First Results from a Broadband Search for Dark Photon Dark Matter in the 44 to 52 µeV Range with a Coaxial Dish Antenna.

We present first results from a dark photon dark matter search in the mass range from 44 to 52 µeV (10.7-12.5 GHz) using a room-temperature dish antenna setup called GigaBREAD. Dark photon dark matter converts to ordinary photons on a cylindrical metallic emission surface with area 0.5 m^{2} and is focused by a novel parabolic reflector onto a horn antenna. Signals are read out with a low-noise receiver system. A first data taking run with 24 days of data does not show evidence for dark photon dark matter in this mass range, excluding dark photon photon mixing parameters χ≳10^{-12} in this range at 90% confidence level. This surpasses existing constraints by about 2 orders of magnitude and is the most stringent bound on dark photons in this range below 49 µeV.

International Care programs for Pediatric Post-COVID Condition (Long COVID) and the way forward.

BACKGROUND: Pediatric Post-COVID-Condition (PPCC) clinics treat children despite limited scientific substantiation. By exploring real-life management of children diagnosed with PPCC, the International Post-COVID-Condition in Children Collaboration (IP4C) aimed to provide guidance for future PPCC care. METHODS: We performed a cross-sectional international, multicenter study on used PPCC definitions; the organization of PPCC care programs and patients characteristics. We compared aggregated data from PPCC cohorts and identified priorities to improve PPCC care. RESULTS: Ten PPCC care programs and six COVID-19 follow-up research cohorts participated. Aggregated data from 584 PPCC patients was analyzed. The most common symptoms included fatigue (71%), headache (55%), concentration difficulties (53%), and brain fog (48%). Severe limitations in daily life were reported in 31% of patients. Most PPCC care programs organized in-person visits with multidisciplinary teams. Diagnostic testing for respiratory and cardiac morbidity was most frequently performed and seldom abnormal. Treatment was often limited to physical therapy and psychological support. CONCLUSIONS: We found substantial heterogeneity in both the diagnostics and management of PPCC, possibly explained by scarce scientific evidence and lack of standardized care. We present a list of components which future guidelines should address, and outline priorities concerning PPCC care pathways, research and international collaboration. IMPACT: Pediatric Post-COVID Condition (PPCC) Care programs have been initiated in many countries. Children with PPCC in different countries are affected by similar symptoms, limiting many to participate in daily life. There is substantial heterogeneity in diagnostic testing. Access to specific diagnostic tests is required to identify some long-term COVID-19 sequelae. Treatments provided were limited to physical therapy and psychological support. This study emphasizes the need for evidence-based diagnostics and treatment of PPCC. The International Post-COVID Collaboration for Children (IP4C) provides guidance for guideline development and introduces a framework of priorities for PPCC care and research, to improve PPCC outcomes.

The AI-driven Drug Design (AIDD) platform: an interactive multi-parameter optimization system integrating molecular evolution with physiologically based pharmacokinetic simulations.

Computer-aided drug design has advanced rapidly in recent years, and multiple instances of in silico designed molecules advancing to the clinic have demonstrated the contribution of this field to medicine. Properly designed and implemented platforms can drastically reduce drug development timelines and costs. While such efforts were initially focused primarily on target affinity/activity, it is now appreciated that other parameters are equally important in the successful development of a drug and its progression to the clinic, including pharmacokinetic properties as well as absorption, distribution, metabolic, excretion and toxicological (ADMET) properties. In the last decade, several programs have been developed that incorporate these properties into the drug design and optimization process and to varying degrees, allowing for multi-parameter optimization. Here, we introduce the Artificial Intelligence-driven Drug Design (AIDD) platform, which automates the drug design process by integrating high-throughput physiologically-based pharmacokinetic simulations (powered by GastroPlus) and ADMET predictions (powered by ADMET Predictor) with an advanced evolutionary algorithm that is quite different than current generative models. AIDD uses these and other estimates in iteratively performing multi-objective optimizations to produce novel molecules that are active and lead-like. Here we describe the AIDD workflow and details of the methodologies involved therein. We use a dataset of triazolopyrimidine inhibitors of the dihydroorotate dehydrogenase from Plasmodium falciparum to illustrate how AIDD generates novel sets of molecules.

