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    Opportunities for repurposing of poly(ADP-ribose) polymerase (PARP) inhibitors for the therapy of non-oncological diseases.
    Br J Pharmacol 2017 Feb 18. Epub 2017 Feb 18.
    Department of Anesthesiology, University of Texas Medical Branch, Galveston, TX, USA.
    The recent clinical availability of the PARP inhibitor Lynparza (olaparib) opens the door for potential therapeutic repurposing for non-oncological indications. Considering (a) the preclinical efficacy data with PARP inhibitors in non-oncological diseases and (b) the risk-benefit ratio of treating patients with a compound that inhibits an enzyme that has physiological roles in the regulation of DNA repair, indications where (a) the severity of the disease is high, (b) the available therapeutic options are limited, and (c) the duration of PARP inhibitor administration could be short, provide first-line options for therapeutic repurposing. These indications are as follows: acute ischemic stroke; traumatic brain injury; septic shock; acute pancreatitis and severe acute lung injury. Read More

    Associations among left ventricular systolic function, tachycardia, and cardiac preload in septic patients.
    Ann Intensive Care 2017 Dec 17;7(1):17. Epub 2017 Feb 17.
    Critical Care Echocardiography Service, Intermountain Medical Center, 5121 S Cottonwood St, Murray, UT, 84157, USA.
    Background: In sepsis, tachycardia may indicate low preload, adrenergic stimulation, or both. Adrenergic overstimulation is associated with septic cardiomyopathy. We sought to determine whether tachycardia was associated with left ventricular longitudinal strain, a measure of cardiac dysfunction. Read More

    Expression profiling of TRIM protein family in THP1-derived macrophages following TLR stimulation.
    Sci Rep 2017 Feb 17;7:42781. Epub 2017 Feb 17.
    Institute of Translational Medicine, Nanchang University, Nanchang, Jiangxi, 330031, China.
    Activated macrophages play an important role in many inflammatory diseases including septic shock and atherosclerosis. However, the molecular mechanisms limiting macrophage activation are not completely understood. Members of the tripartite motif (TRIM) family have recently emerged as important players in innate immunity and antivirus. Read More

    Double-carbapenem combination as salvage therapy for untreatable infections by KPC-2-producing Klebsiella pneumoniae.
    Eur J Clin Microbiol Infect Dis 2017 Feb 16. Epub 2017 Feb 16.
    6th Department of Internal Medicine, Hygeia General Hospital, 4, Erythrou Stavrou Str & Kifisias, Marousi, Athens, Greece, PO:15123.
    We report our experience using the double-carbapenem combination as salvage therapy for patients with untreatable infections caused by KPC-2- producing Klebsiella pneumoniae. A total of 27 patients in two institutions in Athens, Greece suffering from complicated urinary tract infections (16) with or without secondary bacteraemia (four and 12 respectively), primary (six) or catheter-related bloodstream infections (two), HAP or VAP (two) and external ventricular drainage infection (one) were treated exclusively with ertapenem and high-dose prolonged infusion meropenem because in-vitro active antimicrobials were unavailable (19) or failed (four) or were contraindicated (six). Most patients presented with severe infections with median APACHE II score of 17 and 11 of those patients (40. Read More

    Mass spectrometry for the discovery of biomarkers of sepsis.
    Mol Biosyst 2017 Feb 16. Epub 2017 Feb 16.
    Department of Chemistry and Biochemistry and the Harper Cancer Research Institute, University of Notre Dame, Notre Dame, IN, USA.
    Sepsis is a serious medical condition that occurs in 30% of patients in intensive care units (ICUs). Early detection of sepsis is key to prevent its progression to severe sepsis and septic shock, which can cause organ failure and death. Diagnostic criteria for sepsis are nonspecific and hinder a timely diagnosis in patients. Read More

    Organ dysfunction during continuous veno-venous high cut-off hemodialysis in patients with septic acute kidney injury: A prospective observational study.
    PLoS One 2017 16;12(2):e0172039. Epub 2017 Feb 16.
    Department of Health Science, Section of Anesthesiology and Intensive Care, University of Florence, Florence, Italy.
    Background: Continuous veno-venous hemodialysis with high cut-off membranes (HCO-CVVHD) removes inflammatory mediators involved in organ dysfunction during sepsis. The aim of the present study was to assess the variations in SOFA score and identify early predictors of short-term mortality in a cohort of patients with septic shock, treated with HCO-CVVHD for acute kidney injury (AKI).

