Owner-reported health and disease in U.S. senior horses.

BACKGROUND: Information on health care and health status of U.S. senior horses (≥15 years of age) is currently sparse. OBJECTIVES: (A) Provide an overview of owner-reported (1) medical conditions, (2) management/treatment practices for equine metabolic syndrome and pituitary pars intermedia dysfunction (PPID), (3) frequencies of routine health care practices and (4) supplement and pharmaceutical use in U.S. senior horses (≥15 years of age). (B) Evaluate potential risk factors for certain medical conditions and for low routine health care. STUDY DESIGN: Online survey. METHODS: Descriptive and inferential analysis (binomial logistic regression and ANOVA) of 2717 questionnaires from owners of U.S. senior horses. RESULTS: The most common owner-reported veterinary-diagnosed medical conditions were osteoarthritis (30%), dental disorders (15%), lameness (14%), PPID (12%) and ocular disorders (6%). Advancing age was found to be a risk factor for PPID (odds ratio [OR] [95% confidence interval, CI] = 1.14 [1.10-1.18]), dental (OR [95% CI] = 1.18 [1.15-1.22]) and ocular (OR [95% CI] = 1.05 [1.01-1.10]) disorders. Only 36% of horses were free of owner-reported veterinary-diagnosed medical conditions at the time of the survey. During the year prior to the survey, most routine healthcare practices (i.e., veterinary health care, dental care and anthelmintic treatment) were typically undertaken one to two times per year, while farrier visits occurred mostly every 5-6 weeks. Retired senior horses had a higher risk of no health care visits (OR [95% CI] = 2.1 [1.38-3.06]), no dental care (OR [95% CI] = 2.0 [1.31-3.00]) and low farrier attendance (i.e., ≤4 times/year) (OR [95% CI] = 2.4 [1.57-3.63]) compared with senior horses used for pleasure riding. The most frequently administered drug was firocoxib (18%) and joint supplements were the most provided supplements (41%). MAIN LIMITATIONS: Potential recall, response and sampling bias. Risk factor analyses do not establish causal relationships. CONCLUSIONS: Medical conditions are highly prevalent in U.S. senior horses. Retired senior horses have an increased risk of low routine health care.

Weightbearing Computed Tomography Can Accurately Detect Subtle Lisfranc Injury.

BACKGROUND: Early detection of Lisfranc injury is critical for improving clinical outcomes, but diagnosing subtle injury can be difficult. Weightbearing computed tomography (WBCT) allows evaluation of such injuries in 3 dimensions (3D) under physiologic load. This study aimed to assess the utility of 1-, 2-, and 3-dimensional measurements on WBCT to diagnose subtle injury in isolated ligamentous Lisfranc injuries. METHODS: Ten cadaveric specimens underwent WBCT evaluation of the Lisfranc joint complex in the intact state and subsequently with sequential sectioning of the dorsal Lisfranc ligament and interosseous Lisfranc ligament (IOL) to create subtle Lisfranc injury, and finally after transectioning of plantar Lisfranc ligament (PLL) to create the injury conditions for complete ligamentous Lisfranc injury. Measurements under static vertical tibial load of 80 kg were performed on WBCT images including (1) Lisfranc joint (medial cuneiform-base of second metatarsal) volume, (2) Lisfranc joint area, (3) C1-C2 intercuneiform area, (4) C1-M2 distance, (5) C1-C2 distance, (6) M1-M2 intermetatarsal distance, (7) first tarsometatarsal (TMT1) alignment, (8) second tarsometatarsal (TMT2) alignment, (9) TMT1 dorsal step-off distance, and (10) TMT2 dorsal step-off distance. RESULTS: In the subtle Lisfranc injury state, Lisfranc joint volume and area, C1-M2 distance, and M1-M2 distance measurements on WBCT significantly increased, when compared with the intact state (P values .001 to .014). Additionally, Lisfranc joint volume and area, C1-M2 distance, M1-M2 distance, TMT2 alignment, and TMT2 dorsal step-off measurements were increased in the complete Lisfranc injury state. Of all measurements, C1-M2 distance had the largest area under the curve (AUC) of 0.96 (sensitivity = 90%; specificity = 90%), followed by Lisfranc volume (AUC = 0.90; sensitivity = 80%; specificity = 80%) and Lisfranc area (AUC = 0.89; sensitivity = 80%; specificity = 100%). CONCLUSION: In a cadaveric model we found that WBCT scan can increase the diagnostic accuracy for subtle Lisfranc injury. Among the measurements, C1-M2 distance exhibited the highest level of accuracy. The 2D joint area and 3D joint volume also proved to be accurate, with 3D volume measurements of the Lisfranc joint displaying the most significant absolute difference between the intact state and increasing severity of Lisfranc injury. These findings suggest that 2D joint area and 3D joint volume may have potential as supplementary measurements to more accurately diagnose subtle Lisfranc injuries. CLINICAL RELEVANCE: WBCT may help surgeons detect subtle Lisfranc injuries.