Massage therapy for children, adolescents, and young adults: Clinical delivery and effectiveness in hematology and oncology.

BACKGROUND: Children, adolescents, and young adults with hematologic and/or oncologic conditions experience multiple, significant symptoms (e.g., pain, stress, and anxiety), which may be addressed by nonpharmacologic approaches such as massage therapy (MT). The purpose of this study was to describe the clinical delivery of MT provided by a certified pediatric massage therapist and assess effectiveness in two patient groups: those with sickle cell disease (SCD) or hematologic and/or oncologic conditions excluding SCD (HemOnc). METHODS: Investigators conducted a retrospective review of MT sessions provided to patients 0-39 years with hematologic and/or oncologic conditions at a large pediatric academic medical center. RESULTS: Between October 2019 and December 2021, 3015 MT sessions were provided to 243 patients (171 HemOnc; 72 SCD) and documented in the electronic health record. Patients (mean age: 12.21 ± 7.19 years) were generally White (49.4%) or Black/African American (43.2%), non-Hispanic (94.2%), and 52.3% female. Patients in the SCD group (vs. patients in the HemOnc group) reported significantly higher (p < .05) pretreatment pain (6.95 vs. 4.46), stress (6.47 vs. 4.58), and anxiety (6.67 vs. 4.59). All patients reported clinically and statistically significant (p < .001) mean reductions in pain (-2.25 ± 1.87), stress (-2.50 ± 1.73), and anxiety (-2.52 ± 1.69), with patients in the HemOnc group reporting greater mean pain change (-2.54 vs. -1.87) than patients in the SCD group. CONCLUSIONS: This study supports the clinical effectiveness of MT for addressing acute pain, stress, and anxiety among youth with hematologic and/or oncologic conditions. Future research is needed to identify optimal MT utilization.

Broadband Solenoidal Haloscope for Terahertz Axion Detection.

We introduce the Broadband Reflector Experiment for Axion Detection (BREAD) conceptual design and science program. This haloscope plans to search for bosonic dark matter across the [10^{-3},1] eV ([0.24, 240] THz) mass range. BREAD proposes a cylindrical metal barrel to convert dark matter into photons, which a novel parabolic reflector design focuses onto a photosensor. This unique geometry enables enclosure in standard cryostats and high-field solenoids, overcoming limitations of current dish antennas. A pilot 0.7 m^{2} barrel experiment planned at Fermilab is projected to surpass existing dark photon coupling constraints by over a decade with one-day runtime. Axion sensitivity requires <10^{-20} W/sqrt[Hz] sensor noise equivalent power with a 10 T solenoid and 10 m^{2} barrel. We project BREAD sensitivity for various sensor technologies and discuss future prospects.

Early diagnosis of acute kidney injury subsequent to severe hypotension and fluid resuscitation in anaesthetized dogs.

