43 results on '"Willem Joost Wiersinga"'
Search Results
2. Mortality and readmission rates among hospitalized COVID-19 patients with varying stages of chronic kidney disease: a multicenter retrospective cohort
- Author
-
Brent Appelman, Jetta J. Oppelaar, Lani Broeders, Willem Joost Wiersinga, Hessel Peters-Sengers, Liffert Vogt, and the CovidPredict Study Group
- Subjects
Medicine ,Science - Abstract
Abstract Chronic kidney disease (CKD) has been recognized as a highly prevalent risk factor for both the severity of coronavirus disease 2019 (COVID-19) and COVID-19 associated adverse outcomes. In this multicenter observational cohort study, we aim to determine mortality and readmission rates of patients hospitalized for COVID-19 across varying CKD stages. We performed a multicenter cohort study among COVID-19 patients included in the Dutch COVIDPredict cohort. The cohort consists of hospitalized patients from March 2020 until July 2021 with PCR-confirmed SARS-CoV-2 infection or a highly suspected CT scan-based infection with a CORADS score ≥ 4. A total of 4151 hospitalized COVID-19 patients were included of who 389 had a history of CKD before admission. After adjusting for all confounding covariables, in patients with CKD stage 3a, stage 3b, stage 4 and patients with KTX (kidney transplantation), odds ratios of death and readmission compared to patients without CKD ranged from 1.96 to 8.94. We demonstrate an evident increased 12-week mortality and readmission rate in patients with chronic kidney disease. Besides justified concerns for kidney transplant patients, clinicians should also be aware of more severe COVID-19 outcomes and increased vulnerability in CKD patients.
- Published
- 2022
- Full Text
- View/download PDF
3. Probiotics in the Intensive Care Unit
- Author
-
Alex R. Schuurman, Robert F. J. Kullberg, and Willem Joost Wiersinga
- Subjects
microbiome ,probiotics ,intensive care unit ,dysbiosis ,ventilator-associated pneumonia ,Therapeutics. Pharmacology ,RM1-950 - Abstract
The understanding of the gut microbiome in health and disease has shown tremendous progress in the last decade. Shaped and balanced throughout life, the gut microbiome is intricately related to the local and systemic immune system and a multitude of mechanisms through which the gut microbiome contributes to the host’s defense against pathogens have been revealed. Similarly, a plethora of negative consequences, such as superinfections and an increased rate of hospital re-admissions, have been identified when the gut microbiome is disturbed by disease or by the iatrogenic effects of antibiotic treatment and other interventions. In this review, we describe the role that probiotics may play in the intensive care unit (ICU). We discuss what is known about the gut microbiome of the critically ill, and the concept of probiotic intervention to positively modulate the gut microbiome. We summarize the evidence derived from randomized clinical trials in this context, with a focus on the prevention of ventilator-associated pneumonia. Finally, we consider what lessons we can learn in terms of the current challenges, efficacy and safety of probiotics in the ICU and what we may expect from the future. Throughout the review, we highlight studies that have provided conceptual advances to the field or have revealed a specific mechanism; this narrative review is not intended as a comprehensive summary of the literature.
- Published
- 2022
- Full Text
- View/download PDF
4. Minimum quality threshold in pre-clinical sepsis studies (MQTiPSS): an international expert consensus initiative for improvement of animal modeling in sepsis
- Author
-
Marcin F. Osuchowski, Alfred Ayala, Soheyl Bahrami, Michael Bauer, Mihaly Boros, Jean-Marc Cavaillon, Irshad H. Chaudry, Craig M. Coopersmith, Clifford Deutschman, Susanne Drechsler, Philip Efron, Claes Frostell, Gerhard Fritsch, Waldemar Gozdzik, Judith Hellman, Markus Huber-Lang, Shigeaki Inoue, Sylvia Knapp, Andrey V. Kozlov, Claude Libert, John C. Marshall, Lyle L. Moldawer, Peter Radermacher, Heinz Redl, Daniel G. Remick, Mervyn Singer, Christoph Thiemermann, Ping Wang, Willem Joost Wiersinga, Xianzhong Xiao, and Basilia Zingarelli
- Subjects
Guidelines ,Experiment ,Study design ,Humane modeling ,Infection types ,Organ dysfunction ,Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Abstract Background Pre-clinical animal studies precede the majority of clinical trials. While the clinical definitions of sepsis and recommended treatments are regularly updated, a systematic review of pre-clinical models of sepsis has not been done and clear modeling guidelines are lacking. Objective To address this deficit, a Wiggers-Bernard Conference on pre-clinical sepsis modeling was held in Vienna in May 2017. The goal of the conference was to identify limitations of pre-clinical sepsis models and to propose a set of guidelines, defined as the “Minimum Quality Threshold in Pre-Clinical Sepsis Studies” (MQTiPSS), to enhance translational value of these models. Methods A total of 31 experts from 13 countries participated and were divided into 6 thematic working groups (WG): (1) study design, (2) humane modeling, (3) infection types, (4) organ failure/dysfunction, (5) fluid resuscitation, and (6) antimicrobial therapy endpoints. As basis for the MQTiPSS discussions, the participants conducted a literature review of the 260 most highly cited scientific articles on sepsis models (2002–2013). Results Overall, the participants reached consensus on 29 points; 20 at “recommendation” (R) and 9 at “consideration” (C) strength. This executive summary provides a synopsis of the MQTiPSS consensus (Tables 1, 2, and 3). Detailed commentaries to all Rs and Cs are simultaneously published in three separate full-length papers. Conclusions We believe that these recommendations and considerations will serve to bring a level of standardization to pre-clinical models of sepsis and ultimately improve translation of pre-clinical findings. These guideline points are proposed as “best practices” for animal models of sepsis that should be implemented. In order to encourage its wide dissemination, this article is freely accessible in Shock, Infection and Intensive Care Medicine Experimental.
- Published
- 2018
- Full Text
- View/download PDF
5. The emerging role of the microbiota in the ICU
- Author
-
Nora Suzanne Wolff, Floor Hugenholtz, and Willem Joost Wiersinga
- Subjects
Medical emergencies. Critical care. Intensive care. First aid ,RC86-88.9 - Abstract
Abstract This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2018. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2018. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.
- Published
- 2018
- Full Text
- View/download PDF
6. Expression of intra- and extracellular granzymes in patients with typhoid fever.
- Author
-
Hanna K de Jong, Maria Isabel Garcia-Laorden, Arie J Hoogendijk, Christopher M Parry, Rapeephan R Maude, Arjen M Dondorp, Mohammed Abul Faiz, Tom van der Poll, and Willem Joost Wiersinga
- Subjects
Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
Typhoid fever, caused by the intracellular pathogen Salmonella (S.) enterica serovar Typhi, remains a major cause of morbidity and mortality worldwide. Granzymes are serine proteases promoting cytotoxic lymphocytes mediated eradication of intracellular pathogens via the induction of cell death and which can also play a role in inflammation. We aimed to characterize the expression of extracellular and intracellular granzymes in patients with typhoid fever and whether the extracellular levels of granzyme correlated with IFN-γ release.We analyzed soluble protein levels of extracellular granzyme A and B in healthy volunteers and patients with confirmed S. Typhi infection on admission and day of discharge, and investigated whether this correlated with interferon (IFN)-γ release, a cytokine significantly expressed in typhoid fever. The intracellular expression of granzyme A, B and K in subsets of lymphocytic cells was determined using flow cytometry. Patients demonstrated a marked increase of extracellular granzyme A and B in acute phase plasma and a correlation of both granzymes with IFN-γ release. In patients, lower plasma levels of granzyme B, but not granzyme A, were found at day of discharge compared to admission, indicating an association of granzyme B with stage of disease. Peripheral blood mononuclear cells of typhoid fever patients had a higher percentage of lymphocytic cells expressing intracellular granzyme A and granzyme B, but not granzyme K, compared to controls.The marked increase observed in extra- and intracellular levels of granzyme expression in patients with typhoid fever, and the correlation with stage of disease, suggests a role for granzymes in the host response to this disease.
- Published
- 2017
- Full Text
- View/download PDF
7. Expression and function of S100A8/A9 (calprotectin) in human typhoid fever and the murine Salmonella model.
- Author
-
Hanna K De Jong, Ahmed Achouiti, Gavin C K W Koh, Christopher M Parry, Stephen Baker, Mohammed Abul Faiz, Jaap T van Dissel, Albert M Vollaard, Ester M M van Leeuwen, Joris J T H Roelofs, Alex F de Vos, Johannes Roth, Tom van der Poll, Thomas Vogl, and Willem Joost Wiersinga
- Subjects
Arctic medicine. Tropical medicine ,RC955-962 ,Public aspects of medicine ,RA1-1270 - Abstract
BACKGROUND:Typhoid fever, caused by the Gram-negative bacterium Salmonella enterica serovar Typhi, is a major cause of community-acquired bacteremia and death worldwide. S100A8 (MRP8) and S100A9 (MRP14) form bioactive antimicrobial heterodimers (calprotectin) that can activate Toll-like receptor 4, promoting lethal, endotoxin-induced shock and multi-organ failure. We aimed to characterize the expression and function of S100A8/A9 in patients with typhoid fever and in a murine invasive Salmonella model. METHODS AND PRINCIPAL FINDINGS:S100A8/A9 protein levels were determined in acute phase plasma or feces from 28 Bangladeshi patients, and convalescent phase plasma from 60 Indonesian patients with blood culture or PCR-confirmed typhoid fever, and compared to 98 healthy control subjects. To functionally characterize the role of S100A8/A9, we challenged wildtype (WT) and S100A9-/- mice with S. Typhimurium and determined bacterial loads and inflammation 2- and 5- days post infection. We further assessed the antimicrobial function of recombinant S100A8/A9 on S. Typhimurium and S. Typhi replication in vitro. Typhoid fever patients demonstrated a marked increase of S100A8/A9 in acute phase plasma and feces and this increases correlated with duration of fever prior to admission. S100A8/A9 directly inhibited the growth of S. Typhimurium and S. Typhi in vitro in a dose and time dependent fashion. WT mice inoculated with S. Typhimurium showed increased levels of S100A8/A9 in both the liver and the systemic compartment but S100A9-/- mice were indistinguishable from WT mice with respect to bacterial growth, survival, and inflammatory responses, as determined by cytokine release, histopathology and organ injury. CONCLUSION:S100A8/A9 is markedly elevated in human typhoid, correlates with duration of fever prior to admission and directly inhibits the growth of S. Typhimurium and S. Typhi in vitro. Despite elevated levels in the murine invasive Salmonella model, S100A8/A9 does not contribute to an effective host response against S. Typhimurium in mice.
