Clinical Outcomes of Isolated Polyethylene Exchange versus Full Component Revision for the Management of Instability Following Total Knee Arthroplasty.

BACKGROUND: Instability following total knee arthroplasty (TKA) is a common cause for revision. Isolated polyethylene exchange (IPE) can be performed to increase knee joint stability, but results have been mixed. The purpose of this study was to compare the survivorship and patient-reported outcomes of patients undergoing revision TKA for instability with IPE versus full component revision. METHODS: We reviewed 280 primary TKAs undergoing revision TKA for instability. There were 181 knees that underwent revision with IPE, compared to 99 knees treated with full component revision. The mean follow-up was 32.8 months (range, 24.8 to 82.5). Patient demographics, radiographic parameters, prosthesis constraints, reoperations for instability, and patient-reported outcomes were compared. RESULTS: The survivorship for instability was significantly higher at 2 years (99 versus 92%, P = 0.024) and 5 years (94 versus 84%, P = 0.024) for patients undergoing full component revision. Although there was no difference in Knee Injury and Osteoarthritis Outcome Score for Joint Replacements (KOOS Jr) and Veterans RAND 12 (VR-12) physical component scores between the 2 groups at 6 weeks, 1 year, and 2 years after surgery, full revision patients reported greater pain relief (P = 0.006) and greater improvements in VR-12 physical component scores (P = 0.027) at 1 year and KOOS JR scores at 2 years (P = 0.017) compared to IPE patients. Men were associated with an increased risk for recurrent instability following IPE (HR [hazard ratio] 3.3, 95% confidence interval (CI): [1.0 to 10.6]). CONCLUSIONS: Isolated polyethylene exchange was not as reliable or durable compared to full component revision for the management of postoperative instability. These procedures should only be reserved in cases with competent collaterals and when component position, offset, and rotation are optimized.

Reactance inversion in moderate to severe persistent asthma: low birth weight, prematurity effect, and bronchodilator response.

INTRODUCTION: Reactance inversion (RI) has been associated with impaired peripheral airway function in persistent asthma. However, there is little to no data about the difference between asthmatic children with and without RI. This study aimed to detect clinical and lung function differences in moderate-severe asthmatic children with and without RI. METHODS: This study was conducted between 2021 and 2022 in asthmatic school-age children. Impulse oscillometry (IOS) and spirometry were performed according to ATS/ERS standards. RESULTS: A total of 62 patients, with a mean age of 8.4 years, 54.8% were males and were divided into three groups: group 1 (32.3%) with no RI, group 2 (27.4%) with RI but disappearing after bronchodilator test and group 3 (40.3%) with persistent RI after bronchodilator test. Children in groups 2 and 3 had significantly lower birth weights than in group 1. Group 2 had lower gestational age compared to group 1. FEV1 and FEF25-75 of forced vital capacity were significantly lower in groups 2 and 3. In group 3, R5, AX, R5-20, and R5-R20/R5 ratios were significantly higher. Bronchodilator responses (BDR) in X5c, AX, and R5-R20 were significantly different between groups and lower in group 3. CONCLUSION: RI is frequently found in children with moderate-severe persistent asthma, particularly in those with a history of prematurity or low birth weight. In some patients, RI disappears after the bronchodilator test; however, it, persists in those with the worst pulmonary function. RI could be a small airway dysfunction marker.

The structural line between prion and "prion-like": Insights from prion protein and tau.

The concept of 'prion-like' behavior has emerged in the study of diseases involving protein misfolding where fibrillar structures, called amyloids, self-propagate and induce disease in a fashion similar to prions. From a biological standpoint, in order to be considered 'prion-like,' a protein must traverse cells and tissues and further propagate via a templated conformational change. Since 2017, cryo-electron microscopy structures from patient-derived 'prion-like' amyloids, in particular tau, have been presented and revealed structural similarities shared across amyloids. Since 2021, cryo-EM structures from prions of known infectivity have been added to the ex vivo amyloid structure family. In this review, we discuss current proposals for the 'prion-like' mechanisms of spread for tau and prion protein as well as discuss different influencers on structures of aggregates from tauopathies and prion diseases. Lastly, we discuss some of the current hypotheses for what may distinguish structures that are 'prion-like' from transmissible prion structures.

