Dynamic Changes in Lymphocyte Populations Establish Zebrafish as a Thymic Involution Model.

The thymus is the site of T lymphocyte development and T cell education to recognize foreign, but not self, Ags. B cells also reside and develop in the thymus, although their functions are less clear. During "thymic involution," a process of lymphoid atrophy and adipose replacement linked to sexual maturation, thymocytes decline. However, thymic B cells decrease far less than T cells, such that B cells comprise ∼1% of human neonatal thymocytes but up to ∼10% in adults. All jawed vertebrates possess a thymus, and we and others have shown zebrafish (Danio rerio) also have thymic B cells. In this article, we investigated the precise identities of zebrafish thymic T and B cells and how they change with involution. We assessed the timing and specific details of zebrafish thymic involution using multiple lymphocyte-specific, fluorophore-labeled transgenic lines, quantifying the changes in thymic T- and B-lymphocytes pre- versus postinvolution. Our results prove that, as in humans, zebrafish thymic B cells increase relative to T cells postinvolution. We also performed RNA sequencing on D. rerio thymic and marrow lymphocytes of four novel double-transgenic lines, identifying distinct populations of immature T and B cells. Collectively, this is, to our knowledge, the first comprehensive analysis of zebrafish thymic involution, demonstrating its similarity to human involution and establishing the highly genetically manipulatable zebrafish model as a template for involution studies.

Developmental programming of the ovarian reserve in livestock.

Mammalian females are born with a finite number of follicles in their ovaries that is referred to as the ovarian reserve. There is a large amount of variation between females in the number of antral follicles that they are born with, but this number is positively correlated to size of the ovarian reserve, has a strong repeatability within a female, and a moderate heritability. Although the heritability is moderate, numerous external factors including health, nutrition, ambient temperature, and litter size influence the size and function of the ovarian reserve throughout life. Depletion of the ovarian reserve contributes to reproductive senescence, and genetic and epigenetic factors can lead to a more rapid decline in follicle numbers in some females than others. The relationship of the size of the ovarian reserve to development of the reproductive tract and fertility is generally positive, although some studies report antagonistic associations of these traits. It seems likely that management decisions and environmental factors that result in epigenetic modifications to the genome throughout life may cause variability in the function of ovarian genes that influence fecundity and fertility, leading to differences in reproductive longevity among females born with ovarian reserves of similar size. This review summarizes our current understanding of factors influencing size of the ovarian reserve in cattle, sheep, and pigs and the relationship of the ovarian reserve to reproductive tract development and fertility. It provides strategies to apply this knowledge to improve diagnostics for better assessment of fertility and reproductive longevity in female livestock.

Resilience Improves Patient-Reported Outcomes After Orthopaedic Trauma.

OBJECTIVES: To analyze the relationship between patient resilience and patient-reported outcomes after orthopaedic trauma. DESIGN: Retrospective analysis of prospectively collected data. SETTING: Single Level 1 Trauma Center. PATIENT SELECTION CRITERIA: Patients were selected based on completion of the Patient-Reported Outcomes Measurement Information System (PROMIS) and Brief Resilience Scale (BRS) surveys 6 months after undergoing operative fracture fixation following orthopaedic trauma. Patients were excluded if they did not complete all PROMIS and BRS surveys. OUTCOME MEASURES AND COMPARISONS: Resilience, measured by the BRS, was analyzed for its effect on patient-reported outcomes, measured by PROMIS Global Physical Health, Physical Function, Pain Interference, Global Mental Health, Depression, and Anxiety. Variables collected were demographics (age, gender, race, body mass index), injury severity score, and postoperative complications (nonunion, infection). All variables were analyzed with univariate for effect on all PROMIS scores. Variables with significance were included in multivariate analysis. Patients were then separated into high resilience (BRS >4.3) and low resilience (BRS <3.0) groups for additional analysis. RESULTS: A total of 99 patients were included in the analysis. Most patients were male (53%) with an average age of 47 years. Postoperative BRS scores significantly correlated with PROMIS Global Physical Health, Pain Interference, Physical Function, Global Mental Health, Depression, and Anxiety ( P ≤ 0.001 for all scores) at 6 months after injury on both univariate and multivariate analyses. The high resilience group had significantly higher PROMIS Global Physical Health, Physical Function, and Global Mental Health scores and significantly lower PROMIS Pain Interference, Depression, and Anxiety scores ( P ≤ 0.001 for all scores). CONCLUSIONS: Resilience in orthopaedic trauma has a positive association with patient outcomes at 6 months postoperatively. Patients with higher resilience report higher scores in all PROMIS categories regardless of injury severity. Future studies directed at increasing resilience may improve outcomes in patients who experience orthopaedic trauma. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

The Impact of Smoking on Hospital Course and Postoperative Outcomes in Patients With Fracture-Related Infections.

