (89%) subjects had an open ZO. The mean follow-up time was 16.1 months for patients treated with percutaneous ZO and 36.1 months for patients treated with open ZO. Both open and percutaneous studies included in this review showed postoperative improvements in AOFAS, FFI, VISA-A, and VAS scores in patients with IAT. The reported complication rate was 5.8% among patients treated with percutaneous ZO and 10.2% among patients treated with open ZO. Conclusion: Percutaneous ZO is an emerging approach with substantially fewer documented cases compared with the open ZO. Both percutaneous and open ZO appear to be relatively effective treatments for insertional Achilles tendinopathy with Haglund’s deformity. The lower complication rates reported for percutaneous ZO is encouraging. Further investigation with more subjects undergoing percutaneous ZO is clearly needed.

Summary: RNA-binding proteins (RBPs) are emerging as important regulators of cancer pathogenesis. We reveal that the RBPs LARP4A and LARP4B are differentially overexpressed in osteosarcoma and osteosarcoma lung metastases, as well as in prostate cancer. Depletion of LARP4A and LARP4B reduced tumor growth and metastatic spread in xenografts, as well as inhibiting cell proliferation, motility, and migration. Transcriptomic profiling and high-content multiparametric analyses unveiled a central role for LARP4B, but not LARP4A, in regulating cell cycle progression in osteosarcoma and prostate cancer cells, potentially through modulating key cell cycle proteins such as Cyclins B1 and E2, Aurora B, and E2F1. This first systematic comparison between LARP4A and LARP4B assigns new pro-tumorigenic functions to LARP4A and LARP4B in bone and prostate cancer, highlighting their similarities while also indicating distinct functional differences. Uncovering clear biological roles for these paralogous proteins provides new avenues for identifying tissue-specific targets and potential druggable intervention.

ObjectivesThe lack of standardized X-ray imaging remains a challenge for comparative studies on spatial scans acquired from different clinic-specific X-ray scanners. The central objectives of this study are: 1) to delineate mineral density (MD) values, and 2) generate spatial MD maps of various physiologic and pathologic biominerals, and 3) propose a standardization protocol within the safe-operating zone of a CT scanner that underpins normalization of absorbed dose to shape and density of tissues.MethodsA systematic approach to propose a standardization protocol for CT imaging in vivo included: 1) estimation of pathologic MD ranges by performing a comparative meta-analysis on 2009-2019 data from the PubMed database; 2) calibration of cone-beam CT (CBCT) and micro-CT scanners with phantoms of known mineral densities (0, 250, 500, 750 and 3000 mg/cc) and shapes (cylinders and polyhedrons); 3) scanning craniofacial bones (N = 5) and dental tissues (N = 5), and ectopic minerals from humans (N = 3 each, pulp, salivary gland, kidney and prostrate stones, and penile and vascular plaques); 4) underscoring the effect of shape-factor (surface area-to-volume ratio) on MD of biominerals.ResultsHigher MDs of physiologic and pathologic cortical bones (504-1009 mg/cc) compared to trabecular bone (82-212 mg/cc) were observed. An increase in shape-factor increased the CBCT error in MD measurement and revealed that the scanner resolution is dependent on the absorbed dose and shape-factor of detectable features.SignificanceCT scanners should be calibrated with phantoms containing segments of known shape-factors and mineral densities to identify safe-operating zones. The calibrated approach will narrow the gap between length-scale dependent measurements, and will permit spatiotemporal quantitative and reliable detection of pathologies.

Despite their importance in tissue homeostasis and renewal, human pituitary stem cells (PSCs) are incompletely characterized. We describe a human single nucleus RNA-seq and ATAC-seq resource from pediatric, adult, and aged postmortem pituitaries (snpituitaryatlas.princeton.edu) and characterize cell-type-specific gene expression and chromatin accessibility programs for all major pituitary cell lineages. We identify uncommitted PSCs, committing progenitor cells, and sex differences. Pseudotime trajectory analysis indicates that early-life PSCs are distinct from the other age groups. Linear modeling of same-cell multiome data identifies regulatory domain accessibility sites and transcription factors that are significantly associated with gene expression in PSCs compared with other cell types and within PSCs. We identify distinct deterministic mechanisms that contribute to heterogeneous marker expression within PSCs. These findings characterize human stem cell lineages and reveal diverse mechanisms regulating key PSC genes and cell type identity.

