Effects of a moderate exercise regimen on development and puberty attainment of beef heifers reared in drylots at a high stocking density.

This experiment evaluated growth, physiological responses, and puberty attainment in beef heifers reared in drylots with a high stocking density, and provided or not with a moderate exercise regimen. A total of 180 heifers (75% Angus × 25% Brahman) were used in this experiment replicated over 2 yr. Each year, 90 heifers were ranked by age (264 ±â€…1 d) and body weight (BW on day -3; 200 ±â€…2 kg) on day 0, and assigned to a) one of six drylot pens (10 × 14 m pens; 10 heifers per pen) with a stocking density of 14 m2/heifer (DENS), or b) one of three pastures (2-ha pastures; 10 heifers per pasture) with a stocking density of 2,000 m2/heifer (CON). Beginning on day 15, three DENS pens were given access to an exercise area (DENS-EX) 3 times/wk (1 h). Negligible forage was available for CON, whereas heifers from all treatments received the same limit-fed diet (~13 kg/heifer daily). Shrunk BW was recorded after 16 h of feed and water withdrawal on days -3 and 225 to calculate BW gain. Temperament was evaluated on days 0, 128, and 224. Heifers were fitted with a pedometer behind their shoulder on day 0 to record physical activity. Pedometer results and blood samples were collected weekly for progesterone analysis. Hair samples from the tail switch were collected every 28 d. Data were analyzed with pen or pasture as an experimental unit, via ANOVA using the MIXED or GLIMMIX procedures of SAS (SAS Inst. Inc., Cary, NC). Heifers from CON had more (P < 0.01) steps per week compared with DENS and DENS-EX (23,973, 6,706, and 12,354 steps/wk, respectively; SEM = 1,247), and DENS-EX heifers had more (P < 0.01) steps per week compared with DENS. No treatment effects (P ≥ 0.91) were detected for heifer BW gain (~0.820 kg/d). Hair cortisol concentrations were greater (P ≤ 0.05) in DENS and DENS-EX compared with CON beginning on day 56. Exit velocity and temperament score were greater (P ≤ 0.05) in DENS compared with DENS-EX and CON on day 224. Puberty attainment was delayed (treatment × day; P < 0.01) in DENS compared with DENS-EX and CON. A greater (P ≤ 0.05) proportion of CON were pubertal by day 105 compared with DENS and DENS-EX (30.0%, 11.6%, and 15.0%, respectively; SEM = 6.5), while a greater (P < 0.05) proportion of CON and DENS-EX were pubertal by day 154 compared to DENS (61.7%, 66.7%, and 43.3%, respectively; SEM = 6.5). Rearing replacement heifers in drylots with high stocking density has detrimental effects on their puberty attainment, and the moderate exercise regimen partially alleviated this negative outcome.

Replacement beef heifers are often reared in drylots with high stocking density to facilitate feeding and management, or to intensify beef production as availability of grazing areas becomes limited. Studies from our group, however, demonstrated that drylot heifers experience delayed puberty attainment compared with heifers reared on pastures. This negative outcome was associated with chronic stress caused by confinement and restricted physical activity; the latter being a key animal welfare factor with direct effects on reproductive development. Based on this rationale, this experiment evaluated growth, stress-related physiological responses, and puberty attainment heifers reared in drylots and exposed or not to a moderate exercise regimen. Moreover, drylot heifers were compared to contemporary cohorts being reared on pasture. As expected, heifers reared in drylots experienced heightened stress-related physiological responses and delayed puberty attainment compared to pasture heifers. Exposing drylot heifers to the moderate exercise regimen did not alleviate the physiological consequences of chronic stress, but lessened the delay in puberty attainment compared with non-exercised drylot cohorts. Therefore, stocking density and exercise opportunities should be considered to improve heifer welfare and reproductive development in intensive drylot systems, as lack of exercise directly contributes to delayed reproductive development of drylot heifers.

Efficient and reproducible generation of human iPSC-derived cardiomyocytes using a stirred bioreactor.

