Neutrophil-Lymphocyte Ratio and Lymphocyte-Monocyte Ratio correlate with Chronic Prosthetic Joint Infection but are not useful markers for diagnosis.

PURPOSE: To investigate reported correlations between Neutrophil-to-Lymphocyte (NLR) and Lymphocyte-to-Monocyte (LMR) ratios and their value in diagnosis of chronic prosthetic joint infection (PJI) in a large cohort of patients from a single specialist hospital. METHODS: Diagnostic aspirations of 362 patients under investigation for PJI were identified. Of the included patients 185 patients received a final diagnosis of PJI and 177 were classed as aseptic. Established criteria (ICM 2018) were employed to define PJI. Included in the analysis are differential white cell counts, C-Reactive Protein (CRP), Synovial Leukocyte Count, Synovial Alpha-defensin ELISA and Synovial Leukocyte esterase activity. Receiver-operator characteristic (ROC) curves were calculated for each of the available diagnostic tests together with the corresponding area under the curve values (AUC). Youden's index was utilized to identify the optimal diagnostic threshold point for the NLR and LMR. Other diagnostic tests were evaluated as per the threshold values previously defined in the literature and specified in the ICM criteria. RESULTS: Using Youden's Index to identify the optimal NLR cut-off within our cohort we established a value of 2.93. This yielded a sensitivity of 0.60 and specificity of 0.64. The area under the curve (AUC) of a receiving operator characteristics (ROC) curve was 0.625. Regarding the LMR the results demonstrate similar findings; a positive correlation with a diagnosis of infection but poor sensitivity and specificity. The AUC for LMR was 0.633 and was not superior to NLR (P = 0.753). CONCLUSIONS: There is a significant correlation between higher Neutrophil-Lymphocyte and Lymphocyte-Monocyte ratios, and a diagnosis of PJI. The sensitivity and specificity of this calculation is poor and the does not add value to the diagnostic algorithm for PJI. LEVEL OF EVIDENCE: Level III Retrospective Cohort analysis.

Specular reflection contributions to dynamic radiation forces on highly reflecting spheres (L).

Specular reflection contributions to dynamic radiation forces were recently mentioned for highly reflecting spheres to facilitate comparison with forces on cylinders [Marston, Daniel, Fortuner, Kirsteins, and Abawi, J. Acoust. Soc. Am. 149, 3042-3051 (2021)]. Both shapes of reflectors were taken to be illuminated by short-wavelength plane wave double-sideband suppressed-carrier ultrasound. Here, the geometric method of evaluating dynamic forces on spheres is illustrated along with an analysis of the phase of the modulated radiation force. Comparison with partial wave series solutions supports the relevance of the specular reflection analysis for insight into forces on highly reflecting objects in water.

Specular-reflection contributions to static and dynamic radiation forces on circular cylinders.

Interest in the response of highly reflecting objects in water to modulated acoustical radiation forces makes it appropriate to consider contributions to such forces from perfectly reflecting objects to provide insight into radiation forces. The acoustic illumination can have wavelengths much smaller than the object's size, and objects of interest may have complicated shapes. Here, the specular contribution to the oscillating radiation force on an infinite circular cylinder at normal incidence is considered for double-sideband-suppressed carrier-modulated acoustic illumination. The oscillatory magnitude of the specular force decreases monotonically with increasing modulation frequency, and the phase of the oscillating force depends on the relative phase of the sidebands. The phase dependence on the modulation frequency can be reduced with the appropriate selection of a sideband relative-phase parameter. That is a consequence of the significance of rays that are incident on the cylinder having small impact parameters that are nearly backscattered. For one choice of a relative sideband phase, a prior partial wave series (PWS) solution is available, which supports the specular analysis when the PWS is evaluated for a rigid cylinder. The importance of specular contributions for aluminum cylinders in water is noted. A specular analysis for an analogous spherical reflector is also summarized.

Maxwell stress excitation of wire vibrations at difference and sum frequencies of electric currents in separate circuits.

Oscillating electric currents through a wire under tension can excite transverse vibrational modes of the wire when a perpendicular static magnetic field is present and the frequency of the current is close to the natural frequency of the mode of interest. The excitation of the mode is associated with temporally oscillating Maxwell stresses on the wire, often also known as oscillating Lorentz forces. That excitation process is sometimes demonstrated in educational contexts. The investigation here concerns situations where a temporally oscillating magnetic field generated by oscillating electric currents in a cylindrical coil replaces the imposed perpendicular static magnetic field. The frequencies of the currents in the wire and in the coil are related to the frequency of the oscillating stress. In this experiment, this effect is documented for sum-frequency excitation (with input frequencies in the range of half that of the excited lowest vibrational mode of the wire) and the difference-frequency excitation (with input frequencies an order-of-magnitude larger than the mode frequency). This coupling may be useful when it is desirable to use only high-frequency currents. The experiment uses tone-burst stress excitation and a differential photodiode for detecting transverse low-amplitude wire oscillations. Signal envelopes decayed exponentially after the tone-burst.