Ca2+ influx through high-voltage-activated calcium channels (HVACCs) controls diverse cellular functions. A critical feature enabling a singular signal, Ca2+ influx, to mediate disparate functions is diversity of HVACC pore-forming α1 and auxiliary CaVβ1-CaVβ4 subunits. Selective CaVα1 blockers have enabled deciphering their unique physiological roles. By contrast, the capacity to post-translationally inhibit HVACCs based on CaVβ isoform is non-existent. Conventional gene knockout/shRNA approaches do not adequately address this deficit owing to subunit reshuffling and partially overlapping functions of CaVβ isoforms. Here, we identify a nanobody (nb.E8) that selectively binds CaVβ1 SH3 domain and inhibits CaVβ1-associated HVACCs by reducing channel surface density, decreasing open probability, and speeding inactivation. Functionalizing nb.E8 with Nedd4L HECT domain yielded Chisel-1 which eliminated current through CaVβ1-reconstituted CaV1/CaV2 and native CaV1.1 channels in skeletal muscle, strongly suppressed depolarization-evoked Ca2+ influx and excitation-transcription coupling in hippocampal neurons, but was inert against CaVβ2-associated CaV1.2 in cardiomyocytes. The results introduce an original method for probing distinctive functions of ion channel auxiliary subunit isoforms, reveal additional dimensions of CaVβ1 signaling in neurons, and describe a genetically-encoded HVACC inhibitor with unique properties.

Abstract The M4 muscarinic acetylcholine receptor (M4 mAChR) has emerged as a drug target of high therapeutic interest due to its expression in regions of the brain involved in the regulation of psychosis, cognition, and addiction. The mAChR agonist, xanomeline, has provided significant improvement in the Positive and Negative Symptom Scale (PANSS) scores in a Phase II clinical trial for the treatment of patients suffering from schizophrenia. Here we report the active state cryo-EM structure of xanomeline bound to the human M4 mAChR in complex with the heterotrimeric Gi1 transducer protein. Unexpectedly, two molecules of xanomeline were found to concomitantly bind to the monomeric M4 mAChR, with one molecule bound in the orthosteric (acetylcholine-binding) site and a second molecule in an extracellular vestibular allosteric site. Molecular dynamic simulations supports the structural findings, and pharmacological validation confirmed that xanomeline acts as a dual orthosteric and allosteric ligand at the human M4 mAChR. These findings provide a basis for further understanding xanomeline’s complex pharmacology and highlight the myriad of ways through which clinically relevant ligands can bind to and regulate GPCRs.

Background: Hindfoot fusion procedures are common for the treatment of end-stage arthritis or deformity. Surgical treatments for these conditions include talonavicular joint (single) arthrodesis, talonavicular and subtalar (double) arthrodesis, or talonavicular, subtalar, and calcaneocuboid (triple) arthrodesis. This study evaluated the complication rate, revision surgery rate, and hardware removal rate for those treated with either single, double, or triple arthrodesis. Methods: A retrospective review was conducted for patients who underwent single ( Current Procedural Terminology [ CPT ] code 28740), double ( CPT 28725 and 28740), or triple ( CPT 28715) arthrodesis to treat hindfoot arthritis/deformity ( International Classification of Diseases, Ninth Revision [ ICD-9 ] code: 734, International Classification of Diseases, Tenth Revision [ ICD-10 ] codes: M76821, M76822, and M76829) from 2005 to 2022 using the South Carolina Revenue and Fiscal Affairs databank. Data collected included demographics, comorbidities, procedure data, and postoperative outcomes within 1 year of principal surgery. Student t test, chi-squared test, and multivariable logistic regression analysis were utilized during data analysis. Results: A total of 433 patients were identified, with 248 undergoing single arthrodesis, 67 undergoing double arthrodesis, and 118 undergoing triple arthrodesis. There was no significant difference between single, double, and triple arthrodesis in the rate of complications, hardware removals, revision surgeries, or 30-day readmission when controlling for confounding variables. However, a decrease in Charlson Comorbidity Index (CCI) was found to be predictive of an increase in the revision surgery rate (OR = 0.46, 95% CI 0.22-0.85, P = .02). Conclusion: We found no difference in the rate of complications, hardware removals, or revision surgeries in those undergoing single, double, or triple arthrodesis. Surprisingly we found that a lower Charlson Comorbidity Index, indicating a healthier patient had a significant relationship with a higher rate of revision surgery. Further study including radiographic indications for surgery or the impact of overall health status on revision surgery rates may further elucidate the other components of this relationship. Level of Evidence: Level III, cohort study.

