Carbon Footprint of Minor Foot and Ankle Surgery: A Randomized Controlled Trial.

Background: Climate change poses a substantial threat to human health, and operating rooms (ORs) have an outsized environmental impact. The Program for Research in Sustainable Medicine (PRiSM) designed a protocol for minor foot and ankle surgery intended to reduce waste, streamline instrument trays, and minimize laundry. We conducted a randomized controlled trial to compare the carbon footprint of procedures performed using the PRiSM protocol vs a traditional protocol. Methods: Forty adult patients undergoing foreign body removal, hammertoe correction, toe amputation, hardware removal, mass excision, or gastrocnemius recession were randomized to the PRiSM or our "Traditional" protocol. The PRiSM protocol used a smaller instrument tray, fewer drapes and towels, and minimal positioning blankets. No changes were made to surgical site preparation or operative techniques. Environmental impact was estimated using the carbon footprint, measured in kilograms of carbon dioxide equivalents (CO2e). Emissions associated with OR waste, instrument processing, and laundry were calculated. Results: On average, PRiSM cases had a smaller carbon footprint than Traditional cases (17.3 kg CO2e [SD = 3.2] vs 20.6 kg CO2e [SD = 2.0], P < .001). Waste-associated emissions from PRiSM cases were reduced (16.0 kg CO2e [SD = 2.7] vs 18.4 kg CO2e [SD = 1.8], P = .002), as were modeled instrument processing-related emissions (0.34 vs 0.91 kg CO2e). One superficial surgical site infection occurred in each group. Conclusion: We found a small but statistically significant reduction in the environmental impact of minor foot and ankle surgery when using the PRiSM vs Traditional protocol. The environmental impact of these cases was dominated by plastic waste-related emissions. Orthopaedic surgeons should think critically about what components of their surgical setup are truly necessary for patient care, as minor changes in product utilization can have significant impacts on waste and greenhouse gas emissions. Level of Evidence: Level I, randomized controlled trial.

Differences in Baseline Physical Function and Mental Health PROM Scores in Patients With Foot and Ankle Conditions.

BACKGROUND: This study sought to establish normative values for baseline physical and mental health by foot and ankle diagnosis using validated PROMIS scores and to compare the correlation between these 2 outcomes across common diagnoses. Additionally, it investigated the effects associated with chronic vs acute conditions and specific diagnoses on mental health. METHODS: We reviewed baseline PROMIS Physical Function 10a (PF10a) and PROMIS Global-Mental (PGM) scores of 14,245 patients with one of the 10 most common foot and ankle diagnoses seen at our institution between 2016 and 2021. Pearson correlation coefficients were calculated to assess the relationship between PF10a and PGM by diagnosis. A multivariable regression model including age, sex, language, race, ethnicity, education level, income, and Charlson Comorbidity Index was used to determine the associated effect of diagnosis on PGM score. RESULTS: On unadjusted analysis, patients diagnosed with an ankle fracture had the lowest mean physical function, whereas patients with hallux valgus had the highest (PF10a = 33.9 vs 46.7, P < .001). Patients with foot/ankle osteoarthritis had the lowest mean self-reported mental health, whereas patients with hallux rigidus had the highest (PGM = 49.9 vs 53.4, P < .001). PF10a and PGM scores were significantly positively correlated for all diagnoses; the correlation was strongest in patients diagnosed with foot/ankle osteoarthritis or hammertoes (r = 0.511) and weakest in patients with ankle fractures (r = 0.232) or sprains (r = 0.280). Chronic conditions, including hammertoes (ß = -5.1, 95% CI [-5.8, -4.3], P < .001), foot/ankle osteoarthritis (ß = -5.0, 95% CI [-5.7, -4.3], P < .001), and hallux valgus (ß = -4.8, 95% CI [-5.5, -4.1], P < .001) were associated with the largest negative effects on patients' mental health. CONCLUSION: Self-reported physical function and mental health varied across common foot and ankle diagnoses and were more tightly correlated in chronic conditions. The associations between diagnosis and mental health scores appear larger for more chronic diagnoses, including those that are generally associated with relatively unimpaired physical function. LEVEL OF EVIDENCE: Level IV, retrospective, cross-sectional study.

