John T. Mather Memorial Hospital

RATIONALE: Advanced bronchoscopy techniques such as electromagnetic navigation (EMN) have been studied in clinical trials, but there are no randomized studies comparing EMN with standard bronchoscopy. OBJECTIVES: To measure and identify the determinants of diagnostic yield for bronchoscopy in patients with peripheral lung lesions. Secondary outcomes included diagnostic yield of different sampling techniques, complications, and practice pattern variations. METHODS: We used the AQuIRE (ACCP Quality Improvement Registry, Evaluation, and Education) registry to conduct a multicenter study of consecutive patients who underwent transbronchial biopsy (TBBx) for evaluation of peripheral lesions. MEASUREMENTS AND MAIN RESULTS: Fifteen centers with 22 physicians enrolled 581 patients. Of the 581 patients, 312 (53.7%) had a diagnostic bronchoscopy. Unadjusted for other factors, the diagnostic yield was 63.7% when no radial endobronchial ultrasound (r-EBUS) and no EMN were used, 57.0% with r-EBUS alone, 38.5% with EMN alone, and 47.1% with EMN combined with r-EBUS. In multivariate analysis, peripheral transbronchial needle aspiration (TBNA), larger lesion size, nonupper lobe location, and tobacco use were associated with increased diagnostic yield, whereas EMN was associated with lower diagnostic yield. Peripheral TBNA was used in 16.4% of cases. TBNA was diagnostic, whereas TBBx was nondiagnostic in 9.5% of cases in which both were performed. Complications occurred in 13 (2.2%) patients, and pneumothorax occurred in 10 (1.7%) patients. There were significant differences between centers and physicians in terms of case selection, sampling methods, and anesthesia. Medical center diagnostic yields ranged from 33 to 73% (P = 0.16). CONCLUSIONS: Peripheral TBNA improved diagnostic yield for peripheral lesions but was underused. The diagnostic yields of EMN and r-EBUS were lower than expected, even after adjustment.

Abstract Objective To determine the relative effectiveness of dietary macronutrient patterns and popular named diet programmes for weight loss and cardiovascular risk factor improvement among adults who are overweight or obese. Design Systematic review and network meta-analysis of randomised trials. Data sources Medline, Embase, CINAHL, AMED, and CENTRAL from database inception until September 2018, reference lists of eligible trials, and related reviews. Study selection Randomised trials that enrolled adults (≥18 years) who were overweight (body mass index 25-29) or obese (≥30) to a popular named diet or an alternative diet. Outcomes and measures Change in body weight, low density lipoprotein (LDL) cholesterol, high density lipoprotein (HDL) cholesterol, systolic blood pressure, diastolic blood pressure, and C reactive protein at the six and 12 month follow-up. Review methods Two reviewers independently extracted data on study participants, interventions, and outcomes and assessed risk of bias, and the certainty of evidence using the GRADE (grading of recommendations, assessment, development, and evaluation) approach. A bayesian framework informed a series of random effects network meta-analyses to estimate the relative effectiveness of the diets. Results 121 eligible trials with 21 942 patients were included and reported on 14 named diets and three control diets. Compared with usual diet, low carbohydrate and low fat diets had a similar effect at six months on weight loss (4.63 v 4.37 kg, both moderate certainty) and reduction in systolic blood pressure (5.14 mm Hg, moderate certainty v 5.05 mm Hg, low certainty) and diastolic blood pressure (3.21 v 2.85 mm Hg, both low certainty). Moderate macronutrient diets resulted in slightly less weight loss and blood pressure reductions. Low carbohydrate diets had less effect than low fat diets and moderate macronutrient diets on reduction in LDL cholesterol (1.01 mg/dL, low certainty v 7.08 mg/dL, moderate certainty v 5.22 mg/dL, moderate certainty, respectively) but an increase in HDL cholesterol (2.31 mg/dL, low certainty), whereas low fat (−1.88 mg/dL, moderate certainty) and moderate macronutrient (−0.89 mg/dL, moderate certainty) did not. Among popular named diets, those with the largest effect on weight reduction and blood pressure in comparison with usual diet were Atkins (weight 5.5 kg, systolic blood pressure 5.1 mm Hg, diastolic blood pressure 3.3 mm Hg), DASH (3.6 kg, 4.7 mm Hg, 2.9 mm Hg, respectively), and Zone (4.1 kg, 3.5 mm Hg, 2.3 mm Hg, respectively) at six months (all moderate certainty). No diets significantly improved levels of HDL cholesterol or C reactive protein at six months. Overall, weight loss diminished at 12 months among all macronutrient patterns and popular named diets, while the benefits for cardiovascular risk factors of all interventions, except the Mediterranean diet, essentially disappeared. Conclusions Moderate certainty evidence shows that most macronutrient diets, over six months, result in modest weight loss and substantial improvements in cardiovascular risk factors, particularly blood pressure. At 12 months the effects on weight reduction and improvements in cardiovascular risk factors largely disappear. Systematic review registration PROSPERO CRD42015027929.