Category: Ankle; Bunion Introduction/Purpose: Using patient-reported outcomes (PRO) to predict which patients may or may not improve from orthopaedic surgery could be valuable for clinical decision making. The Patient Reported Outcome Instrumentation System (PROMIS) utilizes computerized adaptive testing based on item response theory to decrease administration time while maintaining accuracy. However, the data on the relationship between pre- and post-operative PROMIS scores for elective foot and ankle surgical patients and their ultimate PROs is limited, and the literature is conflicting. The purpose of this study is to assess preoperative PROMIS mobility, physical function (PF), and pain interference (PI) scores to determine their accuracy in predicting patient reported surgery success or failure, and to estimate preoperative score domains associated with patient reported surgery success. Methods: A retrospective chart review was used to identify a cohort of adult patients who underwent operative treatment for at least one foot or ankle surgery between 05/01/2020 – 06/01/2022. Descriptive statistics were calculated to describe the study population, clinical factors, PROMIS scores, and outcomes. Bivariate analyses were performed to assess potential associations between PROMIS score differences with other factors, and PROMIS score differences within levels of other factors. Logistic regression analysis was used to assess potential associations with patient-rated surgery success or failure with patient, clinical, and outcomes data. Significance was determined by associated p-values (p < 0.05). Results: We found that preoperative PROMIS scores for mobility, PF, and PI were not significantly associated with patient-rated surgery success (p=0.092, 0.666, 0.869, respectively). Similarly, in a regression to identify individual factors that influenced patient reported surgical failure, preoperative mobility, PF, and PI scores were all not significant (p=0.095, 0.663, 0.626, respectively). However, preoperative cut-points based on 95% confidence intervals for means were estimated locally to determine the probability of optimal patient reported surgery success, and threshold scores for mobility, PF, and PI were chosen as ≥39, ≥47, and ≤55, respectively. We also found that the only preoperative patient factors that showed higher odds of patient reported surgical failure in a multivariate logistic regression model were age of 50-64 (p=0.004) and diabetes (p=0.006). Conclusion: Our study found no significant associations between preoperative PROMIS scores and patient reported success or failure for foot and ankle surgery. This may be encouraging to surgeons when considering that even patients with seemingly unfavorable preoperative scores have a similar chance as other patients for surgical success and improvement from the patient’s perspective. Additionally, identifying optimal patient PROMIS scores for surgery success can provide an ideal baseline score cutoff for surgeons for comparison when assessing an individual’s chances of surgical success for foot and ankle surgery. However, further study is needed to investigate the clinical utility of these estimates.

Category: Ankle Introduction/Purpose: The utilization of total ankle arthroplasty (TAA) continues to increase, and identifying preoperative factors that influence postoperative outcomes after TAA may be valuable. The use of post-acute care (PAC) facilities has also grown substantially, and discharge to a PAC facility can increase patient morbidity and postoperative costs. The purpose of this study is to define the effect of BMI on discharge to a PAC facility and hospital length of stay (LOS) following TAA. Methods: We performed a retrospective review to identify a large cohort of adult patients who underwent TAA between 2006 - 2020 from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Using overweight patients as the reference BMI group, we estimated a sex- and age- adjusted log-binomial regression model on BMI categories to estimate risk ratios to analyze the association between BMI and risk of being discharged to a PAC facility and/or hospital LOS. Results: Relative to overweight patients, obese patients had 1.47 times the risk (P=0.008), and morbidly obese patients had 2.26 times risk (P < 0.001) of being discharged to a PAC facility after TAA. Males had 0.47 times the risk of females (P < 0.001), and for each year older, patients had 1.07 times the risk (P < 0.001) of being discharged to a PAC facility. There was no difference in hospital LOS for underweight patients, but healthy weight patients stayed an additional 0.29 days (P=0.004), obese patients stayed an additional 0.18 days (P=0.010), and morbidly obese patients stayed an additional 0.34 days (P=0.006). Males stayed 0.30 fewer hospital days than females (P < 0.001), and for each year older, patients stayed 0.011 days longer (P < 0.001). Conclusion: This study found that women and patients who are obese and morbidly obese have a greater LOS and chance to be discharged to a PAC facility. Increasing age is also associated with an increase in LOS and discharge to a PAC. These may be important factors when discussing the postoperative plan with patients prior to TAA.

