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IntroductionCancer-related cognitive impairment (CRCI) can have detrimental effects on quality of life, even among patients with non-central nervous system (CNS) cancers. Several studies have been conducted to explore different markers associated with CRCI to understand its pathobiology. It is proposed that the underlying mechanisms of CRCI are related to a cascade of physiological adaptive events in response to cancer and/or treatment. Hence, peripheral blood would be a logical source to observe and identify these physiological events. This paper outlines the protocol for a scoping review being conducted to summarise the extant literature regarding blood-based biomarkers of CRCI among patients with non-CNS cancer.Methods/analysisMethods will be informed by the updated guidelines of Arksey and O’Malley. The systematic search for literature will include electronic databases, handsearching of key journals and reference lists, forward citation tracking and consultation with content experts. Study selection will be confirmed by duplicate review and calculation of inter-rater reliability. Data to be charted will include study design, sample size, cancer and treatment characteristics, demographic characteristics, cognitive variable/s and biomarkers assessed, associations between cognitive functioning and biomarkers (including statistics used), and rigour in biomarker sample collection and processing. Results will be presented through: (1) a descriptive numerical summary of studies, including a flow diagram based on the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement, (2) a list of blood-based biomarkers associated with CRCI and (3) a narrative overview developed through collaboration among the research team and consultation with content experts.DisseminationThe findings of this review will highlight current directions and gaps in the current body of evidence that may lead to improved rigour in future CRCI investigations. The dissemination of this work will be facilitated through the involvement of clinicians and researchers on the research team, an external consultation process and the presentation of the results through scholarly publication and presentation.

We sought to conduct a quality improvement initiative to compare the wash quality and speed of autologous red blood cell (RBC) processing of four autotransfusion devices during cardiac surgery. Using a prospective observational cohort study approach, we prospectively evaluated four commercially available autologous cell savage devices (autoLog IQ™, Medtronic plc, Minneapolis, MN, USA [135 mL]; Xtra™, LivaNova, plc, Houston, TX, USA [125 mL, 225 mL]; Cell Saver® Elite®+, Haemonetics Corp., Boston, MA, USA [125 mL, 225 mL]; and CATSmart®, Fresenius Kabi AG, Bad Homburg vor der Höhe, Germany) in adult patients undergoing cardiac surgery. Device settings were determined by manufacturer recommendations for optimal wash quality. We collected pre- and postprocessing samples, volumes, and processing times from each device to calculate removal ratios of heparin, potassium, plasma free hemoglobin (PfHb), white blood cells (WBCs), platelets, reinfusion concentrations of heparin and potassium, and red blood cell (RBC) recovery rates. A total of 130 consecutive patients underwent autologous cell salvage, but 15 cases were excluded because of incomplete data. All devices removed > 99% heparin, > 95% potassium, > 94% platelets, and > 85% PfHb from collected shed blood. Comparison of processing sets showed significant differences in median [interquartile range] WBC removal ratios, ranging from 26 [19-33]% to 59 [42-68]%, and median heparin reinfusion concentrations, which ranged from 0.09 [0.08-0.11] to 0.63 [0.55-0.70] U·mL processed red cells. Median RBC recovery rates also showed significant differences between processing sets, ranging from 8 [8-10] mL RBC·min to 24 [22-25] mL RBC·min . Wash quality and processing speed differed between autotransfusion devices and processing sets. These findings may have clinical implications when large volumes of shed blood are processed and reinfused.

