Mark Flemmer

Bio: Mark Flemmer is an academic researcher from Eastern Virginia Medical School. The author has contributed to research in topics: Whipple's disease & Norovirus. The author has an hindex of 9, co-authored 27 publications receiving 1295 citations.

Narrative review: the management of acute decompensated heart failure.

Abstract: Acute decompensated heart failure (ADHF) is the most common reason for hospitalization in Western nations. The prognosis of patients admitted to hospital with ADHF is poor, with up to 64% being readmitted within the first 90 days after discharge and with a 1-year mortality approximating 20%. Epidemiological studies suggest that the majority of patients hospitalized with ADHF receive treatment that is inadequate and which is not based on scientific evidence. Furthermore, emerging data suggest that the "conventional" therapeutic interventions for ADHF including morphine, high-dose diuretics, and inotropic agents may be harmful. The goal of this review is to provide evidence-based recommendations for the diagnosis and management of ADHF.

The immune response to surgery and trauma: Implications for treatment.

Abstract: BackgroundInfection after surgery and trauma is a major cause of increased morbidity, mortality, and cost. Alterations of the hosts immune system following these insults is believed to be responsible for the increased risk of infection. The hosts’ immune response to tissue injury is widely believed

The risk of catheter-related bloodstream infection with femoral venous catheters as compared to subclavian and internal jugular venous catheters: a systematic review of the literature and meta-analysis.

Abstract: Background: Catheter-related bloodstream infections are an important cause of morbidity and mortality in hospitalized patients. Current guidelines recommend that femoral venous access should be avoided to reduce this complication (1A recommendation). However, the risk of catheter-related bloodstream infections from femoral as compared to subclavian and internal jugular venous catheterization has not been systematically reviewed. Objective: A systematic review of the literature to determine the risk of catheter-related bloodstream infections related to nontunneled central venous catheters inserted at the femoral site as compared to subclavian and internal jugular placement. Data Sources: MEDLINE, Embase, Cochrane Register of Controlled Trials, citation review of relevant primary and review articles, and an Internet search (Google). Study Selection: Randomized controlled trials and cohort studies that reported the frequency of catheter-related bloodstream infections (infections per 1,000 catheter days) in patients with nontunneled central venous catheters placed in the femoral site as compared to subclavian or internal jugular placement. Data Extraction: Data were abstracted on study design, study size, study setting, patient population, number of catheters at each insertion site, number of catheter-related bloodstream infections, and the prevalence of deep venous thrombosis. Studies were subgrouped according to study design (cohort and randomized controlled trials). Meta-analytic techniques were used to summarize the data. Data Synthesis: Two randomized controlled trials (1006 catheters) and 8 cohort (16,370 catheters) studies met the inclusion criteria for this systematic review. Three thousand two hundred thirty catheters were placed in the subclavian vein, 10,958 in the internal jugular and 3,188 in the femoral vein for a total of 113,652 catheter days. The average catheter-related bloodstream infections density was 2.5 per 1,000 catheter days (range 0.6–7.2). There was no significant difference in the risk of catheter-related bloodstream infections between the femoral and subclavian/internal jugular sites in the two randomized controlled trials (i.e., no level 1A evidence). There was no significant difference in the risk of catheterrelated bloodstream infections between the femoral and subclavian sites. The internal jugular site was associated with a significantly lower risk of catheter-related bloodstream infections compared to the femoral site (risk ratio 1.90; 95% confidence interval 1.21–2.97, p = .005, I 2 = 35%). This difference was explained by two of the studies that were statistical outliers. When these two studies were removed from the analysis there was no significant difference in the risk of catheter-related bloodstream infections between the femoral and internal jugular sites (risk ratio 1.35; 95% confidence interval 0.84–2.19, p = 0.2, I 2 = 0%). Meta-regression demonstrated a signifi cant interaction between the risk of infection and the year of publication (p = .01), with the femoral site demonstrating a higher risk of infection in the earlier studies. There was no significant difference in the risk of catheter-related bloodstream infection between the subclavian and internal jugular sites. The risk of deep venous thrombosis was assessed in the two randomized controlled trials. A metaanalysis of this data demonstrates that there was no difference in the risk of deep venous thrombosis when the femoral site was compared to the subclavian and internal jugular sites combined. There was, however, significant heterogeneity between studies. Conclusions: Although earlier studies showed a lower risk of catheter-related bloodstream infections when the internal jugular was compared to the femoral site, recent studies show no difference in the rate of catheter-related bloodstream infections between the three sites. (Crit Care Med 2012; 40: 2479–2485)