Cortical Thickness Correlates of Go/No-go and Motor Sequencing in Mild Cognitive Impairment and Suspected Alzheimer Disease Dementia.

BACKGROUND: While the cognitive hallmark of typical Alzheimer's disease (AD) is impaired memory consolidation, increasing evidence suggests that the frontal lobes and associated executive functions are also impacted. OBJECTIVE: We examined two neurobehavioral executive function tasks and associations with cortical thickness in patients diagnosed with mild cognitive impairment (MCI), suspected AD dementia, and a healthy control group. METHODS: First, we compared group performances on a go/no-go (GNG) task and on Luria's Fist-Edge-Palm (FEP) motor sequencing task. We then examined correlations between neurobehavioral task performance and the thickness of frontal cortical regions, AD signature regions, broader unbiased brain regions, and white matter hyperintensities (WMH). RESULTS: Participants with MCI performed worse than healthy controls, but better than participants with suspected AD dementia on both tasks. Both GNG and FEP (to a slightly greater extent) tasks showed diffuse associations with most AD signature regions and multiple additional regions within the temporal, parietal, and occipital cortices. Similarly, both tasks showed significant associations with all other cognitive tasks examined. Of the frontal regions examined, only the middle frontal gyrus and pars opercularis were associated with performance on these tasks. Interactions between the precuneus and transtemporal gyri were most predictive of GNG task performance, while the interaction between superior temporal and lingual gyri was most predictive of FEP task performance. CONCLUSION: This study replicates difficulties with both GNG and FEP tasks in participants with MCI and AD dementia. Both tasks showed widespread associations with the cortical thickness of various brain structures rather than localizing to frontal regions, consistent with the diffuse nature of AD.

Treatment of mares with the non-steroidal anti-inflammatory drug (NSAID) phenylbutazone transiently affects in vitro maturation of equine oocytes and blastocyst development after Intracytoplasmic Sperm Injection (ICSI).

Mares enrolled in assisted reproductive technologies (ARTs) programs are often treated with non-steroidal anti-inflammatory drugs (NSAIDs), particularly phenylbutazone (Bute), due to chronic lameness. The current study was performed to determine the effect of Bute administration on the developmental competence of in vitro-matured equine oocytes subjected to Intracytoplasmic Sperm Injection (ICSI). In a Preliminary Study, immature cumulus-oocyte complexes (COCs) recovered by post-mortem ovary harvested from two healthy mares (n = 2) treated for 10 days with Bute (4.4 mg/kg, PO, BID), and four non-treated healthy mares (n = 4), were matured in vitro and subjected to Piezo-driven ICSI. Lower oocyte in vitro maturation [Bute: 25% (3/12) vs. Control: 61% (28/46)] and blastocyst rates [Bute: 0% (0/12) vs. Control: 18% (5/28)] were observed in the Bute-treated when compared to the Control mares (P < 0.05). In the Main Experiment, a group of healthy mares (n = 9) received a daily dose of Bute (4.4 mg/kg, orally, SID) for 10 days. A control group of mares (n = 10) was treated with an equal volume of placebo. Mares in both groups were subjected to ultrasound-guided transvaginal oocyte aspiration (TVA) on days 3, 33, and 77 following the last dose of Bute (PT). Recovered COCs from both mare groups were matured in vitro and subjected to Piezo-driven ICSI. By day-3 PT, oocyte in vitro maturation rate was similar between mare groups [Bute: 65% (36/55) vs. Control: 67% (78/116); P > 0.05], while oocyte recovery [Bute: 53% (55/103) vs. Control: 70% (116/166)], cleavage [Bute: 31% (11/36) vs. Control: 62% (48/78)] and blastocyst rates [Bute: [0%] (0/36) vs. Control: 28% (22/78)] were significantly different (P < 0.05). By day 33 PT and 77 PT, differences on oocyte recovery, in vitro maturation, cleavage, and blastocyst rates were not observed between mare groups. In summary, the administration of Bute for 10 consecutive days (4.4 mg/kg, PO, SID, or BID) is associated with a decrease in the ability of immature equine oocytes to undergo in vitro-maturation (Preliminary Study) and develop to the blastocyst stage following ICSI (Preliminary Study and Main Experiment). This negative effect appeared to be transient, as 30- and 77-days post-treatment, no differences on in vitro maturation, cleavage or blastocyst rates were observed.