    Methods: An observational prospective multicenter cohort study was conducted in four mixed medical-surgical ICUs. Read More

    The new sepsis definition: limitations and contribution to research and diagnosis of sepsis.
    Curr Opin Anaesthesiol 2017 Feb 15. Epub 2017 Feb 15.
    aDepartment of Anesthesiology and Critical Care, SMUR and Burn Unit, GH Saint-Louis-Lariboisière-Fernand Widal University Hospitals, Assistance Publique-Hôpitaux de Paris bInfection and Epidemiology Department, Human Histopathology and Animal Models Unit, Institut Pasteur cUniversity Paris Diderot, Sorbonne Paris Cité dU 942 INSERM, Paris, France.
    Purpose Of Review: Based on recent clinical, epidemiological, and pathophysiological data, a third international consensus conference was carried out to define new criteria of sepsis in February 2016. This review presents the different items of this new definition, their limitations and their contribution to research and diagnosis of sepsis, in comparison with the previous definitions.

    Recent Findings: Incidence, management, and pathophysiological knowledge of sepsis have improved over the past 20 years. Read More

    Thiamine as a Renal Protective Agent in Septic Shock: A Secondary Analysis of a Randomized, Double-Blind, Placebo-Controlled Trial.
    Ann Am Thorac Soc 2017 Feb 16. Epub 2017 Feb 16.
    Beth Israel Deaconess Medical Center, Emergency Medicine , One Deaconess Road , West Clinical Center 2 , Boston, Massachusetts, United States , 02215 ;
    Rationale: Acute kidney injury (AKI) is common in patients with sepsis and has been associated with high mortality rates. The provision of thiamine to septic patients may reduce the incidence and severity of sepsis-related AKI and thereby prevent renal failure requiring renal replacement therapy (RRT).

    Objectives: To test the hypothesis that thiamine supplementation mitigates kidney injury in septic shock. Read More

    Commentary.
    Ann Pharmacother 2017 Feb 1:1060028017694376. Epub 2017 Feb 1.
    1 UC Health - University of Cincinnati Medical Center Department of Pharmacy Services, Cincinnati, Ohio.
    Obesity presents a growing challenge in critically ill patients because of variable medication pharmacokinetics and pharmacodynamics. Vasopressors used in the treatment of septic shock, including norepinephrine, are dosed using weight-based (WB) or non-weight-based (NWB) strategies. Retrospective research has evaluated the effect of total body weight and body mass index on vasopressor requirements, consequently finding that obese patients require less total vasopressor per kilogram to obtain clinical end points such as mean arterial pressure. Read More

    Non-fermentative Gram-negative rods bacteremia in children with cancer: a 14-year single-center experience.
    Infection 2017 Feb 15. Epub 2017 Feb 15.
    Pediatric Infectious Diseases, Hadassah-Hebrew University Medical Center, Jerusalem, Israel.
    Purpose: Data on non-fermentative Gram-negative rods (NFGNR) bacteremia in children with malignancies are limited. The aim of this study was to present clinical picture, antimicrobial susceptibility pattern, risk factors for resistance and outcome in NFGNR bacteremia in children with cancer.

    Methods: All episodes of NFGNR bacteremia occurring during 2001-2014 in children with cancer in a tertiary-care hospital were retrospectively analyzed. Read More

    Impact of preoperative steroid or immunosuppressant use on short-term outcomes following colectomy in Crohn's disease patients.
    Tech Coloproctol 2017 Feb 15. Epub 2017 Feb 15.
    Department of Colorectal Surgery, Columbia University Medical Center, Presbyterian Hospital, New York, NY, 10032, USA.
    Background: Evaluating the impact of steroid or immunosuppressants (SI) therapy prior to colectomy in Crohn's disease (CD) patients on postoperative septic and colectomy-specific outcomes using the American College of Surgeons (ACS)-National Surgical Quality Improvement Program (NSQIP)-targeted colectomy database.

    Methods: All CD patients undergoing colectomy were retrieved from the 2012-2013 NSQIP-targeted database. Thirty-day postoperative outcomes were compared for patients who were on steroids or immunosuppressants (SI) within the 30 days prior to colectomy to the others using univariable and multivariable analyses. Read More

    Left ventricular systolic dysfunction during septic shock: the role of loading conditions.
    Intensive Care Med 2017 Feb 15. Epub 2017 Feb 15.
    AP-HP, Hôpitaux universitaires Henri Mondor, DHU A-TVB, Service de Réanimation Médicale, 94010, Créteil, France.
    Purpose: The clinical significance of septic myocardial dysfunction is controversial, a fact that may be explained by the influence of loading conditions. Many indices may be useful to characterize cardiac function during septic shock, but their feasibility and physiological coherence in the clinical setting are unknown.

