Publications by authors named "Mark Davies"

658 Publications

The changing face of central chondrosarcoma of bone. One UK-based orthopaedic oncology unit's experience of 33 years referrals.

J Clin Orthop Trauma 2021 Jun 27;17:106-111. Epub 2021 Feb 27.

Orthopaedic Oncology, Royal Orthopaedic Hospital, Birmingham, B21 3AP, United Kingdom.

Aim: To ascertain the changing incidence over time of the three commonest primary sarcomas of bone. Data obtained with particular reference to central chondrosarcoma from the annual referral rate to a large UK-based specialist orthopaedic oncology unit. To discuss how the "barnyard pen" analogy of cancers previously applied to certain commoner cancers can also be applicable to central chondrosarcoma (CS) of bone.

Materials And Methods: A retrospective review was conducted of a computerised database identifying all central cartilage tumours (CCT) of bone, including enchondroma and CS subtypes, between 1985 and 2018. These were compared with the referrals of the other two commonest primary sarcomas of bone, osteosarcoma and Ewing sarcoma.

Results: There was a total of 1507 CS showing a 68% overall increase in annual referral rate/incidence over the study period. 68% cases were the borderline malignant lesions now known as atypical cartilaginous tumour (ACT). The annual referral rate/incidence of this entity increased by 194% over the 30 years. Whereas, the annual referral rate/incidence for osteosarcoma and Ewing sarcoma was static for the past 20 years.

Conclusion: The annual incidence of central CS of bone showed a marked increase over the 33-year period as compared with both osteosarcoma and Ewing sarcoma. This is especially in the ACT category and is thought to be due to the increased provision of MRI scanning flagging up a rise in incidental findings. The spectrum of CCTs from benign to highly malignant elegantly fits the "barn yard" pen analogy and could prove useful as an explanatory tool for patients and clinicians unfamiliar with these diseases.
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http://dx.doi.org/10.1016/j.jcot.2021.02.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7972956PMC
June 2021

Exploring the relationship between electronic health records and provider burnout: A systematic review.

J Am Med Inform Assoc 2021 Feb 28. Epub 2021 Feb 28.

Center for Quality, Effectiveness and Outcomes in Cardiovascular Diseases, Division of Vascular and Endovascular Surgery, University of Texas Health Science Center at San Antonio, San Antonio, Texas, USA.

Objective: Stress and burnout due to electronic health record (EHR) technology has become a focus for burnout intervention. The aim of this study is to systematically review the relationship between EHR use and provider burnout.

Materials And Methods: A systematic literature search was performed on PubMed, EMBASE, PsychInfo, ACM Digital Library in accordance with the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) statement. Inclusion criterion was original research investigating the association between EHR and provider burnout. Studies that did not measure the association objectively were excluded. Study quality was assessed using the Medical Education Research Study Quality Instrument. Qualitative synthesis was also performed.

Results: Twenty-six studies met inclusion criteria. The median sample size of providers was 810 (total 20 885; 44% male; mean age 53 [range, 34-56] years). Twenty-three (88%) studies were cross-sectional studies and 3 were single-arm cohort studies measuring pre- and postintervention burnout prevalence. Burnout was assessed objectively with various validated instruments. Insufficient time for documentation (odds ratio [OR], 1.40-5.83), high inbox or patient call message volumes (OR, 2.06-6.17), and negative perceptions of EHR by providers (OR, 2.17-2.44) were the 3 most cited EHR-related factors associated with higher rates of provider burnout that was assessed objectively.

Conclusions: The included studies were mostly observational studies; thus, we were not able to determine a causal relationship. Currently, there are few studies that objectively assessed the relationship between EHR use and provider burnout. The 3 most cited EHR factors associated with burnout were confirmed and should be the focus of efforts to improve EHR-related provider burnout.
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http://dx.doi.org/10.1093/jamia/ocab009DOI Listing
February 2021

Serological Profiling of Group A Streptococcus Infections in Acute Rheumatic Fever.

Clin Infect Dis 2021 Feb 26. Epub 2021 Feb 26.

School of Medical Sciences, University of Auckland, Auckland, New Zealand.

Rheumatic fever is a serious post-infectious sequela of Group A Streptococcus (GAS). Prior GAS exposures were mapped in sera using a large panel of M-type specific peptides. Rheumatic fever patients had serological evidence of significantly more GAS exposures than matched controls suggesting immune priming by repeat infections contributes to pathogenesis.
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http://dx.doi.org/10.1093/cid/ciab180DOI Listing
February 2021

Digital Footprint of Academic Vascular Surgeons in the Southern United States on Physician Rating Websites: Cross-sectional Evaluation Study.

JMIR Cardio 2021 Feb 24;5(1):e22975. Epub 2021 Feb 24.

Division of Vascular Surgery, Department of Surgery, UT Health San Antonio, San Antonio, TX, United States.

Background: The internet has become a popular platform for patients to obtain information and to review the health care providers they interact with. However, little is known about the digital footprint of vascular surgeons and their interactions with patients on social media.

Objective: This study aims to understand the activity of academic vascular surgeons on physician rating websites.

Methods: Information on attending vascular surgeons affiliated with vascular residency or with fellowships in the Southern Association for Vascular Surgery (SAVS) was collected from public sources. A listing of websites containing physician ratings was obtained via literature reviews and Google search. Open access websites with either qualitative or quantitative evaluations of vascular surgeons were included. Closed access websites were excluded. Ranking scores from each website were converted to a standard 5-point scale for comparison.