OBJECTIVES: To assess the relationship between patient smoking status and fracture-related infection (FRI) characteristics including patient symptoms at FRI presentation, bacterial species of FRI, and rates of fracture union. DESIGN: Retrospective cohort study. SETTING: Urban level 1 trauma center. PATIENT SELECTION CRITERIA: All patients undergoing reoperation for FRI from January 2013 to April 2021 were identified through manual review of an institutional database. OUTCOME MEASURES AND COMPARISONS: Data including patient demographics, fracture characteristics, infection presentation, and hospital course were collected through review of the electronic medical record. Patients were grouped based on current smoker versus nonsmoker status. Hospital course and postoperative outcomes of these groups were then compared. Risk factors of methicillin-resistant Staphylococcus aureus (MRSA) infection, Staphylococcus epidermidis infection, and sinus tract development were evaluated using multivariable logistic regression. RESULTS: A total of 301 patients, comprising 155 smokers (51%) and 146 nonsmokers (49%), undergoing FRI reoperation were included. Compared with nonsmokers, smokers were more likely male (69% vs. 56%, P = 0.024), were younger at the time of FRI reoperation (41.7 vs. 49.5 years, P < 0.001), and had lower mean body mass index (27.2 vs. 32.0, P < 0.001). Smokers also had lower prevalence of diabetes mellitus (13% vs. 25%, P = 0.008) and had higher Charlson Comorbidity Index 10-year estimated survival (93% vs. 81%, P < 0.001). Smokers had a lower proportion of S. epidermidis infections (11% vs. 20%, P = 0.037), higher risk of nonunion after index fracture surgery (74% vs. 61%, P = 0.018), and higher risk of sinus tracts at FRI presentation (38% vs. 23%, P = 0.004). On multivariable analysis, smoking was not found to be associated with increased odds of MRSA infection. CONCLUSIONS: Among patients who develop a FRI, smokers seemed to have better baseline health regarding age, body mass index, diabetes mellitus, and Charlson Comorbidity Index 10-year estimated survival compared with nonsmokers. Smoking status was not significantly associated with odds of MRSA infection. However, smoking status was associated with increased risk of sinus tract development and nonunion and lower rates of S. epidermidis infection at the time of FRI reoperation. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Does pes anserinus tenotomy affect surgical site infection rate in operative tibial plateau fractures?

PURPOSE: To assess if pes anserinus tenotomy (PAT) during definitive open reduction and internal fixation (ORIF) of tibial plateau fractures is associated with a decreased risk of surgical site infection (SSI) and other postoperative complications. METHODS: A retrospective review of all adults who underwent ORIF for tibial plateau fractures from April 2005 to February 2022 at single level 1 trauma center was performed. Patients who had a medial approach to the plateau with minimum three-month follow-up were required for inclusion. All patients with fasciotomy for compartment syndrome or with traumatically avulsed or damaged pes anserinus prior to ORIF were excluded. Two groups were created: those who received a pes anserinus tenotomy with repair (PAT group) and those whose pes anserinus were spared and left intact (control group). Patient demographics, injury and operative characteristics, and surgical outcomes were compared. The primary outcomes were rates of deep and superficial SSI. RESULTS: The PAT group had significantly lower rates of deep SSI (9.2% vs. 19.7%, P = 0.009), superficial SSI (14.2% vs. 26.5%), P = 0.007), and any SSI (15.8% vs. 28.9%, P = 0.005). Multiple logistic regression showed that heart failure (aOR = 7.215, 95% CI 2.291-22.719, P < 0.001), and presence of open fracture (aOR = 4.046, 95% CI 2.074-7.895, P < 0.001) were independently associated with increased odds of deep SSI, while PAT was associated with a decreased odds of deep SSI (aOR = 0.481, 95% CI 0.231-0.992, P = 0.048). PAT had significantly lower rates of unplanned return to the operating room (20.8% vs. 33.7%, P = 0.010) and implant removal (10.0% vs. 18.0%, P = 0.042). CONCLUSION: While these data do not allow for discussion of functional recovery or strength, pes anserinus tenotomy was independently associated with significantly lower rates of infection, unplanned operation, and implant removal. LEVEL OF EVIDENCE: Level III.

