Chemotherapy-induced gut microbiome disruption, inflammation, and cognitive decline in female patients with breast cancer.

Chemotherapy is notorious for causing behavioral side effects (e.g., cognitive decline). Notably, the gut microbiome has recently been reported to communicate with the brain to affect behavior, including cognition. Thus, the aim of this clinical longitudinal observational study was to determine whether chemotherapy-induced disruption of the gut microbial community structure relates to cognitive decline and circulating inflammatory signals. Fecal samples, blood, and cognitive measures were collected from 77 patients with breast cancer before, during, and after chemotherapy. Chemotherapy altered the gut microbiome community structure and increased circulating TNF-α. Both the chemotherapy-induced changes in microbial relative abundance and decreased microbial diversity were related to elevated circulating pro-inflammatory cytokines TNF-α and IL-6. Participants reported subjective cognitive decline during chemotherapy, which was not related to changes in the gut microbiome or inflammatory markers. In contrast, a decrease in overall objective cognition was related to a decrease in microbial diversity, independent of circulating cytokines. Stratification of subjects, via a reliable change index based on 4 objective cognitive tests, identified objective cognitive decline in 35% of the subjects. Based on a differential microbial abundance analysis, those characterized by cognitive decline had unique taxonomic shifts (Faecalibacterium, Bacteroides, Fusicatenibacter, Erysipelotrichaceae UCG-003, and Subdoligranulum) over chemotherapy treatment compared to those without cognitive decline. Taken together, gut microbiome change was associated with cognitive decline during chemotherapy, independent of chemotherapy-induced inflammation. These results suggest that microbiome-related strategies may be useful for predicting and preventing behavioral side effects of chemotherapy.

Maternal social environment shapes yolk testosterone allocation and embryonic neural gene expression in tree swallows.

Offspring from females breeding in competitive social environments are often exposed to more testosterone (T) during embryonic development, which can affect traits from growth to behavior in potentially adaptive ways. Despite the important role of maternally derived steroids in shaping offspring development, the molecular mechanisms driving these processes are currently unclear. Here, we use tree swallows (Tachycineta bicolor) to explore the effects of the maternal social environment on yolk T concentrations and genome-wide patterns of neural gene expression in embryos. We measured aggressive interactions among females breeding at variable densities and collected their eggs at two timepoints, including the day laid to measure yolk T concentrations and on embryonic day 11 to measure gene expression in whole brain samples. We found that females breeding in high-density sites experienced elevated rates of physical aggression and their eggs had higher yolk T concentrations. A differential gene expression and weighted gene co-expression network analysis indicated that embryos from high-density sites experienced an upregulation of genes involved in hormone, circulatory, and immune processes, and these gene expression patterns were correlated with yolk T levels and aggression. Genes implicated in neural development were additionally downregulated in embryos from high-density sites. These data highlight how early neurogenomic processes may be affected by the maternal social environment, giving rise to phenotypic plasticity in offspring.

Elucidating the pathogenesis behind arteriovenous malformations of the central nervous system: a bibliometric analysis.

Arteriovenous malformations (AVMs) are vascular malformations of the central nervous system (CNS) with potential for significant consequences. The exact pathophysiologic mechanism of AVM formation is not fully understood. This study aims to evaluate bibliometric parameters and citations of the literature of AVMs to provide an overview of how the field has evolved. We performed an electronic search on Web of Science to identify the top 100 published and indexed articles with the highest number of citations discussing the pathogenesis of AVMs. This study yielded 1863 articles, of which the top 100 were selected based on the highest total citation count. These articles included 24% basic science, 46% clinical, and 30% review articles. The most-cited article was a clinical article from 2003, and the most recent was published in 2022. The median number of authors was 6, with the highest being 46 for a clinical article. The top 5 journals were identified, with the highest impact factor being 20.1. 13 countries were identified, with the US contributing the most articles (approximately 70%). Regarding genes of investigation, VEGF was one of the early genes investigated, while more interested in RAS/MAPK has been garnered since 2015. There is a growing interest in AVM genomics and pathogenesis research. While progress has been made in understanding clinical aspects and risk factors, the exact pathophysiological mechanisms and genetic basis of AVM formation remain incompletely understood. Further investigation of key genes in AVM pathogenesis can allow identification of potential therapeutic targets.

A quantitative framework for patient-specific collision detection in proton therapy.

