User:Larryhbern

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Larry Bernstein, MD, Chief Scientific Officer, Member of the Board, Expert, Author, Writer Roles at http://pharmaceuticalintelligence.com Chief Scientific Officer, Member of the Board

Research Categories OWNER: 1. Biomarkers & Medical Diagnostics 2. Clinical Trials and IRB related issues

Acute and Chronic Disease Classifications Biomarker Discovery and Validation Cardiovascular Research Clinical Laboratory-Related Issues Healthcare and Hospital Costs Health Information Technology and Workflow Redesign Metabolomics Metabolic Derangements Nutraceuticals Nutrigenomics Nutrition Nutrition and Phytochemistry

Selected Posts Oxidative stress of hyperhomocysteinemia August 25, 2012 The Open Clinical Chemistry Journal, 2011, 4, 34-44 1874-2416/11… Transthyretin and Lean Body Mass in Stable and Stressed State August 25, 2012 Chapter 20 Plasma Transthyretin Reflects the Fluctuations of Lean Body… Automated Inferential Diagnosis of SIRS, Sepsis August 1, 2012 Medical Informatics View Chapter 1 Statement of Inferential Second Opinion … Realtime Clinical Expert Support August 1, 2012 Special Considerations in Blood Lipoproteins, Viscosity, Assessment and Treatment What is the role of plasma viscosity in hemostasis and vascular disease risk? The Amazing Structure and Adaptive Functioning of the Kidneys: Nitric Oxide – Part I Nitric Oxide and iNOS have Key Roles in Kidney Diseases – Part II The Molecular Biology of Renal Disorders: Nitric Oxide – Part III New Insights on Nitric Oxide donors – Part IV Nitric Oxide Function in Coagulation Coagulation: Transition from a familiar model tied to laboratory testing, and the new cellular-driven model

112 Peer reviewed journal articles, 7 book chapters

Born 1941 High School: Mumford, Detroit, MI, USA BS, MS, MD: Wayne State University, Detroit, MI Resident and USPDF in Pathology and Biochemistry: 1970-1973. Univ Calif San Diego, La Jolla, CA. Averill A. Liebow & Nathan O. Kaplan AFIP, Orthopedic Pathology Br, 1973-1974, Lt Cmdr, USN. Washington, DC. under Lent C. Johnson. Academic Career: 1975, Univ S Fla, Tampa, 1975-1977, Pathology, under Herschel Sidransky. Career Highlight: Chief of Chemistry and Blood Bank, Bridgeport Hospital, 1983-2002; Chief of Clinical Pathology, Methodist Hospital of Brooklyn, Park Slope, Brooklyn, 2002-2007. Retired.

BIO Larry H Bernstein, MD, FCAP Principal & CEO, Triplex Medical Science http://pharmaceuticalintelligence.com/contributors-biographies/larry-bernstein/ Selected Peer Reviewed publications 1. Rosser A. Rudolph, Larry H. Bernstein,and Joseph Babb. Information Induction for Predicting Acute Myocardial Infarction. CLIN CHEM 1988; 34(10): 2031-2038. 2. Zarich SW, Bradley K, Mayall ID, Bernstein LH. Minor elevations in troponin T values enhance risk assessment in emergency department patients with suspected myocardial ischemia: analysis of novel troponin T cut-off values. Clin Chim Acta 2004; 343:223-29. 3. Bernstein, L.H.; Devakonda, A.; Engelman, E.; Pancer, G.; Ferrara, J.; Rucinski, J.; Raoof, S.; George, L.; Melniker, L. The Role of Procalcitonin in the Diagnosis of Sepsis and Patient Assignment to Medical Intensive Care. J Clinical Ligand Assay, 2007; 30 (3-4):98-104 Older patients, make up a large part of the ICU population and tend to have an acute stressful condition superimposed on chronic illness. The effects of anorexia, hypermetabolism, and malabsorption on these patients lead to substantial nitrogen losses. The most widely used methods for assessing malnutrition are the Subjective Global Assessment (SGA); TTR, and a combination of laboratory and biochemical features. The simplest of these, transthyretin (TTR) has become a commonly assayed protein in assessing PEM status. Clinical studies indicate that determination of the TTR level may allow for earlier recognition of malnutrition risk and timely intervention. Since TTR has a relatively short circulating half-life, it is expected to respond rapidly in response to metabolic support. TTR production decreases after 14 days of consuming a diet that provides only 60% of required proteins. Rapid turnover proteins, such as transthyretin (half-life < 2 days) respond early to nutrition support, and reflect a delayed return to anabolic status.It is particularly helpful in removing interpretation bias, and it is an excellent measure of the systemic inflammatory response concurrent with a preexisting state of chronic inanition. In the ICU patients we studied, TTR removed interpretation bias because the sickest patients experienced an uncommon delayed return of TTR to normal levels with adequate nutritional support. DevakondaA, et al,Transthyretin as a marker to predict outcome in critically ill patients,ClinBiochem(2008),doi:10.1016/j.clinbiochem.2008.06.016 Protein energy malnutrition; Critically ill patients; Stress hypermetabolism; Transthyretin; Multivariate classification.