OBJECTIVES: To document changes in urinary biomarker concentration and conventional diagnostic tests of acute kidney injury (AKI) following hypotension and fluid resuscitation in anaesthetized dogs. STUDY DESIGN: Experimental, repeated measures, prospective study. ANIMALS: A group of six male adult Greyhound dogs. METHODS: Following general anaesthesia, severe hypotension was induced by phlebotomy, maintaining mean arterial blood pressure (MAP) < 40 mmHg for 60 minutes, followed by resuscitation with intravenous gelatine solution to maintain MAP > 60 mmHg for 3 hours. Following euthanasia, renal tissue was examined by light microscopy (LM) and transmission electron microscopy (TEM). Urinary and serum concentrations of neutrophil gelatinase-associated lipocalin (NGAL), cystatin C (CysC), and gamma-glutamyl transpeptidase (GGT), serum creatinine and urine output were measured at baseline and hourly until euthanasia. Data are presented as mean and 95% confidence interval and analysed using repeated measures analysis of variance with Dunnett's adjustment, p < 0.05. RESULTS: Structural damage to proximal renal tubular cells was evident on LM and TEM. Urinary biomarker concentrations were significantly elevated from baseline, peaking 2 hours after haemorrhage at 19.8 (15.1-25.9) ng mL-1 NGAL (p = 0.002), 2.54 (1.64-3.43) mg mL-1 CysC (p = 0.009) and 2043 (790-5458) U L-1 GGT (p < 0.001). Serum creatinine remained within a breed-specific reference interval in all dogs. Urinary protein-creatinine ratio (UPC) was significantly elevated in all dogs from 1 hour following haemorrhage. CONCLUSIONS AND CLINICAL RELEVANCE: Urinary NGAL, CysC and GGT concentrations, and UPC were consistently elevated within 1 hour of severe hypotension, suggesting that proximal renal tubules are damaged in the earliest stage of ischaemia-reperfusion AKI. Measurement of urinary biomarkers may allow early diagnosis of AKI in anaesthetized dogs. Urinary GGT concentration and UPC are particularly useful as they can be measured on standard biochemistry analysers.

Serum creatinine is a poor marker of a predicted change in muscle mass in lactating sows.

Serum creatinine (SCr) in humans has proven to be a reliable biomarker of body protein breakdown and/or muscle mass change. This study set out to investigate the potential of SCr to indicate a loss in sow muscle mass over lactation, validated against 3 methyl histidine (3MH) and blood urea nitrogen (BUN), markers of dietary and/or body protein breakdown. A total of 40 sows were allocated to four treatment groups aimed to induce body weight changes by restrictively feeding sows using a stepwise percentage reduction model. Data were pooled and reallocated into three groups representing the 25th , 50th and 75th percentiles based on body weight change over lactation in the range -22.3 to -4.1% (treatment 25), -4.0 to 6.2% (Treatment 50), and 6.3-15.2% (Treatment 75). Indirect measures for the prediction of protein (3MH, BUN) or fat change (caliper, P2) were taken on entry into the farrowing house, day 5 of lactation, and at weaning. Serum was collected on these days, and SCr, 3MH and BUN were analysed. Piglet weaning weight and average daily feed intake did not differ between treatments (p > .05). There were no changes (p > .05) in indirect measures of body composition (sow caliper score, P2) and analytes (SCr, 3MH, BUN) over lactation. By day 20, those sows in treatment 25 had higher (p < .05) 3MH concentrations whilst changes from day 5 to 20 were not different (p > .05) and did not correlate with SCr change (p > .05) but were highly correlated to BUN change (R2 = 0.691, p < .001). The data suggested that concentrations of SCr and BUN may have been the result of dietary and/or body protein breakdown and/or changes in muscle mass. In the current testing conditions, SCr was not a reliable marker of changes in muscle mass.

Caspase-1 causes truncation and aggregation of the Parkinson's disease-associated protein α-synuclein.

The aggregation of α-synuclein (aSyn) leading to the formation of Lewy bodies is the defining pathological hallmark of Parkinson's disease (PD). Rare familial PD-associated mutations in aSyn render it aggregation-prone; however, PD patients carrying wild type (WT) aSyn also have aggregated aSyn in Lewy bodies. The mechanisms by which WT aSyn aggregates are unclear. Here, we report that inflammation can play a role in causing the aggregation of WT aSyn. We show that activation of the inflammasome with known stimuli results in the aggregation of aSyn in a neuronal cell model of PD. The insoluble aggregates are enriched with truncated aSyn as found in Lewy bodies of the PD brain. Inhibition of the inflammasome enzyme caspase-1 by chemical inhibition or genetic knockdown with shRNA abated aSyn truncation. In vitro characterization confirmed that caspase-1 directly cleaves aSyn, generating a highly aggregation-prone species. The truncation-induced aggregation of aSyn is toxic to neuronal culture, and inhibition of caspase-1 by shRNA or a specific chemical inhibitor improved the survival of a neuronal PD cell model. This study provides a molecular link for the role of inflammation in aSyn aggregation, and perhaps in the pathogenesis of sporadic PD as well.