BACKGROUND: Beam modifying accessories for proton therapy often need to be placed in close proximity of the patient for optimal dosimetry. However, proton treatment units are larger in size and as a result the planned treatment geometry may not be achievable due to collisions with the patient. A framework that can accurately simulate proton treatment geometry is desired. PURPOSE: A quantitative framework was developed to model patient-specific proton treatment geometry, minimize air gap, and avoid collisions. METHODS: The patient's external contour is converted into the International Electrotechnique Commission (IEC) gantry coordinates following the patient's orientation and each beam's gantry and table angles. All snout components are modeled by three-dimensional (3D) geometric shapes such as columns, cuboids, and frustums. Beam-specific parameters such as isocenter coordinates, snout type and extension are used to determine if any point on the external contour protrudes into the various snout components. A 3D graphical user interface is also provided to the planner to visualize the treatment geometry. In case of a collision, the framework's analytic algorithm quantifies the maximum protrusion of the external contour into the snout components. Without a collision, the framework quantifies the minimum distance of the external contour from the snout components and renders a warning if such distance is less than 5 cm. RESULTS: Three different snout designs are modeled. Examples of potential collision and its aversion by snout retraction are demonstrated. Different patient orientations, including a sitting treatment position, as well as treatment plans with multiple isocenters, are successfully modeled in the framework. Finally, the dosimetric advantage of reduced air gap enabled by this framework is demonstrated by comparing plans with standard and reduced air gaps. CONCLUSION: Implementation of this framework reduces incidence of collisions in the treatment room. In addition, it enables the planners to minimize the air gap and achieve better plan dosimetry.

Clostridioides difficile utilizes siderophores as an iron source and FhuDBGC contributes to ferrichrome uptake.

IMPORTANCE: This study is the first example of C. difficile growing with siderophores as the sole iron source and describes the characterization of the ferric hydroxamate uptake ABC transporter (FhuDBGC). This transporter shows specificity to the siderophore ferrichrome. While not required for pathogenesis, this transporter highlights the redundancy in iron acquisition mechanisms that C. difficile uses to compete for iron during an infection.

Can handgrip strength measurements predict postural balance performance in older women?

OBJECTIVES: The link between handgrip strength and postural balance in older adults is not well understood. This study aimed to examine the correlations between postural balance performance and handgrip peak force and rate of force development (RFD) measurements in older women. METHODS: Twenty older women (67 ± 5 years) participated in this study. Handgrip contractions were used to assess peak force, peak RFD, and RFD at 0-100 (RFD100) and 0-200 (RFD200) ms. Postural balance was evaluated using a commercially designed balance testing device, which provides a measurement of static stability based on the sway index. RESULTS: There were significant correlations between sway index and handgrip peak force (r = -0.497, P = 0.026), peak RFD (r = -0.552, P = 0.012), RFD100 (r = -0.539, P = 0.014), and RFD200 (r = -0.499, P = 0.025). Stepwise multiple regression analysis indicated that handgrip peak RFD was the single best predictor of sway index (R2 = 0.305). The other variables, including peak force, did not add any unique variance to the stepwise prediction model. CONCLUSION: These findings suggest that handgrip strength, and in particular peak RFD, may be an effective parameter at predicting postural balance performance in older women.

Achieving Optimal Population Cardiovascular Health Requires an Interdisciplinary Team and a Learning Healthcare System: A Scientific Statement From the American Heart Association.

Population cardiovascular health, or improving cardiovascular health among patients and the population at large, requires a redoubling of primordial and primary prevention efforts as declines in cardiovascular disease mortality have decelerated over the past decade. Great potential exists for healthcare systems-based approaches to aid in reversing these trends. A learning healthcare system, in which population cardiovascular health metrics are measured, evaluated, intervened on, and re-evaluated, can serve as a model for developing the evidence base for developing, deploying, and disseminating interventions. This scientific statement on optimizing population cardiovascular health summarizes the current evidence for such an approach; reviews contemporary sources for relevant performance and clinical metrics; highlights the role of implementation science strategies; and advocates for an interdisciplinary team approach to enhance the impact of this work.

Sacubitril/Valsartan Off-Label Uses for Heart Failure.