In the last decade human iPSC-derived cardiomyocytes (hiPSC-CMs) proved to be valuable for cardiac disease modeling and cardiac regeneration, yet challenges with scale, quality, inter-batch consistency, and cryopreservation remain, reducing experimental reproducibility and limiting clinical translation. Here, we report a robust cardiac differentiation protocol that uses Wnt modulation and a stirred suspension bioreactor to produce on average 124 million hiPSC-CMs with >90% purity using a variety of hiPSC lines (19 differentiations; 10 iPSC lines). After controlled freeze and thaw, bioreactor-derived CMs (bCMs) showed high viability (>90%), interbatch reproducibility in cellular morphology, function, drug response and ventricular identity, which was further supported by single cell transcriptomes. bCMs on microcontact printed substrates revealed a higher degree of sarcomere maturation and viability during long-term culture compared to monolayer-derived CMs (mCMs). Moreover, functional investigation of bCMs in 3D engineered heart tissues showed earlier and stronger force production during long-term culture, and robust pacing capture up to 4 Hz when compared to mCMs. bCMs derived from this differentiation protocol will expand the applications of hiPSC-CMs by providing a reproducible, scalable, and resource efficient method to generate cardiac cells with well-characterized structural and functional properties superior to standard mCMs.

Increased rates of hospital-onset Staphylococcus aureus bacteraemia in National Health Service acute trusts in England between June 2020 and March 2021: a national surveillance review.

A large increase in hospital-onset and intensive-care-unit-onset Staphylococcus aureus bacteraemia rates in English acute trusts was observed between 2020 and 2021, coinciding with reported increases in coronavirus disease (COVID-19) cases and associated hospitalizations. Many of these S. aureus bacteraemia cases were defined as co-/secondary infections to COVID-19. Over the same period, increases in the percentage of ventilator-associated pneumonia-related bacteraemia were also found. The COVID-19 pandemic appears to have contributed to the increase in hospital-onset S. aureus bacteraemia in England; further studies are needed to better understand the impacts on patient outcomes.

Tbx5 maintains atrial identity by regulating an atrial enhancer network.

Understanding how the atrial and ventricular chambers of the heart maintain their distinct identity is a prerequisite for treating chamber-specific diseases. Here, we selectively inactivated the transcription factor Tbx5 in the atrial working myocardium of the neonatal mouse heart to show that it is required to maintain atrial identity. Atrial Tbx5 inactivation downregulated highly chamber specific genes such as Myl7 and Nppa , and conversely, increased the expression of ventricular identity genes including Myl2 . Using combined single nucleus transcriptome and open chromatin profiling, we assessed genomic accessibility changes underlying the altered atrial identity expression program, identifying 1846 genomic loci with greater accessibility in control atrial cardiomyocytes compared to KO aCMs. 69% of the control-enriched ATAC regions were bound by TBX5, demonstrating a role for TBX5 in maintaining atrial genomic accessibility. These regions were associated with genes that had higher expression in control aCMs compared to KO aCMs, suggesting they act as TBX5-dependent enhancers. We tested this hypothesis by analyzing enhancer chromatin looping using HiChIP and found 510 chromatin loops that were sensitive to TBX5 dosage. Of the loops enriched in control aCMs, 73.7% contained anchors in control-enriched ATAC regions. Together, these data demonstrate a genomic role for TBX5 in maintaining the atrial gene expression program by binding to atrial enhancers and preserving tissue-specific chromatin architecture of atrial enhancers.

Osteochondritis Dissecans of the Capitellum of the Elbow: Improved Outcomes in Surgically Treated Versus Nonoperatively Treated Patients at Long-Term Follow-up.

