Lung quantitative ultrasound to stage and monitor interstitial lung diseases.

Chronic interstitial lung diseases (ILDs) require frequent point-of-care monitoring. X-ray-based methods lack resolution and are ionizing. Chest computerized tomographic (CT) scans are expensive and provide more radiation. Conventional ultrasound can detect severe lung damage via vertical artifacts (B-lines). However, this information is not quantitative, and the appearance of B-lines is operator- and system-dependent. Here we demonstrate novel ultrasound-based biomarkers to assess severity of ILDs. Lung alveoli scatter ultrasound waves, leading to a complex acoustic signature, which is affected by changes in alveolar density due to ILDs. We exploit ultrasound scattering in the lung and combine quantitative ultrasound (QUS) parameters, to develop ultrasound-based biomarkers that significantly correlate (p = 1e-4 for edema and p = 3e-7 for fibrosis) to the severity of pulmonary fibrosis and edema in rodent lungs. These innovative QUS biomarkers will be very significant for monitoring severity of chronic ILDs and response to treatment, especially in this new era of miniaturized and highly portable ultrasound devices.

Instantly adhesive and ultra-elastic patches for dynamic organ and wound repair.

Bioadhesive materials and patches are promising alternatives to surgical sutures and staples. However, many existing bioadhesives do not meet the functional requirements of current surgical procedures and interventions. Here, we present a translational patch material that exhibits instant adhesion to tissues (2.5-fold stronger than Tisseel, an FDA-approved fibrin glue), ultra-stretchability (stretching to >300% its original length without losing elasticity), compatibility with rapid photo-projection (<2 min fabrication time/patch), and ability to deliver therapeutics. Using our established procedures for the in silico design and optimization of anisotropic-auxetic patches, we created next-generation patches for instant attachment to tissues while conforming to a broad range of organ mechanics ex vivo and in vivo. Patches coated with extracellular vesicles derived from mesenchymal stem cells demonstrate robust wound healing capability in vivo without inducing a foreign body response and without the need for patch removal that can cause pain and bleeding. We further demonstrate a single material-based, void-filling auxetic patch designed for the treatment of lung puncture wounds.

Do Hypoalbuminaemia Increase the Risk of Surgical Site Infection in Neck of Femur Fracture Patients: A Systematic Review and Meta-Analysis.

Serum albumin plays an important role in physiological and inflammatory haemostasis, and low serum levels are linked with an increased incidence of surgical site infections (SSI). Although this has been demonstrated in the spine and elective arthroplasty settings, there is a paucity of evidence with regard to the effect of low serum albumin on rates of SSI following surgery for adult patients suffering from traumatic and acute hip fractures. A systematic review was conducted using the PRISMA guidelines. Four databases were searched for randomised controlled trials (RCTs), cohort studies, and case-controlled studies. The risk of bias was assessed using the Newcastle-Ottawa Score (NOS). Data was collected and pooled using RevMan Web software. Results were reported as odds ratios (OR) with 95% confidence intervals (CI) and statistical significance of p <0.05. An inverse variance model was used in the meta-analysis. Six retrospective studies (five cohorts and one case-control) with a total of 43,059 patients were included. 45.3% (n=19 496) had low serum albumin (<3.5 g/dL). Hypoalbuminemia was associated with a significantly higher risk of any form of SSI (OR 1.25, p=0.008) and deep SSI (OR 1.76, p=0.05). There was no statistical significance between hypoalbuminemia and the incidence of superficial SSI (OR 1.06, p=0.77). Organ-space SSI was associated with hypoalbuminemia, although one study reported this with poor statistical significance (OR 8.74, p<0.054). Hypoalbuminemia increases the risk of most forms of surgical site infections, both superficial and deep. There is a weak conclusion to draw between the incidence of deep-space organ infections and low serum albumin.

Lung Quantitative Ultrasound to Stage and Monitor Interstitial Lung Diseases.

