Description of Standardized Planes and Angles for Percutaneous Supra-acetabular Screw Placement.

BACKGROUND: Percutaneous screw fixation for pelvic fractures has become a minimally invasive alternative to an open operation. The complex anatomy of the pelvis renders this procedure challenging. The objective of this study was to assess standardized angles and dimensions of safety zones within a 3 D computed tomography model for optimal supra-acetabular screw placement. METHODS: Computed tomography scans of 107 patients that suffered major trauma without showing any bone injury of the pelvis were collected. Using a software-based analysis, raw computed tomography data were transformed into 3 D models to set standardized landmarks and determine the possible insertion corridor. RESULTS: Screws not exceeding a length of 97 mm in females and 106.4 mm in males were, in 95% of the evaluated cases, insertable without cortical bone penetration. The safety zone was 6.6 mm for females and 7.9 mm for males. Screws not exceeding these diameters were safely insertable in 95% of the cases. For the midsagittal plane, the angle was 36.4 ± 5.1 on the left and 34.7 ± 2.9 on the right (p = 0.008). For the anterior pelvic plane, the angle was 31.3 ± 4.5° on the left and 34.0 ± 4.8° on the right (p = 0.008). CONCLUSIONS: Percutaneous fixation using supra-acetabular screws is a promising method to treat simple supra-acetabular fractures. These results may improve its safe utilization and could facilitate its broader clinical application.

Periprosthetic joint infection caused by kytococcus schroeteri: The first reported case and a review of the literature.

Oftentimes, Gram-positive cocci are the cause for periprosthetic joint infections (PJI). Most of these infections include bacteria such as Staphylococcus aureus, Staphylococcus epidermidis or other coagulase-negative staphylococci. We here present the first case of a PJI caused by Kytococcus schroeteri. While being a Gram-positive coccus, it is very rarely the cause for infections in the human body. K. schroeteri is part of the micrococcus branch and often encountered as a symbiotic bacterium living on the skin. Regarding its pathogenic potential, not a lot is known since less than a few dozen human infections have been reported worldwide. Furthermore, many of the cases reported are either associated with implanted material, especially heart valves, or associated with patients whose immune response is deficient. Only 3 reports of osteoarticular infections are described so far.

Genomic diversity and differentiation between island and mainland populations of white-tailed eagles (Haliaeetus albicilla).

Divergence in the face of high dispersal capabilities is a documented but poorly understood phenomenon. The white-tailed eagle (Haliaeetus albicilla) has a large geographic dispersal capability and should theoretically be able to maintain genetic homogeneity across its dispersal range. However, following analysis of the genomic variation of white-tailed eagles, from both historical and contemporary samples, clear signatures of ancient biogeographic substructure across Europe and the North-East Atlantic is observed. The greatest genomic differentiation was observed between island (Greenland and Iceland) and mainland (Denmark, Norway and Estonia) populations. The two island populations share a common ancestry from a single mainland population, distinct from the other sampled mainland populations, and despite the potential for high connectivity between Iceland and Greenland they are well separated from each other and are characterized by inbreeding and little variation. Temporal differences also highlight a pattern of regional populations persisting despite the potential for admixture. All sampled populations generally showed a decline in effective population size over time, which may have been shaped by four historical events: (1) Isolation of refugia during the last glacial period 110-115,000 years ago, (2) population divergence following the colonization of the deglaciated areas ~10,000 years ago, (3) human population expansion, which led to the settlement in Iceland ~1100 years ago, and (4) human persecution and exposure to toxic pollutants during the last two centuries.

The sequences of 150,119 genomes in the UK Biobank.