- Published
- 2015
- Full Text
- View/download PDF
8. The Platelet Lipidome Is Altered in Patients with COVID-19 and Correlates with Platelet Reactivity
- Author
-
Alex R. Schuurman, Valentine Léopold, Liza Pereverzeva, Osoul Chouchane, Tom D. Y. Reijnders, Justin de Brabander, Renée A. Douma, Michel van Weeghel, Eric Wever, Bauke V. Schomaker, Frédéric M. Vaz, Willem Joost Wiersinga, Cornelis van't Veer, Tom van der Poll, Center of Experimental and Molecular Medicine, Graduate School, AII - Inflammatory diseases, Laboratory Genetic Metabolic Diseases, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, APH - Personalized Medicine, APH - Methodology, and Infectious diseases
- Subjects
Blood Platelets ,P-Selectin ,platelets ,platelet activation ,Humans ,COVID-19 ,lipidomics ,Receptor, PAR-1 ,Hematology ,plasmalogens ,Triglycerides - Abstract
Background Activated platelets have been implicated in the proinflammatory and prothrombotic phenotype of coronavirus disease 2019 (COVID-19). While it is increasingly recognized that lipids have important structural and signaling roles in platelets, the lipidomic landscape of platelets during infection has remained unexplored. Objective To investigate the platelet lipidome of patients hospitalized for COVID-19. Methods We performed untargeted lipidomics in platelets of 25 patients hospitalized for COVID-19 and 23 noninfectious controls with similar age and sex characteristics, and with comparable comorbidities. Results Twenty-five percent of the 1,650 annotated lipids were significantly different between the groups. The significantly altered part of the platelet lipidome mostly comprised lipids that were less abundant in patients with COVID-19 (20.4% down, 4.6% up, 75% unchanged). Platelets from COVID-19 patients showed decreased levels of membrane plasmalogens, and a distinct decrease of long-chain, unsaturated triacylglycerols. Conversely, platelets from patients with COVID-19 displayed class-wide higher abundances of bis(monoacylglycero)phosphate and its biosynthetic precursor lysophosphatidylglycerol. Levels of these classes positively correlated with ex vivo platelet reactivity—as measured by P-selectin expression after PAR1 activation—irrespective of disease state. Conclusion Taken together, this investigation provides the first exploration of the profound impact of infection on the human platelet lipidome, and reveals associations between the lipid composition of platelets and their reactivity. These results warrant further lipidomic research in other infections and disease states involving platelet pathophysiology.
- Published
- 2022
9. Severe coronavirus disease 2019 in a patient with HIV-2 infection
- Author
-
Marc van der Valk, Willem Joost Wiersinga, Center of Experimental and Molecular Medicine, Infectious diseases, AII - Infectious diseases, APH - Digital Health, APH - Personalized Medicine, and APH - Global Health
- Subjects
2019-20 coronavirus outbreak ,Coronavirus disease 2019 (COVID-19) ,SARS-CoV-2 ,business.industry ,Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) ,Immunology ,Human immunodeficiency virus (HIV) ,COVID-19 ,HIV Infections ,medicine.disease_cause ,Virology ,Infectious Diseases ,HIV-2 ,medicine ,Humans ,Immunology and Allergy ,business - Published
- 2021
10. Intestinal transkingdom analysis on the impact of antibiotic perturbation in health and critical illness
- Author
-
W.M. de Vos, Cormac M. Kinsella, MJ Schultz, L. van den Hoek, Willem Joost Wiersinga, W. J. de Jonge, T. van der Poll, Bastiaan W. Haak, Jacqueline M. Lankelma, Robert F. J. Kullberg, Theodorus B. M. Hakvoort, Sarantos Kostidis, Ricard Argelaguet, T. van Gool, Floor Hugenholtz, and Martin Giera
- Subjects
0303 health sciences ,030306 microbiology ,medicine.drug_class ,Critically ill ,Antibiotics ,Functional impact ,Systemic immunity ,Biology ,biology.organism_classification ,Microbiology ,03 medical and health sciences ,Data sequences ,Critical illness ,medicine ,Protozoa ,Microbiome ,030304 developmental biology - Abstract
Bacterial microbiota play a critical role in mediating local and systemic immunity, and shifts in these microbial communities have been linked to impaired outcomes in critical illness. Emerging data indicate that other intestinal organisms, including bacteriophages, viruses of eukaryotes, fungi, and protozoa, are closely interlinked with the bacterial microbiota and their host, yet their collective role during antibiotic perturbation and critical illness remains to be elucidated. Here, multi-omics factor analysis (MOFA), a novel computational strategy to systematically integrate viral, fungal and bacterial sequence data, we describe the functional impact of exposure to broad-spectrum antibiotics in healthy volunteers and critically ill patients. We observe that a loss of the anaerobic intestinal environment is directly correlated with an overgrowth of aerobic pathobionts and their corresponding bacteriophages, as well as an absolute enrichment of opportunistic yeasts capable of causing invasive disease. These findings further illustrate the complexity of transkingdom interactions within the intestinal environment, and show that modulation of the bacterial component of the microbiome has implications extending beyond this kingdom alone.
- Published
- 2020
11. Antibiotic treatment for 6 days versus 12 days in patients with severe cellulitis: a multicentre randomized, double-blind, placebo-controlled, non-inferiority trial
- Author
-
Judith Branger, Willem Joost Wiersinga, Brent C. Opmeer, Robin Soetekouw, Sanjay U. C. Sankatsing, Kees Brinkman, Jan M. Prins, F. N. Lauw, Duncan R Cranendonk, A. I. M. Hoepelman, Jan Veenstra, M.A. van Agtmael, A.H. Pijlman, Jan Jelrik Oosterheert, P. J. de Vries, APH - Methodology, Clinical Research Unit, Infectious diseases, AII - Infectious diseases, Center of Experimental and Molecular Medicine, and Internal medicine
- Subjects
Microbiology (medical) ,medicine.medical_specialty ,medicine.drug_class ,Antibiotics ,Population ,Placebo ,law.invention ,Flucloxacillin ,Randomized controlled trial ,law ,Diabetes mellitus ,Internal medicine ,Medicine ,education ,education.field_of_study ,business.industry ,Cellulitis ,General Medicine ,Antibiotic therapy ,medicine.disease ,Confidence interval ,Infectious Diseases ,Duration ,Randomized clinical trial ,business ,medicine.drug - Abstract
Objectives: To investigate whether antibiotic treatment of 6 days' duration is non-inferior to treatment for 12 days in patients hospitalized for cellulitis. Methods: This multicentre, randomized, double-blind, placebo-controlled, non-inferiority trial enrolled adult patients hospitalized for severe cellulitis who were treated with intravenous flucloxacillin. At day 6 participants with symptom improvement who were afebrile were randomized between an additional 6 days of oral flucloxacillin or placebo in a 1:1 ratio, stratified for diabetes and hospital. The primary outcome was cure by day 14, without relapse by day 28. Secondary outcomes included a modified cure assessment and relapse rate by day 90. Results: Between August 2014 and June 2017, 151 of 248 included participants were randomized. The intention-to-treat population consisted of 76 and 73 participants allocated to 12 and 6 days of antibiotic therapy, respectively (mean age 62 years, 67% males, 24% diabetics); 38/76 (50.0%) and 36/73 (49.3%) were cured in the 12- and 6-day groups respectively (ARR 0.7 percentage points, 95%CI: –15.0 to 16.3). Cure rates were 56/76 (73.7%) and 49/73 (67.1%) with the modified cure assessment (ARR 6.6, 95%CI: –8.0 to 20.8). After initial cure without relapse, day 90 relapse rates were higher in the 6-day group (6% versus 24%, p < 0.05). Conclusions: Given the wide confidence intervals, we can neither confirm nor refute our hypothesis that 6 days of therapy is non-inferior to 12 days of therapy. However, a 6-day course resulted in significantly more frequent relapses by day 90. These findings require confirmation in future studies.
- Published
- 2020
12. Western-type diet influences mortality from necrotising pancreatitis and demonstrates a central role for butyrate
- Author
-
Olga Zaborina, Sanjiv Hyoju, Marc G. Besselink, Demi van Dalen, John C. Alverdy, Fons F. van den Berg, Marja A. Boermeester, Hjalmar C. van Santvoort, Willem Joost Wiersinga, AGEM - Amsterdam Gastroenterology Endocrinology Metabolism, Surgery, AII - Infectious diseases, Graduate School, Center of Experimental and Molecular Medicine, and Infectious diseases
- Subjects
acute pancreatitis ,medicine.drug_class ,Antibiotics ,Physiology ,Butyrate ,Gut flora ,Systemic inflammation ,antibiotics ,Cecum ,Mice ,Immune system ,medicine ,Animals ,Humans ,Pancreas ,biology ,business.industry ,Pancreatitis, Acute Necrotizing ,Gastroenterology ,bacterial infection ,Fecal Microbiota Transplantation ,biology.organism_classification ,medicine.disease ,butyrate ,Gastrointestinal Microbiome ,Mice, Inbred C57BL ,Butyrates ,Disease Models, Animal ,medicine.anatomical_structure ,Phenotype ,Diet, Western ,Disease Progression ,Pancreatitis ,Acute pancreatitis ,medicine.symptom ,business ,diet - Abstract
ObjectiveThe gut microbiota are the main source of infections in necrotising pancreatitis. We investigated the effect of disruption of the intestinal microbiota by a Western-type diet on mortality and bacterial dissemination in necrotising pancreatitis and its reversal by butyrate supplementation.DesignC57BL/6 mice were fed either standard chow or a Western-type diet for 4 weeks and were then subjected to taurocholate-induced necrotising pancreatitis. Blood and pancreas were collected for bacteriology and immune analysis. The cecum microbiota composition of mice was analysed using 16S rRNA gene amplicon sequencing and cecal content metabolites were analysed by targeted (ie, butyrate) and untargeted metabolomics. Prevention of necrotising pancreatitis in this model was compared between faecal microbiota transplantation (FMT) from healthy mice, antibiotic decontamination against Gram-negative bacteria and oral or systemic butyrate administration. Additionally, the faecal microbiota of patients with pancreatitis and healthy subjects were analysed.ResultsMortality, systemic inflammation and bacterial dissemination were increased in mice fed Western diet and their gut microbiota were characterised by a loss of diversity, a bloom ofEscherichia coliand an altered metabolic profile with butyrate depletion. While antibiotic decontamination decreased mortality, Gram-positive dissemination was increased. Both oral and systemic butyrate supplementation decreased mortality, bacterial dissemination, and reversed the microbiota alterations. Paradoxically, mortality and bacterial dissemination were increased with FMT administration. Finally, patients with acute pancreatitis demonstrated an increase in Proteobacteria and a decrease of butyrate producers compared with healthy subjects.ConclusionButyrate depletion and its repletion appear to play a central role in disease progression towards necrotising pancreatitis.
- Published
- 2019
13. The emerging role of the microbiota in the ICU
- Author
-
Willem Joost Wiersinga, Nora S. Wolff, and Floor Hugenholtz
- Subjects
0301 basic medicine ,Critical Illness ,MEDLINE ,Nutritional Status ,Review ,Critical Care and Intensive Care Medicine ,Bioinformatics ,03 medical and health sciences ,0302 clinical medicine ,RNA, Ribosomal, 16S ,Humans ,Medicine ,GeneralLiterature_REFERENCE(e.g.,dictionaries,encyclopedias,glossaries) ,RNA RIBOSOMAL 16S ,business.industry ,RC86-88.9 ,Microbiota ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,RNA ,030208 emergency & critical care medicine ,Nutritional status ,Medical emergencies. Critical care. Intensive care. First aid ,lcsh:RC86-88.9 ,Ribosomal RNA ,3. Good health ,Intensive Care Units ,030104 developmental biology ,Critical illness ,business - Abstract
This article is one of ten reviews selected from the Annual Update in Intensive Care and Emergency Medicine 2018. Other selected articles can be found online at https://www.biomedcentral.com/collections/annualupdate2018. Further information about the Annual Update in Intensive Care and Emergency Medicine is available from http://www.springer.com/series/8901.