Purpose: To (1) report the long-term outcomes associated with both operative and nonoperative management of capitellar osteochondritis dissecans (OCD), (2) identify factors associated with failure of nonoperative management, and (3) determine whether delay in surgery affects final outcomes. Methods: All patients who received a diagnosis of capitellar OCD from 1995-2020 within a geographic cohort were included. Medical records, imaging studies, and operative reports were manually reviewed to record demographic data, treatment strategies, and outcomes. The cohort was divided into 3 groups: (1) nonoperative management, (2) early surgery, and (3) delayed surgery. Delayed surgery (surgery ≥6 months after symptom onset) was considered failure of nonoperative management. Results: Fifty elbows with a mean follow-up period of 10.5 years (median, 10.3 years; range, 1-25 years) were studied. Of these, 7 (14%) were definitively treated nonoperatively, 16 (32%) underwent delayed surgery after at least 6 months of failed nonoperative treatment, and 27 (54%) underwent early surgical intervention. When compared with nonoperative management, surgical management resulted in superior Mayo Elbow Performance Index pain scores (40.1 vs 33, P = .04), fewer mechanical symptoms (9% vs 50%, P < .01), and better elbow flexion (141° vs 131°, P = .01) at long-term follow-up. Older patients trended toward increased failure of nonoperative management (P = .06). The presence of an intra-articular loose body predicted failure of nonoperative management (P = .01; odds ratio, 13). Plain radiography and magnetic resonance imaging had poor sensitivities for identifying loose bodies (27% and 40%, respectively). Differences in outcomes after early versus delayed surgical management were not observed. Conclusions: Nonoperative management of capitellar OCD failed 70% of the time. Elbows that did not undergo surgery had slightly more symptoms and decreased functional outcomes compared with those treated surgically. The greatest predictors of failure of nonoperative treatment were older age and presence of a loose body; however, an initial trial of nonoperative treatment did not adversely impact the success of future surgery. Level of Evidence: Level III, retrospective cohort study.

The Association Between Preoperative International Normalized Ratio Values and Postoperative Outcomes including Mortality in Geriatric Femoral Neck Fractures Treated With Hemiarthroplasty.

OBJECTIVES: To evaluate the association between preoperative international normalized ratio (INR) and postoperative mortality and other outcomes after hemiarthroplasty for geriatric femoral neck fractures. DESIGN: Retrospective cohort study. SETTING: A single Level-I trauma center. PATIENTS/PARTICIPANTS: Patients ≥55 years of age with OTA/AO 31B proximal femur fractures [1556 patients (1616 hips)]. INTERVENTION: Hip hemiarthroplasty. MAIN OUTCOME MEASUREMENTS: Ninety-day mortality, postoperative transfusion within 72 hours, and 90-day postoperative outcomes. RESULTS: Adjusting for confounders, the association of preoperative INR and 90-day mortality was not statistically significant [hazard ratio (HR): 1.3; 95% confidence interval (CI): 0.97, 1.8; P = 0.08]. Dementia (HR: 1.9; 95% CI: 1.4-2.6; P < 0.001), Charlson Comorbidity Index (HR: 1.1; 95% CI: 1.1-1.2; P < 0.001), and age by decade (HR: 1.4; 95% CI: 1.1-1.8; P = 0.002) were associated with 90-day mortality. Increasing INR was significantly associated with blood transfusion [odds ratio (OR) 1.4; 95% CI 1.03-1.6; P = 0.031]. Preoperative hemoglobin <10 g/dL (OR 13.7; 95% CI 8.4-23.3; P < 0.001) was also associated with a postoperative transfusion, whereas intraoperative tranexamic acid use (OR 0.3; 95% CI 0.2-0.5; P < 0.001) was inversely associated with postoperative transfusion rate. INR was associated with superficial wound infection (HR: 2.0; 95% CI: 1.1-3.7; P = 0.02) and noninfected wound complications (HR: 1.6; 95% CI: 1.1-2.4; P = 0.007). Risk of superficial infection increased when INR was >1.8. CONCLUSION: When controlling for confounders, preoperative INR was not significantly associated with 90-day mortality. Underlying medical conditions contribute to postoperative mortality more than an elevated INR. However, INR is associated with superficial wound complications. This risk becomes statistically significant as INR rises above 1.8. LEVEL OF EVIDENCE: Prognostic Level III. See Instructions for Authors for a complete description of levels of evidence.

In Vivo Dissection of Chamber-Selective Enhancers Reveals Estrogen-Related Receptor as a Regulator of Ventricular Cardiomyocyte Identity.