Automating the analysis of facial emotion expression dynamics: A computational framework and application in psychotic disorders.

Facial emotion expressions play a central role in interpersonal interactions; these displays are used to predict and influence the behavior of others. Despite their importance, quantifying and analyzing the dynamics of brief facial emotion expressions remains an understudied methodological challenge. Here, we present a method that leverages machine learning and network modeling to assess the dynamics of facial expressions. Using video recordings of clinical interviews, we demonstrate the utility of this approach in a sample of 96 people diagnosed with psychotic disorders and 116 never-psychotic adults. Participants diagnosed with schizophrenia tended to move from neutral expressions to uncommon expressions (e.g., fear, surprise), whereas participants diagnosed with other psychoses (e.g., mood disorders with psychosis) moved toward expressions of sadness. This method has broad applications to the study of normal and altered expressions of emotion and can be integrated with telemedicine to improve psychiatric assessment and treatment.

Primary Care Physician Preferences Regarding Communication from Orthopaedic Surgeons.

BACKGROUND: Musculoskeletal consultations constitute a growing portion of primary care physician (PCP) referrals. Optimizing communication between PCPs and orthopaedists can potentially reduce time spent in the electronic medical record (EMR) as well as physician burnout. Little is known about the preferences of PCPs regarding communication from orthopaedic surgeons. Hence, the present study investigated, across a large health network, the preferences of PCPs regarding communication from orthopaedists. METHODS: A total of 175 PCPs across 15 practices within our health network were surveyed. These providers universally utilized Epic as their EMR platform. Five-point, labeled Likert scales were utilized to assess the PCP-perceived importance of communication from orthopaedists in specific clinical scenarios. PCPs were further asked to report their preferred method of communication in each scenario and their overall interest in communication from orthopaedists. Logistic regression analyses were performed to determine whether any PCP characteristics were associated with the preferred method of communication and the overall PCP interest in communication from orthopaedists. RESULTS: A total of 107 PCPs (61.1%) responded to the survey. PCPs most commonly rated communication from orthopaedists as highly important in the scenario of an orthopaedist needing information from the PCP. In this scenario, PCPs preferred to receive an Epic Staff Message. Scenarios involving a recommendation for surgery, hospitalization, or a major clinical change were also rated as highly important. In these scenarios, an Epic CC'd Chart rather than a Staff Message was preferred. Increased after-hours EMR use was associated with diminished odds of having a high interest in communication from orthopaedists (odds ratio, 0.65; 95% confidence interval, 0.48 to 0.88; p = 0.005). Ninety-three PCPs (86.9%) reported spending 1 to 1.5 hours or more per day in Epic after normal clinical hours, and 27 (25.2%) spent >3 hours per day. Forty-six PCPs (43.0%) reported experiencing ≥1 symptom of burnout. CONCLUSIONS: There were distinct preferences among PCPs regarding clinical communication from orthopaedic surgeons. There was also evidence of substantial burnout and after-hours work effort by PCPs. These results may help to optimize communication between PCPs and orthopaedists while reducing the amount of time that PCPs spend in the EMR.

Psychosis superspectrum II: neurobiology, treatment, and implications.

Alternatives to traditional categorical diagnoses have been proposed to improve the validity and utility of psychiatric nosology. This paper continues the companion review of an alternative model, the psychosis superspectrum of the Hierarchical Taxonomy of Psychopathology (HiTOP). The superspectrum model aims to describe psychosis-related psychopathology according to data on distributions and associations among signs and symptoms. The superspectrum includes psychoticism and detachment spectra as well as narrow subdimensions within them. Auxiliary domains of cognitive deficit and functional impairment complete the psychopathology profile. The current paper reviews evidence on this model from neurobiology, treatment response, clinical utility, and measure development. Neurobiology research suggests that psychopathology included in the superspectrum shows similar patterns of neural alterations. Treatment response often mirrors the hierarchy of the superspectrum with some treatments being efficacious for psychoticism, others for detachment, and others for a specific subdimension. Compared to traditional diagnostic systems, the quantitative nosology shows an approximately 2-fold increase in reliability, explanatory power, and prognostic accuracy. Clinicians consistently report that the quantitative nosology has more utility than traditional diagnoses, but studies of patients with frank psychosis are currently lacking. Validated measures are available to implement the superspectrum model in practice. The dimensional conceptualization of psychosis-related psychopathology has implications for research, clinical practice, and public health programs. For example, it encourages use of the cohort study design (rather than case-control), transdiagnostic treatment strategies, and selective prevention based on subclinical symptoms. These approaches are already used in the field, and the superspectrum provides further impetus and guidance for their implementation. Existing knowledge on this model is substantial, but significant gaps remain. We identify outstanding questions and propose testable hypotheses to guide further research. Overall, we predict that the more informative, reliable, and valid characterization of psychopathology offered by the superspectrum model will facilitate progress in research and clinical care.