More Similar than Different: Memory, Executive Functions, Cortical Thickness, and Glucose Metabolism in Biomarker-Positive Alzheimer's Disease and Behavioral Variant Frontotemporal Dementia.

Background: Alzheimer's disease (AD) and behavioral variant frontotemporal dementia (bvFTD) are typically associated with very different clinical and neuroanatomical presentations; however, there is increasing recognition of similarities. Objective: To examine memory and executive functions, as well as cortical thickness, and glucose metabolism in AD and bvFTD signature brain regions. Methods: We compared differences in a group of biomarker-defined participants with Alzheimer's disease and a group of clinically diagnosed participants with bvFTD. These groups were also contrasted with healthy controls (HC). Results: As expected, memory functions were generally more impaired in AD, followed by bvFTD, and both clinical groups performed more poorly than the HC group. Executive function measures were similar in AD compared to bvFTD for motor sequencing and go/no-go, but bvFTD had more difficulty with a set shifting task. Participants with AD showed thinner cortex and lower glucose metabolism in the angular gyrus compared to bvFTD. Participants with bvFTD had thinner cortex in the insula and temporal pole relative to AD and healthy controls, but otherwise the two clinical groups were similar for other frontal and temporal signature regions. Conclusions: Overall, the results of this study highlight more similarities than differences between AD and bvFTD in terms of cognitive functions, cortical thickness, and glucose metabolism. Further research is needed to better understand the mechanisms mediating this overlap and how these relationships evolve longitudinally.

Two artificial intelligence models underperform on examinations in a veterinary curriculum.

OBJECTIVE: Advancements in artificial intelligence (AI) and large language models have rapidly generated new possibilities for education and knowledge dissemination in various domains. Currently, our understanding of the knowledge of these models, such as ChatGPT, in the medical and veterinary sciences is in its nascent stage. Educators are faced with an urgent need to better understand these models in order to unleash student potential, promote responsible use, and align AI models with educational goals and learning objectives. The objectives of this study were to evaluate the knowledge level and consistency of responses of 2 platforms of ChatGPT, namely GPT-3.5 and GPT-4.0. SAMPLE: A total of 495 multiple-choice and true/false questions from 15 courses used in the assessment of third-year veterinary students at a single veterinary institution were included in this study. METHODS: The questions were manually entered 3 times into each platform, and answers were recorded. These answers were then compared against those provided by the faculty members coordinating the courses. RESULTS: GPT-3.5 achieved an overall performance score of 55%, whereas GPT-4.0 had a significantly (P < .05) greater performance score of 77%. Importantly, the performance scores of both platforms were significantly (P < .05) below that of the veterinary students (86%). CLINICAL RELEVANCE: Findings of this study suggested that veterinary educators and veterinary students retrieving information from these AI-based platforms should do so with caution.

Retirement risk factors, exercise management and muscle mass in US senior horses.

BACKGROUND: Information on the management and health of US senior horses (≥15 years of age) is currently limited. OBJECTIVES: Provide information on (1) primary use of US senior horses, (2) reasons and risk factors for horse retirement, (3) exercise management, (4) prevalence of low muscle mass and (5) risk factors for, and owner-perceived consequences of, low muscle mass. STUDY DESIGN: Online survey. METHODS: Survey responses from 2717 owners of U.S.-resident senior horses (≥15 years of age) were analysed descriptively and inferentially, using ordered and binomial logistic regression, ANOVA and the Kruskal-Wallis test. RESULTS: The most frequently reported primary uses were pleasure riding/driving (38.5%) and full retirement (39.8%). Most horses (61.5%) were retired between 15 and 24 years of age, with health problems being the main reason. Age, female sex, Thoroughbred breed and various medical conditions were identified as risk factors for retirement. In working horses (i.e., those not retired or semi-retired), exercise intensity was negatively associated with age. The owner-reported prevalence of low muscle mass in all horses was 17.2% (95%CI = 15.7-18.7). In those affected by low muscle mass, the ability to work and welfare-related aspects were commonly perceived to be impaired. Increasing age, sex (gelding), pituitary pars intermedia dysfunction, osteoarthritis, laminitis and primary use (retired and semi-retired vs. use for competition) were identified as risk factors for owner-reported low muscle mass. MAIN LIMITATIONS: Potential response, recall and sampling bias. Causal relationships cannot be established. CONCLUSIONS: Although structured exercise into old age may provide health benefits (as seen in elderly people), a large proportion of horses were fully retired in the current study. Senior horses were mainly retired for health problems and characterising these problems may aid in extending their work/active life. Low muscle mass was perceived to affect horses' welfare and ability to work, and identification of prevention and treatment strategies is therefore warranted.