A Pilot Study to Assess Clinical Utility and User Experience of Professional Continuous Glucose Monitoring Among People With Type 2 Diabetes.

IN BRIEF Glucose variability is a potential independent risk factor of poor clinical outcome among people with diabetes, with adequate measurement technically difficult and cumbersome. For this study, a novel 14-day continuous sensor was used to assess glucose variability among people with type 2 diabetes (T2D). The aim was to characterize glucose profiles for up to 2 weeks in T2D and to survey device utilization in a standard clinical setting and its potential to collect clinically meaningful data.

Bessel beam expansion of linear focused ultrasound.

Previous work on scattering by Bessel beams shows that expansion of incident sound fields in term of these beams has application to scattering [P. L. Marston, J. Acoust. Soc. Am. 122, 247-252 (2007)]. In this work, an expression for the expansion coefficients of propagating, axisymmetric, sound fields are derived. In this paper, this expression is applied to a linear focused axisymmetric sound field and is expanded in terms of Bessel beam components. This is done for focused beams radiated from a spherical cap source. A physical optics model is applied to sound propagation close to the source to facilitate the calculation of the Bessel beam expansion coefficients. This type of model is useful for focused scattering [P. L. Marston and D. S. Langley, J. Acoust. Soc. Am. 73, 1464-1475 (1983)]. Once the expansion coefficients are found, the sound field can be evaluated by superposition. The model agrees approximately with Chen, Schwarz, and Parker [J. Acoust. Soc. Am. 94, 2979-2991 (1993)] and O'Neil [J. Acoust. Soc. Am. 21, 516-526 (1949)] on axis and with direct integration of a Kirchhoff integral both on and off axis. This type of expansion will have applications to scattering problems.

Observation and modeling of acoustic scattering from a rubber spherical shell.

Acoustic backscattering from a rubber spherical shell in water is observed to contain a delayed enhancement, demonstrated to be associated with a waveguide path along the shell. This path is somewhat analogous to that of the Lamb wave observed on metallic shells. Rubber is a unique material because of its subsonic sound speed relative to water, and because shear coupling is often small enough to be neglected in typical models, making it fluid-like. This makes rubber a material of interest for coating and cloaking underwater devices and vehicles. Both fluid and elastic rubber partial wave series models are tested, using experimentally measured longitudinal and shear speeds, attenuation, and rubber density. A finite element model for the shell is also developed. Comparison of the models and experiments highlights the importance of the waveguide path to the overall scattering. Estimates for the group and phase velocities of the lowest order propagating mode in the shell are determined through waveguide normal mode analysis and Sommerfeld-Watson theory, and are shown to give good agreement with experiments in predicting the time of arrival of the waveguide path.

The adaptor protein Shc integrates growth factor and ECM signaling during postnatal angiogenesis.

Angiogenesis requires integration of cues from growth factors, extracellular matrix (ECM) proteins, and their receptors in endothelial cells. In the present study, we show that the adaptor protein Shc is required for angiogenesis in zebrafish, mice, and cell-culture models. Shc knockdown zebrafish embryos show defects in intersegmental vessel sprouting in the trunk. Shc flox/flox; Tie2-Cre mice display reduced angiogenesis in the retinal neovascularization model and in response to VEGF in the Matrigel plug assay in vivo. Functional studies reveal a model in which Shc is required for integrin-mediated spreading and migration specifically on fibronectin, as well as endothelial cell survival in response to VEGF. Mechanistically, Shc is required for activation of the Akt pathway downstream of both integrin and VEGF signaling, as well as for integration of signals from these 2 receptors when cells are grown on fibronectin. Therefore, we have identified a unique mechanism in which signals from 2 critical angiogenic signaling axes, integrins and VEGFR-2, converge at Shc to regulate postnatal angiogenesis.

Bmper inhibits endothelial expression of inflammatory adhesion molecules and protects against atherosclerosis.