Results: A total of 6238 quantitative and 967 qualitative reviews were written for 287 physicians (236 males, 82.2%) across 16 websites that met the inclusion criteria out of the 62 websites screened. The surgeons affiliated with the integrated vascular residency and vascular fellowship programs in SAVS had a median of 8 (IQR 7-10) profiles across 16 websites, with only 1 surgeon having no web presence in any of the websites. The median number of quantitative ratings for each physician was 17 (IQR 6-34, range 1-137) and the median number of narrative reviews was 3 (IQR 2-6, range 1-28). Vitals, WebMD, and Healthgrades were the only 3 websites where over a quarter of the physicians were rated, and those rated had more than 5 ratings on average. The median score for the quantitative reviews was 4.4 (IQR 4.0-4.9). Most narrative reviews (758/967, 78.4%) were positive, but 20.2% (195/967) were considered negative; only 1.4% (14/967) were considered equivocal. No statistical difference was found in the number of quantitative reviews or in the overall average score in the physician ratings between physicians with social media profiles and those without social media profiles (departmental social media profile: median 23 vs 15, respectively, P=.22; personal social media profile: median 19 vs 14, respectively, P=.08).

Conclusions: The representation of vascular surgeons on physician rating websites is varied, with the majority of the vascular surgeons represented only in half of the physician rating websites The number of quantitative and qualitative reviews for academic vascular surgeons is low. No vascular surgeon responded to any of the reviews. The activity of vascular surgeons in this area of social media is low and reflects only a small digital footprint that patients can reach and review.
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http://dx.doi.org/10.2196/22975DOI Listing
February 2021

A Daily Diagnostic Multidisciplinary Meeting to Reduce Time to Definitive Diagnosis in the Context of Primary Bone and Soft Tissue Sarcoma.

J Multidiscip Healthc 2021 15;14:115-123. Epub 2021 Jan 15.

The Royal Orthopaedic Hospital NHS Foundation Trust, Birmingham, UK.

Background And Objectives: Cancer services are under increasing pressure to deliver waiting time targets. Our service has seen referral numbers increase to over 3000 per annum, with more than 80% coming from secondary care. In order to deliver a responsive service, the department has introduced a daily diagnostic multidisciplinary meeting (DMDT) with the aim being stratification of resources by directing rapid access to clinics and diagnostics to those felt to be at greatest risk of malignancy at the start of the pathway. It also aimed to improve communication with patients and referrers, consistency in decision making and deliver improved diagnostic turn-around times in a sustainable manner. An evaluation was undertaken to assess whether the introduction of the DMDT has improved the pathway, the primary endpoint being a reduction in time to definitive diagnosis (TTDD). Secondary endpoints included measurements of efficiency and whether there has been a reduction in variation in practice.

Methods: Retrospective access to a prospective database over a 1-month period before (2015) and after (2018) the intervention.

Results: The introduction of the DMDT has led to a reduction in TTDD (7 days). The service also has an added benefit in reducing average total patient miles travelled over the course of diagnosis by 22.68 miles.

Conclusion: The introduction of a diagnostic MDT at the start of the pathway does lead to an improvement in service efficiency and a reduction in TTDD.
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http://dx.doi.org/10.2147/JMDH.S266014DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7816218PMC
January 2021

Critical analysis of the quality of internet resources for patients with varicose veins.

J Vasc Surg Venous Lymphat Disord 2020 Dec 17. Epub 2020 Dec 17.

Division of Vascular and Endovascular Surgery, Department of Surgery, Long School of Medicine, University of Texas Health Science Center at San Antonio, San Antonio, Tex; South Texas Center for Vascular Care, South Texas Medical Center, San Antonio, Tex. Electronic address:

Objective: Patients increasingly seek information on their medical conditions from the internet. The present study evaluated the quality and readability of readily available online patient resources for varicose veins.

Methods: An internet search for "varicose veins" was conducted using the meta-search engines Yippy and Dogpile and the general search engines Google, Yahoo, and Bing with a cleared-cache web browser in July 2019. Two trained raters scored the websites separately on the dimensions of accessibility, accountability, interactivity, structure, and content. Any discrepancies were discussed, and a consensus was reached. Readability was calculated using four readability metric systems. Rater consistency was evaluated using kappa, weighted kappa, and interrater correlation coefficient, as indicated.

Results: A total of 189 websites met the inclusion criteria. The total median quality score was 15.6 (interquartile range [IQR], 13.1-20.5; range, 7.4-31.3) of 38. The websites scored a median of 4 (IQR, 1-8) of 15 for accountability, 2 (IQR, 2-2) of 5 for interactivity, 4 (IQR, 2-4) of 4 for organization, and 6.4 (IQR, 3.9-7.9) of 14 for weighted content. Most websites (81.5%) were accessible. However, the overall readability was poor. The median Flesch-Kincaid reading ease score was 55.1 (IQR, 49.4-6.7), indicating that the text was fairly difficult to read. The median grade level was 10th grade using both the Flesch-Kincaid grade level and simple measure of the Gobbledygook index and 11th to 12th grade using the new Dale-Chall readability formula. Government websites were the most accountable, featured the best content, and were the most readable. The website traffic had a positive, nonlinear correlation with the total score and a negative, nonlinear correlation with the website rank (or position on the search result page). Website rank correlated negatively with the total score, although the correlation was weak.

Conclusions: The quality of the online patient resources on varicose veins varies greatly, and the readability for most sites is poor. Government-sponsored websites had the highest quality and were the most readable. Physicians are advised to consider providing a list of appropriate websites to their patients to better inform them, avoid confusion, and ensure appropriate delivery of accurate and readable information.
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http://dx.doi.org/10.1016/j.jvsv.2020.12.072DOI Listing
December 2020

Recruiting trainees to surgery in the United States and Canadian system - What strategies are effective?

Am J Surg 2021 02 3;221(2):410-423. Epub 2020 Dec 3.

Division of Vascular and Endovascular Surgery, University of Texas Health at San Antonio, San Antonio, TX, USA; South Texas Center for Vascular Care South Texas Medical Center, San Antonio, TX, USA. Electronic address:

Background: There has been increasing concerns regarding the declining number of medical students entering surgical residencies. The aim of this study is to analyze strategies and outcomes to enhance recruitment to the surgical specialties.

