Constructive Memory and Conscious Experience.

Episodic memory relies on constructive processes that support simulating novel future events by flexibly recombining elements of past experiences, and that can also give rise to memory errors. In recent studies, we have developed methods to characterize the cognitive and neural processes that support conscious experiences linked to this process of episodic recombination, both when people simulate novel future events and commit recombination-related memory errors. In this Perspective, we summarize recent studies that illustrate these phenomena, and discuss broader implications for characterizing the basis of conscious experiences associated with constructive memory from a cognitive neuroscience perspective.

Return to Duty in Military Servicemembers After High Tibial Osteotomy Not Associated With Preoperative Radiographic Parameters : A Retrospective Analysis.

Background: Evidence on return to sports/work after high tibial osteotomy (HTO) is limited, especially in a young, high-demand population. Purpose: To (1) identify whether preoperative knee pathology or intraoperative correction was associated with successful return to duty (RTD) and (2) assess whether postoperative complications and reoperation were associated with failure to RTD. Study Design: Case series; Level of Evidence, 4. Methods: We performed a retrospective cohort study of a consecutive series of patients in the Military Health System aged 18 to 55 years with medial compartment osteoarthritis who underwent HTO between 2003 and 2018. Concomitant meniscal and cartilage procedures were included, while cases with concomitant ligamentous procedures were excluded. The inclusion criteria were as follows: active-duty military status, minimum 2-year follow-up, preoperative knee radiographs, and pre- and postoperative long-leg alignment radiographs. Preoperative Kellgren-Lawrence grades and pre- and postoperative hip-knee-ankle angles were measured. The primary outcome was RTD. Failure was defined as knee-related medical separation from the military or conversion to total knee arthroplasty. The secondary outcome was reoperation. Results: A total of 55 HTOs were performed in 50 patients who met the inclusion criteria, with a mean age of 39 years old (range, 22.8-55 years). The mean follow-up was 5 years (range, 2.1-10.7 years). Ten knees (18.2%) failed HTO (1 conversion to total knee arthroplasty, 9 medical separations), 15 additional knees (27.3%) had permanent activity restrictions, and 30 knees (54.5%) returned to duty without restrictions. Reoperation occurred in 36.4% of knees and was associated with medical separation (P = .039). Younger age was associated with medical separation (P = .003) and permanent restrictions (P = .006). Patients with a postoperative varus deformity of >5° were more likely to undergo medical separation (P = .023). Conclusion: In a young, high-demand population, HTO succeeded in returning 54.5% of knees to full duty without restriction despite 36.4% of knees requiring reoperation. Residual varus deformity or reoperation was associated with lower RTD rates. No association was identified between RTD and preoperative osteoarthritis grading or deformity.

Diagnosis and Management of Thoracic Myelopathy.

Thoracic myelopathy can be a challenging condition to diagnose and treat. Successful outcomes depend on early recondition of the pathology and appropriate surgical referral in cases of progressive neurologic deterioration. The thoracic cord is tethered in kyphosis by the dentate ligaments and contains a tenuous blood supply. These conditions make the thoracic cord particularly susceptible to external compression and ischemic damage. Careful preoperative planning with specific attention to the location and source of thoracic stenosis is critical to successful decompression and complication avoidance. The purpose of this discussion is to outline the common sources of thoracic myelopathy and current recommendations regarding diagnosis and management. The review concludes with an overview of the most up-to-date literature regarding clinical outcomes.

Structured and disordered regions of Ataxin-2 contribute differently to the specificity and efficiency of mRNP granule formation.

