Risk factors for treatment failure in orthopedic device-related methicillin-resistant Staphylococcus aureus infection

The purpose of this study was to determine the clinical and microbiological risk factors for treatment failure of methicillin-resistant Staphylococcus aureus (MRSA) orthopedic device-related infection (ODRI). A retrospective cohort study of patients with MRSA ODRI who were treated at Geneva University Hospitals between 2000 and 2008 was undertaken. Stored MRSA isolates were retrieved for genetic characterization and determination of the vancomycin minimum inhibitory concentration (MIC). Fifty-two patients were included, of whom 23 (44%) had joint arthroplasty and 29 (56%) had osteosynthesis. All 41 of the retrieved MRSA isolates were susceptible to vancomycin (MIC ≤ 2mg/L) and 35 (85%) shared genetic characteristics of the South German clone (ST228). During a median follow-up of 391days (range, 4-2,922days), 18 patients (35%) experienced treatment failure involving MRSA persistence or recurrence. Microbiological factors such as infection with the predominant clone and a vancomycin MIC of 2mg/L were not associated with treatment failure. Using a Cox proportional hazards model, implant retention (hazard ratio [HR], 4.9; 95% confidence interval [CI], 1.3-18.2; P = 0.017) and single-agent antimicrobial therapy (HR, 4.4; 95% CI, 1.2-16.3; P = 0.025) were independent predictors of treatment failure after debridement. Therapy using a combination of antimicrobials should be considered for patients with MRSA ODRI, especially when implant removal is not feasibl

Magnetism, FeS colloids, and Origins of Life

A number of features of living systems: reversible interactions and weak bonds underlying motor-dynamics; gel-sol transitions; cellular connected fractal organization; asymmetry in interactions and organization; quantum coherent phenomena; to name some, can have a natural accounting via $physical$ interactions, which we therefore seek to incorporate by expanding the horizons of `chemistry-only' approaches to the origins of life. It is suggested that the magnetic 'face' of the minerals from the inorganic world, recognized to have played a pivotal role in initiating Life, may throw light on some of these issues. A magnetic environment in the form of rocks in the Hadean Ocean could have enabled the accretion and therefore an ordered confinement of super-paramagnetic colloids within a structured phase. A moderate H-field can help magnetic nano-particles to not only overcome thermal fluctuations but also harness them. Such controlled dynamics brings in the possibility of accessing quantum effects, which together with frustrations in magnetic ordering and hysteresis (a natural mechanism for a primitive memory) could throw light on the birth of biological information which, as Abel argues, requires a combination of order and complexity. This scenario gains strength from observations of scale-free framboidal forms of the greigite mineral, with a magnetic basis of assembly. And greigite's metabolic potential plays a key role in the mound scenario of Russell and coworkers-an expansion of which is suggested for including magnetism.Comment: 42 pages, 5 figures, to be published in A.R. Memorial volume, Ed Krishnaswami Alladi, Springer 201

Long-term outcomes of small head metal-on-metal compared to ceramic-on-polyethylene primary total hip arthroplasty: a registry-based cohort study

Purpose: We aimed to compare the long-term outcomes of small-head (28 mm) metal-on-metal (MoM) total hip arthroplasty (THA) to ceramic-on-polyethylene (CoP) THA using the same cup. Methods: All primary elective MoM and CoP THAs performed 1998–2011 were prospectively included in a local registry. Patients were followed until 31 December 2022. Outcomes were all-cause revision, complications and mortality. The uncemented Morscher 28 mm monobloc press-fit cup was used in all THAs. Results: Overall, 3257 THAs were included, 864 MoM (mean age 63) and 2393 CoP THAs (mean age 72). Mean follow-up of the cohort was 12.9 years (maximum 26.8 years). Revision for any cause was performed in 85 MoM and 79 CoP THAs. Cumulative incidence of all-cause revision at 20 years was 13.2% (95% CI 10.6 to 16.3) in MoM and 6.3% (95% CI 4.8 to 8.3) in CoP group. Adjusted hazard ratio for all-cause revision was 1.88 (95% CI 1.34 to 2.65) comparing MoM vs. CoP. Diagnoses at revision were mainly aseptic loosening (33%) and adverse local tissue reactions (33%) in MoM and aseptic loosening in CoP group (44%). The smoothed hazard function revealed the largest difference in instantaneous revision rate between three and 14 years postoperative. After that period no difference was observed. Conclusion: Overall, the cumulative risk of all-cause revision was almost twice as high in patients with a small head MoM as compared to a CoP THA over the 20-year period. However, most of the excess in revisions among MoM patients occurred between three and 14 years postoperative

Comparative analysis of selected exhaled breath biomarkers obtained with two different temperature-controlled devices