Methods: A systematic literature PRISMA-based search was performed. Study quality and bias were assessed. Meta-analysis was performed using DerSimonian Laird method.

Results: Of 3288 unique titles identified, 73 studies met inclusion criteria. Median study unique sample size was 84 participants (range 15-910). Subjective interest was reported in 59 studies, while objective match rate was reported by only 21 studies. The cumulative odds of students interested in the studied specialty was 1.98 (95% CI 1.47-2.67, I = 0%) and in any surgical specialty was 1.40 (95% 1.01-1.95, I = 37%) after an intervention compared to baseline.

Conclusion: While studies show increased odds of "interested in" a surgical specialty, the results may be subject to high selective and confounding biases.
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http://dx.doi.org/10.1016/j.amjsurg.2020.12.006DOI Listing
February 2021

Role of Glutathione in Buffering Excess Intracellular Copper in .

mBio 2020 12 1;11(6). Epub 2020 Dec 1.

Department of Biosciences, Durham University, Durham, United Kingdom

Copper (Cu) is an essential metal for bacterial physiology but in excess it is bacteriotoxic. To limit Cu levels in the cytoplasm, most bacteria possess a transcriptionally responsive system for Cu export. In the Gram-positive human pathogen (group A [GAS]), this system is encoded by the operon. This study demonstrates that although the site of GAS infection represents a Cu-rich environment, inactivation of the Cu efflux gene does not reduce virulence in a mouse model of invasive disease. , Cu treatment leads to multiple observable phenotypes, including defects in growth and viability, decreased fermentation, inhibition of glyceraldehyde-3-phosphate dehydrogenase (GapA) activity, and misregulation of metal homeostasis, likely as a consequence of mismetalation of noncognate metal-binding sites by Cu. Surprisingly, the onset of these effects is delayed by ∼4 h even though expression of is upregulated immediately upon exposure to Cu. Further biochemical investigations show that the onset of all phenotypes coincides with depletion of intracellular glutathione (GSH). Supplementation with extracellular GSH replenishes the intracellular pool of this thiol and suppresses all the observable effects of Cu treatment. These results indicate that GSH buffers excess intracellular Cu when the transcriptionally responsive Cu export system is overwhelmed. Thus, while the operon is responsible for Cu , GSH has a role in Cu and allows bacteria to maintain metabolism even in the presence of an excess of this metal ion. The control of intracellular metal availability is fundamental to bacterial physiology. In the case of copper (Cu), it has been established that rising intracellular Cu levels eventually fill the metal-sensing site of the endogenous Cu-sensing transcriptional regulator, which in turn induces transcription of a copper export pump. This response caps intracellular Cu availability below a well-defined threshold and prevents Cu toxicity. Glutathione, abundant in many bacteria, is known to bind Cu and has long been assumed to contribute to bacterial Cu handling. However, there is some ambiguity since neither its biosynthesis nor uptake is Cu-regulated. Furthermore, there is little experimental support for this physiological role of glutathione beyond measuring growth of glutathione-deficient mutants in the presence of Cu. Our work with group A provides new evidence that glutathione increases the threshold of intracellular Cu availability that can be tolerated by bacteria and thus advances fundamental understanding of bacterial Cu handling.
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http://dx.doi.org/10.1128/mBio.02804-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7733945PMC
December 2020

Estimating life years lost to diabetes: outcomes from analysis of National Diabetes Audit and Office of National Statistics data.

Cardiovasc Endocrinol Metab 2020 Dec 2;9(4):183-185. Epub 2020 Jun 2.

The Ipswich Diabetes Centre and Research Unit, Ipswich Hospital NHS Trust.

With sustained growth of diabetes numbers, sustained patient engagement is essential. Using nationally available data, we have shown that the higher mortality associated with a diagnosis of T1DM/T2DM could produces loss of 6.4 million future life years in the current UK population. In the model, the 'average' person with T1DM (age 42.8 years) has a life expectancy from now of 32.6 years, compared to 40.2 years in the equivalent age non diabetes mellitus population, corresponding to lost life years (LLYs) of 7.6 years/average person. The 'average' person with T2DM (age 65.4 years) has a life expectancy from now of 18.6 years compared to the 20.3 years for the equivalent non diabetes mellitus population, corresponding to LLY of 1.7 years/average person. We estimate that for both T1DM and T2DM, one year with HbA1c >58 mmol/mol loses around 100 life days. Linking glycaemic control to mortality has the potential to focus minds on effective engagement with therapy and lifestyle recommendation adherence.
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http://dx.doi.org/10.1097/XCE.0000000000000210DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673790PMC
December 2020

MRI predictors of revision surgery after primary lumbar discectomy.

J Clin Neurosci 2020 Nov 27;81:442-446. Epub 2020 Oct 27.

Department of Neurosurgery, St. George Hospital, Kogarah, New South Wales, Australia.

The prognostic significance of preoperative MRI findings in patients undergoing discectomy is incompletely understood. Identifying the radiological predictors of revision surgery on pre-operative MRI can guide management decisions and potentially prevent multiple surgeries. We included 181 patients who underwent primary lumbar discectomy between 2010 and 2014. All patients were contacted via a short telephone interview to determine if they had revision surgery within 5 years of their index surgery. Preoperative MRI of the lumbosacral spine was evaluated for various radiological factors including type of disc herniation, anatomical location of herniation, direction of herniation, degree of disc degeneration, end plate changes and presence of listhesis. Other potential confounders including age, gender, smoking status and index level of surgery were also recorded. Multivariate model of all radiological predictors and confounders were developed and a step-wise approach was used to remove insignificant variables in order to develop final significant multivariate model. P value of <0.05 was considered statistically significant. Patients with retrolisthesis were found to be 2.7 times more likely than the patients without listhesis to require revision surgery (p = 0.019). Patients with foraminal disc herniation were 3.45 times more likely than the patients with paramedian disc herniation to require revision surgery (p = 0.026). Other MRI predictors failed to achieve statistical significance. Based on the data presented patients with retrolisthesis and/or foraminal disc herniation should be counselled on the relatively higher risk of revision surgery when proceeding with discectomy, or alternative options should be considered.
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http://dx.doi.org/10.1016/j.jocn.2020.09.057DOI Listing
November 2020

Repurposing a neurodegenerative disease drug to treat Gram-negative antibiotic-resistant bacterial sepsis.

