DOES MAGNETIC RESONANCE IMAGING PROVIDE SUPERIOR RELIABILITY FOR ACHILLES AND PATELLAR TENDON CROSS-SECTIONAL AREA MEASUREMENTS COMPARED WITH ULTRASOUND IMAGING?

This study investigated the reliability of Achilles and patellar tendon cross-sectional area (CSA) measurement using ultrasound imaging (USI) and magnetic resonance imaging (MRI). Fifteen healthy adults were imaged twice on two occasions, interrupted by a tendon loading protocol. Tendon CSA segmentations were conducted by an experienced and an inexperienced rater blinded to information regarding subject, session and loading status. USI provided good test-retest reliability (intra-class correlation coefficient [ICC] 2,1 > 0.85, standard error of measurement [SEM] 5%-6%), while with MRI it was excellent (ICC 2,1 > 0.92, SEM 4%) for the experienced rater. This study suggests that MRI provides superior reliability for tendon CSA measurements compared with USI. However, the difference in reliability between the methods was small, and the results were inconclusive regarding objectivity and sensitivity to change when assessed based on the effect of loading. We concluded that both methods can be used for reliable CSA measurements of the Achilles and patellar tendons when using a highly standardized measurement protocol and when conducted by an experienced rater. (C) 2019 World Federation for Ultrasound in Medicine & Biology. All rights reserved.Peer reviewe

Antimicrobial resistance among migrants in Europe: a systematic review and meta-analysis

BACKGROUND: Rates of antimicrobial resistance (AMR) are rising globally and there is concern that increased migration is contributing to the burden of antibiotic resistance in Europe. However, the effect of migration on the burden of AMR in Europe has not yet been comprehensively examined. Therefore, we did a systematic review and meta-analysis to identify and synthesise data for AMR carriage or infection in migrants to Europe to examine differences in patterns of AMR across migrant groups and in different settings. METHODS: For this systematic review and meta-analysis, we searched MEDLINE, Embase, PubMed, and Scopus with no language restrictions from Jan 1, 2000, to Jan 18, 2017, for primary data from observational studies reporting antibacterial resistance in common bacterial pathogens among migrants to 21 European Union-15 and European Economic Area countries. To be eligible for inclusion, studies had to report data on carriage or infection with laboratory-confirmed antibiotic-resistant organisms in migrant populations. We extracted data from eligible studies and assessed quality using piloted, standardised forms. We did not examine drug resistance in tuberculosis and excluded articles solely reporting on this parameter. We also excluded articles in which migrant status was determined by ethnicity, country of birth of participants' parents, or was not defined, and articles in which data were not disaggregated by migrant status. Outcomes were carriage of or infection with antibiotic-resistant organisms. We used random-effects models to calculate the pooled prevalence of each outcome. The study protocol is registered with PROSPERO, number CRD42016043681. FINDINGS: We identified 2274 articles, of which 23 observational studies reporting on antibiotic resistance in 2319 migrants were included. The pooled prevalence of any AMR carriage or AMR infection in migrants was 25·4% (95% CI 19·1-31·8; I2 =98%), including meticillin-resistant Staphylococcus aureus (7·8%, 4·8-10·7; I2 =92%) and antibiotic-resistant Gram-negative bacteria (27·2%, 17·6-36·8; I2 =94%). The pooled prevalence of any AMR carriage or infection was higher in refugees and asylum seekers (33·0%, 18·3-47·6; I2 =98%) than in other migrant groups (6·6%, 1·8-11·3; I2 =92%). The pooled prevalence of antibiotic-resistant organisms was slightly higher in high-migrant community settings (33·1%, 11·1-55·1; I2 =96%) than in migrants in hospitals (24·3%, 16·1-32·6; I2 =98%). We did not find evidence of high rates of transmission of AMR from migrant to host populations. INTERPRETATION: Migrants are exposed to conditions favouring the emergence of drug resistance during transit and in host countries in Europe. Increased antibiotic resistance among refugees and asylum seekers and in high-migrant community settings (such as refugee camps and detention facilities) highlights the need for improved living conditions, access to health care, and initiatives to facilitate detection of and appropriate high-quality treatment for antibiotic-resistant infections during transit and in host countries. Protocols for the prevention and control of infection and for antibiotic surveillance need to be integrated in all aspects of health care, which should be accessible for all migrant groups, and should target determinants of AMR before, during, and after migration. FUNDING: UK National Institute for Health Research Imperial Biomedical Research Centre, Imperial College Healthcare Charity, the Wellcome Trust, and UK National Institute for Health Research Health Protection Research Unit in Healthcare-associated Infections and Antimictobial Resistance at Imperial College London