Right Atrial Anomalous Muscle Bundle Presenting with Acute Superior Vena Cava Syndrome and Pulmonary Embolism: Surgical Management.

BACKGROUND: An anomalous muscle bundle (AMB) crossing the right atrial cavity represents a pathologic finding with unproved clinical significance. This congenital anomaly may be difficult to recognize via echocardiography and could be confused with other intracavitary lesions. METHODS: We report the case of a 53-year-old woman presented to the cardiovascular service with acute superior vena cava (SVC) syndrome and submassive pulmonary embolism. RESULTS: The patient underwent venography, confirming SVC stenosis. A ventilation/perfusion lung scan showed 2 sizable perfusion defects because of pulmonary embolism. Magnetic resonance imaging and echocardiography imaging demonstrated a right atrium (RA) mass. Surgery was then carried out using standard cardiopulmonary bypass; the right atrial muscle bundle was excised, and SVC reconstruction was performed. The patient was discharged uneventfully and remains symptom-free at 2-year follow-up. CONCLUSIONS: In cases of nonmalignant pathology of SVC syndrome, appropriate studies should be conducted to exclude potential congenital abnormalities such as this AMB in the RA. Open-heart surgery is a viable treatment option in select cases.

Respiratory oxygen uptake is associated with survival in a cohort of ventilated trauma and burn patients.

BACKGROUND: Little data is available in the literature about the role of end tidal oxygen in critically ill patients. We sought to identify the association between the level of respiratory oxygen and clinical outcomes in critically-ill ventilated trauma and burn patients. METHODS: A retrospective cohort of 55 trauma and burn patients from 2010 to 2016 was collected. Exposures of interest included a) expiratory end tidal oxygen (ETO2) and b) the difference between FiO2 and ETO2 (uptake). Associations of clinical characteristics with ETO2 and oxygen uptake were examined using a Spearman correlation. The relationships between discharge status, demographics, injury type, severity, and clinical characteristics were examined using chi-square (or Fisher's exact) tests and two-sample t-tests. Multivariable analyses using linear and logistic regression were performed to determine whether expiratory end tidal oxygen or oxygen uptake was an independent predictor of clinical outcomes. RESULTS: Mean age for the patients was 46.3±18.2years with 41 (74.6%) male and 34 (61.8%) white. In the cohort, 27 (49.1%) of patients had burns and 28 (50.9%) blunt trauma. Oxygen uptake was negatively correlated with lactic acid, minute ventilation, total ICU days, and ventilator days (p<0.05). Patients who died demonstrated lower oxygen uptake than those alive, oxygen uptake remained significantly associated with discharge status after adjusting for potential confounders (p=0.028). CONCLUSION: A narrowed difference between ETO2 and inspiratory oxygen is associated with increased mortality in a cohort of ventilated trauma and burn patients. Future research is needed to further elucidate the role of respiratory oxygen level in larger, prospective studies.

Urinary neutrophil gelatinase-associated lipocalin concentration changes after acute haemorrhage and colloid-mediated reperfusion in anaesthetized dogs.