Purpose We sought to conduct a quality improvement initiative to compare the wash quality and speed of autologous red blood cell (RBC) processing of four autotransfusion devices during cardiac surgery. Methods Using a prospective observational cohort study approach, we prospectively evaluated four commercially available autologous cell savage devices (autoLog IQ™, Medtronic plc, Minneapolis, MN, USA [135 mL]; Xtra™, LivaNova, plc, Houston, TX, USA [125 mL, 225 mL]; Cell Saver® Elite®+, Haemonetics Corp., Boston, MA, USA [125 mL, 225 mL]; and CATSmart®, Fresenius Kabi AG, Bad Homburg vor der Höhe, Germany) in adult patients undergoing cardiac surgery. Device settings were determined by manufacturer recommendations for optimal wash quality. We collected pre- and postprocessing samples, volumes, and processing times from each device to calculate removal ratios of heparin, potassium, plasma free hemoglobin (PfHb), white blood cells (WBCs), platelets, reinfusion concentrations of heparin and potassium, and red blood cell (RBC) recovery rates. Results A total of 130 consecutive patients underwent autologous cell salvage, but 15 cases were excluded because of incomplete data. All devices removed > 99% heparin, > 95% potassium, > 94% platelets, and > 85% PfHb from collected shed blood. Comparison of processing sets showed significant differences in median [interquartile range] WBC removal ratios, ranging from 26 [19–33]% to 59 [42–68]%, and median heparin reinfusion concentrations, which ranged from 0.09 [0.08–0.11] to 0.63 [0.55–0.70] U·mL −1 processed red cells. Median RBC recovery rates also showed significant differences between processing sets, ranging from 8 [8–10] mL RBC·min −1 to 24 [22–25] mL RBC·min −1 . Conclusion Wash quality and processing speed differed between autotransfusion devices and processing sets. These findings may have clinical implications when large volumes of shed blood are processed and reinfused.

Abstract Background Circuit-induced hemolysis is relatively common in extracorporeal membrane oxygenation (ECMO) patients. Intravascular release of cell-free hemoglobin can lead to complications and requires timely recognition. Validation of plasma free hemoglobin (PFH) measurement using a direct spectrophotometric method is presented. Methodology We evaluated a method modified from Kahn et al. (Ann Clin Lab Sci 1981;11:126–31) on a stand-alone spectrophotometer (Cary 60) and compared its performance to the semiquantitative H-index on an Abbott Alinity c, including precision, linearity, recovery, reference interval verification, interference, and stability. Method comparison was performed relative to the H-index and the same method on a different spectrophotometer (Beckman DU 720). Lipemia interference was performed on the Cary 60, Cary 3500, and Beckman DU 720. Surrogate biomarkers for hemolysis detection were also investigated in ECMO patients. Results The PFH method on the Cary 60 demonstrated imprecision ranging from 1% (96.0 mg/dL) to 4% (3.0 mg/dL), linearity to 100 mg/dL, and recovery >80% for values >2 mg/dL hemoglobin-spiked plasma. Dilution expanded the reportable range to the maximum dilution tested (1000 mg/dL). Lipemia interfered with PFH measurement by the direct method, but the same method on the Cary 3500 was resistant to lipemia. Bilirubin did not cause significant interference. Direct and H-index methods were comparable with a mean difference of 5.03 mg/dL (95% CI −1.38, 11.44). Lactate dehydrogenase was the most reliable surrogate biomarker for hemolysis. with AUC of 0.921 (0.894, 0.949) at >50 mg/dL. Conclusion PFH measurement by a direct spectrophotometric method is more precise and sensitive compared to the H-index; however, PFH measurement is susceptible to lipemia unless performed on a high-end spectrophotometer.

At least 50 Kansas City officers responded to the scene including Police Chief James Corwin early in the day. FBI agents also had assembled. Police last week had asked the FBI to consider adding [Shauntay L. Henderson] to its 10 Most Wanted list. That decision is still pending.