- Published
- 2018
14. 'Antibiotic treatment for 6 days versus 12 days in patients with severe cellulitis' - Author's reply
- Author
-
Willem Joost Wiersinga, Jan M. Prins, Duncan R Cranendonk, Graduate School, AII - Infectious diseases, Infectious diseases, and Center of Experimental and Molecular Medicine
- Subjects
Microbiology (medical) ,medicine.medical_specialty ,medicine.drug_class ,business.industry ,Antibiotics ,MEDLINE ,Cellulitis ,General Medicine ,medicine.disease ,Anti-Bacterial Agents ,Infectious Diseases ,Internal medicine ,medicine ,Humans ,In patient ,business - Published
- 2020
15. Minimum Quality Threshold in Pre-Clinical Sepsis Studies (MQTiPSS): an international expert consensus initiative for improvement of animal modeling in sepsis
- Author
-
Basilia Zingarelli, Lyle L. Moldawer, Alfred Ayala, Daniel G. Remick, Susanne Drechsler, Michael Bauer, John C. Marshall, Sylvia Knapp, Judith Hellman, Peter Radermacher, Claes Frostell, Irshad H. Chaudry, Willem Joost Wiersinga, Xianzhong Xiao, Markus Huber-Lang, Marcin F. Osuchowski, Clifford S. Deutschman, Gerhard Fritsch, Mervyn Singer, Waldemar Gozdzik, Shigeaki Inoue, Andrey V. Kozlov, Craig M. Coopersmith, Christoph Thiemermann, Jean-Marc Cavaillon, Ping Wang, Claude Libert, Philip A. Efron, Soheyl Bahrami, Mihály Boros, Heinz Redl, Center of Experimental and Molecular Medicine, Infectious diseases, and AII - Infectious diseases
- Subjects
0301 basic medicine ,Biomedical Research ,Standardization ,Organ dysfunction ,Review ,030204 cardiovascular system & hematology ,Critical Care and Intensive Care Medicine ,THERAPIES ,Antimicrobial therapy ,Experiment ,0302 clinical medicine ,Medicine and Health Sciences ,Medicine ,Executive summary ,Fluid resuscitation ,lcsh:Medical emergencies. Critical care. Intensive care. First aid ,Hematology ,General Medicine ,Expert Opinion ,Infectious Diseases ,Emergency Medicine ,Public Health and Health Services ,SHOCK ,medicine.symptom ,Infection ,STANDARDS ,Microbiology (medical) ,medicine.medical_specialty ,Consensus ,Best practice ,Clinical Sciences ,MEDLINE ,Infection types ,Guidelines ,Microbiology ,Sepsis ,03 medical and health sciences ,Animals ,Humane modeling ,Intensive care medicine ,Animal ,business.industry ,Inflammatory and immune system ,Biology and Life Sciences ,Study design ,lcsh:RC86-88.9 ,Guideline ,medicine.disease ,Emergency & Critical Care Medicine ,Clinical trial ,030104 developmental biology ,Disease Models ,business ,Working group ,030217 neurology & neurosurgery - Abstract
Background: Pre-clinical animal studies precede the majority of clinical trials. While the clinical definitions of sepsis and recommended treatments are regularly updated, a systematic review of pre-clinical models of sepsis has not been done and clear modeling guidelines are lacking. Objective: To address this deficit, a Wiggers-Bernard Conference on pre-clinical sepsis modeling was held in Vienna in May 2017. The goal of the conference was to identify limitations of pre-clinical sepsis models and to propose a set of guidelines, defined as the "Minimum Quality Threshold in Pre-Clinical Sepsis Studies" (MQTiPSS), to enhance translational value of these models. Methods: A total of 31 experts from 13 countries participated and were divided into 6 thematic working groups (WG): (1) study design, (2) humane modeling, (3) infection types, (4) organ failure/dysfunction, (5) fluid resuscitation, and (6) antimicrobial therapy endpoints. As basis for the MQTiPSS discussions, the participants conducted a literature review of the 260 most highly cited scientific articles on sepsis models (2002-2013). Results: Overall, the participants reached consensus on 29 points; 20 at "recommendation" (R) and 9 at "consideration" (C) strength. This executive summary provides a synopsis of the MQTiPSS consensus (Tables 1, 2, and 3). Detailed commentaries to all Rs and Cs are simultaneously published in three separate full-length papers. Conclusions: We believe that these recommendations and considerations will serve to bring a level of standardization to pre-clinical models of sepsis and ultimately improve translation of pre-clinical findings. These guideline points are proposed as "best practices" for animal models of sepsis that should be implemented. In order to encourage its wide dissemination, this article is freely accessible in Shock, Infection and Intensive Care Medicine Experimental.
- Published
- 2018
16. Effect of Antibiotic-Mediated Microbiome Modulation on Rotavirus Vaccine Immunogenicity: A Human, Randomized-Control Proof-of-Concept Trial
- Author
-
Ester M. M. van Leeuwen, Barry L. Hykes, Michael Boele van Hensbroek, Vanessa C. Harris, Baoming Jiang, Daniel E. Velasquez, Willem Joost Wiersinga, E. M. Kemper, Bastiaan W. Haak, Lindsay Droit, Scott A. Handley, Guy A.M. Berbers, AII - Amsterdam institute for Infection and Immunity, APH - Health Behaviors & Chronic Diseases, Graduate School, APH - Global Health, AII - Infectious diseases, AGEM - Digestive immunity, Pharmacy, AGEM - Endocrinology, metabolism and nutrition, Experimental Immunology, Global Health, General Paediatrics, Center of Experimental and Molecular Medicine, and Infectious diseases
- Subjects
0301 basic medicine ,Immunoglobulin A ,Adult ,Male ,medicine.drug_class ,Antibiotics ,medicine.disease_cause ,Vaccines, Attenuated ,Microbiology ,Pneumococcal Vaccines ,03 medical and health sciences ,Feces ,Immune system ,Immunogenicity, Vaccine ,Vancomycin ,Virology ,Rotavirus ,medicine ,Tetanus Toxoid ,Humans ,Microbiome ,biology ,Immunogenicity ,Rotavirus Vaccines ,Rotavirus vaccine ,Anti-Bacterial Agents ,Gastrointestinal Microbiome ,Virus Shedding ,030104 developmental biology ,Immunology ,biology.protein ,Parasitology ,Female ,medicine.drug - Abstract
Rotavirus vaccines (RVV) protect against childhood gastroenteritis caused by rotavirus (RV) but have decreased effectiveness in low- and middle-income settings. This proof-of-concept, randomized-controlled, open-label trial tested if microbiome modulation can improve RVV immunogenicity. Healthy adults were randomized and administered broad-spectrum (oral vancomycin, ciprofloxacin, metronidazole), narrow-spectrum (vancomycin), or no antibiotics and then vaccinated with RVV, 21 per group per protocol. Baseline anti-RV IgA was high in all subjects. Although antibiotics did not alter absolute anti-RV IgA titers, RVV immunogenicity was boosted at 7 days in the narrow-spectrum group. Further, antibiotics increased fecal shedding of RV while also rapidly altering gut bacterial beta diversity. Beta diversity associated with RVV immunogenicity boosting at day 7 and specific bacterial taxa that distinguish RVV boosters and RV shedders were identified. Despite the negative primary endpoint, this study demonstrates that microbiota modification alters the immune response to RVV and supports further exploration of microbiome manipulation to improve RVV immunogenicity. Rotavirus vaccines (RVV) are less effective in poor-resourced settings. This randomized-controlled trial in adults tested the effect of microbiome modulation via broad-spectrum, narrow-spectrum, or no antibiotics on RVV performance. Absolute anti-RV IgA titer did not change. However, antibiotics resulted in higher day-7 boosting and increased RV-antigen shedding.
- Published
- 2018
17. Biomarkers in Sepsis
- Author
-
Tom van der Poll, Willem Joost Wiersinga, Tjitske S. R. van Engelen, Brendon P. Scicluna, AII - Infectious diseases, Graduate School, AII - Amsterdam institute for Infection and Immunity, Infectious diseases, Epidemiology and Data Science, Center of Experimental and Molecular Medicine, and APH - Quality of Care
- Subjects
0301 basic medicine ,Systems biology ,Physiologic process ,Critical Care and Intensive Care Medicine ,Bioinformatics ,Risk profile ,Procalcitonin ,Sepsis ,03 medical and health sciences ,0302 clinical medicine ,Medicine ,Humans ,business.industry ,fungi ,food and beverages ,Proteins ,030208 emergency & critical care medicine ,General Medicine ,medicine.disease ,030104 developmental biology ,Biomarker (medicine) ,RNA ,business ,Biomarkers ,Omics technologies - Abstract
A biomarker is a characteristic by which a (patho) physiologic process can be identified. Biomarkers can be of diagnostic value (to discriminate infection from noninfectious conditions or to determine the causative pathogen), of prognostic value (to assign risk profiles and predict outcome), and in the future may be of theranostic value (to aid in the selection and monitoring of therapy). Systems biology provides a promising tool for the discovery of novel biomarkers. Biomarkers can be the key to personalized targeted treatment in the future clinical management of sepsis
- Published
- 2017
18. Anti-Inflammatory Cytokines, Soluble Receptors, and Natural Antagonists
- Author
-
Willem Joost Wiersinga and Tom van der Poll
- Subjects
Chemistry ,medicine.drug_class ,medicine ,Pattern recognition receptor ,Interleukin ,Pharmacology ,Receptor ,Anti-inflammatory - Published
- 2017
19. Melioidosis in Africa: should we be looking more closely?
- Author
-
Willem Joost Wiersinga, Martin P. Grobusch, Emma Birnie, and Direk Limmathurotsakul
- Subjects
Male ,Microbiology (medical) ,medicine.medical_specialty ,Burkholderia pseudomallei ,Melioidosis ,Disease epidemiology ,Microbiology ,Patient care ,Southeast asia ,Diagnosis, Differential ,parasitic diseases ,Epidemiology ,medicine ,Animals ,Humans ,Intensive care medicine ,Gnathostomiasis ,biology ,medicine.disease ,biology.organism_classification ,Antibodies, Bacterial ,Malaria ,Africa ,Immunology ,Female - Abstract
ABSTRACT Melioidosis is a life-threatening infection caused by the Gram-negative bacterium Burkholderia pseudomallei, mainly found in Southeast Asia. Recently, African foci have been identified, although reports remain mostly anecdotal. In Africa, multiple febrile diseases have been erroneously attributed to malaria in the past, and many cases of fever remain mis- or undiagnosed. Vigilance for previously under-recognized pathogens may enhance our understanding of disease epidemiology and facilitate improvement of patient care. Melioidosis may be such a condition. We summarize data on melioidosis in Africa and discuss the future directions for epidemiological, clinical and bacteriological studies. We conclude that searching for old bugs in new places is no academic treasure hunt but a clinically relevant activity to pursue.