Sacubitril/valsartan is an angiotensin receptor/neprilysin inhibitor that the Food and Drug Administration has indicated to reduce the risk of cardiovascular hospitalization and death in patients with left ventricular ejection fraction below normal and with no specified ejection-fraction cut-off. However, clinically significant patient groups were excluded or minimally represented in sacubitril/valsartan's pivotal clinical trials. Clinicians often encounter scenarios in which a sacubitril/valsartan off-label use may be beneficial, but limited resources are available to evaluate the efficacy and safety in these patients. This state-of-the-art review describes contemporary literature for sacubitril/valsartan Food and Drug Administration off-label indications to help clinicians assess its appropriateness in these selected, clinically important groups of patients: those with acute decompensated heart failure, acute coronary syndrome, peripartum cardiomyopathy, chemotherapy-induced cardiomyopathy, adult congenital heart disease, cardiomyopathy in dialysis patients, right ventricular failure, or durable left ventricular assist device.

Tipping the balance: The role of seed density, abiotic filters, and priority effects in seed-based wetland restoration.

Sowing native seeds is a common approach to reintroduce native plants to degraded systems. However, this method is often overlooked in wetland restoration despite the immense global loss of diverse native wetland vegetation. Developing guiding principles for seed-based wetland restoration is critical to maximize native plant recovery, particularly in previously invaded wetlands. Doing so requires a comprehensive understanding of how restoration manipulations, and their interactions, influence wetland plant community assembly. With a focus on the invader Phragmites australis, we established a series of mesocosm experiments to assess how native sowing density, invader propagule pressure, abiotic filters (water and nutrients), and native sowing timing (i.e., priority effects) interact to influence plant community cover and biomass in wetland habitats. Increasing the density of native seeds yielded higher native cover and biomass, but P. australis suppression with increasing sowing densities was minimal. Rather, community outcomes were largely driven by invader propagule pressure: P. australis densities of ≤500 seeds/m2 maintained high native cover and biomass. Low-water conditions increased the susceptibility of P. australis to dominance by native competitors. Early sowing of native seeds showed a large and significant benefit to native cover and biomass, regardless of native sowing density, suggesting that priority effects can be an effective restoration manipulation to enhance native plant establishment. Given the urgent wetland restoration need combined with the limited studies on seed-based wetland restoration, these findings provide guidance on restoration manipulations that are grounded in ecological theory to improve seed-based wetland restoration outcomes.

Economic Impact of Ambulatory Clinical Pharmacists in an Advanced Heart Failure Clinic.

BACKGROUND: Clinical pharmacists play pivotal roles in multidisciplinary heart failure (HF) teams through the management of HF pharmacotherapy, but no study has examined the economic impact of HF ambulatory clinical pharmacists in an advanced HF clinic. OBJECTIVE: The objective of the study was to evaluate the economic impact of HF ambulatory clinical pharmacist interventions in an advanced HF clinic using a cost-benefit analysis. METHODS: This prospective observational study detailed HF ambulatory clinical pharmacist interventions over 6 months in an advanced HF clinic in a single-center tertiary teaching hospital. The economic impact of the interventions was estimated based on the indirect cost savings with pharmacist interventions and direct cost savings recommendations. A cost-benefit analysis was performed to assess the cost of delivering the interventions compared with the benefits generated by clinical pharmacists. Results were reported as a benefit-cost ratio and net benefits. RESULTS: HF ambulatory clinical pharmacists made a total of 2,361 provider-accepted interventions over 6 months. Overall, the 3 most common intervention types were medication reconciliation (28.7%), dose change (20.8%), and addition of medication (12.3%). Anticoagulation (21.2%) was the most common intervened class of medication, followed by sodium-glucose cotransporter-2 inhibitor (12.3%) and angiotensin receptor neprilysin inhibitor (9.2%). The total net benefits were $55,553.24 over 6 months and the benefit-cost ratio was 1.55. CONCLUSION AND RELEVANCE: The addition of cardiology clinical pharmacists to an advanced HF clinic may be financially justified and cost-beneficial.

Psychometric validity and reliability of the 10- and 2-item Connor-Davidson resilience scales among a national sample of Americans responding to the Covid-19 pandemic: an item response theory analysis.