GBS hyaluronidase mediates immune suppression in a TLR2/4- and IL-10-dependent manner during pregnancy-associated infection.

IMPORTANCE: Bacteria such as GBS can cause infections during pregnancy leading to preterm births, stillbirths, and neonatal infections. The interaction between host and bacterial factors during infections in the placenta is not fully understood. GBS secretes a hyaluronidase enzyme that is thought to digest host hyaluronan into immunosuppressive disaccharides that dampen TLR2/4 signaling, leading to increased bacterial dissemination and adverse outcomes. In this study, we show that GBS HylB mediates immune suppression and promotes bacterial infection during pregnancy that requires TLR2, TLR4, and IL-10. Understanding the interaction between host and bacterial factors can inform future therapeutic strategies to mitigate GBS infections.

Surface-based correlates of cognition along the Alzheimer's continuum in a memory clinic population.

Composite cognitive measures in large-scale studies with biomarker data for amyloid and tau have been widely used to characterize Alzheimer's disease (AD). However, little is known about how the findings from these studies translate to memory clinic populations without biomarker data, using single measures of cognition. Additionally, most studies have utilized voxel-based morphometry or limited surface-based morphometry such as cortical thickness, to measure the neurodegeneration associated with cognitive deficits. In this study, we aimed to replicate and extend the biomarker, composite study relationships using expanded surface-based morphometry and single measures of cognition in a memory clinic population. We examined 271 clinically diagnosed symptomatic individuals with mild cognitive impairment (N = 93) and Alzheimer's disease dementia (N = 178), as well as healthy controls (N = 29). Surface-based morphometry measures included cortical thickness, sulcal depth, and gyrification index within the "signature areas" of Alzheimer's disease. The cognitive variables pertained to hallmark features of Alzheimer's disease including verbal learning, verbal memory retention, and language, as well as executive function. The results demonstrated that verbal learning, language, and executive function correlated with the cortical thickness of the temporal, frontal, and parietal areas. Verbal memory retention was correlated to the thickness of temporal regions and gyrification of the inferior temporal gyrus. Language was related to the temporal regions and the supramarginal gyrus' sulcal depth and gyrification index. Executive function was correlated with the medial temporal gyrus and supramarginal gyrus sulcal depth, and the gyrification index of temporal regions and supramarginal gyrus, but not with the frontal areas. Predictions of each of these cognitive measures were dependent on a combination of structures and each of the morphometry measurements, and often included medial temporal gyrus thickness and sulcal depth. Overall, the results demonstrated that the relationships between cortical thinning and cognition are widespread and can be observed using single measures of cognition in a clinically diagnosed AD population. The utility of sulcal depth and gyrification index measures may be more focal to certain brain areas and cognitive measures. The relative importance of temporal, frontal, and parietal regions in verbal learning, language, and executive function, but not verbal memory retention, was replicated in this clinic cohort.

Body Mass Index (BMI) Cutoffs and Racial, Ethnic, Sex, or Age Disparities in Patients Treated With Total Ankle Arthroplasty.