Sci Transl Med 2020 11;12(570)

School of Chemistry and Molecular Biosciences and Australian Infectious Diseases Research Centre, The University of Queensland, Queensland 4072, Australia.

The emergence of polymyxin resistance in carbapenem-resistant and extended-spectrum β-lactamase (ESBL)-producing bacteria is a critical threat to human health, and alternative treatment strategies are urgently required. We investigated the ability of the hydroxyquinoline analog ionophore PBT2 to restore antibiotic sensitivity in polymyxin-resistant, ESBL-producing, carbapenem-resistant Gram-negative human pathogens. PBT2 resensitized , , , and to last-resort polymyxin class antibiotics, including the less toxic next-generation polymyxin derivative FADDI-287, in vitro. We were unable to select for mutants resistant to PBT2 + FADDI-287 in polymyxin-resistant containing a plasmid-borne gene or carrying a chromosomal mutation. Using a highly invasive strain engineered for polymyxin resistance through mutation, we successfully demonstrated the efficacy of PBT2 + polymyxin (colistin or FADDI-287) for the treatment of Gram-negative sepsis in immunocompetent mice. In comparison to polymyxin alone, the combination of PBT2 + polymyxin improved survival and reduced bacterial dissemination to the lungs and spleen of infected mice. These data present a treatment modality to break antibiotic resistance in high-priority polymyxin-resistant Gram-negative pathogens.
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http://dx.doi.org/10.1126/scitranslmed.abb3791DOI Listing
November 2020

Use of Patient Health Records to Quantify Drug-Related Pro-arrhythmic Risk.

Cell Rep Med 2020 Aug 25;1(5):100076. Epub 2020 Aug 25.

Roche Pharmaceutical Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche AG, Basel, Switzerland.

There is an increasing expectation that computational approaches may supplement existing human decision-making. Frontloading of models for cardiac safety prediction is no exception to this trend, and ongoing regulatory initiatives propose use of high-throughput data combined with computational models for calculating proarrhythmic risk. Evaluation of these models requires robust assessment of the outcomes. Using FDA Adverse Event Reporting System reports and electronic healthcare claims data from the Truven-MarketScan US claims database, we quantify the incidence rate of arrhythmia in patients and how this changes depending on patient characteristics. First, we propose that such datasets are a complementary resource for determining relative drug risk and assessing the performance of cardiac safety models for regulatory use. Second, the results suggest important determinants for appropriate stratification of patients and evaluation of additional drug risk in prescribing and clinical support algorithms and for precision health.
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http://dx.doi.org/10.1016/j.xcrm.2020.100076DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7659582PMC
August 2020

The "two-cut monorail" technique, for the over-the-wire removal of the Impella CP device.

J Vasc Surg Cases Innov Tech 2020 Dec 22;6(4):622-625. Epub 2020 Sep 22.

Department of Surgery, University of Nebraska Medical Center, Omaha, Neb.

The Impella is a percutaneously placed intra-arterial flow pump positioned across the aortic valve for circulatory support. A limitation of the Impella is that it lacks a central wire channel, to maintain intra-arterial wire access when removing the device. Open surgical arterial cutdown is needed for the removal of the Impella CP placed emergently, without the use of preclose sutures. This case review describes an alternative removal method for the aforementioned occasions.
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http://dx.doi.org/10.1016/j.jvscit.2020.09.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7599379PMC
December 2020

The lateral transligamentous approach to the talar dome.

Foot Ankle Surg 2020 Oct 12. Epub 2020 Oct 12.

Liverpool University Hospitals NHS Foundation Trust, Liverpool, United Kingdom; University of Liverpool, Liverpool, United Kingdom.

Introduction: Anatomic reduction of talar body fractures is critical in restoring congruency to the talocrural joint. Previous studies have indicated 43% talar body access with a single incision and without malleolar osteotomy. The aim of this study was to investigate the percentage talar body exposure when using the lateral transligamentous approach.

Methods: The lateral transligamentous approach to the talus was undertaken in 10 fresh frozen cadaveric specimens by surgeons inexperienced in the approach following demonstration of the technique. An incision was made on the anterolateral aspect of the ankle augmented by the removal of the anterior talofibular ligament (ATFL) and the calcaneofibular ligament (CFL) from their fibular insertions. A bone lever was then placed behind the lateral aspect of the talus and levered forward with the foot in equinus and inversion. A mark was made on the talar dome where an instrument could be placed 90 degrees to the talar surface. The talus was subsequently disarticulated and high-resolution images were taken of the talar dome surface. The images were overlain with a reproducible nine-grid division. Accessibility to each zone within the grid was documented using the mark made on the talar surface. ImageJ software was used to calculate the surface area exposed with each approach.

Results: The mean percentage area of talar dome available through the transligamentous approach was 77.3% (95% confidence interval 73.3, 81.3). In all specimens the complete lateral talar process was accessible, along with the lateral and dorsomedial aspect of the talar neck. This approach gives complete access to Zones 1, 2, 3, 5 & 6 with partial access to Zones 4, 8 & 9.

Conclusion: The lateral transligamentous approach to the talus provides significantly greater access to the talar dome as compared to standard approaches. The residual surface area that is inaccessible with this approach is predominantly within Zones 4,7 and 8, the posteromedial corner.

Level Of Clinical Evidence: V.
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http://dx.doi.org/10.1016/j.fas.2020.10.003DOI Listing
October 2020

Global genomic epidemiology of Streptococcus pyogenes.