Capabilities and Limitations of Student-Led Free Vision Screening Programs in the United States.

Purpose: The Consortium of Student-Led Eye Clinics (CSLEC), founded in 2021, administered a comprehensive survey to document the types of services, most common diagnoses, and follow-up care protocols offered by student-led free vision screening programs (SLFVSP) in the United States. Methods: An 81-question institutional review board (IRB)-approved survey was administered to student-led vision screening eye clinics from October 1, 2022 to February 24, 2023. Results: Sixteen SLFVSPs were included in the final analysis, of which 81% (n = 13) conducted variations of fundoscopic examinations and 75% (n = 12) measured intraocular pressure. Cataracts and diabetic retinopathy were reported as the most frequent diagnoses by the majority of SLFVSPs (n = 9, 56%); non-mobile SLFVSPs more commonly reported cataract as a frequent diagnosis (P < 0.05). Most patients screened at participating programs were uninsured or met federal poverty guidelines. Prescription glasses were offered by 56% of the programs (n = 9). SLFVSPs that directly scheduled follow-up appointments reported higher attendance rates (66.5%) than those that only sent referrals (20%). Transportation was the most cited barrier for follow-up appointment attendance. Conclusions: SLFVSPs, one community vision screening initiative subtype, vary significantly in scope and capabilities of identifying vision threatening disease. The follow-up infrastructure is not uniformly robust and represents a key target for improving care delivery to at-risk populations. Translational Relevance: The CSLEC aims to develop a consensus-based standardization for the scope of screening services, offer guidelines for diagnostic criteria, promote real-time data stewardship, and identify means to improve follow-up care mechanisms in member communities.

Principles and procedures for revising the hierarchical taxonomy of psychopathology.

Quantitative, empirical approaches to establishing the structure of psychopathology hold promise to improve on traditional psychiatric classification systems. The Hierarchical Taxonomy of Psychopathology (HiTOP) is a framework that summarizes the substantial and growing body of quantitative evidence on the structure of psychopathology. To achieve its aims, HiTOP must incorporate emerging research in a systematic, ongoing fashion. In this article, we describe the historical context and grounding of the principles and procedures for revising the HiTOP framework. Informed by strengths and shortcomings of previous classification systems, the proposed revisions protocol is a formalized system focused around three pillars: (a) prioritizing systematic evaluation of quantitative evidence by a set of transparent criteria and processes, (b) balancing stability with flexibility, and (c) promoting inclusion over gatekeeping in all aspects of the process. We detail how the revisions protocol will be applied in practice, including the scientific and administrative aspects of the process. Additionally, we describe areas of the HiTOP structure that will be a focus of early revisions and outline challenges for the revisions protocol moving forward. The proposed revisions protocol is designed to ensure that the HiTOP framework reflects the current state of scientific knowledge on the structure of psychopathology and fulfils its potential to advance clinical research and practice. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

Non-mutagenic impurities - Recent industry experience of using dose durational limits in drug development.

Absence of clear guidance on the qualification threshold for non-mutagenic impurities during clinical development is a source of inconsistency in both sponsor qualification approaches and health authority requests. A survey was conducted in March 2020 with 6 member companies of the European Federation of Pharmaceutical Industries and Associations (EFPIA). Thirteen examples were gathered of where non-International Council for Harmonisation (ICH) limits have been used in regulatory submissions for various indications and stages of development, together with the regulatory outcomes. As expected, few challenges were faced in early clinical development, with health authorities generally commenting that sponsors should work towards ICH Q3A and Q3B guideline specification limits as development progresses. However, inconsistent health authority requests were noted even for early phase clinical trials in late-stage oncology patients. For an optimised use of resources, consistent approaches would have the benefit of supporting faster access of safe medicines to patients while including Replacement, Reduction and Refinement (the 3Rs) considerations with respect to animal testing.