Crystallization-Induced Flower-like Superstructures via Peptoid Helix Assembly.

We report a unique method to construct hierarchical superstructures based on molecular programming of peptidomimetics. Chiral steric hindrance in the polymer backbone stabilizes peptoid helices that crystallize into nanosheets during solvent evaporation. The stacking of nanosheets results in flower-like superstructures. The helical peptoid, nucleated from chiral monomers, is characterized as locally stiffer and more extended than the unstructured peptoid. Molecular dynamics (MD) simulations further suggest a constraint on the dihedral angles and a preference toward the trans configuration, resulting in an extended chain structure. The nanosheet assemblies at various length scales indicate an extent of intermolecular ordering amplified by chiral steric hindrance. Such molecular programming and processing protocols will benefit the future design and controlled assembly of hierarchical peptidomimetics.

Contribution of the Medial Iliofemoral Ligament to Hip Stability After Total Hip Arthroplasty Through the Direct Anterior Approach.

BACKGROUND: Dislocation after total hip arthroplasty (THA) is a primary reason for THA revision. During THA through the direct anterior approach (DAA), the iliofemoral ligament, which provides the main resistance to external rotation (ER) of the hip, is commonly partially transected. We asked: (1) what is the contribution of the medial iliofemoral ligament to resisting ER after DAA THA? and (2) how much resistance to ER can be restored by repairing the ligament? METHODS: A fellowship-trained surgeon performed DAA THA on 9 cadaveric specimens. The specimens were computed tomography scanned before and after implantation. Prior to testing, the ER range of motion of each specimen to impingement in neutral and 10° of extension was computationally predicted. Each specimen was tested on a 6-degrees-of-freedom robotic manipulator. The pelvis was placed in neutral and 10° of extension. The femur was externally rotated until it reached the specimen's impingement target. Total ER torque was recorded with the medial iliofemoral ligament intact, after transecting the ligament, and after repair. Torque at extremes of motion was calculated for each condition. To isolate the contribution of the native ligament, the torque for the transected state was subtracted from both the native and repaired conditions. RESULTS: The medial iliofemoral ligament contributed an average of 68% (range, 34 to 87) of the total torque at the extreme of motion in neutral and 80% (58 to 97) in 10° of extension. The repaired ligament contributed 17% (1 to 54) of the total torque at the extreme of motion in neutral and 14% (5 to 38) in 10° of extension, restoring on average 18 to 25% of the native resistance against ER. CONCLUSIONS: The medial iliofemoral ligament was an important contributor to the hip torque at the extreme of motion during ER. Repairing the ligament restored a fraction of its ability to generate torque to resist ER.

AlphaFold-assisted structure determination of a bacterial protein of unknown function using X-ray and electron crystallography.

Macromolecular crystallography generally requires the recovery of missing phase information from diffraction data to reconstruct an electron-density map of the crystallized molecule. Most recent structures have been solved using molecular replacement as a phasing method, requiring an a priori structure that is closely related to the target protein to serve as a search model; when no such search model exists, molecular replacement is not possible. New advances in computational machine-learning methods, however, have resulted in major advances in protein structure predictions from sequence information. Methods that generate predicted structural models of sufficient accuracy provide a powerful approach to molecular replacement. Taking advantage of these advances, AlphaFold predictions were applied to enable structure determination of a bacterial protein of unknown function (UniProtKB Q63NT7, NCBI locus BPSS0212) based on diffraction data that had evaded phasing attempts using MIR and anomalous scattering methods. Using both X-ray and micro-electron (microED) diffraction data, it was possible to solve the structure of the main fragment of the protein using a predicted model of that domain as a starting point. The use of predicted structural models importantly expands the promise of electron diffraction, where structure determination relies critically on molecular replacement.

The Impact of Noise and Brightness on Object Detection Methods.