Chronic interstitial lung diseases (ILDs) require frequent point-of-care monitoring. X-ray-based methods lack resolution and are ionizing. Chest computerized tomographic (CT) scans are expensive and provide more radiation. Conventional ultrasound can detect severe lung damage via vertical artifacts (B-lines). However, this information is not quantitative, and the appearance of B-lines is operator- and system-dependent. Here we demonstrate novel ultrasound-based biomarkers to assess severity of ILDs. Lung alveoli scatter ultrasound waves, leading to a complex acoustic signature, which is affected by changes in alveolar density due to ILDs. We exploit ultrasound scattering in the lung and combine Quantitative Ultrasound (QUS) parameters, to develop ultrasound-based biomarkers that significantly correlate to the severity of pulmonary fibrosis and edema in rodent lungs. These innovative QUS biomarkers will be very significant for monitoring severity of chronic ILDs and response to treatment, especially in this new era of miniaturized and highly portable ultrasound devices.

Paradoxical Changes: EMMPRIN Tissue and Plasma Levels in Marfan Syndrome-Related Thoracic Aortic Aneurysms.

Background: Thoracic aortic aneurysms (TAAs) associated with Marfan syndrome (MFS) are unique in that extracellular matrix metalloproteinase inducer (EMMPRIN) levels do not behave the way they do in other cardiovascular pathologies. EMMPRIN is shed into the circulation through the secretion of extracellular vesicles. This has been demonstrated to be dependent upon the Membrane Type-1 MMP (MT1-MMP). We investigated this relationship in MFS TAA tissue and plasma to discern why unique profiles may exist. Methods: Protein targets were measured in aortic tissue and plasma from MFS patients with TAAs and were compared to healthy controls. The abundance and location of MT1-MMP was modified in aortic fibroblasts and secreted EMMPRIN was measured in conditioned culture media. Results: EMMPRIN levels were elevated in MFS TAA tissue but reduced in plasma, compared to the controls. Tissue EMMPRIN elevation did not induce MMP-3, MMP-8, or TIMP-1 expression, while MT1-MMP and TIMP-2 were elevated. MMP-2 and MMP-9 were reduced in TAA tissue but increased in plasma. In aortic fibroblasts, EMMPRIN secretion required the internalization of MT1-MMP. Conclusions: In MFS, impaired EMMPRIN secretion likely contributes to higher tissue levels, influenced by MT1-MMP cellular localization. Low EMMPRIN levels, in conjunction with other MMP analytes, distinguished MFS TAAs from controls, suggesting diagnostic potential.

Real-World Data on Antibiotic Group Treatment in European Livestock: Drivers, Conditions, and Alternatives.

Major efforts have been made by veterinary professionals to reduce the need for antibiotic use in animals. An online survey launched by the Federation of Veterinarians of Europe (FVE) aimed to gather responses from practicing veterinarians with field experience in metaphylactic livestock group treatment. Only 17% of all veterinarians (n = 183/1087, all species-specific responses merged) applied metaphylactic group treatments to 75% or more of all their treatments. Significantly less metaphylactic group treatments were reported in mixed practices (p = 0.002) and practices specialized in cattle (p < 0.001) as well as small (p = 0.007) and very small practices (p = 0.009). Gram-negative bacteria, mostly composed of Enterobacteriaceae and Pasteurellaceae, were considered by 75.3% (n = 967/1385) as the most devastating bacterial pathogens. Respondents alleged morbidity (20.1%, n = 201/998) and mortality (42.2%, n = 421/998) as major consequences for animal health and welfare if metaphylaxis would be banned. Responding veterinarians pointed towards vaccinations; improved biosecurity, including hygiene measures; and improved herd health management as the three most effective alternative measures to prevent metaphylactic treatment. However, more research is needed on how to implement appropriate alternatives in a holistic hurdle approach. Active support on a national level will be necessary for the development and application of targeted veterinary treatment guidelines for practitioners, which promote the understanding of drivers and include initiation criteria for metaphylactic group treatments in livestock.

Determining the ideal osteotomy for stemless total shoulder replacement: a cadaveric study.