    Methods: Hemodynamic and echocardiographic data with tissue Doppler and speckle tracking were prospectively recorded on the first 3 days of human septic shock. Read More

    From amino acids polymers, antimicrobial peptides, and histones, to their possible role in the pathogenesis of septic shock: a historical perspective.
    J Inflamm Res 2017 1;10:7-15. Epub 2017 Feb 1.
    Institute of Dental Sciences, Faculty of Dental Medicine, The Hebrew University of Jerusalem.
    This paper describes the evolution of our understanding of the biological role played by synthetic and natural antimicrobial cationic peptides and by the highly basic nuclear histones as modulators of infection, postinfectious sequelae, trauma, and coagulation phenomena. The authors discuss the effects of the synthetic polymers of basic poly α amino acids, poly l-lysine, and poly l-arginine on blood coagulation, fibrinolysis, bacterial killing, and blood vessels; the properties of natural and synthetic antimicrobial cationic peptides as potential replacements or adjuncts to antibiotics; polycations as opsonizing agents promoting endocytosis/phagocytosis; polycations and muramidases as activators of autolytic wall enzymes in bacteria, causing bacteriolysis and tissue damage; and polycations and nuclear histones as potential virulence factors and as markers of sepsis, septic shock, disseminated intravasclar coagulopathy, acute lung injury, pancreatitis, trauma, and other additional clinical disorders. Read More

    Complication profile, failure to rescue, and mortality following elective endovascular aortic aneurysm repair.
    Am J Surg 2017 Feb 8. Epub 2017 Feb 8.
    Department of Radiology, Dwight D. Eisenhower Army Medical Center, Ft. Gordon, GA, USA.
    Introduction: Understanding the relationship between patient risk factors, postoperative complications, and morbidity and mortality is important when considering elective endovascular aortic aneurysm repair (E-EVAR) performed to prevent aneurysm rupture mortality. We aimed to stratify complications in E-EVAR and explore their relationship with postoperative death.

    Methods: E-EVAR cases from 2012 NSQIP were identified. Read More

    Use of stepwise lactate kinetics-oriented hemodynamic therapy could improve the clinical outcomes of patients with sepsis-associated hyperlactatemia.
    Crit Care 2017 Feb 16;21(1):33. Epub 2017 Feb 16.
    Department of Critical Care Medicine, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, 100730, China.
    Background: Setting lactate kinetics at >30% might improve the clinical outcomes of patients with sepsis-associated hyperlactatemia. The aim of this study was to explore the outcome benefits of stepwise lactate kinetics vs central venous oxygen saturation (ScvO2)-oriented hemodynamic therapy at 6 h as the protocol goal during early resuscitation.

    Methods: The relevant parameters and adverse events after different targets in 360 randomly assigned patients with sepsis-associated hyperlactatemia were recorded and compared. Read More

    Transcriptomic meta-analysis reveals up-regulation of gene expression functional in osteoclast differentiation in human septic shock.
    PLoS One 2017 15;12(2):e0171689. Epub 2017 Feb 15.
    National Institute of Biomedical Genomics, Kalyani, West Bengal, India.
    Septic shock is a major medical problem with high morbidity and mortality and incompletely understood biology. Integration of multiple data sets into a single analysis framework empowers discovery of new knowledge about the condition that may have been missed by individual analysis of each of these datasets. Electronic search was performed on medical literature and gene expression databases for selection of transcriptomic studies done in circulating leukocytes from human subjects suffering from septic shock. Read More

    Recent Insights into the Molecular Mechanisms Underlying Pyroptosis and Gasdermin Family Functions.
    Trends Immunol 2017 Feb 11. Epub 2017 Feb 11.
    Department of Early Discovery Biochemistry, Genentech, South San Francisco, CA 94080, USA. Electronic address:
    Pyroptosis is an inflammatory form of cell death that not only protects multicellular organisms from invading pathogenic bacteria and microbial infections, but can also lead to sepsis and lethal septic shock if overactivated. Here, we present an overview of recent developments within the pyroptosis field, beginning with the discovery of Gasdermin D (GSDMD) as a substrate of caspase-1 and caspase-11 upon detection of cytosolic lipopolysaccharide (LPS). Cleavage releases the N-terminal domain of GSDMD, causing it to form cytotoxic pores in the plasma membrane of cells. Read More