- Published
- 2015
20. The Intestinal Microbiome in Infectious Diseases: The Clinical Relevance of a Rapidly Emerging Field
- Author
-
Willem Joost Wiersinga, Michael Boele van Hensbroek, Vanessa C. Harris, Bastiaan W. Haak, APH - Health Behaviors & Chronic Diseases, Graduate School, APH - Global Health, AII - Infectious diseases, Global Health, General Paediatrics, Amsterdam institute for Infection and Immunity, Infectious diseases, and Center of Experimental and Molecular Medicine
- Subjects
0301 basic medicine ,medicine.medical_specialty ,business.industry ,microbiology ,Review Article ,infectious diseases ,intestinal microbiome ,3. Good health ,immunology ,03 medical and health sciences ,030104 developmental biology ,Oncology ,Infectious disease (medical specialty) ,Intestinal Microbiome ,Host organism ,medicine ,Clinical significance ,Intestinal bacteria ,Microbiome ,Intensive care medicine ,business ,Infectious Disease Medicine - Abstract
The field of infectious disease is undergoing a paradigm shift as the intestinal microbiome is becoming understood. The aim of this review is to inform infectious disease physicians of the potential relevance of the intestinal microbiome to their practice. We searched Medline using both index and text words relating to infectious diseases, microbiome, and probiotics. Relevant articles published up through 2017 were reviewed within Rayyan. The review illustrates pathophysiologic concepts linking the microbiome and infectious diseases; specifically, the intestinal microbiome’s relevance to early immune development, the microbiome and enteric infections, the microbiome’s relevance in compromised hosts, and antimicrobial resistance. Within each subject, there are specific examples of diseases and at-risk patient populations where a role for the microbiome has been strongly established. This provides an overview of the significance of the intestinal microbiome to microbiology, pediatric and adult infectious diseases with an underpinning of concepts useful for the practicing clinician.
- Published
- 2017
21. List of Contributors
- Author
-
Fredrick M. Abrahamian, Michael J. Aldape, Edelweiss Aldasoro, Upton D. Allen, Hythem Al-Sum, Milan J. Anadkat, Katherine Anders, Emmanouil Angelakis, Brian John Angus, Anastasia Antoniadou, Fabio Arena, Joop E. Arends, Jose R. Arribas, Andrew W. Artenstein, John C. Atherton, John N. Aucott, Tar-Ching Aw, Hilary M. Babcock, Robin Bailey, Thomas C. Bailey, Adam Z. Banks, David J. Barillo, Ernie-Paul Barrette, Martijn P. Bauer, Roger Bayston, C. Ben Beard, Justin Beardsley, Nick J. Beeching, Rodolfo E. Bégué, Guido Beldi, Constance A. Benson, Elie F. Berbari, Jean-Michel Berenger, Christoph Berger, Jose I. Bernardino, Jacques Bille, Alexander C. Billioux, Ari Bitnun, Iain Blair, Stéphane Blanche, Thomas P. Bleck, Chantal P. Bleeker-Rovers, Gijs Bleijenberg, Karen C. Bloch, Johannes Blum, Emily A. Blumberg, Robert A. Bonomo, Marc J.M. Bonten, Rafik Bourayou, Emilio Bouza, K. Ashley Brandt, Florence Bretelle, Sylvain Brisse, Warwick J. Britton, Itzhak Brook, Matthijs C. Brouwer, Sarah K. Browne, Amy E. Bryant, Silja Bühler, Eileen M. Bulger, R. Mark L. Buller, Leah A. Burke, Christian Burri, Marcus W. Butler, Thierry Calandra, David P. Calfee, Antonia Calvo-Cano, D. William Cameron, Joseph A. Carcillo, Gail Carson, Stephen T. Chambers, Remi N. Charrel, Vinh Chau Van Nguyen, Stéphane Chevaliez, Tom M. Chiller, Eirini Christaki, Kevin K. Chung, David B. Clifford, Nathan Clumeck, Jonathan Cohen, John Collinge, Christopher P. Conlon, Curdin Conrad, Fiona J. Cooke, Jennifer Rittenhouse Cope, G. Ralph Corey, John H. Cross, Burke A. Cunha, Cheston B. Cunha, Benoit D'Journo, George L. Daikos, Johannes M.A. Daniels, Robert N. Davidson, Nicholas P.J. Day, Kevin M. De Cock, Thushan I. de Silva, Henry J.C. de Vries, Stéphane de Wit, Julie Delaloye, David W. Denning, David T. Dennis, Shireesha Dhanireddy, Elodi J. Dielubanza, David J. Diemert, Mehmet Doganay, Tom Doherty, Christiane Dolecek, Arjen M. Dondorp, Abby Douglas, Michel Drancourt, Grégory Dubourg, Michael N. Dudley, Guillaume Durand, Benjamin J. Eckhardt, Androulla Efstratiou, Miquel B. Ekkelenkamp, Ambika Eranki, Hakan Erdem, Gerome V. Escota, Heather L. Evans, Alice Chijioke Eziefula, Florence Fenollar, Alan Fenwick, Joshua Fierer, Roger G. Finch, James M. Fleckenstein, Christina Forstner, Federico Foschi, Pierre-Edouard Fournier, Martyn A. French, Kenneth L. Gage, Lynne S. Garcia, Joaquim Gascon, Arturo S. Gastañaduy, Philippe Gautret, William M. Geisler, Khalil G. Ghanem, Tommaso Giani, Maddalena Giannella, Bruce L. Gilliam, Michel Gilliet, Carol A. Glaser, Youri Glupczynski, John W. Gnann, Ellie J.C. Goldstein, Bruno Gottstein, Frederique Gouriet, Patti E. Gravitt, Michael D. Green, Stephen T. Green, Andreas H. Groll, Roy M. Gulick, Arjun Gupta, Gilbert Habib, Stephan Harbarth, Marianne Harris, Frederick G. Hayden, David J. Hetem, Philip C. Hill, Bernard Hirschel, Aimee C. Hodowanec, Louis Hoffart, Christian Hoffmann, Steven M. Holland, Peter W. Horby, David J. Horne, Sami Hraiech, Mark W. Hull, Angela Huttner, Richard J.M. Ingram, Jasmin Islam, Michael G. Ison, Scott H. James, Claire Jenkins, Stephen G. Jenkins, Jørgen Skov Jensen, Christine Johnston, Theodore B. Jones, Stephen J. Jordan, Kathleen G. Julian, Yasuyuki Kato, Carol A. Kauffman, Keith S. Kaye, Michael P. Keane, James Keeney, Paul Kelly, Stephen J. Kent, Winfried V. Kern, Yoav Keynan, Andrea A. Kim, Isabelle Koné-Paut, Chris Kosmidis, Aloys C.M. Kroes, Frank P. Kroon, Thomas G. Ksiazek, F. Matthew Kuhlmann, Ed J. Kuijper, Jennie H. Kwon, George B. Kyei, Karine Lacombe, Philippe Lagacé-Wiens, Jean-Christophe Lagier, Theresa Lamagni, Luce Landraud, Fanny Lanternier, Kerry L. LaPlante, Stephen D. Lawn, Steven J. Lawrence, Hakan Leblebicioglu, Nelson Lee, James E. Leggett, Philippe Lehours, Pierre-Yves Levy, Rainer G. Leyh, Rebecca A. Lillis, Direk Limmathurotsakul, Jennifer Lin, H.D. Alan Lindquist, Benjamin A. Lipsky, Christina Liscynesky, David Looney, Olivier Lortholary, Franklin D. Lowy, Benjamin J. Luft, Philip A. Mackowiak, Paul A. MacPherson, Valérie Maghraoui-Slim, Patrick W. Mallon, Julie E. Mangino, Oriol Manuel, Oscar Marchetti, Kristen M. Marks, Kieren A. Marr, Jeanne Marrazzo, Jonas Marschall, David H. Martin, Frédéric Matonti, Richard S. Matulewicz, Kenneth H. Mayer, Russell J. McCulloh, Rose McGready, Rennatus Mdodo, Simon Mead, Francis Mégraud, Graeme Meintjes, Sarah C. Metcalf, Marian G. Michaels, Giovanni Battista Migliori, Michael A. Miles, Alastair Miller, Matthew J. Mimiaga, Marie-Paule Mingeot-Leclercq, Elizabeth Ann Misch, Makedonka Mitreva, Julio S.G. Montaner, Caroline B. Moore, Patricia Muñoz, Jose Muñoz, Clinton K. Murray, Didier Musso, Mable Mutengo, Misha M. Mutizwa, Kurt G. Naber, Pavithra Natarajan, Santiago Neme, Paul N. Newton, Ronald A. Nichols, Lindsay E. Nicolle, François Nosten, Luigi D. Notarangelo, Thomas B. Nutman, Paul Nyirjesy, P. Ronan O'Connell, Steven M. Opal, L. Peter Ormerod, Douglas R. Osmon, Marie Boulze Pankert, Giuseppe Pantaleo, Laurent Papazian, Diane M. Parente, Philippe Parola, Shadi Parsaei, Manuel A. Pascual, Rupa Patel, Eleni Patrozou, Jean-Michel Pawlotsky, Sharon J. Peacock, Jean-Claude Pechère, Ivan Pelegrin, Barry S. Peters, Edgar J.G. Peters, Jeannine M. Petersen, Lyle R. Petersen, Vidmantas Petraitis, Luu-Ly Pham, Albert Picado, Adrian Pilatz, Benoit Pilmis, María-Jesús Pinazo, Mathias W. Pletz, Jason M. Pogue, Evelyn L. Polgreen, Philip M. Polgreen, Klara M. Posfay-Barbe, William G. Powderly, Rachel Presti, Guy Prod'hom, Mirja Puolakkainen, Thomas C. Quinn, Didier Raoult, Raymund R. Razonable, Robert C. Read, Robert R. Redfield, Rob J. Rentenaar, Steven J. Reynolds, Camillo Ribi, Malcolm D. Richardson, Michele L. Ritter, Antoine Roch, Jürgen Kurt Rockstroh, Amanda Rojek, José R. Romero, Suzan H.M. Rooijakkers, Daniel Rosenbluth, Sergio D. Rosenzweig, Gian Maria