Clustering of multi-tissue transcriptomes in gilts with normal cyclicity or delayed puberty reveals genes related to pubertal development†.

In gilts, puberty is marked by standing estrus in the presence of a boar. Delayed puberty (DP; failure to display pubertal estrus) is a major reason for gilt removal. To investigate the physiological determinants underlying DP in gilts, transcriptomic data from tissues relevant to estrus and puberty, such as mediobasal hypothalamus, anterior pituitary gland, ovarian cortex, olfactory bulb, amygdala, and hippocampus, were obtained from age-matched DP (n = 8) and cyclic control gilts at follicular phase (n = 8) and luteal phase (n = 8) of the estrous cycle. A gene expression module analysis via three-way gene × individual × tissue clustering using tensor decomposition identified pituitary and ovary gene modules contributing to regulation of pubertal development. Analysis of gene expression in the hypothalamic-pituitary-ovary axis identified reduced expression of hypothalamic genes critical for stimulating gonadotropin secretion (KISS1 and TAC3) and reduced expression of LHB in the anterior pituitary of DP gilts compared with their cyclic counterparts. Consequently, luteinizing hormone-induced genes in the ovary important for folliculogenesis (OXTR, RUNX2, and PTX3) were less expressed in DP gilts. Other intrafollicular genes (AHR, PTGS2, PTGFR, and IGFBP7) and genes in the steroidogenesis pathways (STAR and CYP11A1) necessary to complete the ovulatory cascade were also less expressed in DP gilts. This is the first clustering of multi-tissue expression data from DP and cyclic gilts to identify genes differentially expressed in gilts of similar ages but at different levels of sexual development. A critical lack of gonadotropin support and reduced ovarian responsiveness underlie DP in gilts.

An extreme model of fertility in sheep demonstrates the basis of controversies surrounding antral follicle count and circulating concentrations of anti-Müllerian hormone as predictors of fertility in ruminants.

Ovarian ultrasonography and measurement of circulating concentrations of anti-Müllerian hormone (AMH) have been used to estimate follicle number and predict fertility in mammalian females, but no study has evaluated follicle number and circulating concentrations of AMH in ewes known to differ in fertility. We tested the hypothesis that ewes that had failed to lamb (BARREN) in four consecutive annual breeding seasons of 21-35 d have fewer follicles and diminished circulating concentrations of AMH compared to closely matched ewes that consistently produced lambs (FERTILE) under the same breeding protocols. Once identified, BARREN ewes (n = 19) were paired by breed and sire to a FERTILE control ewe (n = 19) and reproductive tracts were recovered at necropsy. Visible antral follicles in both ovaries were counted and a representative cross section of one ovary was embedded for histological evaluation of pre-antral follicle numbers. Paired t-tests indicated that BARREN ewes had fewer antral follicles, fewer primordial follicles, and decreased circulating concentrations of AMH compared to FERTILE ewes (P ≤ 0.01), but there were ewes in each fertility classification that had ovarian phenotypes like the opposite fertility classification. The best technologies we have currently for estimating follicle numbers are ultrasonography and measurement of circulating concentrations of AMH, but no single technique is perfect for predicting fertility. A better understanding of the under-lying biological mechanisms linking AMH, folliculogenesis, and fertility is required to improve the use of measurements of follicle number for predicting fertility in livestock.

Outcomes of SARS-CoV-2 infection among patients with orthopaedic fracture surgery in the National COVID Cohort Collaborative (N3C).

