Immune-Targeted Therapies for Depression: Current Evidence for Antidepressant Effects of Monoclonal Antibodies.

Importance: Increasing evidence suggests a potential role of immune-modulatory drugs for treatment-resistant depression. This scoping review explores the emerging evidence regarding the antidepressant effects of monoclonal antibodies (mAbs), a relatively newer class of immune therapeutics with favorable safety profile.Observations: PubMed was searched up to November 2023 for English publications addressing the antidepressant effects of mAbs, including meta-analyses, randomized controlled trials, open-label, single-arm studies, and case series. Several mAbs have shown potential antidepressant effects, but most studies in primary inflammatory disorders included patients with mild depression. Only infliximab and sirukumab were directly examined in individuals with primary depression. mAbs that do not require laboratory monitoring, such as ixekizumab and dupilumab, could hold potential promise if future studies establish their safety profile regarding suicide risk.Conclusions and Relevance: The use of several mAbs for the treatment of primary inflammatory disorders has been associated with improvement of comorbid depressive symptoms. Given their unique mechanisms of action, mAbs may offer a new hope for depressed patients who do not respond to currently available antidepressants. Further research addressing individuals with more severe depressive symptoms is essential. Direct examination of antidepressant effects of mAbs in people with primary depressive disorders is also crucial to refine their clinical use in the treatment of depression.

Mono-methylation of lysine 27 at histone 3 confers lifelong susceptibility to stress.

Histone post-translational modifications are critical for mediating persistent alterations in gene expression. By combining unbiased proteomics profiling and genome-wide approaches, we uncovered a role for mono-methylation of lysine 27 at histone H3 (H3K27me1) in the enduring effects of stress. Specifically, mice susceptible to early life stress (ELS) or chronic social defeat stress (CSDS) displayed increased H3K27me1 enrichment in the nucleus accumbens (NAc), a key brain-reward region. Stress-induced H3K27me1 accumulation occurred at genes that control neuronal excitability and was mediated by the VEFS domain of SUZ12, a core subunit of the polycomb repressive complex-2, which controls H3K27 methylation patterns. Viral VEFS expression changed the transcriptional profile of the NAc, led to social, emotional, and cognitive abnormalities, and altered excitability and synaptic transmission of NAc D1-medium spiny neurons. Together, we describe a novel function of H3K27me1 in the brain and demonstrate its role as a "chromatin scar" that mediates lifelong stress susceptibility.

Exploring the influence of slaughterhouse type and slaughtering steps on Campylobacter jejuni contamination in chicken meat: A cluster analysis approach.

Campylobacter jejuni (C. jejuni), a foodborne pathogen, poses notable hazards to human health and has significant economic implications for poultry production. This study aimed to assess C. jejuni contamination levels in chicken carcasses from both backyard and commercial slaughterhouses in Chiang Mai province, Thailand. It also sought to examine the effects of different slaughtering practices on contamination levels and to offer evidence-based recommendations for reducing C. jejuni contamination. Through the sampling of 105 chicken carcasses and subsequent enumeration of C. jejuni, the study captured the impact of various slaughtering practices. Utilizing k-modes clustering on the observational and bacterial count data, the research identified distinct patterns of contamination, revealing higher levels in backyard operations compared to commercial ones. The application of k-modes clustering highlighted the impact of critical slaughtering practices, particularly chilling, on contamination levels. Notably, samples with the lowest bacterial counts were typically from the chilling step, a practice predominantly found in commercial facilities. This observation underpins the recommendation for backyard slaughterhouses to incorporate ice in their post-evisceration soaking process. Mimicking commercial practices, this chilling method aims to inhibit C. jejuni growth by reducing carcass temperature, thereby enhancing food safety. Furthermore, the study suggests backyard operations adopt additional measures observed in commercial settings, like segregating equipment for each slaughtering step and implementing regular cleaning protocols. These strategic interventions are pivotal in reducing contamination risks, advancing microbiological safety in poultry processing, and aligning with global food safety enhancement efforts.