Antibiotic resistance genes (ARGs) are widespread among bacteria. However, not all ARGs pose serious threats to public health, highlighting the importance of identifying those that are high-risk. Here, we developed an ‘omics-based’ framework to evaluate ARG risk considering human-associated-enrichment, gene mobility, and host pathogenicity. Our framework classifies human-associated, mobile ARGs (3.6% of all ARGs) as the highest risk, which we further differentiate as ‘current threats’ (Rank I; 3%) - already present among pathogens - and ‘future threats’ (Rank II; 0.6%) - novel resistance emerging from non-pathogens. Our framework identified 73 ‘current threat’ ARG families. Of these, 35 were among the 37 high-risk ARGs proposed by the World Health Organization and other literature; the remaining 38 were significantly enriched in hospital plasmids. By evaluating all pathogen genomes released since framework construction, we confirmed that ARGs that recently transferred into pathogens were significantly enriched in Rank II (‘future threats’). Lastly, we applied the framework to gut microbiome genomes from fecal microbiota transplantation donors. We found that although ARGs were widespread (73% of genomes), only 8.9% of genomes contained high-risk ARGs. Our framework provides an easy-to-implement approach to identify current and future antimicrobial resistance threats, with potential clinical applications including reducing risk of microbiome-based interventions. Antibiotic resistance genes are common but not all are of high risk to human health. Here, the authors develop an omics-based framework for ranking genes by risk that incorporates level of enrichment in human associated environments, gene mobility, and host pathogenicity.

Fecal microbiota transplantation is a compelling treatment for recurrent Clostridium difficile infections, with potential applications against other diseases associated with changes in gut microbiota. But variability in fecal bacterial communities-believed to be the therapeutic agent-can complicate or undermine treatment efficacy. To understand the effects of transplant preparation methods on living fecal microbial communities, we applied a DNA-sequencing method (PMA-seq) that uses propidium monoazide (PMA) to differentiate between living and dead fecal microbes, and we created an analysis pipeline to identify individual bacteria that change in abundance between samples. We found that oxygen exposure degraded fecal bacterial communities, whereas freeze-thaw cycles and lag time between donor defecation and transplant preparation had much smaller effects. Notably, the abundance of Faecalibacterium prausnitzii-an anti-inflammatory commensal bacterium whose absence is linked to inflammatory bowel disease-decreased with oxygen exposure. Our results indicate that some current practices for preparing microbiota transplant material adversely affect living fecal microbial content and highlight PMA-seq as a valuable tool to inform best practices and evaluate the suitability of clinical fecal material.

Background. Recurrent Clostridium difficile infection (CDI) with poor response to standard antimicrobial therapy is a growing medical concern. We aimed to investigate the outcomes of fecal microbiota transplant (FMT) for relapsing CDI using a frozen suspension from unrelated donors, comparing colonoscopic and nasogastric tube (NGT) administration. Methods. Healthy volunteer donors were screened and a frozen fecal suspension was generated. Patients with relapsing/refractory CDI were randomized to receive an infusion of donor stools by colonoscopy or NGT. The primary endpoint was clinical resolution of diarrhea without relapse after 8 weeks. The secondary endpoint was self-reported health score using standardized questionnaires. Results. A total of 20 patients were enrolled, 10 in each treatment arm. Patients had a median of 4 (range, 2–16) relapses prior to study enrollment, with 5 (range, 3–15) antibiotic treatment failures. Resolution of diarrhea was achieved in 14 patients (70%) after a single FMT (8 of 10 in the colonoscopy group and 6 of 10 in the NGT group). Five patients were retreated, with 4 obtaining cure, resulting in an overall cure rate of 90%. Daily number of bowel movements changed from a median of 7 (interquartile range [IQR], 5–10) the day prior to FMT to 2 (IQR, 1–2) after the infusion. Self-ranked health score improved significantly, from a median of 4 (IQR, 2–6) before transplant to 8 (IQR, 5–9) after transplant. No serious or unexpected adverse events occurred. Conclusions. In our initial feasibility study, FMT using a frozen inoculum from unrelated donors is effective in treating relapsing CDI. NGT administration appears to be as effective as colonoscopic administration. Clinical Trials Registration. NCT01704937.