BACKGROUND: Cardiac chamber-selective transcriptional programs underpin the structural and functional differences between atrial and ventricular cardiomyocytes (aCMs and vCMs). The mechanisms responsible for these chamber-selective transcriptional programs remain largely undefined. METHODS: We nominated candidate chamber-selective enhancers (CSEs) by determining the genome-wide occupancy of 7 key cardiac transcription factors (GATA4, MEF2A, MEF2C, NKX2-5, SRF, TBX5, TEAD1) and transcriptional coactivator P300 in atria and ventricles. Candidate enhancers were tested using an adeno-associated virus-mediated massively parallel reporter assay. Chromatin features of CSEs were evaluated by performing assay of transposase accessible chromatin sequencing and acetylation of histone H3 at lysine 27-HiChIP on aCMs and vCMs. CSE sequence requirements were determined by systematic tiling mutagenesis of 29 CSEs at 5 bp resolution. Estrogen-related receptor (ERR) function in cardiomyocytes was evaluated by Cre-loxP-mediated inactivation of ERRα and ERRγ in cardiomyocytes. RESULTS: We identified 134 066 and 97 506 regions reproducibly occupied by at least 1 transcription factor or P300, in atria or ventricles, respectively. Enhancer activities of 2639 regions bound by transcription factors or P300 were tested in aCMs and vCMs by adeno-associated virus-mediated massively parallel reporter assay. This identified 1092 active enhancers in aCMs or vCMs. Several overlapped loci associated with cardiovascular disease through genome-wide association studies, and 229 exhibited chamber-selective activity in aCMs or vCMs. Many CSEs exhibited differential chromatin accessibility between aCMs and vCMs, and CSEs were enriched for aCM- or vCM-selective acetylation of histone H3 at lysine 27-anchored loops. Tiling mutagenesis of 29 CSEs identified the binding motif of ERRα/γ as important for ventricular enhancer activity. The requirement of ERRα/γ to activate ventricular CSEs and promote vCM identity was confirmed by loss of the vCM gene profile in ERRα/γ knockout vCMs. CONCLUSIONS: We identified 229 CSEs that could be useful research tools or direct therapeutic gene expression. We showed that chamber-selective multi-transcription factor, P300 occupancy, open chromatin, and chromatin looping are predictive features of CSEs. We found that ERRα/γ are essential for maintenance of ventricular identity. Finally, our gene expression, epigenetic, 3-dimensional genome, and enhancer activity atlas provide key resources for future studies of chamber-selective gene regulation.

Tbx5 maintains atrial identity in post-natal cardiomyocytes by regulating an atrial-specific enhancer network.

Understanding how the atrial and ventricular heart chambers maintain distinct identities is a prerequisite for treating chamber-specific diseases. Here, we selectively knocked out (KO) the transcription factor Tbx5 in the atrial working myocardium to evaluate its requirement for atrial identity. Atrial Tbx5 inactivation downregulated atrial cardiomyocyte (aCM) selective gene expression. Using concurrent single nucleus transcriptome and open chromatin profiling, genomic accessibility differences were identified between control and Tbx5 KO aCMs, revealing that 69% of the control-enriched ATAC regions were bound by TBX5. Genes associated with these regions were downregulated in KO aCMs, suggesting they function as TBX5-dependent enhancers. Comparing enhancer chromatin looping using H3K27ac HiChIP identified 510 chromatin loops sensitive to TBX5 dosage, and 74.8% of control-enriched loops contained anchors in control-enriched ATAC regions. Together, these data demonstrate TBX5 maintains the atrial gene expression program by binding to and preserving the tissue-specific chromatin architecture of atrial enhancers.

Incidence and Epidemiology of Symptomatic Capitellar Osteochondritis Dissecans of the Elbow: A United States Population-Based Study Over a 25-Year Period.