Intraarticular Injections in the Foot and Ankle: Medication Selection Patterns and Perceived Risk Of Chondrotoxicity.

Background: Intraarticular corticosteroid injections (ICIs) are widely used to treat foot and ankle conditions. Although laboratory studies indicate certain corticosteroids and local anesthetics used in ICIs are associated with chondrotoxic effects, and selected agents such as ropivacaine and triamcinolone may have less of these features, clinical evidence is lacking. We aimed to identify the patterns of drug selection, perceptions of injectate chondrotoxicity, and rationale for medication choice among surgeons in the American Orthopaedic Foot & Ankle Society (AOFAS). Methods: An e-survey including demographics, practice patterns, and rationale was disseminated to 2011 AOFAS members. Frequencies and percentages were calculated for demographic data, anesthetic and steroid choice, rationale for injectate choice, and perception of chondrotoxicity. Bivariate analysis was used to identify practice patterns significantly associated with perceptions of injectate risk and rationale. Results: In total, 387 surveys were completed. Lidocaine and triamcinolone were the most common anesthetic and corticosteroid used (51.2% and 39.3%, respectively). Less than half of respondents felt corticosteroids or local anesthetics bear risk of chondrotoxicity. Respondents agreeing that corticosteroids are chondrotoxic were more likely to use triamcinolone (P = .037). Respondents agreeing local anesthetics risk chondrotoxicity were less likely to use lidocaine (P = .023). Respondents choosing a local anesthetic based on literature were more likely to use ropivacaine (P < .001). Conclusion: Corticosteroid and local anesthetic use in ICIs varied greatly. Rationale for ICI formulation was also variable, as the clinical implications are largely unknown. Those who recognized potential chondrotoxicity and who chose based on literature were more likely to choose ropivacaine and triamcinolone, as reflected in the basic science literature. Further clinical studies are needed to establish guidelines that shape foot and ankle ICI practices based on scientific evidence and reduce the variation identified by this study. Level of Evidence: Level IV, cross-sectional survey study.

Efficiency and perceived safety of foot and ankle procedures performed on the preoperative stretcher versus operating room table.

BACKGROUND: Foot and ankle surgeons often perform minor surgeries on the preoperative stretcher instead of the operating room table. We examined whether stretcher-based and operating room table-based procedures differed with respect to operating room efficiency and staff perceptions. METHODS: We retrospectively reviewed medical records of patients undergoing minor foot and ankle surgery at an ambulatory surgery centre. We collected 'time to start', the duration between patient arrival in the operating room and incision time, and 'time to exit', the duration between procedure end time and patient exit from the operating room. Staff were surveyed regarding their perceptions of stretcher-based and operating room table-based procedures. RESULTS: 'Time to start' was significantly shorter for stretcher-based procedures, but 'time to exit' was not. Seventeen (81%) staff members thought stretcher-based procedures increased operating room efficiency. Thirteen (62%) thought stretcher-based procedures bettered staff safety. Nineteen (91%) thought stretcher-based procedures were equivalent to or better than operating room table-based procedures for patient safety. Most (67%) would recommend stretcher-based procedures. CONCLUSION: We found small but significant time savings associated with stretcher-based procedures. Without adapting surgical scheduling practices, the impact of stretcher-based procedures on overall operating room efficiency is questionable. Nevertheless, the majority of OR staff think stretcher-based procedures increase OR efficiency and are safer for staff. LEVEL OF EVIDENCE: Level IV, Retrospective case series.

Sensitization Assessment of Extractables and Leachables in Pharmaceuticals: ELSIE Database Analysis.