PURPOSE: Psychometric validity/reliability of 10-item and 2-item abbreviations of the Connor-Davidson Resilience Scale (CD-RISC-10; CD-RISC-2) was investigated via item response theory and classic approaches. METHODS: We sampled 5023 adult American participants in a June/July 2020 survey on the COVID-19 pandemic's psychological effects. Our questionnaire incorporated the CD-RISC-10 with other validated measures. CD-RISC-10 items were ranked on item-to-scale correlations, loadings on a one-factor confirmatory factor analysis model, and item slope/threshold parameters plus information curves from a unidimensional graded response model. Concurrent validity of the highest ranked item pair was evaluated vis-à-vis the CD-RISC-10 and CD-RISC-2. Internal consistency, based on average variance extracted (AVE) and multiple reliability coefficients, was also compared. Convergent/divergent validity was tested by correlating anxiety, depression, fear of COVID-19, anxiety sensitivity, coping, and personality measures with both scales and the highest ranked item pair. Binary agreement/classification indexes assessed inter-rater reliability. RESULTS: Items 2 and 9 from CD-RISC-10 ranked the highest. Reliability coefficients were > 0.93, > 0.72, and > 0.82 for the CD-RISC-10, CD-RISC-2, vs summation of items 2 and 9. AVEs were 0.66, 0.67, and 0.77. CD-RISC abbreviations and the summation of items 2 and 9 correlated negatively with anxiety (> - 0.43), depression (> - 0.42), and fear of COVID-19 (> - 0.34); positively with emotional stability (> 0.53) and conscientiousness (> 0.40). Compared to the CD-RISC-2, summative scores of items 2 and 9 more efficiently classified/discriminated high resilience on the CD-RISC-10. CONCLUSION: We confirmed construct validity/reliability of copyrighted CD-RISC abbreviations. The CD-RISC-10's items 2 and 9 were psychometrically more salient than the CD-RISC-2.

Evaluation of the Efficacy of Doxycycline, Ciprofloxacin, Levofloxacin, and Co-trimoxazole Using In Vitro and In Vivo Models of Q Fever.

Q fever, caused by the intracellular pathogen Coxiella burnetii, is traditionally treated using tetracycline antibiotics, such as doxycycline. Doxycycline is often poorly tolerated, and antibiotic-resistant strains have been isolated. In this study, we have evaluated a panel of antibiotics (doxycycline, ciprofloxacin, levofloxacin, and co-trimoxazole) against C. burnetii using in vitro methods (determination of MIC using liquid and solid media; efficacy assessment in a THP cell infection model) and in vivo methods (wax moth larvae and mouse models of infection). In addition, the schedule for antibiotic treatment has been evaluated, with therapy initiated at 24 h pre- or postchallenge. Both doxycycline and levofloxacin limited overt clinical signs during treatment in the AJ mouse model of aerosol infection, but further studies are required to investigate the possibility of disease relapse or incomplete bacterial clearance after the antibiotics are stopped. Levofloxacin was well tolerated and therefore warrants further investigation as an alternative to the current recommended treatment with doxycycline.

Derangement of hepatic polyamine, folate, and methionine cycle metabolism in cystathionine beta-synthase-deficient homocystinuria in the presence and absence of treatment: Possible implications for pathogenesis.

Cystathionine beta-synthase deficient homocystinuria (HCU) is a life-threatening disorder of sulfur metabolism. Our knowledge of the metabolic changes induced in HCU are based almost exclusively on data derived from plasma. In the present study, we present a comprehensive analysis on the effects of HCU upon the hepatic metabolites and enzyme expression levels of the methionine-folate cycles in a mouse model of HCU. HCU induced a 10-fold increase in hepatic total homocysteine and in contrast to plasma, this metabolite was only lowered by approximately 20% by betaine treatment indicating that this toxic metabolite remains unacceptably elevated. Hepatic methionine, S-adenosylmethionine, S-adenosylhomocysteine, N-acetlymethionine, N-formylmethionine, methionine sulfoxide, S-methylcysteine, serine, N-acetylserine, taurocyamine and N-acetyltaurine levels were also significantly increased by HCU while cysteine, N-acetylcysteine and hypotaurine were all significantly decreased. In terms of polyamine metabolism, HCU significantly decreased spermine and spermidine levels while increasing 5'-methylthioadenosine. Betaine treatment restored normal spermine and spermidine levels but further increased 5'-methylthioadenosine. HCU induced a 2-fold induction in expression of both S-adenosylhomocysteine hydrolase and methylenetetrahydrofolate reductase. Induction of this latter enzyme was accompanied by a 10-fold accumulation of its product, 5-methyl-tetrahydrofolate, with the potential to significantly perturb one­carbon metabolism. Expression of the cytoplasmic isoform of serine hydroxymethyltransferase was unaffected by HCU but the mitochondrial isoform was repressed indicating differential regulation of one­carbon metabolism in different sub-cellular compartments. All HCU-induced changes in enzyme expression were completely reversed by either betaine or taurine treatment. Collectively, our data show significant alterations of polyamine, folate and methionine cycle metabolism in HCU hepatic tissues that in some cases, differ significantly from those observed in plasma, and have the potential to contribute to multiple aspects of pathogenesis.