BACKGROUND: Acute kidney injury (AKI) remains a deadly condition. Tissue inhibitor of metalloproteinases (TIMP)-2 and insulin-like growth factor binding protein (IGFBP)7 are two recently discovered urinary biomarkers for AKI. We now report on the development, and diagnostic accuracy of two clinical cutoffs for a test using these markers. METHODS: We derived cutoffs based on sensitivity and specificity for prediction of Kidney Disease: Improving Global Outcomes Stages 2-3 AKI within 12 h using data from a previously published multicenter cohort (Sapphire). Next, we verified these cutoffs in a new study (Opal) enrolling 154 critically ill adults from six sites in the USA. RESULTS: One hundred subjects (14%) in Sapphire and 27 (18%) in Opal met the primary end point. The results of the Opal study replicated those of Sapphire. Relative risk (95% CI) in both studies for subjects testing at ≤0.3 versus >0.3-2 were 4.7 (1.5-16) and 4.4 (2.5-8.7), or 12 (4.2-40) and 18 (10-37) for ≤0.3 versus >2. For the 0.3 cutoff, sensitivity was 89% in both studies, and specificity 50 and 53%. For 2.0, sensitivity was 42 and 44%, and specificity 95 and 90%. CONCLUSIONS: Urinary [TIMP-2]•[IGFBP7] values of 0.3 or greater identify patients at high risk and those >2 at highest risk for AKI and provide new information to support clinical decision-making. CLINICAL TRIALS REGISTRATION: Clintrials.gov # NCT01209169 (Sapphire) and NCT01846884 (Opal).

BACKGROUND: Sentinel lymph node (SLN) status is an important prognostic factor for patients with breast cancer, which is currently determined in clinical practice by invasive SLN biopsy. PURPOSE: To noninvasively predict SLN metastasis in breast cancer using dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) intra- and peritumoral radiomics features combined with or without clinicopathologic characteristics of the primary tumor. STUDY TYPE: Retrospective. POPULATION: A total of 163 breast cancer patients (55 positive SLN and 108 negative SLN). FIELD STRENGTH/SEQUENCE: -weighted DCE-MRI. ASSESSMENT: A total of 590 radiomic features were extracted for each patient from both intratumoral and peritumoral regions of interest. To avoid overfitting, the dataset was randomly separated into a training set (∼67%) and a validation set (∼33%). The prediction models were built with the training set using logistic regression on the most significant radiomic features in the training set combined with or without clinicopathologic characteristics. The prediction performance was further evaluated in the independent validation set. STATISTICAL TESTS: Mann-Whitney U-test, Spearman correlation, least absolute shrinkage selection operator (LASSO) regression, logistic regression, and receiver operating characteristic (ROC) analysis were performed. RESULTS: Combining radiomic features with clinicopathologic characteristics, six features were automatically selected in the training set to establish the prediction model of SLN metastasis. In the independent validation set, the area under ROC curve (AUC) was 0.869 (NPV = 0.886). Using radiomic features alone in the same procedure, 4 features were selected and the validation set AUC was 0.806 (NPV = 0.824). DATA CONCLUSION: This is the first attempt to demonstrate the feasibility of using DCE-MRI radiomics to predict SLN metastasis in breast cancer. Clinicopathologic characteristics improved the prediction performance. This study provides noninvasive methods to evaluate SLN status for guiding further treatment of breast cancer patients, and can potentially benefit those with negative SLN, by eliminating unnecessary invasive lymph node removal and the associated complications, which is a step further towards precision medicine. LEVEL OF EVIDENCE: 1 Technical Efficacy: Stage 2 J. Magn. Reson. Imaging 2019;49:131-140.