Infect Genet Evol 2020 12 2;86:104609. Epub 2020 Nov 2.

Department of Microbiology and Immunology, University of Melbourne at the Peter Doherty Institute for Infection and Immunity, Melbourne, VIC, Australia. Electronic address:

Streptococcus pyogenes is one of the Top 10 human infectious disease killers worldwide causing a range of clinical manifestations in humans. Colonizing a range of ecological niches within its sole host, the human, is key to the ability of this opportunistic pathogen to cause direct and post-infectious manifestations. The expansion of genome sequencing capabilities and data availability over the last decade has led to an improved understanding of the evolutionary dynamics of this pathogen within a global framework where epidemiological relationships and evolutionary mechanisms may not be universal. This review uses the recent publication by Davies et al., 2019 as an updated global framework to address S. pyogenes population genomics, highlighting how genomics is being used to gain new insights into evolutionary processes, transmission pathways, and vaccine design.
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http://dx.doi.org/10.1016/j.meegid.2020.104609DOI Listing
December 2020

A Flexible, Microfluidic, Dispensing System for Screening Drug Combinations.

Micromachines (Basel) 2020 Oct 18;11(10). Epub 2020 Oct 18.

Bernal Institute, University of Limerick, Limerick V94 T9PX, Ireland.

It is known that in many cases a combination of drugs is more effective than single-drug treatments both for reducing toxicity and increasing efficacy. With the advent of organoid screens, personalised medicine has become possible for many diseases. Automated pipetting to well plates is the pharmaceutical industry standard for drug screening, but this is relatively expensive and slow. Here, a rotary microfluidic system is presented that can test all possible drug combinations at speed with the use of droplets. For large numbers of combinations, it is shown how the experimental scale is reduced by considering drug dilutions and machine learning. As an example, two cases are considered; the first is a three-ring and three radii configuration and the second is a four ring and forty-eight radii configuration. Between these two, all other cases are shown to be possible. The proposed commercial instrument is shown to be flexible, the user choosing which wells to fill and which driver-computational sub-routine to select. The major issues addressed here are the programming theory of the instrument and the reduction of droplets to be generated by drug dilutions and machine learning.
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http://dx.doi.org/10.3390/mi11100943DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7603205PMC
October 2020

In silico characterisation of stand-alone response regulators of Streptococcus pyogenes.

PLoS One 2020 19;15(10):e0240834. Epub 2020 Oct 19.

School of Health and Sports Sciences, University of the Sunshine Coast, Sippy Downs, Queensland, Australia.

Bacterial "stand-alone" response regulators (RRs) are pivotal to the control of gene transcription in response to changing cytosolic and extracellular microenvironments during infection. The genome of group A Streptococcus (GAS) encodes more than 30 stand-alone RRs that orchestrate the expression of virulence factors involved in infecting multiple tissues, so causing an array of potentially lethal human diseases. Here, we analysed the molecular epidemiology and biological associations in the coding sequences (CDSs) and upstream intergenic regions (IGRs) of 35 stand-alone RRs from a collection of global GAS genomes. Of the 944 genomes analysed, 97% encoded 32 or more of the 35 tested RRs. The length of RR CDSs ranged from 297 to 1587 nucleotides with an average nucleotide diversity (π) of 0.012, while the IGRs ranged from 51 to 666 nucleotides with average π of 0.017. We present new evidence of recombination in multiple RRs including mga, leading to mga-2 switching, emm-switching and emm-like gene chimerization, and the first instance of an isolate that encodes both mga-1 and mga-2. Recombination was also evident in rofA/nra and msmR loci with 15 emm-types represented in multiple FCT (fibronectin-binding, collagen-binding, T-antigen)-types, including novel emm-type/FCT-type pairings. Strong associations were observed between concatenated RR allele types, and emm-type, MLST-type, core genome phylogroup, and country of sampling. No strong associations were observed between individual loci and disease outcome. We propose that 11 RRs may form part of future refinement of GAS typing systems that reflect core genome evolutionary associations. This subgenomic analysis revealed allelic traits that were informative to the biological function, GAS strain definition, and regional outbreak detection.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240834PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7571705PMC
December 2020

THE EXTENT OF HEEL ULCERATION INFLUENCES THE OUTCOMES IN PATIENTS WITH ISOLATED INFRA-POPLITEAL LIMB THREATENING CRITICAL ISCHEMIA.

J Vasc Surg 2020 Oct 5. Epub 2020 Oct 5.

Division of Vascular and Endovascular Surgery Department of Surgery, Long School of Medicine, University of Texas Health at San Antonio, San Antonio, Texas; South Texas Center for Vascular Care, South Texas Medical Center, San Antonio, Texas. Electronic address:

Background: The aim of this study was to assess the impact of the extent of heel ulceration on outcomes of limb threatening critical ischemia due to isolated Infra-popliteal disease METHODS: A retrospective review identified 989 patients with isolated Infra-popliteal disease and heel ulceration between 2001 and 2018. The heel was defined as the back of the foot, extending from the Achilles tendon around the plantar surface, it covers the apex of the calcaneum bone. Heel ulceration was categorized into three groupings by area: <5cm, 5-10cm and >10 cm. Interventions were endovascular (ENDO), bypass (OPEN), major Amputation (AMP) and Wound care (WOUND). Intention to treat analysis by patient was performed. 30-day outcomes and Amputation-Free Survival (AFS; survival without major amputation) were evaluated.