BACKGROUND: The objective of this study was to investigate the outcomes of COVID-19-positive patients undergoing orthopaedic fracture surgery using data from a national database of U.S. adults with a COVID-19 test for SARS-CoV-2. METHODS: This is a retrospective cohort study using data from a national database to compare orthopaedic fracture surgery outcomes between COVID-19-positive and COVID-19-negative patients in the United States. Participants aged 18-99 with orthopaedic fracture surgery between March and December 2020 were included. The main exposure was COVID-19 status. Outcomes included perioperative complications, 30-day all-cause mortality, and overall all-cause mortality. Multivariable adjusted models were fitted to determine the association of COVID-positivity with all-cause mortality. RESULTS: The total population of 6.5 million patient records was queried, identifying 76,697 participants with a fracture. There were 7,628 participants in the National COVID Cohort who had a fracture and operative management. The Charlson Comorbidity Index was higher in the COVID-19-positive group (n = 476, 6.2 %) than the COVID-19-negative group (n = 7,152, 93.8 %) (2.2 vs 1.4, p<0.001). The COVID-19-positive group had higher mortality (13.2 % vs 5.2 %, p<0.001) than the COVID-19-negative group with higher odds of death in the fully adjusted model (Odds Ratio=1.59; 95 % Confidence Interval: 1.16-2.18). CONCLUSION: COVID-19-positive participants with a fracture requiring surgery had higher mortality and perioperative complications than COVID-19-negative patients in this national cohort of U.S. adults tested for COVID-19. The risks associated with COVID-19 can guide potential treatment options and counseling of patients and their families. Future studies can be conducted as data accumulates. LEVEL OF EVIDENCE: Level III.

Relationships of genomic estimated breeding values for age at puberty, birth weight, and growth during development in normal cyclic and acyclic gilts.

Managing replacement gilts to reach optimal body weight and growth rate for boar stimulation and first breeding is a key component for sow reproductive longevity and producer profitability. Failure to display pubertal estrus remains a major reason that gilts are culled from the herd. Puberty is metabolically gated so evaluating phenotypic and genetic relationships between birth weight and growth traits with age at puberty and acyclicity can provide valuable insight for efficient gilt development. Data on a litter of origin of the gilt, average daily gain at different stages of development, and age at puberty were available for age-matched cyclic (n = 4,861) and acyclic gilts (prepubertal anestrus, n = 578; behavioral anestrus, n = 428). Genomic estimated breeding values were predicted for each trait using genomic best linear unbiased prediction. Primiparous sows produced more acyclic gilts than multiparous sows (P < 0.05). Accounting for effects of parity and litter size, prepubertal anestrus gilts were heavier at birth and behaviorally anestrus gilts grew faster during the finisher period compared to cyclic gilts (P < 0.05), reflecting possible prenatal programming that negatively affects optimal pubertal development and antagonistic effects between adolescent growth and expression of estrus of gilts from first parity sows. Regression of phenotypic age at puberty with lifetime growth rate (birth to selection) showed a negative linear relationship whereas genomic estimated breeding values showed a negative quadratic relationship indicating that gilts with the least and greatest growth are less optimal as replacements. The slopes of these relationships are small with low negative phenotypic (r = -0.06) and genetic correlations (r = -0.13). The addition of data from acyclic gilts did not substantially change the estimates for genetic relationships between growth and pubertal onset. Although this study identified differences in birth weight and growth rate between cyclic and acyclic gilts the genetic relationships are weak, suggesting that genetic selection for these traits can be achieved separately. Avoiding the smallest and largest gilts in a cohort born to first parity sows could result in gilts with optimal development and reduce the proportion of replacement gilts that are acyclic.

Failure to display pubertal estrus is major reason replacement gilts are culled from the herd. Two types of prebreeding estrus failure are delay in attaining puberty due to sexual immaturity known as prepubertal anestrus (PPA) and silent ovulation without signs of estrus known as behavioral anestrus (BA). For efficient gilt development, it is important to understand what contributes to these acyclic phenotypes. Comparison of birth weight and growth rate in age-matched cyclic, PPA, and BA gilts showed that PPA gilts were heavier at birth and BA gilts grew faster during the finisher period, reflecting negative effects of larger birth weight and faster growth on sexual maturity and behavioral estrus. The genetic relationship between growth and puberty onset indicated that gilts with the least and greatest growth rates are less optimal as replacements. A selection criterion to avoid the smallest and largest gilts in a cohort could result in gilts with optimal development for boar stimulation and reduce the proportion of acyclic gilts. This management strategy would be most effective if targeted to first parity sows.

Dynamic Changes in Lymphocyte Populations Establish Zebrafish as a Thymic Involution Model.