OBJECTIVE: To determine changes in urine neutrophil gelatinase-associated lipocalin concentration (uNGAL) in anaesthetized Greyhound dogs that developed acute tubular damage following haemorrhage and resuscitation with colloid-based fluids. STUDY DESIGN: Prospective experimental study. ANIMALS: Seven healthy adult entire male Greyhound dogs. METHODS: During isoflurane anaesthesia, approximately 50 mL kg(-1) of blood was removed to maintain mean arterial pressure (MAP) ≤40 mmHg for 1 hour followed by gelatin-based colloid administration to maintain MAP ≥60 mmHg for 3 hours. Data, including oxygen extraction ratio and uNGAL, were collected before (T0) and immediately following (T1) haemorrhage, and hourly during reperfusion (T2-T4). After T4, dogs were euthanized and renal tissue was collected for histology. Statistical analysis was performed using repeated-measures one-way anova. Data are presented as means (95% confidence interval). RESULTS: Histology identified renal tubular epithelial damage in all dogs. Urine NGAL concentration increased from 12.1 (0-30.6) ng mL(-1) at T0 to 122.0 (64.1-180.0) ng mL(-1) by T3. Compared with T0, uNGAL was significantly higher at T3 (p = 0.016) and was increased 24-fold. CONCLUSIONS AND CLINICAL RELEVANCE: Despite wide individual variation in baseline uNGAL, increases in uNGAL were observed in all dogs, suggesting that this biomarker has the potential to detect renal tubular injury following haemorrhage-induced hypotension and colloid-mediated reperfusion.

New-onset refractory status epilepticus (NORSE)--The potential role for immunotherapy.

New-onset refractory status epilepticus (NORSE) is defined as a state of persistent seizures with no identifiable etiology in patients without preexisting epilepsy that lasts longer than 24h despite optimal therapy. Management of NORSE is challenging, and the role of immunotherapy (IT) is unclear. We identified patients fulfilling the criteria for NORSE at a single institution. These patients were described, analyzed, and compared with NORSE cases available from the literature. Finally, a pooled analysis of available case series was conducted to compare the outcomes in patients who received IT with those not treated with IT during the course of NORSE in order to generate hypotheses for further research. In our case series, NORSE was diagnosed in 11 patients (9 females) with a mean age of 48 years and a mean duration of 54.4 days. Autoantibodies were identified in 7 patients, of which anti-GAD (glutamic acid decarboxylase) and anti-NMDAR (N-methyl-D-aspartate receptor) were most frequent. Of the 11 patients, 8 were treated with IT (intravenous steroids, immunoglobulins, plasmapheresis, or a combination), and 4 received chemotherapy. Of the 8 patients treated with IT, 6 had favorable outcomes (defined as any outcome other than death, vegetative state, or inability to take care of oneself) compared with 0 out of 3 patients who did not receive IT. Difference in outcomes was significant (p=0.026). Pooled analysis of all identified case series, including ours, showed a statistically significant effect (p=0.022), with favorable outcomes in 42% of the patients who received any IT compared with 20% in those who did not. In all patients with refractory SE and negative comprehensive investigations, a diagnosis of NORSE should be considered. This would aid planning for early immunotherapy. Currently, only Class IV evidence for the use of immunotherapy in NORSE is available. Prospective multicenter studies are necessary to assess the true efficacy of IT in NORSE.

Predictors of systemic inflammatory response syndrome in ischemic stroke undergoing systemic thrombolysis with intravenous tissue plasminogen activator.