Surgical site infection after gastrointestinal surgery in high-income, middle-income, and low-income countries: a prospective, international, multicentre cohort study

Background: Surgical site infection (SSI) is one of the most common infections associated with health care, but its importance as a global health priority is not fully understood. We quantified the burden of SSI after gastrointestinal surgery in countries in all parts of the world. Methods: This international, prospective, multicentre cohort study included consecutive patients undergoing elective or emergency gastrointestinal resection within 2-week time periods at any health-care facility in any country. Countries with participating centres were stratified into high-income, middle-income, and low-income groups according to the UN's Human Development Index (HDI). Data variables from the GlobalSurg 1 study and other studies that have been found to affect the likelihood of SSI were entered into risk adjustment models. The primary outcome measure was the 30-day SSI incidence (defined by US Centers for Disease Control and Prevention criteria for superficial and deep incisional SSI). Relationships with explanatory variables were examined using Bayesian multilevel logistic regression models. This trial is registered with ClinicalTrials.gov, number NCT02662231. Findings: Between Jan 4, 2016, and July 31, 2016, 13 265 records were submitted for analysis. 12 539 patients from 343 hospitals in 66 countries were included. 7339 (58·5%) patient were from high-HDI countries (193 hospitals in 30 countries), 3918 (31·2%) patients were from middle-HDI countries (82 hospitals in 18 countries), and 1282 (10·2%) patients were from low-HDI countries (68 hospitals in 18 countries). In total, 1538 (12·3%) patients had SSI within 30 days of surgery. The incidence of SSI varied between countries with high (691 [9·4%] of 7339 patients), middle (549 [14·0%] of 3918 patients), and low (298 [23·2%] of 1282) HDI (p < 0·001). The highest SSI incidence in each HDI group was after dirty surgery (102 [17·8%] of 574 patients in high-HDI countries; 74 [31·4%] of 236 patients in middle-HDI countries; 72 [39·8%] of 181 patients in low-HDI countries). Following risk factor adjustment, patients in low-HDI countries were at greatest risk of SSI (adjusted odds ratio 1·60, 95% credible interval 1·05–2·37; p=0·030). 132 (21·6%) of 610 patients with an SSI and a microbiology culture result had an infection that was resistant to the prophylactic antibiotic used. Resistant infections were detected in 49 (16·6%) of 295 patients in high-HDI countries, in 37 (19·8%) of 187 patients in middle-HDI countries, and in 46 (35·9%) of 128 patients in low-HDI countries (p < 0·001). Interpretation: Countries with a low HDI carry a disproportionately greater burden of SSI than countries with a middle or high HDI and might have higher rates of antibiotic resistance. In view of WHO recommendations on SSI prevention that highlight the absence of high-quality interventional research, urgent, pragmatic, randomised trials based in LMICs are needed to assess measures aiming to reduce this preventable complication

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Severity of desaturations reflects OSA-related daytime sleepiness better than AHI

Study Objectives: The aim was to investigate how the severity of apneas, hypopneas, and related desaturations is associated with obstructive sleep apnea (OSA)-related daytime sleepiness. Methods: Multiple Sleep Latency Tests and polysomnographic recordings of 362 patients with OSA were retrospectively analyzed and novel diagnostic parameters (eg, obstruction severity and desaturation severity), incorporating severity of apneas, hypopneas, and desaturations, were computed. Conventional statistical analysis and multivariate analyses were utilized to investigate connection of apnea-hypopnea index (AHI), oxygen desaturation index (ODI), conventional hypoxemia parameters, and novel diagnostic parameters with mean daytime sleep latency (MSL). Results: In the whole population, 10% increase in values of desaturation severity (risk ratio = 2.01,

Detailing the influence of PEO-coated biodegradable Mg-based implants on the lacuno-canalicular network in sheep bone: A pilot study