BACKGROUND: The relationship between gut microbial community composition at the higher-taxonomic order level and local and systemic immunologic abnormalities in HIV disease may provide insight into how bacterial translocation impacts HIV disease. METHODS: Antiretroviral-naive patients with HIV underwent upper endoscopy before and 9 months after starting antiretroviral treatment. Duodenal tissue was paraffin-embedded for immunohistochemical analysis and digested for fluorescence activated cell sorting for T-cell subsets and immune activation (CD38+/HLA-DR+) enumeration. Stool samples were provided from patients and control subjects for comparison. Metagenomic microbial DNA was extracted from feces for optimized 16S ribosomal RNA gene (rDNA) real-time quantitative polymerase chain reaction assays designed to quantify panbacterial loads and the relative abundances of proinflammatory Enterobacteriales order and the dominant Bacteroidales and Clostridiales orders. RESULTS: Samples from 10 HIV subjects before initiating and from six subjects receiving antiretroviral treatment were available for analysis. There was a trend for a greater proportion of Enterobacteriales in HIV-positive subjects compared with control subjects (P = 0.099). There were significant negative correlations between total bacterial load and duodenal CD4 and CD8 T-cell activation levels (r = -0.74, P = 0.004 and r = -0.67, P = 0.013, respectively). The proportions of Enterobacteriales and Bacteroidales were significantly correlated with duodenal CD4 T-cell depletion and peripheral CD8 T-cell activation, respectively. CONCLUSIONS: These data represent the first report of quantitative molecular and cellular correlations between total/universal and order-level gut bacterial populations and gastrointestinal-associated lymphoid tissue levels of immune activation in HIV-infected subjects. The correlations between lower overall 16S rDNA levels and tissue immune activation suggest that the gut microbiome may contribute to immune activation and influence HIV progression.

BACKGROUND: Cardiac troponin I (cTnI) is a powerful tool to aid in the diagnosis of myocardial infarction and cardiac muscle damage. We describe an assay that overcomes problems of early assays that were often affected by cTnI degradation, assay interference, poor sensitivity, and imprecision. METHODS: The analytical performance of the Access AccuTnI assay (Beckman Coulter) was evaluated at five institutions. Controls, zero calibrator, and diluted patient samples were used to determine precision, detection limit, functional sensitivity, and linearity. The 97.5 and 99 percentiles of a reference population were determined. Common interferents and heterophilic patient samples were tested. Equimolarity was determined by assaying samples with various ratios of free and complexed cTnI. Matched samples drawn into serum, EDTA, lithium heparin, and sodium heparin sample tubes were compared. RESULTS: Total imprecision (CVs) was 4.0-8.8% between 0.40 and 31 microg/L cTnI. The detection limit was <0.01 microg/L. The 97.5 percentile upper reference limit (URL) was 0.03 microg/L (CV = 20%), and the 99 percentile URL was 0.04 microg/L (CV = 14%). Total CVs of 10% and 20% were seen at and above 0.06 and 0.03 microg/L, respectively. The assay was linear to >60 microg/L and not affected by common assay interferents. An equimolar response was observed with free, complexed, phosphorylated, and dephosphorylated forms of cTnI. Results were 4% lower in serum and 14% lower in EDTA plasma than in lithium heparin plasma (P <0.01), independent of cTnI concentration. CONCLUSION: AccuTnI is a sensitive and precise assay for the measurement of cTnI.

We propose a generalization of the Bagger-Lambert-Gustavsson action as a candidate for the description of an arbitrary number of M2-branes. The action is formulated in terms of $\mathcal{N}=2$ superfields in three dimensions and corresponds to an extension of the usual superfield formulation of Chern-Simons matter theories. Demanding gauge invariance of the resulting theory does not imply the total antisymmetry of the underlying 3-Lie algebra structure constants. We relax this condition and propose a class of examples for these generalized 3-Lie algebras. We also discuss various associated ordinary Lie algebras.

