"The real benefit to the patient [of echocardiography] is not the technical skill, but rather the application of intellectual input... information, communication and teamwork are essential" Jos Roelandt, 1993
Of all the imaging techniques used in intensive care, echocardiography has come to the fore, in particular due to its accessibility, immediate availability and applicability as a point-of-care technique, thereby removing the risks of transportation of the critically ill. Over the preceding 20 years evidence has continued to emerge for its extended use in the acute/emergency setting, to the extent that it is now included in national and international guidelines relating to the universal definition of myocardial infarction, as well as in shock pathways, and as an adjunctive technique in advanced life support. Its potential scope is huge, with applications relating to monitoring, cardiac pathophysiology and coronary perfusion as well as its more evident use to define cardiac anatomy.
The three main uses of ultrasound to interrogate the heart relate to the way in which the technique is used: first, as an extension to the clinical examination using binary questions and 2D imaging only (focused cardiac ultrasound, FoCUS) which forms the basis of 'basic' techniques. Second, incorporating the full range of echocardiographic techniques for diagnostic capability (echocardiography), and third, selective application of the full range of techniques in order to answer specific questions raised in the critical care/emergency arena (targeted echocardiography). This includes speckle strain/strain-rate to determine abnormalities of myocardial function suggestive of myocarditis, calculation of myocardial electromechanical efficiency in order to maximise cardiac output, recognition of parameters that suggest restrictive right ventricular physiology, with the requirement for modification of ventilatory techniques and parameters, detection of myocardial ischaemia, estimation of LVEDP and LAP, and its application in the institution, monitoring and weaning of mechanical circulatory support.
Drs. Lorenzen and Escobar’s CMC X-Ray Mastery Project: October CasesSean M. Fox
Drs. Breeanna Lorenzen and Daniel Escobar are Emergency Medicine Residents and interested in medical education. With the guidance of Dr. Michael Gibbs, a notable Professor of Emergency Medicine, they aim to help augment our understanding of emergent imaging. Follow along with the EMGuideWire.com team as they post these educational, self-guided radiology slides. This set will cover:
- Disconnect VP shunt
- PFO Closure Device
- Implanted Baclofen Pump
- Pnuemobilia
- Common Bile Duct Stent
- Dextrocardia
- Implantable Cardioverter Device
- Left Ventricular Assist Device (LVAD)
EMGuideWire's Radiology Reading Room: Stress-Induced CardiomyopathySean M. Fox
The Department of Emergency Medicine at Carolinas Medical Center is passionate about education! Dr. Michael Gibbs is a world-renowned clinician and educator and has helped guide numerous young clinicians on the long path of Mastery of Emergency Medical Care. With his oversight, the EMGuideWire team aim to help augment our understanding of emergent imaging. You can follow along with the EMGuideWire.com team as they post these educational, self-guided radiology slides or you can also use this section to learn more in-depth about specific conditions and diseases. This Radiology Reading Room pertains to Stress-Induced Cardiomyopathy and is brought to you by Jenna Pallansch, MD, Claire Lawson, NP, Shelby Hixson, PA, Emily Lipsitz, PA, Ashley Moore-Gibbs, DNP, Laszlo Littmann, MD, and John Symanski, MD.
Drs. Escobar’s CMC X-Ray Mastery Project: November CasesSean M. Fox
Drs. Daniel Escobar, Angela Pikus, and Alex Blackwell are Emergency Medicine Residents and interested in medical education. They are joined by Marianne Dannemiller, PA who is an APP for Sanger Heat & Vascular Institute. With the guidance of Dr. Michael Gibbs, a notable Professor of Emergency Medicine, they aim to help augment our understanding of emergent imaging. Follow along with the EMGuideWire.com team as they post these educational, self-guided radiology slides. This set will cover:
- Aortic Aneursym
- Endovascular Aortic Repair (EVAR)
- EVAR Endoleak
- Right Sided Aortic Arch
- Tension Pneumothorax
- Thyroid Mass
Drs. Milam and Thomas's CMC X-Ray Mastery Project: December CasesSean M. Fox
Drs. Claire Milam and Alyssa Thomas are Emergency Medicine Residents and interested in medical education. With the guidance of Dr. Michael Gibbs, a notable Professor of Emergency Medicine, they aim to help augment our understanding of emergent imaging. Follow along with the EMGuideWire.com team as they post these monthly educational, self-guided radiology slides on: Cryptococcal Pneumonia, Coarctation of the Thoracic Aorta, Pulmonary Contusion, Ruptured Left Hemidiaphragm, Septic Pulmonary Emboli
EMGuideWire's Radiology Reading Room: Hypertrophic CardiomyopathySean M. Fox
The Department of Emergency Medicine at Carolinas Medical Center is passionate about education! Dr. Michael Gibbs is a world-renowned clinician and educator and has helped guide numerous young clinicians on the long path of Mastery of Emergency Medical Care. With his oversight, the EMGuideWire team aim to help augment our understanding of emergent imaging. You can follow along with the EMGuideWire.com team as they post these educational, self-guided radiology slides or you can also use this section to learn more in-depth about specific conditions and diseases. This Radiology Reading Room pertains to Hypertrophic Cardiomyopathy and is brought to you by Ashley Moore-Gibbs, DNP, Claire Lawson, NP, Laszlo Littmann, MD, and John Symanski, MD.
EMGuideWire's Radiology Reading Room on Pediatric Adult Aortic CoarctationSean M. Fox
The Department of Emergency Medicine at Carolinas Medical Center is passionate about education! Dr. Michael Gibbs is a world-renowned clinician and educator and has helped guide numerous young clinicians on the long path of Mastery of Emergency Medical Care. With his oversight, the EMGuideWire team aim to help augment our understanding of emergent imaging. You can follow along with the EMGuideWire.com team as they post these monthly educational, self-guided radiology slides or you can also use this section to learn more in-depth about specific conditions and diseases. This Radiology Reading Room pertains to Pediatric and Adult Aortic Coarctation and is brought to you by Jennifer Potter, MD and Elizabeth Olson, MD.
Drs. Potter and Richardson's CMC Pediatric X-Ray Mastery: April CasesSean M. Fox
Drs. Potter and Richardson are interested in education and Pediatric Emergency Medicine. Follow along with the EMGuideWire.com team and Dr. Michael Gibbs as they post these educational, self-guided radiology slides on Pediatric Emergency Medicine Radiology Topics including:
• VP Shunt Disconnection
• E-cigarette Vaping Associated Lung Injury
• Apical Lung Mass
• Pulmonary Metastasis
• Vascular Ring
"The real benefit to the patient [of echocardiography] is not the technical skill, but rather the application of intellectual input... information, communication and teamwork are essential" Jos Roelandt, 1993
Of all the imaging techniques used in intensive care, echocardiography has come to the fore, in particular due to its accessibility, immediate availability and applicability as a point-of-care technique, thereby removing the risks of transportation of the critically ill. Over the preceding 20 years evidence has continued to emerge for its extended use in the acute/emergency setting, to the extent that it is now included in national and international guidelines relating to the universal definition of myocardial infarction, as well as in shock pathways, and as an adjunctive technique in advanced life support. Its potential scope is huge, with applications relating to monitoring, cardiac pathophysiology and coronary perfusion as well as its more evident use to define cardiac anatomy.
The three main uses of ultrasound to interrogate the heart relate to the way in which the technique is used: first, as an extension to the clinical examination using binary questions and 2D imaging only (focused cardiac ultrasound, FoCUS) which forms the basis of 'basic' techniques. Second, incorporating the full range of echocardiographic techniques for diagnostic capability (echocardiography), and third, selective application of the full range of techniques in order to answer specific questions raised in the critical care/emergency arena (targeted echocardiography). This includes speckle strain/strain-rate to determine abnormalities of myocardial function suggestive of myocarditis, calculation of myocardial electromechanical efficiency in order to maximise cardiac output, recognition of parameters that suggest restrictive right ventricular physiology, with the requirement for modification of ventilatory techniques and parameters, detection of myocardial ischaemia, estimation of LVEDP and LAP, and its application in the institution, monitoring and weaning of mechanical circulatory support.
Drs. Lorenzen and Escobar’s CMC X-Ray Mastery Project: October CasesSean M. Fox
Drs. Breeanna Lorenzen and Daniel Escobar are Emergency Medicine Residents and interested in medical education. With the guidance of Dr. Michael Gibbs, a notable Professor of Emergency Medicine, they aim to help augment our understanding of emergent imaging. Follow along with the EMGuideWire.com team as they post these educational, self-guided radiology slides. This set will cover:
- Disconnect VP shunt
- PFO Closure Device
- Implanted Baclofen Pump
- Pnuemobilia
- Common Bile Duct Stent
- Dextrocardia
- Implantable Cardioverter Device
- Left Ventricular Assist Device (LVAD)
EMGuideWire's Radiology Reading Room: Stress-Induced CardiomyopathySean M. Fox
The Department of Emergency Medicine at Carolinas Medical Center is passionate about education! Dr. Michael Gibbs is a world-renowned clinician and educator and has helped guide numerous young clinicians on the long path of Mastery of Emergency Medical Care. With his oversight, the EMGuideWire team aim to help augment our understanding of emergent imaging. You can follow along with the EMGuideWire.com team as they post these educational, self-guided radiology slides or you can also use this section to learn more in-depth about specific conditions and diseases. This Radiology Reading Room pertains to Stress-Induced Cardiomyopathy and is brought to you by Jenna Pallansch, MD, Claire Lawson, NP, Shelby Hixson, PA, Emily Lipsitz, PA, Ashley Moore-Gibbs, DNP, Laszlo Littmann, MD, and John Symanski, MD.