HYPOTHESIS: We sought to determine the angle of osteotomy that produces a circular humeral cut surface. METHODS: A total of 49 cadaveric shoulders, from 25 cadavers, underwent sequential humeral head osteotomy from 180° (vertical, in line with the humeral diaphyseal shaft), in 10° increments, until the rotator cuff insertion was encountered. At each stage, the anteroposterior (AP) and superoinferior (SI) distances were recorded. The data were analyzed for normality and then assessed to determine the optimum cut angle. RESULTS: The AP/SI ratio is an indication of roundness. Plotting values of 1 - AP/SI (ie, error) vs. cut angle allowed us to plot the likelihood of producing a circular cut surface using a third-order curve that created the best fit to the data set (R2 = 0.99). The results from this study suggest that the optimum osteotomy angle that produces a circular cut surface is 23° from the vertical. The cohort data illustrated that at this angle, the average roundness error was 1% with a 95% confidence limit of <1%. There was no significant difference (P > .05) between sexes. CONCLUSION: The humeral head shape changes from oval to circular and then to an oval cut surface as the osteotomy angle increases from the vertical toward the horizontal. The range of angles within which the cut surface is circular, within a 10% error margin, is 18°-27° from the vertical, which is much less than the traditional osteotomy angle of 45°.

Detecting pulmonary nodules by using ultrasound multiple scattering.

Although X-Ray Computed Tomography (CT) is widely used for detecting pulmonary nodules inside the parenchyma, it cannot be used during video-assisted surgical procedures. Real-time, non-ionizing, ultrasound-based techniques are an attractive alternative for nodule localization to ensure safe resection margins during surgery. Conventional ultrasound B-mode imaging of the lung is challenging due to multiple scattering. However, the multiple scattering contribution can be exploited to detect regions inside the lung containing no scatterers. Pulmonary nodules are homogeneous regions in contrast to the highly scattering parenchyma containing millions of air-filled alveoli. We developed a method relying on mapping the multiple scattering contribution inside the highly scattering lung to detect and localize pulmonary nodules. Impulse response matrices were acquired in ex-vivo pig and dog lungs using a linear array transducer to semi-locally investigate the backscattered field. Extracting the multiple-scattering contribution using singular-value decomposition and combining it with a depression detection algorithm allowed us to detect and localize regions with less multiple scattering, associated with the nodules. The feasibility of this method was demonstrated in five ex-vivo lungs containing a total of 20 artificial nodules. Ninety-five percent of the nodules were detected. Nodule depth and diameter significantly correlated with their ex-vivo CT-estimated counterparts (R = 0.960, 0.563, respectively).

In Vivo Assessment of Pulmonary Fibrosis and Pulmonary Edema in Rodents Using Ultrasound Multiple Scattering.

Idiopathic pulmonary fibrosis (IPF) affects 200 000 patients in the United States of America. IPF is responsible for changes in the micro-architecture of the lung parenchyma, such as thickening of the alveolar walls, which reduces compliance and elasticity. In this study, we verify the hypothesis that changes in the microarchitecture of the lung parenchyma can be characterized by exploiting multiple scattering of ultrasound waves by the alveolar structure. Ultrasound propagation in a highly scattering regime follows a diffusion process, which can be characterized using the diffusion constant. We hypothesize that in a fibrotic lung, the thickening of the alveolar wall reduces the amount of air (compared with a healthy lung), thereby minimizing the scattering events. Pulmonary fibrosis is created in Sprague-Dawley rats by instilling bleomycin into the airway. The rats are studied within 3 weeks after bleomycin administration. Using a 128-element linear array transducer operating at 7.8 MHz, in vivo experimental data are obtained from Sprague-Dawley rats and the transport mean free path (L*) and backscatter frequency shift (BFS) are evaluated. Significant differences ( ) in the L* values between control and fibrotic rats and in the BFS values between fibrotic and edematous rats showcase the potential of these parameters for diagnosis and monitoring of IPF.

Should the Tibiotalar Angle Be Measured Using an AP or Mortise Radiograph? Does It Matter?