The application of deep learning to image and video processing has become increasingly popular nowadays. Employing well-known pre-trained neural networks for detecting and classifying objects in images is beneficial in a wide range of application fields. However, diverse impediments may degrade the performance achieved by those neural networks. Particularly, Gaussian noise and brightness, among others, may be presented on images as sensor noise due to the limitations of image acquisition devices. In this work, we study the effect of the most representative noise types and brightness alterations on images in the performance of several state-of-the-art object detectors, such as YOLO or Faster-RCNN. Different experiments have been carried out and the results demonstrate how these adversities deteriorate their performance. Moreover, it is found that the size of objects to be detected is a factor that, together with noise and brightness factors, has a considerable impact on their performance.

Intravenous magnesium sulfate for asthma exacerbations in children: Systematic review with meta-analysis.

BACKGROUND: Asthma is the most prevalent chronic disease in children and constitutes a significant healthcare burden. First-line therapy for acute asthma exacerbations is well established. However, secondary treatments, including intravenous magnesium sulfate (IV-MgSO4), remain variable due to scarcity of data on its efficacy and safety. OBJECTIVE: To assess the effectiveness and safety of IV-MgSO4 as a second line of treatment in managing children with asthma exacerbations. METHODS: We searched five databases from inception until April 2023 on randomized clinical trials of IV-MgSO4 in children with acute asthma exacerbations. The primary outcomes were hospitalization rate and length, and change in the severity score. Secondary outcomes included percentage increase in peak expiratory flow rate (PEFR), hospital re-admission rate, need and length for pediatric intensive care unit (PICU) treatment, and adverse effects. Meta-analysis was performed for three outcomes with estimated odds ratios (ORs) or mean differences (MDs) and 95% confidence intervals (CIs). RESULTS: Eleven studies met the final criteria. In comparison to control, administration of IV-MgSO4 was associated with a reduced hospitalization risk (OR 0.15; 95%CI: 0.03, 0.73) in four studies, and improvement of lung function (MD 26.77% PEFR; 95%CI: 18.41, 54.79) in two studies. There were no significant differences in the length of stay between groups. Due to heterogeneity, a narrative synthesis of other outcomes was performed. CONCLUSION: The use of IV-MgSO4 demonstrated a reduction in the hospitalization rate and PEFR improvement in children with asthma exacerbations. Adverse effects were rare. Further well-designed studies are needed to better determine the efficacy and safety profile of IV-MgSO4.

Unveiling the inherent physical-chemical dynamics: Direct measurements of hydrothermal fluid flow, heat, and nutrient outflow at the Tagoro submarine volcano (Canary Islands, Spain).

Tagoro is one of the few submarine volcanoes in the world that has been monitored since its early eruptive stage in 2011 to present day. After six multidisciplinary oceanographic cruises conducted between 2014 and 2023 to gather a comprehensive dataset of georeferenced video-imagery and in situ measurements of hydrothermal flow velocities and hydrothermal fluid samples, we provide a robust characterization of the ongoing hydrothermal fluid velocity, heat flux, and nutrient release, along with an accurate delimitation of the hydrothermal field area. Our results reveal that Tagoro hydrothermal system extends from the main hydrothermal crater up to the summit, covering an area of 7600 m2. This hydrothermal field comprises thousands of small individual vents, displaying diverse morphologies such as crevices and delicate chimney-like structures, irregularly scattered across the dominant diffuse venting surface. Hydrothermal fluid temperatures and velocities at the substratum level reveal a clustered spatial distribution, ranging from 21.0 to 33.3 °C and 1.6-26.8 cm min-1, respectively. Furthermore, our findings indicate a discernible correlation between hydrothermal fluid temperature and vent density, while significant differences were observed between velocities from diffuse and focused areas. Additionally, heat fluxes exceed 200 MW across the entire active region, with heat flux values ranging from 6.06 to 146.87 kW m-2 and dissolve inorganic nutrient concentrations exhibit significant enrichments, comparable to the magnitude of important nutrient sources in the area as upwelling systems or mesoscale structures.

The John N. Insall Award: Does Melatonin Improve Subjective Sleep Quality After Total Knee Arthroplasty? A Randomized, Placebo-Controlled Trial.