The U.S. physician-scientist (PS) workforce is invaluable to the nation's biomedical research effort. It is through biomedical research that certain diseases have been eliminated, cures for others have been discovered, and medical procedures and therapies that save lives have been developed. Yet, the U.S. PS workforce has both declined and aged over the last several years. The resulting decreased inflow and outflow to the PS pipeline renders the system vulnerable to collapsing suddenly as the senior workforce retires. In November 2015, the Alliance for Academic Internal Medicine hosted a consensus conference on the PS workforce to address issues impacting academic medical schools, with input from early-career PSs based on their individual experiences and concerns. One of the goals of the conference was to identify current impediments in attracting and supporting PSs and to develop a new set of recommendations for sustaining the PS workforce in 2016 and beyond. This Perspective reports on the opportunities and factors identified at the conference and presents five recommendations designed to increase entry into the PS pipeline and nine recommendations designed to decrease attrition from the PS workflow.

The treatment of osteoarthritis of the knee is a difficult problem. In the senior author's opinion, nonaggressive arthroscopic debridement of the knee is an effective procedure to relieve pain and restore function in patients with osteoarthritis of the knee. A subjective telephone interview of patients done 10 or more years after arthroscopic debridement evaluated the long term results of this treatment in patients with osteoarthritis of the knee. The patients all were candidates for total knee replacement who selected arthroscopy as a temporizing procedure. Of the 191 knees in patients undergoing arthroscopic debridement, 77 patients (91 knees) were contacted for followup. Sixty-seven percent of the 91 knees did not have total knee arthroplasty at an average of 13.2 years followup. The Tegner activity score averaged 3.5 and patient satisfaction averaged 8.6 on a 0 to 10 scale. Twenty-one patients (30 knees) or (33%) had total knee arthroplasty at an average of 6.7 years. Seven of these had total knee arthroplasty within 2 years of arthroscopic debridement. Six of these seven knees had Outerbridge Grade 4 articular cartilage changes and clinically significant meniscus tears. Seven of the 19 knees (37%) with Outerbridge Grade 4 changes in 80% of one knee compartment did not require total knee arthroplasty after greater than 10 year followup. The difficulties in long term followup in this patient population is evident, yet the number of patients who had a functional lifestyle after arthroscopic debridement was notable.

Summary Background Obesity is a risk factor for non‐alcoholic steatohepatitis (NASH) and increases the risk of several cancer types including cancers of the liver. Bariatric surgery can provide durable weight loss, but little is known about the later development of hepatocellular carcinoma (HCC) after surgery. Aim To determine whether bariatric surgery reduces the risk of HCC. Methods We performed a comprehensive literature search of major databases (from inception to November 2020) to identify studies which assess the incidence and risk of HCC following bariatric surgery. Pooled data were assessed using a random‐effects model expressed in terms of odds ratio (OR), incidence rate ratio and 95% confidence interval (CI). Results Nine studies (two abstracts and seven full texts) were included for meta‐analysis which involved 19 514 750 patients (18 423 546 controls and 1 091 204 bariatric patients). Pooled unadjusted odds ratio (OR) was 0.40 (95% CI: 0.28‐0.57) which favoured bariatric surgery, though with high heterogeneity (I 2 : 79%). Using an adjusted model derived from matched cohorts (five studies) yielded an OR of 0.63 (95% CI: 0.53‐0.75) with moderate heterogeneity (I 2 : 38%). The pooled rate/1000 person‐years was 0.05 (95% CI: 0.02‐0.07) in bariatric surgery patients and 0.34 (95% CI: 0.20‐0.49) in the control group with an incidence rate ratio of 0.28 (95% CI: 0.18‐0.42). Conclusion Bariatric surgery is associated with a decreased risk of HCC.