The thymus is the site of T lymphocyte development and T cell education to recognize foreign, but not self, antigens. B cells also reside and develop in the thymus, although their functions are less clear. During 'thymic involution,' a process of lymphoid atrophy and adipose replacement linked to sexual maturation, thymocytes decline. However, thymic B cells decrease far less than T cells, such that B cells comprise ~1% of human neonatal thymocytes, but up to ~10% in adults. All jawed vertebrates possess a thymus, and we and others have shown zebrafish (Danio rerio) also have thymic B cells. Here, we investigated the precise identities of zebrafish thymic T and B cells and how they change with involution. We assessed the timing and specific details of zebrafish thymic involution using multiple lymphocyte-specific, fluorophore-labeled transgenic lines, quantifying the changes in thymic T- and B-lymphocytes pre- vs. post-involution. Our results prove that, as in humans, zebrafish thymic B cells increase relative to T cells post-involution. We also performed RNA sequencing (RNA-seq) on D. rerio thymic and marrow lymphocytes of four novel double-transgenic lines, identifying distinct populations of immature T and B cells. Collectively, this is the first comprehensive analysis of zebrafish thymic involution, demonstrating its similarity to human involution, and establishing the highly genetically-manipulatable zebrafish model as a template for involution studies.

How do surgeons decide when to treat proximal humerus fractures with operative versus nonoperative management?

PURPOSE: The objective of this study was to determine the underlying factors that drive the decision for surgeons to pursue operative versus nonoperative management for proximal humerus fractures (PHF) and if fellowship training had an impact on these decisions. METHODS: An electronic survey was distributed to members of the Orthopaedic Trauma Association and the American Shoulder and Elbow Surgeons Society to assess differences in patient selection for operative versus nonoperative management of PHF. Descriptive statistics were reported for all respondents. RESULTS: A total of 250 fellowship trained Orthopaedic Surgeons responded to the online survey. A greater proportion of trauma surgeons preferred nonoperative management for displaced PHF fractures in patients over the age of 70. Operative management was preferred for older patients with fracture dislocations (98%), limited humeral head bone subchondral bone (78%), and intraarticular head split (79%). Similar proportions of trauma surgeons and shoulder surgeons cited that acquiring a CT was crucial to distinguish between operative and nonoperative management. CONCLUSION: We found that surgeons base their decisions on when to operate primarily on patient's comorbidities, age, and the amount of fracture displacement when treating younger patients. Further, we found a greater proportion of trauma surgeons elected to proceed with nonoperative management in patients older than the age of 70 years old as compared to shoulder surgeons.

Comparison of Total Ankle Replacement and Ankle Arthrodesis for Ankle Arthropathy in Patients With Bleeding Disorders: A Systematic Review and Meta-Analysis.

BACKGROUND: There is limited literature comparing the publications on ankle arthrodesis (AA) and total ankle arthroplasty (TAA) in the setting of hemophilic arthropathy. Our objective is to systematically review the existing literature and to assess ankle arthroplasty as an alternative to ankle arthrodesis in this patient population. METHODS: This systematic review was conducted and presented according to the PRISMA statement standards. A search was conducted on March 7-10, 2023, using MEDLINE (via PubMed), Embase, Scopus, ClinicalTrials.gov, CINAHL Plus with Full Text, and the Cochrane Central Register of Controlled Studies. This search was restricted to full-text human studies published in English, and articles were screened by 2 masked reviewers. Systematic reviews, case reports with less than 3 subjects, letters to the editor, and conference abstracts were excluded. Two independent reviewers rated study quality using the MINORS tool. RESULTS: Twenty-one of 1226 studies were included in this review. Thirteen articles reviewed the outcomes associated with AA in hemophilic arthropathy whereas 10 reviewed the outcomes associated with TAA. Two of our studies were comparative and reviewed the outcomes of both AA and TAA. Additionally, 3 included studies were prospective. Studies showed that the degree of improvement in American Orthopaedic Foot & Ankle Society hindfoot-ankle score, visual analog scale pain scores, and the mental and physical component summary scores of the 36-Item Short Form Health Survey were similar for both surgeries. Complication rates were also similar between the 2 surgeries. Additionally, studies showed a significant improvement in ROM after TAA. CONCLUSION: Although the level of evidence in this review varies and results should be interpreted with caution, the current literature suggests similar clinical outcomes and complication rates between TAA and AA in this patient population.

Use of Computed Tomography Angiography to Predict Complications in Tibia Fractures: A Multicenter Retrospective Analysis.