OBJECTIVE: Bone morphogenetic proteins (Bmps) are important mediators of inflammation and atherosclerosis, though their mechanism of action is not fully understood. To better understand the contribution of the Bmp signaling pathway in vascular inflammation, we investigated the role of Bmper (Bmp endothelial cell precursor-derived regulator), an extracellular Bmp modulator, in an induced in vivo model of inflammation and atherosclerosis. METHODS AND RESULTS: We crossed apolipoprotein E-deficient (ApoE(-/-)) mice with mice missing 1 allele of Bmper (Bmper(+/-) mice used in the place of Bmper(-/-) mice that die at birth) and measured the development of atherosclerosis in mice fed a high-fat diet. Bmper haploinsufficiency in ApoE(-/-) mice (Bmper(+/-);ApoE(-/-) mice) led to a more severe phenotype compared with Bmper(+/+);ApoE(-/-) mice. Bmper(+/-);ApoE(-/-) mice also exhibited increased Bmp activity in the endothelial cells in both the greater and lesser curvatures of the aortic arch, suggesting a role for Bmper in regulating Bmp-mediated inflammation associated with laminar and oscillatory shear stress. Small interfering RNA knockdown of Bmper in human umbilical vein endothelial cells caused a dramatic increase in the inflammatory markers intracellular adhesion molecule 1 and vascular cell adhesion molecule 1 at rest and after exposure to oscillatory and laminar shear stress. CONCLUSIONS: We conclude that Bmper is a critical regulator of Bmp-mediated vascular inflammation and that the fine-tuning of Bmp and Bmper levels is essential in the maintenance of normal vascular homeostasis.

Elevated IL-7 availability does not account for T cell proliferation in moderate lymphopenia.

Lymphopenia-induced proliferation (LIP) is a proliferative program initiated in response to T cell insufficiency caused by acute or chronic immunodepletion. Studies of lymphopenic mice have demonstrated that the cytokine IL-7 and TCR signaling are critical for LIP. We examined how these two factors impact T cell proliferation following transfer into moderately lymphopenic mice. In this study, we show that moderate lymphopenia (∼25% of wild-type lymphocytes) of IL-7Rα knock-in mutant (IL-7Rα(449F)) mice supports T cell proliferation, although with decreased frequency and kinetics compared with cells transferred to severely lymphopenic (5% of wild-type lymphocytes) IL-7Rα(-/-) hosts. Although previous studies have demonstrated that elevated IL-7 levels play an important role in LIP, IL-7 availability was not elevated in IL-7Rα(449F) mice. However, moderate lymphopenia increased access of transferred T cells to self-peptide presented on APCs that can trigger TCR signaling and proliferation. Importantly, we did not detect significant changes in TCR Vß usage of proliferated T cells recovered from either moderately or severely lymphopenic hosts. Our work demonstrates that polyclonal T cells retain a diverse TCR repertoire following proliferation mediated by either self-peptide-MHC interaction alone or in combination with IL-7, and that T cell reconstitution is most efficient in the presence of increased IL-7 availability.

Flash glucose monitoring in type 2 diabetes managed with basal insulin in the USA: a retrospective real-world chart review study and meta-analysis.

INTRODUCTION: Evidence supporting use of continuous glucose monitoring in type 2 diabetes treated with basal insulin is unclear. This real-world study aimed to assess the impact on glycated hemoglobin (HbA1c) of flash glucose monitoring use in adults with type 2 diabetes managed with basal insulin. RESEARCH DESIGN AND METHODS: Medical records were reviewed for adult individuals with type 2 diabetes using basal insulin for ≥1 year with or without additional antihyperglycemic medication, HbA1c 8.0%-12.0% prior to FreeStyle Libre Flash Glucose Monitoring use for ≥90 days and an HbA1c measurement recorded between 90 and 194 days after device use. Exclusion criteria included utilization of bolus insulin. Meta-analysis data are from the current study (USA) and a similar Canadian cohort. RESULTS: Medical record analysis (n=100) from 8 USA study sites showed significant HbA1c decrease of 1.4%±1.3%, from 9.4%±1.0% at baseline to 8.0%±1.2% after device use, p<0.0001 (mean±SD).Meta-analysis of medical records from USA and Canada sites (n=191) showed HbA1c significantly decreased by 1.1%±0.14% (mean±SE), from baseline 9.2%±1.0% to 8.1%±1.1%, p≤0.0001, with moderate to high heterogeneity between sites (Q=43.9, I2=74.9, p<0.0001) explained by differences in baseline HbA1c between sites.The HbA1c improvement in both groups was observed by age group, body mass index, duration of insulin use and sex at birth. CONCLUSIONS: In a real-world retrospective USA study and a meta-analysis of a larger USA and Canada cohort, HbA1c significantly reduced in basal insulin-treated type 2 diabetes, without bolus insulin initiation and following the commencement of flash glucose monitoring technology.