Objective: Gabapentin (GBP) is a commonly used anticonvulsant and analgesic for the treatment of epilepsy and neuropathic pain. GBP is also frequently prescribed off-label for psychiatric disorders despite a lack of rigorous, comprehensive studies. However, there is growing evidence that GBP may be effective for the treatment of several of these indications. This review aimed to perform a systematic review of published literature on the efficacy of GBP in the treatment of various psychiatric illnesses and substance use disorders. Methods: This review was performed according to the PRISMA guidelines. The PubMed and Ovid MEDLINE databases were screened and filtered by using specific search terms and inclusion/exclusion criteria. The search terms generated 2,604 results, after excluding all duplicates and applying the inclusion/exclusion criteria, a total of 53 papers were retained for detailed review. Results: This literature review concludes that GBP appears to be effective in the treatment of various forms of anxiety disorders. It shows some effectiveness in bipolar disorder as an adjunctive therapeutic agent, while the evidence for monotherapy is inconclusive. In substance use disorders, GBP is effective for acute alcohol withdrawal symptoms with mild to moderate severity, it reduces cravings, improves the rate of abstinence and delays return to heavy drinking. GBP can be helpful for the treatment of opioid dependence, but there is limited evidence to support it. GBP may have therapeutic potential for cannabis use disorder. No significant effect of GBP use has yet been conclusively observed in the treatment of OCD, PTSD, depression, or cocaine and amphetamine abuse. Conclusion: GBP appears to be effective in the treatment of some forms of anxiety disorders, and alcohol withdrawals or dependence, albeit it is effective often as an adjunctive medication rather than as a monotherapeutic agent. More rigorous larger clinical trials are required to resolve the contradictory existing data for the efficacy of GBP. It is worth noticing that numerous clinical studies on this subject are open-label trials, which are inherently less rigorously analyzed. Therefore, more extensive large randomized controlled trials are required to examine not only the effectiveness of GBP but also its safety and tolerance.

BACKGROUND: In medical intensive care unit (MICU) patients, the predictors of post-discharge sleep disturbance and functional disability are poorly understood. ICU delirium is a risk factor with a plausible link to sleep disturbance and disability. This study evaluated the prevalence of self-reported post-ICU sleep disturbance and increased functional disability, and their association with MICU delirium and other ICU factors. METHODS: This was an observational cohort study of MICU patients enrolled in a biorepository and assessed upon MICU admission by demographics, comorbidities, and baseline characteristics. Delirium was assessed daily using the Confusion Assessment Method for the ICU. Telephone follow-up interview instruments occurred after hospital discharge and included the Pittsburgh Sleep Quality Index (PSQI), and basic and instrumental activities of daily living (BADLs, IADLs) for disability. We define sleep disturbance as a PSQI score > 5 and increased disability as an increase in composite BADL/IADL score at follow-up relative to baseline. Multivariable regression modeled the associations of delirium and other MICU factors on follow-up PSQI scores and change in disability scores. RESULTS: PSQI and BADL/IADL instruments were completed by 112 and 122 participants, respectively, at mean 147 days after hospital discharge. Of those surveyed, 63% had sleep disturbance by PSQI criteria, and 37% had increased disability by BADL/IADL scores compared to their pre-MICU baseline. Total days of MICU delirium (p = 0.013), younger age (p = 0.013), and preexisting depression (p = 0.025) were significantly associated with higher PSQI scores at follow-up. Lower baseline disability (p < 0.001), older age (p = 0.048), and less time to follow-up (p = 0.024) were significantly associated with worsening post-ICU disability, while the occurrence of MICU delirium showed a trend toward association (p = 0.077). CONCLUSIONS: After adjusting for important covariates, total days of MICU delirium were significantly associated with increased post-discharge sleep disturbance. Delirium incidence showed a trend toward association with increased functional disability in the year following discharge.

Surgical navigation has been shown to improve the accuracy of bone preparation and limb alignment in total knee arthroplasty (TKA). Previous work has shown the effectiveness of various types of navigation systems. Here, for the first time, we assessed the accuracy of a novel imageless semiautonomous handheld robotic sculpting system in performing bone resection and preparation in TKA using cadaveric specimens. In this study, we compared the planned and final implant placement in 18 cadaveric specimens undergoing TKA using the new tool. Eight surgeons carried out the procedures using three types of implant designs. A quantitative analysis was performed to determine the translational, angular, and rotational differences between the planned and achieved positions of the implants. The mean femoral flexion, varus/valgus, and rotational error was -2.0°, -0.1°, and -0.5°, respectively. The mean tibial posterior slope, and varus/valgus error was -0.2°, and -0.2°, respectively. We obtained higher flexion errors for the femoral implant when using cut-guides as compared to using a bur for cutting the bones. The image-free robotic sculpting tool achieved accurate implementation of the surgical plan with small errors in implant placement. Future studies will focus on determining how well the accurate implant placement translates into a clinical and functional benefit for the patient.