Quality by design is the foundation of the risk management framework for extractables and leachables (E&Ls) recommended by the Extractables and Leachables Safety Information Exchange (ELSIE). Following these principles during the selection of materials for pharmaceutical product development minimizes the presence of highly toxic substances and decreases the health risk of potential leachables in the drug product. Therefore, in the context of the broad arena of chemicals, it is important to distinguish E&Ls as a subset of chemicals and evaluate this relevant chemical space to derive appropriate analytical and safety thresholds. When considering the health hazards posed by E&Ls, one area presenting a challenge is understanding the sensitization potential and whether it poses a risk to patients. A dataset of E&Ls compiled by ELSIE (n=466) was analysed to determine the prevalence and potency of skin sensitizers in this chemical subset and explore a scientifically justified approach to the sensitization assessment of potential leachables in parenteral drug products. Approximately half of the compounds (56%, 259/466) had sensitization data recorded in the ELSIE database and of these, 20% (52/259) are potential skin sensitizers. Only 3% (8/259) of the E&L dataset with sensitization data were considered potent (strong or extreme) sensitizers following in silico analysis and expert review, illustrating that potent sensitizers are not routinely observed as leachables in pharmaceutical products. Our analysis highlights that in silico potency prediction and expert review are key tools during the sensitization assessment process for E&Ls. The results confirm where material selection is anticipated to mitigate the risk of presence of strong and/or extreme sensitizers (e.g., extractable testing via ISO 10993-10), and that implementing thresholds per ICH M7 and/or Masuda-Herrera et al. provides a reasonably conservative approach for establishing the analytical testing and safety thresholds.

Modeling relations between event-related potential factors and broader versus narrower dimensions of externalizing psychopathology.

The organization of the Hierarchical Taxonomy of Psychopathology (HiTOP) model provides unique opportunities to evaluate whether neural risk measures operate as indicators of broader latent liabilities (e.g., externalizing proneness) or narrower expressions (e.g., antisociality and alcohol abuse). Following this approach, the current study recruited a sample of 182 participants (54% female) who completed measures of externalizing psychopathology (also internalizing) and associated traits. Participants also completed three tasks (Flanker-No Threat, Flanker-Threat, and Go/No-Go tasks) with event-related potential (ERP) measurement. Three variants of two research domain criteria (RDoC)-based neurophysiological indicators-P3 and error-related negativity (ERN)-were extracted from these tasks and used to model two latent ERP factors. Scores on these two ERP factors independently predicted externalizing factor scores when accounting for their covariance with sex-suggesting distinct neural processes contributing to the broad externalizing factor. No predictive relation with the broad internalizing factor was found for either ERP factor. Analyses at the finer-grained level revealed no unique predictive relations of either ERP factor with any specific externalizing symptom variable when accounting for the broad externalizing factor, indicating that ERN and P3 index general liability for problems in this spectrum. Overall, this study provides new insights about neural processes in externalizing psychopathology at broader and narrower levels of the HiTOP hierarchy. (PsycInfo Database Record (c) 2023 APA, all rights reserved).

The Fate of Delayed Unions After Isolated Ankle Fusion.

BACKGROUND: Nonunion remains the most common major complication of ankle arthrodesis. Although previous studies have reported delayed union or nonunion rates, few have elaborated on the clinical course of patients experiencing delayed union. In this retrospective cohort study, we sought to understand the trajectory of patients with delayed union by determining the rate of clinical success and failure and whether the extent of fusion on computed tomography scan (CT) was associated with outcomes. METHODS: Delayed union was defined as incomplete (<75%) fusion on CT between 2 and 6 months postoperatively. Thirty-six patients met the inclusion criterion: isolated tibiotalar arthrodesis with delayed union. Patient-reported outcomes were obtained including patient satisfaction with their fusion. Success was defined as patients who were not revised and reported satisfaction. Failure was defined as patients who required revision or reported being not satisfied. Fusion was assessed by measuring the percentage of osseous bridging across the joint on CT. The extent of fusion was categorized as absent (0%-24%), minimal (25%-49%), or moderate (50%-74%). RESULTS: We determined the clinical outcome of 28 (78%) patients with mean follow-up of 5.6 years (range, 1.3-10.2). The majority (71%) of patients failed. On average, CT scans were obtained 4 months after attempted ankle fusion. Patients with minimal or moderate fusion were more likely to succeed clinically than those with "absent" fusion (P = .040). Of those with absent fusion, 11 of 12 (92%) failed. In patients with minimal or moderate fusion, 9 of 16 (56%) failed. CONCLUSION: We found that 71% of patients with a delayed union at roughly 4 months after ankle fusion required revision or were not satisfied. Patients with less than 25% fusion on CT had an even lower rate of clinical success. These findings may help surgeons in counseling and managing patients experiencing a delayed union after ankle fusion. LEVEL OF EVIDENCE: Level IV, retrospective cohort study.