BACKGROUND: Systemic inflammatory response syndrome (SIRS) is an inflammatory process associated with poor outcomes in acute ischemic stroke (AIS) patients. However, no study to date has investigated predictors of SIRS in AIS patients treated with intravenous (IV) tissue plasminogen activator (tPA). METHODS: Consecutive patients were retrospectively reviewed for evidence of SIRS during their acute hospitalization. SIRS was defined as the presence of 2 or more of the following: (1) body temperature less than 36°C or greater than 38°C, (2) heart rate greater than 90, (3) respiratory rate greater than 20, or (4) white blood cell count less than 4000/mm or greater than 12,000/mm or more than 10% bands for more than 24 hours. Those diagnosed with an infection were excluded. A scoring system was created to predict SIRS based on patient characteristics available at the time of admission. Logistic regression was used to evaluate potential predictors of SIRS using a sensitivity cutoff of ≥65% or area under the curve of .6 or more. RESULTS: Of 212 patients, 44 had evidence of SIRS (21%). Patients with SIRS were more likely to be black (61% versus 54%; P = .011), have lower median total cholesterol at baseline (143 versus 167 mg/dL; P = .0207), and have history of previous stroke (51% versus 35%; P = .0810). Ranging from 0 to 6, the SIRS prediction score consists of African American (2 points), history of hypertension (1 point), history of previous stroke (1 point), and admission total cholesterol less than 200 (2 points). Patients with an SIRS score of 4 or more were 3 times as likely to develop SIRS when compared with patients with a score of ≤3 (odds ratio = 2.815, 95% confidence interval 1.43-5.56, P = .0029). CONCLUSIONS: In our sample of IV tPA-treated AIS patients, clinical and laboratory characteristics available on presentation were able to identify patients likely to develop SIRS during their acute hospitalization. Validation is required in other populations. If validated, this score could assist providers in predicting who will develop SIRS after treatment with IV tPA.

Welfare and performance benefits of shade provision during summer for feedlot cattle in a temperate climatic zone.

There is increasing interest from cattle lot-feeders in the use of shade to mitigate the effects of a potential heat stress event, though it is unclear whether the reported benefits of shade in previous studies conducted in more high-risk heat stress zones are pertinent in cooler temperate zones. The objectives of this study were to measure the welfare and performance benefits of shade provision for lot-fed cattle at a commercial feedlot located in a mild heat-stress risk zone in Western Australia. Six blocks of black Angus (Bos taurus) steers were inducted into the feedlot over six time-windows across a southern hemisphere summer, with 80 cattle per block housed in a partially shaded pen (providing 3.125 m2 of shade per animal) and 80 in an unshaded pen. Parameters assessed in 960 cattle over the first 70 days in the feedlot included weight gain, feed intake, and physiological and behavioral indices of overall health and welfare. Over the months of October through to May in which the experiment was conducted, shaded cattle demonstrated a modest 0.13 kg overall increase in average daily gain across the 70-day feedlot period (P = 0.13). There was no difference in dry matter intake between any block or treatment. The physiological and behavioral markers of health and welfare revealed that, even during to hottest times of the experiment, the cattle were quite able to thermoregulate, via increased panting and seeking shade (if available), to maintain physiological homeostasis. In addition, we measured the effect of heat stress and shade provision on the affective state of the cattle. Qualitative behavioral assessment was used to indicate that the cattle in the 'no stress' temperature humidity index (THI) category and the shaded cattle in the 'moderate stress' THI category displayed the most positive demeanor (P < 0.05), being described as more 'settled and sociable', while the unshaded cattle in the 'moderate stress' THI category and all cattle in the 'severe stress' THI category were described as more 'agitated/anxious' (P < 0.05). Overall, the findings from the present study suggest that there are definite welfare and modest performance benefits associated with providing cattle with shade in summer in a feedlot situated in a temperate climatic zone.

Mind-Body Interventions for Youth with Chronic Medical Conditions: A Scoping Review of the Literature.