Understanding the tibiotalar angle (TTA) is key to planning for deformity correction. The TTA is an important radiographic tool to determine alignment or malalignment of the ankle and hindfoot. Two methods of measuring the TTA have been described: the midline TTA (MTTA) and the lateral TTA (LTTA). The aim of this study was to compare the 2 angles as measured on mortise and anteroposterior (AP) radiographs in a series of normal and pathological cases. A radiographic review was performed of sequential ankle AP and mortise radiographs taken between January 2016 and September 2017 across 4 specialist orthopedic centers. Patients were categorized into a normal group, where patients had normal radiological appearances, and an arthritis group, where patients had radiographic arthritis. The MTTA and the LTTA were measured. The overall mean ± standard deviation MTTA was 88.7° ± 5.1°, and mean LTTA was 87.5° ± 5.2° (p < .01). There was no statistically significant difference between the MTTA and LTTA in the normal group or on AP radiographs alone (p = .09). There was a statistically significant difference between the MTTA and LTTA in the arthritis group (p < .01) and when measured on mortise radiographs (p = .02). The MTTA had no difference when measured on the AP and mortise radiographs. There was a statistically significant difference in the LTTA between AP and mortise radiographs (p = .04). We have shown the MTTA to be a reliable and reproducible tool in all patients, on AP and mortise radiographs. The type of radiograph does not alter the measurement of deformity. In contrast, we have shown the LTTA to be unreliable and statistically different when measured on AP and mortise radiographs.

Blowing dust and highway safety in the southwestern United States: Characteristics of dust emission "hotspots" and management implications.

Despite the widespread media attention of chain-reaction traffic incidents and property damage caused by windblown dust in the U.S. and elsewhere in the world, very few studies have provided in-depth analysis on this issue. Remote sensing and field observations reveal that wind erosion in the southwestern U.S. typically occurs in localized source areas, characterized as "hotspots", while most of the landscape is not eroding. In this study, we identified the spatial and temporal distribution patterns of hotspots that may contribute dust blowing onto highways in the southwestern U.S. We further classified the hotspots for the potential of blowing dust production based upon field observations and wind erosion modeling. Results of land use and land cover show that shrubland, grassland, and cropland accounted for 42%, 31%, and 21% of the overall study area, respectively. However, of the 620 total hotspots identified, 164 (26%), 141 (22%), and 234 (38%) are located on shrubland, grassland, and cropland, respectively. Barren land represented 0.9% of the land area but 8% of the dust hotspots. While a majority of these hotspots are located close to highways, we focused on 55 of them, which are located <1km to adjacent highways and accessible via non-private roads. Field investigations and laboratory analysis showed that soils at these hotspot sites are dominated by sand and silt particles with threshold shear velocities ranging from 0.17-0.78m s-1, largely depending on the land use of the hotspot sites. Dust emission modeling showed that 13 hotspot sites could produce annual emissions >3.79kg m-2, yielding highly hazardous dust emissions to ground transportation with visibility <200m. Results of location, timing, and magnitude of the dust production at the hotspots are critical information for highway authorities to make informed and timely management decisions when wind events strike.

Assessment of Lungs for Transplant Recovered from Uncontrolled Donation after Circulatory Determination of Death Donors.