Background: The rising prevalence of obesity among American adults has disproportionately affected Black adults and women. Furthermore, body mass index (BMI) has historically been used as a relative contraindication to many total joint arthroplasty (TJA) procedures, including total ankle arthroplasty. The purpose of this study was to investigate potential disparities in patient eligibility for total ankle arthroplasty based on race, ethnicity, sex, and age by applying commonly used BMI cutoffs to the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) database. Methods: Patients in the ACS-NSQIP database who underwent TAA from 2011 to 2020 were retrospectively reviewed in a cross-sectional analysis. BMI cutoffs of <50, <45, <40, and <35 were then applied. The eligibility rate for TAA was examined for each BMI cutoff, and findings were stratified by race, ethnicity, sex, and age. Independent t tests, chi-squared tests, and Fisher exact tests were performed to compare differences at an α = 0.05. Results: A total of 1215 of 1865 TAA patients (65.1%) were included after applying the exclusion criteria. Black patients had disproportionately lower rates of eligibility at the most stringent BMI cutoff of <35 (P = .004). Hispanic patients had generally lower rates of eligibility across all BMI cutoffs. In contrast, Asian American and Pacific Islander patients had higher rates of eligibility at the BMI cutoffs of <35 (P = .033) and <40 (P = .039), and White non-Hispanic patients had higher rates of eligibility across all BMI cutoffs. Females had lower eligibility rates across all BMI cutoffs. Ineligible patients were also younger compared to eligible patients across all BMI cutoffs. Conclusion: Stringent BMI cutoffs may disproportionately disqualify Black, female, and younger patients from receiving total ankle arthroplasty. Level of Evidence: Level III, retrospective cross-sectional study.

CD1 and iNKT cells mediate immune responses against the GBS hemolytic lipid toxin induced by a non-toxic analog.

Although hemolytic lipids have been discovered from many human pathogens including Group B Streptococcus (GBS), strategies that neutralize their function are lacking. GBS is a leading cause of pregnancy-associated neonatal infections, and adult GBS infections are on the rise. The GBS hemolytic lipid toxin or granadaene, is cytotoxic to many immune cells including T and B cells. We previously showed that mice immunized with a synthetic nontoxic analog of granadaene known as R-P4 had reduced bacterial dissemination during systemic infection. However, mechanisms important for R-P4 mediated immune protection was not understood. Here, we show that immune serum from R-P4-immunized mice facilitate GBS opsonophagocytic killing and protect naïve mice from GBS infection. Further, CD4+ T cells isolated from R-P4-immunized mice proliferated in response to R-P4 stimulation in a CD1d- and iNKT cell-dependent manner. Consistent with these observations, R-P4 immunized mice lacking CD1d or CD1d-restricted iNKT cells exhibit elevated bacterial burden. Additionally, adoptive transfer of iNKT cells from R-P4 vaccinated mice significantly reduced GBS dissemination compared to adjuvant controls. Finally, maternal R-P4 vaccination provided protection against ascending GBS infection during pregnancy. These findings are relevant in the development of therapeutic strategies targeting lipid cytotoxins.

Abdominal Sonographic Evaluation: In the Field, at the Hospital, and After Surgery.

Abdominal sonography is currently a routine procedure in the evaluation of colic in the horse. This imaging technique is used in both the assessment of the horse presented in the emergency setting with acute colic and the assessment of the horse presented for chronic or recurrent colic in the nonemergency setting. Sonography for colic evaluation is used by specialists in different disciplines and by general practitioners in the ambulatory and hospital settings. In this review, we will focus on indications and clinical interpretation of findings as well as recent developments in abdominal sonography.

Transfusion of hyperimmune plasma for protecting foals against Rhodococcus equi pneumonia.

The bacterium Rhodococcus equi causes pneumonia in foals that is prevalent at breeding farms worldwide. In the absence of an effective vaccine, transfusion of commercial plasma from donor horses hyperimmunised against R. equi is used by many farms to reduce the incidence of pneumonia among foals at farms where the disease is endemic. The effectiveness of hyperimmune plasma for controlling R. equi pneumonia in foals has varied considerably among reports. The purposes of this narrative review are: (1) to review early studies that provided a foundational basis for the practice of transfusion of hyperimmune plasma that is widespread in the United States and in many other countries; (2) to summarise current knowledge of hyperimmune plasma for preventing R. equi pneumonia; (3) to provide an interpretive summary of probable explanations for the variable results among studies evaluating the effectiveness of transfusion of hyperimmune plasma for reducing the incidence of R. equi pneumonia; (4) to review mechanisms by which hyperimmune plasma might mediate protection; and (5) to consider risks of transfusing foals with hyperimmune plasma. Although the weight of evidence supports the practice of transfusing foals with hyperimmune plasma to prevent R. equi pneumonia, many important gaps in our knowledge of this topic remain including the volume/dose of hyperimmune plasma to be transfused, the timing(s) of transfusion, and the mechanism(s) by which hyperimmune plasma mediates protection. Transfusing foals with hyperimmune plasma is expensive, labour-intensive, and carries risks for foals; therefore, alternative approaches for passive and active immunisation to prevent R. equi pneumonia are greatly needed.