Ataxin-2 (ATXN2) is a gene implicated in spinocerebellar ataxia type II (SCA2), amyotrophic lateral sclerosis (ALS) and Parkinsonism. The encoded protein is a therapeutic target for ALS and related conditions. ATXN2 (or Atx2 in insects) can function in translational activation, translational repression, mRNA stability and in the assembly of mRNP-granules, a process mediated by intrinsically disordered regions (IDRs). Previous work has shown that the LSm (Like-Sm) domain of Atx2, which can help stimulate mRNA translation, antagonizes mRNP-granule assembly. Here we advance these findings through a series of experiments on Drosophila and human Ataxin-2 proteins. Results of Targets of RNA Binding Proteins Identified by Editing (TRIBE), co-localization and immunoprecipitation experiments indicate that a polyA-binding protein (PABP) interacting, PAM2 motif of Ataxin-2 may be a major determinant of the mRNA and protein content of Ataxin-2 mRNP granules. Transgenic Experiments with transgenic Drosophila indicate that while the Atx2-LSm domain may protect against neurodegeneration, structured PAM2- and unstructured IDR- interactions both support Atx2-induced cytotoxicity. Taken together, the data lead to a proposal for how Ataxin-2 interactions are remodelled during translational control and how structured and non-structured interactions contribute differently to the specificity and efficiency of RNP granule condensation as well as to neurodegeneration.

Development of a mutant aerosolized ACE2 that neutralizes SARS-CoV-2 in vivo.

The rapid evolution of SARS-CoV-2 variants highlights the need for new therapies to prevent disease spread. SARS-CoV-2, like SARS-CoV-1, uses the human cell surface protein angiotensin-converting enzyme 2 (ACE2) as its native receptor. Here, we design and characterize a mutant ACE2 that enables rapid affinity purification of a dimeric protein by altering the active site to prevent autoproteolytic digestion of a C-terminal His10 epitope tag. In cultured cells, mutant ACE2 competitively inhibits lentiviral vectors pseudotyped with spikes from multiple SARS-CoV-2 variants and infectious SARS-CoV-2. Moreover, the protein can be nebulized and retains virus-binding properties. We developed a system for the delivery of aerosolized ACE2 to K18-hACE2 mice and demonstrated protection by our modified ACE2 when delivered as a prophylactic agent. These results show proof-of-concept for an aerosolized delivery method to evaluate anti-SARS-CoV-2 agents in vivo and suggest a new tool in the ongoing fight against SARS-CoV-2 and other ACE2-dependent viruses. IMPORTANCE: The rapid evolution of SARS-CoV-2 variants poses a challenge for immune recognition and antibody therapies. However, the virus is constrained by the requirement that it recognizes a human host receptor protein. A recombinant ACE2 could protect against SARS-CoV-2 infection by functioning as a soluble decoy receptor. We designed a mutant version of ACE2 with impaired catalytic activity to enable the purification of the protein using a single affinity purification step. This protein can be nebulized and retains the ability to bind the relevant domains from SARS-CoV-1 and SARS-CoV-2. Moreover, this protein inhibits viral infection against a panel of coronaviruses in cells. Finally, we developed an aerosolized delivery system for animal studies and show the modified ACE2 offers protection in an animal model of COVID-19. These results show proof-of-concept for an aerosolized delivery method to evaluate anti-SARS-CoV-2 agents in vivo and suggest a new tool in the ongoing fight against SARS-CoV-2.

Novel strategy: Identifying new markers for demyelination in diabetic distal symmetrical polyneuropathy.