Detailed knowledge of how diversity in the sequence of the human genome affects phenotypic diversity depends on a comprehensive and reliable characterization of both sequences and phenotypic variation. Over the past decade, insights into this relationship have been obtained from whole-exome sequencing or whole-genome sequencing of large cohorts with rich phenotypic data1,2. Here we describe the analysis of whole-genome sequencing of 150,119 individuals from the UK Biobank3. This constitutes a set of high-quality variants, including 585,040,410 single-nucleotide polymorphisms, representing 7.0% of all possible human single-nucleotide polymorphisms, and 58,707,036 indels. This large set of variants allows us to characterize selection based on sequence variation within a population through a depletion rank score of windows along the genome. Depletion rank analysis shows that coding exons represent a small fraction of regions in the genome subject to strong sequence conservation. We define three cohorts within the UK Biobank: a large British Irish cohort, a smaller African cohort and a South Asian cohort. A haplotype reference panel is provided that allows reliable imputation of most variants carried by three or more sequenced individuals. We identified 895,055 structural variants and 2,536,688 microsatellites, groups of variants typically excluded from large-scale whole-genome sequencing studies. Using this formidable new resource, we provide several examples of trait associations for rare variants with large effects not found previously through studies based on whole-exome sequencing and/or imputation.

Mercury contamination and potential health risks to Arctic seabirds and shorebirds.

Since the last Arctic Monitoring and Assessment Programme (AMAP) effort to review biological effects of mercury (Hg) on Arctic biota in 2011 and 2018, there has been a considerable number of new Arctic bird studies. This review article provides contemporary Hg exposure and potential health risk for 36 Arctic seabird and shorebird species, representing a larger portion of the Arctic than during previous AMAP assessments now also including parts of the Russian Arctic. To assess risk to birds, we used Hg toxicity benchmarks established for blood and converted to egg, liver, and feather tissues. Several Arctic seabird populations showed Hg concentrations that exceeded toxicity benchmarks, with 50 % of individual birds exceeding the "no adverse health effect" level. In particular, 5 % of all studied birds were considered to be at moderate or higher risk to Hg toxicity. However, most seabirds (95 %) were generally at lower risk to Hg toxicity. The highest Hg contamination was observed in seabirds breeding in the western Atlantic and Pacific Oceans. Most Arctic shorebirds exhibited low Hg concentrations, with approximately 45 % of individuals categorized at no risk, 2.5 % at high risk category, and no individual at severe risk. Although the majority Arctic-breeding seabirds and shorebirds appeared at lower risk to Hg toxicity, recent studies have reported deleterious effects of Hg on some pituitary hormones, genotoxicity, and reproductive performance. Adult survival appeared unaffected by Hg exposure, although long-term banding studies incorporating Hg are still limited. Although Hg contamination across the Arctic is considered low for most bird species, Hg in combination with other stressors, including other contaminants, diseases, parasites, and climate change, may still cause adverse effects. Future investigations on the global impact of Hg on Arctic birds should be conducted within a multi-stressor framework. This information helps to address Article 22 (Effectiveness Evaluation) of the Minamata Convention on Mercury as a global pollutant.

Increased rate of enteric bacteria as cause of periprosthetic joint infections in patients with liver cirrhosis.

INTRODUCTION: Periprosthetic joint infections (PJI) are a major complication in joint-arthroplasty. Rifampicin is often used as an additional agent to treat PJI, because it penetrates bacterial biofilms. However, rifaximin, belonging to the same antibiotic class as rifampicin, is frequently used to prevent episodes of hepatic encephalopathy in patients with cirrhosis and may induce resistance to rifampicin. The aim of this study was to examine the microbial pattern of periprosthetic joint infections in cirrhotic patients and to test the hypothesis that intake of rifaximin increases the rate of resistance to rifampicin in periprosthetic joint infections. METHODS: A cohort of cirrhotic patients and PJI (n = 25) was analysed on the characteristics of bacterial isolates from sonication and tissue analysis. In a second step a subgroup analysis on the development of rifampicin resistant bacterial specimens, depending on the intake of rifaximin (8 rifaximin intake patients vs. 13 non rifaximin intake patients) was performed. RESULTS: Intestinal bacteria were found in 50% of the specimens, which was significantly more frequent than in a control cohort. By comparison of the single bacterial isolates, rifampicin resistance was detected in 69.2% (9/13) of the rifaximin-intake samples. In contrast, the non-rifaximin-intake isolates only were resistant to rifampicin in 22.2% (4/18) of the cases (p = 0.01). The odds ratio for developing a rifampicin-resistance through rifaximin intake was calculated as OR = 13.5. CONCLUSION: Periprosthetic joint infections have a high incidence of being caused by enteric bacteria in cirrhotic patients. Due to this change in microbial pattern and the innate resistance to rifampicin of most of gram-negative bacteria, the therapy with rifampicin should be carefully considered. The association between the use of rifaximin and developed resistance to rifampicin has a major impact on the treatment of PJI.