OBJECTIVES: To assess the ability of computed tomography angiography identified infrapopliteal vascular injury to predict complications in tibia fractures that do not require vascular surgical intervention. DESIGN: Multicenter retrospective review. SETTING: Six Level I trauma centers. PATIENTS AND INTERVENTION: Two hundred seventy-four patients with tibia fractures (OTA/AO 42 or 43) who underwent computed tomography angiography maintained a clinically perfused foot not requiring vascular surgical intervention and were treated with an intramedullary nail. Patients were grouped by the number of vessels below the trifurcation that were injured. MAIN OUTCOME MEASUREMENTS: Rates of superficial and deep infection, amputation, unplanned reoperation to promote bone healing (nonunion), and any unplanned reoperation. RESULTS: There were 142 fractures in the control (no-injury) group, 87 in the one-vessel injury group, and 45 in the two-vessel injury group. Average follow-up was 2 years. Significantly higher rates of nerve injury and flap coverage after wound breakdown were observed in the two-vessel injury group. The two-vessel injury group had higher rates of deep infection (35.6% vs. 16.9%, P = 0.030) and unplanned reoperation to promote bone healing (44.4% vs. 23.9%, P = 0.019) compared with controls, as well as increased rates of any unplanned reoperation compared with control and one-vessel injury groups (71.1% vs. 39.4% and 51.7%, P < 0.001), respectively. There were no significant differences in rates of superficial infection or amputation. CONCLUSIONS: Tibia fractures with two-vessel injuries were associated with higher rates of deep infection and unplanned reoperation to promote bone healing compared with those without vascular injury, as well as increased rates of any unplanned reoperation compared with controls and fractures with one-vessel injury. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Not All Proximal Humerus Fractures Do Well Without Surgery: Anterior Translation Predicts the Need for Surgery.

OBJECTIVES: To evaluate the effect of translation on a large series of low-energy proximal humerus fractures initially treated nonoperatively. DESIGN: Retrospective multicenter analysis. SETTING: Five level-one trauma centers. PATIENTS/PARTICIPANTS: Two hundred ten patients (152 F; 58 M), average age 64, with 112 left- and 98 right-sided low-energy proximal humerus fractures (OTA/AO 11-A-C). INTERVENTION: All patients were initially treated nonoperatively and were followed for an average of 231 days. Radiographic translation in the sagittal and coronal planes was measured. Patients with anterior translation were compared with those with posterior or no translation. Patients with ≥80% anterior humeral translation were compared with those with <80% anterior translation, including those with no or posterior translation. MAIN OUTCOMES: The primary outcome was failure of nonoperative treatment resulting in surgery and the secondary outcome was symptomatic malunion. RESULTS: Nine patients (4%) had surgery, 8 for nonunion and 1 for malunion. All 9 patients (100%) had anterior translation. Anterior translation compared with posterior or no sagittal plane translation was associated with failure of nonoperative management requiring surgery ( P = 0.012). In addition, of those with anterior translation, having ≥80% anterior translation compared with <80% was also associated with surgery ( P = 0.001). Finally, 26 patients were diagnosed with symptomatic malunion, of whom translation was anterior in 24 and posterior in 2 ( P = 0.0001). CONCLUSIONS: In a multicenter series of proximal humerus fractures, anterior translation of >80% was associated with failure of nonoperative care resulting in nonunion, symptomatic malunion, and potential surgery. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Risk Factors for Prolonged Hospital Stay After Femoral Neck Fracture.

The purpose of this study was to investigate the association between pre-operative anemia and prolonged hospital stay among geriatric patients with operative femoral neck fractures. This retrospective cohort study was performed at a level I trauma center and included geriatric patients with femoral neck fractures (OTA/AO 31) and operative treatment with Current Procedural Terminology code 27236. Exclusion criteria were admission to the intensive care unit, evacuation of subdural hematoma, and conditions requiring exploratory laparotomy. A total of 207 individuals, with data collected between January 2015 and August 2019 and age 65 years and older, were included in the analysis. Linear regression was used to evaluate the association between anemia and length of stay adjusting for potential confounders. Anemia was defined using preoperative hematocrit. The primary outcome was prolonged length of stay, defined as 5 or more days. The group was 65% women. The mean age was 80.2 years (range, 64-98 years). The majority (61%) of patients had anemia. American Society of Anesthesiologists classification was associated with preoperative anemia (P=.02). Patients with anemia had a 16% higher risk of prolonged length of stay compared with patients without anemia (81% vs 65%, P=.009). In the linear regression model, preoperative hematocrit was associated with length of stay (P=.032) when adjusted for sex, age, preoperative tranexamic acid, preoperative hemoglobin, postoperative hemoglobin, and postoperative hematocrit. Length of stay was approximately 1 week in this study, with anemia being a statistically significant risk factor for prolonged length of stay. Health care providers and administrators can consider anemia on admission when predicting length of stay. [Orthopedics. 2023;46(4):211-217.].