BACKGROUND: Sleep disturbance is a common problem following total knee arthroplasty (TKA). The objective of this study was to determine if exogenous melatonin improves sleep quality following primary TKA. METHODS: A randomized, double-blind, placebo-controlled trial was conducted. A total of 172 patients undergoing unilateral TKA for primary knee osteoarthritis were randomized to receive either 5 mg melatonin (n = 86) or 125 mg vitamin C placebo (n = 86) nightly for 6 weeks. The primary outcome was the Pittsburgh Sleep Quality Index (PSQI) at 6 weeks and 90 days postoperatively. Secondary outcomes included 6-week and 90-day patient-reported outcome measures (PROMs), morphine milligram equivalents prescribed, medication compliance, adverse events, and 90-day readmissions. RESULTS: Mean PSQI scores worsened at 6 weeks before returning to the preoperative baseline at 90 days in both groups. There were no differences in PSQI scores between melatonin and placebo groups at 6 weeks (10.2 ± 4.2 versus 10.5 ± 4.4, P = .66) or 90 days (8.1 ± 4.1 versus 7.5 ± 4.0, P = .43). Melatonin did not improve the Knee Injury and Osteoarthritis Outcome Score for Joint Replacement, Lower Extremity Activity Scale, Visual Analog Scale for pain, or Veterans Rand 12 Physical Component Score or Mental Component Score at 6 weeks or 90 days. Poor sleep quality was associated with worse PROMs at 6 weeks and 90 days on univariate and multivariable analyses, but melatonin did not modify these associations. There were no differences in morphine milligram equivalents prescribed, medication compliances, adverse events, or 90-day readmissions between both groups. CONCLUSIONS: Exogenous melatonin did not improve subjective sleep quality or PROMs at 6 weeks or 90 days following TKA. Poor sleep quality was associated with worse patient-reported function and pain. Our results do not support the routine use of melatonin after TKA.

Proximal radiolucent lines around fully hydroxyapatite-coated tapered femoral stems: should we be concerned?

INTRODUCTION: Radiolucent lines occasionally develop around the proximal aspect of fully hydroxyapatite (HA)-coated tapered femoral stems after total hip arthroplasty (THA). It was hypothesised that distal wedging of stems may predispose to proximal radiolucent line formation, which may negatively impact clinical outcome. METHODS: All primary THA performed with a collarless fully HA-coated stem that had a minimum of 1 year of radiographic follow-up were identified in a surgical database (n = 244). Radiographic measures of proximal femoral morphology and femoral canal fill at the middle and distal thirds of the stem were analysed for association with the presence of proximal radiolucent lines. Linear regression was used to explore any association between radiolucent lines and patient reported outcome measures (PROMs), available in 61% of patients. RESULTS: Proximal radiolucent lines developed in 31 cases (12.7%) at final follow-up. Dorr A femoral morphology and increased canal-fill at the distal ⅓ of the stem correlated with the development of radiolucent lines (p < 0.001). No correlation was observed between pain or PROMs and the presence of proximal radiolucent lines. DISCUSSION: We observed an unexpectedly high incidence of proximal femoral radiolucent lines about collarless fully HA coated stems. Distal-only implant wedging in Dorr A bone may compromise proximal fixation. Although this finding did not correlate with short-term outcomes, the long-term clinical impact requires further study.

Higher levels of insulin-like growth factor-1 in cord blood associate with risk of asthma at age 3.

RATIONALE: Experimental studies and epidemiological data in adults suggest that somatomedin-C (insulin-like growth factor-1, IGF-1) may play a role in asthma by modulating airway inflammation, bronchial hyperreactivity, and airway smooth muscle hyperplasia. However, its role in children with asthma is not well understood. METHODS: We established a birth cohort with 339 Chilean pregnant mothers enrolled at the time of delivery from December 2014 to January 2016. We obtained cord blood at birth and followed the offspring every 6 months until 30 months of age, recording data on atopy, wheezing, and other respiratory illnesses. We measured IGF-1 in cord blood and determined the Asthma Predictive Index (API) at 30 months. The cohort was divided according to the API. RESULTS: Complete data were available for 307/339 (91%) dyads, including 44 preschoolers with API+ and 263 with API-. Demographic characteristics were similar between groups, but mothers of API+ children had a higher prevalence of obesity, previous use of oral contraceptives, and higher education than those of API- children. API+ children had higher birth weight and significantly higher IGF-1 in cord blood (37.4 ± 13.2 in API+ vs. 30.5 ± 13.0 ng/ml in API-, p = .01). In the multivariable analysis, IGF-1 in cord blood remained independently associated with a higher risk of asthma (adjusted OR for API+ per ng/ml higher IGF-1 = 1.03 [1.0-1.06], p = .015). CONCLUSIONS: Higher insulin-like growth factor-1 in cord blood is associated with asthma risk in the preschool years.