4. Bernstein LH, Zions MY, Haq SA, Zarich S, Rucinski J, Seamonds B, Berger S, Lesley DY, Fleischman W, Heitner JF: Effect of renal function loss on NT-proBNP level variations. Clin Biochem; 2009;42(10-11):1091-8 [PMID: 19298805] OBJECTIVE: NT-proBNP level is used for the detection of acute CHF and as a predictor of survival. However, a number of factors, including renal function, may affect the NT-proBNP levels. This study aims to provide a more precise way of interpreting NT-proBNP levels based on GFR, independent of age. METHODS: This study includes 247 pts in whom CHF and known confounders of elevated NT-proBNP were excluded, to show the relationship of GFR in association with age. The effect of eGFR on NT-proBNP level was adjusted by dividing 1000 x log(NT-proBNP) by eGFR then further adjusting for age in order to determine a normalized NT-proBNP value. RESULTS: The normalized NT-proBNP levels were affected by eGFR independent of the age of the patient. CONCLUSION: A normalizing function based on eGFR eliminates the need for an age-based reference ranges for NT-proBNP. Kidney Function Tests. Natriuretic Peptide, Brain / blood. Peptide

5. David G, Bernstein LH, Coifman RR. Generating Evidence Based Interpretation of Hematology Screens via Anomaly Characterization. The Open Clinical Chemistry Journal, 2011; 4:10-16. ISSN 1874-2416/11. Bentham Journal. Introduction: We propose an automated nutritional assessment (ANA) algorithm that provides a method for malnutrition risk prediction with high accuracy and reliability. Materials and Methods: The database used for this study is a file of 432 patients, where each patient is described by 4 laboratory parameters and 11 clinical parameters. A malnutrition risk assessment of low (1), moderate (2) or high (3) was assigned by a dietitian for each patient. An algorithm for data organization and classification via characteristic metrics is proposed. For each patient, the algorithm characterizes its unique profile and builds a characteristic metric to identify similar patients who are mapped into a classification. Results: The algorithm assigned a malnutrition risk level for each patient based on different training sizes that were taken out of the data. Our method resulted in an average error (distance between the automated score and the real score) of 0.386, 0.3507, 0.3454, 0.34 and 0.2907 for 10%, 30%, 50%, 70% and 90% training sizes, respectively. Our method outperformed the compared method even when our method used a smaller training set then the compared method. In addition, we show that the laboratory parameters themselves are sufficient for the automated risk prediction and adding the clinical parameters does not improve the accuracy. We present an organization of the patients into several clusters and sub-clusters. These clusters correspond to low risk areas, low-moderate risk areas, moderate risk areas, moderate-high risk areas and high risk areas. The organization and visualization methods provide a tool for exploration and navigation of the data points. Discussion: The problem of rapidly identifying risk and severity of malnutrition is crucial for minimizing medical and surgical complications associated with previsit under-nutrition, chronic illness affecting swallowing, eating, and weight loss.

6. Brugler L, Stankovic AK, Schlefer M, Bernstein L. A simplified nutrition screen for hospitalized patients using readily available laboratory and patient information. Nutrition 2005; 21(6): 650-658 Results: The analysis demonstrated the characteristics that correlated best with MRC risk level assignment were: the occurrence of a wound (p=2.5e-14), poor oral intake (p=3.2e-14), malnutrition related admission diagnosis (p=3.9e-9), serum albumin value (p=1.4e-31), hemoglobin value (p=3.3e-10), and total lymphocyte count (p=1.4e-29). The 6 variable model had an R2 of 0.773 and p = 4.6e-116. A second model had 4 variables (malnutrition related admission diagnosis, serum albumin value, hemoglobin value and total lymphocyte count) and 3 (high, moderate and low) versus 4 (high, moderate, low and no) MRC risk levels with an R2 of 0.721 and p = 1.6e-104. Discussion: The ability of admission information to accurately reflect MRC risk is crucial to early initiation of restorative medical nutrition therapy (MNT), the efficient utilization of nutrition care resources and compliance with regulatory requirements. There is currently no uniform or proved standard for identifying MRC risk within 24 hours of acute care admission. The ideal nutrition screen correlates well with the occurrence of MRCs and also contains parameters that can be quickly and routinely obtained at admission. The six and even four parameter models described above meet both criteria and they can be uniformly used by hospitals to screen patients for MRC risk.7. Larry H. Bernstein, and James Rucinski. The relationship between granulocyte maturation and theseptic state measurement of granulocyte maturation may improve the early diagnosis of the septic state, Clin Chem Lab Med 2011;49 DOI 10.1515/CCLM.2011.688