Objective The National Institute of Health (NIH) supports the academic career of scientists across the United States (U.S.). It promotes and sponsors scientists in conducting wide-ranging clinical and basic science research. Depending on the duration, research type, and budget, there are various types of grants awarded by NIH. Despite considerable advancement in biomedical sciences, female researchers remain underrepresented in obtaining NIH funding. Through this study, we aim to highlight the gender trends in NIH funding and grants. By doing this, we aim to facilitate effective future policymaking to help achieve gender parity in NIH grants and awards. Methods The data were obtained from the NIH Research Portfolio Online Reporting Tool (RePORT). The extracted data by gender were tabulated showing percentages of females as Research Grant Investigators, Research Career Development Award Recipients and Kirschstein-National Research Service Award (NRSA) Trainees and Fellows, recipients of Research Grants, Research Project Grants (RPGs), and R01 equivalent grants including types 1 or 2, over two decades (1999-2019). Absolute percentage change was also calculated and included in the tables. Results The percentage of females as NIH Research Grant Investigators has increased at centers, research centers as well as for RPGs and Small Business Innovation Research and Small Business Technology Transfer (SBIR/STTR) programs. For Research Career Development Award Recipients and Kirschstein-NRSA Trainees and Fellows, the proportion of female pre-doctoral institutional trainees, post-doctoral fellows, post-doctoral institutional trainees, mentored research career awardees, and other research career awardees have steadily increased. However, there was a decrease in the percentage of female pre-doctoral fellow awardees. The percentage of females receiving all RPGs, R01-New (type 1) and R01-Renewal (type 2) grants has also decreased. Conclusion Despite an overall increase in the percentage of female researchers successfully receiving NIH grants and awards, they continue to lag compared to their male counterparts. With the increasing number of female doctoral graduates, it is imperative to address this disparity in NIH funding.

Today's nurse leaders are challenged to successfully implement and sustain healthy work environments and promote staff engagement. Authentic leaders possess inner core values that are consistent with the nursing profession. Authentic nurse leaders are able to create a healthy work environment that leads to engaged nurses. The first aim of this study was to develop the authentic nurse leadership conceptual framework and instrument. The second was to identify nurses' perception of authentic nurse leader attributes, grounded in the nursing discipline, that support a healthy work environment and promote nurse engagement. A crossover design was employed to compare the Authentic Nurse Leadership Questionnaire (ANLQ) with the Authentic Leadership Questionnaire, which has been used for leaders from multiple disciplines. The study sample consisted of 309 registered nurses, whose work includes at least 50% direct patient care. Results of the study indicate that the ANLQ is valid and reliable; ANLQ concepts were statistically supported by both exploratory and confirmatory factor analyses. The ANLQ better identified nursing values, as indicated by a stronger relationship with nurse work-life and nurse engagement.

A retrospective review of patient falls in a 248-bed acute-care community hospital was conducted in order to quantify the number of patient falls and identify what factors resulted in these falls. The author reports these results and describes specific measures that were implemented in an attempt to reduce the number of falls in the organization.

Our primary objective was to determine if immediate-release methylphenidate is an effective treatment for oppositional defiant disorder diagnosed from mother's report in children with both chronic multiple tic disorder and attention-deficit hyperactivity disorder (ADHD). Children (n = 31) aged 6 to 12 years received placebo and 3 doses of methylphenidate twice daily for 2 weeks each under double-blind conditions and were assessed with ratings scales and laboratory measures. Results indicated significant improvement in both oppositional and ADHD behaviors with medication; however, the magnitude of treatment effect varied considerably as a function of disorder (ADHD > Oppositional behaviors), informant (teacher > mother), assessment instrument, and specific oppositional behavior (rebellious > disobeys rules). Drug response was comparable with that in children (n = 26) who did not have diagnosed oppositional defiant disorder, but comorbidity appeared to alter the perceived benefits for ADHD according to mother's report. Methylphenidate is an effective short-term treatment for oppositional behavior in children with comorbid ADHD and chronic multiple tic disorder.