On-Demand ICS + FABA Combinations in 6-11-Year-Old Children.

In recent years, some new concepts have been added to asthma treatment such as "anti-inflammatory reliever" (ß2-agonist use associated to an inhaled corticosteroid (ICS) as a reliever treatment) that combines the benefits of both therapies and provides short- and long-term benefits for treatment in asthma patients. Robust evidence has been presented in patients over 12 years, and the main changes in the international guidelines for asthma treatment were originally made in this age group. However, a few suggestions have been added to treatments in younger patients, in part because of the scarce evidence that exists in this group. We aim to analyze the information regarding the utilization of ICS + fast-acting beta-agonist (FABA) combination in children between 6 and 11 years. Although up until today only three published trials exist (two studies use beclomethasone + albuterol and one study uses budesonide + formoterol), they provide significant information on the benefits of ICS + FABA use in this population.

Disability and COVID-19: Challenges, testing, vaccination, and postponement and avoidance of medical care among minoritized communities.

BACKGROUND: People with disabilities face heightened vulnerability to COVID-19. OBJECTIVE: This study investigated (1) the relationships between disability and COVID-19-related challenges, testing, vaccination, and infection and (2) predictors of loss of healthcare coverage and postponement and avoidance of medical care during the pandemic. METHODS: This cross-sectional study was conducted in Miami, Florida, between March 2021 and February 2022 as part of the NIH Rapid Acceleration of Diagnostics-Underserved Populations initiative. Disability was defined using a standard measure that assesses six universal functions. Participants reported sociodemographic data, COVID-19 testing, infection history, challenges, and healthcare history. Vaccinations were confirmed with medical records and COVID-19 positivity was assessed using real-time reverse transcription-polymerase chain reaction. Statistical analyses included multivariable logistic regression. RESULTS: Among 1,689 participants with a median age of 57.0, 50.6% were male, and 48.9% were non-Hispanic Black. Disability was associated with greater odds of all assessed COVID-19 challenges: healthcare (aOR:1.60; 95% CI:1.23-2.07), housing (aOR:2.15; 95% CI:1.62-2.87), insufficient food (aOR:1.97; 95% CI:1.54-2.52), water scarcity (aOR:2.33; 95% CI:1.60-3.37), medications (aOR:2.04; 95% CI:1.51-2.77), and transportation (aOR:2.56; 95% CI:1.95-3.36). Those reporting employment disability were less likely to have received COVID-19 testing (81.1% vs. 85.3%, p = 0.026) or to have history of COVID-19 positivity (aOR:0.63; 95% CI:0.44-0.92). Disability predicted avoidance (aOR:2.76; 95% CI:1.95-3.91) and postponement (aOR: 2.24; 95% CI:1.72-2.91) of medical care. CONCLUSIONS: Disability is associated with higher odds of COVID-19 challenges and postponement and avoidance of medical care. Those reporting employment disability had a lower likelihood of COVID-19 testing. Public health responses to healthcare crises should prioritize the special challenges of people living with disabilities.

Trimethylamine N-Oxide as a Mediator Linking Peripheral to Central Inflammation: An In Vitro Study.