An increasing prevalence of bone-related injuries and aging geriatric populations continue to drive the orthopaedic implant market. A hierarchical analysis of bone remodelling after material implantation is necessary to better understand the relationship between implant and bone. Osteocytes, which are housed and communicate through the lacuno-canalicular network (LCN), are integral to bone health and remodelling processes. Therefore, it is essential to examine the framework of the LCN in response to implant materials or surface treatments.Biodegradable materials offer an alternative solution to permanent implants, which may require revision or removal surgeries. Magnesium alloys have resurfaced as promising materials due to their bone-like properties and safe degradation in vivo. To further tailor their degradation capabilities, surface treatments such as plasma electrolytic oxidation (PEO) have demonstrated to slow degradation.For the first time, the influence of a biodegradable material on the LCN is investigated by means of non-destructive 3D imaging. In this pilot study, we hypothesize noticeable variations in the LCN caused by altered chemical stimuli introduced by the PEO-coating.Utilising synchrotron-based transmission X-ray microscopy, we have characterised morphological LCN differences around uncoated and PEO-coated WE43 screws implanted into sheep bone. Bone specimens were explanted after 4, 8, and 12 weeks and regions near the implant surface were prepared for imaging. Findings from this investigation indicate that the slower degradation of PEO-coated WE43 induces healthier lacunar shapes within the LCN. However, the stimuli perceived by the uncoated material with higher degradation rates induces a greater connected LCN better prepared for bone disturbance

Assessing the long-term in vivo degradation behavior of magnesium alloys - a high resolution synchrotron radiation micro computed tomography study

Biodegradable magnesium (Mg) implants are emerging as a potential game changer in implant technology in situations where the implant temporarily supports the bone thereby avoiding secondary surgery for implant removal. However, the consequences of the alteration in the degradation rate to bone healing and the localization of degradation and alloying products in the long term remain unknown. In this study, we present the long-term osseointegration of three different biodegradable Mg alloys, Mg-10Gd, Mg-4Y-3RE and Mg-2Ag, which were implanted into rabbit femur for 6 and 9 months. In addition, we have investigated the effect of blood pre-incubation on the in vivo performance of the aforementioned alloys. Using high-resolution synchrotron radiation based micro computed tomography, the bone implant contact (BIC), bone volume fraction (BV/TV) and implant morphology were studied. The elemental traces have been characterized using micro X-ray fluorescence. Qualitative histological evaluation of the surrounding bone was also performed. Matured bone formed around all three implant types and Ca as well as P which represent parts of the degradation layer were in intimate contact with the bone. Blood pre-incubation prior to implantation significantly improved BIC in Mg-2Ag screws at 9 months. Despite different implant degradation morphologies pointing toward different degradation dynamics, Mg-10Gd, Mg-4Y-3RE and Mg-2Ag induced a similar long-term bone response based on our quantified parameters. Importantly, RE elements Gd and Y used in the alloys remained at the implantation site implying that they might be released later on or might persist in the implantation site forever. As the bone formation was not disturbed by their presence, it might be concluded that Gd and Y are non-deleterious. Consequently, we have shown that short and mid-term in vivo evaluations do not fully represent indicators for long-term osseointegration of Mg-based implants

Methods for the purification and detection of single nucleotide KRAS mutations on extrachromosomal circular DNA in human plasma

Abstract Backgrounds Despite recent advances, many cancers are still detected too late for curative treatment. There is, therefore, a need for the development of new diagnostic methods and biomarkers. One approach may arise from the detection of extrachromosomal circular DNA (eccDNA), which is part of cell‐free DNA in human plasma. Aims First, we assessed and compared two methods for the purification of eccDNA from plasma. Second, we tested for an easy diagnostic application of eccDNA liquid biopsy‐based assays. Materials & Methods For the comparison we tested a solid‐phase silica purification method and a phenol/chloroform method with salt precipitation. For the diagnostic application of eccDNA we developed and tested a qPCR primer‐based SNP detection system, for the detection of two well‐established cancer‐causing KRAS mutations (G12V and G12R) on circular DNA. This investigation was supported by purifying, sequencing, and analysing clinical plasma samples for eccDNAs containing KRAS mutant alleles in 0.5 mL plasma from 16 pancreatic ductal adenocarcinoma patients and 19 healthy controls. Results In our method comparison we observed, that following exonuclease treatment a lower eccDNA yield was found for the phenol/chloroform method (15.7%–26.7%) compared with the solid‐phase purification approach (47.8%–65.9%). For the diagnostic application of eccDNA tests, the sensitivity of the tested qPCR assay only reached ~10−3 in a background of 105 wild type (wt) KRAS circular entities, which was not improved by general amplification or primer‐based inhibition of wt KRAS amplification. Furthermore, we did not detect eccDNA containing KRAS in any of the clinical samples. Discussion A potential explanation for our inability to detect any KRAS mutations in the clinical samples may be related to the general low abundance of eccDNA in plasma. Conclusion Taken together our results provide a benchmark for eccDNA purification methods while raising the question of what is required for the optimal fast and sensitive detection of SNP mutations on eccDNA with greater sensitivity than primer‐based qPCR detection