Objective: To develop a novel strategy for identifying acquired demyelination in diabetic distal symmetrical polyneuropathy (DSP). Background: Motor nerve conduction velocity (CV) slowing in diabetic DSP exceeds expectations for pure axonal loss thus implicating superimposed acquired demyelination. Methods: After establishing demyelination confidence intervals by regression analysis of nerve conduction data from chronic inflammatory demyelinating polyneuropathy (CIDP), we prospectively studied CV slowing in 90 diabetic DSP patients with and without at least one motor nerve exhibiting CV slowing (groups A and B) into the demyelination range by American Academy of Neurology (AAN) criteria respectively and 95 amyotrophic lateral sclerosis (ALS) patients. Simultaneously, secretory phospholipase A2 (sPLA2) activity was assessed in both diabetic groups and 46 healthy controls. Results: No ALS patient exhibited CV slowing in more than two motor nerves based on AAN criteria or the confidence intervals. Group A demonstrated a significantly higher percentage of patients as compared to group B fulfilling the above criteria, with an additional criterion of at least one motor nerve exhibiting CV slowing in the demyelinating range and a corresponding F response in the demyelinating range by AAN criteria (70.3 % vs. 1.9 %; p < 0.0001). Urine sPLA2 activity was increased significantly in diabetic groups as compared to healthy controls (942.9 ± 978.0 vs. 591.6 ± 390.2 pmol/min/ml, p < 0.05), and in group A compared to Group B (1328.3 ± 1274.2 vs. 673.8 ± 576.9 pmol/min/ml, p < 0.01). More patients with elevated sPLA2 activity and more than 2 motor nerves with CV slowing in the AAN or the confidence intervals were identified in group A as compared to group B (35.1 % vs. 5.7 %, p < 0.001). Furthermore, 13.5 % of patients in diabetic DSP Group A, and no patients in diabetic DSP Group B, fulfilled an additional criterion of more than one motor nerve with CV slowing into the demyelinating range with its corresponding F response into the demyelinating range by AAN criteria. Conclusion: A combination of regression analysis of electrodiagnostic data and a urine biological marker of systemic inflammation identifies a subgroup of diabetic DSP with superimposed acquired demyelination that may respond favorably to immunomodulatory therapy.

Heterologous prime-boost vaccination drives early maturation of HIV broadly neutralizing antibody precursors in humanized mice.

A protective HIV vaccine will likely need to induce broadly neutralizing antibodies (bnAbs). Vaccination with the germline-targeting immunogen eOD-GT8 60mer adjuvanted with AS01B was found to induce VRC01-class bnAb precursors in 97% of vaccine recipients in the IAVI G001 phase 1 clinical trial; however, heterologous boost immunizations with antigens more similar to the native glycoprotein will be required to induce bnAbs. Therefore, we designed core-g28v2 60mer, a nanoparticle immunogen to be used as a first boost after eOD-GT8 60mer priming. We found, using a humanized mouse model approximating human conditions of VRC01-class precursor B cell diversity, affinity, and frequency, that both protein- and mRNA-based heterologous prime-boost regimens induced VRC01-class antibodies that gained key mutations and bound to near-native HIV envelope trimers lacking the N276 glycan. We further showed that VRC01-class antibodies induced by mRNA-based regimens could neutralize pseudoviruses lacking the N276 glycan. These results demonstrated that heterologous boosting can drive maturation toward VRC01-class bnAb development and supported the initiation of the IAVI G002 phase 1 trial testing mRNA-encoded nanoparticle prime-boost regimens.

A Translaminar Spacetime Code Supports Touch-Evoked Traveling Waves.

Linking sensory-evoked traveling waves to underlying circuit patterns is critical to understanding the neural basis of sensory perception. To form this link, we performed simultaneous electrophysiology and two-photon calcium imaging through transparent NeuroGrids and mapped touch-evoked cortical traveling waves and their underlying microcircuit dynamics. In awake mice, both passive and active whisker touch elicited traveling waves within and across barrels, with a fast early component followed by a variable late wave that lasted hundreds of milliseconds post-stimulus. Strikingly, late-wave dynamics were modulated by stimulus value and correlated with task performance. Mechanistically, the late wave component was i) modulated by motor feedback, ii) complemented by a sparse ensemble pattern across layer 2/3, which a balanced-state network model reconciled via inhibitory stabilization, and iii) aligned to regenerative Layer-5 apical dendritic Ca 2+ events. Our results reveal a translaminar spacetime pattern organized by cortical feedback in the sensory cortex that supports touch-evoked traveling waves. GRAPHICAL ABSTRACT AND HIGHLIGHTS: Whisker touch evokes both early- and late-traveling waves in the barrel cortex over 100's of millisecondsReward reinforcement modulates wave dynamics Late wave emergence coincides with network sparsity in L23 and time-locked L5 dendritic Ca 2+ spikes Experimental and computational results link motor feedback to distinct translaminar spacetime patterns.

An automated computational data pipeline to rapidly acquire, score, and rank toxicological data for ecological hazard assessment.