Drs. Escobar’s CMC X-Ray Mastery Project: November CasesSean M. Fox
Drs. Daniel Escobar, Angela Pikus, and Alex Blackwell are Emergency Medicine Residents and interested in medical education. They are joined by Marianne Dannemiller, PA who is an APP for Sanger Heat & Vascular Institute. With the guidance of Dr. Michael Gibbs, a notable Professor of Emergency Medicine, they aim to help augment our understanding of emergent imaging. Follow along with the EMGuideWire.com team as they post these educational, self-guided radiology slides. This set will cover:
- Aortic Aneursym
- Endovascular Aortic Repair (EVAR)
- EVAR Endoleak
- Right Sided Aortic Arch
- Tension Pneumothorax
- Thyroid Mass
Drs. Milam and Thomas's CMC X-Ray Mastery Project: December CasesSean M. Fox
Drs. Claire Milam and Alyssa Thomas are Emergency Medicine Residents and interested in medical education. With the guidance of Dr. Michael Gibbs, a notable Professor of Emergency Medicine, they aim to help augment our understanding of emergent imaging. Follow along with the EMGuideWire.com team as they post these monthly educational, self-guided radiology slides on: Cryptococcal Pneumonia, Coarctation of the Thoracic Aorta, Pulmonary Contusion, Ruptured Left Hemidiaphragm, Septic Pulmonary Emboli
EMGuideWire's Radiology Reading Room: Hypertrophic CardiomyopathySean M. Fox
The Department of Emergency Medicine at Carolinas Medical Center is passionate about education! Dr. Michael Gibbs is a world-renowned clinician and educator and has helped guide numerous young clinicians on the long path of Mastery of Emergency Medical Care. With his oversight, the EMGuideWire team aim to help augment our understanding of emergent imaging. You can follow along with the EMGuideWire.com team as they post these educational, self-guided radiology slides or you can also use this section to learn more in-depth about specific conditions and diseases. This Radiology Reading Room pertains to Hypertrophic Cardiomyopathy and is brought to you by Ashley Moore-Gibbs, DNP, Claire Lawson, NP, Laszlo Littmann, MD, and John Symanski, MD.
EMGuideWire's Radiology Reading Room on Pediatric Adult Aortic CoarctationSean M. Fox
The Department of Emergency Medicine at Carolinas Medical Center is passionate about education! Dr. Michael Gibbs is a world-renowned clinician and educator and has helped guide numerous young clinicians on the long path of Mastery of Emergency Medical Care. With his oversight, the EMGuideWire team aim to help augment our understanding of emergent imaging. You can follow along with the EMGuideWire.com team as they post these monthly educational, self-guided radiology slides or you can also use this section to learn more in-depth about specific conditions and diseases. This Radiology Reading Room pertains to Pediatric and Adult Aortic Coarctation and is brought to you by Jennifer Potter, MD and Elizabeth Olson, MD.
Drs. Potter and Richardson's CMC Pediatric X-Ray Mastery: April CasesSean M. Fox
Drs. Potter and Richardson are interested in education and Pediatric Emergency Medicine. Follow along with the EMGuideWire.com team and Dr. Michael Gibbs as they post these educational, self-guided radiology slides on Pediatric Emergency Medicine Radiology Topics including:
• VP Shunt Disconnection
• E-cigarette Vaping Associated Lung Injury
• Apical Lung Mass
• Pulmonary Metastasis
• Vascular Ring
Dr. Michael Gibbs's CMC X Ray Mastery Project - Week #8 CasesSean M. Fox
Dr. Michael Gibbs is a Professor of Emergency Medicine and interested in educating others. Radiology is a passion of his. Follow along with the EMGuideWire.com team as they post Dr. Gibbs's weekly educational, self-guided radiology slides on: Parapneumonic Effusion, Traumatic Aortic Disruption, Right Upper Lobe Pneumonia, Pulmonary Metastatic Disease, Type A Aortic Dissection, Left Mainstem Bronchus Obstruction due to Mucous Plugging
Drs. Milam and Thomas's CMC X-Ray Mastery Project: April CasesSean M. Fox
Drs. Claire Milam and Alyssa Thomas are Emergency Medicine Residents and interested in medical education. With the guidance of Dr. Michael Gibbs, a notable Professor of Emergency Medicine, they aim to help augment our understanding of emergent imaging. Follow along with the EMGuideWire.com team as they post these monthly educational, self-guided radiology slides on:
• Esophageal Perforation
• Perforated Viscous
• Pneumothorax
• Traumatic Diaphragmatic Hernia
• Pulmonary Contusion
• COVID-19 associated Pneumonia
• COVID-19
• Influenza Like Illness
EMGuideWire's Radiology Reading Room: Pericardial EffusionSean M. Fox
The Department of Emergency Medicine at Carolinas Medical Center is passionate about education! Dr. Michael Gibbs is a world-renowned clinician and educator and has helped guide numerous young clinicians on the long path of Mastery of Emergency Medical Care. With his oversight, the EMGuideWire team aim to help augment our understanding of emergent imaging. You can follow along with the EMGuideWire.com team as they post these educational, self-guided radiology slides or you can also use this section to learn more in-depth about specific conditions and diseases. This Radiology Reading Room pertains to Spontaneous Pericardial Effusion and is brought to you by Chelsea Wilson, MD, and Emily Lipsitz, PA-C.
EMGuideWire's Radiology Reading Room: Septic Pulmonary EmboliSean M. Fox
The Department of Emergency Medicine at Carolinas Medical Center is passionate about education! Dr. Michael Gibbs is a world-renowned clinician and educator and has helped guide numerous young clinicians on the long path of Mastery of Emergency Medical Care. With his oversight, the EMGuideWire team aim to help augment our understanding of emergent imaging. You can follow along with the EMGuideWire.com team as they post these monthly educational, self-guided radiology slides or you can also use this section to learn more in-depth about specific conditions and diseases. This Radiology Reading Room pertains to Septic Pulmonary Emboli and is brought to you by Victoria Serven, MD, Travis Barlock, MD, and Katherine Sillman, NP.
Drs. Potter and Richardson's CMC Pediatric X-Ray Mastery November CasesSean M. Fox
Drs. Potter and Richardson are interested in education and Pediatric Emergency Medicine. Follow along with the EMGuideWire.com team and Dr. Michael Gibbs as they post these educational, self-guided radiology slides on Pediatric Emergency Medicine Radiology Topics including:
- Tension Pneumothorax
- Atelectasis
- Esophageal Obstruction / Achalasia
- Right Upper Lobe Mass
- Right Upper and Right Middle Lobectomies
- Esophageal Foreign Body
- Transposition of the Great Vessels
Drs. Lorenzen and Barlock’s CMC X-Ray Mastery Project: September CasesSean M. Fox
Drs. Breeanna Lorenzen and Travis Barlock are Emergency Medicine Residents and interested in medical education. With the guidance of Dr. Michael Gibbs, a notable Professor of Emergency Medicine, they aim to help augment our understanding of emergent imaging. Follow along with the EMGuideWire.com team as they post these educational, self-guided radiology slides. This set will cover:
• Aortic Transection
• Hemothorax
• Innominate Artery Transection
• Dextrocardia
• Situs Inversus
• Pneumonia
• Complete Lung Consolidation
• Septic Pulmonary Emboli
• Pulmonary Metastases
• Pneumothorax
Drs. Lena, Avery, and Davis’s CMC Abdominal Imaging Mastery Project: August C...Sean M. Fox
Dr. Kelsey Lena is an Emergency Medicine Resident and Drs. Michael Avery and Joshua Davis are Surgery Residents at Carolinas Medical Center in Charlotte, NC. They are interested in medical education. With the guidance of Drs. Kyle Cunningham and Michael Gibbs, they aim to help augment our understanding of emergent abdominal imaging. Follow along with the EMGuideWire.com team as they post these monthly educational, self-guided radiology slides. This month’s topics include:
• Splenic Rupture
• Obstructive jaundice
• Ovarian Torsion
EMGuideWire's Radiology Reading Room: Spontaneous PneumothoraxSean M. Fox
The Department of Emergency Medicine at Carolinas Medical Center is passionate about education! Dr. Michael Gibbs is a world-renowned clinician and educator and has helped guide numerous young clinicians on the long path of Mastery of Emergency Medical Care. With his oversight, the EMGuideWire team aim to help augment our understanding of emergent imaging. You can follow along with the EMGuideWire.com team as they post these monthly educational, self-guided radiology slides or you can also use this section to learn more in-depth about specific conditions and diseases. This Radiology Reading Room pertains to Spontaneous Pneumothorax and is brought to you by Elizabeth Olson, MD, and Janet Lorenz, NP.