RATIONALE: To address the lung donor shortage, we obtained institutional review board and US Food and Drug Administration approval to transplant lungs recovered from uncontrolled donation after circulatory determination of death donors (uDCDDs). OBJECTIVES: To compare outcomes of recipients of lungs recovered from uDCDDs vs. brain-dead donors. METHODS: After consent and screening, lungs recovered from uDCDDs were assessed by 4 hours ex vivo lung perfusion (EVLP) and computed tomography (CT) scan. MEASUREMENTS AND MAIN RESULTS: Over the course of 29 months, 502 potential uDCDDs younger than 66 years were identified in a single county, with death declaration by emergency medical services and four emergency departments in this and two other countries. We determined reasons that lungs from these uDCDDs were not able to be transplanted: uDCDDs could not have lungs recovered (224), next-of-kin could not be found or refused to discuss (67), next-of-kin refused (48), medical examiner case (39), logistics/missed (35), and miscellaneous (35). There were 247 medical contraindications: 141 pulmonary and 106 nonpulmonary. Lungs were recovered from 31 uDCDDs. Thirteen lungs did not have EVLP: 5 injured lungs (one pulmonary embolism [PE] with perforated infarct, two motor vehicle crash with severe injuries, one adhesion, and one lightning strike), two large PE, two prolonged ischemic time, two obvious chronic obstructive pulmonary disease, one technical, and one consent withdrawn. Eighteen lungs had EVLP: 10 with immediate edema (three PE, three unknown down time, three long ischemic time, and one ruptured aneurysm into L pleural space, making long cardiopulmonary resuscitation ineffective), and one myocarditis, possible lung involvement. In three lungs, CT showed edema after EVLP: one poor flush and poor EVLP performance, one edema after myocardial infarction (MI) with 10-year history of chronic heart failure, and one edema with MI, resuscitated, arrested again. One concurrent pneumonia was diagnosed by bronchoscopy, CT, and cultures; one patient had chronic obstructive pulmonary disease with small subpleural blebs and poor collapse, confirmed by CT. Two uDCDDs with MIs were suitable but not transplanted: no consented recipient from one large blood type B uDCDD, and the senior surgeon was unavailable to transplant suitable lungs from a uDCDD and did not allow the transplant. CONCLUSIONS: The objective was not met: no lungs from uDCDDs were transplanted. uDCDDs can be a source of lungs for transplant. Resolving logistical challenges and better use of first-person authorization, allowing organ recovery without next-of-kin consent or knowledge of death, could increase yield. Donor medical problems were higher than expected and may limit the effect of uDCDDs on the lung donor pool. CLINICAL TRIAL REGISTRATION: NCT01615484.

Patient compliance with venous thromboembolism prophylaxis (VTE).

Venous thromboembolic disease (VTE) comprises pulmonary embolism (PE) and deep vein thrombosis (DVT), and causes morbidity and mortality, particularly in trauma and orthopaedic patients. Prevalence of 0.9% and 1.2% respectively are reported, with mortality rates up to 13.8%. Chemical thromboprophylactic agents including low molecular weight heparin (LMWH) are considered cost effective in reducing VTE risk. Evidence for anti-platelets including Aspirin for VTE prophylaxis is less compelling and is not supported as monotherapy. There has been no published data on patient compliance with LMWH in trauma outpatients. We aimed to determine whether trauma outpatients accept LMWH after discussing their VTE risk and the evidence for prophylaxis. For those accepting prophylaxis, we also investigated their compliance for the duration of immobilisation. Lower limb injured patients treated with external immobilisation over a 6 month period at our major trauma centre were included. On completion of immobilisation, they were requested to complete a 17-point questionnaire. Patients declining injectable subcutaneous LMWH as prophylaxis were offered Aspirin 75 mg as a second line agent. Seventy-five questionnaires were completed and five were excluded. Nineteen patients required surgical intervention for their injury, 51 were managed non-operatively. Thirty-one patients accepted LMWH and 30 chose Aspirin as an alternative. Nine patients declined or were not commenced on prophylaxis. Nineteen reported no missed Aspirin doses and 25 reported no missed LMWH doses. No patients reported missed doses due to pain, side effects or cessation of treatment for another reason. The mean average pain score recorded on the VAS was 3.8. No patients in the study were diagnosed with a VTE. LMWH is a recognised chemical thromboprophylactic and is well tolerated by patients for VTE risk reduction in lower limb immobilised outpatients. With poor evidence supporting Aspirin as a solo prophylactic agent, our local policy has withdrawn Aspirin for this purpose.

Characterization of the Lung Parenchyma Using Ultrasound Multiple Scattering.