Syntheses and solid-state structures of two cofacial (bis)dipyrrin dichromium complexes in different charge states.

The dichromium Pacman complex (tBudmx)Cr2Cl2·C4H10O (1) [(tBudmx)H2 is a dimethylxanthene-bridged cofacial (bis)dipyrrin, C49H58N4O] was synthesized by salt metathesis using anhydrous CrCl2 and previously reported (tBudmx)K2. Treatment of 1 with two equivalents of the reductant potassium graphite afforded K2(tBudmx)Cr2Cl2(thf)3·0.5C4H10O·0.5C4H8O (thf is tetrahydrofuran, C4H8O) (2), with both potassium ions intercalated between the pyrrolic subunits. Comparison of the solid-state structures for 1 and 2 reveals minimal changes in the primary coordination sphere of each Cr ion, with notable elongation of the dipyrrin C-C and C-N bonds upon reduction, consistent with computational support for a ligand-based reduction.

Treatment Strategies and Outcomes for Osteochondritis Dissecans of the Capitellum.

BACKGROUND: The optimum management of osteochondritis dissecans (OCD) of the capitellum is a widely debated subject. PURPOSE: To better understand the efficacy of different surgical modalities and nonoperative treatment of OCD as assessed by radiological and clinical outcomes and return to sports. STUDY DESIGN: Systematic review; Level of evidence, 4. METHODS: A systematic review of all treatment studies published between January 1975 and June 2020 was performed following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. A total of 76 clinical studies, including 1463 patients, were suitable for inclusion. Aggregate analysis and subgroup analysis of individual patient data were performed to compare the functional and radiographic outcomes between the various nonoperative and surgical treatment options for capitellar OCD. A unified grading system (UGS; grades 1-4) was developed from existing validated classification systems to allow a comparison of patients with similar-grade OCD lesions in different studies according to their treatment. Patient-level data were available for 352 patients. The primary outcome measures of interest were patient-reported functional outcome, range of motion (ROM), and return to sports after treatment. The influences of the capitellar physeal status, location of the lesion, and type of sports participation were also assessed. Each outcome measure was evaluated according to the grade of OCD and treatment method (debridement/microfracture, fragment fixation, osteochondral autograft transplantation [OATS], or nonoperative treatment). RESULTS: No studies reported elbow scores or ROM for nonoperatively treated patients. All surgical modalities resulted in significantly increased postoperative ROM and elbow scores for stable (UGS grades 1 and 2) and unstable lesions (UGS grades 3 and 4). There was no significant difference in the magnitude of improvement or overall scores according to the type of surgery for stable or unstable lesions. Return to sports was superior with nonoperative treatment for stable lesions, whereas surgical treatment was superior for unstable lesions. Patients with an open capitellar physis had superior ROM for stable and unstable lesions, but there was no correlation with lesion location and the outcomes of OATS versus fragment fixation for high-grade lesions. CONCLUSION: Nonoperative treatment was similar in outcomes to surgical treatment for low-grade lesions, whereas surgical treatment was superior for higher grade lesions. There is currently insufficient evidence to support complex reconstructive techniques for high-grade lesions compared with microfracture/debridement alone.

Improving Equity of Care for Patients with Limited English Proficiency Using Quality Improvement Methodology.

Disparate clinical outcomes have been reported for patients with Limited English Proficiency (LEP) in the emergency department setting, including increased length of stay, diagnostic error rates, readmission rates, and dissatisfaction. Our emergency department had no standard processes for LEP patient identification or interpreter encounter documentation and a higher rate of 48-hour LEP return visits (RV) than English proficient patients. The aim was to eliminate gaps by increasing appropriate interpreter use and documentation (AIUD) for Spanish-speaking LEP (LEP-SS) patients from 35.7% baseline (10/17-05/18) to 100% by October 2020. METHODS: LEP-SS patient data were reviewed in the electronic medical record to determine the AIUD and RV rates. Using the Model for Improvement and multiple Plan-Do-Study-Act (PDSA) cycles, a multi-disciplinary team encouraged stakeholder engagement and identified improvement opportunities, implemented an electronic tracking board LEP icon (PDSA1), standardized documentation using an LEP Form linked to the icon (PDSA2), and included color changes to the icon for team situational awareness (PDSA3). RESULTS: The mean of LEP-SS patients with AIUD improved from 35.7% to 64.5% without significant changes in balancing measures. During the postintervention period (6/1/2018-10/31/2020), no special cause variation was noted from the baseline 48-hour emergency department RV rates for LEP patients (3.1%) or English proficient patients (2.6%). CONCLUSIONS: While the RV rate was not affected, this project is part of a multi-faceted approach aiming to positively impact this outcome measure. Significant improvements in AIUD were achieved without affecting balancing measures.