Diabetes and macrovascular disease

Abstract: Cardiovascular disease (CVD) is the major cause of morbidity and mortality in patients with diabetes Macrovascular events, including stroke, myocardial infarction (MI), and peripheral arterial disease (PAD), occur earlier than in nondiabetics and the underlying pathologies are often more diffuse and severe Diabetic arteriopathy, which encompasses endothelial dysfunction, hypercoagulability, changes in blood flow, and platelet abnormalities, contributes to the early evolution of these events Tight glucose and blood pressure control improves the vascular status of these patients by varying degrees Antiplatelet agents have also been shown to be effective in the secondary prevention of cardiovascular events In the ideal world, every risk factor would be addressed and each diabetic would have excellent glycemic control, a low normal blood pressure, a low LDL, and be prescribed an ACE inhibitor, together with aspirin and clopidogrel If this is done, this emerging epidemic of macrovascular disease will be contained

Do dietary supplements have beneficial health effects in industrialized nations: what is the evidence?

Abstract: Background: Dietary supplements are regularly used by at least half of the American population, yet the health benefits of these agents are unclear. Objective: A systematic review to determine the benefits and risks of dietary supplements in Westernized societies. Data Sources: MEDLINE, Embase, Cochrane Register of Controlled Trials and citation review of relevant articles. Study Selection: Randomized, placebo-controlled clinical trials in non-pregnant Westernized adults that evaluated clinical outcomes of nutritional supplements. Data Extraction: Data were abstracted on study design, study size, study setting, patient population, dietary intervention and clinical outcomes. The outcome of each study was classified as non-beneficial, beneficial or harmful according to whether theend-point(s) of interest reached statistical significance. Data Synthesis: Sixty-three studies met the criteria for our systematic review. No benefit was recorded in 45 studies, with 10 of these showing a trend towards harm and wit...

Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.)

Abstract: This document represents the first collaboration between 2 organizations-the American Society for Parenteral and Enteral Nutrition and the Society of Critical Care Medicine-to describe best practices in nutrition therapy in critically ill children. The target of these guidelines is intended to be the pediatric critically ill patient (>1 month and 2-3 days in a PICU admitting medical, surgical, and cardiac patients. In total, 2032 citations were scanned for relevance. The PubMed/MEDLINE search resulted in 960 citations for clinical trials and 925 citations for cohort studies. The EMBASE search for clinical trials culled 1661 citations. In total, the search for clinical trials yielded 1107 citations, whereas the cohort search yielded 925. After careful review, 16 randomized controlled trials and 37 cohort studies appeared to answer 1 of the 8 preidentified question groups for this guideline. We used the GRADE criteria (Grading of Recommendations, Assessment, Development, and Evaluation) to adjust the evidence grade based on assessment of the quality of study design and execution. These guidelines are not intended for neonates or adult patients. The guidelines reiterate the importance of nutrition assessment-particularly, the detection of malnourished patients who are most vulnerable and therefore may benefit from timely intervention. There is a need for renewed focus on accurate estimation of energy needs and attention to optimizing protein intake. Indirect calorimetry, where feasible, and cautious use of estimating equations and increased surveillance for unintended caloric underfeeding and overfeeding are recommended. Optimal protein intake and its correlation with clinical outcomes are areas of great interest. The optimal route and timing of nutrient delivery are areas of intense debate and investigations. Enteral nutrition remains the preferred route for nutrient delivery. Several strategies to optimize enteral nutrition during critical illness have emerged. The role of supplemental parenteral nutrition has been highlighted, and a delayed approach appears to be beneficial. Immunonutrition cannot be currently recommended. Overall, the pediatric critical care population is heterogeneous, and a nuanced approach to individualizing nutrition support with the aim of improving clinical outcomes is necessary.

Guidelines for the Provision and Assessment of Nutrition Support Therapy in the Adult Critically Ill Patient: Society of Critical Care Medicine (SCCM) and American Society for Parenteral and Enteral Nutrition (A.S.P.E.N.).