ß-Amino Acids Reduce Ternary Complex Stability and Alter the Translation Elongation Mechanism.

Templated synthesis of proteins containing non-natural amino acids (nnAAs) promises to expand the chemical space available to biological therapeutics and materials, but existing technologies are still limiting. Addressing these limitations requires a deeper understanding of the mechanism of protein synthesis and how it is perturbed by nnAAs. Here we examine the impact of nnAAs on the formation and ribosome utilization of the central elongation substrate: the ternary complex of native, aminoacylated tRNA, thermally unstable elongation factor, and GTP. By performing ensemble and single-molecule fluorescence resonance energy transfer measurements, we reveal that both the (R)- and (S)-ß2 isomers of phenylalanine (Phe) disrupt ternary complex formation to levels below in vitro detection limits, while (R)- and (S)-ß3-Phe reduce ternary complex stability by 1 order of magnitude. Consistent with these findings, (R)- and (S)-ß2-Phe-charged tRNAs were not utilized by the ribosome, while (R)- and (S)-ß3-Phe stereoisomers were utilized inefficiently. (R)-ß3-Phe but not (S)-ß3-Phe also exhibited order of magnitude defects in the rate of translocation after mRNA decoding. We conclude from these findings that non-natural amino acids can negatively impact the translation mechanism on multiple fronts and that the bottlenecks for improvement must include the consideration of the efficiency and stability of ternary complex formation.

Role of ferroptosis in radiation-induced soft tissue injury.

Ionizing radiation has been pivotal in cancer therapy since its discovery. Despite its therapeutic benefits, IR causes significant acute and chronic complications due to DNA damage and the generation of reactive oxygen species, which harm nucleic acids, lipids, and proteins. While cancer cells are more vulnerable to ionizing radiation due to their inefficiency in repairing damage, healthy cells in the irradiated area also suffer. Various types of cell death occur, including apoptosis, necrosis, pyroptosis, autophagy-dependent cell death, immunogenic cell death, and ferroptosis. Ferroptosis, driven by iron-dependent lipid peroxide accumulation, has been recognized as crucial in radiation therapy's therapeutic effects and complications, with extensive research across various tissues. This review aims to summarize the pathways involved in radiation-related ferroptosis, findings in different organs, and drugs targeting ferroptosis to mitigate its harmful effects.

Hepatitis C-related knowledge and attitude among adults on probation in a large US city.

BACKGROUND: Hepatitis C virus (HCV) continues to cause significant morbidity and mortality within the US, and disproportionately impacts those involved with the criminal justice system. Despite this, knowledge and attitudes regarding HCV treatment among adults on probation have not been well studied. We conducted a cross-sectional survey of adults on probation accessing on-site HCV testing and linkage services at the adult probation department in Denver, Colorado. The survey assessed general knowledge of HCV and HCV treatment, as well as attitudes surrounding HCV treatment that might reflect medical mistrust. We used bivariate and multivariable logistic regression to identify factors associated with previous HCV testing, previous HCV treatment, and HCV antibody positivity at the time the survey was conducted. RESULTS: A total of 402 participants completed all or a portion of the survey. 69% of the participants were cis-gender men; 29% were white, 27% were Black, and 30% were Hispanic/Latinx. Fewer than half of participants correctly identified that HCV infection is commonly asymptomatic (46%), that there is currently no vaccine that prevents HCV (19%), and that reinfection after treatment is possible (47%). Very few participants felt that side-effects (9%) or cost of treatment (10%) were barriers to care. Many participants believed that racial disparities exist in the treatment of HCV (59%). The belief that people who use substances are treated inequitably by health care providers was also commonly reported (35% of participants). Self-reported injection drug use and higher HCV-related knowledge were positively associated with previous testing for HCV. Higher HCV-related knowledge was positively associated with HCV antibody positivity at the time of survey completion, though the magnitude of the association was small. CONCLUSION: Interventions are needed to increase knowledge of HCV, to improve access to HCV testing and treatment, and to reduce bias associated with HCV and substance use within the probation population.