Dr. Escobar’s CMC X-Ray Mastery Project: December CasesSean M. Fox
Drs. Daniel Escobar, Angela Pikus, and Alex Blackwell are Emergency Medicine Residents and interested in medical education. With the guidance of Dr. Michael Gibbs, a notable Professor of Emergency Medicine, they aim to help augment our understanding of emergent imaging. Follow along with the EMGuideWire.com team as they post these educational, self-guided radiology slides. This set will cover:
- Blunt hemothorax
- Pulmonary contusion
- Lung Cancer with Bone Metastases
- Pneumomediastinum
- Pneumopericardium
Drs. Lorenzen and Escobar’s CMC X-Ray Mastery Project: August CasesSean M. Fox
Drs. Breeanna Lorenzen and Daniel Escobar are Emergency Medicine Residents and interested in medical education. With the guidance of Dr. Michael Gibbs, a notable Professor of Emergency Medicine, they aim to help augment our understanding of emergent imaging. Follow along with the EMGuideWire.com team as they post these educational, self-guided radiology slides. This set will cover:
- Malignant Pleural Effusion
- Pericardial Effusion
- Traumatic Aortic Disruption
- Femoral Guidewire migration
- Disconnected HeRO graft
- Flail Chest
- Pulmonary Contusion
EMGuideWire's Radiology Reading Room: PneumoniaSean M. Fox
The Department of Emergency Medicine at Carolinas Medical Center is passionate about education! Dr. Michael Gibbs is a world-renowned clinician and educator and has helped guide numerous young clinicians on the long path of Mastery of Emergency Medical Care. With his oversight, the EMGuideWire team aim to help augment our understanding of emergent imaging. You can follow along with the EMGuideWire.com team as they post these monthly educational, self-guided radiology slides or you can also use this section to learn more in-depth about specific conditions and diseases. This Radiology Reading Room pertains to Pneumonia and is brought to you by Elissabeth Hagler, MD and Tom Shuman, MD. Guest Editor is Michael Leonard, MD, Infectious Disease specialist.
Dr. Michael Gibbs's CMC X-Ray Mastery Project - Week #6 CasesSean M. Fox
Dr. Michael Gibbs is a Professor of Emergency Medicine and interested in educating others. Radiology is a passion of his. Follow along with the EMGuideWire.com team as they post Dr. Gibbs's weekly educational, self-guided radiology slides on: Colonic perforation, free air, coarctation, multifocal pneumonia, several pneumothoraces, Oral Gastric Tube in right mainstem bronchus, Traumatic aortic disruption, Scoliosis, lung metastases, pneumomediastinum
EMGuideWire's Radiology Reading Room: Peripartum CardiomyopathySean M. Fox
The Department of Emergency Medicine at Carolinas Medical Center is passionate about education! Dr. Michael Gibbs is a world-renowned clinician and educator and has helped guide numerous young clinicians on the long path of Mastery of Emergency Medical Care. With his oversight, the EMGuideWire team aim to help augment our understanding of emergent imaging. You can follow along with the EMGuideWire.com team as they post these educational, self-guided radiology slides or you can also use this section to learn more in-depth about specific conditions and diseases. This Radiology Reading Room pertains to Peripartum Cardiomyopathy and is brought to you by Kaley El-Arab, MD, Blaire Langa, NP, Claire Lawson, NP, and Ashley Moore Gibbs, DNP. It is has the special guest editors: Richard Musialowski, MD and Laszlo Littmann, MD.
EMGuideWire's Radiology Reading Room: Diaphragm Injury CasesSean M. Fox
The Department of Emergency Medicine at Carolinas Medical Center is passionate about education! Dr. Michael Gibbs is a world-renowned clinician and educator and has helped guide numerous young clinicians on the long path of Mastery of Emergency Medical Care. With his oversight, the EMGuideWire team aim to help augment our understanding of emergent imaging. You can follow along with the EMGuideWire.com team as they post these educational, self-guided radiology slides or you can also use this section to learn more in-depth about specific conditions and diseases. This Radiology Reading Room pertains to Diaphragm Injury and is brought to you by Jacob Leedekerken, MD, Chelsea Wilson, MD, and Travis Barlock, MD. It is has special guest editor: Kyle Cunningham, MD
Dr. Michael Gibbs's CMC X Ray Mastery Project - Week #8 CasesSean M. Fox
Dr. Michael Gibbs is a Professor of Emergency Medicine and interested in educating others. Radiology is a passion of his. Follow along with the EMGuideWire.com team as they post Dr. Gibbs's weekly educational, self-guided radiology slides on: Parapneumonic Effusion, Traumatic Aortic Disruption, Right Upper Lobe Pneumonia, Pulmonary Metastatic Disease, Type A Aortic Dissection, Left Mainstem Bronchus Obstruction due to Mucous Plugging
Drs. Milam and Thomas's CMC X-Ray Mastery Project: April CasesSean M. Fox
Drs. Claire Milam and Alyssa Thomas are Emergency Medicine Residents and interested in medical education. With the guidance of Dr. Michael Gibbs, a notable Professor of Emergency Medicine, they aim to help augment our understanding of emergent imaging. Follow along with the EMGuideWire.com team as they post these monthly educational, self-guided radiology slides on:
• Esophageal Perforation
• Perforated Viscous
• Pneumothorax
• Traumatic Diaphragmatic Hernia
• Pulmonary Contusion
• COVID-19 associated Pneumonia
• COVID-19
• Influenza Like Illness
EMGuideWire's Radiology Reading Room: Pericardial EffusionSean M. Fox
The Department of Emergency Medicine at Carolinas Medical Center is passionate about education! Dr. Michael Gibbs is a world-renowned clinician and educator and has helped guide numerous young clinicians on the long path of Mastery of Emergency Medical Care. With his oversight, the EMGuideWire team aim to help augment our understanding of emergent imaging. You can follow along with the EMGuideWire.com team as they post these educational, self-guided radiology slides or you can also use this section to learn more in-depth about specific conditions and diseases. This Radiology Reading Room pertains to Spontaneous Pericardial Effusion and is brought to you by Chelsea Wilson, MD, and Emily Lipsitz, PA-C.
EMGuideWire's Radiology Reading Room: Septic Pulmonary EmboliSean M. Fox
The Department of Emergency Medicine at Carolinas Medical Center is passionate about education! Dr. Michael Gibbs is a world-renowned clinician and educator and has helped guide numerous young clinicians on the long path of Mastery of Emergency Medical Care. With his oversight, the EMGuideWire team aim to help augment our understanding of emergent imaging. You can follow along with the EMGuideWire.com team as they post these monthly educational, self-guided radiology slides or you can also use this section to learn more in-depth about specific conditions and diseases. This Radiology Reading Room pertains to Septic Pulmonary Emboli and is brought to you by Victoria Serven, MD, Travis Barlock, MD, and Katherine Sillman, NP.
Drs. Potter and Richardson's CMC Pediatric X-Ray Mastery November CasesSean M. Fox
Drs. Potter and Richardson are interested in education and Pediatric Emergency Medicine. Follow along with the EMGuideWire.com team and Dr. Michael Gibbs as they post these educational, self-guided radiology slides on Pediatric Emergency Medicine Radiology Topics including:
- Tension Pneumothorax
- Atelectasis
- Esophageal Obstruction / Achalasia
- Right Upper Lobe Mass
- Right Upper and Right Middle Lobectomies
- Esophageal Foreign Body
- Transposition of the Great Vessels
Drs. Lorenzen and Barlock’s CMC X-Ray Mastery Project: September CasesSean M. Fox
Drs. Breeanna Lorenzen and Travis Barlock are Emergency Medicine Residents and interested in medical education. With the guidance of Dr. Michael Gibbs, a notable Professor of Emergency Medicine, they aim to help augment our understanding of emergent imaging. Follow along with the EMGuideWire.com team as they post these educational, self-guided radiology slides. This set will cover:
• Aortic Transection
• Hemothorax
• Innominate Artery Transection
• Dextrocardia
• Situs Inversus
• Pneumonia
• Complete Lung Consolidation
• Septic Pulmonary Emboli
• Pulmonary Metastases
• Pneumothorax
Drs. Lena, Avery, and Davis’s CMC Abdominal Imaging Mastery Project: August C...Sean M. Fox
Dr. Kelsey Lena is an Emergency Medicine Resident and Drs. Michael Avery and Joshua Davis are Surgery Residents at Carolinas Medical Center in Charlotte, NC. They are interested in medical education. With the guidance of Drs. Kyle Cunningham and Michael Gibbs, they aim to help augment our understanding of emergent abdominal imaging. Follow along with the EMGuideWire.com team as they post these monthly educational, self-guided radiology slides. This month’s topics include:
• Splenic Rupture
• Obstructive jaundice
• Ovarian Torsion
EMGuideWire's Radiology Reading Room: Spontaneous PneumothoraxSean M. Fox
The Department of Emergency Medicine at Carolinas Medical Center is passionate about education! Dr. Michael Gibbs is a world-renowned clinician and educator and has helped guide numerous young clinicians on the long path of Mastery of Emergency Medical Care. With his oversight, the EMGuideWire team aim to help augment our understanding of emergent imaging. You can follow along with the EMGuideWire.com team as they post these monthly educational, self-guided radiology slides or you can also use this section to learn more in-depth about specific conditions and diseases. This Radiology Reading Room pertains to Spontaneous Pneumothorax and is brought to you by Elizabeth Olson, MD, and Janet Lorenz, NP.