Category: Ankle Introduction/Purpose: Total ankle arthroplasty (TAA) is an effective treatment for various ankle pathologies, but some concern remains for the relatively high associated complication and failure rates relative to major joint arthroplasty of the hip and knee. Patient body mass index (BMI) is a modifiable and potentially important preoperative variable when evaluating postoperative complications. The purpose of this study is to evaluate the effect of BMI on the acute postoperative complication rate after TAA. Methods: We performed a retrospective review to identify a large cohort of adult patients who underwent TAA between 2006 - 2020 from the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Using overweight patients as the reference BMI group, we estimated log-binomial models to estimate risk ratios on outcomes, while also adjusting for sex and age, in order to investigate whether there was a significant difference in complication rate between the BMI groups. Results: We found that, relative to overweight patients, there was no statistically significant difference in the risk of acute complications for underweight (p-value=0.062), healthy weight (p-value=0.800), obese (p-value=0.993), or morbidly obese (p- value=0.781) patients who underwent TAA. There was also no statistically significant difference in the risk of acute complications based on age (p-value=0.876) or sex (p-value=0.696) for TAA. Additionally, there was no significant difference between the BMI groups when comparing how many patients had a complication out of the total number of patients in their respective BMI group for either major complications (p-value=0.9835) or minor complications (p-value=0.0578). Conclusion: We found that BMI, age, and sex did not lead to a statistically significant difference in the risk of complications, even when stratified by major vs minor complications, within 30 days postoperatively for TAA.

Category: Hindfoot; Other Introduction/Purpose: A calcaneal osteotomy is often included as part of the treatment in planovalgus and cavovarus foot deformities. Often this is done through an open approach where complications of wound infection and sural nerve injury are common. More recently, this strategy has been modified using minimally invasive techniques. A percutaneous approach, in comparison to the standard open calcaneal osteotomy, allows for reduced postoperative complication and decreased pain compared to an open procedure. This retrospective chart review aims to evaluate the postoperative outcomes of patients undergoing calcaneal osteotomy via a minimally invasive percutaneous approach in foot reconstructive surgery to assess early functional outcomes, complication rate and revision rates. Methods: One fellowship-trained foot and ankle orthopaedic surgeon at one academic institution performed minimally invasive calcaneal osteotomy on 20 patients. All cases were completed between March 2021 and March 2023. Patient charts were reviewed for outcome data including complication rate, union rate, revision rate, and Patient-Reported Outcomes Measurement Information System (PROMIS) scores. Results: Participants included 15 females and 5 males, 4 of whom were smokers. Average age was 42.2 years. Average BMI was 32.3, and average follow up was 130.4 days. Complications included 1/20 patients had a postoperative wound breakdown of the screw site requiring incision and debridement with closure and 2/20 cases of sural neuritis. One resolved 6 months after treatment and the other was present but became less symptomatic. All participants achieved union, and there were no revisions. All shifts corrected hindfoot deformity either via medializing or lateralizing osteotomy. Average preoperative PROMIS scores in the domains of physical function, pain interference, and mobility were 36.8 (28.6-46), 67.1 (54.3-78), and 34.6 (25-40), respectively. Average postoperative PROMIS scores were 35.7 (21-76), 62.3 (39-76), and 33.4 (16-75), respectively. Conclusion: Minimally invasive calcaneal osteotomy appears to be an efficacious and safe treatment option for the correction of cavovarus and planovalgus hindfoot deformities with the ability to obtain appropriate hindfoot correction with low complication rates and high union rates. Early outcome measures show a favorable pain interference PROMIS score as well as a trend in improvements in PROMIS physical function scores. Longer term data will need to be done to assess long term functional outcome and revision rates.

Category: Bunion; Midfoot/Forefoot Introduction/Purpose: Bunions are one of the most common pathologies treated by orthopedic foot and ankle surgeons. The usage of minimally invasive and percutaneous surgical techniques continues to rise due to evidence of less pain, improved functional outcomes and low recurrence rates. Still, concern regarding heat generation during these procedures, osteonecrosis of bone, and nonunion persists. Literature suggests cool irrigation is superior to room temperature irrigation, but the question remains if irrigation is needed at all. This study evaluates the heat generation during percutaneous bunion surgery and analyzes the use of cooled irrigation compared to no irrigation at all. This study tested the hypothesis that cool irrigation would lead to overall lower heat generation compared to no irrigation at all. Methods: 5 matched paired cadavers (10 legs) were used to simulate MIS first metatarsal distal transverse osteotomy for all trials. Prior to osteotomy, 4 temperature probes were inserted as to the border where the Shannon burr would travel along the osteotomy site (Image 1). Probes were secured by suture and temperature was recorded using K-type thermocouples. All trials were completed using a pulse technique of 20 seconds on, 5 seconds off with a Shannon Burr and fluoroscopic guidance. Trials were complete with continuous cold irrigation (N=5) and without any irrigation at all (N=4). Temperatures were evaluated at baseline, during burring, and after burring to assess total heat generation and dissipation. A two-tailed t-test was used to analyze differences in heat generation and dissipation between procedures completed with irrigation and without irrigation (P < 0.05). Results: 5 cadavers with a mean age of 86.2 were evaluated (10 total simulations, 9 analyzed). Cadavers underwent 1 trial with irrigation, and 1 without on opposite feet. 88.9% of patients showed heat generation below the level of bone necrosis (50 oC). One trial with irrigation temperature rose to 79.1oC. Matching specimen without irrigation had probe failure and no temperature was obtained. Average burr time was 51.2±2.4 seconds with irrigation, and 35±0.5 seconds without. Irrigation was associated with a significant increase in burr time (P=0.002). Average temperature change was 13.62±11.9 and 0.7±0.5 during burring, 7.1±1.8 and 5.8±0.3 after burring in procedures with and without irrigation, respectively. No significant difference was detected between heat generation in irrigated vs non-irrigated procedures (P = 0.371, 0.548). Conclusion: This study found that in a cadaveric model the use of cooled irrigation, compared to no irrigation, did not lead to a significant difference in the heat generation during MIS first metatarsal distal transverse osteotomy. However, 1 out of the 9 samples used in this study showed a heat generation above 50 oC. Additionally, to our surprise the use of irrigation led to a significant increase in burring time. This may be useful information for a surgeon when considering the usage of cooled irrigation to reduce the potential risk of osteonecrosis when performing a MIS first metatarsal distal transverse osteotomy.