Probing Baculovirus Vector Gene Essentiality for Foreign Gene Expression Using a CRISPR-Cas9 System.

The baculovirus expression vector system (BEVS) has now found acceptance in both research laboratories and industry, which can be attributed to many of its key features including the limited host range of the vectors, their non-pathogenicity to humans, and the mammalian-like post-translational modification (PTMs) that can be achieved in insect cells. In fact, this system acts as a middle ground between prokaryotes and higher eukaryotes to produce complex biologics. Still, industrial use of the BEVS lags compared to other platforms. We have postulated that one reason for this has been a lack of genetic tools that can complement the study of baculovirus vectors, while a second reason is the co-production of the baculovirus vector with the desired product. While some genetic enhancements have been made to improve the BEVS as a production platform, the genome remains under-scrutinized. This chapter outlines the methodology for a CRISPR-Cas9-based transfection-infection assay to probe the baculovirus genome for essential/nonessential genes that can potentially maximize foreign gene expression under a promoter of choice.

Affective, perceptual and physiologic responses to isokinetic contractions under blood flow restriction.

BACKGROUND: Blood flow restriction (BFR) has been shown to enhance the effectiveness of low load resistance exercise, but less research has examined its utility in conjunction with maximal isokinetic contractions, which may depend on the restrictive pressure and speed of contraction. METHODS: Individuals reported to the laboratory for three visits to complete three sets of 20 maximal elbow flexion exercises at 60°/s and 300°/s under 0%, 40% and 80% of their arterial occlusion pressure. Muscle thickness was measured before and after exercise, and ratings of discomfort, perceived activation, and exercise-induced feelings were obtained at the completion of each exercise. Fatigue was assessed as the decline in average peak torque across the three sets. RESULTS: A total of 27 individuals (11 females, 16 males) completed the study. There was a significant interaction for torque at both 60°/s and 300°/s (P<0.001), with each increasing pressure resulting in greater fatigue. Muscle swelling was present across all conditions but was lowest in the 40% BFR condition applied during the 300°/s speed. At both 60°/s and 300°/s speeds, the 80% BFR pressure was associated with lower enjoyment, greater discomfort, and greater perceived activation (all P<0.05). CONCLUSIONS: The combined effects of BFR to maximal isokinetic contractions increased fatigue with less of an impact on muscle swelling. These results indicate that BFR may enhance the effectiveness of long-term isokinetic training, but it is also important to consider the addition of BFR was associated with lower levels of enjoyment and greater discomfort which may decrease adherence.

Factors associated with having uncontrolled asthma in rural Appalachia.

BACKGROUND: Chronic respiratory disease disproportionately affects residents of Appalachia, particularly those residing in Central Appalachia. Asthma is particularly burdensome to Central Appalachian residents regarding cost and disability. Improving our understanding of how to mitigate these burdens requires understanding the factors influencing asthma control among individuals with asthma living in Central Appalachia, specifically rural Kentucky. METHODS: This community-based, cross-sectional epidemiologic study used survey data to identify characteristics associated with uncontrolled and controlled asthma. The designation of "uncontrolled asthma" was based on a self-report of ≥ 2 asthma exacerbations in the past year. Individuals with ≤ 1 or no exacerbations were considered to have controlled asthma. Chi-square or Fisher exact tests assessed the association between categorical variables and asthma control categories. Logistic regression was conducted to determine the impact of factors on the likelihood of uncontrolled asthma. RESULTS: In a sample of 211 individuals with self-reported asthma, 29% (n = 61, 46 females) had uncontrolled asthma. Predictors of uncontrolled asthma included depression (odds ratio 2.61, 95% CI 1.22-5.61, p = .014) and living in multi-unit housing (odds ratio 4.99, 95% CI 1.47-16.96, p = .010) when controlling for age, sex, financial status, and occupation. Being overweight or obese was not a predictor of uncontrolled asthma. Physical activity and BMI did not predict the likelihood of uncontrolled asthma. CONCLUSION: This study highlights significant challenges rural communities in Appalachian Kentucky face in managing asthma. Factors like depression, housing conditions, and a lack of self-management strategies play pivotal roles in asthma control in this population.