    Coinfection of Leishmania guyanensis and Human Immunodeficiency Virus-Acquired Immune Deficiency Syndrome: Report of a Case of Disseminated Cutaneous Leishmaniasis in Ecuador.
    Am J Trop Med Hyg 2017 Feb 13. Epub 2017 Feb 13.
    The Kuvin Center for the Study of Infectious and Tropical Diseases, The Hebrew University of Jerusalem, Jerusalem, Israel.
    Reported herein is the first case of Leishmania-human immunodeficiency virus (HIV) coinfection in Ecuador. In Ecuador, HIV infections overlap endemic areas of leishmaniasis. Immunosuppression is a well-established risk factor for developing severe disease. Read More

    Inadvertent Skipping of Steroids in Septic Shock Leads to a Diagnosis of Adult Onset Still's Disease.
    Cureus 2017 Jan 14;9(1):e978. Epub 2017 Jan 14.
    Department of General Medicine, Indira Gandhi Medical College & Research Institute, Pondicherry, India.
    Adult onset Still's disease is uncommon in middle-aged and elderly individuals and can rarely present with shock; shock is usually associated with disseminated intravascular coagulation, multiorgan dysfunction syndrome or acute respiratory distress syndrome. We report a post-menopausal woman with arthritis, fever, pneumonitis and hypotension which was managed as septic shock. Steroids were inadvertently missed during the second day of hospitalization in the intensive care unit. Read More

    Macrophage Migration Inhibitory Factor as an Emerging Drug Target to Regulate Antioxidant Response Element System.
    Oxid Med Cell Longev 2017 16;2017:8584930. Epub 2017 Jan 16.
    Pharmaceutical Research Division, Takeda Pharmaceutical Company Ltd., 26-1 Muraoka-Higashi 2-Chome, Fujisawa, Kanagawa 251-8555, Japan.
    Oxidative stress is involved in pathophysiology and pathological conditions of numerous human diseases. Thus, understanding the mechanisms underlying the redox homeostasis in cells and organs is valuable for discovery of therapeutic drugs for oxidative stress-related diseases. Recently, by applying chemical biology approach with an ARE activator, BTZO-1, we found macrophage migration inhibitory factor (MIF) as a new regulator of antioxidant response element- (ARE-) mediated gene transcription. Read More

    Neurologic complications of sepsis.
    Handb Clin Neurol 2017 ;141:675-683
    Neurocritical Care Unit, Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.
    Over the past decades, the incidence of sepsis and resultant neurologic sequelae has increased, both in industrialized and low- or middle-income countries, by approximately 5% per year. Up to 300 patients per 100 000 population per year are reported to suffer from sepsis, severe sepsis, and septic shock. Mortality is up to 30%, depending on the precision of diagnostic criteria. Read More

    A case report of primary necrotising fasciitis of the breast: A rare but deadly entity requiring rapid surgical management.
    Int J Surg Case Rep 2017 Jan 23;31:221-224. Epub 2017 Jan 23.
    Blacktown Hospital, NSW, Australia.
    Introduction: Necrotising fasciitis of the breast is a rare entity with very few cases reported in the literature. It is rapidly progressive and can lead to sepsis and multi-organ failure without prompt medical and surgical management.

    Presentation Of Case: We describe a case of a non-diabetic 23-year-old female with primary necrotising fasciitis of the right breast. Read More

    SOFA score in septic patients: incremental prognostic value over age, comorbidities, and parameters of sepsis severity.
    Intern Emerg Med 2017 Feb 10. Epub 2017 Feb 10.
    High-Dependency Unit, Department of Clinical and Experimental Medicine, Azienda Ospedaliero-Universitaria Careggi, Lg. Brambilla 3, 50134, Florence, Italy.
    Several widely used scoring systems for septic patients have been validated in an ICU setting, and may not be appropriate for other settings like Emergency Departments (ED) or High-Dependency Units (HDU), where a relevant number of these patients are managed. The purpose of this study is to find reliable tools for prognostic assessment of septic patients managed in an ED-HDU. In 742 patients diagnosed with sepsis/severe sepsis/septic shock, not-intubated, admitted in ED between June 2008 and April 2016, SOFA, qSOFA, PIRO, MEWS, Charlson Comorbidity Index, MEDS, and APACHE II were calculated at ED admission (T0); SOFA and MEWS were also calculated after 24 h of ED-High-Dependency Unit stay (T1). Read More