A review of constraints and solutions for collecting raptor samples and contextual data for a European Raptor Biomonitoring Facility.

The COST Action 'European Raptor Biomonitoring Facility' (ERBFacility) aims to develop pan-European raptor biomonitoring in support of better chemicals management in Europe, using raptors as sentinel species. This presents a significant challenge involving a range of constraints that must be identified and addressed. The aims of this study were to: (1) carry out a comprehensive review of the constraints that may limit the gathering in the field of raptor samples and contextual data, and assess their relative importance across Europe; and (2) identify and discuss possible solutions to the key constraints that were identified. We applied a participatory approach to identify constraints and to discuss feasible solutions. Thirty-one constraints were identified, which were divided into four categories: legal, methodological, spatial coverage, and skills constraints. To assess the importance of the constraints and their possible solutions, we collected information through scientific workshops and by distributing a questionnaire to stakeholders in all the countries involved in ERBFacility. We obtained 74 answers to the questionnaire, from 24 of the 39 COST participating countries. The most important constraints identified were related to the collection of complex contextual data about sources of contamination, and the low number of existing raptor population national/regional monitoring schemes and ecological studies that could provide raptor samples. Legal constraints, such as permits to allow the collection of invasive samples, and skills constraints, such as the lack of expertise to practice necropsies, were also highlighted. Here, we present solutions for all the constraints identified, thus suggesting the feasibility of establishing a long-term European Raptor Sampling Programme as a key element of the planned European Raptor Biomonitoring Facility.

Correction: Early diagnosis of sepsis in emergency departments, time to treatment, and association with mortality: An observational study.

[This corrects the article DOI: 10.1371/journal.pone.0227652.].

Disease-specific variant pathogenicity prediction significantly improves variant interpretation in inherited cardiac conditions.

PURPOSE: Accurate discrimination of benign and pathogenic rare variation remains a priority for clinical genome interpretation. State-of-the-art machine learning variant prioritization tools are imprecise and ignore important parameters defining gene-disease relationships, e.g., distinct consequences of gain-of-function versus loss-of-function variants. We hypothesized that incorporating disease-specific information would improve tool performance. METHODS: We developed a disease-specific variant classifier, CardioBoost, that estimates the probability of pathogenicity for rare missense variants in inherited cardiomyopathies and arrhythmias. We assessed CardioBoost's ability to discriminate known pathogenic from benign variants, prioritize disease-associated variants, and stratify patient outcomes. RESULTS: CardioBoost has high global discrimination accuracy (precision recall area under the curve [AUC] 0.91 for cardiomyopathies; 0.96 for arrhythmias), outperforming existing tools (4-24% improvement). CardioBoost obtains excellent accuracy (cardiomyopathies 90.2%; arrhythmias 91.9%) for variants classified with >90% confidence, and increases the proportion of variants classified with high confidence more than twofold compared with existing tools. Variants classified as disease-causing are associated with both disease status and clinical severity, including a 21% increased risk (95% confidence interval [CI] 11-29%) of severe adverse outcomes by age 60 in patients with hypertrophic cardiomyopathy. CONCLUSIONS: A disease-specific variant classifier outperforms state-of-the-art genome-wide tools for rare missense variants in inherited cardiac conditions ( https://www.cardiodb.org/cardioboost/ ), highlighting broad opportunities for improved pathogenicity prediction through disease specificity.

The Performance of a Dithiothreitol-Based Diagnostic System in Diagnosing Periprosthetic Joint Infection Compared to Sonication Fluid Cultures and Tissue Biopsies.