gBLUP-GWAS identifies candidate genes, signaling pathways, and putative functional polymorphisms for age at puberty in gilts.

Successful development of replacement gilts determines their reproductive longevity and lifetime productivity. Selection for reproductive longevity is challenging due to low heritability and expression late in life. In pigs, age at puberty is the earliest known indicator for reproductive longevity and gilts that reach puberty earlier have a greater probability of producing more lifetime litters. Failure of gilts to reach puberty and display a pubertal estrus is a major reason for early removal of replacement gilts. To identify genomic sources of variation in age at puberty for improving genetic selection for early age at puberty and related traits, gilts (n = 4,986) from a multigeneration population representing commercially available maternal genetic lines were used for a genomic best linear unbiased prediction-based genome-wide association. Twenty-one genome-wide significant single nucleotide polymorphisms (SNP) located on Sus scrofa chromosomes (SSC) 1, 2, 9, and 14 were identified with additive effects ranging from -1.61 to 1.92 d (P < 0.0001 to 0.0671). Novel candidate genes and signaling pathways were identified for age at puberty. The locus on SSC9 (83.7 to 86.7 Mb) was characterized by long range linkage disequilibrium and harbors the AHR transcription factor gene. A second candidate gene on SSC2 (82.7 Mb), ANKRA2, is a corepressor for AHR, suggesting a possible involvement of AHR signaling in regulating pubertal onset in pigs. Putative functional SNP associated with age at puberty in the AHR and ANKRA2 genes were identified. Combined analysis of these SNP showed that an increase in the number of favorable alleles reduced pubertal age by 5.84 ± 1.65 d (P < 0.001). Candidate genes for age at puberty showed pleiotropic effects with other fertility functions such as gonadotropin secretion (FOXD1), follicular development (BMP4), pregnancy (LIF), and litter size (MEF2C). Several candidate genes and signaling pathways identified in this study play a physiological role in the hypothalamic-pituitary-gonadal axis and mechanisms permitting puberty onset. Variants located in or near these genes require further characterization to identify their impact on pubertal onset in gilts. Because age at puberty is an indicator of future reproductive success, these SNP are expected to improve genomic predictions for component traits of sow fertility and lifetime productivity expressed later in life.

Selecting for replacement gilts is challenging because sow reproductive traits are lowly heritable and expressed late in life. Age at puberty is the earliest indicator of future reproductive success of gilts. Genetic selection for early onset of puberty could be feasible with the availability of molecular genetic predictors for age at puberty. To identify genomic sources associated with variation in age at puberty in gilts, a large-scale genome-wide association study was conducted at the U.S Meat Animal Research Center, Clay Center, Nebraska. Novel genomic associations for age at puberty were identified. Several candidate genes identified for age at puberty are involved in signaling pathways that regulate ovarian functions and pubertal onset. Potential causative genetic variants for age at puberty were identified within the candidate genes. These novel SNP are important new markers for use in genomic selection of replacement gilts with early puberty and provide critical new insight into biological mechanisms important for pubertal development in gilts.

Management of open pelvic ring injuries.

Open pelvic ring injuries are rare clinical entities that require multidisciplinary care. Due to the scarcity of this injury, there is no well-defined treatment algorithm. As a result, conflicting evidence surrounding various aspects of care including wound management and fecal diversion remain. Previous studies have shown mortality reaching 50% in open pelvic ring injuries, nearly five times higher than closed pelvic ring injuries. Early mortality is due to exsanguinating hemorrhage, while late mortality is due to wound sepsis and multiorgan system failure. With advancements in trauma care and ATLS protocols, there has been an improved survival rate reported in published case series. Major considerations when treating these injuries include aggressive resuscitation with hemorrhage control, diagnosis of associated injuries, prevention of wound sepsis with early surgical management, and definitive skeletal fixation. Classification systems for categorization and management of bony and soft tissue injury related to pelvic ring injuries have been established. Fecal diversion has been proposed to decrease rates of sepsis and late mortality. While clear indications are lacking due to limited studies, previous studies have reported benefits. Further large-scale studies are necessary for adequate evaluation of treatment protocols of open pelvic ring injuries. Understanding the role of fecal diversion, avoidance of primary closure in open pelvic ring injuries, and importance of well-coordinated care amongst surgical teams can optimize patient outcomes.