Background: There are limited data on the incidence of capitellar osteochondritis dissecans (OCD) in the United States (US) population. Purpose: To determine the incidence of symptomatic capitellar OCD in a representative US subpopulation and identify changes in its incidence over time and to investigate the relationship between the incidence of capitellar OCD and patient sex and age. Study Design: Descriptive epidemiology study. Methods: A retrospective review was performed of patients aged ≤24 years from Olmsted County, Minnesota, with symptomatic capitellar OCD over a 25-year period (1995-2019). Patients with acute osteochondral injuries, Panner disease, and hereditary arthropathy were excluded. Poisson regression was utilized to identify the predictors of a capitellar OCD diagnosis. Incidence rates (per 100,000) were assessed for changes over time. Age groups of younger (10-15 years) versus older (16-24 years) patients were compared. Results: A total of 45 patients (78% male) were identified. The mean age was 14.5 years (range, 10-24 years); 31 patients were in the younger group, and 14 patients were in the older group. Sport participation was seen in 89%of patients; 90% were overhead athletes, and 58% were throwing athletes. The incidence of capitellar OCD was 6.0 per 100,000 overall, 9.5 per 100,000 for male patients, and 2.6 per 100,000 for female patients. The incidence was highest for male patients in the younger group (15.3/100,000) and lowest for female patients in the older group (0.8/100,000). The estimated incidence rate ratio for younger versus older patients was 3.3 (P < .001), and the incidence rate ratio for male versus female patients was 3.5 (P < .001). There were no changes in the incidence of capitellar OCD over time as a continuous or 5-year categorical variable (P = .290 and P = .460, respectively). Overall, 82% of patients were treated surgically. There were no significant changes in surgical rates over time. Conclusion: In this US subpopulation, the overall incidence of symptomatic capitellar OCD between the ages of 10 and 24 years was 6.0 per 100,000 over the 25-year period studied, which is higher than previously reported US estimates. Incidence rates and treatment strategies did not change significantly over time.

Implementing nitrous oxide cracking technology in the labour ward to reduce occupational exposure and environmental emissions: a quality improvement study.

Nitrous oxide, a potent greenhouse gas, is a common labour analgesic. One method which may reduce its carbon footprint is to 'crack' the exhaled gas into nitrogen and oxygen using catalytic destruction. In this quality improvement project, based on environmental monitoring and staff feedback, we assessed the impact of nitrous oxide cracking technology in the maternity setting. Mean ambient nitrous oxide levels were recorded during the final 30 minutes of uncomplicated labour in 36 cases and plotted on a run chart. Interventions were implemented in four stages, comprising: stage 1, baseline (12 cases); stage 2, cracking with nitrous oxide delivered and scavenged via a mouthpiece (eight cases); stage 3, cracking with nitrous oxide via a facemask with an air-filled cushion (eight cases); stage 4, cracking with nitrous oxide via a low-profile facemask, and enhanced coaching on the use of the technology (eight cases). The median ambient nitrous oxide levels were 71% lower than baseline in stage 2 and 81% lower in stage 4. Staff feedback was generally positive, though some found the technology to be cumbersome; successful implementation relies on effective staff engagement. Our results indicate that cracking technology can reduce ambient nitrous oxide levels in the obstetric setting, with potential for reductions in environmental impacts and occupational exposure.

Acute versus delayed radial head arthroplasty for the treatment of radial head fractures.

BACKGROUND: Radial head arthroplasty (RHA) is an important tool in the acute treatment of comminuted radial head and neck fractures. RHA is also performed in a delayed manner after failed open reduction and internal fixation, for fracture malunion or nonunion, and other chronic post-traumatic elbow disorders where restoration of the lateral column of the elbow is considered necessary. The relative efficacy and longevity of acute vs. delayed RHA is unknown. We sought to compare clinical, radiographic, and patient-reported outcomes between these groups. METHODS: We identified patients ≥18 years old who underwent an RHA between 2000 and 2018 and then extracted 135 total elbows with a mean follow-up of 2.3 years that sustained isolated radial head fractures (30%), terrible triad injuries (66%), or Essex-Lopresti injuries (4%). The acute cohort (RHA: <12 weeks) contained 101 elbows that underwent surgery at a mean of 0.6 weeks (range, 0 days to 7 weeks, 96% <2 weeks) from injury, whereas the delayed cohort (RHA: 12 weeks to 2 years) contained 34 elbows that underwent surgery at a mean of 36 weeks (range, 14-82 weeks) from injury. Patients in the acute group had a higher percentage of terrible triad injuries (75% vs. 40%, P < .001) and Mason 3 fractures (98% vs. 45%, P < .001). RESULTS: At the final follow-up, 13 of 101 patients in the acute cohort (13%) and 7 of 34 patients in the delayed cohort (21%) required implant revision or resection. A total of 25 patients (25%) in the acute cohort and 12 patients (35%) in the delayed cohort required a reoperation. Kaplan-Meier 2-year survival estimates free of implant resection or revision (90% acute, 86% delayed) and reoperation (76% acute, 70% delayed) were similar between groups. In patients with 5-year follow-up, there was an increased rate of revision or resection in the delayed group (30% vs. 13%). Two-year survival estimates free of radiographic loosening were 80% in the acute cohort vs. 57% in the delayed cohort (P = .04). Mayo Elbow Performance Score at 2 years demonstrated mean scores of 83 and 79 in the acute and delayed groups, respectively, with 71% of the acute cohort and 64% of the delayed cohort achieving good or excellent scores. CONCLUSIONS: Our results demonstrated that although 2-year Kaplan-Meier survival free of revision or resection estimates and reoperation rates was equivalent between the groups, the delayed group experienced worse Mayo Elbow Performance Score outcomes, a higher revision or resection rate at 5 years, and an increased rate of radiographic loosening.