Gene swapping in the human microbiome Horizontal gene transfer — the exchange of genetic material between different species or lineages — is an important factor in bacterial evolution. A study of human microbiome data comprising more than 2,000 full bacterial genomes shows that this environment is a hotbed of horizontal gene transfer: pairs of bacteria isolated from the human body are 25-fold more likely to share transferred DNA than pairs from other environments. Thus microbial ecology — rather than phylogeny or geography — is the most important driver of the patterns of horizontal gene exchange. Further analysis revealed 42 unique antibiotic-resistance genes that had been transferred between human and agricultural isolates, and 43 transfers across national borders. Horizontal gene transfer (HGT), the acquisition of genetic material from non-parental lineages, is known to be important in bacterial evolution 1 , 2 . In particular, HGT provides rapid access to genetic innovations, allowing traits such as virulence 3 , antibiotic resistance 4 and xenobiotic metabolism 5 to spread through the human microbiome. Recent anecdotal studies providing snapshots of active gene flow on the human body have highlighted the need to determine the frequency of such recent transfers and the forces that govern these events 4 , 5 . Here we report the discovery and characterization of a vast, human-associated network of gene exchange, large enough to directly compare the principal forces shaping HGT. We show that this network of 10,770 unique, recently transferred (more than 99% nucleotide identity) genes found in 2,235 full bacterial genomes, is shaped principally by ecology rather than geography or phylogeny, with most gene exchange occurring between isolates from ecologically similar, but geographically separated, environments. For example, we observe 25-fold more HGT between human-associated bacteria than among ecologically diverse non-human isolates ( P = 3.0 × 10 −270 ). We show that within the human microbiome this ecological architecture continues across multiple spatial scales, functional classes and ecological niches with transfer further enriched among bacteria that inhabit the same body site, have the same oxygen tolerance or have the same ability to cause disease. This structure offers a window into the molecular traits that define ecological niches, insight that we use to uncover sources of antibiotic resistance and identify genes associated with the pathology of meningitis and other diseases.

A Western lifestyle with high salt consumption can lead to hypertension and cardiovascular disease. High salt may additionally drive autoimmunity by inducing T helper 17 (T H 17) cells, which can also contribute to hypertension. Induction of T H 17 cells depends on gut microbiota; however, the effect of salt on the gut microbiome is unknown. Here we show that high salt intake affects the gut microbiome in mice, particularly by depleting Lactobacillus murinus . Consequently, treatment of mice with L. murinus prevented salt-induced aggravation of actively induced experimental autoimmune encephalomyelitis and salt-sensitive hypertension by modulating T H 17 cells. In line with these findings, a moderate high-salt challenge in a pilot study in humans reduced intestinal survival of Lactobacillus spp., increased T H 17 cells and increased blood pressure. Our results connect high salt intake to the gut–immune axis and highlight the gut microbiome as a potential therapeutic target to counteract salt-sensitive conditions. High salt intake changed the gut microbiome and increased T H 17 cell numbers in mice, and reduced intestinal survival of Lactobacillus species, increased the number of T H 17 cells and increased blood pressure in humans. Gut microbes worth their salt The role of the gut microbiota in human disease is becoming increasingly recognized. In this study, Dominik Müller and colleagues report that a diet high in salt alters the composition of the gut microbiota in mice, causing pronounced depletion of the commensal Lactobacillus murinus and reduced production of indole metabolites. Previous work has suggested that a high salt diet leads to the generation of pathogenic T helper 17 (T H 17) cells, which have been linked to hypertension and autoimmunity. The authors show that treatment of mice on a high salt diet with L. murinus prevents salt-induced aggravation of actively induced autoimmune encephalomyelitis and salt-sensitive hypertension, through the suppression of T H 17 cells. In a pilot study in a small number of humans, the authors also show that high-salt challenge induces an increase in blood pressure and T H 17 cells, associated with a reduction in Lactobacillus in the gut. However, future work is required to determine whether the findings for mice are translatable to humans.