Dr. Escobar’s CMC X-Ray Mastery Project: December CasesSean M. Fox
Drs. Daniel Escobar, Angela Pikus, and Alex Blackwell are Emergency Medicine Residents and interested in medical education. With the guidance of Dr. Michael Gibbs, a notable Professor of Emergency Medicine, they aim to help augment our understanding of emergent imaging. Follow along with the EMGuideWire.com team as they post these educational, self-guided radiology slides. This set will cover:
- Blunt hemothorax
- Pulmonary contusion
- Lung Cancer with Bone Metastases
- Pneumomediastinum
- Pneumopericardium
Drs. Lorenzen and Escobar’s CMC X-Ray Mastery Project: August CasesSean M. Fox
Drs. Breeanna Lorenzen and Daniel Escobar are Emergency Medicine Residents and interested in medical education. With the guidance of Dr. Michael Gibbs, a notable Professor of Emergency Medicine, they aim to help augment our understanding of emergent imaging. Follow along with the EMGuideWire.com team as they post these educational, self-guided radiology slides. This set will cover:
- Malignant Pleural Effusion
- Pericardial Effusion
- Traumatic Aortic Disruption
- Femoral Guidewire migration
- Disconnected HeRO graft
- Flail Chest
- Pulmonary Contusion
EMGuideWire's Radiology Reading Room: PneumoniaSean M. Fox
The Department of Emergency Medicine at Carolinas Medical Center is passionate about education! Dr. Michael Gibbs is a world-renowned clinician and educator and has helped guide numerous young clinicians on the long path of Mastery of Emergency Medical Care. With his oversight, the EMGuideWire team aim to help augment our understanding of emergent imaging. You can follow along with the EMGuideWire.com team as they post these monthly educational, self-guided radiology slides or you can also use this section to learn more in-depth about specific conditions and diseases. This Radiology Reading Room pertains to Pneumonia and is brought to you by Elissabeth Hagler, MD and Tom Shuman, MD. Guest Editor is Michael Leonard, MD, Infectious Disease specialist.
Dr. Michael Gibbs's CMC X-Ray Mastery Project - Week #6 CasesSean M. Fox
Dr. Michael Gibbs is a Professor of Emergency Medicine and interested in educating others. Radiology is a passion of his. Follow along with the EMGuideWire.com team as they post Dr. Gibbs's weekly educational, self-guided radiology slides on: Colonic perforation, free air, coarctation, multifocal pneumonia, several pneumothoraces, Oral Gastric Tube in right mainstem bronchus, Traumatic aortic disruption, Scoliosis, lung metastases, pneumomediastinum
EMGuideWire's Radiology Reading Room: Peripartum CardiomyopathySean M. Fox
The Department of Emergency Medicine at Carolinas Medical Center is passionate about education! Dr. Michael Gibbs is a world-renowned clinician and educator and has helped guide numerous young clinicians on the long path of Mastery of Emergency Medical Care. With his oversight, the EMGuideWire team aim to help augment our understanding of emergent imaging. You can follow along with the EMGuideWire.com team as they post these educational, self-guided radiology slides or you can also use this section to learn more in-depth about specific conditions and diseases. This Radiology Reading Room pertains to Peripartum Cardiomyopathy and is brought to you by Kaley El-Arab, MD, Blaire Langa, NP, Claire Lawson, NP, and Ashley Moore Gibbs, DNP. It is has the special guest editors: Richard Musialowski, MD and Laszlo Littmann, MD.
EMGuideWire's Radiology Reading Room: Diaphragm Injury CasesSean M. Fox
The Department of Emergency Medicine at Carolinas Medical Center is passionate about education! Dr. Michael Gibbs is a world-renowned clinician and educator and has helped guide numerous young clinicians on the long path of Mastery of Emergency Medical Care. With his oversight, the EMGuideWire team aim to help augment our understanding of emergent imaging. You can follow along with the EMGuideWire.com team as they post these educational, self-guided radiology slides or you can also use this section to learn more in-depth about specific conditions and diseases. This Radiology Reading Room pertains to Diaphragm Injury and is brought to you by Jacob Leedekerken, MD, Chelsea Wilson, MD, and Travis Barlock, MD. It is has special guest editor: Kyle Cunningham, MD
IOSR Journal of Dental and Medical Sciences is one of the speciality Journal in Dental Science and Medical Science published by International Organization of Scientific Research (IOSR). The Journal publishes papers of the highest scientific merit and widest possible scope work in all areas related to medical and dental science. The Journal welcome review articles, leading medical and clinical research articles, technical notes, case reports and others.
In 2014, US healthcare spending exceeded $3.0 trillion with nearly 1/3 spent on hospitalizations. Informed by real-world data from an Electronic Health Record (EHR) database of clinical and administrative records spanning 273 million encounters for 60 million patients in 600+ hospitals across the US, Boston Strategic Partners (BSP) Clinical Insights report, Hospital Treated Sepsis, estimates 30% of all hospital discharges involve treatment of infectious organisms.
Sepsis is responsible for an estimated 12% of all hospital stays. At an average cost of $15,500 per occurrence, we estimate that hospitalizations for severe infections account for $212 billion in annual spending or 7% of total healthcare expenditure. In this report, we conduct an in-depth analysis of sepsis patient characteristics, medication management, costs, and laboratory testing.
The Hospital-Treated Sepsis Report is available at www.bostonsp.com/reports
Gram-positive bacteria are the likely causative agents of most sepsis infections. Physicians treat the vast majority of these infections with vancomycin, piperacillin-tazobactam, levofloxacin, and ceftriaxone. From 2010-2015, drug-resistant organisms caused an astonishing 40% of bacterial sepsis infections. After confirmatory diagnosis, over half of sepsis patients undergo a change in antibiotic therapy.
This report provides quantitative, objective data captured by hospitals contributing to Cerner Health Facts. This data provides real-world patient encounters and reflects real physician decisions and encounter characteristics (e.g. patient response to therapy and outcomes) in key areas, such as antibiotic resistant pathogens and antimicrobial stewardship.
Fluoroquinolone resistant rectal colonization predicts risk of infectious com...TC İÜ İTF Üroloji AD
Fluoroquinolone resistant rectal colonization predicts risk of infectious complications after transrectal prostate biopsy. Evidence based on journal club by Samed Verep
Hospital treated pneumonia - Diagnosis and TreatmentBostonsp
In 2014, US healthcare spending exceeded $3.0 trillion with nearly 1/3 spent on hospitalizations. Informed by real-world data from an Electronic Health Record (EHR) database of clinical and administrative records spanning 273 million encounters for 60 million patients in 600+ hospitals across the US, Boston Strategic Partners (BSP) Clinical Insights report, Hospital-Treated Pneumonia, estimates 30% of all hospital discharges involve treatment of infectious organisms. Pneumonia is responsible for an estimated 12% of all hospital stays. At an average cost of $15,500 per occurrence, we estimate that hospitalizations for severe infections account for around $212 billion in annual spending or 7% of total healthcare expenditure. In this report, we conduct an in-depth analysis of pneumonia patient characteristics, medication management, costs, and laboratory testing.
Hospital-Treated Pneumonia is available at www.bostonsp.com/reports.
Gram-negative bacteria are the likely causative agents of most pneumonia infections and physicians treat most of these patients with levofloxacin, ceftriaxone, and azithromycin. From 2010-2015, drug resistant organisms caused a surprising 20% of bacterial pneumonia infections.
This report provides quantitative, objective data captured by hospitals contributing to Cerner Health Facts. This data provides real-world patient encounters and reflects real physician decisions and encounter characteristics (e.g. patient response to therapy and outcomes) in key areas, such as antibiotic resistant pathogens and antimicrobial stewardship.
Abstract
In response to the rapidly rising intravenous opioid abuse epidemic, the United States Food and Drug Administration is currently promoting the development of prescription opioid tablets that are specifically formulated to deter abuse. Opana ER®; (Endo Pharmaceuticals) recently underwent reformulation to include a crush-resistant coating. Only recently described, illicit intravenous injection of reformulated Opana ER®; is associated with a distinctive clinical syndrome of thrombotic microangiopathy. Ten patients with the appropriate history and presenting symptoms were identified within an 8 month interval (July 2012 through February 2013) at the University of Tennessee Medical Center (UTMC) Knoxville with ICD-9 code of 446.6 (thrombotic microangiopathy) by electronic search. Review of laboratory data, electronic medical records, blood product usage, and total hospital admission charges were compiled for these individual patients. We report the clinicopathologic findings and correlating laboratory data for a group of patients presenting with thrombotic microangiopathy and documented recent history of intravenous Opana ER®; injection. We also report the economic impact and effect on blood product utilization by this study group.