Speciation of inorganic arsenic in aqueous samples using a novel hydride generation microfluidic paper-based analytical device (µPAD).

The development of the first microfluidic paper-based analytical device (µPAD) for the speciation of inorganic arsenic in environmental aqueous samples as arsenite (As(III)) and arsenate (As(V)) which implements hydride generation on a paper platform is described. The newly developed µPAD has a 3D configuration and uses Au(III) chloride as the detection reagent. Sodium borohydride is used to generate arsine in the device's sample zone by reducing As(III) in the presence of hydrochloric acid or both As(III) and As(V) (total inorganic As) in the presence of sulfuric acid. Arsine then diffuses across a hydrophobic porous polytetrafluoroethylene membrane into the device's detection zone where it reduces Au(III) to Au nanoparticles. This results in a color change which can be related to the concentration of As(III) or total inorganic As (i.e., As(III) and As(V)) concentration. Under optimal conditions, the µPAD is characterized by a limit of detection of 0.43 mg L-1 for total inorganic As (As(III) + As(V)) and 0.41 mg L-1 for As(III) and a linear calibration range in both cases of 1.2-8.0 mg As L-1. The newly developed µPAD-based method was validated by applying it to groundwater and freshwater samples and comparing the results with those obtained by conventional atomic spectrometric techniques.

A manifold learning approach for gesture recognition from micro-Doppler radar measurements.

A recent paper (Mhaskar (2020)) introduces a straightforward and simple kernel based approximation for manifold learning that does not require the knowledge of anything about the manifold, except for its dimension. In this paper, we examine how the pointwise error in approximation using least squares optimization based on similarly localized kernels depends upon the data characteristics and deteriorates as one goes away from the training data. The theory is presented with an abstract localized kernel, which can utilize any prior knowledge about the data being located on an unknown sub-manifold of a known manifold. We demonstrate the performance of our approach using a publicly available micro-Doppler data set, and investigate the use of different preprocessing measures, kernels, and manifold dimensions. Specifically, it is shown that the localized kernel introduced in the above mentioned paper when used with PCA components leads to a near-competitive performance to deep neural networks, and offers significant improvements in training speed and memory requirements. To demonstrate the fact that our methods are agnostic to the domain knowledge, we examine the classification problem in a simple video data set.

CMYA5 establishes cardiac dyad architecture and positioning.

Cardiac excitation-contraction coupling requires dyads, the nanoscopic microdomains formed adjacent to Z-lines by apposition of transverse tubules and junctional sarcoplasmic reticulum. Disruption of dyad architecture and function are common features of diseased cardiomyocytes. However, little is known about the mechanisms that modulate dyad organization during cardiac development, homeostasis, and disease. Here, we use proximity proteomics in intact, living hearts to identify proteins enriched near dyads. Among these proteins is CMYA5, an under-studied striated muscle protein that co-localizes with Z-lines, junctional sarcoplasmic reticulum proteins, and transverse tubules in mature cardiomyocytes. During cardiac development, CMYA5 positioning adjacent to Z-lines precedes junctional sarcoplasmic reticulum positioning or transverse tubule formation. CMYA5 ablation disrupts dyad architecture, dyad positioning at Z-lines, and junctional sarcoplasmic reticulum Ca2+ release, leading to cardiac dysfunction and inability to tolerate pressure overload. These data provide mechanistic insights into cardiomyopathy pathogenesis by demonstrating that CMYA5 anchors junctional sarcoplasmic reticulum to Z-lines, establishes dyad architecture, and regulates dyad Ca2+ release.