Category: Hindfoot; Ankle Introduction/Purpose: Minimally invasive percutaneous (MIS) calcaneal osteotomy has become more popular due to low risk of nerve injury and wound complications. The Shannon burr is often used to perform these osteotomies despite concern for the heat generation. Temperatures above 50oC may lead to osteonecrosis of bone. A recent MIS calcaneal cadaveric model study showed that cool irrigation led to less heat generation than room temperature irrigation. However, questions remain if irrigation is needed at all. This study evaluates heat generation during MIS calcaneal osteotomies and analyzes whether the use of cooled irrigation significantly decreases the temperature of the burring process compared to no irrigation at all. Our hypothesis was that cool irrigation would lead to overall lower heat generation compared to no irrigation. Methods: 5 matched paired cadavers (10 legs) were used to simulate a MIS calcaneal osteotomy for all trials. Prior to the osteotomy, 4 temperature probes were inserted as to the border where the Shannon burr would travel along the osteotomy site (Image 1). Probes were secured by suture and temperature was recorded using K-type thermocouples. All trials were complete using a pulse technique of 20 seconds on, 5 seconds off with a Shannon Burr and fluoroscopic guidance. Trials were complete with continuous cold irrigation (N=5) and without any irrigation at all (N=4). Temperatures were evaluated at baseline, during burring, and after burring to assess total heat generation and dissipation. A two-tailed t-test was used to analyze differences in heat generation and dissipation between procedures completed with irrigation and without irrigation (P < 0.05). Results: 5 cadavers with a mean age of 86.2 were evaluated for a total of 10 simulations, 9 analyzed. All cadavers underwent 1 trial with irrigation, and 1 without on opposite feet. Average drill time was 124±24.5 seconds with irrigation, and 118.8±43.9 seconds without (P=0.915). 77.8% of procedures showed heat generation below the level of bone necrosis (50 oC). 2 procedures without irrigation generated heat above this threshold (54.3 oC, 54.7 oC). Average change in temperature was 15.1±4.6 and 22.9±8.7 during drilling, 8.4±1.7 and 10.7±5.3 after drilling in procedures with and without irrigation, respectively. There was no significant difference detected between heat generation during or after burring in irrigated vs non-irrigated procedures (P = 0.426, 0.661). Conclusion: This cadaveric study found that the use of cooled irrigation compared to no irrigation did not lead to a significant difference in the heat generation during a MIS calcaneal osteotomy. However, 2 out of the 9 samples used in this study showed a heat generation above 50 o C, and both were done without the use of irrigation. This may be useful information for a surgeon when considering the usage of cooled irrigation to reduce the potential risk of osteonecrosis when performing a MIS calcaneal osteotomy.

Understanding cell types and mechanisms of dental growth is essential for reconstruction and engineering of teeth. Therefore, we investigated cellular composition of growing and non-growing mouse and human teeth. As a result, we report an unappreciated cellular complexity of the continuously-growing mouse incisor, which suggests a coherent model of cell dynamics enabling unarrested growth. This model relies on spatially-restricted stem, progenitor and differentiated populations in the epithelial and mesenchymal compartments underlying the coordinated expansion of two major branches of pulpal cells and diverse epithelial subtypes. Further comparisons of human and mouse teeth yield both parallelisms and differences in tissue heterogeneity and highlight the specifics behind growing and non-growing modes. Despite being similar at a coarse level, mouse and human teeth reveal molecular differences and species-specific cell subtypes suggesting possible evolutionary divergence. Overall, here we provide an atlas of human and mouse teeth with a focus on growth and differentiation.