Precision behavioral phenotyping as a strategy for uncovering the biological correlates of psychopathology.

Our capacity to measure diverse aspects of human biology has developed rapidly in the past decades, but the rate at which these techniques have generated insights into the biological correlates of psychopathology has lagged far behind. The slow progress is partly due to the poor sensitivity, specificity and replicability of many findings in the literature, which have in turn been attributed to small effect sizes, small sample sizes and inadequate statistical power. A commonly proposed solution is to focus on large, consortia-sized samples. Yet it is abundantly clear that increasing sample sizes will have a limited impact unless a more fundamental issue is addressed: the precision with which target behavioral phenotypes are measured. Here, we discuss challenges, outline several ways forward and provide worked examples to demonstrate key problems and potential solutions. A precision phenotyping approach can enhance the discovery and replicability of associations between biology and psychopathology.

Review of factors resulting in systemic biases in the screening, assessment, and treatment of individuals at clinical high-risk for psychosis in the United States.

Background: Since its inception, research in the clinical high-risk (CHR) phase of psychosis has included identifying and exploring the impact of relevant socio-demographic factors. Employing a narrative review approach and highlighting work from the United States, sociocultural and contextual factors potentially affecting the screening, assessment, and service utilization of youth at CHR were reviewed from the current literature. Results: Existing literature suggests that contextual factors impact the predictive performance of widely used psychosis-risk screening tools and may introduce systemic bias and challenges to differential diagnosis in clinical assessment. Factors reviewed include racialized identity, discrimination, neighborhood context, trauma, immigration status, gender identity, sexual orientation, and age. Furthermore, racialized identity and traumatic experiences appear related to symptom severity and service utilization among this population. Conclusions: Collectively, a growing body of research from the United States and beyond suggests that considering context in psychosis-risk assessment can provide a more accurate appraisal of the nature of risk for psychosis, render more accurate results improving the field's prediction of conversion to psychosis, and enhance our understanding of psychosis-risk trajectories. More work is needed in the U.S. and across the globe to uncover how structural racism and systemic biases impact screening, assessment, treatment, and clinical and functional outcomes for those at CHR.

The Effects of Sociodemographic Factors on Baseline Patient-Reported Outcome Measures in Patients with Foot and Ankle Conditions.

BACKGROUND: Racial and ethnic care disparities persist within orthopaedics in the United States. This study aimed to deepen our understanding of which sociodemographic factors most impact patient-reported outcome measure (PROM) score variation and may explain racial and ethnic disparities in PROM scores. METHODS: We retrospectively reviewed baseline PROMIS (Patient-Reported Outcomes Measurement Information System) Global-Physical (PGP) and PROMIS Global-Mental (PGM) scores of 23,171 foot and ankle patients who completed the instrument from 2016 to 2021. A series of regression models was used to evaluate scores by race and ethnicity after adjusting in a stepwise fashion for household income, education level, primary language, Charlson Comorbidity Index (CCI), sex, and age. Full models were utilized to compare independent effects of predictors. RESULTS: For the PGP and PGM, adjusting for income, education level, and CCI reduced racial disparity by 61% and 54%, respectively, and adjusting for education level, language, and income reduced ethnic disparity by 67% and 65%, respectively. Full models revealed that an education level of high school or less and a severe CCI had the largest negative effects on scores. CONCLUSIONS: Education level, primary language, income, and CCI explained the majority (but not all) of the racial and ethnic disparities in our cohort. Among the explored factors, education level and CCI were predominant drivers of PROM score variation. LEVEL OF EVIDENCE: Prognostic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Scope of the Problem: Ankle Arthroscopy.