Rossolini, Ethan Rubinstein, Greg Ryan, Steven A. Safren, Vikrant V. Sahasrabuddhe, Pekka A.I. Saikku, Mohammad M. Sajadi, Michelle R. Salvaggio, Carlos A.Q. Santos, Michael J. Satlin, Anthony J. Schaeffer, Christoph Schimmer, Robert T. Schooley, Richard F. Schumacher, Beverly E. Sha, Daniel S. Shapiro, Gerard Sheehan, David M. Shlaes, Shmuel Shoham, Cameron P. Simmons, Dennis W. Simon, Matthew S. Simon, Kari A. Simonsen, Mary P.E. Slack, Tyrel T. Smith, Jack D. Sobel, Maria Souli, Shruti Sridhar, James M. Steckelberg, Dennis L. Stevens, Heather Strah, A. Willem Sturm, Somnuek Sungkanuparph, Sarah J. Tabrizi, Evelina Tacconelli, Chen Sabrina Tan, Randy A. Taplitz, Guillemette Thomas, Lora D. Thomas, Franck Thuny, Guy Thwaites, Frederic Tissot, Tone Tønjum, Francesca J. Torriani, Christian Toso, Paul M. Tulkens, Allan R. Tunkel, Claire E. Turner, Andrew P. Ustianowski, Françoise van Bambeke, Reinout van Crevel, Diederik van de Beek, Christian van Delden, Menno M. van der Eerden, Jos W.M. van der Meer, Tom van der Poll, Jakko van Ingen, Jos van Putten, Bernard P. Vaudaux, Sten H. Vermund, Raphael P. Viscidi, Kumar Visvanathan, Govinda S. Visvesvara, Lorenz von Seidlein, Florian M.E. Wagenlehner, Anna Wald, Thomas J. Walsh, David C. Warhurst, David W. Warnock, David A. Warrell, Mary J. Warrell, Adilia Warris, Richard R. Watkins, David J. Weatherall, Rainer Weber, Wolfgang Weidner, Jonathan R. White, Peter J. White, James Whitehorn, Richard J. Whitley, Christopher J.M. Whitty, Willem Joost Wiersinga, Mark H. Wilcox, Thomas N. Williams, Cara C. Wilson, Mary Elizabeth Wilson, Hilmar Wisplinghoff, Robin Wood, Richard G. Wunderink, David Wyles, Zhi-Tao Yang, Jonathan S. Yoder, Najam A. Zaidi, Andrea J. Zimmer, Jane N. Zuckerman, and Alimuddin Zumla
- Published
- 2017
22. Sepsis
- Author
-
Tom Van Der Poll and Willem Joost Wiersinga
- Published
- 2017
23. The coagulation system in melioidosis: from pathogenesis to new treatment strategies
- Author
-
Tom van der Poll, Willem Joost Wiersinga, and Liesbeth M. Kager
- Subjects
Microbiology (medical) ,Burkholderia pseudomallei ,Melioidosis ,medicine.medical_treatment ,Inflammation ,Disease ,Microbiology ,Sepsis ,Pathogenesis ,Virology ,Fibrinolysis ,medicine ,Animals ,Humans ,Blood Coagulation ,biology ,medicine.disease ,biology.organism_classification ,Blood Coagulation Factors ,Pneumonia ,Infectious Diseases ,Immunology ,medicine.symptom ,Protein C - Abstract
Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is a dreadful disease common in South-East Asia and Northern Australia and is characterized by chronic suppurative lesions and pneumonia. Melioidosis may evolve into severe sepsis with multi-organ failure with high mortalities, despite proper antibiotic therapy. Besides activation of a strong pro-inflammatory host response, the coagulation system plays an important role during melioidosis, which is thought to be host-protective. In particular, a procoagulant state together with downregulation of anticoagulant pathways and activation of fibrinolysis are present, all closely interrelated with parameters of inflammation. This review presents an overview of recent studies in which the role of coagulation, anti-coagulation and fibrinolysis during melioidosis was investigated both in patients and in experimental settings.
- Published
- 2014
24. Platelets aid in host defense during melioidosis
- Author
-
Jerry Ware, A. F. de Vos, Anita E. Grootemaat, Gavin C. K. W. Koh, Theodora A. M. Claushuis, Willem Joost Wiersinga, C. van 't Veer, Baidong Hou, L. E. H. Van Der Donk, Daisy I. Picavet, Emma Birnie, T. van der Poll, and N. N. Van Der Wel
- Subjects
Melioidosis ,Host (biology) ,medicine ,Platelet ,Host defence ,Infectious and parasitic diseases ,RC109-216 ,Biology ,melioidosis, platelets, host defence ,medicine.disease ,Microbiology - Abstract
No abstract available
- Published
- 2017
25. Host innate immune responses to sepsis
- Author
-
Tom van der Poll, Stije J. Leopold, Willem Joost Wiersinga, and Duncan R Cranendonk
- Subjects
Microbiology (medical) ,protease activated receptors ,myeloid related protein (Mrp)-8/14 ,Immunology ,Virulence ,Review ,Biology ,Microbiology ,Sepsis ,sepsis ,Immune system ,medicine ,Humans ,coagulation ,Receptor ,Pathogen ,innate immunity ,danger-associated molecular patterns (DAMP) ,Inflammation ,Innate immune system ,Host (biology) ,activated protein C ,Toll-Like Receptors ,Pattern recognition receptor ,pattern recognition receptors ,medicine.disease ,Immunity, Innate ,neutrophil extracellular traps (NET) ,Infectious Diseases ,pathogen-associated molecular patterns (PAMP) ,Receptors, Pattern Recognition ,Host-Pathogen Interactions ,Cytokines ,Parasitology ,Signal Transduction - Abstract
The immune response to sepsis can be seen as a pattern recognition receptor-mediated dysregulation of the immune system following pathogen invasion in which a careful balance between inflammatory and anti-inflammatory responses is vital. Invasive infection triggers both pro-inflammatory and anti-inflammatory host responses, the magnitude of which depends on multiple factors, including pathogen virulence, site of infection, host genetics, and comorbidities. Toll-like receptors, the inflammasomes, and other pattern recognition receptors initiate the immune response after recognition of danger signals derived from microorganisms, so-called pathogen-associated molecular patterns or derived from the host, so-called danger-associated molecular patterns. Further dissection of the role of host–pathogen interactions, the cytokine response, the coagulation cascade, and their multidirectional interactions in sepsis should lead toward the development of new therapeutic strategies in sepsis.
- Published
- 2013
26. Significant Correlation Between the Infant Gut Microbiome and Rotavirus Vaccine Response in Rural Ghana
- Author
-
Vanessa C, Harris, George, Armah, Susana, Fuentes, Katri E, Korpela, Umesh, Parashar, John C, Victor, Jacqueline, Tate, Carolina, de Weerth, Carlo, Giaquinto, Willem Joost, Wiersinga, Kristen D C, Lewis, and Willem M, de Vos
- Subjects
Male ,Rotavirus ,Rural Population ,Bacteria ,Bacteroidetes ,Rotavirus Vaccines ,Infant ,Antibodies, Viral ,Microarray Analysis ,Vaccines, Attenuated ,Ghana ,Rotavirus Infections ,Gastroenteritis ,Gastrointestinal Microbiome ,Immunoglobulin A ,Streptococcus bovis ,Feces ,Pregnancy ,Case-Control Studies ,Humans ,Female ,Immunity, Mucosal - Abstract
Rotavirus (RV) is the leading cause of diarrhea-related death in children worldwide and 95% of RV-associated deaths occur in Africa and Asia where RV vaccines (RVVs) have lower efficacy. We hypothesize that differences in intestinal microbiome composition correlate with the decreased RVV efficacy observed in poor settings. We conducted a nested, case-control study comparing prevaccination, fecal microbiome compositions between 6-week old, matched RVV responders and nonresponders in rural Ghana. These infants' microbiomes were then compared with 154 age-matched, healthy Dutch infants' microbiomes, assumed to be RVV responders. Fecal microbiome analysis was performed in all groups using the Human Intestinal Tract Chip. We analyzed findings in 78 Ghanaian infants, including 39 RVV responder and nonresponder pairs. The overall microbiome composition was significantly different between RVV responders and nonresponders (FDR, 0.12), and Ghanaian responders were more similar to Dutch infants than nonresponders (P = .002). RVV response correlated with an increased abundance of Streptococcus bovis and a decreased abundance of the Bacteroidetes phylum in comparisons between both Ghanaian RVV responders and nonresponders (FDR, 0.008 vs 0.003) and Dutch infants and Ghanaian nonresponders (FDR, 0.002 vs 0.009). The intestinal microbiome composition correlates significantly with RVV immunogenicity and may contribute to the diminished RVV immunogenicity observed in developing countries.