Results: Three hundred and eighty-four patients (58% male, average age 65 years; 768 vessels) underwent isolated endovascular tibial intervention, 124 patients (45% male, average age 59 years) underwent popliteal tibial vein bypass for limb threatening critical ischemia, 219 (52% male, average age 67 years) underwent major amputation and 242 (49% male, average age 66 years) underwent wound care. There was no difference in 30-day MACE in the ENDO and OPEN groups, while there were significantly more events in the AMP group (P= .03). 30-day MALE and 30-day Amputation were equivalent between the OPEN and ENDO groups Outcomes of 5-year AFS were superior in the OPEN (37±8%; mean ± SEM %) vs. ENDO (27±9%) groups (P= .04). WOUND had a 5-year AFS of 20±9%, which was not significantly different to ENDO. Patients with heel ulcers of <5cm had better AFS (47±8%) than those with 5-10cm heel ulceration (24±9%). Heel ulcers >10 cm were associated with markedly worse 5-yr AFS outcomes (0±0%). The presence of ESRD, osteomyelitis, uncontrolled diabetes (Hb >10%) and frailty in tandem with a heel ulcer >10 cm were predictive of poor AFS.

Conclusions: Increasing areas of heel ulcers in association with osteomyelitis and systemic comorbidities are associated with worsening 30-day outcomes and 5-yr AFS irrespective of the therapy chosen.
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http://dx.doi.org/10.1016/j.jvs.2020.08.144DOI Listing
October 2020

Prophage exotoxins enhance colonization fitness in epidemic scarlet fever-causing Streptococcus pyogenes.

Nat Commun 2020 10 6;11(1):5018. Epub 2020 Oct 6.

Australian Infectious Diseases Research Centre and School of Chemistry and Molecular Biosciences, The University of Queensland, St. Lucia, QLD, Australia.

The re-emergence of scarlet fever poses a new global public health threat. The capacity of North-East Asian serotype M12 (emm12) Streptococcus pyogenes (group A Streptococcus, GAS) to cause scarlet fever has been linked epidemiologically to the presence of novel prophages, including prophage ΦHKU.vir encoding the secreted superantigens SSA and SpeC and the DNase Spd1. Here, we report the molecular characterization of ΦHKU.vir-encoded exotoxins. We demonstrate that streptolysin O (SLO)-induced glutathione efflux from host cellular stores is a previously unappreciated GAS virulence mechanism that promotes SSA release and activity, representing the first description of a thiol-activated bacterial superantigen. Spd1 is required for resistance to neutrophil killing. Investigating single, double and triple isogenic knockout mutants of the ΦHKU.vir-encoded exotoxins, we find that SpeC and Spd1 act synergistically to facilitate nasopharyngeal colonization in a mouse model. These results offer insight into the pathogenesis of scarlet fever-causing GAS mediated by prophage ΦHKU.vir exotoxins.
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http://dx.doi.org/10.1038/s41467-020-18700-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538557PMC
October 2020

Intraosseous lipomas originating from simple bone cysts.

Skeletal Radiol 2021 Apr 1;50(4):801-806. Epub 2020 Oct 1.

Department of Radiology, Robert Jones and Agnes Hunt Orthopaedic Hospital NHS Foundation Trust, Oswestry, Shropshire, SY10 7AQ, UK.

Purpose: Fatty or part-fatty intraosseous lesions are occasionally encountered while imaging the skeletal system. A number of case reports have proposed involution of calcaneal bone cysts to intraosseous lipomas, but this has never been proven. This paper sets out to prove that simple bone cysts (SBCs) can involute to fatty lesions indistinguishable from intraosseous lipomas.

Materials And Methods: The pathology and PACS databases at 2 specialist orthopedic hospitals were retrospectively interrogated for all cases of intraosseous lipomas or SBCs with cross-sectional imaging follow-up for SBCs and precursor or follow-up imaging for intraosseous lipomas, in the time period from August 2007 to December 2016. For intraosseous lipoma cases, these were only included if change in imaging appearances was observed.

Results: There was no case of change in the appearance in intraosseous lipomas. Six cases of SBC with cross-sectional imaging follow-up were identified in one participating hospital and none in the other. The 6 cases were comprised of 4 male and 2 female patients. Two were located in the proximal humerus, one in the proximal tibia, and 3 in the os calcis. All cases demonstrated filling in of the cystic lesion with fat from the periphery, in 2 cases complete filling in, and in 4 cases partial fatty conversion.

Conclusion: SBCs can heal with fatty conversion of the cystic cavity, with partly cystic remnants. It is proposed that at least part of the so-called intraosseous lipomas are healed simple bone cysts.
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http://dx.doi.org/10.1007/s00256-020-03628-0DOI Listing
April 2021

Ten Commandments for the Diagnosis of Bone Tumors.

Semin Musculoskelet Radiol 2020 Jun 28;24(3):203-213. Epub 2020 Sep 28.

Department of Immunology, Genetics and Pathology (Oncology) and Department of Surgical Sciences (Radiology), Uppsala University Hospital, Uppsala, Sweden.

The diagnosis of tumors and tumorlike lesions of bone is a routine part of both general and specialist radiologic practices. The spectrum of disorders ranges from the small incidental lesion to the potentially life-limiting malignancies whether primary or secondary. In this review, authored by experts from several European orthopaedic oncology centers, we present a collection of pieces of advice in the form of 10 commandments. Adherence in daily practice to this guidance should help minimize adverse patient experiences and outcomes.
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http://dx.doi.org/10.1055/s-0040-1708873DOI Listing
June 2020

NeoSTRESS: Study of Transfer and Retrieval Environmental StressorS upon neonates via a smartphone application - Sound.

J Paediatr Child Health 2020 Sep;56(9):1396-1401

Faculty of Medicine, School of Clinical Medicine, University of Queensland, Brisbane, Queensland, Australia.

Aim: This study aimed to measure sound exposure during neonatal retrieval, determine whether this varied with mode of transport, and compare noise exposure to recommended levels in neonatal intensive care units. We also aimed to assess the acceptability of using a smartphone application to measure sound.

Setting: Neonatal retrieval service in Brisbane, Australia.