NUR 440 Evidence TableStudy CitationDesignMethodSample.docxvannagoforth
NUR 440 Evidence Table
Study Citation
Design
Method
Sample
Data Collection
Data Analysis
Validity
Reliability
Magill, S. S., O’Leary, E., Janelle, S. J., Thompson, D. L., Dumyati, G., Nadle, J., & Ray, S. M. (2018). Changes in prevalence of health care–associated infections in US Hospitals. New England Journal of Medicine, 379(18), 1732-1744.
Longitudinal and multivariable log-binomial regression modeling
At Emerging Infections Program sites in 10 states, we recruited up to 25 hospitals in each site area, prioritizing hospitals that had participated in the 2011 survey.
Random samples of patients in acute care locations were selected from hospitals’ morning censuses on the survey date with the use of the method that had been used in the 2011 survey
Trained staff of the Emerging Infections Program sites reviewed medical records on the survey date or retrospectively to collect basic demographic and clinical data.
In 2015, a total of 12,299 patients in 199 hospitals were surveyed, as compared with 11,282 patients in 183 hospitals in 2011. Pneumonia, gastrointestinal infections and surgical-site infections were the most common health care–associated infections.
The CDC determined the survey to be a non-research activity.
Point-prevalence surveys of health care–associated infections in health care settings complement location- or infection-specific National Healthcare Safety Network data.
Zuarez-Easton, S., Zafran, N., Garmi, G., & Salim, R. (2017). Postcesarean wound infection: prevalence, impact, prevention, and management challenges. International journal of women's health, 9, 81.
Randomized trials, cohort, case–control, review, and meta-analysis were eligible.
Several electronic databases were searched from inception through June 2016: MEDLINE, PubMed, Ovid, and the Cochrane Library.
100,000 maternities compared to the period between 2003 and 2005
Data was collected through maternal comorbidities, appropriate antibiotic prophylaxis, and evidence-based surgical techniques practices.
Cesarean delivery is one of the most frequent surgical interventions performed worldwide and accounts for up to 60% of deliveries in a number of countries
Two authors (SZE and RS) selected articles first through focused review of abstracts. Eligible studies underwent full-text review.
The research Reviewed maternal death in the UK over a period of 3 years (2006–2008).
Chu, K., Maine, R., & Trelles, M. (2015). Cesarean section surgical site infections in sub-Saharan Africa: a multi-country study from Medecins Sans Frontieres. World journal of surgery, 39(2), 350-355.
Logistic regression was used to model determinants of SSI.
This study included data from four emergency obstetric programs supported by Medecins sans Frontieres, from Burundi, the Democratic Republic of Congo (DRC), and Sierra Leone.
1,276 women underwent CS.
Data were prospectively collected using a standardized paper form and then entered into an electronic database.
Baseline characteristics w ...
The dimensions of healthcare quality refer to various attributes or aspects that define the standard of healthcare services. These dimensions are used to evaluate, measure, and improve the quality of care provided to patients. A comprehensive understanding of these dimensions ensures that healthcare systems can address various aspects of patient care effectively and holistically. Dimensions of Healthcare Quality and Performance of care include the following; Appropriateness, Availability, Competence, Continuity, Effectiveness, Efficiency, Efficacy, Prevention, Respect and Care, Safety as well as Timeliness.
ICH Guidelines for Pharmacovigilance.pdfNEHA GUPTA
The "ICH Guidelines for Pharmacovigilance" PDF provides a comprehensive overview of the International Council for Harmonisation of Technical Requirements for Pharmaceuticals for Human Use (ICH) guidelines related to pharmacovigilance. These guidelines aim to ensure that drugs are safe and effective for patients by monitoring and assessing adverse effects, ensuring proper reporting systems, and improving risk management practices. The document is essential for professionals in the pharmaceutical industry, regulatory authorities, and healthcare providers, offering detailed procedures and standards for pharmacovigilance activities to enhance drug safety and protect public health.
Defecation
Normal defecation begins with movement in the left colon, moving stool toward the anus. When stool reaches the rectum, the distention causes relaxation of the internal sphincter and an awareness of the need to defecate. At the time of defecation, the external sphincter relaxes, and abdominal muscles contract, increasing intrarectal pressure and forcing the stool out
The Valsalva maneuver exerts pressure to expel faeces through a voluntary contraction of the abdominal muscles while maintaining forced expiration against a closed airway. Patients with cardiovascular disease, glaucoma, increased intracranial pressure, or a new surgical wound are at greater risk for cardiac dysrhythmias and elevated blood pressure with the Valsalva maneuver and need to avoid straining to pass the stool.
Normal defecation is painless, resulting in passage of soft, formed stool
CONSTIPATION
Constipation is a symptom, not a disease. Improper diet, reduced fluid intake, lack of exercise, and certain medications can cause constipation. For example, patients receiving opiates for pain after surgery often require a stool softener or laxative to prevent constipation. The signs of constipation include infrequent bowel movements (less than every 3 days), difficulty passing stools, excessive straining, inability to defecate at will, and hard feaces
IMPACTION
Fecal impaction results from unrelieved constipation. It is a collection of hardened feces wedged in the rectum that a person cannot expel. In cases of severe impaction the mass extends up into the sigmoid colon.
DIARRHEA
Diarrhea is an increase in the number of stools and the passage of liquid, unformed feces. It is associated with disorders affecting digestion, absorption, and secretion in the GI tract. Intestinal contents pass through the small and large intestine too quickly to allow for the usual absorption of fluid and nutrients. Irritation within the colon results in increased mucus secretion. As a result, feces become watery, and the patient is unable to control the urge to defecate. Normally an anal bag is safe and effective in long-term treatment of patients with fecal incontinence at home, in hospice, or in the hospital. Fecal incontinence is expensive and a potentially dangerous condition in terms of contamination and risk of skin ulceration
HEMORRHOIDS
Hemorrhoids are dilated, engorged veins in the lining of the rectum. They are either external or internal.
FLATULENCE
As gas accumulates in the lumen of the intestines, the bowel wall stretches and distends (flatulence). It is a common cause of abdominal fullness, pain, and cramping. Normally intestinal gas escapes through the mouth (belching) or the anus (passing of flatus)
FECAL INCONTINENCE
Fecal incontinence is the inability to control passage of feces and gas from the anus. Incontinence harms a patient’s body image
PREPARATION AND GIVING OF LAXATIVESACCORDING TO POTTER AND PERRY,
An enema is the instillation of a solution into the rectum and sig
Leading the Way in Nephrology: Dr. David Greene's Work with Stem Cells for Ki...Dr. David Greene Arizona
As we watch Dr. Greene's continued efforts and research in Arizona, it's clear that stem cell therapy holds a promising key to unlocking new doors in the treatment of kidney disease. With each study and trial, we step closer to a world where kidney disease is no longer a life sentence but a treatable condition, thanks to pioneers like Dr. David Greene.
Global launch of the Healthy Ageing and Prevention Index 2nd wave – alongside...ILC- UK
The Healthy Ageing and Prevention Index is an online tool created by ILC that ranks countries on six metrics including, life span, health span, work span, income, environmental performance, and happiness. The Index helps us understand how well countries have adapted to longevity and inform decision makers on what must be done to maximise the economic benefits that comes with living well for longer.
Alongside the 77th World Health Assembly in Geneva on 28 May 2024, we launched the second version of our Index, allowing us to track progress and give new insights into what needs to be done to keep populations healthier for longer.
The speakers included:
Professor Orazio Schillaci, Minister of Health, Italy
Dr Hans Groth, Chairman of the Board, World Demographic & Ageing Forum
Professor Ilona Kickbusch, Founder and Chair, Global Health Centre, Geneva Graduate Institute and co-chair, World Health Summit Council
Dr Natasha Azzopardi Muscat, Director, Country Health Policies and Systems Division, World Health Organisation EURO
Dr Marta Lomazzi, Executive Manager, World Federation of Public Health Associations
Dr Shyam Bishen, Head, Centre for Health and Healthcare and Member of the Executive Committee, World Economic Forum
Dr Karin Tegmark Wisell, Director General, Public Health Agency of Sweden
Antibiotic Stewardship by Anushri Srivastava.pptxAnushriSrivastav
Stewardship is the act of taking good care of something.
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
WHO launched the Global Antimicrobial Resistance and Use Surveillance System (GLASS) in 2015 to fill knowledge gaps and inform strategies at all levels.
ACCORDING TO apic.org,
Antimicrobial stewardship is a coordinated program that promotes the appropriate use of antimicrobials (including antibiotics), improves patient outcomes, reduces microbial resistance, and decreases the spread of infections caused by multidrug-resistant organisms.
ACCORDING TO pewtrusts.org,
Antibiotic stewardship refers to efforts in doctors’ offices, hospitals, long term care facilities, and other health care settings to ensure that antibiotics are used only when necessary and appropriate
According to WHO,
Antimicrobial stewardship is a systematic approach to educate and support health care professionals to follow evidence-based guidelines for prescribing and administering antimicrobials
In 1996, John McGowan and Dale Gerding first applied the term antimicrobial stewardship, where they suggested a causal association between antimicrobial agent use and resistance. They also focused on the urgency of large-scale controlled trials of antimicrobial-use regulation employing sophisticated epidemiologic methods, molecular typing, and precise resistance mechanism analysis.