Biased signaling in κ-opiod receptors (KOR) offer an attractive strategy for pain management. Here the authors identify determinants of KOR signaling bias using structural methods in combination with molecular dynamics simulations.

Auxiliary subunit molecular diversity is an unexploited target for developing ion channel inhibitors. Here, the authors develop a general approach to inhibit ion channels based on the resident auxiliary subunit isoform to elucidate unique functions of distinct ion channel macromolecular complexes.

In vertebrates with elongated auditory organs, mechanosensory hair cells (HCs) are organised such that complex sounds are broken down into their component frequencies along a proximal-to-distal long (tonotopic) axis. Acquisition of unique morphologies at the appropriate position along the chick cochlea, the basilar papilla, requires that nascent HCs determine their tonotopic positions during development. The complex signalling within the auditory organ between a developing HC and its local niche along the cochlea is poorly understood. Using a combination of live imaging and NAD(P)H fluorescence lifetime imaging microscopy, we reveal that there is a gradient in the cellular balance between glycolysis and the pentose phosphate pathway in developing HCs along the tonotopic axis. Perturbing this balance by inhibiting different branches of cytosolic glucose catabolism disrupts developmental morphogen signalling and abolishes the normal tonotopic gradient in HC morphology. These findings highlight a causal link between graded morphogen signalling and metabolic reprogramming in specifying the tonotopic identity of developing HCs.

The purpose of this study is to identify demographics, etiology, comorbidities, treatment, complications, and outcomes for older patients with open ankle fractures. Patients ≥60 years old who sustained an open ankle fracture between January 1, 2004 and March 31, 2014 at 6 Level 1 trauma centers were retrospectively reviewed. Univariate analysis using chi-squared or Student's t test was performed to identify associations between preoperative variables and 2 postoperative outcomes of interest: amputation and 1-year mortality. Multivariate analysis was performed using stepwise logistical regression to identify independent predictors of postoperative amputation and 1-year mortality. Of the 162 total patients, the most common mechanism of injury was a ground-level fall (51.9%). The most common fracture types were bimalleolar fractures (52.5%) followed by trimalleolar fractures (26.5%), with 41.5% of the fractures classified as Gustilo Anderson Classification Type 2 and 38.6% classified as Type 3A. The average number of surgeries required per patient was 2.1. Complications included: 15.4% superficial infection rate, 9.9% deep infection rate, and 9.3% amputation rate. The 1-year mortality rate was 13.6% and the overall mortality rate was 25.9%. Male gender and fracture type were found to be independent predictors for amputation after surgery (p =.009,.005, respectively). Older age and having diabetes were independent predictors for 1-year mortality after surgery (p =.021,.005 respectively). Overall, open ankle fractures in older individuals were associated with high rates of amputation and mortality. [ABSTRACT FROM AUTHOR]

Objectives: To compare the ability of SureSmileTM, InsigniaTM and InvisalignTM to achieve predicted intra-arch tooth positions and further compare their objective grading scores for alignment/rotations, marginal ridge relationships and buccolingual inclination.

Stephanie J Chiu,1,2 Simon J Hickman,2,3 Irene M Pepper,1,2 Jennifer HY Tan,1,2 John Yianni,2,4 Joanna M Jefferis1,2,5 1Department of Ophthalmology, Royal Hallamshire Hospital, Sheffield, UK; 2Department of Medical Education, University of Sheffield, Sheffield, UK; 3Department of Neurology, Royal Hallamshire Hospital, Sheffield, UK; 4Department of Neurosurgery, Royal Hallamshire Hospital, Sheffield, UK; 5Department of Neuro-Ophthalmology, Manchester Royal Eye Hospital, Manchester, UKCorrespondence: Joanna M JefferisManchester Royal Eye Hospital, Oxford Road, Manchester, M13 9WL, UKTel +44 0161 276 1234Email jojefferis@doctors.org.ukAbstract: Vestibular schwannomas (VSs), also called acoustic neuromas, are benign intracranial neoplasms of the vestibulocochlear (VIII) cranial nerve. Management options include “wait-and-scan,” stereotactic radiosurgery and surgical resection. Due to the proximity of the VIII nerve to the facial (VII) nerve in the cerebello-pontine angle, the VII nerve is particularly vulnerable to the effects of surgical resection. This can result in poor eye closure, lagophthalmos and resultant corneal exposure post VS resection. Additionally, compression from the tumor or resection can cause trigeminal (V) nerve damage and a desensate cornea. The combination of an exposed and desensate cornea puts the eye at risk of serious ocular complications including persistent epithelial defects, corneal ulceration, corneal vascularization, corneal melting and potential perforation. The abducens (VI) nerve can be affected by a large intracranial VS causing raised intracranial pressure (a false localizing sign) or as a result of damage to the VI nerve at the time of resection. Other types of neurogenic strabismus are rare and typically transient. Contralaterally beating nystagmus as a consequence of vestibular dysfunction is common post-operatively. This generally settles to pre-operative levels as central compensation occurs. Ipsilaterally beating nystagmus post-operatively should prompt investigation for post-operative cerebrovascular complications. Papilledema (and subsequent optic atrophy) can occur as a result of a large VS causing raised intracranial pressure. Where papilledema follows surgical resection of a VS, it can indicate that cerebral venous sinus thrombosis has occurred. Poor visual function following VS resection can result as a combination of all these potential complications and is more likely with larger tumors.Keywords: vestibular schwannoma, post-operative complications, papilledema, facial nerve paralysis, neurotrophic keratopathy, nystagmus