    New Consensus Definitions for Sepsis and Septic Shock: Implications for Treatment Strategies and Drug Development?
    Drugs 2017 Feb 10. Epub 2017 Feb 10.
    Section of Anaesthesia, Pain Medicine and Intensive Care, Department of Surgery and Cancer, Imperial College London, London, UK.
    Sepsis continues to escape a precise diagnostic definition. The most recent consensus definition, termed Sepsis-3, highlights the importance of the maladaptive and potentially life-threatening host response to infection. After briefly reviewing the history and epidemiology of sepsis, we go on to describe some of the challenges encountered when classifying such a heterogenous disease state. Read More

    [Saccharomyces cerevisiae invasive infection: The first reported case in Morocco].
    J Mycol Med 2017 Feb 7. Epub 2017 Feb 7.
    Service de bactériologie, hôpital militaire d'instruction Mohammed V de Rabat, Oujda, Maroc; Faculté de médecine et de pharmacie, université Mohammed V de Rabat, Oujda, Maroc.
    Saccharomyces cerevisiae is a cosmopolitan yeast, widely used in agro-alimentary and pharmaceutical industry. Its impact in human pathology is rare, but maybe still underestimated compared to the real situation. This yeast is currently considered as an emerging and opportunistic pathogen. Read More

    Minocycline Prevents the Impairment of Hippocampal Long-Term Potentiation in the Septic Mouse.
    Shock 2017 Feb 9. Epub 2017 Feb 9.
    *Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, Sapporo, Japan †Emergency and Critical Care Center, Hokkaido University Hospital, Sapporo, Japan.
    Sepsis-associated encephalopathy is a major complication during sepsis, and an effective treatment remains unknown. Although minocycline (MINO) has neuroprotective effects and is an attractive candidate for treating sepsis-associated encephalopathy, the effect of MINO on synaptic plasticity during sepsis is still unclear. In the present study, we investigated the effects of MINO on long-term potentiation (LTP) in the hippocampus in a cecal ligation and puncture (CLP) mouse model. Read More

    Activated niacin receptor HCA2 inhibits chemoattractant-mediated macrophage migration via Gβγ/PKC/ERK1/2 pathway and heterologous receptor desensitization.
    Sci Rep 2017 Feb 10;7:42279. Epub 2017 Feb 10.
    College of Life Sciences, Zhejiang University, Yu Hang Tang Load 388, Hangzhou, PR China.
    The niacin receptor HCA2 is implicated in controlling inflammatory host responses with yet poorly understood mechanistic basis. We previously reported that HCA2 in A431 epithelial cells transduced Gβγ-protein kinase C- and Gβγ-metalloproteinase/EGFR-dependent MAPK/ERK signaling cascades. Here, we investigated the role of HCA2 in macrophage-mediated inflammation and the underlying mechanisms. Read More

    Superior accuracy of mid-regional proadrenomedullin for mortality prediction in sepsis with varying levels of illness severity.
    Ann Intensive Care 2017 Dec 10;7(1):15. Epub 2017 Feb 10.
    Service de Réanimation Médicale, Hôpital Bocage Central, C.H.U. DIJON, 14 rue Gaffarel, B.P. 77908-21079, Dijon Cedex, France.
    Background: The use of novel sepsis biomarkers has increased in recent years. However, their prognostic value with respect to illness severity has not been explored. In this work, we examined the ability of mid-regional proadrenomedullin (MR-proADM) in predicting mortality in sepsis patients with different degrees of organ failure, compared to that of procalcitonin, C-reactive protein and lactate. Read More

    [Purtscher-like retinopathy as a complication of acute pancreatitis].
    Rozhl Chir 2016 ;95(12):449-452
    Introduction: Purtscher-like retinopathy as a complication of acute pancreatitis is a disease which causes generalized retinal and macular oedema associated with retinal surface haemorrhage, which results in a permanent, sometimes partially reversible visual loss.