Abstract: A.S.P.E.N. and SCCM are both nonprofit organizations composed of multidisciplinary healthcare professionals. The mission of A.S.P.E.N. is to improve patient care by advancing the science and practice of clinical nutrition and metabolism. The mission of SCCM is to secure the highest quality care for all critically ill and injured patients. Guideline Limitations: These A.S.P.E.N.−SCCM Clinical Guidelines are based on general conclusions of health professionals who, in developing such guidelines, have balanced potential benefits to be derived from a particular mode of medical therapy against certain risks inherent with such therapy. However, practice guidelines are not intended as absolute requirements. The use of these practice guidelines does not in any way project or guarantee any specific benefit in outcome or survival. The judgment of the healthcare professional based on individual circumstances of the patient must always take precedence over the recommendations in these guidelines. The guidelines offer basic recommendations that are supported by review and analysis of the current literature, other national and international guidelines, and a blend of expert opinion and clinical practicality. The population of critically ill patients in an intensive care unit (ICU) is not homogeneous. Many of the studies on which the guidelines are based are limited by sample size, patient heterogeneity, variability in disease severity, lack of baseline nutritional status, and insufficient statistical power for analysis. Periodic Guideline Review and Update: This particular report is an update and expansion of guidelines published by A.S.P.E.N. and SCCM in 2009 (1). Governing bodies of both A.S.P.E.N. and SCCM have mandated that these guidelines be updated every three to five years. The database of randomized controlled trials (RCTs) that served as the platform for the analysis of the literature was assembled in a joint “harmonization process” with the Canadian Clinical Guidelines group. Once completed, each group operated separately in their interpretation of the studies and derivation of guideline recommendations (2). The current A.S.P.E.N. and SCCM guidelines included in this paper were derived from data obtained via literature searches by the authors through December 31, 2013. Although the committee was aware of landmark studies published after this date, these data were not included in this manuscript. The process by which the literature was evaluated necessitated a common end date for the search review. Adding a last-minute landmark trial would have introduced bias unless a formalized literature search was re-conducted for all sections of the manuscript. Target Patient Population for Guideline: The target of these guidelines is intended to be the adult (≥ 18 years) critically ill patient expected to require a length of stay (LOS) greater than 2 or 3 days in a medical ICU (MICU) or surgical ICU (SICU). The current guidelines were expanded to include a number of additional subsets of patients who met the above criteria, but were not included in the previous 2009 guidelines. Specific patient populations addressed by these expanded and updated guidelines include organ failure (pulmonary, renal, and liver), acute pancreatitis, surgical subsets (trauma, traumatic brain injury [TBI], open abdomen [OA], and burns), sepsis, postoperative major surgery, chronic critically ill, and critically ill obese. These guidelines are directed toward generalized patient populations but, like any other management strategy in the ICU, nutrition therapy should be tailored to the individual patient. Target Audience: The intended use of these guidelines is for all healthcare providers involved in nutrition therapy of the critically ill, primarily physicians, nurses, dietitians, and pharmacists. Methodology: The authors compiled clinical questions reflecting key management issues in nutrition therapy. A committee of multidisciplinary experts in clinical nutrition composed of physicians, nurses, pharmacists, and dietitians was jointly convened by the two societies.

Adverse effects of immune-checkpoint inhibitors: epidemiology, management and surveillance.

Abstract: Immune-checkpoint inhibitors (ICIs), including anti-cytotoxic T lymphocyte antigen 4 (CTLA-4), anti-programmed cell death 1 (PD-1) and anti-programmed cell death 1 ligand 1 (PD-L1) antibodies, are arguably the most important development in cancer therapy over the past decade. The indications for these agents continue to expand across malignancies and disease settings, thus reshaping many of the previous standard-of-care approaches and bringing new hope to patients. One of the costs of these advances is the emergence of a new spectrum of immune-related adverse events (irAEs), which are often distinctly different from the classical chemotherapy-related toxicities. Owing to the growing use of ICIs in oncology, clinicians will increasingly be confronted with common but also rare irAEs; hence, awareness needs to be raised regarding the clinical presentation, diagnosis and management of these toxicities. In this Review, we provide an overview of the various types of irAEs that have emerged to date. We discuss the epidemiology of these events and their kinetics, risk factors, subtypes and pathophysiology, as well as new insights regarding screening and surveillance strategies. We also highlight the most important aspects of the management of irAEs.