Malnutrition and dental caries in early childhood remain persistent and intertwined global health challenges, particularly for indigenous and geographically-remote populations. To examine the prevalence and associations between early childhood dental caries, parent-reported mouth pain and malnutrition in the Amazonian region of Ecuador, we conducted a cross-sectional study of the oral health and nutrition status of 1407 children from birth through age 6 in the "Alli Kiru" program (2011-2013). We used multivariate regression analysis to examine relationships between severe caries, parent-reported mouth pain measures, and nutritional status. The prevalence of dental caries was 65.4%, with 44.7% of children having deep or severe caries, and 33.8% reporting mouth pain. The number of decayed, missing and filled teeth (dmft) increased dramatically with age. Malnutrition was prevalent, with 35.9% of children stunted, 1.1% wasted, 7.4% underweight, and 6.8% overweight. As mouth pain increased in frequency, odds for severe caries increased. For each unit increase in mouth pain frequency interfering with sleeping, children had increased odds for being underweight (Adjusted Odds Ratio (AOR): 1.27; 95% CI: 1.02-1.54) and decreased odds for being overweight (AOR: 0.76; 95% CI: 0.58-0.97). This relationship was most pronounced among 3-6 year-olds. Early childhood caries, mouth pain and malnutrition were prevalent in this sample of young children. Parent-reported mouth pain was associated with severe caries, and mouth pain interfering with sleeping was predictive of poor nutritional status. We demonstrate the utility of a parsimonious parent-reported measure of mouth pain to predict young children's risk for severe early childhood caries and malnutrition, which has implications for community health interventions.

ErbB (Erythroblastic Leukemia Viral Oncogene Homolog) receptor tyrosine kinases are critical for tissue development and maintenance, and frequently become oncogenic when mutated or overexpressed. In vitro analysis of ErbB receptor kinases can be difficult because of their large size and poor water solubility. Here we report improved production and assembly of the correctly folded full-length EGF receptor (EGFR) into nanolipoprotein particles (NLPs). NLPs are ~10 nm in diameter discoidal cell membrane mimics composed of apolipoproteins surrounding a lipid bilayer. NLPs containing EGFR were synthesized via incubation of baculovirus-produced recombinant EGFR with apolipoprotein and phosphoplipids under conditions that favor self-assembly. The resulting EGFR-NLPs were the correct size, formed dimers and multimers, had intrinsic autophosphorylation activity, and retained the ability to interact with EGFR-targeted ligands and inhibitors consistent with previously-published in vitro binding affinities. We anticipate rapid adoption of EGFR-NLPs for structural studies of full-length receptors and drug screening, as well as for the in vitro characterization of ErbB heterodimers and disease-relevant mutants.

Background: Perioperative blood glucose control has been demonstrated to influence outcomes following spine surgery, though this association has not been fully elucidated in patients with traumatic spine injuries. This study sought to determine the association between perioperative blood glucose levels and complications or outcomes in patients undergoing spine surgery due to injury. Methods: A retrospective review was conducted to identify patients who underwent spine surgery due to traumatic injuries between 1 March 2020 and 29 September 2022 at a single academic institution. Descriptive factors, complications, and outcomes were compared between those with a postoperative blood glucose level of <200 mg/dL and those with a preoperative glucose of <200 mg/dL. Results: Patients with a post- and preoperative blood glucose of ≥200 mg/dL had significantly higher odds of respiratory complications (OR = 2.1, 2.1, P = 0.02, 0.03), skin/wound complications (OR = 2.2, 2.8, P = 0.04, 0.03), and increased hospital length of stay (OR = 9.6, 12.1, P = 0.02, 0.03) compared with those with blood glucose of <200 mg/dL. Those with postoperative glucose ≥200 mg/dL also had significantly higher odds of inpatient mortality (OR = 4.5, P = 0.04) when controlling for confounding factors. Neither pre- nor postoperative blood glucose of ≥200 mg/dL was associated with an improvement in American Spinal Injury Association Impairment Scale score at the final follow-up when controlling for multiple confounding factors (P = 0.44, 0.06). Conclusion: Elevated blood glucose both pre- and postoperatively was associated with an increased rate of postoperative complications and negative postoperative outcomes. However, there was no association between elevated blood glucose levels and neurological recovery following traumatic spinal injury. [ABSTRACT FROM AUTHOR]