    Case Report: The case report presented in this article refers to the case of a 36-year-old woman with severe acute pancreatitis. The pancreatitis led to the development of acute respiratory insufficiency with signs of septic shock and consequently, the patient was transferred to the critical care unit. Read More

    Septic Shock of Unknown Origin: A Case Report of a Pseudoaneurysm of the Mitral-Aortic Intervalvular Fibrosa.
    J Clin Med Res 2017 Mar 25;9(3):225-228. Epub 2017 Jan 25.
    Cardiology Department, Tondela-Viseu Hospital Centre, Viseu, Portugal.
    Pseudoaneurysm of the mitral-aortic intervalvular fibrosa (P-MAIVF) is a rare complication of infective endocarditis and trauma, particularly of aortic valve surgery. Clinical symptoms are usually unspecific and generally due to complications. Transesophageal echocardiography (TEE) is the most commonly used exam to diagnose P-MAIVF. Read More

    Complement-mediated thrombotic microangiopathy secondary to sepsis-induced disseminated intravascular coagulation successfully treated with eculizumab: A case report.
    Medicine (Baltimore) 2017 Feb;96(6):e6056
    aDepartment of Trauma and Critical Care Medicine, University of Miyazaki Hospital, Miyazaki, Japan bDepartment of General Internal Medicine, Saitama Medical University, Saitama, Japan.
    Secondary thrombotic microangiopathies (TMAs) are induced by several underlying conditions; most are resolved by treating background disease. Eculizumab is a human monoclonal antibody that blocks the final stage of the complement system and effectively treats atypical hemolytic uremic syndrome (aHUS). In this report, we present a patient with TMA secondary to sepsis- induced coagulopathy, who was successfully treated with eculizumab. Read More

    Glucocorticoid Receptor Polymorphisms and Outcomes in Pediatric Septic Shock.
    Pediatr Crit Care Med 2017 Feb 7. Epub 2017 Feb 7.
    1Department of Pediatrics, UCSF Benioff Children's Hospital Oakland, Oakland, CA. 2Department of Pediatrics, Children's Hospital of Orange County, Orange, CA. 3Department of Pediatrics, Children's Mercy Hospital, Kansas City, MO. 4Department of Pediatrics, Penn State Hershey Children's Hospital, Hershey, PA. 5Department of Pediatrics, Akron Children's Hospital, Akron, OH. 6Department of Pediatrics, The Children's Hospital of Philadelphia, Philadelphia, PA. 7Department of Pediatrics, Texas Children's Hospital and Baylor College of Medicine, Houston, TX. 8Department of Pediatrics, Miami Children's Hospital, Miami, FL. 9Department of Pediatrics, C.S. Mott Children's Hospital at the University of Michigan, Ann Arbor, MI. 10Department of Pediatrics, Children's Hospital of Wisconsin, Milwaukee, WI. 11Department of Pediatrics, Children's National Health System, Washington, DC. 12Department of Pediatrics, Children's Hospital and Clinics of Minnesota, Minneapolis, MN. 13Department of Pediatrics, Riley Hospital for Children, Indianapolis, IN. 14Department of Pediatrics, Hackensack University Medical Center, Joseph M. Sanzari Children's Hospital, Hackensack, NJ. 15Department of Pediatrics, Children's Healthcare of Atlanta at Egleston, Atlanta, GA. 16Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, Cincinnati, OH. 17Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH.
    Objective: Polymorphisms of the glucocorticoid receptor gene are associated with outcome and corticosteroid responsiveness among patients with inflammatory disorders. We conducted a candidate gene association study to test the hypothesis that these polymorphisms are associated with outcome and corticosteroid responsiveness among children with septic shock.

    Design: We genotyped 482 children with septic shock for the presence of two glucocorticoid receptor polymorphisms (rs56149945 and rs41423247) associated with increased sensitivity and one glucocorticoid receptor polymorphism (rs6198) associated with decreased sensitivity to corticosteroids. Read More

    Role of Skin Biopsies in the Diagnosis of Hemophagocytic Lymphohistiocytosis.
    Am J Dermatopathol 2017 Jan 26. Epub 2017 Jan 26.
    *Department of Dermatology, University of Puerto Rico-School of Medicine, San Juan, Puerto Rico; and †Transitional Year Program, University of Puerto Rico-School of Medicine, San Juan, Puerto Rico.
    This is a report of a 15-year-old female who presented with a skin eruption and clinical features consistent with severe sepsis and septic shock. A diagnosis of acquired hemophagocytic lymphohistiocytosis (HLH) was made and confirmed by bone marrow analysis. Skin biopsy showed hemophagocytosis and CD163-positive staining of macrophages. Read More