- Published
- 2016
27. Immunosuppression associated with interleukin-1R-associated-kinase-M upregulation predicts mortality in Gram-negative sepsis (melioidosis)
- Author
-
Willem Joost Wiersinga, Tom van der Poll, Arjen M. Dondorp, Cornelis van 't Veer, Sharon J. Peacock, Nicholas P. J. Day, Petra S. van den Pangaart, Infectious diseases, Center of Experimental and Molecular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam institute for Infection and Immunity, and Other departments
- Subjects
Adult ,Male ,Melioidosis ,Adolescent ,medicine.medical_treatment ,Critical Care and Intensive Care Medicine ,Polymerase Chain Reaction ,Proinflammatory cytokine ,Sepsis ,Young Adult ,Intensive care ,medicine ,Immune Tolerance ,Humans ,Aged ,DNA Primers ,Aged, 80 and over ,biology ,Base Sequence ,Burkholderia pseudomallei ,business.industry ,Interleukin ,Immunosuppression ,Middle Aged ,bacterial infections and mycoses ,medicine.disease ,biology.organism_classification ,Up-Regulation ,Cytokine ,Interleukin-1 Receptor-Associated Kinases ,Immunology ,bacteria ,Cytokines ,Chemokines ,business - Abstract
Objectives: Sepsis is associated with immunosuppression (characterized by a reduced rapacity of circulating monocytes to release proinflammatory cytokines), which has been implicated in late mortality. Melioidosis, caused by the Gram-negative bacterium Burkholderia pseudomallei, is an important cause of community-acquired sepsis in Southeast Asia with a mortality of up to 40%. Previous in vitro and murine studies have suggested a key role for the so-called negative regulators of the toll-like receptor (TLR) signaling pathway in immunosuppression. In this study, we investigated the expression of these negative TLR regulators in patients with septic melioidosis in association with the responsiveness of peripheral blood leukocytes of these patients to lipopolysaccharide and B. pseudomallei. Design: Ex vivo study. Setting: Academic research laboratory. Patients: Thirty-two healthy controls and 34 patients with sepsis caused by S. pseudomallei. Interventions: None. Measurements: 1) Plasma cytokine levels; 2) ex vivo cytokine production capacity of whole blood; and 3) purified mononuclear cell-derived messenger RNA (mRNA) levels of key inhibitory molecules of the TLR-signaling cascade were investigated. Main Results: In accordance with an immunosuppressed state, whole blood of patents demonstrated a strongly decreased capacity to release the proinflammatory cytokines tumor necrosis factor-alpha, interleukin-1 beta, and the chemokine intedeukin-8 after ex vivo stimulation with lipopolysaccharide or B. pseudomallei Analysis of myeloid-differentiation-88-short, interleukin-1R-associated-kinase (IRAK)-M, IRAK-1, suppressor-of-cytokine signaling-3, Src-homology-2-domain-containing inositol-5-phosphatose-1, single-immunoglobulin-interleukin-1R-related-molecule, and A20 mRNA expression in purified mononuclear cells showed decreased IRAK-1 and elevated IRAK-M expression in patents with septic melioidosis. Immunosuppression was correlated with mortality; furthermore, patents who eventually died had higher IRAK-M mRNA levels on admission than the patents who survived. Conclusions: Immunosuppression in sepsis caused by B. pseudomallei is associated with an upregulation of IRAK-M and an indicator of poor outcome. (Crit Care Med 2009; 37:569-576)
- Published
- 2016
28. The Systemic Pro-Inflammatory Response in Sepsis
- Author
-
Willem Joost Wiersinga, Hanna K. de Jong, and Tom van der Poll
- Subjects
Innate immune system ,Acute-phase protein ,Inflammation ,Biology ,medicine.disease ,Systemic Inflammatory Response Syndrome ,Complement system ,Sepsis ,Systemic inflammatory response syndrome ,Mice ,Downregulation and upregulation ,Gene Expression Regulation ,Immunology ,Host-Pathogen Interactions ,medicine ,Leukocytes ,Immunology and Allergy ,Animals ,Cytokines ,Humans ,Macrophage migration inhibitory factor ,medicine.symptom ,Blood Coagulation - Abstract
The systemic inflammatory response syndrome (SIRS) is the predominantly cytokine-mediated, pro-inflammatory response of the host to invading pathogens and is considered the hallmark sign of sepsis. Molecular components of this response can be divided into cytokines, plasma cascades and acute phase proteins while the predominant cellular components are leukocytes and the endothelium. High-throughput genetic profiling studies have led to increased insights into leukocyte regulation during sepsis. New players in the pro-inflammatory cytokine network include interleukin-17, high-mobility group box-1 protein, macrophage migration inhibitory factor, the myeloid-related proteins Mrp8 and Mrp14, and soluble triggering receptor expressed on myeloid cells-1. Activation of coagulation with concurrent downregulation of anticoagulant systems and fibrinolysis are almost universally present in septic patients with SIRS. Increasing evidence points to an extensive cross-talk between inflammation and coagulation, in which the protease-activated cell receptors play an important role. Sepsis causes excessive activation of the complement system in which C5a plays a key part. Further dissection of the role of host-pathogen interactions, the cytokine network, the coagulation cascade, the complement system and their multidirectional interactions in sepsis will pave the way for new treatment targets that can modify the excessive and collective activation of all these systems. Copyright (C) 2010 S. Karger AG, Basel
- Published
- 2010
29. Immunity to Burkholderia pseudomallei
- Author
-
Tom van der Poll and Willem Joost Wiersinga
- Subjects
Microbiology (medical) ,Burkholderia pseudomallei ,Melioidosis ,Neutrophils ,Toll-Like Receptors ,Biology ,biochemical phenomena, metabolism, and nutrition ,medicine.disease ,biology.organism_classification ,bacterial infections and mycoses ,Virology ,Microbiology ,Infectious Diseases ,Immunity ,medicine ,Humans ,bacteria - Abstract
Purpose of review Largely due to its recognition as a biological threat agent current knowledge on, melioidosis. caused by the Gram-negative bacterium Burkholderia pseudomallei, has increased tremendously over the last years. This review summarizes current understanding on the molecular characterization of B. pseudomallei and the immunology of melioidosis Recent findings The genome of B. pseudomallei is composed of two chromosomes of which the largest part represents the. B. pseudomallei core genome, whereas the remaining accessory genome has been associated with bacterial virulence. Virulence factors, most notably quorum sensing, type III secretion system, lipopolysaccharide and other surface polysaccharides, flagella and various factors essential for the intracellular life cycle of B. pseudomallei, have been further characterized. The neutrophils play a critical in host defense, which is initiated by the Toll-like receptors. The proinflammatory immune response - including the activation of coagulation - and its regulation have been further dissected. Summary Severe melioidosis can probably be seen as the clinical manifestation of a pathogen recognition receptor mediated dysregulation of the immune response to invading B. pseudomallei. B. pseudomallei employs numerous tactics to evade the immune response. Studies on host-pathogen interactions in melioidosis have identified a whole range of potential new treatment targets
- Published
- 2009
30. Expression of intra- and extracellular granzymes in patients with typhoid fever
- Author
-
Tom van der Poll, Willem Joost Wiersinga, M A Faiz, Arie J. Hoogendijk, Christopher M. Parry, Arjen M. Dondorp, Hanna K. de Jong, Maria Isabel Garcia-Laorden, Rapeephan R. Maude, Marks, F, Center of Experimental and Molecular Medicine, AII - Infectious diseases, Other departments, Infectious diseases, and Amsterdam institute for Infection and Immunity
- Subjects
Bacterial Diseases ,Male ,0301 basic medicine ,Physiology ,T-Lymphocytes ,Fevers ,NK cells ,Pathology and Laboratory Medicine ,Salmonella Typhi ,Granzymes ,White Blood Cells ,Animal Cells ,Salmonella ,Immune Physiology ,Medicine and Health Sciences ,Typhoid ,Cytotoxic T cell ,Lymphocytes ,Prospective Studies ,Innate Immune System ,Bangladesh ,biology ,T Cells ,lcsh:Public aspects of medicine ,Middle Aged ,Flow Cytometry ,Bacterial Pathogens ,3. Good health ,Killer Cells, Natural ,Infectious Diseases ,Medical Microbiology ,Cytokines ,Female ,Cellular Types ,Pathogens ,Intracellular ,Research Article ,Adult ,lcsh:Arctic medicine. Tropical medicine ,lcsh:RC955-962 ,Immune Cells ,Immunology ,Cytotoxic T cells ,Microbiology ,Typhoid fever ,Interferon-gamma ,Young Adult ,03 medical and health sciences ,Signs and Symptoms ,Enterobacteriaceae ,Diagnostic Medicine ,medicine ,Extracellular ,Humans ,Lymphocyte Count ,Typhoid Fever ,Microbial Pathogens ,Blood Cells ,Bacteria ,Organisms ,Public Health, Environmental and Occupational Health ,Biology and Life Sciences ,lcsh:RA1-1270 ,Cell Biology ,Molecular Development ,medicine.disease ,Granzyme B ,030104 developmental biology ,Granzyme ,Immune System ,Case-Control Studies ,biology.protein ,Granzyme A ,Granzyme K ,Developmental Biology - Abstract
Background Typhoid fever, caused by the intracellular pathogen Salmonella (S.) enterica serovar Typhi, remains a major cause of morbidity and mortality worldwide. Granzymes are serine proteases promoting cytotoxic lymphocytes mediated eradication of intracellular pathogens via the induction of cell death and which can also play a role in inflammation. We aimed to characterize the expression of extracellular and intracellular granzymes in patients with typhoid fever and whether the extracellular levels of granzyme correlated with IFN-γ release. Methods and principal findings We analyzed soluble protein levels of extracellular granzyme A and B in healthy volunteers and patients with confirmed S. Typhi infection on admission and day of discharge, and investigated whether this correlated with interferon (IFN)-γ release, a cytokine significantly expressed in typhoid fever. The intracellular expression of granzyme A, B and K in subsets of lymphocytic cells was determined using flow cytometry. Patients demonstrated a marked increase of extracellular granzyme A and B in acute phase plasma and a correlation of both granzymes with IFN-γ release. In patients, lower plasma levels of granzyme B, but not granzyme A, were found at day of discharge compared to admission, indicating an association of granzyme B with stage of disease. Peripheral blood mononuclear cells of typhoid fever patients had a higher percentage of lymphocytic cells expressing intracellular granzyme A and granzyme B, but not granzyme K, compared to controls. Conclusion The marked increase observed in extra- and intracellular levels of granzyme expression in patients with typhoid fever, and the correlation with stage of disease, suggests a role for granzymes in the host response to this disease., Author summary Typhoid fever is an (sub)acute febrile illness that remains an important global burden with more than 27 million cases worldwide each year and an estimated 217,000 deaths. During infection by Salmonella (S.) Typhi, the etiologic agent for typhoid fever, a cascade of antimicrobial functions is triggered and causes release of signaling and cytotoxic proteins for the rapid control of the infection. Granzymes are proteins promoting cytotoxic lymphocytes mediated eradication of intracellular pathogens via the induction of cell death and which can also play a role in inflammation. In the present study we analyzed extracellular levels of different granzymes in healthy volunteers and patients with confirmed S. Typhi infection at the time of admission and discharge, as well as their correlation with levels of interferon (IFN)-γ, a cytokine significantly expressed in typhoid fever. Patients demonstrated a marked increase of extracellular released granzyme A and B in acute phase plasma, which correlated with IFN-γ levels, while granzyme B levels were associated with disease stage. Intracellular expression of both granzymes was also increased in patients compared to controls. In conclusion, granzymes are markedly elevated in human typhoid and correlate with stage of disease, suggesting their involvement in the host response to the disease.
- Published
- 2017
31. Gut Microbiome and Host Defense Interactions during Critical Illness
- Author
-
Willem Joost Wiersinga, Tim J. Schuijt, and T. van der Poll
- Subjects
education.field_of_study ,business.industry ,Population ,Inflammation ,Systemic inflammation ,medicine.disease ,Sepsis ,medicine.anatomical_structure ,Immune system ,Paneth cell ,Immunology ,medicine ,Microbiome ,medicine.symptom ,business ,education ,Multiple organ dysfunction syndrome - Abstract
For many years it has been hypothesized that the gut has an important detrimental role in promoting systemic inflammation and infection in the critically ill. During stress and mucosal hypoxia, the mucosa is damaged and host defenses break down causing translocation of bacteria and bacterial toxins which are thought to contribute to the overwhelming inflammation associated with sepsis and multiorgan failure [1, 2]. New emerging data on the role of the microbiome have forced us to reassess the old ‘gut as motor of sepsis’ hypothesis. The gut microbiome consists of a diverse and vast population of microbes that has an important protective impact on immune effector functions during both health and disease (Fig. 1). It has become clear that the intestinal microbiome, consisting of more bacteria than the total number of cells in the human body, can be seen as an exteriorized organ that exerts numerous functions in the host response against infections [3, 4]. In addition to the more localized influence of the microbiome on the intestinal immune system, recent data show that the microbiome also plays a key role in systemic activation of the immune system contributing to the effective killing of invading pathogens [5]. The clinical relevance of these new insights is underscored by the notion that antibiotic treatment — which on any given day is received by almost three quarters of all patients on the intensive care unit (ICU) [6] — can largely deplete the microbiome. This review focuses on key aspects of the role of the intestinal microbiome in the immune response against pathogens and the importance of intestinal homeostasis for critically ill patients.