Frontal and temporal lobe correlates of verbal learning and memory in aMCI and suspected Alzheimer's disease dementia.

Alzheimer's disease is primarily known for deficits in learning and retaining new information. This has long been associated with pathological changes in the mesial temporal lobes. The role of the frontal lobes in memory in Alzheimer's disease is less well understood. In this study, we examined the role of the frontal lobes in learning, recognition, and retention of new verbal information, as well as the presence of specific errors (i.e., intrusions and false-positive errors). Participants included one hundred sixty-seven patients clinically diagnosed with amnestic mild cognitive impairment or suspected Alzheimer's disease dementia who were administered the California Verbal Learning Test and completed high-resolution MRI. We confirmed the role of the mesial temporal lobes in learning and retention, including the volumes of the hippocampus, entorhinal cortex, and parahippocampal gyrus. In addition, false-positive errors were associated with all volumes of the mesial temporal lobes and widespread areas within the frontal lobes. Errors of intrusion were related to the supplementary motor cortex and hippocampus. Most importantly, the mesial temporal lobes interacted with the frontal lobes for learning, recognition, and memory errors. Lower volumes in both regions explained more performance variance than any single structure. This study supports the interaction of the frontal lobes with the temporal lobes in many aspects of memory in Alzheimer's disease.

Spatial profiling of the placental chorioamniotic membranes reveals upregulation of immune checkpoint proteins during Group B Streptococcus infection in a nonhuman primate model.

Background: Preterm birth is a leading cause of neonatal mortality, which is often complicated by intrauterine infection and inflammation. We have established a nonhuman primate model of Group B Streptococcus (GBS, Streptococcus agalactiae) infection-associated preterm birth. Immune checkpoints are modulators of the immune response by activating or suppressing leukocyte function and are understudied in preterm birth. The objective of this study was to spatially profile changes in immune protein expression at the maternal-fetal interface during a GBS infection with a focus on immune checkpoints. Methods: Twelve nonhuman primates (pigtail macaques, Macaca nemestrina) received a choriodecidual inoculation of either: 1) 1-5 X 108 colony forming units (CFU) of hyperhemolytic/hypervirulent GBS (GBSΔcovR, N=4); 2) an isogenic/nonpigmented strain (GBS ΔcovRΔcylE, N=4); or, 3) saline (N=4). A Cesarean section was performed at preterm labor or 3 days after GBS infection or 7 days after saline inoculation. Nanostring GeoMx® Digital Spatial Profiling technology was used to segment protein expression within the amnion, chorion, and maternal decidua at the inoculation site using an immuno-oncology panel targeting 56 immunoproteins enriched in stimulatory and inhibitory immune checkpoint proteins or their protein ligands. Statistical analysis included R studio, Kruskal-Wallis, Pearson and Spearman tests. Results: Both inhibitory and stimulatory immune checkpoint proteins were significantly upregulated within the chorioamniotic membranes and decidua (VISTA, LAG3, PD-1, CD40, GITR), as well as their ligands (PD-L1, PD-L2, CD40L; all p<0.05). Immunostaining for VISTA revealed positive (VISTA+) cells, predominantly in the chorion and decidua. There were strong correlations between VISTA and amniotic fluid concentrations of IL-1ß, IL-6, IL-8, and TNF-α (all p<0.05), as well as maternal placental histopathology scores (p<0.05). Conclusion: Differential regulation of multiple immune checkpoint proteins in the decidua at the site of a GBS infection indicates a major perturbation in immunologic homeostasis that could benefit the host by restricting immune-driven pathologies or the pathogen by limiting immune surveillance. Protein expression of VISTA, an inhibitory immune checkpoint, was upregulated in the chorion and decidua after GBS infection. Investigating the impact of innate immune cell expression of inhibitory immune checkpoints may reveal new insights into placental host-pathogen interactions at the maternal-fetal interface.

Virulence, phenotype and genotype characteristics of invasive group B Streptococcus isolates obtained from Swedish pregnant women and neonates.