<p>Abstract</p> <p>Background</p> <p>The collection of exhaled breath condensate (EBC) is a suitable and non-invasive method for evaluation of airway inflammation. Several studies indicate that the composition of the condensate and the recovery of biomarkers are affected by physical characteristics of the condensing device and collecting circumstances. Additionally, there is an apparent influence of the condensing temperature, and often the level of detection of the assay is a limiting factor. The ECoScreen2 device is a new, partly single-use disposable system designed for studying different lung compartments.</p> <p>Methods</p> <p>EBC samples were collected from 16 healthy non-smokers by using the two commercially available devices ECoScreen2 and ECoScreen at a controlled temperature of -20°C. EBC volume, pH, NOx, LTB₄, PGE₂, 8-isoprostane and cys-LTs were determined.</p> <p>Results</p> <p>EBC collected with ECoScreen2 was less acidic compared to ECoScreen. ECoScreen2 was superior concerning condensate volume and detection of biomarkers, as more samples were above the detection limit (LTB₄and PGE₂) or showed higher concentrations (8-isoprostane). However, NOx was detected only in EBC sampled by ECoScreen.</p> <p>Conclusion</p> <p>ECoScreen2 in combination with mediator specific enzyme immunoassays may be suitable for measurement of different biomarkers. Using this equipment, patterns of markers can be assessed that are likely to reflect the complex pathophysiological processes in inflammatory respiratory disease.</p

Exhaled breath condensate pH as a biomarker of COPD severity in ex-smokers

Endogenous airway acidification, as assessed by exhaled breath condensate (EBC) pH, is present in patients with stable COPD. The aim of this study was to measure EBC pH levels in a large cohort of COPD patients and to evaluate associations with functional parameters according to their smoking status

Genetic polymorphisms in MDR1, CYP3A4 and CYP3A5 genes in a Ghanaian population: a plausible explanation for altered metabolism of ivermectin in humans?

<p>Abstract</p> <p>Background</p> <p>Ivermectin, a substrate of multidrug resistance (MDR1) gene and cytochrome P450 (CYP) 3A4, has been used successfully in the treatment of onchocerciasis in Ghana. However, there have been reports of suboptimal response in some patients after repeated treatment. Polymorphisms in host MDR1 and CYP3A genes may explain the observed suboptimal response to ivermectin. We genotyped relevant functional polymorphisms of MDR1 and CYP3A in a random sample of healthy Ghanaians and compared the data with that of ivermectin-treated patients with a view to exploring the relationship between suboptimal response to ivermectin and MDR1 and CYP3A allelic frequencies.</p> <p>Methods</p> <p>Using PCR-RFLP, relevant polymorphic alleles of MDR1 and CYP3A4 genes were analysed in 204 randomly selected individuals and in 42 ivermectin treated patients.</p> <p>Results</p> <p>We recorded significantly higher MDR1 (3435T) variant allele frequency in suboptimal responders (21%) than in patients who responded to treatment (12%) or the random population sample (11%). <it>CYP3A4*1B</it>, <it>CYP3A5*3 </it>and <it>CYP3A5*6 </it>alleles were detected at varied frequencies for the sampled Ghanaian population, responders and suboptimal responders to ivermectin. <it>CYP3A5*1/CYP3A5*1 </it>and <it>CYP3A5*1/CYP3A5*3 </it>genotypes were also found to be significantly different for responders and suboptimal responders. Haplotype (*1/*1/*3/*1) was determined to be significantly different between responders and suboptimal responders indicating a possible role of these haplotypes in treatment response with ivermectin.</p> <p>Conclusion</p> <p>A profile of pharmacogenetically relevant variants for MDR1, CYP3A4 and CYP3A5 genes has been generated for a random population of 204 Ghanaians to address the scarcity of data within indigenous African populations. In 42 patients treated with ivermectin, difference in MDR1 variant allele frequency was observed between suboptimal responders and responders.</p

Analysis of nitrogen oxides (NOx) in the exhaled breath condensate (EBC) of subjects with asthma as a complement to exhaled nitric oxide (FeNO) measurements: a cross-sectional study

<p>Abstract</p> <p>Background</p> <p>The study of pulmonary biomarkers with noninvasive methods, such as the analysis of exhaled breath condensate (EBC), provides a useful approach to the pathophysiology of asthma. Although many recent publications have applied such methods, numerous methodological pitfalls remain. The first stage of our study consisted of validating methods for the collection, storage and analysis of EBC; we next sought to clarify the utility of analysing nitrogen oxides (NOx) in the EBC of asthmatics, as a complement to measuring exhaled nitric oxide (FeNO).</p> <p>Methods</p> <p>This hospital-based cross-sectional study included 23 controls matched with 23 asthmatics. EBC and FeNO were performed and respiratory function measured. Intra-assay and intra-subject reproducibility were assessed for the analysis of NOx in the EBC of 10 healthy subjects.</p> <p>Results</p> <p>The intraclass correlation coefficient (ICC) was excellent for intra-assay reproducibility and was moderate for intra-subject reproducibility (Fermanian's classification). NOx was significantly higher in asthmatics (geometric mean [IQR] 14.4 μM [10.4 - 19.7] vs controls 9.9 μM [7.5 - 15.0]), as was FeNO (29.9 ppb [17.9 - 52.4] vs controls 9.6 ppb [8.4 - 14.2]). FeNO also increased significantly with asthma severity.</p> <p>Conclusions</p> <p>We validated the procedures for NOx analysis in EBC and confirmed the need for assays of other biomarkers to further our knowledge of the pathophysiologic processes of asthma and improve its treatment and control.</p