- Published
- 2012
32. Therapy-Resistant Opsoclonus-Myoclonus Syndrome Secondary to HIV-1 Infection
- Author
-
Jan M. Prins, Willem Joost Wiersinga, Diederik van de Beek, Amsterdam institute for Infection and Immunity, Infectious diseases, Amsterdam Neuroscience, and Neurology
- Subjects
Microbiology (medical) ,medicine.medical_specialty ,Therapy resistant ,Gabapentin ,business.industry ,MEDLINE ,Human immunodeficiency virus (HIV) ,medicine.disease ,medicine.disease_cause ,Treatment failure ,Infectious Diseases ,Text mining ,Internal medicine ,Opsoclonus myoclonus syndrome ,medicine ,business ,medicine.drug - Published
- 2012
33. Plasminogen activator inhibitor type I contributes to protective immunity during experimental Gram-negative sepsis (melioidosis)
- Author
-
Liesbeth M. Kager, M.M. Levi, Willem Joost Wiersinga, Joost C. M. Meijers, T. van der Poll, C. van 't Veer, Joris J. T. H. Roelofs, Other departments, Infectious diseases, Center of Experimental and Molecular Medicine, Amsterdam Cardiovascular Sciences, Amsterdam institute for Infection and Immunity, Pathology, and Vascular Medicine
- Subjects
Male ,medicine.medical_specialty ,Melioidosis ,Burkholderia pseudomallei ,medicine.medical_treatment ,Inflammation ,Biology ,Proinflammatory cytokine ,Sepsis ,Mice ,Fibrinolysis ,Plasminogen Activator Inhibitor 1 ,medicine ,Animals ,Mice, Knockout ,Hematology ,medicine.disease ,biology.organism_classification ,Mice, Inbred C57BL ,Immunology ,Histopathology ,medicine.symptom ,Plasminogen activator - Abstract
Summary. Background: Melioidosis is a frequent cause of sepsis in Southeast Asia caused by the Gram-negative bacterium Burkholderia pseudomallei. Patients with melioidosis have elevated circulating levels of plasminogen activator inhibitor type 1 (PAI-1), an important regulator of inflammation and fibrinolysis. Objectives: In this study, we aimed to investigate the role of PAI-1 during melioidosis. Methods: Wild-type (WT) and PAI-1-deficient (PAI-1–/1−/−) mice were intranasally infected with B. pseudomallei. Mice were killed after 24, 48 or 72 h. Lungs, liver and blood were harvested for measurement of bacterial loads, cytokines, clinical chemistry, histopathology, and coagulation parameters. Additionally, survival studies were performed. Results: PAI-1−/− mice demonstrated enhanced susceptibility to B. pseudomallei infection, as shown by a strongly increased mortality rate (100% vs. 58% among WT mice, P
- Published
- 2011
34. Diabetes does not influence activation of coagulation, fibrinolysis or anticoagulant pathways in Gram-negative sepsis (melioidosis)
- Author
-
Willem Joost Wiersinga, Rapeephan R. Maude, Gavin C. K. W. Koh, Direk Limmathurotsakul, Sharon J. Peacock, Nicholas P. J. Day, Tom van der Poll, Joost C. M. Meijers, Center of Experimental and Molecular Medicine, Amsterdam Cardiovascular Sciences, Vascular Medicine, Amsterdam institute for Infection and Immunity, and Infectious diseases
- Subjects
0301 basic medicine ,Adult ,Male ,Melioidosis ,Burkholderia pseudomallei ,medicine.medical_treatment ,030106 microbiology ,Fibrinogen ,Sepsis ,Diabetes Complications ,03 medical and health sciences ,0302 clinical medicine ,Diabetes mellitus ,Fibrinolysis ,medicine ,Humans ,030212 general & internal medicine ,Blood Coagulation ,Aged ,biology ,business.industry ,Antithrombin ,Hematology ,Middle Aged ,medicine.disease ,biology.organism_classification ,Immunology ,Female ,business ,Gram-Negative Bacterial Infections ,Protein C ,Biomarkers ,medicine.drug ,Follow-Up Studies - Abstract
SummaryDiabetes is associated with a disturbance of the haemostatic balance and is an important risk factor for sepsis, but the influence of diabetes on the pathogenesis of sepsis remains unclear. Melioidosis (Burkholderia pseudomallei infection) is a common cause of community-acquired sepsis in Southeast Asia and northern Australia. We sought to investigate the impact of pre-existing diabetes on the coagulation and fibrinolytic systems during sepsis caused by B. pseudomallei. We recruited a cohort of 44 patients (34 with diabetes and 10 without diabetes) with culture-proven melioidosis. Diabetes was defined as a pre-admission diagnosis of diabetes or an HbA1c>7.8% at enrolment. Thirty healthy blood donors and 52 otherwise healthy diabetes patients served as controls. Citrated plasma was collected from all subjects; additionally in melioidosis patients follow-up specimens were collected seven and ≥28 days after enrolment where possible. Relative to uninfected healthy controls, diabetes per se (i.e. in the absence of infection) was Characterised by a procoagulant effect. Melioidosis was associated with activation of coagulation (thrombin-antithrombin complexes (TAT), prothrombin fragment F1+2 and fibrinogen concentrations were elevated; PT and PTT prolonged), suppression of anti-coagulation (antithrombin, protein C, total and free protein S levels were depressed) and abnormalities of fibrinolysis (D-dimer and plasmin-antiplasmin complex [PAP] were elevated). Remarkably, none of these haemostatic alterations were influenced by pre-existing diabetes. In conclusion, although diabetes is associated with multiple abnormalities of coagulation, anticoagulation and fibrinolysis, these changes are not detectable when superimposed on the background of larger abnormalities attributable to B. pseudomallei sepsis.
- Published
- 2011
35. Osteopontin is not crucial to protective immunity during murine tuberculosis
- Author
-
Gerritje J. W. van der Windt, Sandrine Florquin, Catharina W. Wieland, Tom van der Poll, Willem Joost Wiersinga, Center of Experimental and Molecular Medicine, Amsterdam institute for Infection and Immunity, Intensive Care Medicine, Infectious diseases, and Pathology
- Subjects
CD4-Positive T-Lymphocytes ,Tuberculosis ,medicine.medical_treatment ,Immunology ,Inflammation ,CD8-Positive T-Lymphocytes ,Tuberculin ,Mycobacterium tuberculosis ,Interferon-gamma ,Mice ,Immune system ,stomatognathic system ,Macrophages, Alveolar ,medicine ,Immunology and Allergy ,Animals ,Hypersensitivity, Delayed ,Osteopontin ,Tuberculosis, Pulmonary ,Mice, Knockout ,biology ,Original Articles ,medicine.disease ,biology.organism_classification ,Acquired immune system ,Mice, Inbred C57BL ,Cytokine ,biology.protein ,medicine.symptom ,CD8 - Abstract
Upon infection with Mycobacterium (M.) tuberculosis, the development of a strong T helper 1 (Th1)-mediated adaptive immune response is considered as being most important for containment of the infection. Osteopontin (OPN) is a phosphorylated glycoprotein that is chemotactic for inflammatory cells and has been implicated in the induction of Th1 responses and granulomatous disease. We tested the hypothesis that OPN facilitates protective immunity during M. tuberculosis infection using wild-type (WT) and OPN knockout (KO) mice in a model of pulmonary tuberculosis. OPN expression was up-regulated in alveolar macrophages and lymphoid cells during M. tuberculosis infection. There were no significant differences in bacterial outgrowth, inflammation or recruitment of lymphocytes, macrophages and polymorphonuclear cells in the lungs after 2 and 5 weeks of infection. However, the numbers of CD4(+) and CD8(+) T cells were reduced in the absence of OPN 5 weeks after infection. Similar concentrations of cytokine were observed in lungs from both WT mice and OPN KO mice; however, there was a trend towards decreased levels of interferon-gamma (IFN-gamma) in OPN KO mice 5 weeks after infection. Despite an unaltered immune response in the early phase of tuberculosis, OPN KO mice had a modest survival advantage. Of note, both pulmonary bacterial loads and lung inflammation were reduced in these mice 31 weeks after infection. These data suggest that OPN is not crucial for protective immunity upon M. tuberculosis infection and during the late phase of tuberculosis may even be detrimental for the host.
- Published
- 2009
36. The Host Response to Sepsis
- Author
-
Willem Joost Wiersinga, T. van der Poll, Tijmen J. Hommes, Center of Experimental and Molecular Medicine, Graduate School, Infectious diseases, and Amsterdam institute for Infection and Immunity
- Subjects
Modern medicine ,Lipopolysaccharide ,biology ,business.industry ,medicine.medical_treatment ,medicine.disease ,Sepsis ,chemistry.chemical_compound ,Cytokine ,Immune system ,chemistry ,Monoclonal ,Immunology ,medicine ,biology.protein ,Tumor necrosis factor alpha ,Antibody ,business - Abstract
Sir William Osler, probably the most influential physician in the English-speaking world at the turn of the century more than a hundred years ago, wrote the following about sepsis in his famous text book, The Evolution of Modern Medicine (1904): “Except on few occasions, the patient appears to die from the body’s response to infection rather than from it”. The assumption that sepsis is the consequence of an overwhelming inflammatory reaction of the patient to microorganisms was widely accepted for many years. Current knowledge indicates that this paradigm is oversimplified and only partially true. The original theory that sepsis mortality is caused by an overstimulated immune system was based on studies in animals that were infused with large doses of bacteria or bacterial products, in particular lipopolysaccharide (LPS), the toxic component of the Gram-negative bacterial cell wall. Such infusions result in a brisk systemic release of an array of pro-inflammatory mediators of which many have been found to be directly responsible for the death of the host. In a hallmark manuscript published in 1985, Beutler and colleagues reported that elimination of the early activity of the pro-inflammatory cytokine, tumor necrosis factor (TNF)-α, after intravenous injection of LPS prevented death in mice [1]. Two years later, these results were confirmed by Tracey and colleagues, who showed that a monoclonal anti-TNF-α antibody protected baboons against lethal Gram-negative sepsis [2]. Since then, anti-TNF-α therapies have been found to be protective in a number of sepsis models in which bacteria or bacterial products were administered systemically as a bolus or a brief infusion [3].
- Published
- 2009
37. Inflammation, endothelium, and coagulation in sepsis
- Author
-
Willem Joost Wiersinga, Marcel Levi, Tom van der Poll, Marcel Schouten, Infectious diseases, Center of Experimental and Molecular Medicine, Vascular Medicine, and AII - Amsterdam institute for Infection and Immunity
- Subjects
Blood Platelets ,Endothelium ,medicine.medical_treatment ,Immunology ,Inflammation ,Models, Biological ,Thromboplastin ,Sepsis ,Von Willebrand factor ,Fibrinolysis ,von Willebrand Factor ,medicine ,Immunology and Allergy ,Humans ,Endothelial dysfunction ,Coagulation factor II receptor ,Blood Coagulation ,biology ,Heparin ,Anticoagulants ,Cell Biology ,medicine.disease ,medicine.anatomical_structure ,biology.protein ,Endothelium, Vascular ,medicine.symptom ,Protein C ,medicine.drug - Abstract
Sepsis is a systemic response to infection, and symptoms are produced by host defense systems rather than by the invading pathogens. Amongst the most prominent features of sepsis, contributing significantly to its outcome, is activation of coagulation with concurrent down-regulation of anticoagulant systems and fibrinolysis. Inflammation-induced coagulation on its turn contributes to inflammation. Another important feature of sepsis, associated with key symptoms such as hypovolemia and hypotension, is endothelial dysfunction. Under normal conditions, the endothelium provides for an anticoagulant surface, a property that is lost in sepsis. In this review, data about the interplay between inflammation and coagulation in sepsis are summarized with a special focus on the influence of the endothelium on inflammation-induced coagulation and vice versa. Possible procoagulant properties of the endothelium are described, such as expression of tissue factor (TF) and von Willebrand factor and interaction with platelets. Possible procoagulant roles of microparticles, circulating endothelial cells and endothelial apoptosis, are also discussed. Moreover, the important roles of the endothelium in down-regulating the anticoagulants TF pathway inhibitor, antithrombin, and the protein C (PC) system and inhibition of fibrinolysis are discussed. The influence of coagulation on its turn on inflammation and the endothelium is described with a special focus on protease-activated receptors (PARs). We conclude that the relationship between endothelium and coagulation in sepsis is tight and that further research is needed, for example, to better understand the role of activated PC signaling via PAR-1, the role of the endothelial PC receptor herein, and the role of the glycocalyx.