Postoperative Medial Malleolar Fractures in Total Ankle Replacement Are Associated With Decreased Medial Malleolar Width and Varus Malalignment: A Case-Control Study.

BACKGROUND: There are limited data regarding risk factors associated with periprosthetic medial malleolar fractures in total ankle arthroplasty (TAA). This case-control study aimed to identify the risk factors and analyze the effect of prophylactic screw fixation in preventing a medial malleolar fracture after TAA. METHODS: A case-control study was conducted on 149 patients who underwent primary TAA. Twenty patients with postoperative medial malleolar fractures >4 weeks postoperatively (cases) were identified. An additional 129 patients (controls) were randomly selected from the TAA database. Radiographic evaluation included tibial component coronal alignment and postoperative medial malleolar width. Demographics and radiographic variables were compared between cohorts. Logistic regression was used to investigate the association between medial malleolar fracture and postoperative coronal alignment, medial malleolar width, and prophylactic fixation of the medial malleolus. RESULTS: Mean (SD) medial malleolar width was significantly smaller in the fracture cohort (8.52 mm [1.6]) than in the control group (11.78 mm [1.74]) (P < .001). Mean (SD) tibial component coronal alignment was 92.17 degrees (2.77) in the fracture cohort and 90.21 degrees (1.66) in the control group (P = .002). Regression analysis identified a significant negative association between postoperative medial malleolar width and the probability of fracture (OR = 0.06, 95% CI 0.01, 0.26, P < .001). Varus malalignment of the tibial component was positively associated with the probability of fracture (OR = 1.90, 95% CI 1.27, 2.86, P = .002). Prophylactic screw fixation resulted in more than 90% reduction in the odds of a fracture (OR = 0.04, 95% CI 0.01, 0.45, P = .01). ROC curve analysis determined a medial malleolar width of 10.3 mm as a potential threshold for predicting fracture. CONCLUSION: Decreased medial malleolar width and postoperative varus malalignment were associated with an increased risk of postoperative medial malleolar fracture. Therefore, surgeons should consider prophylactic screw fixation in patients with a medial malleolar width <10.3 mm or at risk of postoperative varus deformity.

Fe/Thiol Cooperative Hydrogen Atom Transfer Olefin Hydrogenation: Mechanistic Insights That Inform Enantioselective Catalysis.

Asymmetric hydrogenation of activated olefins using transition metal catalysis is a powerful tool for the synthesis of complex molecules, but traditional metal catalysts have difficulty with enantioselective reduction of electron-neutral, electron-rich, and minimally functionalized olefins. Hydrogenation based on radical, metal-catalyzed hydrogen atom transfer (mHAT) mechanisms offers an outstanding opportunity to overcome these difficulties, enabling the mild reduction of these challenging olefins with selectivity that is complementary to traditional hydrogenations with H2. Further, mHAT presents an opportunity for asymmetric induction through cooperative hydrogen atom transfer (cHAT) using chiral thiols. Here, we report insights from a mechanistic study of an iron-catalyzed achiral cHAT reaction and leverage these insights to deliver stereocontrol from chiral thiols. Kinetic analysis and variation of silane structure point to the transfer of hydride from silane to iron as the likely rate-limiting step. The data indicate that the selectivity-determining step is quenching of the alkyl radical by thiol, which becomes a more potent H atom donor when coordinated to iron(II). The resulting iron(III)-thiolate complex is in equilibrium with other iron species, including FeII(acac)2, which is shown to be the predominant off-cycle species. The enantiodetermining nature of the thiol trapping step enables enantioselective net hydrogenation of olefins through cHAT using a commercially available glucose-derived thiol catalyst with up to 80:20 enantiomeric ratio. To the best of our knowledge, this is the first demonstration of asymmetric hydrogenation via iron-catalyzed mHAT. These findings advance our understanding of cooperative radical catalysis and act as a proof of principle for the development of enantioselective iron-catalyzed mHAT reactions.