PURPOSE: The aim of this study was to evaluate the performance of a commercially available dithiothreitol (DTT) kit for routine use in diagnosing periprosthetic joint infections (PJIs) in comparison to conventional microbiological tissue specimens and sonication procedures in a maximal care hospital. METHODS: We applied the DTT system in 40 consecutive cases of revision arthroplasty (23 PJIs and 17 aseptic revisions), with an exchange or a removal of components. The hardware components were split between the DTT system and the conventional sonication procedure. At least three tissue biopsies and a joint fluid specimen were sent for microbiological and histopathological analysis. Data was analysed retrospectively to compare between the different methods. RESULTS: Cultures of the DTT fluid showed a sensitivity of 65% and specificity of 100%, as referenced to conventional microbiological cultures. Sonication had better sensitivity (75%) but lower specificity (85%). The categorical agreement of DTT cultures compared to sonication fluid cultures was 78% (31/40). Neither pathogen type, infection duration nor antibiotic pretreatment influenced the accuracy of the DTT, but a low pH in the DTT seemed to be associated with false-negative results. CONCLUSION: DTT was inferior in sensitivity when diagnosing PJIs compared to sonication fluid cultures and tissue biopsies. A low pH in the DTT fluid correlated with false-negative results. Nevertheless, the closed system of the DTT kit avoids contamination and false-positive results, and DTT can be an alternative where sonication is not available.

Outcome of repeated multi-stage arthroplasty with custom-made acetabular implants in patients with severe acetabular bone loss: a case series.

BACKGROUND: Failed reconstruction in cases of severe acetabular bone loss, with or without pelvic discontinuity, in revision total hip arthroplasty (rTHA) remains a great challenge in orthopaedic surgery. The aim of this study was to describe the outcome of a "second" rTHA with "custom-made acetabular components (CMACs)" after a previously failed reconstruction with CMACs. METHODS: 4 patients with severe acetabular bone loss (Paprosky Type IIIB), who required a second rTHA after a previously failed reconstruction with CMAC, due to prosthetic joint infection (PJI), were included in our retrospective study. All prostheses had been constructed on the basis of thin-layer computed-tomography scans of the pelvis. The second rTHA was considered unsuccessful in the event of PJI or aseptic loosening (AL) with need for renewed CMAC explantation. RESULTS: The treatment success rate after second rTHA with a CMAC was 50% (2 of 4). In the successful cases, the visual analogue scale (VAS) score and Harris Hip Score (HHS) after the second rTHA (VAS range 2-4; HHS range 45-58 points) did not differ from those after the first rTHA, before onset of symptoms (VAS: range 2-4; HHS: range 47-55 points). In the failed cases, the second CMACs needed to be explanted due to PJI, with renewed detection of previous pathogens. Patients with treatment failure of the second CMAC had required a higher number of revision surgeries after explantation of the first CMAC than patients with a successful outcome. CONCLUSIONS: In patients with severe acetabular bone loss and previously failed rTHA with CMACs, repeat rTHA with a CMAC may be a solid treatment option for patients with an "uncomplicated" multi-stage procedure, i.e., without persisting infection after explantation of the original CMAC. While the outcome in terms of clinical function does not appear negatively affected by such a "second attempt," the complication rate and risk of reinfection, nonetheless, is high.

Difficult-to-treat pathogens significantly reduce infection resolution in periprosthetic joint infections.

Periprosthetic joint infection (PJI) is a feared complication after arthroplasty. Our hypothesis was that PJI caused by difficult-to-treat (DTT) pathogens has a worse outcome compared with non-DTT PJI. Routine clinical data on 77 consecutive patients with confirmed PJI treated with 2-stage exchange arthroplasty were placed in DTT and non-DTT PJI groups and analyzed. The main outcome variable was that the patient was definitively free of infection after 2 years. We found definitive infection resolution in 31 patients in the DTT group (68.9%) and 28 patients (87.5%) in the non-DTT group (P < 0.05). The necessity for revision surgery until assumed resolution of infection was significantly more frequent in the DTT group with 4.72 ± 3.03 operations versus 2.41 ± 3.02 operations in the non-DTT group (P < 0.05). PJI caused by DTT bacteria is associated with significantly higher numbers of revision operations and significantly inferior definitive infection resolution.

Early diagnosis of sepsis in emergency departments, time to treatment, and association with mortality: An observational study.