Manipulations of the gut microbiome alter chemotherapy-induced inflammation and behavioral side effects in female mice.

Chemotherapy treatment is associated with acute behavioral side effects (fatigue, anorexia) that significantly reduce patient quality of life and are dose-limiting, thereby increasing mortality (Kidwell et al., 2014). Disruptions to gut homeostasis (diarrhea, constipation, microbial dysbiosis) are also observed in patients receiving chemotherapy. In non-oncological patients, facets of mental health (fatigue, anxiety, depression) correlate with alterations in the gut microbiome, suggestive of a contribution of the gut in CNS disease etiology. The potential gut-to-brain pathway is poorly understood in patients receiving chemotherapy. Our prior studies have demonstrated a correlation between chemotherapy treatment, gut changes, peripheral and central inflammation, and behavioral symptoms in mice. Here we aimed to determine the extent to which chemotherapy-associated gut manipulations modulate the behavioral and biological consequences of chemotherapy. We measured sickness behaviors, peripheral and central inflammatory mediators, and anxiety in conventional or germ-free female mice: 1) cohabitating with mice of the opposite treatment group, 2) pre-treated with broad-spectrum antibiotics, or 3) given an intra-gastric gavage of gut content from chemotherapy-treated mice. In cohabitation studies, presumed coprophagia promoted body mass recovery, however strong associations with inflammation and behavior were not observed. Reduction of gut microbial alpha diversity via antibiotics did not prevent chemotherapy-associated side effects, however the relative abundances of the genera Tyzzerella, Romboutsia, and Turicibacter correlated with circulating inflammatory (IL-1ß) and behavioral outcomes (lethargy, anxiety-like behavior). A gut microbiota transplant from chemotherapy-treated mice decreased central locomotion in open field testing, increased circulating CXCL1, and increased hippocampal Il6 and Tnfa in germ-free mice compared to germ-free mice that received a transplant from vehicle-treated mice. Taken together, these data provide further evidence that the gut microbiota likely contributes to the development of chemotherapy-associated side effects. This work has significant implications in the future treatment of anxiety in patients, and warrants future studies using microbe-based treatment options.

Imaging mass spectrometry: a new way to distinguish dermal contact from administration of cocaine, using a single fingerprint.

Here we show a new and significant application area for mass spectrometry imaging. The potential for fingerprints to reveal drug use has been widely reported, with potential applications in forensics and workplace drug testing. However, one unsolved issue is the inability to distinguish between drug administration and contamination by contact. Previous work using bulk mass spectrometry analysis has shown that this distinction can only be definitively made if the hands are washed prior to sample collection. Here, we illustrate how three mass spectrometry imaging approaches, desorption electrospray ionisation (DESI), matrix assisted laser desorption ionisation (MALDI) and time of flight secondary ion mass spectrometry (ToF-SIMS) can be used to visualise fingerprints at different pixel sizes, ranging from the whole fingerprint down to the pore structure. We show how each of these magnification scales can be used to distinguish between cocaine use and contact. We also demonstrate the first application of water cluster SIMS to a fingerprint sample, which was the sole method tested here that was capable of detecting excreted drug metabolites in fingerprints, while providing spatial resolution sufficient to resolve individual pore structure. We show that after administration of cocaine, lipids and salts in the fingerprint ridges spatially correlate with the cocaine metabolite, benzoylecgonine. In contrast after contact, we have observed that cocaine and its metabolite show a poor spatial correlation with the flow of the ridges.

A pilot multicentre randomised controlled trial of lidocaine infusion in women undergoing breast cancer surgery.