    Association between cytokine response, the LRINEC score and outcome in patients with necrotising soft tissue infection: a multicentre, prospective study.
    Sci Rep 2017 Feb 8;7:42179. Epub 2017 Feb 8.
    Center for Infectious Medicine, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden.
    Early assessment of necrotising soft tissue infection (NSTI) is challenging. Analysis of inflammatory markers could provide important information about disease severity and guide decision making. For this purpose, we investigated the association between cytokine levels and the Laboratory Risk Indicator for Necrotising Fasciitis (LRINEC)-score, disease severity and mortality in NSTI patients. Read More

    Suspected atypical haemolytic uraemic syndrome in two post-partum patients with foetal-death in utero responding to eculizumab.
    Nephrology (Carlton) 2017 Feb;22 Suppl 1:18-22
    Department of Nephrology, Austin Hospital, Victoria, Australia.
    Background: Atypical haemolytic uraemic syndrome (aHUS) is a rare condition with the triad of microangiopathic haemolytic anaemia, thrombocytopenia and acute kidney injury. Other conditions that present in a similar manner peri-partum include thrombotic thrombocytopaenic purpura, and pregnancy associated conditions including HELLP syndrome (haemolysis, elevated liver enzymes and low platelets), severe pre-eclampsia and less commonly acute fatty liver of pregnancy.

    Case Reports: We describe two cases of suspected aHUS, who presented post-partum with foetal death-in-utero at 33 and 37 weeks respectively. Read More

    Increased Time to Initial Antimicrobial Administration Is Associated With Progression to Septic Shock in Severe Sepsis Patients.
    Crit Care Med 2017 Feb 6. Epub 2017 Feb 6.
    1University of Kansas School of Medicine, Kansas City, Kansas. 2Division of Pulmonary and Critical Care, Department of Internal Medicine, University of Kansas, Kansas City, Kansas.
    Objectives: To determine if time to initial antimicrobial is associated with progression of severe sepsis to septic shock.

    Design: Retrospective cohort.

    Setting: Six hundred fifty-six bed urban academic medical center. Read More

    Structural And Dynamic Insights into A Glycine-Mediated Short Analogue of A Designed Peptide in Lipopolysaccharide Micelles: Correlation Between Compact Structure And Anti-Endotoxin Activity.
    Biochemistry 2017 Feb 7. Epub 2017 Feb 7.
    In this study, we report an interaction study of a 13-residue analogue peptide VG13P (VARGWGRKCPLFG), derived from designed VG16KRKP peptide (VARGWKRKCPLFGKGG), with Lys6Gly mutation and removal of last three residues Lys14-Gly15-Gly16, in lipopolysaccharide (LPS), a major component of the outer-membrane of Gram-negative bacteria and responsible for sepsis or septic shock. VG13P displays an enhanced anti-endotoxin property as evident from significant reduction in LPS-induced TNF-α gene expression levels in monocytic cell line, while it retains almost unchanged antimicrobial activity as its parent VG16KRKP against Gram-negative bacterial as well as fungal pathogens. In addition, in vitro LPS binding properties of VG13P in comparison to its parent VG16KRKP also remained unhindered; suggesting that the flexible C-terminal end of VG16KRKP may not play a major role in its observed anti bacterial and LPS binding properties. Read More

    Therapeutic Restoration of Endothelial Glycocalyx in Sepsis.
    J Pharmacol Exp Ther 2017 Feb 6. Epub 2017 Feb 6.
    New York Medical College;
    Endothelial glycocalyx (EG) is disintegrated during sepsis. We showed (Am J Pathol, 2016) that this occurs very early in the course of sepsis and its prevention improves survival of mice with sepsis. Here, we sought to investigate the possibility to pharmacologically accelerate the restoration of disintegrated EG in sepsis. Read More

    Bacteremia due to Carbapenem-resistant Enterobacteriaceae (CRE): A Multicenter Clinical and Molecular Epidemiologic Analysis in the Nation's Epicenter for CRE.
    Antimicrob Agents Chemother 2017 Feb 6. Epub 2017 Feb 6.
    Public Health Research Institute, Rutgers New Jersey Medical School, Newark, NJ.
    Although the New York/New Jersey (NY/NJ) area is an epicenter for carbapenem-resistant Enterobacteriaceae (CRE), there are few multicenter studies of CRE from this region. We characterized patients with CRE bacteremia in 2013 at eight NY/NJ medical centers and determined the prevalence of carbapenem resistance among Enterobacteriaceae bloodstream isolates and CRE resistance mechanisms, genetic backgrounds, capsular types (cps), and antimicrobial susceptibilities. Of 121 patients with CRE bacteremia, 50% had cancer or transplantation. Read More