Systemic inflammation is elevated among both HIV-uninfected and HIV-infected young MSM.

: Evidence suggests that systemic inflammation increases due to HIV infection. C-reactive protein (CRP), interleukin (IL)-6 and tumour necrosis factor (TNF)-α values were compared between HIV-positive and HIV-negative young MSM and transgender women. CRP values were more than 3 mg/l among 49.8% of participants. HIV status was not significantly associated with CRP nor IL-6. TNF-α was significantly higher among HIV-positive participants. These results suggest the need for further study of the causes and health consequences of elevated systemic inflammation among this population.

Review of thromboembolic prophylaxis in patients attending Cork University Hospital.

BACKGROUND: Although preventable, venous thromboembolism remains a common cause of hospital acquired morbidity and mortality. Guidelines, such as the one produced by the American College of Chest Physicians (ACCP), are aimed at reducing hospital associated venous thromboemboli. Unfortunately the majority of studies have revealed inadequate adherence to these guidelines. OBJECTIVE: The objective of this study was to evaluate the use of venous thromboembolism prophylaxis at Cork University Hospital. SETTING: Cork University Hospital, Wilton, Cork, Ireland. METHODS: Data from the patient's chart, drug kardex and laboratory results were recorded during April 2010. A Caprini score, a venous thromboembolism risk factor assessment tool, was subsequently calculated for each patient based on data collected. Appropriate prophylaxis was determined after examining data collected, Caprini score and prophylactic regime according to the ACCP 8th edition guidelines. MAIN OUTCOME MEASURE: Primary outcome was to analyse adherence to VTE prophylaxis guidelines. RESULTS: A total of 394 patients met the inclusion criteria and were reviewed, of which, 60% (n = 236) were medical and 37% (n = 146) were surgical patients. In total 63% of patients received some form of venous thromboembolism prophylaxis. Furthermore, 54% of medical and 76% of surgical patients received prophylaxis. However only 37% of the patients studied received appropriate thromboprophylaxis according to the ACCP 8th edition guidelines (Geerts et al. in chest 133(6 Suppl):381S-453S, 2008). Additionally 51% of surgical and 27% of medical patients received appropriate prophylaxis. CONCLUSION: Data collected from Cork University Hospital revealed poor adherence to international venous thromboembolism prophylaxis guidelines. As stated in the ACCP 8th edition guidelines, every hospital should develop a formal strategy for venous thromboembolism prevention (Geerts et al. in chest 133(6 Suppl):381S-453S, 2008). In order to improve adherence to guidelines, Cork University Hospital should develop, implement and re-evaluate a specific protocol for venous thromboembolism prophylaxis.

Spatial signaling networks converge at the adaptor protein Shc.

Endothelial cells, which are located at the interface between the blood and the vessel wall, respond dynamically to a variety of stimuli initiating signaling cascades that regulate cardiovascular development, physiology and pathology. These inputs include soluble factors that bind to their receptors, integrin-matrix interactions, cell-cell contacts and mechanical forces due to the flowing blood. While these stimuli can mediate unique downstream signals, it is well-accepted that signaling pathways are highly interwoven into complex signaling networks with several levels of cross-talk, integration and coordination. Recent studies suggest that several signaling networks coalesce at the adaptor protein Shc.

Shc coordinates signals from intercellular junctions and integrins to regulate flow-induced inflammation.

Atherosclerotic plaques develop in regions of the vasculature associated with chronic inflammation due to disturbed flow patterns. Endothelial phenotype modulation by flow requires the integration of numerous mechanotransduction pathways, but how this is achieved is not well understood. We show here that, in response to flow, the adaptor protein Shc is activated and associates with cell-cell and cell-matrix adhesions. Shc activation requires the tyrosine kinases vascular endothelial growth factor receptor 2 and Src. Shc activation and its vascular endothelial cadherin (VE-cadherin) association are matrix independent. In contrast, Shc binding to integrins requires VE-cadherin but occurs only on specific matrices. Silencing Shc results in reduction in both matrix-independent and matrix-dependent signals. Furthermore, Shc regulates flow-induced inflammatory signaling by activating nuclear factor kappaB-dependent signals that lead to atherogenesis. In vivo, Shc is activated in atherosclerosis-prone regions of arteries, and its activation correlates with areas of atherosclerosis. Our results support a model in which Shc orchestrates signals from cell-cell and cell-matrix adhesions to elicit flow-induced inflammatory signaling.