Background and purpose: Little is known about the applicability, utilization, and effectiveness of mind-body interventions (MBIs) for conditions that are not predominantly pain, neoplastic, or psychiatric, particularly in pediatric patients. This scoping review describes research pertaining to such interventions in youth with nonpain, noncancer, and nonpsychiatric predominant chronic medical conditions. Methods: Searches of EBSCO CINAHL, Elsevier Scopus, Ovid for MEDLINE, and Ovid PsycInfo were conducted to investigate MBIs in youth under 18 years of age with nonpain, noncancer, and nonpsychiatric predominant chronic medical conditions. Articles published between 2010 and 2020 were included. Abstracts were screened by three authors for inclusion, and disagreements were resolved by a designated author. Selected full-text articles were divided among all authors for review of study quality, intervention feasibility and acceptability, and effectiveness. Results: The search yielded 1010 titles with 15 meeting the final inclusion criteria, studying a total of 641 youth. Participants ranged in age from 6 to 19 years (included studies had data on participants <18 years reported separately); 61.5% were female (n = 394) and 38.5% were male (n = 247). The two most common conditions studied were asthma and irritable bowel syndrome, with yoga being the most popular intervention. Overall, MBIs showed promising preliminary evidence for improving symptoms and quality of life in youth with chronic medical conditions. Conclusion: MBIs have been successfully delivered and show promise in symptom palliation and quality of life improvement for youth with a variety of chronic medical conditions. More data from high-quality randomized controlled trials are needed to further characterize the effectiveness of specific modalities for specific conditions.

Systemic inflammatory response syndrome in tissue-type plasminogen activator-treated patients is associated with worse short-term functional outcome.

BACKGROUND AND PURPOSE: Systemic inflammatory response syndrome (SIRS) is a generalized inflammatory state. The primary goal of the study was to determine whether differences exist in outcomes in SIRS and non-SIRS intravenous tissue-type plasminogen activator-treated patients. METHODS: Consecutive patients were retrospectively reviewed for the evidence of SIRS during their admission. SIRS was defined as the presence of ≥2 of the following: body temperature<36°C or >38°C, heart rate>90, respiratory rate>20, and white blood cells<4000/mm or >12 000 mm, or >10% bands. Patients diagnosed with infection (via positive culture) were excluded. RESULTS: Of the 241 patients, 44 had evidence of SIRS (18%). Adjusting for pre-tissue-type plasminogen activator National Institutes of Health Stroke Scale, age, and race, SIRS remained a predictor of poor functional outcome at discharge (odds ratio [OR], 2.58; 95% confidence interval [CI], 1.16-5.73; P=0.0197). CONCLUSIONS: In our sample of tissue-type plasminogen activator-treated (tPA) patients, ~1 in 5 patients developed SIRS. Furthermore, we found the presence of SIRS to be associated with poor short-term functional outcomes and prolonged length of stay.

Single-use instrumentation, cutting blocks, and trials decrease contamination during total knee arthroplasty: a prospective comparison of navigated and nonnavigated cases.

The purpose of this prospective controlled trial was to determine whether decrease in contamination could be achieved in nonnavigated and navigated total knee arthroplasties by replacing traditional saws, cutting blocks, and trials with specialized saws and single-use cutting blocks and trials. Various tray wrapping metrics during total knee arthroplasty were measured in 400 procedures performed by 8 different surgeons at 6 institutions. Instrumentation contamination was determined by counting the number of tray sterility indicators, pans, and instruments that were compromised. The results show that a decrease in contamination was evident in 57% (nonnavigated) and 32% (navigated) fewer compromises of tray sterility indicators, pans, and instruments. Single-use instruments show promising benefits, but further study is needed to confirm safety and efficacy before they can be widely adopted. The authors believe that the use of single-use instruments, cutting guides, and trial implants for total knee arthroplasty will play an increasing role in decreasing operating room contamination and potential deep infections.

Risk stratification for acute pulmonary embolism.