Risk Factors for Early Conversion Total Hip Arthroplasty After Pipkin IV Femoral Head Fracture.

OBJECTIVES: To determine risk factors for early conversion total hip arthroplasty (THA) in Pipkin IV femoral head fractures. DESIGN: Retrospective cohort. SETTING: Two level I trauma centers. PATIENTS AND INTERVENTION: One hundred thirty-seven patients with Pipkin IV fractures meeting inclusion criteria with 1 year minimum follow-up managed from 2009 to 2019. MAIN OUTCOME MEASUREMENT: Patients were separated into groups by the Orthopaedic Trauma Association/AO Foundation (OTA/AO) classification of femoral head fracture: 31C1 (split-type fractures) and 31C2 (depression-type fractures). Multivariable regression was performed after univariate analysis comparing patients requiring conversion THA with those who did not. RESULTS: We identified 65 split-type fractures, 19 (29%) underwent conversion THA within 1 year. Surgical site infection ( P = 0.002), postoperative hip dislocation ( P < 0.0001), and older age ( P = 0.049) resulted in increased rates of conversion THA. However, multivariable analysis did not identify independent risk factors for conversion. There were 72 depression-type fractures, 20 (27.8%) underwent conversion THA within 1 year. Independent risk factors were increased age ( P = 0.01) and posterior femoral head fracture location ( P < 0.01), while infrafoveal femoral head fracture location ( P = 0.03) was protective against conversion THA. CONCLUSION: Pipkin IV fractures managed operatively have high overall risk of conversion THA within 1 year (28.5%). Risk factors for conversion THA vary according to fracture subtype. Hip joint survival of fractures subclassified OTA/AO 31C1 likely depends on patient age and postoperative outcomes such as surgical site infection and redislocation. Pipkin IV fractures subclassified to OTA/AO 31C2 type with suprafoveal and posterior head impaction and older age should be counseled of high conversion risk with consideration for alternative management options. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

Risk Factors for Nonunion of Distal Femur Fractures.

OBJECTIVES: To determine patient, fracture, and construct related risk factors associated with nonunion of distal femur fractures. DESIGN: Retrospective cohort study. SETTING: Academic Level I trauma center. PARTICIPANTS: Patients 18 years and older presenting with OTA/AO 33A and 33C distal femur fractures from 2004 to 2020. A minimum follow-up of 6 months was required for inclusion. OTA/AO 33B and periprosthetic fractures were excluded, 438 patients met inclusion criteria for the study. MAIN OUTCOMES: The primary outcome of the study was fracture nonunion defined as a return to the OR for management of inadequate bony healing. Patient demographics, comorbidities, injury characteristics, fixation type, and construct variables were assessed for association with distal femur fracture nonunion. Secondary outcomes include conversion to total knee arthroplasty, surgical site infection, and other reoperation. RESULTS: The overall nonunion rate was 13.8% (61/438). The nonunion group was compared directly with the fracture union group for statistical analysis. There were no differences in age, sex, mechanism of injury, Injury Severity Score, and time to surgery between the groups. Lateral locked plating characteristics including length of plate, plate metallurgy, screw density, and working length were not significantly different between groups. Increased body mass index [odds ratio (OR), 1.05], chronic anemia (OR, 5.4), open fracture (OR, 3.74), and segmental bone loss (OR, 2.99) were independently associated with nonunion. Conversion to total knee arthroplasty (TKA) ( P = 0.005) and surgical site infection ( P < 0001) were significantly more common in the nonunion group. CONCLUSION: Segmental bone loss, open fractures, chronic anemia, and increasing body mass index are significant risk factors in the occurrence of distal femoral nonunion. Lateral locked plating characteristics did not seem to affect nonunion rates. Further investigation into the prevention of nonunion should focus on fracture fixation constructs and infection prevention. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.