Chronic postoperative pain is common after breast cancer surgery. Peri-operative lidocaine infusion may prevent the development of chronic postoperative pain, but a large-scale trial is required to test this hypothesis. It is unclear whether a pragmatic, multicentre trial design that is consistent with expert guidance, addresses the limitations of previous studies, and overcomes existing translational barriers is safe, effective and feasible. We conducted a double-blind, randomised controlled pilot study in 150 patients undergoing breast cancer surgery across three hospitals in Western Australia. Patients received lidocaine, or equivalent volumes of saline, as an intravenous bolus (1.5 mg.kg-1 ) and infusion (2 mg.kg-1 .h-1 ) intra-operatively, and a subcutaneous infusion (1.33 mg.kg-1 .h-1 ) postoperatively for up to 12 h on a standard surgical ward, with novel safety monitoring tools in place. The co-primary outcomes were: in-hospital safety events; serum levels of lidocaine during intravenous and subcutaneous infusion; and annualised enrolment rates per site with long-term data capture. In-hospital safety events were rare, and similar in the placebo and lidocaine arms (3% vs. 1%). Median (IQR [range]) serum lidocaine levels during intravenous (2.16 (1.74-2.83 [1.12-6.06]) µg.ml-1 , n = 41) and subcutaneous (1.52 (1.28-1.83 [0.64-2.85]) µg.ml-1 , n = 48) infusion were comparable with previous trials reporting improved pain outcomes. Annualised enrolment approximated 50 patients per site per year, with high levels of protocol adherence and ≥ 99% capture of outcomes at 3 and 6 months. The adjusted odds ratio (95%CI) for postoperative pain at 6 months in the lidocaine arm was 0.790 (0.370-1.684). We conclude that this trial, as designed, is safe, effective and feasible in patients undergoing breast cancer surgery, and a larger-scale trial is planned.

CPAP adherence reduces cardiovascular risk among older adults with obstructive sleep apnea.

STUDY OBJECTIVES: To examine (1) the impact of adherence to continuous positive airway pressure (CPAP) therapy on risk for cardiovascular (CVD) events among a nationally representative sample of older adults with obstructive sleep apnea (OSA), and (2) the heterogeneity of this effect across subgroups defined by race, sex, and socioeconomic status. METHODS: We conducted a retrospective cohort study among Medicare beneficiaries aged ≥ 65 years with OSA (2009-2013). Monthly indicators of CPAP adherence (charges for machines, masks, or supplies) were summed over 25 months to create a CPAP adherence variable. New CVD events (ischemic heart disease, cardiac and peripheral procedures) were modeled as a function of CPAP adherence using generalized estimating equations. Heterogeneity of the effect of CPAP on new CVD events was evaluated based on race, sex, and socioeconomic status. RESULTS: Among 5024 beneficiaries diagnosed with OSA who initiated CPAP, 1678 (33%) demonstrated new CVD events. Following adjustment for demographic and clinical characteristics, CPAP adherence was associated with reduced risk of new CVD events (hazard ratio 0.95; 95% confidence interval 0.94, 0.96) over 25 months. When analyses were stratified by time since the first CPAP charge, the protective effect remained significant for the 12- and 6-month, but not 3-month, outcome models. No significant differences were observed in the protective effect of CPAP based on race, sex, or socioeconomic status. CONCLUSIONS: In this national study of older adult Medicare beneficiaries with OSA, CPAP adherence was associated with greatly reduced risk for CVD events. This risk reduction was consistent across race, sex, and socioeconomic subgroups.

Functional Outcomes in Patients Admitted to the Intensive Care Unit with Traumatic Brain Injury and Exposed to Hyperoxia: A Retrospective Multicentre Cohort Study.