    Endogenous thrombin potential as marker of procoagulant response that can be useful in early stage of sepsis.
    Blood Coagul Fibrinolysis 2017 Feb 3. Epub 2017 Feb 3.
    aFaculty of Medicine, University of Novi Sad, Clinical Centre of Vojvodina, Emergency Centre, Department of Anesthesia and Reanimation bFaculty of Medicine, University of Novi Sad, Clinical Centre of Vojvodina, Clinic for Infectious Diseases cFaculty of Medicine, University of Novi Sad dFaculty of Medicine, University of Novi Sad, Institute of Child and Adolescent Health Care of Vojvodina, Clinic of Pediatric Surgery eLaboratory Medicine center, Department of Hematology, Hemostasis, and Prevention of Thrombosis, Faculty of Medicine, Clinical Center of Vojvodina, University of Novi Sad, Novi Sad, Vojvodina, Serbia.
    Sepsis is associated with complex procoagulant and anticoagulant changes that modify inflammatory response. Identification of coagulation markers that can differentiate useful procoagulant response from adverse alteration of clotting mechanism in patient with sepsis. In total, 150 patients who fulfilled criteria for diagnosis of sepsis were included in this study. Read More

    Efficacy of postoperative polymyxin B hemoperfusion in secondary peritonitis patients with septic shock: a propensity-matched analysis.
    Int J Artif Organs 2017 Feb 4;39(12):603-610. Epub 2017 Feb 4.
     Kidney Research Center, Department of Nephrology, Chang Gung Memorial Hospital, Taipei - Taiwan.
    Introduction: Severe sepsis and septic shock is still a challenge. Polymyxin B hemoperfusion (PMX) is a device designed to remove circulating endotoxin by adsorption, which is reported to improve treatment outcomes. This study aimed to further verify the efficacy of PMX on postoperative, peritonitis, septic shock patients. Read More

    Micheliolide provides protection of mice against Staphylococcus aureus and MRSA infection by down-regulating inflammatory response.
    Sci Rep 2017 Feb 6;7:41964. Epub 2017 Feb 6.
    Department of Immunology and Microbiology, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
    A major obstacle to therapy in intensive care units is sepsis caused by severe infection. In recent years gram-positive (G(+)) bacteria, most commonly staphylococci, are thought to be the main pathogens. Micheliolide (MCL) was demonstrated to provide a therapeutic role in rheumatoid arthritis, inflammatory intestinal disease, colitis-associated cancer, and lipopolysaccharide (LPS, the main component of G(-) bacterial cell wall) induced septic shock. Read More

    Continuous Hemodiafiltration with an AN69ST Hemofilter (AN69ST-CHDF) as FGF-23-Lowering Therapy.
    Clin Lab 2016 Dec;62(12):2349-2354
    Background: Recent studies have shown that fibroblast growth factor-23 (FGF-23) is elevated not only in chronic kidney disease (CKD), but also in acute illnesses such as acute kidney injury, septic shock, and acute heart failure. FGF-23 would be not only a simple biomarker but also a direct toxic factor in acute illness. Therefore, lowering circulating FGF-23 levels in clinical practice would be an exciting and valuable interventional strategy. Read More

    Epidemiological and mortality trends in infective endocarditis, a 17-year population-based prospective study.
    Cardiovasc Diagn Ther 2017 Feb;7(1):27-35
    Cardiology Department, Hôpital La Timone, Marseille, France.
    Background: The population at risk, the clinical and microbiological features of infective endocarditis (IE) have changed. Aim of our study was to evaluate the contemporary epidemiological trends, over a 17-year period in a definite region of Tuscany, Italy, to analyze the clinical outcomes and associated prognostic factors.

    Methods: From 1 January 1998 to 31 December 2014, all patients with a definite diagnosis of IE were prospectively entered in a data-base. Read More

    Immune Reconstitution Inflammatory Syndrome: Opening Pandora's Box.
    Case Rep Infect Dis 2017 9;2017:5409254. Epub 2017 Jan 9.
    Clinical Immunology Unit, Porto Hospital Centre, Porto, Portugal.
    One of the purposes of antiretroviral therapy (ART) is to restore the immune system. However, it can sometimes lead to an aberrant inflammatory response and paradoxical clinical worsening known as the immune reconstitution inflammatory syndrome (IRIS). We describe a 23-year-old male, HIV1 infected with a rapid progression phenotype, who started ART with TCD4+ of 53 cells/mm(3) (3,3%) and HIV RNA = 890000 copies/mL (6 log). Read More

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