The purpose of the study described here was to showcase the application of ultrasound to quantitative characterization of the micro-architecture of the lung parenchyma to predict the extent of pulmonary edema. The lung parenchyma is a highly complex and diffusive medium for which ultrasound techniques have remained qualitative. The approach presented here is based on ultrasound multiple scattering and exploits the complexity of ultrasound propagation in the lung structure. The experimental setup consisted of a linear transducer array with an 8-MHz central frequency placed in contact with the lung surface. The diffusion constant D and transport mean free path L* of the lung parenchyma were estimated by separating the incoherent and coherent intensities in the near field and measuring the growth of the incoherent diffusive halo over time. Significant differences were observed between the L* values obtained in healthy and edematous rat lungs in vivo. In the control rat lung, L* was found to be 332 µm (±48.8 µm), whereas in the edematous lung, it was 1040 µm (±90 µm). The reproducibility of the measurements of L* and D was tested in vivo and in phantoms made of melamine sponge with varying air volume fractions. Two-dimensional finite difference time domain numerical simulations were carried out on rabbit lung histology images with varying degrees of lung collapse. Significant correlations were observed between air volume fraction and L* in simulation (r = -0.9542, p < 0.0117) and sponge phantom (r = -0.9932, p < 0.0068) experiments. Ex vivo measurements of a rat lung in which edema was simulated by adding phosphate-buffered saline revealed a linear relationship between the fluid volume fraction and L*. These results illustrate the potential of methods based on ultrasound multiple scattering for the quantitative characterization of the lung parenchyma.

Fabrication and mechanical properties of composite based on ß-chitin and polyacrylic acid.

Squid ß-chitin has been exfoliated in aqueous acrylic acid (AA), after which a composite film of chitin microfibrils in polyacrylic acid (PAA) has been prepared by in situ polymerization of the AA. The segregated chitin fibrils in the composite are 4-6nm in diameter, with an aspect ratio >250. After drying cast films of the composites containing 1, 2 and 3% (w/w) chitin at 140°C for four hours, there was a dramatic resistance to swelling in water, in that the dried films showed only small changes in shape and properties after four hours immersed in water.The most profound impact of the reinforcement on the mechanical properties is observed at high relative humidity (RH), when the PAA is in the rubbery state. At 97.5% RH and room temperature, the elastic moduli of the composites with 1, 2 and 3% (w/w) chitin were 150, 230 and 2100MPa respectively, compared to 65MPa for pure PAA. The main contribution to the filler-reinforcing effect is the high aspect ratio of fibrils and non-covalent interactions, but the stability in water suggests the presence of chemical bonding between the PAA and chitin.

Structure of ß-chitin from Berryteuthis magister and its transformation during whisker preparation and polymerization filling.

Models for the structures of the ß-chitin-protein complex of native and deproteinized squid pen (Berryteuthis magister) based on SAXS and WAXS data are proposed. Chitin fibrils of 25 Å in diameter and persistence length of 1200 Å are immersed in protein matrix. Average distance between fibrils is 42 Å. Deproteinization of the squid pen led to disappearance of the lateral fibril order stabilized by the protein matrix of the native sample. Swelling in water and acrylic acid resulted in an increase in the chitin 010 D-spacing to 14 and 18 Å, respectively. A preparation routine for individual chitin nanofibers of few microns in length and with diameter of 40-60 Å has been developed. During exfoliation of the chitin in acrylic acid the degree of acetylation does not change. Chitin-based nanocomposites can be prepared by polymerization of acrylic acid in swelled deproteinized samples which takes place mainly in the interfibrillar space of ß-chitin mainly.

Olecranon bursitis: a systematic overview.

BACKGROUND: Olecranon bursitis is a common condition where the bursal cavity, superficial to the olecranon, becomes inflamed. This can occur either with or without infection and has been given pseudonyms relating to the repeated minor trauma from external pressure that often predisposes. As a result of the multiple aetiologies, olecranon bursitis can present to any medical specialty with reasonable frequency and, although many therapies are described, a single, evidence-based and standardized treatment pathway is not well described. METHODS: We summarize the key points within the literature and subsequently propose an evidence-based treatment pathway. RESULTS: Relevant evidence is presented from appropriate publications to add rational to existing decision-making processes, together with personal experience and suggested operative bursectomy techniques from an established upper limb surgeon. The common and significant aetiologies are summarized and, in particular, red flag symptoms are highlighted by way of warning to the unsuspecting investigator. CONCLUSIONS: The conclusion is provided in diagrammatic form, providing a suggested treatment pathway from history and examination through to operative intervention.