BACKGROUND: Insulin-like growth factor-binding protein 7 (IGFBP7) and tissue inhibitor of metalloproteinases-2 (TIMP-2) have demonstrated significantly improved diagnostic performance in assessing risk for acute kidney injury (AKI) compared with existing biomarkers. We present the findings of a multi-site trial to determine the reference intervals for these biomarkers in apparently healthy adults and those with stable chronic morbid conditions without AKI. METHODS: A urine specimen was collected from apparently healthy subjects (N=378) and subjects with at least one stable chronic morbidity (N=372). Specimens were kept frozen until analysis with the NephroCheck® Test (Astute Medical). The test is comprised of fluorescence immunoassays for IGFBP7 and TIMP-2 and is used with the Astute140® Meter which quantifies the concentration of each biomarker. The meter multiplies the concentrations of IGFBP7 and TIMP-2 and displays the result as a numerical value ([IGFBP7]∙[TIMP-2]) expressed in (ng/ml)(2)/1000 which is called the AKIRisk™ Score. RESULTS: The reference intervals (inner 95%) for [IGFBP7]∙[TIMP-2] in all subjects (N=750), apparently healthy subjects, and subjects with stable chronic morbidities were 0.04-2.22, 0.04-2.25, and 0.05-2.20 (ng/ml)(2)/1000 respectively. There was no statistical difference between reference intervals for apparently healthy and chronic stable morbid cohorts (p=0.42). CONCLUSIONS: Our investigation showed that urine [IGFBP7]∙[TIMP-2] values were not elevated in patients with stable chronic morbidities who did not have AKI.

Extracellular matrix plays a role in differentiation and phenotype development of its resident cells. Although cardiac extracellular matrix from the contractile tissues has been studied and utilized in tissue engineering, extracellular matrix properties of the pacemaking sinoatrial node are largely unknown. In this study, the biomechanical properties and biochemical composition and distribution of extracellular matrix in the sinoatrial node were investigated relative to the left ventricle. Extracellular matrix of the sinoatrial node was found to be overall stiffer than that of the left ventricle and highly heterogeneous with interstitial regions composed of predominantly fibrillar collagens and rich in elastin. The extracellular matrix protein distribution suggests that resident pacemaking cardiomyocytes are enclosed in fibrillar collagens that can withstand greater tensile strength while the surrounding elastin-rich regions may undergo deformation to reduce the mechanical strain in these cells. Moreover, basement membrane-associated adhesion proteins that are ligands for integrins were of low abundance in the sinoatrial node, which may decrease force transduction in the pacemaking cardiomyocytes. In contrast to extracellular matrix of the left ventricle, extracellular matrix of the sinoatrial node may reduce mechanical strain and force transduction in pacemaking cardiomyocytes. These findings provide the criteria for a suitable matrix scaffold for engineering biopacemakers.

BACKGROUND: We examined the concordance of 13 commercial cardiac troponin (cTn) assays [point-of-care, high-sensitivity (hs), and conventional] using samples distributed across a continuum of results. METHODS: cTnI (11 assays) and cTnT (2 assays) were measured in 191 samples from 128 volunteers. cTn assays included Abbott (iSTAT, STAT, and hs), Alere (Cardio 3), Beckman (AccuTnI+3), Pathfast (cTnI-II), Ortho (Vitros), Siemens (LOCI, cTnI-Ultra, Xpand, Stratus CS), and Roche [4th Generation (Gen), hs]. Manufacturer-derived 99th percentile cutoffs were used to classify results as positive or negative. Alternative 99th percentile cutoffs were tested for some assays. Correlation was assessed using Passing-Bablok linear regression, bias was examined using Bland-Altman difference plots, and concordance/discordance of each method comparison was determined using the McNemar method. RESULTS: Regression slopes ranged from 0.63 to 1.87, y-intercepts from 0.00 to 0.03 ng/mL, and r values from 0.93 to 0.99. The cTnT methods had a slope of 0.93, y-intercept of 0.02 ng/mL, and r value of 0.99. For the cTnI assays, positive, negative, and overall concordance was 76.2%-100%, 66.0%-100%, and 82.9%-98.4%, respectively. Overall concordance between the 4th Gen cTnT and hsTnT assays was 88.9%. A total of 30 of the 78 method comparisons showed significant differences in classification of samples (P <0.001); the iSTAT showed 10, hsTnT showed 9, AccuTnI+3 showed 5, Xpand showed 5, and Stratus CS showed 1. Using alternative 99th percentile cutoffs to those listed by manufacturers lowered the method discordance by 6-fold, from 30 to 5 (all involved iSTAT). CONCLUSIONS: These data provide insight into characteristics of cTn methods and will assist the healthcare community in setting expectations for relationships among commercial cTn assays.