Group B streptococci (GBS) are bacteria that can cause preterm birth and invasive neonatal disease. Heterogeneous expression of virulence factors enables GBS to exist as both commensal bacteria and to become highly invasive. A molecular epidemiological study comparing GBS bacterial traits, genotype and host characteristics may indicate whether it is possible to predict the risk of perinatal invasive GBS disease and more accurately target intrapartum antibiotic prophylaxis. A total of 229 invasive GBS isolates from Swedish pregnant women or neonates were assessed for virulence and phenotypic traits: hemolysis zone, hemolytic pigment (Granada agar), Streptococcus B Carrot Broth (SBCB) assay, CAMP factor, and hyaluronidase activity. Genes regulating hemolytic pigment synthesis (covR/covS, abx1, stk1, stp1) were sequenced. Of the virulence factors and phenotypes assessed, a Granada pigment or SBCB score ≥ 2 captured more than 90% of EOD isolates with excellent inter-rater reliability. High enzyme activity of hyaluronidase was observed in 16% (36/229) of the invasive GBS isolates and notably, in one case of stillbirth. Hyaluronidase activity was also significantly higher in GBS isolates obtained from pregnant/postpartum individuals versus the stillbirth or neonatal invasive isolates (p < 0.001). Sequencing analysis found that abx1 (g.T106I), stk1 (g.T211N), stp1 (g.K469R) and covS (g.V343M) variants were present significantly more often in the higher (Granada pigment score ≥ 2) versus lower pigmented isolates (p < 0.001, each variant). Among the 203 higher Granada pigment scoring isolates, 22 (10.8%) isolates had 3 of the four sequence variants and 10 (4.9%) had 2 of the four sequence variants. Although heterogeneity in GBS virulence factor expression was observed, the vast majority were more highly pigmented and contained several common sequence variants in genes regulating pigment synthesis. High activity of hyaluronidase may increase risk for stillbirth and invasive disease in pregnant or postpartum individuals. Our findings suggest that testing for GBS pigmentation and hyaluronidase may, albeit imperfectly, identify pregnant people at risk for invasive disease and represent a step towards a personalized medical approach for the administration of intrapartum antibiotic prophylaxis.

Non-emergent Conditions of the Ankle, Hindfoot, and Midfoot in Elderly Patients Are as Mobility Limiting as Congestive Heart Failure.

BACKGROUND: Mobility limitations are well linked to increased morbidity and mortality. Older patients with chronic pathologies of the foot and ankle can suffer from significant mobility limitations; however, the magnitude of limitation experienced by this cohort is not well characterized. Conversely, the effects of congestive heart failure (CHF) on patient mobility are routinely assessed via the New York Heart Association (NYHA) classification. New York Heart Association classification is determined by a patient's physical activity limitation and is strongly correlated to functional status. We hypothesized that non-emergent conditions of the foot and ankle would be as mobility limiting as CHF. METHODS: Life-Space Mobility Assessments (LSAs) were prospectively collected from orthopaedic patients at their preoperative visits and from CHF patients at a cardiology clinic. Patients over the age of 50 years were included in this study. Congestive heart failure patients NYHA class II or greater were included. The non-emergent foot and ankle cohort included Achilles tendonitis, ankle joint cartilage defects, ankle arthritis, subtalar arthritis, and midfoot arthritis. Patient demographics and LSA scores were analyzed using Mann-Whitney U and chi-squared tests. RESULTS: A total of 96 elderly, non-emergent foot and ankle operative patients and 45 CHF patients met inclusion criteria. All medical comorbidities, except smoking status, were significantly more prevalent in the CHF cohort. No statistical difference was observed between CHF and preoperative foot and ankle LSA scores (56.1 vs 62.4, P = .320). Life-Space Mobility Assessment scores in the foot and ankle cohort were significantly improved relative to CHF patients, at 6-month and 1-year postoperative visits (P = .028, P < .0001, respectively). CONCLUSION: Non-emergent ankle, hindfoot, and midfoot pathology is associated with similar mobility limitation to that of NYHA class II and III CHF. Older patients undergoing elective foot and ankle procedures exceeded the mobility of CHF patients at 6 months post-operation, and the mobility gains persisted at 1-year post-operation. LEVELS OF EVIDENCE: Level II: Prospective cohort study.

The Rise of Total Ankle Arthroplasty Use: A Database Analysis Describing Case Volumes and Incidence Trends in the United States Between 2009 and 2019.