Unlike human teeth, mouse incisors grow throughout life, based on stem and progenitor cell activity. Here the authors generate single cell RNA-seq comparative maps of continuously-growing mouse incisor, non-growing mouse molar and human teeth, combined with lineage tracing to reveal dental cell complexity.

Summary: Despite their importance in tissue homeostasis and renewal, human pituitary stem cells (PSCs) are incompletely characterized. We describe a human single nucleus RNA-seq and ATAC-seq resource from pediatric, adult, and aged postmortem pituitaries (snpituitaryatlas.princeton.edu) and characterize cell-type-specific gene expression and chromatin accessibility programs for all major pituitary cell lineages. We identify uncommitted PSCs, committing progenitor cells, and sex differences. Pseudotime trajectory analysis indicates that early-life PSCs are distinct from the other age groups. Linear modeling of same-cell multiome data identifies regulatory domain accessibility sites and transcription factors that are significantly associated with gene expression in PSCs compared with other cell types and within PSCs. We identify distinct deterministic mechanisms that contribute to heterogeneous marker expression within PSCs. These findings characterize human stem cell lineages and reveal diverse mechanisms regulating key PSC genes and cell type identity.

A Correction to this paper has been published: https://doi.org/10.1038/s41420-021-00445-9

Background: Metatarsalgia is a common diagnosis for patients with forefoot pain. Many have proposed metatarsal fat pad atrophy is a cause of metatarsalgia and therefore have suggested fat grafting instead of distal metatarsal osteotomies to treat metatarsalgia. For fat grafting to be a viable treatment, fat pad atrophy should correlate with metatarsalgia. This study looked to determine the relationship between metatarsal fat pad thickness and metatarsalgia and the correlation between metatarsal fat pad thickness and patient-reported outcomes. Methods: We conducted a retrospective review of patients with metatarsalgia and those with foot or ankle osteoarthritis who had a nonweightbearing MRI performed between February 1, 2021, and March 1, 2023. Data collected included demographics, PROMIS scores, metatarsal fat pad thickness in the second and third rays of the affected foot, and thinnest area on coronal section, measured on MRI. Student t test was used to compare continuous variables, whereas the χ2 test was used to compare categorical variables. Multivariable linear regression models were used to control for potential confounding factors. Results: A total of 112 patients were included in this study. Patients with metatarsalgia were significantly more likely to have a lower body mass index (29.3 vs 32.0, P =.03) than patients with osteoarthritis, but this finding was not present when controlling for confounding variables. We found no significant difference in fat pad thickness between patients with metatarsalgia vs patients with foot or ankle osteoarthritis (P =.43). We found no correlation between metatarsal fat pad thickness and pain interference (P =.59), physical function (P =.64), or mobility (P =.94) PROMIS scores. Conclusion: In this retrospective comparative study of a relatively small cohort we found no significant difference in metatarsal fat pad thickness for patients with metatarsalgia vs patients with foot and ankle osteoarthritis based on nonweightbearing MRI, and no association between metatarsal fat pad thickness and patient-reported outcomes. Level of Evidence: Level III, case control study. [ABSTRACT FROM AUTHOR]

Human oral soft tissues provide the first barrier of defence against chronic inflammatory disease and hold a remarkable scarless wounding phenotype. Tissue homeostasis requires coordinated actions of epithelial, mesenchymal, and immune cells. However, the extent of heterogeneity within the human oral mucosa and how tissue cell types are affected during the course of disease progression is unknown. Using single-cell transcriptome profiling we reveal a striking remodelling of the epithelial and mesenchymal niches with a decrease in functional populations that are linked to the aetiology of the disease. Analysis of ligand–receptor interaction pairs identify potential intercellular hubs driving the inflammatory component of the disease. Our work establishes a reference map of the human oral mucosa in health and disease, and a framework for the development of new therapeutic strategies.