BACKGROUND: Early recognition of sepsis is critical for timely initiation of treatment. The first objective of this study was to assess the timeliness of diagnostic procedures for recognizing sepsis in emergency departments. We define diagnostic procedures as tests used to help diagnose the condition of patients. The second objective was to estimate associations between diagnostic procedures and time to antibiotic treatment, and to estimate associations between time to antibiotic treatment and mortality. METHODS: This observational study from 24 emergency departments in Norway included 1559 patients with infection and at least two systemic inflammatory response syndrome criteria. We estimated associations using linear and logistic regression analyses. RESULTS: Of the study patients, 72.9% (CI 70.7-75.1) had documented triage within 15 minutes of presentation to the emergency departments, 44.9% (42.4-47.4) were examined by a physician in accordance with the triage priority, 44.4% (41.4-46.9) were adequately observed through continual monitoring of signs while in the emergency department, and 25.4% (23.2-27.7) received antibiotics within 1 hour. Delay or non-completion of these key diagnostic procedures predicted a delay of more than 2.5 hours to antibiotic treatment. Patients who received antibiotics within 1 hour had an observed 30-day all-cause mortality of 13.6% (10.1-17.1), in the timespan 2 to 3 hours after admission 5.9% (2.8-9.1), and 4 hours or later after admission 10.5% (5.7-15.3). CONCLUSIONS: Key procedures for recognizing sepsis were delayed or not completed in a substantial proportion of patients admitted to the emergency department with sepsis. Delay or non-completion of key diagnostic procedures was associated with prolonged time to treatment with antibiotics. This suggests a need for systematic improvement in the initial management of patients admitted to emergency departments with sepsis.

Aerosol Transmission of Gull-Origin Iceland Subtype H10N7 Influenza A Virus in Ferrets.

Subtype H10 influenza A viruses (IAVs) have been recovered from domestic poultry and various aquatic bird species, and sporadic transmission of these IAVs from avian species to mammals (i.e., human, seal, and mink) are well documented. In 2015, we isolated four H10N7 viruses from gulls in Iceland. Genomic analyses showed four gene segments in the viruses were genetically associated with H10 IAVs that caused influenza outbreaks and deaths among European seals in 2014. Antigenic characterization suggested minimal antigenic variation among these H10N7 isolates and other archived H10 viruses recovered from human, seal, mink, and various avian species in Asia, Europe, and North America. Glycan binding preference analyses suggested that, similar to other avian-origin H10 IAVs, these gull-origin H10N7 IAVs bound to both avian-like alpha 2,3-linked sialic acids and human-like alpha 2,6-linked sialic acids. However, when the gull-origin viruses were compared with another Eurasian avian-origin H10N8 IAV, which caused human infections, the gull-origin virus showed significantly higher binding affinity to human-like glycan receptors. Results from a ferret experiment demonstrated that a gull-origin H10N7 IAV replicated well in turbinate, trachea, and lung, but replication was most efficient in turbinate and trachea. This gull-origin H10N7 virus can be transmitted between ferrets through the direct contact and aerosol routes, without prior adaptation. Gulls share their habitat with other birds and mammals and have frequent contact with humans; therefore, gull-origin H10N7 IAVs could pose a risk to public health. Surveillance and monitoring of these IAVs at the wild bird-human interface should be continued.IMPORTANCE Subtype H10 avian influenza A viruses (IAVs) have caused sporadic human infections and enzootic outbreaks among seals. In the fall of 2015, H10N7 viruses were recovered from gulls in Iceland, and genomic analyses showed that the viruses were genetically related with IAVs that caused outbreaks among seals in Europe a year earlier. These gull-origin viruses showed high binding affinity to human-like glycan receptors. Transmission studies in ferrets demonstrated that the gull-origin IAV could infect ferrets, and that the virus could be transmitted between ferrets through direct contact and aerosol droplets. This study demonstrated that avian H10 IAV can infect mammals and be transmitted among them without adaptation. Thus, avian H10 IAV is a candidate for influenza pandemic preparedness and should be monitored in wildlife and at the animal-human interface.

Detection of methicillin-resistant coagulase-negative staphylococci harboring the class A mec complex by MALDI-TOF mass spectrometry.