In this study, the plausible role of trimethylamine N-oxide (TMAO), a microbiota metabolite, was investigated as a link between peripheral inflammation and the inflammation of the central nervous system using different cell lines. TMAO treatment favored the differentiation of adipocytes from preadipocytes (3T3-L1 cell line). In macrophages (RAW 264.7 cell line), which infiltrate adipose tissue in obesity, TMAO increased the expression of pro-inflammatory cytokines. The treatment with 200 µM of TMAO seemed to disrupt the blood-brain barrier as it induced a significant decrease in the expression of occludin in hCMECs. TMAO also increased the expression of pro-inflammatory cytokines in primary neuronal cultures, induced a pro-inflammatory state in primary microglial cultures, and promoted phagocytosis. Data obtained from this project suggest that microbial dysbiosis and increased TMAO secretion could be a key link between peripheral and central inflammation. Thus, TMAO-decreasing compounds may be a promising therapeutic strategy for neurodegenerative diseases.

Morphology Dependent Reactivity of CsOx Nanostructures on Au(111): Binding and Hydrogenation of CO2 to HCOOH.

Cesium oxide (CsOx) nanostructures grown on Au(111) behave as active centers for the CO2 binding and hydrogenation reactions. The morphology and reactivity of these CsOx systems were investigated as a function of alkali coverage using scanning tunneling microscopy (STM), ambient pressure X-ray photoelectron spectroscopy (AP-XPS), and density functional theory (DFT) calculations. STM results show that initially (0.05-0.10 ML) cesium oxide clusters (Cs2O2) grow at the elbow sites of the herringbone of Au(111), subsequently transforming into two-dimensional islands with increasing cesium coverage (>0.15 ML). XPS measurements reveal the presence of suboxidic (CsyO; y ≥ 2) species for the island structures. The higher coverages of cesium oxide nanostructures contain a lower O/Cs ratio, resulting in a stronger binding of CO2. Moreover, the O atoms in the CsyO structure undergo a rearrangement upon the adsorption of CO2 which is a reversible phenomenon. Under CO2 hydrogenation conditions, the small Cs2O2 clusters are hydroxylated, thereby preventing the adsorption of CO2. However, the hydroxylation of the higher coverages of CsyO did not prevent CO2 adsorption, and adsorbed CO2 transformed to HCOO species that eventually yield HCOOH. DFT calculations further confirm that the dissociated H2 attacks the C in the adsorbate to produce formate, which is both thermodynamically and kinetically favored during the CO2 reaction with hydroxylated CsyO. These results demonstrate that cesium oxide by itself is an excellent catalyst for CO2 hydrogenation that could produce formate, an important intermediate for the generation of value-added species. The role of the alkali oxide nanostructures as active centers, not merely as promoters, may have broad implications, wherein the alkali oxides can be considered in the design of materials tuned for specific applications in heterogeneous catalysis.

Dislocation Following Anterior and Posterior Total Hip Arthroplasty in the Setting of Spinal Deformity and Stiffness: Evolving Trends Using a High-Risk Protocol at a Single Tertiary Center.

BACKGROUND: Patients who have spinal stiffness and deformity are at the highest risk for dislocation after total hip arthroplasty (THA). Previous reports of this cohort are limited to antero-lateral and postero-lateral (PL) approaches. We investigated the dislocation rate after direct anterior (DA) and PL approach THA with a contemporary high-risk protocol to optimize stability. METHODS: We investigated patients undergoing THA who had preoperative biplanar imaging from January-December 2019. Patients were identified using radiographic criteria of spinal-stiffness (<10-degree change in sacral slope from standing to seated) and deformity (flatback deformity with >10-degree difference in pelvic incidence and lumbar lordosis). There were 367 patients identified (181 DA, 186 PL). The primary outcome was dislocation rate at 2-years postoperatively. Risk-factors for dislocation were evaluated using logistic regressions (significance level of 0.05). RESULTS: There were 6 (1.6%) dislocations in the entire cohort, with low dislocation rates for both DA (0.6%) and PL-THA (2.7%). We observed increased utilization of dual mobility with larger outer head bearings (>38 mm) with PL-THA (34.4 versus 5.0%, P < .01) and conversely increased utilization of 32-mm femoral-heads with DA-THA (39.4 versus 7.0%, P < .001). Surgical approach (PL) was not a significant risk-factor for dislocation (odds ratio: 5.03, P = .15). Patients who had a history of lumbar-fusion had 8-times higher odds for dislocation (OR: 8.20, P = .020). CONCLUSIONS: To the best of our knowledge, this is the largest series to date evaluating DA and PL-THA in the hip-spine 2B-group. Our results demonstrate lower dislocation rate than expected with either surgical approach using a high-risk protocol.