This article discusses state-of-the-art techniques for predicting risk of death after acute pulmonary embolism (PE), with special attention to how underlying malignancy adversely affects survival after an episode. Current methods of risk stratification generally categorize patients with PE as low-, moderate-, and high-risk for in-hospital adverse outcomes of respiratory failure, circulatory shock, and death. Published risk stratification studies find that patients with PE and an underlying malignancy have a worse prognosis, but no validated risk stratification criteria have been published specifically for these patients. Standard treatment is full-dose heparin followed by oral anticoagulation. The term escalated treatment refers to the use of systemic or intrapulmonary fibrinolytic agents, catheter-based treatment, or surgical embolectomy. Most patients with low-risk PE (normal vital signs and normal serum troponin, brain natriuretic peptide, and normal echocardiography) are treated successfully with standard anticoagulation, and many can be treated as outpatients. In contrast, patients with high-risk PE (systolic blood pressure < 90 mm Hg and no contraindications) often benefit from escalated treatment. Treatment decisions for patients with moderate-risk PE (normotension with evidence of right ventricular damage or dysfunction) are most controversial. Most patients in this category of risk recover with standard therapy, but some benefit from escalated treatment. Patients with cancer with an incidentally discovered PE should be risk stratified the same as those who have clinically suspected PE.

Analytical validation and reference intervals for a commercial multiplex assay to measure five novel biomarkers for acute kidney injury in canine urine.

Novel urinary biomarkers are increasingly utilized for the diagnosis of acute kidney injury (AKI) in dogs. Magnetic-bead based immunoassays for the simultaneous measurement of multiple biomarkers represent a potentially efficient and cost effective tool for investigators; however there is limited data to support their reliable use in dogs. Analytical validation of a commercial multiplex assay for the measurement of five AKI biomarkers: clusterin, cystatin C, kidney-injury molecule 1 (KIM-1), monocyte chemoattractant protein 1 and neutrophil gelatinase-associated lipocalin (NGAL) in canine urine was performed. The effect of pre-analytical factors including potential interfering substances and sample storage methods were investigated. Urine from 110 healthy dogs was used to determine reference intervals for each biomarker measured, according to American Society of Veterinary Clinical Pathology guidelines. Additionally, urine from 21 dogs with pyuria was used to evaluate the impact of pyuria on biomarker concentration. The assay performed with acceptable accuracy and precision for the measurement of NGAL only. Clinically relevant urine concentrations of bilirubin, haemoglobin, and synthetic colloid solutions led to interference (mean percentage difference > +/- 15% compared to control) with measurement of all or some of the biomarkers. All biomarkers were stable in urine stored at 20-22 °C for 2 h, 4 °C for 12 h, or -20 °C for 6 months. Reference intervals could not be established for KIM-1 due to unacceptable measurement imprecision (intra- and inter assay coefficient of variation 45% and 20% respectively). Urine NGAL concentration was significantly elevated in pyuria (P < 0.001).

Ability of different assay platforms to measure renal biomarker concentrations during ischaemia-reperfusion acute kidney injury in dogs.

Several protein biomarkers have been shown to be useful for the early diagnosis of acute kidney injury (AKI) in animals and people. Multiplex assays for measurement of a panel of renal biomarkers in canine samples have recently become available. This study compared the use of two such assays, versus previously validated ELISAs, to measure five biomarkers in canine samples during ischaemia-reperfusion (IR) AKI. Blood and urine was collected from six male anaesthetised greyhounds that underwent 1-h of renal ischaemia (severe hypotension induced by acute haemorrhage) and 2-h of reperfusion (intravenous fluid resuscitation). Histology confirmed presence of acute tubular injury at 2 h of reperfusion. Concentrations of clusterin, cystatin C, kidney-injury molecule 1 (KIM-1), monocyte chemoattractant protein 1, and neutrophil gelatinase-associated lipocalin (NGAL) at baseline and following IR, measured by two different multiplex assays and previously-validated single analyte immunoassays, were compared. Only NGAL was significantly elevated following IR with all assays investigated. Whether concentrations of the other four biomarkers were significantly increased following IR depended on the assay used. Concentrations of cystatin C and KIM-1 measured with the multiplex assays were of a vast magnitude lower than those measured with the corresponding single analyte ELISAs. We conclude that further validation is required before these assays can reliably be used to measure AKI biomarkers in canine samples.