Methods: The Physics Toolbox Sensor Suite application was installed on a Samsung Galaxy S5 smartphone and calibrated for sound measurement. Data were collected during outbound, non-patient legs of 45 retrievals - 25 road, 11 fixed wing aircraft and 9 rotary aircraft journeys. Data were saved to cloud storage, then analysed using PostgreSQL database.

Results: The median sound level was 83 dB (interquartile range 66-91; range 27-≥97 dB). Continuous equivalent sound (L ) was 90 dB across all journeys. Rotary transport was loudest (L 94 dB). Fixed wing (L 89 dB) and road (L 87 dB) journeys also resulted in significant sound exposure. Sound exceeded recommended levels (45 dB) for 99% of all journey time, regardless of the mode of transport.

Conclusions: Neonates encounter harmful sound levels during retrieval - louder than recommended levels for 99% of all retrieval time. Sounds levels were highest in rotary aircraft transport compared to fixed wing or road transport. It is feasible to use a calibrated smartphone application instead of a sound metre.
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http://dx.doi.org/10.1111/jpc.14947DOI Listing
September 2020

The Society for Vascular Surgery Alternative Payment Model Task Force report on opportunities for value-based reimbursement in care for patients with peripheral artery disease.

J Vasc Surg 2021 Apr 12;73(4):1404-1413.e2. Epub 2020 Sep 12.

Dartmouth-Hitchcock Medical Center, Lebanon, NH.

The Society for Vascular Surgery Alternative Payment Model (APM) Taskforce document explores the drivers and implications for developing objective value-based reimbursement plans for the care of patients with peripheral arterial disease (PAD). The APM is a payment approach that highlights high-quality and cost-efficient care and is a financially incentivized pathway for participation in the Quality Payment Program, which aims to replace the traditional fee-for-service payment method. At present, the participation of vascular specialists in APMs is hampered owing to the absence of dedicated models. The increasing prevalence of PAD diagnosis, technological advances in therapeutic devices, and the increasing cost of care of the affected patients have financial consequences on care delivery models and population health. The document summarizes the existing measurement methods of cost, care processes, and outcomes using payor data, patient-reported outcomes, and registry participation. The document also evaluates the existing challenges in the evaluation of PAD care, including intervention overuse, treatment disparities, varied clinical presentations, and the effects of multiple comorbid conditions on the cost potentially attributable to the vascular interventionalist. Medicare reimbursement data analysis also confirmed the prolonged need for additional healthcare services after vascular interventions. The Society for Vascular Surgery proposes that a PAD APM should provide patients with comprehensive care using a longitudinal approach with integration of multiple key medical and surgical services. It should maintain appropriate access to diagnostic and therapeutic advancements and eliminate unnecessary interventions. It should also decrease the variability in care but must also consider the varying complexity of the presenting PAD conditions. Enhanced quality of care and physician innovation should be rewarded. In addition, provisions should be present within an APM for high-risk patients who carry the risk of exclusion from care because of the naturally associated high costs. Although the document demonstrates clear opportunities for quality improvement and cost savings in PAD care, continued PAD APM development requires the assessment of more granular data for accurate risk adjustment, in addition to largescale testing before public release. Collaboration between payors and physician specialty societies remains key.
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http://dx.doi.org/10.1016/j.jvs.2020.08.131DOI Listing
April 2021

Calcifying pseudoneoplasm of the neuraxis: A rare case involving the oculomotor nerve.

Surg Neurol Int 2020 15;11:249. Epub 2020 Aug 15.

Department of Neurosurgery, St George Public Hospital, Gray Street, Australia.

Background: Calcifying pseudoneoplasm of the neuraxis (CAPNON) is a rare entity which can occur at intracranial and spinal locations. Clinical presentation is due to local mass effect rather than tissue infiltration. Lesions causing significant symptoms or are showing radiological progression require surgical resection. Maximal surgical resection is considered curative for this non-neoplastic entity with only two cases of recurrence reported in the literature. Cranial nerve involvement is extremely rare and the presenting neurological deficit is unlikely to improve even with surgical intervention.

Case Description: We describe a case of CAPNON at the right posterior clinoid process with involvement of the right oculomotor nerve in a 38-year-old male. Computed tomography demonstrated an amorphous mass which had intermediate to low T1 and T2 signal on magnetic resonance imaging. The oculomotor nerve was compressed with sign of atrophy. The patient underwent maximal surgical debulking for progressive symptoms of worsening pain and ophthalmoplegia. Postoperatively, the patient's symptoms were stable but did not improve.

Conclusion: Preoperative diagnosis of CAPNON is difficult due to its rarity and nonspecific clinical and radiological findings. Surgical resection is considered in cases with worsening symptoms, progression on serial imaging, or uncertain diagnosis. Relatively inaccessible lesions with little or no clinical symptoms can be observed.
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http://dx.doi.org/10.25259/SNI_386_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7468187PMC
August 2020

Skull Imaging-Radiographs and CT revisited.

Neurol India 2020 Jul-Aug;68(4):732-740

Department of Musculoskeletal Radiology, The Royal Orthopedic Hospital, Bristol Road South, Northfield, Birmingham, UK.

Although rare, skull vault lesions include a vast array of pathology encompassing infection, benign, and malignant bone tumors. Given the large range of potential diagnoses, it is crucial to identify imaging features to differentiate one from another, ensuring early diagnosis. Radiographs are still valuable in modern radiology but have largely been superseded by computed tomography (CT) due to its high spatial resolution. Both are especially important in developing countries where access to magnetic resonance imaging (MRI) may be limited.There are currently several publications outlining imaging appearances of skull vault lesions. However, the majority of literature is dated, with the last dedicated textbook published in 1980 (Principles of X-ray diagnosis of the skull). Despite overlapping features, a few lesions have "aunt minnie," type classical characteristics, which we will highlight. Most vault lesions also appear as a spectrum depending on location and the exact stage of the disease. A small subset within each disease entity also has atypical features not widely discussed in the current literature. In this pictorial review, we hope to focus on radiographic and CT imaging appearances to help differentiate between various skull vault lesions.
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http://dx.doi.org/10.4103/0028-3886.293481DOI Listing
August 2020

Bacterial colonisation of the endotracheal tube in ventilated very preterm neonates: A retrospective cohort study.