BACKGROUND: Ankle arthrodesis has been the mainstay treatment for end-stage ankle arthritis. The popularity of total ankle arthroplasty (TAA) has been on the rise due to improved implant design and postoperative outcomes. The purpose of this study was to describe the basic epidemiology and trends of annual procedure volumes and incidence in the general American population as well as in different population subgroups from 2009 to 2019. We hypothesize that the incidence of TAA has significantly risen while the median length of hospital stay has decreased nationwide. METHODS: The IBM MarketScan database was queried for patients who underwent TAA from January 2009 to December 2019 based on Current Procedural Terminology coding. Population estimates from the US Census Bureau were used to calculate the annual incidence of TAA. Procedural volume and incidence were calculated for annual sums, gender, age subgroups, inpatient and outpatient TAA, as well as in four statistical geographic regions in the United States. Median length of hospital stay was calculated and trended annually for inpatient TAA. RESULTS: A total of 41,060 primary TAAs were identified in the database from 2009 to 2019, in which 52.5% were performed in males. Annual volumes increased by 136.1%, from 2180 to 5147 procedures nationwide. Incidence reported per 100 000 population increased by 120.8%. Both inpatient and outpatient procedures have increased, by 242.5% and 86.6%, respectively. Median length of hospital stay decreased from 3 days in 2009 to 1 day in 2019 and did not differ between genders. Growth in incidence was demonstrated in males and females above the age of 54 years with the largest growth in annual incidence found between 65 and 74 years. Incidence rose in the South and West of the United States by 111.8% and 136.5%, respectively. CONCLUSION: We found that annual volumes and incidence rates of primary TAA has increased between 2009 and 2019. Although both inpatient and outpatient surgery have become more frequent, inpatient volumes and incidence have increased almost 3 times more than those of outpatient surgery. Length of hospital stay decreased over the study years. When adjusted for the same study period, the cumulative annual growth rates of TAA were found to be 2 times greater than total knee arthroplasty and 3.6 times greater than total hip arthroplasty. LEVEL OF EVIDENCE: Level III, retrospective database review.

Effect of Obesity on Patient-Perceived Outcomes After First Metatarsophalangeal Joint Arthrodesis.

BACKGROUND: While first metatarsophalangeal joint (MTPJ) arthrodesis is a common and effective procedure, there is a paucity of studies examining obesity's effect on outcomes of 1st MTPJ arthrodesis. This study's purpose was to evaluate patient-reported outcomes following 1st MTPJ arthrodesis in obese versus non-obese patients. METHODS: A retrospective cohort study of 94 patients undergoing first MTPJ fusion over the age of 18 with a diagnosis of hallux valgus or hallux rigidus was performed. Surgical and postoperative outcomes were examined preoperatively and at 6 and 12 months follow-up via Visual Analog Pain scale (VAS), and Short Form 36 (SF-36) surveys, and data were stratified into 2 patient groups: BMI < 30 (n = 62, mean age 63.9 ± 9.1 and ≥ 30 (n = 32, mean age 61.9 ± 8.4). RESULTS: Average overall VAS and SF-36 physical component scores improved significantly at 6 months (P < .001, .006) and 1 year postoperative visits (P < .001, .007) with no differences in survey scores, outcomes, or complications between weight groups. CONCLUSION: Our study showed first MTPJ fusion improves short-term pain and physical quality-of-life in arthritic obese and non-obese patients without differences in nonunion, complications, or patient-reported measures. LEVEL OF EVIDENCE: Level III, Prognostic, Case-Control Study.

Mast cell-derived factor XIIIA contributes to sexual dimorphic defense against group B streptococcal infections.

Invasive bacterial infections remain a major cause of human morbidity. Group B streptococcus (GBS) are Gram-positive bacteria that cause invasive infections in humans. Here, we show that factor XIIIA-deficient (FXIIIA-deficient) female mice exhibited significantly increased susceptibility to GBS infections. Additionally, female WT mice had increased levels of FXIIIA and were more resistant to GBS infection compared with isogenic male mice. We observed that administration of exogenous FXIIIA to male mice increased host resistance to GBS infection. Conversely, administration of a FXIIIA transglutaminase inhibitor to female mice decreased host resistance to GBS infection. Interestingly, male gonadectomized mice exhibited decreased sensitivity to GBS infection, suggesting a role for gonadal androgens in host susceptibility. FXIIIA promoted GBS entrapment within fibrin clots by crosslinking fibronectin with ScpB, a fibronectin-binding GBS surface protein. Thus, ScpB-deficient GBS exhibited decreased entrapment within fibrin clots in vitro and increased dissemination during systemic infections. Finally, using mice in which FXIIIA expression was depleted in mast cells, we observed that mast cell-derived FXIIIA contributes to host defense against GBS infection. Our studies provide insights into the effects of sexual dimorphism and mast cells on FXIIIA expression and its interactions with GBS adhesins that mediate bacterial dissemination and pathogenesis.