Antimicrobial Stewardship(AMS) refers to the optimal selection, dosing, and duration of antimicrobial treatment resulting in the best clinical outcome with minimal side effects to the patients and minimal impact on subsequent resistance.
According to the 2019 report, in the US, more than 2.8 million antibiotic-resistant infections occur each year, and more than 35000 people die. In addition to this, it also mentioned that 223,900 cases of Clostridoides difficile occurred in 2017, of which 12800 people died. The report did not include viruses or parasites
VISION
Being proactive
Supporting optimal animal and human health
Exploring ways to reduce overall use of antimicrobials
Using the drugs that prevent and treat disease by killing microscopic organisms in a responsible way
GOAL
to prevent the generation and spread of antimicrobial resistance (AMR). Doing so will preserve the effectiveness of these drugs in animals and humans for years to come.
being to preserve human and animal health and the effectiveness of antimicrobial medications.
to implement a multidisciplinary approach in assembling a stewardship team to include an infectious disease physician, a clinical pharmacist with infectious diseases training, infection preventionist, and a close collaboration with the staff in the clinical microbiology laboratory
to prevent antimicrobial overuse, misuse and abuse.
to minimize the developme
CRISPR-Cas9, a revolutionary gene-editing tool, holds immense potential to reshape medicine, agriculture, and our understanding of life. But like any powerful tool, it comes with ethical considerations.
Unveiling CRISPR: This naturally occurring bacterial defense system (crRNA & Cas9 protein) fights viruses. Scientists repurposed it for precise gene editing (correction, deletion, insertion) by targeting specific DNA sequences.
The Promise: CRISPR offers exciting possibilities:
Gene Therapy: Correcting genetic diseases like cystic fibrosis.
Agriculture: Engineering crops resistant to pests and harsh environments.
Research: Studying gene function to unlock new knowledge.
The Peril: Ethical concerns demand attention:
Off-target Effects: Unintended DNA edits can have unforeseen consequences.
Eugenics: Misusing CRISPR for designer babies raises social and ethical questions.
Equity: High costs could limit access to this potentially life-saving technology.
The Path Forward: Responsible development is crucial:
International Collaboration: Clear guidelines are needed for research and human trials.
Public Education: Open discussions ensure informed decisions about CRISPR.
Prioritize Safety and Ethics: Safety and ethical principles must be paramount.
CRISPR offers a powerful tool for a better future, but responsible development and addressing ethical concerns are essential. By prioritizing safety, fostering open dialogue, and ensuring equitable access, we can harness CRISPR's power for the benefit of all. (2998 characters)
The Importance of Community Nursing Care.pdfAD Healthcare
NDIS and Community 24/7 Nursing Care is a specific type of support that may be provided under the NDIS for individuals with complex medical needs who require ongoing nursing care in a community setting, such as their home or a supported accommodation facility.
the IUA Administrative Board and General Assembly meeting
Critical Care Endotypes
1. CRITICAL CARE ENDOTYPES:
Collecting and analyzing large datasets to optimize
diagnosis in the ICU
David Maslove, MD, MS, FRCPC
Department of Critical Care Medicine & School of Computing
Director, CONDUIT Lab
Queen’s University, Kingston, Ontario
6. The new england journal of medicine
erraces(mean,18.8percent[95percentconfidence
interval, 17.1 to 20.5 percent]). Mortality rates did
not differ significantly according to sex (men, 22.0
percent; women, 21.8 percent).
The proportion of patients with sepsis who had
any organ failure, a marker of the severity of illness,
increased over time, from 19.1 percent in the first
11yearsto30.2percentinlateryears.Organfailure
occurredin33.6percentofpatientsduringthemost
recent subperiod, resulting in the identification of
184,060 cases of severe sepsis in 1995 and 256,033
in 2000. Organ failure had a cumulative effect on
mortality: approximately 15 percent of patients
without organ failure died, whereas 70 percent of
patients with three or more failing organs (classi-
fied as having severe sepsis and septic shock) died.
The additive effect of organ failure on mortality was
consistentovertime,withimprovementsinsurvival
being most evident among patients with fewer than
three failing organs. The organs that failed most
frequently in patients with sepsis were the lungs (in
18 percent of patients) and the kidneys (in 15 per-
cent of patients); less frequent were cardiovascular
failure (7 percent), hematologic failure (6 percent),
metabolic failure (4 percent), and neurologic fail-
ure (2 percent).
Figure 1. Population-Adjusted Incidence of Sepsis, According to Sex, 1979–2000.
Points represent the annual incidence rate, and I bars the standard error.
Population-AdjustedIncidenceofSepsis
(no./100,000)
300
200
100
0
1979 1981 1983 1997 1999 200119951985 1987 1989 1991 1993
Women
Men
Sepsis(no./100,000)
400
500
Black
White
Other
resourcesforepidemiologicinvestigationsinwhich
the prospective identification of patients is not fea-
sible.8,10 Using ICD-9-CM codes, Angus et al. cre-
ated a composite profile of sepsis from the 1995
hospital discharge records for seven states.2 They
estimated that there were 751,000 cases of severe
sepsisinthatyear,accountingfor2.1to4.3percent
ofhospitalizationsand11percentofalladmissions
to the ICU. These estimates may overstate the in-
cidence of severe sepsis by as much as a factor of
two to four,26 given that the estimated number of
deathsexceedsthecombinednumbersofdeathsre-
portedinassociationwithnosocomialbloodstream
infections27 and septic shock.28
The population-adjusted incidence of sepsis in
the United States has increased significantly over
the past two decades. The relative frequency of spe-
cific causative organisms has shifted over time, as
indicatedbythepublishedliterature,withtheemer-
gence of fungal pathogens29 and the recent pre-
eminence of gram-positive organisms.20,30 The
occurrence of organ failure increased over time
and was an additive contributor to mortality that
remained consistent among patients of different
races and sexes. The decline in mortality is nota-
ble, given the expected increases associated with
increasing age and the increasing severity of ill-
ness, but it is supported by previous analysis of cu-
mulative data from clinical trials.31 Such changes
are most likely attributabletononspecificimprove-
ments in intensive care,32,33 but diagnostic criteria
andcodingpracticesmayinfluencechangesaswell.
The increasing rate of discharge to nonacute care
medical facilities, in combination with the increas-
ing incidence of sepsis and the decrease in over-
all mortality among patients with sepsis, suggests
the fact that the greatest increase in incidence oc-
curred among women, men are consistently more
Figure 3. Numbers of Cases of Sepsis in the United States, According to
the Causative Organism, 1979–2000.
Points represent the number of cases for the given year, and I bars the stand-
ard error.
5,000
0
1979 1981 1983 1997 1999 200119951985 1987 1989 1991 1993
Figure 4. Overall In-Hospital Mortality Rate among Patients Hospitalized
for Sepsis, 1979–2000.
Mortality averaged 27.8 percent during the first six years of the study and 17.9
percent during the last six years. The I bars represent the standard error.
ProportionofPatientswithSepsisWhoDied
0.30
0.20
0.40
0.10
0.00
1979 1981 1983 1997 1999 200119951985 1987 1989 1991 1993
n engl j med 348;16 www.nejm.org april 17, 2003
confidenceinterval,1.24to1.32])andamongnonwhitepersonsthanamongwhiteper-
sons(meanannualrelativerisk,1.90[95percentconfidenceinterval,1.81to2.00]).Be-
tween 1979 and 2000, there was an annualized increase in the incidence of sepsis of
8.7 percent,fromabout164,000cases(82.7per100,000population)tonearly660,000
cases (240.4 per 100,000 population). The rate of sepsis due to fungal organisms in-
creased by 207percent,withgram-positivebacteriabecomingthepredominantpatho-
gens after 1987. The total in-hospital mortality rate fell from 27.8 percent during the
period from 1979 through 1984 to 17.9 percent during the period from 1995 through
2000,yetthetotalnumberofdeathscontinuedtoincrease.Mortalitywashighestamong
blackmen.Organfailurecontributedcumulativelytomortality,withtemporalimprove-
ments in survival among patients with fewer than three failing organs. The average
length of the hospital stay decreased, and the rate of discharge to nonacute care medi-
cal facilities increased.
conclusions
Theincidenceofsepsisandthenumberofsepsis-relateddeathsareincreasing,although
the overall mortality rate among patients with sepsis is declining. There are also dispar-
itiesamongracesandbetweenmenandwomenintheincidenceofsepsis.Gram-positive
bacteria and fungal organisms are increasingly common causes of sepsis.