Biological Evaluations support Endangered Species Act (ESA) consultation with the US Fish and Wildlife Service and National Marine Fisheries Service by federal action agencies, such as the USEPA, regarding impacts of federal activities on threatened or endangered species. However, they are often time-consuming and challenging to conduct. The identification of pollutant benchmarks or guidance to protect taxa for states and tribes when USEPA has not yet developed criteria recommendations is also of importance to ensure a streamlined approach to Clean Water Act program implementation. Due to substantial workloads, tight regulatory timelines, and the often-protracted length of ESA consultations, there is a need to streamline the development of biological evaluation toxicity assessments for determining the impact of chemical pollutants on ESA-listed species. Moreover, there is limited availability of species-specific toxicity data for many contaminants, further complicating the consultation process. New approach methodologies are being increasingly used in toxicology and chemical safety assessment to rapidly and cost-effectively provide data that can fill gaps in hazard and/or exposure characterization. Here, we present the development of an automated computational pipeline-RASRTox (Rapidly Acquire, Score, and Rank Toxicological data)-to rapidly extract and categorize ecological toxicity benchmark values from curated data sources (ECOTOX, ToxCast) and well-established quantitative structure-activity relationships (TEST, ECOSAR). As a proof of concept, points-of-departure (PODs) generated in RASRTox for 13 chemicals were compared against benchmark values derived using traditional methods-toxicity reference values (TRVs) and water quality criteria (WQC). The RASRTox PODs were generally within an order of magnitude of corresponding TRVs, though less concordant compared with WQC. The greatest utility of RASRTox, however, lies in its ability to quickly and systematically identify critical studies that may serve as a basis for screening value derivation by toxicologists as part of an ecological hazard assessment. As such, the strategy described in this case study can potentially be adapted for other risk assessment contexts and stakeholder needs. Integr Environ Assess Manag 2024;00:1-15. © 2024 Society of Environmental Toxicology & Chemistry (SETAC). This article has been contributed to by U.S. Government employees and their work is in the public domain in the USA.

Videoconference-delivered group Cognitive Behavioral Stress Management for ME/CFS patients who present with severe PEM: A randomized controlled trial.

Background: In Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS), post-exertional malaise (PEM) is associated with greater distress and symptoms. Cognitive Behavioral Stress Management (CBSM) has demonstrated beneficial effects for ME/CFS and may mitigate stress-related triggers of PEM. We tested a virtual CBSM intervention to increase access, and we report on its effects on stress and symptoms in ME/CFS patients with severe PEM. Methods: Data were from a randomized controlled trial (NCT01650636) comparing 10-week videoconference-delivered group CBSM (V-CBSM, n=75) to a 10-week Health Information active control (V-HI, n=75) in Fukuda criteria ME/CFS patients (71 classified as highPEM, 79 lowPEM). Linear regression explored PEM-by-Treatment interactions on overall symptom frequency and intensity, perceived stress, and fatigue-specific interference and intensity, at 5-month follow-up. Logistic regression tested V-CBSM effects on 5-month PEM status. Analyses controlled for age, gender, race/ethnicity, mode of symptom onset, and time since diagnosis. Results: The sample was middle-aged (47.96±10.89 years), mostly women (87%) and non-Hispanic White (65%), with no group differences on these variables or baseline PEM. For highPEM patients, V-CBSM (versus V-HI) demonstrated medium to large effects on follow-up symptom frequency, symptom intensity, fatigue interference, and fatigue intensity (p's < .05) and trending to significant reductions in perceived stress (p =.07). Differences were not evident for lowPEM patients. Treatment predicted follow-up PEM status at a trend (p = .058), with patients receiving V-CBSM demonstrating half the risk of highPEM classification versus V-HI. Conclusions: V-CBSM demonstrates benefits for ME/CFS patients presenting with severe PEM and may reduce the expression of PEM over time.

Secondary analysis of Staphylococcus aureus whole genomes reveals diverse antimicrobial resistance profiles.

Antimicrobial resistance (AMR) in microorganisms is an ongoing threat to human health across the globe. To better characterize the AMR profiles of six strains of Staphylococcus aureus , we performed a secondary analysis that consisted of the following steps: 1) download fastq files from the Sequence Read Archive, 2) perform a de novo genome assembly from the sequencing reads, 3) annotate the assembled contigs, 4) predict the presence of antimicrobial resistance genes. We predicted the presence of 75 unique genes that conferred resistance against 22 unique antimicrobial compounds.