Utility of TTMV-HPV DNA in resolving indeterminate findings during oropharyngeal cancer surveillance.

OBJECTIVES: Clinical and imaging examinations frequently have indeterminate results during cancer surveillance, which can lead to overtreatment and cause psychological and financial harm to the patient. This study addresses the critical need to enhance diagnostic precision and decision-making in the management of HPV-associated oropharyngeal cancer. This study evaluated the utility of tumor tissue-modified viral (TTMV)-HPV DNA to resolve indeterminate disease status following definitive treatment for HPV-associated oropharyngeal cancer. MATERIALS AND METHODS: In this retrospective cohort, patients treated for HPV-associated oropharyngeal cancer at eight U.S. institutions and who received one or more TTMV-HPV DNA tests during post-treatment surveillance between February 2020 and January 2022 were included. RESULTS: Among 543 patients, 210 patients (38.7%; 210/543) experienced one or more clinically indeterminate findings (CIFs) during surveillance, with 503 CIFs recorded. Of those patients with an "indeterminate" disease status at a point during surveillance, 79 were associated with contemporaneous TTMV-HPV DNA testing. TTMV-HPV DNA testing demonstrated high accuracy (97.5%; 77/79) in correctly determining recurrence status. Patients whose disease status was "indeterminate" at the time of a positive TTMV-HPV DNA test were clinically confirmed to recur faster than those whose disease status was "no evidence of disease." Only 3% of patients (17/543) experienced indeterminate TTMV-HPV DNA tests during surveillance. Discordance between TTMV-HPV DNA tests and clinical results was minimal, with only 0.6% (3/543) of patients showing positive tests without recurrence. CONCLUSION: Our findings support the utility of circulating TTMV-HPV DNA in resolving indeterminate disease status and informing the subsequent clinical course.

Galvanic Vestibular Stimulation Advancements for Spatial Disorientation Training.

INTRODUCTION: Spatial disorientation (SD) remains the leading contributor to Class A mishaps in the U.S. Navy, consistent with historical trends. Despite this, SD training for military aircrew is largely confined to the classroom and experiential training replicating SD illusions is limited and infrequent. Static flight simulators are most commonly used for training but offer no vestibular stimulation to the flight crew, omitting the source of vestibular-mediated SD.BACKGROUND: We first cover vestibular-mediated SD illusions which may be replicated through galvanic vestibular stimulation (GVS) in a static environment. GVS is a safe, reliable, low-cost avenue for providing vestibular sensory stimulation. We review the underlying mechanisms of GVS such as the excitement and inhibition of the afferent neurons innervating the vestibular system, particularly in the binaural bipolar electrode montage.APPLICATIONS: Two approaches for how GVS may be used to enhance SD training are examined. The first is a means for providing unreliable vestibular sensory perceptions to pilots, and the second details how GVS can be leveraged for replicating vestibular-mediated SD illusions.DISCUSSION: We recommend GVS be pursued as an enhancement to existing SD training. The ability to disorient aircrew in the safe training environment of a static flight simulator would allow for aircrew familiarization to SD, serving as an opportunity to practice life-saving checklist items to recover from SD. A repeatable training profile that could be worn by military aircrew in a static flight simulator may afford a low-cost training solution to the number one cause of fatalities in military aviation.Allred AR, Lippert AF, Wood SJ. Galvanic vestibular stimulation advancements for spatial disorientation training. Aerosp Med Hum Perform. 2024; 95(7):390-398.

Sit-to-Stand Power Is a Stronger Predictor of Gait Speed than Knee Extension Strength.