ICU MORTALITY (US)
7. 100,000 ICU survivors per year
“Mild cognitive impairment” (40%)
“Moderate TBI” (25%)
BEYOND SURVIVAL
(ONTARIO)
9. -
-
s
,
k
e
-
s
t
r
n
e
e
,
t
m
e
r
a
o
e
.
d
s
s
B
,
Table 1. Clinical trials of biologic response modifiers in sepsis
Target Strategies
Endotoxin (LPS) Monoclonal antibodies
LPS: HA-1A, E5
Enterobacterial common
antigen
Toll-like receptor 4 (TLR4)
antagonists
Eritoran
TAK-242
Anti-CD14
Bactericidal permeability
increasing protein
Taurolidine
Alkaline phosphatase
Polymyxin B
Conjugate
Extracorporeal column
Lipid emulsion
Tumor necrosis factor (TNF) Monoclonal or polyclonal
antibodies
Soluble receptor constructs
Interleukin-1 (IL-1) Recombinant IL-1 receptor
antagonist
Platelet activating factor (PAF) Small molecule inhibitors
PAF acetylhydrolase
Eicosanoids Ibuprofen
Soluble phospholipase
A2 (sPLA2) inhibitor
Nitric oxide L-NMMA
Methylene blue
Hypercoagulability/disseminated
intravascular coagulation (DIC)
APC, Protein C concentrate
TFPI
Antithrombin
Anti-tissue factor antibody
Heparin
Thrombomodulin
Immune suppression Intravenous immunoglobulin
G-CSF, GM-CSF
Interferon g
Endocrinopathy Corticosteroids
Vasopressin
Others Selenium
Lactoferrin
Bradykinin antagonists
Statins
Extracorporeal hemoperfusion
Trends in Molecular Medicine xxx xxxx, Vol. xxx, No. x
Marshall JC. Trends Mol Med; 2014
tients with acute respiratory failure, in-
cluding effects of prone positioning (53–
55), ventilatory strategies (56–58), fluid
management (59), inhaled surfactant
(60), and anti-inflammatory therapies
(61–66). Other RCTs in this category as-
sessed the role of filgrastim in communi-
ty-acquired and nosocomial pneumonia
(67), the effects of selective decontamina-
tion of the digestive tract (68), enteral
nutrition (69), hemofiltration (70), he-
modynamic therapy (71, 72), the poten-
tial benefits of leukocyte-depleted red
blood cell transfusions (73, 74), and the
use of the pulmonary artery catheter
(6–8, 75). Importantly, some studies in
this group were designed to evaluate the
hypothesis that there would be no differ-
ence in mortality among groups, that is,
to show the noninferiority, rather than
the superiority, of a therapeutic strategy:
Chastre et al. (76) showed that adminis-
tration of antibiotics for 8 or 15 days
resulted in similar mortality rates in the
treatment of ventilator-a
monia; in the SAFE stud
administration was show
crystalloid for fluid repl
patients; and Hebert et
that the application of a r
fusion strategy was at le
liberal transfusion strate
Reporting and Metho
ity. We found adequate r
location concealment in
positive studies, six of se
tive studies, and 47 of 5
studies. When we analy
analysis carried out in
study, only five of ten
studies, two of seven
studies, and 37 of 55 (66%
included a precise descri
of analysis in the artic
intention-to-treat analysi
in 66 (90%) of the total
ies. Interestingly, we al
studies that did not clear
a
Cox regression analysis day 28: 1.54 (1.10–2.16), favoring invasive strateg
c
nonresponders to adrenocorticotropic hormone test; d
28-day mortality in all p
regression model: 0.71 (95% confidence interval [CI], 0.53–0.97, p ϭ .03), but sign
rates: ICU mortality relative risk (RR) of 0.89 (95% CI, 0.75–1.05), adjusted odds r
0.78–1.04), adjusted OR of 0.62 (95% CI, 0.36–1.05), p ϭ .08; e
control vs. hemo
Crit Care Med 2008 Vol. 36, No. 4
72 RCTs
“Any effect” (17)
“Positive” (10)
ICU RESEARCH AT A
CROSSROADS
100 studies
0 therapies
11. Current evidence-based research methods
look at the ways in which patients
resemble each other, rather than the
ways in which they differ.
“On average…”
17. •Definitions based on diagnostic criteria
•Criteria are vague
•Criteria are arbitrary
•Criteria can be met in numerous ways
SYNDROMES & ENDOTYPES
18. me
ning an Illness
Box. IOM Diagnostic Criteria for Systemic Exertion
Intolerance Disease
Diagnosis requires that the patient have the following
3 symptoms:
1.Asubstantialreductionorimpairmentintheabilityto
engage in preillness levels of occupational, educa-
tional,social,orpersonalactivitiesthatpersistsformore
than 6 months and is accompanied by fatigue, which is
often profound, is of new or definite onset (not life-
long),isnottheresultofongoingexcessiveexertion,and
is not substantially alleviated by rest AND
2. Postexertional malaisea
AND
3. Unrefreshing sleepa
VAGUE CRITERIA
19. the ALI non-ARDS category of the
AECC definition; TABLE 4), 50% (95%
CI, 48%-51%) of patients met criteria
for moderate ARDS, and 28% (95% CI,
ARDS at baseline progressed to moder-
ate ARDS and 4% (95% CI, 3%-6%) pro-
gressed to severe ARDS within 7 days;
and 13% (95% CI, 11%-14%) of pa-
Table 3. The Berlin Definition of Acute Respiratory Distress Syndrome
Acute Respiratory Distress Syndrome
Timing Within 1 week of a known clinical insult or new or worsening respiratory
symptoms
Chest imaginga Bilateral opacities—not fully explained by effusions, lobar/lung collapse, or
nodules
Origin of edema Respiratory failure not fully explained by cardiac failure or fluid overload
Need objective assessment (eg, echocardiography) to exclude hydrostatic
edema if no risk factor present
Oxygenationb
Mild 200 mm Hg Ͻ PaO2/FIO2 Յ 300 mm Hg with PEEP or CPAP Ն5 cm H2Oc
Moderate 100 mm Hg Ͻ PaO2/FIO2 Յ 200 mm Hg with PEEP Ն5 cm H2O
Severe PaO2/FIO2 Յ 100 mm Hg with PEEP Ն5 cm H2O
Abbreviations: CPAP, continuous positive airway pressure; FIO2, fraction of inspired oxygen; PaO2, partial pressure of
arterial oxygen; PEEP, positive end-expiratory pressure.
aChest radiograph or computed tomography scan.
bIf altitude is higher than 1000 m, the correction factor should be calculated as follows: [PaO2/FIO2ϫ(barometric pressure/
760)].
cThis may be delivered noninvasively in the mild acute respiratory distress syndrome group.
ARBITRARY CRITERIA
20. MEETING SYNDROME
CRITERIA
ort, EBM emphasizes the similarities between patients, lea
hich they differ. These differences many of which occur a
en as inextricably linked to a comprehensive understanding
mulation of effective, individualized treatment plans. In th
bstantial physiologic heterogeneity amongst groups of patien
mixed outcomes in the setting of randomized trials, and so
ere is growing appreciation of the limitations of the curre
earch,3
and an increasing appetite to develop new methods
ur current understanding of human illnesses, and of the d
perience them, remains imprecise. This uncertainty is reflec
any are syndromic in nature, described by a constellation of
ssic diagnosis for systemic lupus requires that at least 4 o
esent, resulting in 11
4
+ 11
5
+ 11
6
+· · ·+ 11
11
= 1816 way
cumstances arise in the diagnosis of critical illness. Sepsi
21. Objective: -
Design: -
-
Methods:
-
-
Surviving Sepsis Campaign: International
Guidelines for Management of Severe Sepsis
and Septic Shock: 2012
R. Phillip Dellinger, MD1
; Mitchell M. Levy, MD2
; Andrew Rhodes, MB BS3
; Djillali Annane, MD4
;
Herwig Gerlach, MD, PhD5
; Steven M. Opal, MD6
; Jonathan E. Sevransky, MD7
; Charles L. Sprung, MD8
;
Ivor S. Douglas, MD9
; Roman Jaeschke, MD10
; Tiffany M. Osborn, MD, MPH11
; Mark E. Nunnally, MD12
;
Sean R. Townsend, MD13
; Konrad Reinhart, MD14
; Ruth M. Kleinpell, PhD, RN-CS15
;
Derek C.Angus, MD, MPH16
; Clifford S. Deutschman, MD, MS17
; Flavia R. Machado, MD, PhD18
;
Gordon D. Rubenfeld, MD19
; Steven A.Webb, MB BS, PhD20
; Richard J. Beale, MB BS21
;
Jean-Louis Vincent, MD, PhD22
; Rui Moreno, MD, PhD23
; and the Surviving Sepsis Campaign
Guidelines Committee including the Pediatric Subgroup*
Critical Care Medicine
0090-3493
10.1097/CCM.10.1097/CCM.0b013e31827e83af
LWW
Special Article
Special Article
SEPSIS SYNDROMES
22. Special Article
TABLE 1. Diagnostic Criteria for Sepsis
Infection, documented or suspected, and some of the following:
General variables
Fever (> 38.3°C)
Hypothermia (core temperature < 36°C)
Heart rate > 90/min–1
or more than two SD above the normal value for age
Tachypnea
Altered mental status
Significant edema or positive fluid balance (> 20mL/kg over 24hr)
Hyperglycemia (plasma glucose > 140mg/dL or 7.7 mmol/L) in the absence of diabetes
Inflammatory variables
Leukocytosis (WBC count > 12,000 µL–1
)
Leukopenia (WBC count < 4000 µL–1
)
Normal WBC count with greater than 10% immature forms
Plasma C-reactive protein more than two SD above the normal value
Plasma procalcitonin more than two SD above the normal value
Hemodynamic variables
Arterial hypotension (SBP < 90mm Hg, MAP < 70mm Hg, or an SBP decrease > 40mm Hg in adults or less than two SD
below normal for age)
Organ dysfunction variables
Arterial hypoxemia (Pao2
/FIO2
< 300)
Acute oliguria (urine output < 0.5mL/kg/hr for at least 2 hrs despite adequate fluid resuscitation)
Creatinine increase > 0.5mg/dL or 44.2 µmol/L
Coagulation abnormalities (INR > 1.5 or aPTT > 60 s)
Ileus (absent bowel sounds)
Thrombocytopenia (platelet count < 100,000 µL–1
)
Hyperbilirubinemia (plasma total bilirubin > 4mg/dL or 70 µmol/L)
Tissue perfusion variables
Hyperlactatemia (> 1 mmol/L)
Decreased capillary refill or mottling
° °
Crit Care Med
Arbitrary
Vague
Met in many ways
SEPSIS SYNDROMES
38. RESEARCH Open Access
Identification of sepsis subtypes in critically ill
adults using gene expression profiling
David M Maslove1,2*
, Benjamin M Tang3,4
and Anthony S McLean3
Abstract
Introduction: Sepsis is a syndromic illness that has traditionally been defined by a set of broad, highly sensitive
clinical parameters. As a result, numerous distinct pathophysiologic states may meet diagnostic criteria for sepsis,
leading to syndrome heterogeneity. The existence of biologically distinct sepsis subtypes may in part explain the
lack of actionable evidence from clinical trials of sepsis therapies. We used microarray-based gene expression data
from adult patients with sepsis in order to identify molecularly distinct sepsis subtypes.