Continuous drain irrigation as a risk mitigation strategy for postoperative pancreatic fistula: a meta-analysis.

BACKGROUND: Postoperative pancreatic fistula serves as the principle cause for the morbidity and mortality observed after pancreatectomy. Continuous drain irrigation as a treatment strategy for infected pancreatic necrosis has previously been described; however, its role adter pancreatectomy has yet to be determined. The aim of this study was to determine whether continuous drain irrigation reduces postoperative pancreatic fistula. METHODS: A meta-analysis of the pre-existing literature was performed. The primary end point was whether continuous drain irrigation reduced postoperative pancreatic fistula after pancreatectomy. The secondary end point evaluated its impact on postoperative morbidity, mortality, and length of stay. RESULTS: Nine articles involving 782 patients were included. Continuous drain irrigation use was associated with a statistically significant reduction in postoperative pancreatic fistula rates (odds ratio [95% confidence interval] 0.40 [0.19-0.82], P = .01). Upon subgroup analysis, a significant reduction in clinically relevant postoperative pancreatic fistula was also noted (odds ratio 0.37 [0.20-0.66], P = .0008). A reduction in postoperative complications was also observed-delayed gastric emptying (0.45 [0.24-0.84], P = .01) and the need for re-operation (0.33 [0.11-0.96], P = .04). This reduction in postoperative complications translated into a reduced length of stay (mean difference -2.62 [-4.97 to -0.26], P = .03). CONCLUSION: Continuous drain irrigation after pancreatectomy is a novel treatment strategy with a limited body of published evidence. After acknowledging the limitations of the data, initial analysis would suggest that it may serve as an effective risk mitigation strategy against postoperative pancreatic fistula. Further research in a prospective context utilizing patient risk stratification for fistula development is, however, required to define its role within clinical practice.

Active surveillance of low-grade prostate cancer using the SurACaP Criteria: A multi-institutional series with a median follow-up of 10years.

PURPOSE: To report on the oncological outcomes of active surveillance (AS) in low-grade prostate cancer (PCa) patients using the French SurACaP protocol, with a focus on long-term outcomes. METHODS: This multicenter study recruited patients with low-grade PCa between 2007 and 2013 in four referral centers in France. The cohort included patients meeting the SurACaP inclusion criteria, i.e., aged ≤75years, with low-grade PCa (i.e., ISUP 1), clinical stage T1c/T2a, PSA ≤10ng/mL and ≤3 positive cores and tumor length ≤3mm per core. The SurACaP protocol included a digital rectal examination every six months, PSA level measurement every three months for the first two years after inclusion and twice a year thereafter, a confirmatory biopsy in the first year after inclusion, and then follow-up biopsy every two years or if disease progression was suspected. Multiparametric magnetic resonance imaging (mpMRI) was progressively included over the study period. RESULTS: A total of 86 consecutive patients were included, with a median follow-up of 10.6 years. Only one patient developed metastases and died of PCa. The estimated rates of grade reclassification and treatment-free survival at 15 years were 53.4% and 21.2%, respectively. A negative mpMRI at baseline and a negative confirmatory biopsy were significantly associated with a lower risk of disease progression (P<0.05). CONCLUSIONS: AS using the French SurACaP protocol is a safe and valuable strategy for patients with low-risk PCa, with excellent oncological outcomes after more than 10 years' follow-up. Future studies are crucial to broaden the inclusion criteria and develop a personalized, risk based AS protocol with the aim of de-escalating follow-up examinations. LEVEL OF EVIDENCE: Grade 4.

Performance of the first-trimester Fetal Medicine Foundation competing risks model for preeclampsia prediction: an external validation study in Brazil.