With a growing aging population, the routine assessment of physical function may become a critical component of clinical practice. The purpose of this cross-sectional study is to compare two common assessments of muscular function: (1) isometric knee extension strength (KES) and (2) sit-to-stand (STS) muscle power tests, in predicting objective physical function (i.e., gait speed) in aging adults. 84 adults (56% female, mean (SD) age = 66.6 (9.4) years) had their relative KES, STS power, usual gait speed (UGS), and fast gait speed (FGS) assessed. Multiple linear regression examined the associations between KES, STS power, and gait outcomes. When entered in separate models, KES and STS power were both independently associated with UGS and FGS (Std. ß = 0.35-0.44 and 0.42-0.55 for KES and STS power, respectively). When entered in the same model, STS power was associated with UGS and FGS (Std. ß = 0.37 [95%CI: 0.15, 0.58] and 0.51 [95%CI: 0.31, 0.70], respectively), while KES was only associated with FGS (Std. ß = 0.25 [95%CI: 0.02, 0.48]). STS power seems to be a valid indicator of function in aging adults. Its feasibility as a screening tool for "low" function in the primary care setting should be explored.

The Mlh1-Pms1 endonuclease uses ATP to preserve DNA discontinuities as strand discrimination signals to facilitate mismatch repair.

In eukaryotic post-replicative mismatch repair, MutS homologs (MSH) detect mismatches and recruit MLH complexes to nick the newly replicated DNA strand upon activation by the replication processivity clamp, PCNA. This incision enables mismatch removal and DNA repair. Biasing MLH endonuclease activity to the newly replicated DNA strand is crucial for repair. In reconstituted in vitro assays, PCNA is loaded at pre-existing discontinuities and orients the major MLH endonuclease Mlh1-Pms1/MLH1-PMS2 (yeast/human) to nick the discontinuous strand. In vivo, newly replicated DNA transiently contains discontinuities which are critical for efficient mismatch repair. How these discontinuities are preserved as strand discrimination signals during the window of time where mismatch repair occurs is unknown. Here, we demonstrate that yeast Mlh1-Pms1 uses ATP binding to recognize DNA discontinuities. This complex does not efficiently interact with PCNA, which partially suppresses ATPase activity, and prevents dissociation from the discontinuity. These data suggest that in addition to initiating mismatch repair by nicking newly replicated DNA, Mlh1-Pms1 protects strand discrimination signals, aiding in maintaining its own strand discrimination signposts. Our findings also highlight the significance of Mlh1-Pms1's ATPase activity for inducing DNA dissociation, as mutant proteins deficient in this function become immobilized on DNA post-incision, explaining in vivo phenotypes.

A Divergent Platelet Transcriptome in Patients with Lipedema and Lymphedema.

Lipedema and lymphedema are physically similar yet distinct diseases that are commonly misdiagnosed. We previously reported that lipedema and lymphedema are associated with increased risk for venous thromboembolism (VTE). The underlying etiology of the prothrombotic profile observed in lipedema and lymphedema is unclear, but may be related to alterations in platelets. Our objective was to analyze the platelet transcriptome to identify biological pathways that may provide insight into platelet activation and thrombosis. The platelet transcriptome was evaluated in patients with lymphedema and lipedema, then compared to control subjects with obesity. Patients with lipedema were found to have a divergent transcriptome from patients with lymphedema. The platelet transcriptome and impacted biological pathways in lipedema were surprisingly similar to weight-matched comparators, yet different when compared to overweight individuals with a lower body mass index (BMI). Differences in the platelet transcriptome for patients with lipedema and lymphedema were found in biological pathways required for protein synthesis and degradation, as well as metabolism. Key differences in the platelet transcriptome for patients with lipedema compared to BMI-matched subjects involved metabolism and glycosaminoglycan processing. These inherent differences in the platelet transcriptome warrant further investigation, and may contribute to the increased risk of thrombosis in patients with lipedema and lymphedema.

Differential effects of opioid receptor antagonism on the anti-dyskinetic and anti-parkinsonian effects of sub-anesthetic ketamine treatment in a preclinical model.