BACKGROUND: Supplemental oxygen administration to critically ill patients is ubiquitous in the intensive care unit (ICU). Uncertainty persists as to whether hyperoxia is benign in patients with traumatic brain injury (TBI), particularly in regard to their long-term functional neurological outcomes. METHODS: We conducted a retrospective multicenter cohort study of invasively ventilated patients with TBI admitted to the ICU. A database linkage between the Australian and New Zealand Intensive Care Society Adult Patient Database (ANZICS-APD) and the Victorian State Trauma Registry (VSTR) was utilized. The primary exposure variable was minimum acute physiology and chronic health evaluation (APACHE) III PaO2 in the first 24 h of ICU. We defined hypoxia as PaO2 < 60 mmHg, normoxia as 60-299 mmHg, and hyperoxia as ≥ 300 mmHg. The primary outcome was a Glasgow Outcome Scale-Extended (GOSE) < 5 at 6 months while secondary outcomes included 12 and 24 months GOSE and mortality at each of these timepoints. Additional sensitivity analyses were undertaken in the following subgroups: isolated head injury, patients with operative intervention, head injury severity, and PaO2 either subcategorized by increments of 60 mmHg or treated as a continuous variable. RESULTS: A total of 3699 patients met the inclusion criteria. The mean age was 42.8 years, 77.7% were male and the mean acute physiology and chronic health evaluation (APACHE) III score was 60.1 (26.3). 2842 patients experienced normoxia, and 783 hyperoxia. The primary outcome occurred in 1470 (47.1%) of patients overall with 1123 (47.1%) from the normoxia group and 312 (45.9%) from the hyperoxia group-odds ratio 0.99 (0.78-1.25). No significant differences in outcomes between groups at 6, 12, and 24 months were observed. Sensitivity analyses did not identify subgroups that were adversely affected by exposure to hyperoxia. CONCLUSIONS: No associations were observed between hyperoxia in ICU during the first 24 h and adverse neurological outcome at 6 months in ventilated TBI patients.

Relationships between hamstring morphological characteristics and postural balance in elderly men.

OBJECTIVES: The link between hamstring morphology and postural balance performance in older adults is not well understood. This study aimed to examine the relationships between hamstring morphological characteristics of muscle size (cross-sectional area [CSA]) and quality (echo intensity [EI]) and postural balance with the eyes open and closed in elderly men. METHODS: Nineteen healthy elderly men (age= 73±4 years) participated in this study. Muscle CSA and EI were determined from ultrasound scans of the hamstrings. Postural balance was assessed with the eyes open and closed using a commercially designed balance testing device, which provides a measurement of static stability based on the sway index. RESULTS: The sway index with eyes closed was significantly related to muscle EI (r=0.474; P=0.040) but not CSA (r=0.021; P=0.932). The sway index with eyes open was not related to muscle CSA (r= -0.036; P=0.883) or EI (r=-0.079; P=0.747). CONCLUSIONS: The significant relationship observed between the sway index with eyes closed and muscle EI suggests that hamstring muscle quality may be a characteristic relevant to postural balance in the absence of visual feedback. These findings may provide important insight regarding the morphological mechanisms involved in maintaining balance and in the development of proper training programs aimed at improving postural stability in older individuals.

Borderline anaemia and postoperative outcome in women undergoing major abdominal surgery: a retrospective cohort study.

Pre-operative anaemia is typically diagnosed with a haemoglobin concentration < 120 g.l-1 for women and < 130 g.l-1 for men on the basis of limited evidence. This retrospective cohort study stratified women undergoing elective, major abdominal surgery based on pre-operative haemoglobin concentration: anaemic (< 120 g.l-1 ); borderline anaemic (120-129 g.l-1 ); and non-anaemic (> 130 g.l-1 ). Data from 1554 women were analysed. Women with borderline anaemia had a greater incidence of postoperative complications (55 (16%) vs. 110 (11%); p = 0.026), longer duration of hospital stay (median (IQR [range]) 3 (1-6 [0-69]) days vs. 2 (1-5 [0-80]) days; p = 0.017) and fewer days alive and out of hospital at postoperative day 30 (median (IQR [range]) 27 (23-29 [0-30]) vs. 28 (25-29 [0-30]) days; p = 0.017) compared with non-anaemic women. However, after matched cohort analysis, these outcome differences no longer remained statistically significant. After multivariable adjustment for procedure, Charlson comorbidity index and patient age, a negative relationship between logarithmic pre-operative haemoglobin concentration and duration of stay was found (parameter estimate (standard error) -0.006 (0.003) vs. 0.003 (0.003) for a haemoglobin concentration < 130 g.l-1 vs. > 130 g.l-1 , respectively; p = 0.03); the difference in duration of stay was approximately 50% greater for women with a haemoglobin concentration of 120 g.l-1 compared with those with a haemoglobin concentration of 130 g.l-1 . Although the contribution of borderline anaemia to the incidence of postoperative complications is uncertain, the current diagnostic criteria should be re-assessed.