Recent Antibiotic Treatment Impacts Serum and Synovial Laboratory Values in Early Periprosthetic Joint Infection Workup.

BACKGROUND: Accurately detecting early postoperative periprosthetic joint infection (PJI) following total hip arthroplasty (THA) and total knee arthroplasty (TKA) remains challenging. The purpose of our study was to determine the impact of antibiotics given prior to laboratory evaluation on the reliability of serologic and synovial fluid tests to identify PJI in the early postoperative period. METHODS: We identified 49,861 primary total hip arthroplasties and total knee arthroplasties performed between 2000 and 2019. Among these patients, 21 hips and 28 knees that underwent arthrocentesis within 12 weeks of their arthroplasty were identified as infected. Patients who had received antibiotics within 2 weeks prior to laboratory evaluation were compared to those who had not. Median values of C-reactive protein, erythrocyte sedimentation rate, synovial white blood cell (WBC) count, synovial neutrophil percentage, and synovial absolute neutrophil count were compared between groups. The false negative rate for detecting PJI using laboratory values was compared using published cutoffs for PJI in the early postoperative period. RESULTS: Median values of C-reactive protein (105 vs 22 mg/L; P = .006), synovial WBC count (57,591 vs 4,473 cells/µL; P = .003), synovial neutrophil percentage (94% vs 76%; P = .004), and synovial absolute neutrophil count (50,748 vs 2,804 cells/µL; P < .001) were significantly lower in patients who received antibiotics compared to those who did not. False negative rates for detecting PJI were significantly higher for synovial WBC and synovial neutrophil percentage in patients treated with antibiotics compared to untreated patients. CONCLUSION: False negative rates for detecting early PJI when using published cutoffs were markedly higher in antibiotic-treated patients compared to untreated patients for synovial WBC count and synovial neutrophil percentage. LEVEL OF EVIDENCE: Level IV retrospective review.

Outcomes of Intramedullary Nail Fixation for Metastatic Disease: Impending and Pathologic Fractures.

BACKGROUND/AIM: Intramedullary nail (IMN) fixation has become a treatment mean for impending and pathologic femur fractures. Currently there continues to be a lack of data examining functional outcomes, complications, and survivorship of patients treated with IMNs for metastatic disease of the femur. PATIENTS AND METHODS: We retrospectively identified 183 IMNs placed for impending (n=145) or pathologic (n=38) metastatic fractures from 2010 to 2018. Functional outcomes and complications including blood transfusions, venous thromboembolisms (VTEs) and reoperations were studied. RESULTS: Patients with impending lesions were more likely to be ambulatory at final follow-up (pathologic: 82%, impending: 99%, p<0.0001) and reported greater musculoskeletal tumor society scores (p<0.0001). Likewise, pathologic fractures were associated with greater discharge to non-home locations (p<0.0001) and were more likely to require a postoperative transfusion (pathologic: 66%, impending: 22%, p=0.0001). However, there was no difference in the incidence of VTEs (p=1.00) or reoperations (p=0.69) between cohorts. Patients treated for impending fractures had improved overall survival at 1 year (54% vs. 26%, p<0.0001). CONCLUSION: IMN fixation was durable in impending and pathologic femoral fractures. Early identification of metastases remains critical as patients treated for impending lesions had greater functional outcomes, fewer complications and improved survivorship compared to patients treated for pathologic fractures.

Rising rates of hospital-onset Klebsiella spp. and Pseudomonas aeruginosa bacteraemia in NHS acute trusts in England: a review of national surveillance data, August 2020-February 2021.