Multiscale morphological analysis of bone microarchitecture around Mg-10Gd implants

The utilization of biodegradable magnesium (Mg)-based implants for restoration of bone function following trauma represents a transformative approach in orthopaedic application. One such alloy, magnesium-10 weight percent gadolinium (Mg-10Gd), has been specifically developed to address the rapid degradation of Mg while enhancing its mechanical properties to promote bone healing. Previous studies have demonstrated that Mg-10Gd exhibits favorable osseointegration; however, it exhibits distinct ultrastructural adaptation in comparison to conventional implants like titanium (Ti). A crucial aspect that remains unexplored is the impact of Mg-10Gd degradation on the bone microarchitecture. To address this, we employed hierarchical three-dimensional imaging using synchrotron radiation in conjunction with image-based finite element modelling. By using the methods outlined, the vascular porosity, lacunar porosity and the lacunar-canaliculi network (LCN) morphology of bone around Mg-10Gd in comparison to Ti in a rat model from 4 weeks to 20 weeks post-implantation was investigated. Our investigation revealed that within our observation period, the degradation of Mg-10Gd implants was associated with significantly lower (p < 0.05) lacunar density in the surrounding bone, compared to Ti. Remarkably, the LCN morphology and the fluid flow analysis did not significantly differ for both implant types. In summary, a more pronounced lower lacunae distribution rather than their morphological changes was detected in the surrounding bone upon the degradation of Mg-10Gd implants. This implies potential disparities in bone remodelling rates when compared to Ti implants. Our findings shed light on the intricate relationship between Mg-10Gd degradation and bone microarchitecture, contributing to a deeper understanding of the implications for successful osseointegration

Multiscale morphological analysis of bone microarchitecture around Mg-10Gd implants

The utilization of biodegradable magnesium (Mg)-based implants for restoration of bone function following trauma represents a transformative approach in orthopaedic application. One such alloy, magnesium-10 weight percent gadolinium (Mg-10Gd), has been specifically developed to address the rapid degradation of Mg while enhancing its mechanical properties to promote bone healing. Previous studies have demonstrated that Mg-10Gd exhibits favorable osseointegration; however, it exhibits distinct ultrastructural adaptation in comparison to conventional implants like titanium (Ti). A crucial aspect that remains unexplored is the impact of Mg-10Gd degradation on the bone microarchitecture. To address this, we employed hierarchical three-dimensional imaging using synchrotron radiation in conjunction with image-based finite element modelling. By using the methods outlined, the vascular porosity, lacunar porosity and the lacunar-canaliculi network (LCN) morphology of bone around Mg-10Gd in comparison to Ti in a rat model from 4 weeks to 20 weeks post-implantation was investigated. Our investigation revealed that within our observation period, the degradation of Mg-10Gd implants was associated with significantly lower (p < 0.05) lacunar density in the surrounding bone, compared to Ti. Remarkably, the LCN morphology and the fluid flow analysis did not significantly differ for both implant types. In summary, a more pronounced lower lacunae distribution rather than their morphological changes was detected in the surrounding bone upon the degradation of Mg-10Gd implants. This implies potential disparities in bone remodelling rates when compared to Ti implants. Our findings shed light on the intricate relationship between Mg-10Gd degradation and bone microarchitecture, contributing to a deeper understanding of the implications for successful osseointegration