Sub-anesthetic ketamine treatment has been shown to be an effective therapy for treatment-resistant depression and chronic pain. Our group has previously shown that sub-anesthetic ketamine produces acute anti-parkinsonian, and acute anti-dyskinetic effects in preclinical models of Parkinson's disease (PD). Ketamine is a multifunctional drug and exerts effects through blockade of N-methyl-d-aspartate receptors but also through interaction with the opioid system. In this report, we provide detailed pharmacokinetic rodent data on ketamine and its main metabolites following an intraperitoneal injection, and second, we explore the pharmacodynamic properties of ketamine in a rodent PD model with respect to the opioid system, using naloxone, a pan-opioid receptor antagonist, in unilateral 6-hydroxydopamine-lesioned male rats, treated with 6 mg/kg levodopa (l-DOPA) to establish a model of l-DOPA-induced dyskinesia (LID). As previously reported, we showed that ketamine (20 mg/kg) is highly efficacious in reducing LID and now report that the magnitude of this effect is resistant to naloxone (3 and 5 mg/kg). The higher naloxone dose of 5 mg/kg, however, led to an extension of the time-course of the LID, indicating that opioid receptor activation, while not a prerequisite for the anti-dyskinetic effects of ketamine, still exerts an acute modulatory effect. In contrast to the mild modulatory effect on LID, we found that naloxone added to the anti-parkinsonian activity of ketamine, further reducing the akinetic phenotype. In conclusion, our data show opioid receptor blockade differentially modulates the acute anti-parkinsonian and anti-dyskinetic actions of ketamine, providing novel mechanistic information to support repurposing ketamine for individuals with LID.

Preoperative Degenerative Changes at the Tibial Sesamoid-Metatarsal Joint in Hallux Valgus: Association With Postoperative Patient-Reported Outcomes After Modified Lapidus Procedure.

Background: Degenerative changes at the sesamoid-metatarsal joints (SMJs) may be a source of pain following hallux valgus surgery. The aims of this study were to describe degenerative changes at the SMJs on weightbearing computed tomography (WBCT) scans and, secondarily, investigate their association with 1-year patient-reported outcome scores following a modified Lapidus procedure for hallux valgus. We hypothesized that reduced joint space in the SMJs would correlate with worse patient-reported outcomes. Methods: Fifty-seven hallux valgus patients who underwent a modified Lapidus procedure had preoperative and minimum 5-month postoperative WBCT scans, and preoperative and at least 1-year postoperative PROMIS physical function (PF), pain interference, and pain intensity scores were included. Degenerative changes at the SMJs were measured using distance mapping between the sesamoids and first metatarsal head on preoperative and postoperative WBCT scans. The minimum and average distances between the first metatarsal head and tibial sesamoid (tibial-SMJ) for each patient preoperatively and postoperatively were measured. Sesamoid station was measured on WBCT scans using a 0 to 3 grading system. Linear regression was used to investigate the correlations between minimum preoperative and postoperative tibial-SMJ distances and 1-year postoperative PROMIS scores. Results: The median minimum and average tibial-SMJ distances increased from 0.82 mm (interquartile range [IQR] 0.40-1.03 mm) and 1.62 mm (IQR 1.37-1.75 mm) preoperative to 1.09 mm (IQR 0.96-1.23 mm) and 1.73 mm (IQR 1.60-1.91 mm) postoperative (P < .001 and P < .001), respectively. In a subset of patients with complete sesamoid reduction, we found an association between preoperative minimum tibial-SMJ distance and 1-year postoperative PROMIS PF scores (coefficient 7.2, P = .02). Conclusion: Following the modified Lapidus procedure, there was a statistically significant increase in the tibial-SMJ distance. Additionally, in patients with reduced sesamoids postoperatively, reduced preoperative tibial-SMJ distance correlated with worse PROMIS PF scores. Level of Evidence: Level IV, case series.