Increases in hospital-onset Klebsiella spp. and Pseudomonas aeruginosa bacteraemia rates in England were observed between August 2020 and February 2021 to the highest levels recorded since the start of mandatory surveillance in April 2017. Cases were extracted from England's mandatory surveillance database for key Gram-negative bloodstream infections. Incidence rates for hospital-onset bacteraemia cases increased from 8.9 (N=255) to 14.9 (N=394) per 100,000 bed-days for Klebsiella spp. [incidence rate ratio (IRR) 1.7, P<0.001], and from 4.9 (N=139) to 6.2 (N=164) per 100,000 bed-days for P. aeruginosa (IRR 1.3, P<0.001) (August 2020-February 2021). These incidence rates were higher than the average rates observed during the same period in the previous 3 years. These trends coincided with an increase in the percentage of hospital-onset bacteraemia cases that were also positive for severe acute respiratory syndrome coronavirus-2.

Laboratory Value Effectiveness in Predicting Early Postoperative Periprosthetic Joint Infection After Total Hip Arthroplasty.

BACKGROUND: Diagnosing early periprosthetic joint infection (PJI) after primary total hip arthroplasty (THA) remains challenging. We sought to validate optimal laboratory value cutoffs for detecting early PJIs in a series of primary THAs from one institution. METHODS: We retrospectively identified 22,795 primary THAs performed between 2000 and 2019. Within 12 weeks, 43 hips (43 patients) underwent arthrocentesis. Patients were divided into 2 groups: evaluation ≤6 weeks or 6-12 weeks following THA. The 2011 Musculoskeletal Infection Society major criteria for PJI diagnosed PJI in 15 patients. Mann-Whitney U-tests were used to compare median laboratory values and receiver operating characteristic curve analysis was used to evaluate optimal cutoff values. RESULTS: Both within 6 weeks and between 6 and 12 weeks postoperatively, median C-reactive protein (CRP), erythrocyte sedimentation rate, synovial white blood cell (WBC) count, neutrophil percentage, and absolute neutrophil count (ANC) values were significantly higher in infected THAs. Optimal cutoffs within 6 weeks were: CRP ≥100 mg/L, synovial WBCs ≥4390 cells/µL, neutrophil percentage ≥74%, and ANC ≥3249 cells/µL. Between 6 and 12 weeks, optimal cutoffs were: CRP ≥33 mg/L, synovial WBCs ≥26,995 cells/µL, neutrophil percentage ≥93%, and ANC ≥25,645 cells/µL. CONCLUSION: Early PJI following THA should be suspected within 6 weeks with CRP ≥100 mg/L or synovial WBCs ≥4390 cells/µL. Between 6 and 12 weeks postoperatively, cutoffs of CRP ≥33 mg/L, synovial fluid WBC ≥26,995 cells/µL, and neutrophil percentage ≥93% diagnosed PJI with high accuracy. LEVEL OF EVIDENCE: Level IV Diagnostic.

Rat Calvarial Bone Regeneration by 3D-Printed ß-Tricalcium Phosphate Incorporating MicroRNA-200c.

Advanced fabrication methods for bone grafts designed to match defect sites that combine biodegradable, osteoconductive materials with potent, osteoinductive biologics would significantly impact the clinical treatment of large bone defects. In this study, we engineered synthetic bone grafts using a hybrid approach that combined three-dimensional (3D-)printed biodegradable, osteoconductive ß-tricalcium phosphate (ß-TCP) with osteoinductive microRNA(miR)-200c. 3D-printed ß-TCP scaffolds were fabricated utilizing a suspension-enclosing projection-stereolithography (SEPS) process to produce constructs with reproducible microarchitectures that enhanced the osteoconductive properties of ß-TCP. Collagen coating on 3D-printed ß-TCP scaffolds slowed the release of plasmid DNA encoding miR-200c compared to noncoated constructs. 3D-printed ß-TCP scaffolds coated with miR-200c-incorporated collagen increased the transfection efficiency of miR-200c of both rat and human BMSCs and additionally increased osteogenic differentiation of hBMSCs in vitro. Furthermore, miR-200c-incorporated scaffolds significantly enhanced bone regeneration in critical-sized rat calvarial defects. These results strongly indicate that bone grafts combining SEPS 3D-printed osteoconductive biomaterial-based scaffolds with osteoinductive miR-200c can be used as superior bone substitutes for the clinical treatment of large bone defects.