BACKGROUND: The current version of the Fetal Medicine Foundation competing risks model for preeclampsia prediction has not been previously validated in Brazil. OBJECTIVE: This study aimed (1) to validate the Fetal Medicine Foundation combined algorithm for the prediction of preterm preeclampsia in the Brazilian population and (2) to describe the accuracy and calibration of the Fetal Medicine Foundation algorithm when considering the prophylactic use of aspirin by clinical criteria. STUDY DESIGN: This was a cohort study, including consecutive singleton pregnancies undergoing preeclampsia screening at 11 to 14 weeks of gestation, examining maternal characteristics, medical history, and biophysical markers between October 2010 and December 2018 in a university hospital in Brazil. Risks were calculated using the 2018 version of the algorithm available on the Fetal Medicine Foundation website, and cases were classified as low or high risk using a cutoff of 1/100 to evaluate predictive performance. Expected and observed cases with preeclampsia according to the Fetal Medicine Foundation-estimated risk range (≥1 in 10; 1 in 11 to 1 in 50; 1 in 51 to 1 in 100; 1 in 101 to 1 in 150; and <1 in 150) were compared. After identifying high-risk pregnant women who used aspirin, the treatment effect of 62% reduction in preterm preeclampsia identified in the Combined Multimarker Screening and Randomized Patient Treatment with Aspirin for Evidence-Based Preeclampsia Prevention trial was used to evaluate the predictive performance adjusted for the effect of aspirin. The number of potentially unpreventable cases in the group without aspirin use was estimated. RESULTS: Among 2749 pregnancies, preterm preeclampsia occurred in 84 (3.1%). With a risk cutoff of 1/100, the screen-positive rate was 25.8%. The detection rate was 71.4%, with a false positive rate of 24.4%. The area under the curve was 0.818 (95% confidence interval, 0.773-0.863). In the risk range ≥1/10, there is an agreement between the number of expected cases and the number of observed cases, and in the other ranges, the predicted risk was lower than the observed rates. Accounting for the effect of aspirin resulted in an increase in detection rate and positive predictive values and a slight decrease in the false positive rate. With 27 cases of preterm preeclampsia in the high-risk group without aspirin use, we estimated that 16 of these cases of preterm preeclampsia would have been avoided if this group had received prophylaxis. CONCLUSION: In a high-prevalence setting, the Fetal Medicine Foundation algorithm can identify women who are more likely to develop preterm preeclampsia. Not accounting for the effect of aspirin underestimates the screening performance.

The Language of Creativity: Evidence from Humans and Large Language Models.

Recent developments in computerized scoring via semantic distance have provided automated assessments of verbal creativity. Here, we extend past work, applying computational linguistic approaches to characterize salient features of creative text. We hypothesize that, in addition to semantic diversity, the degree to which a story includes perceptual details, thus transporting the reader to another time and place, would be predictive of creativity. Additionally, we explore the use of generative language models to supplement human data collection and examine the extent to which machine-generated stories can mimic human creativity. We collect 600 short stories from human participants and GPT-3, subsequently randomized and assessed on their creative quality. Results indicate that the presence of perceptual details, in conjunction with semantic diversity, is highly predictive of creativity. These results were replicated in an independent sample of stories (n = 120) generated by GPT-4. We do not observe a significant difference between human and AI-generated stories in terms of creativity ratings, and we also observe positive correlations between human and AI assessments of creativity. Implications and future directions are discussed.

Carotid Cavernous Fistula.

Carotid cavernous fistulae (CCFs) are arteriovenous shunts involving the cavernous sinus. CCFs are defined as direct or indirect. Direct CCFs are treated by deconstructive or reconstructive techniques depending on whether the affected internal carotid artery is required to perfuse the ipsilateral cerebral hemisphere, as determined by a balloon test occlusion. Indirect CCFs, or dural fistulae of the cavernous sinus wall, are most often treated with transvenous embolization. Stereotactic radiosurgery is reserved for cases of indirect CCFs that are not completely obliterated by embolization. Overall, cure rates are high with relatively low complication rates.

Artificial Neural Network Analysis Examining Substance Use Problems Co-Occurring with Anxiety and Depressive Disorders Among Adults Receiving Mental Health Treatment.