Ankle arthroscopy has seen increased utilization and application in recent years. Through the advent of improved instrumentation and techniques, indications have been expanded to include the management of traumatic, degenerative, inflammatory, and neoplastic conditions. It is important to review anterior and posterior ankle arthroscopies along with the history, pertinent anatomy, techniques, indications, and complications as well as gain insight into the future of ankle arthroscopy.

Scope of the Problem: Tendoscopy and Small Joint Arthroscopy of the Foot and Ankle.

It is important to identify and describe practical applications of arthroscopy in the management of foot and ankle pathology. Utilization of the arthroscope provides a minimally invasive means of evaluating and addressing pathology. It obviates the need for a large open approach, which has additional value in the setting of a multiprocedure surgery. In addition to reducing surgical time, arthroscopy provides a potentially enhanced field of view and an adequate working space to address injury. As interest in minimally invasive options grows, the need for safe, effective tendoscopic and arthroscopic options in the foot and ankle increases. A clear and high-yield reference is needed with which to approach these procedures.

A Novel Technique Identifies Valve-Like Pathways Entering and Exiting Schlemm's Canal in Macaca nemestrina Primates With Similarities to Human Pathways.

Purpose: The aim of the study was 1) to describe a novel combination of techniques that permit immunohistochemistry imaging of Schlemm's canal inlet (SIV) and outlet (SOV) valve-like structures, 2) to identify tissue-level SIV adhesive relationships linking the trabecular meshwork (TM) to hinged collagen leaflets at the Schlemm's canal (SC) external wall, and 3) to determine whether the SIV lumen wall's adhesive vascular markers are similar to those of the SC inner wall endothelium. Materials and Methods: Anterior segments of 16 M. nemestrina primates underwent immunohistochemistry (IHC) labeling. We perfused fluorescent microspheres into 12 of the eyes. Limbal tissues were divided into quadrants, viscoelastic introduced into SC, tissues fixed, immunohistochemistry performed, radial segments cut, tissues clarified, and confocal microscopy performed. Finally, we generated ImageJ 3D projections encompassing the TM, SC, and distal pathways. Results: IHC imaging identified 3D relationships between SIV, collector channel ostia, collector channels (CC), SOV, and intrascleral channels. Imaging depth increased 176.9%, following clarification (p < 0.0001). Imaging demonstrated CD31, collagen type 1 and 4 in the walls of the SIV lumen and more distal pathways. In eight eyes, 384 segments were examined, 447 SIV identified, and 15.4% contained microspheres. Conclusion: Our technique's imaging depth permitted the identification of SIV linkage between the TM and SOV. We found comparable cell-cell adhesion molecules (CD31) and basement membrane components in the SC inner wall and SIV lumen walls. Recent OCT studies have suggested that SIV tensional relationships may control CC entrance dimensions that regulate distal resistance. Cellular adhesive properties sustain SIV tensional relationships. These SIV cell-cell and cell-basement membrane properties warrant further study because abnormalities could be a factor in the IOP elevation of glaucoma.

Framework for sensitization assessment of extractables and leachables in pharmaceuticals.

During the toxicological assessment of extractables and leachables in drug products, localized hazards such as irritation or sensitization may be identified. Typically, because of the low concentration at which leachables occur in pharmaceuticals, irritation is of minimal concern; therefore, this manuscript focuses on sensitization potential. The primary objective of performing a leachable sensitization assessment is protection against Type IV induction of sensitization, rather than prevention of an elicitation response, as it is not possible to account for the immunological state of every individual. Sensitizers have a wide range of potencies and those which induce sensitization upon exposure at a low concentration (i.e. strong, or extreme sensitizers) pose the highest risk to patients and should be the focus of the risk assessment. The Extractables and Leachables Safety Information Exchange (ELSIE) consortium has reviewed the status of dermal, respiratory, and systemic risk assessment in cosmetic and pharmaceutical industries, and proposes a framework to evaluate the safety of known or potential dermal sensitizers in pharmaceuticals. Due to the lack of specific regulatory guidance on this topic, the science-driven risk-based approach proposed by ELSIE encourages consistency in the toxicological assessment of extractables and leachables to maintain high product quality and ensure patient safety.