- Published
- 2008
38. Activation of coagulation with concurrent impairment of anticoagulant mechanisms correlates with a poor outcome in severe melioidosis
- Author
-
Nicholas P. J. Day, T. van der Poll, Joost C. M. Meijers, Sharon J. Peacock, Willem Joost Wiersinga, Marcel Levi, C. van 't Veer, Infectious diseases, Center of Experimental and Molecular Medicine, Amsterdam Cardiovascular Sciences, Vascular Medicine, and Amsterdam institute for Infection and Immunity
- Subjects
Adult ,Male ,Melioidosis ,Adolescent ,medicine.medical_treatment ,Sepsis ,Fibrinolysis ,medicine ,Humans ,Blood Coagulation ,Aged ,Blood coagulation test ,Aged, 80 and over ,biology ,medicine.diagnostic_test ,Burkholderia pseudomallei ,business.industry ,Antithrombin ,Hematology ,Middle Aged ,Prognosis ,biology.organism_classification ,medicine.disease ,Survival Rate ,Treatment Outcome ,Case-Control Studies ,Immunology ,Female ,Blood Coagulation Tests ,business ,Plasminogen activator ,Biomarkers ,Protein C ,medicine.drug ,Partial thromboplastin time - Abstract
Summary. Background: Melioidosis, which is caused by infection with the Gram-negative bacterium Burkholderia pseudomallei, is an important cause of sepsis in South-East Asia with a mortality of up to 40%. Knowledge of the involvement of coagulation and fibrinolysis in the pathogenesis of melioidosis is highly limited. Objective: To define the involvement of the coagulation and fibrinolytic systems in patients with severe melioidosis. Methods: Parameters of coagulation and fibrinolysis were measured in 34 patients with culture proven septic melioidosis and 32 healthy controls. Results: Patients demonstrated strong activation of the coagulation system, as reflected by high plasma levels of soluble tissue factor, the prothrombin fragment F1+2 and thrombin–antithrombin complexes (TATc), and consumption of coagulation factors resulting in a prolonged prothrombin time and activated partial thromboplastin time. Concurrently, anticoagulant pathways were downregulated in patients: protein C, protein S, and antithrombin levels were all decreased when compared to controls. Patients also demonstrated evidence of activation and inhibition of fibrinolysis, as reflected by elevated concentrations of tissue-type plasminogen activator (tPA), plasminogen activator inhibitor type 1, plasmin-α2-antiplasmin complexes (PAPc) and D-dimer. High TATc/PAPc ratios in patients pointed to a predominance of the prothrombotic pathway in melioidosis. Furthermore, soluble thrombomodulin levels were increased. The extent of coagulation activation correlated with mortality; patients who went on to die had higher TATc, F1+2, tPA and PAPc and lower protein C and antithrombin levels on admission than patients who survived. Conclusions: The coagulation system is strongly activated during melioidosis. A high degree of activation of the coagulation system is an indicator of poor outcome in patients with melioidosis.
- Published
- 2008
39. Is the septic response good or bad?
- Author
-
Tom van der Poll, Willem Joost Wiersinga, Infectious diseases, Center of Experimental and Molecular Medicine, and Amsterdam institute for Infection and Immunity
- Subjects
Sepsis ,medicine.medical_specialty ,Infectious Diseases ,business.industry ,Inflammatory response ,Immunology ,Medicine ,business ,Intensive care medicine ,medicine.disease - Abstract
A careful balance between the inflammatory and anti-inflammatory response is vital in order to survive the daily invasion of pathogens. Sepsis has always been regarded as the result of an exacerbated detrimental inflammatory response towards invading bacteria. However, recent insights have forced us to rethink this sepsis paradigm. This review discusses the latest trends and developments in the sepsis field and helps to set the stage for the current debate on whether the sepsis response is good or bad.
- Published
- 2007
40. Expression and Function of S100A8/A9 (Calprotectin) in Human Typhoid Fever and the Murine Salmonella Model
- Author
-
Thomas Vogl, Jaap T. van Dissel, Albert M Vollaard, Ahmed Achouiti, Willem Joost Wiersinga, Hanna K. de Jong, Christopher M. Parry, Ester M. M. van Leeuwen, Johannes Roth, Alex F. de Vos, Gavin C. K. W. Koh, Joris J. T. H. Roelofs, Stephen Baker, Tom van der Poll, M A Faiz, Center of Experimental and Molecular Medicine, Other departments, AII - Amsterdam institute for Infection and Immunity, Experimental Immunology, ACS - Amsterdam Cardiovascular Sciences, Pathology, and Infectious diseases
- Subjects
Salmonella ,lcsh:Arctic medicine. Tropical medicine ,lcsh:RC955-962 ,Bacteremia ,Inflammation ,Spleen ,Biology ,wc_269 ,medicine.disease_cause ,Salmonella typhi ,Polymerase Chain Reaction ,Typhoid fever ,Microbiology ,S100A8 ,Mice ,03 medical and health sciences ,0302 clinical medicine ,medicine ,Animals ,Calgranulin B ,Humans ,Calgranulin A ,Blood culture ,Typhoid Fever ,qw_131 ,030304 developmental biology ,0303 health sciences ,qw_4 ,medicine.diagnostic_test ,lcsh:Public aspects of medicine ,wc_270 ,Public Health, Environmental and Occupational Health ,lcsh:RA1-1270 ,medicine.disease ,3. Good health ,Toll-Like Receptor 4 ,Infectious Diseases ,medicine.anatomical_structure ,Gene Expression Regulation ,Immunology ,medicine.symptom ,Calprotectin ,Leukocyte L1 Antigen Complex ,Research Article ,030215 immunology - Abstract
Background Typhoid fever, caused by the Gram-negative bacterium Salmonella enterica serovar Typhi, is a major cause of community-acquired bacteremia and death worldwide. S100A8 (MRP8) and S100A9 (MRP14) form bioactive antimicrobial heterodimers (calprotectin) that can activate Toll-like receptor 4, promoting lethal, endotoxin-induced shock and multi-organ failure. We aimed to characterize the expression and function of S100A8/A9 in patients with typhoid fever and in a murine invasive Salmonella model. Methods and principal findings S100A8/A9 protein levels were determined in acute phase plasma or feces from 28 Bangladeshi patients, and convalescent phase plasma from 60 Indonesian patients with blood culture or PCR-confirmed typhoid fever, and compared to 98 healthy control subjects. To functionally characterize the role of S100A8/A9, we challenged wildtype (WT) and S100A9-/- mice with S. Typhimurium and determined bacterial loads and inflammation 2- and 5- days post infection. We further assessed the antimicrobial function of recombinant S100A8/A9 on S. Typhimurium and S. Typhi replication in vitro. Typhoid fever patients demonstrated a marked increase of S100A8/A9 in acute phase plasma and feces and this increases correlated with duration of fever prior to admission. S100A8/A9 directly inhibited the growth of S. Typhimurium and S. Typhi in vitro in a dose and time dependent fashion. WT mice inoculated with S. Typhimurium showed increased levels of S100A8/A9 in both the liver and the systemic compartment but S100A9-/- mice were indistinguishable from WT mice with respect to bacterial growth, survival, and inflammatory responses, as determined by cytokine release, histopathology and organ injury. Conclusion S100A8/A9 is markedly elevated in human typhoid, correlates with duration of fever prior to admission and directly inhibits the growth of S. Typhimurium and S. Typhi in vitro. Despite elevated levels in the murine invasive Salmonella model, S100A8/A9 does not contribute to an effective host response against S. Typhimurium in mice., Author Summary Bacterial pathogens are recognized by the host upon infection through interactions between their virulence factors and host cell receptors leading to the activation and recruitment of innate immune cells. Salmonella Typhi, the etiologic agent for typhoid fever, however harbors a number of factors, such as a polysaccharide capsule, which prevent the detection of these virulence factors, and thereby dampens the innate host response. Besides bacterial virulence factors, the host can detect endogenous danger molecules which are released upon tissue damage. S100A8/A9, an extracellular protein complex, is such a danger signal that is able to further amplify the systemic inflammatory response upon infection. In the present study we investigated the role of S100A8/A9 during invasive Salmonella infection and observed a marked increase of this protein in patients with typhoid fever, which correlates with disease stage and severity. Furthermore we found that S100A8/A9 directly inhibited the growth of Salmonella species in vitro thereby functioning as an antimicrobial. When mice were infected with Salmonella, the levels of S100A8/A9 were also elevated but mice lacking this protein did not have an altered host response to infection. The role and importance of the elevated levels of S100A8/A9 in human typhoid fever requires further study.
- Published
- 2015
41. Dengue fever-induced hemolytic uremic syndrome
- Author
-
Willem Joost Wiersinga, Peter J. de Vries, Cornelis G. Scheepstra, Suzanne E. Geerlings, Jocelyn S. Kasanardjo, Hans L. Zaaijer, AII - Amsterdam institute for Infection and Immunity, Cardiology, Infectious diseases, Medical Microbiology and Infection Prevention, and APH - Amsterdam Public Health
- Subjects
Microbiology (medical) ,Infectious Diseases ,business.industry ,Immunology ,Medicine ,business ,medicine.disease ,Dengue fever - Published
- 2006
42. Local tract metastasis of prostatic adenocarcinoma 8 years after (125)iodine brachytherapy
- Author
-
Theo M. de Reijke, Leo E.C.M. Blank, Willem Joost Wiersinga, and Other departments
- Subjects
medicine.medical_specialty ,Pathology ,Prostatic adenocarcinoma ,business.industry ,Urology ,medicine.medical_treatment ,Brachytherapy ,medicine.disease ,Metastasis ,Radiation therapy ,medicine.anatomical_structure ,Prostate ,Interstitial radiotherapy ,medicine ,Adenocarcinoma ,Prostate disease ,Radiology ,business - Published
- 2001
43. LOCAL TRACT METASTASIS OF PROSTATIC ADENOCARCINOMA 8 YEARS AFTER 125IODINE BRACHYTHERAPY
- Author
-
WILLEM JOOST WIERSINGA, THEO. M. DE REIJKE, and LEO E. C. M. BLANK
- Subjects
Urology - Published
- 2001
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.