Objective: The co-occurrence of anxiety disorders, depressive disorders, and substance use problems was examined. Methods: The Mental Health Client-Level Data dataset was used to conduct logistic regression models and an artificial neural network analysis. Logistic regression analyses were conducted among adults with anxiety (n = 547,473) or depressive disorders (n = 1,610,601) as their primary diagnosis who received treatment in a community mental health center. The artificial neural network analysis was conducted with the entire sample (N = 2,158,074). Results: Approximately 30% of the sample had co-occurring high-risk substance use or substance use disorder. Characteristics including region of treatment receipt, age, education, gender, race and ethnicity, and the presence of co-occurring anxiety and depressive disorders were associated with the co-occurring high-risk substance use or a substance use disorder. Conclusions: Findings from this study highlight the importance of mental health facilities to screen for and provide integrated treatment for co-occurring disorders.

Head-to-head comparison of appropriate use criteria for knee arthroplasty: A multicenter cohort study.

Objective: To determine, in a head-to-head comparison, which of two RAND-based knee replacement appropriateness criteria is optimal based on comparison to an externally validated method of judging good versus poor outcome. Design: Longitudinal data from the Osteoarthritis Initiative (OAI) and the Multicenter Osteoarthritis Study (MOST) were combined to produce a dataset of 922 persons with knee arthroplasty, 602 of which had adequate data for RAND classification and had their surgery within one year prior to a study visit. Data were used to determine appropriateness classification (i.e., Appropriate, Inconclusive, Rarely Appropriate) using modified versions of the first-generation and second-generation Escobar system. Growth curve analyses and multivariable regression were used to compare the two systems. Results: Neither system associated with the gold standard measure of good versus poor outcome. Distributions of appropriateness categories for the second-generation system were inconsistent with current evidence for knee arthroplasty outcome. For example, 16% of participants were classified as Appropriate and 64% as Rarely Appropriate for pain outcome. Distributions for the first-generation system aligned with current evidence. Conclusion: The first-generation modified version of the Escobar appropriateness system is superior to the newer version but neither version associated with our gold standard growth curve analyses. Both systems only differentiate between patient classification groups preoperatively and up to ten months following surgery. Reliance on appropriateness criteria to inform long-term outcome is not warranted.

Fasciotomy following North American pit viper envenomation in Texas 2004-2021.

INTRODUCTION: North American pit viper envenomation occurs over 4,000 times annually in the United States, with polyvalent Fab antivenom being the primary treatment. Fasciotomy is occasionally performed due to concerns about compartment syndrome. We utilized our direct access to Texas Poison Center Network data to create a new snakebite abstraction form and database on relevant available information between 2004 and 2021 and to identify, describe, and estimate the incidence of fasciotomy following pit viper envenomation in Texas. METHODS: We searched the Texas Poison Center Network database for cases during 2004-2021 using keywords such as fasciotomy, surgery, compartment pressure, and compartment syndrome. Descriptive statistics summarized the data. RESULTS: Of 16,911 reported envenomations, 0.69 percent involved fasciotomies (n = 117). Most common bite sites were digits/hands and lower extremities. Patients who underwent fasciotomy were typically male, aged 20-59, and 10 years younger than the total snakebite population. Only 6 percent of reported compartment syndrome cases had a compartment pressure measurement. Antivenom was administered in 101 (86.3 percent) cases, 92 (91.1 percent) of which received only Fab antivenom product. Patients with bites from rattlesnakes (47.9 percent) were associated with most fasciotomies. DISCUSSION: Our findings suggest a potential increase in snakebite exposures, accompanied by a decrease in fasciotomies. Overall, copperheads constituted the majority of snakebites, but most fasciotomies were from rattlesnake envenomations (47.9 percent). In this cohort, compartment syndrome diagnosis and decisions regarding fasciotomy were primarily based on clinical evaluation/surgeon expertise without compartment pressure measurements. Despite the efficacy of antivenom, only 86.3 percent of patients in our study received antivenom. CONCLUSIONS: Fasciotomy after North American pit viper envenomation in Texas is uncommon (0.69 percent) and has decreased over time, possibly due to increased antivenom use or surgeon comfort with nonsurgical management.