How Much Protection Does a Collar Provide? Assessing Risk of Early Periprosthetic Femur Fractures Following Total Hip Arthroplasty in Elderly Patients.

BACKGROUND: Periprosthetic fractures (PPFs) account for approximately 25% of early revisions following total hip arthroplasty (THA). Cemented femoral fixation is associated with a lower-risk of PPF, and collared-cementless stems may reduce the risk as well. The objective of this study was to compare early-PPF rates between cemented, collared-cementless, and non-collared cementless stems in elderly patients. METHODS: A consecutieve-series of 11,522 primary THAs performed between 2016 and 2021 at our institution in patients >65 years of age was identified. Stem types used were categorized as cemented, collared-cementless, or non-collared cementless. Patients undergoing THA who had cemented-stems were older, more commonly women, and more likely to have a posterior-approach. To reduce confounding of patient characteristics, we matched patients in the 3 stem-categories according to age, sex, and body mass index. This generated 3-groups (cemented, collared-cementless, and non-collared cementless) consisting of 936 patients per group. The mean age of these 2,808 patients was 73 years, the mean body mass index was 27, and 67% were women. Logistic regressions were used to evaluate risk-factors for early-PPF. In the entire cohort of primary THA in elderly patients, there were 85 early PPFs (0.7%) over the study period. RESULTS: Non-collared cementless stems were associated with an increased risk of early PPF (OR: 3.11; P = .03) compared to collared-cementless stems. There were no early PPFs in the matched cemented cohort, 6 early PPFs in the matched collared-cementless cohort, and 16 early-PPFs in the matched non-collared cementless cohort (0% versus 0.64% versus 1.71%, P < .001). CONCLUSIONS: In this large-series of patients >65 years of age undergoing primary THA, cemented stem fixation had the lowest incidence of early PPF, but collared-cementless stems had a nearly 3-fold decrease in risk for early PPF compared to non-collared cementless stems.

Role of LCN2 in a murine model of hindlimb ischemia and in peripheral artery disease patients, and its potential regulation by miR-138-5P.

BACKGROUND AND AIMS: Peripheral arterial disease (PAD) is a leading cause of morbimortality worldwide. Lipocalin-2 (LCN2) has been associated with higher risk of amputation or mortality in PAD and might be involved in muscle regeneration. Our aim is to unravel the role of LCN2 in skeletal muscle repair and PAD. METHODS AND RESULTS: WT and Lcn2-/- mice underwent hindlimb ischemia. Blood and crural muscles were analyzed at the inflammatory and regenerative phases. At day 2, Lcn2-/- male mice, but not females, showed increased blood and soleus muscle neutrophils, and elevated circulating pro-inflammatory monocytes (p < 0.05), while locally, total infiltrating macrophages were reduced (p < 0.05). Moreover, Lcn2-/- soleus displayed an elevation of Cxcl1 (p < 0.001), and Cxcr2 (p < 0.01 in males), and a decrease in Ccl5 (p < 0.05). At day 15, Lcn2 deficiency delayed muscle recovery, with higher density of regenerating myocytes (p < 0.04) and arterioles (αSMA+, p < 0.025). Reverse target prediction analysis identified miR-138-5p as a potential regulator of LCN2, showing an inverse correlation with Lcn2 mRNA in skeletal muscles (rho = -0.58, p < 0.01). In vitro, miR-138-5p mimic reduced Lcn2 expression and luciferase activity in murine macrophages (p < 0.05). Finally, in human serum miR-138-5p was inversely correlated with LCN2 (p ≤ 0.001 adjusted, n = 318), and associated with PAD (Odds ratio 0.634, p = 0.02, adjusted, PAD n = 264, control n = 54). CONCLUSIONS: This study suggests a possible dual role of LCN2 in acute and chronic conditions, with a probable role in restraining inflammation early after skeletal muscle ischemia, while being associated with vascular damage in PAD, and identifies miR-138-5p as one potential post-transcriptional regulator of LCN2.