J Paediatr Child Health 2020 Oct 17;56(10):1607-1612. Epub 2020 Aug 17.

Grantley Stable Neonatal Unit, Royal Brisbane and Women's Hospital, Brisbane, Queensland, Australia.

Aim: To determine the rate, type and timing of bacterial endotracheal tube (ETT) colonisation in neonates born <32 weeks gestational age (GA); and if bacterial colonisation is associated with chronic lung disease (CLD), septicaemia, length-of-stay or mortality.

Methods: All intubated newborns born <32 weeks GA were included. Endotracheal aspirates were routinely obtained three times-per-week. Cohort was divided into three colonisation groups: no growth, normal respiratory flora only, significant bacteria. Logistic regression was performed to identify if ETT bacterial colonisation was associated with CLD, septicaemia or mortality. A general linear model was fitted for length-of-stay.

Results: ETT aspirates were sent from 1054 infants: no growth n = 319, only normal respiratory flora n = 357, and significant bacteria n = 378. ETTs became colonised in 70%, most in the first week of life (82%). Most grew normal respiratory flora (642 infants). In those with significant bacteria, 40% grew Gram-negative species; Klebsiella in 34%. Staphylococcus aureus grew in 104 patients. Adjusted odds ratios for CLD (43% of cohort) compared with no growth were, for normal respiratory flora, 0.58 (95% confidence interval (CI) 0.34-0.99) and, for significant bacteria, 0.48 (95% CI 0.24-0.93). With no overall association between colonisation group and CLD in the adjusted model P = 0.07. The odds of septicaemia (10% of cohort) were 4.50 (95% CI 1.98-10.23, P < 0.001) times greater for significant bacteria compared with no growth. No significant associated was found with mortality or length-of-stay.

Conclusions: Bacterial colonisation of ETTs is common. It is associated with more septicaemia. There was no significant association with CLD, longer admission or mortality.
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http://dx.doi.org/10.1111/jpc.15046DOI Listing
October 2020

Reporting standards for endovascular aortic repair of aneurysms involving the renal-mesenteric arteries.

J Vasc Surg 2021 Jan 29;73(1S):4S-52S. Epub 2020 Jun 29.

Department of Vascular and Endovascular Surgery, MedStar Health, Washington, D.C.

Endovascular aortic aneurysm repair of complex aortic aneurysms requires incorporation of side branches using specially designed aortic stent grafts with fenestrations, directional branches, or parallel stent grafts. These techniques have been increasingly used and reported in the literature. The purpose of this document is to clarify and to update terminology, classification systems, measurement techniques, and end point definitions that are recommended for reports dealing with endovascular repair of complex abdominal and thoracoabdominal aortic aneurysms involving the renal and mesenteric arteries.
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http://dx.doi.org/10.1016/j.jvs.2020.06.011DOI Listing
January 2021

The value of the modern vascular surgeon to the health care system: A report from the Society for Vascular Surgery Valuation Work Group.

J Vasc Surg 2021 Feb 23;73(2):359-371.e3. Epub 2020 Jun 23.

Department of Surgery, Advocate Lutheran General Hospital, Park Ridge, Ill; Rosalind Franklin University Chicago Medical School, North Chicago, Ill.

Vascular surgeons provide an important service to the health care system. They are capable of treating a wide range of disease processes that affect both the venous and arterial systems. Their presence broadens the complexity and diversity of services that a health care system can offer both in the outpatient setting and in the inpatient setting. Because of their ability to control hemorrhage, they are critical to a safe operating room environment. The vascular surgery service line has a positive impact on hospital margin through both the direct vascular profit and loss and the indirect result of assisting other surgical and medical services in providing care. The financial benefits of a vascular service line will hold true for a wide range of alternative payment models, such as bundled payments or capitation. To fully leverage a modern vascular surgeon's skill set, significant investment is required from the health care system that is, however, associated with substantial return on the investment.
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http://dx.doi.org/10.1016/j.jvs.2020.05.056DOI Listing
February 2021

Increase of emm1 isolates among group A Streptococcus strains causing scarlet fever in Shanghai, China.

Int J Infect Dis 2020 Sep 17;98:305-314. Epub 2020 Jun 17.

Department of Microbiology, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, PR China. Electronic address:

Objective: Scarlet fever epidemics caused by group A Streptococcus (GAS) have been ongoing in China since 2011. However, limited data are available on the dynamic molecular characterizations of the epidemic strains.

Method: Epidemiological data of scarlet fever in Shanghai were obtained from the National Notifiable Infectious Disease Surveillance System. Throat swabs of patients with scarlet fever and asymptomatic school-age children were cultured. Illumina sequencing was performed on 39emm1 isolates.

Results: The annual incidence of scarlet fever was 7.5-19.4/100,000 persons in Shanghai during 2011-2015, with an average GAS carriage rate being 7.6% in school-age children. The proportion ofemm1 GAS strains increased from 3.8% in 2011 to 48.6% in 2014; they harbored a superantigen profile similar to emm12 isolates, except for the speA gene. Two predominant clones, SH001-emm12, and SH002-emm1, circulated in 66.9% of scarlet fever cases and 44.8% of carriers. Genomic analysis showed emm1 isolates throughout China constituted distinct clades, enriched by the presence of mobile genetic elements carrying the multidrug-resistant determinants ermB and tetM and virulence genes speA, speC, and spd1.

Conclusion: A significant increase in the proportion ofemm1 strains occurred in the GAS population, causing scarlet fever in China. Ongoing surveillance is warranted to monitor the dynamic changes of GAS clones.
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http://dx.doi.org/10.1016/j.ijid.2020.06.053DOI Listing
September 2020