The aim of this study was to test the identification of methicillin resistance in coagulase-negative staphylococci by routine matrix-assisted laser desorption/ionization time of flight mass spectrometry (MALDI-TOF MS). SCCmec cassettes of type II, III and VIII encode a small peptide called PSM-mec in the vicinity of mecA. It is visible at m/z 2415 during MALDI-TOF MS of whole cells of Staphylococcus aureus. In view of the fact that psm-mec has been identified in methicillin-resistant coagulase-negative staphylococci, we evaluated a collection of clinical coagulase-negative staphylococci, that contained 77.03% of methicillin-resistant isolates, for the presence of the structural gene encoding PSM-mec and the appearance of the corresponding signal during mass spectroscopy. In MALDI-TOF MS spectra, 89.65% of the strains that harbored the gene yielded the correct signal, corresponding to a sensitivity of 0.897 and a specificity of 1.0. However, regarding detection of methicillin resistance, i. e. considering all resistant strains as positive regardless of the presence of the gene, the overall sensitivity of the test decreased to 0.285, due to the fact that only 29.43% of all resistant isolates contained psm-mec. In conclusion, the presence of the signal in MALDI-TOF MS quickly indicates methicillin-resistance in coagulase-negative staphylococci but its absence does not indicate susceptibility to methicillin.

Activity of ceftobiprole against Staphylococcus spec. isolates derived from foreign body associated infections.

Antibiotic therapy is essential in foreign body associated infections. The treatment regime should aim at high tissue concentrations, high bioavailability, high biofilm penetration and good tolerance. We investigated whether the new cephalosporin ceftobiprole is active against clinical isolates from musculoskeletal foreign body associated infections. One hundred ninety-six staphylococci isolates (coagulase negative staphylococci and Staphylococcus aureus) derived from foreign body associated infections were tested towards susceptibility to ceftobiprole, using a test strip assay and broth microdilution. The MIC for all strains S. aureus indicated susceptibility to ceftobiprole. The MIC of only two strains of coagulase negative staphylococci was above 2 mg/L. Our results show that ceftobiprole might be considered as an off-label treatment option in foreign body associated infections.

Novel Diagnostics in Revision Arthroplasty: Implant Sonication and Multiplex Polymerase Chain Reaction.

In orthopedic patients, foreign body-associated infections, especially periprosthetic joint infections (PJIs), are a devastating complication of arthroplasty. Infection requires complex treatment, may result in long hospitalization and causes considerable costs. Multiple surgical revisions can be necessary in these patients, with a loss in function as well as in quality of life. The routine preoperative diagnostics include blood examination for C-reactive protein (CRP) and other biomarkers, as well as joint aspirate analysis for cell count, differentiation, and culture. Intraoperative specimens for histology and microbiology are also standard procedure. The microbiological examination of removed implants with sonication, in combination with the implementation of molecular biology techniques in microbiology, represent two novel techniques currently employed to enhance the differential diagnostics of PJI. We present here the step-wise procedure of analyzing joint aspirate and sonication fluid, using a cartridge-based multiplex polymerase chain reaction (PCR) system. Results were matched against conventional cultures and consensus criteria for PJI. Conventional microbiological cultures from tissue biopsies, joint aspirate and sonication fluid showed a sensitivity of 66.7%, 66.7%, and 88.9%, respectively, and a specificity of 82.3%, 54.6%, and 61.5%, respectively. The PCR diagnostic of the sonication fluid and the joint fluid showed a sensitivity of 50.0% and 55.6%, respectively, and both a specificity of 100.0%. Both PCR diagnostics combined had a sensitivity of 66.7% and a specificity of 100.0%. The multiplex PCR therefore presents a rapid diagnostic tool with moderate sensitivity but high specificity in diagnosing PJI.

Successful Therapy of a Multidrug-Resistant Extended-Spectrum ß-Lactamase-Producing and Fluoroquinolone-Resistant Salmonella enterica Subspecies enterica Serovar Typhi Infection Using Combination Therapy of Meropenem and Fosfomycin.

We report a traveler who acquired a Salmonella enterica subspecies enterica serovar Typhi strain with resistance against ß-lactams, cephalosporins (extended-spectrum ß-lactamase-producing type SHV-12), and quinolones (plasmid-mediated quinolone resistance gene qnrB7). After clinical deterioration using meropenem monotherapy, treatment success was achieved after commencement of fosfomycin in conjunction with high-dose meropenem. The case illustrates clinical challenges of multidrug-resistant S. Typhi.