Methods: We used partitioning around medoids (PAM) and hierarchical clustering of gene expression profiles
from neutrophils taken from a cohort of septic patients in order to identify distinct subtypes. Using the medoids
learned from this cohort, we then clustered a second independent cohort of septic patients, and used the
resulting class labels to evaluate differences in clinical parameters, as well as the expression of relevant
pharmacogenes.
Results: We identified two sepsis subtypes based on gene expression patterns. Subtype 1 was characterized by
increased expression of genes involved in inflammatory and Toll receptor mediated signaling pathways, as well as
a higher prevalence of severe sepsis. There were differences between subtypes in the expression of
pharmacogenes related to hydrocortisone, vasopressin, norepinephrine, and drotrecogin alpha.
Conclusions: Sepsis subtypes can be identified based on different gene expression patterns. These patterns may
generate hypotheses about the underlying pathophysiology of sepsis and suggest new ways of classifying septic
patients both in clinical practice, and in the design of clinical trials.
Keywords: Sepsis, severe sepsis, septic shock, gene expression profiling, microarray analysis, biomedical informatics,
critical care, intensive care
Maslove et al. Critical Care 2012, 16:R183
http://ccforum.com/content/16/5/R183
10
ering
−40 −20 0 20 40
−20−1001020
Final PAM clustering
Component 1
Component2
each plot, the patients are plotted within a two-dimensional
s in the first plot are colored according to the cluster
nbank. The colors in the second and third plots reflect the
results of the clustering at that stage. (A) Initial clustering
Page 4 of 11
between patients with sepsis and non-sepsis controls.
This latter approach has the potential to exclude genes
that may be important in differentiating sepsis subtypes,
rather than differentiating sepsis from controls.
Our results highlight the complexity and heterogeneity
of sepsis at the molecular level, a finding in keeping with
were obtained from neutrophils collected within
24 hours of admission to the ICU. While it has been sug-
gested that the tissue used and timing of microarray ana-
lysis could have a significant impact on gene expression
studies in sepsis [33], the experimental conditions were
similar for all patients and for both cohorts, so that dif-
−40 −20 0 20 40
−20−10010
Validation cohort clustering
Component 1
Component2
Figure 4 Validation cohort clustering. Clusters resulting from assignment of the validation cohort samples to the closest derivation medoid.
Maslove et al. Critical Care 2012, 16:R183
http://ccforum.com/content/16/5/R183
Page 7 of 11
Derivation Validation
40. Mortality (%) Male (%) Severe sepsis (%) Ventilated (%) Dialysis (%) Pressors (%)
0.00.10.20.30.40.50.60.7
Subtype1
Subtype 2
Length of stay (d) Age Apache II Apache III SAPS II
020406080
Subtype1
Subtype 2
*
CLINICAL
FEATURES
41. Pharmacogenes
Gene ID Fold Change
drotrecogin alpha
TFPI 1.74
SERPINB2 1.61
CP 1.52
GGCX 1.49
SERPIND1 1.58
SERPINB6 1.82
SERPINE1 1.43
THBD 0.53
F5 0.48
vasopressin
GNG11 1.73
GNG5 1.43
GNAQ 0.58
hydrocortisone
5-LOX 0.34
ANXA1 0.64
norepinephrine
NNMT 1.32
MOXD1 1.42
PharmGKB
Reduction of the multiple organ injury and dysfunction caused
by endotoxemia in 5-lipoxygenase knockout mice and by
the 5-lipoxygenase inhibitor zileuton
Marika Collin,* Antonietta Rossi,†
Salvatore Cuzzocrea,‡
Nimesh S. A. Patel,* Rosanna Di Paola,‡
Julia Hadley,* Massimo Collino,* Lidia Sautebin,†
and Christoph Thiemermann*,1
*Centre for Experimental Medicine, Nephrology & Critical Care, The William Harvey Research Institute,
Queen Mary, University of London, United Kingdom; †
Department of Experimental Pharmacology, Universita`
‘Federico II’, Naples, Italy; and ‡
Department of Clinical and Experimental Medicine and Pharmacology,
University of Messina, Italy
Abstract: The role of 5-lipoxygenase (5-LOX) in
the pathophysiology of the organ injury/dysfunc-
tion caused by endotoxin is not known. Here, we
investigate the effects of treatment with 5-LOX
INTRODUCTION
Inflammation is a complex set of interactions among soluble
mediators, circulating cells, and vessel walls and may arise in
lipopolysaccharide (LPS; Escherichia coli, 6 mg/kg
i.v.) or vehicle (saline). 5-LOX؊/؊
mice and wild-
type littermate controls were treated with LPS (E.
coli, 20 mg/kg intraperitoneally) or vehicle (sa-
line). Endotoxemia for 6 h in rats or 16 h in mice
resulted in liver injury/dysfunction (increase in the
serum levels of aspartate aminotransferase, alanine
aminotransferase, ␥-glutamyl transferase, alkaline
phosphatase, bilirubin), renal dysfunction (creati-
nine), and pancreatic injury (lipase, amylase). Ab-
sence of functional 5-LOX (zileuton treatment or
targeted disruption of the 5-LOX gene) reduced
the multiple organ injury/dysfunction caused by
endotoxemia. Polymorphonuclear leukocyte infil-
tration (myeloperoxidase activity) in the lung and
ileum as well as pulmonary injury (histology) were
markedly reduced in 5-LOX؊/؊
mice. Zileuton also
reduced the LPS-induced expression of CD11b/
CD18 on rat leukocytes. We propose that endog-
enous 5-LOX metabolites enhance the degree of
multiple organ injury/dysfunction caused by severe
endotoxemia by promoting the expression of the
adhesion molecule CD11b/CD18 and that inhibi-
tors of 5-LOX may be useful in the therapy of the
organ injury/dysfunction associated with endotoxic
shock. J. Leukoc. Biol. 76: 961–970; 2004.
Key Words: shock ⅐ 2-integrins ⅐ CD11a/CD18 ⅐ CD11b/CD18
⅐ leukotrienes
5-LOX is predominantly expressed by cells of myeloid origin,
particularly neutrophils, eosinophils, macrophages/monocytes,
and mast cells [4, 5]. LTs are involved in the genesis of
inflammation and edema, because of their effects on vascular
permeability, plasma extravasation, and diapedesis of white
blood cells [6, 7], and they may also play an important role in
adaptive immune responses [8]. There is now good evidence
that LTs play a pivotal role in the pathophysiology of asthma [9,
10] and psoriasis [11, 12], as well as in conditions associated
with ischemia-reperfusion (I/R) of skin [13, 14], brain [15], and
kidney [13, 16, 17]. LTs also play a physiological role in the
host defense against microbial infections [18].
LTB4 is a proinflammatory mediator that activates polymor-
phonuclear leukocytes (PMN), thus changing their shape and
promoting their binding to endothelium by inducing the ex-
pression of cell-adhesion molecules. The localization of leuko-
cytes to the site of inflammation requires several families of
adhesion molecules. Firm adhesion of leukocytes to the micro-
vascular endothelium is dependent on the function of the class
of adhesion molecules called 2-integrins, which are expressed
on neutrophil surface and interact with members of the immu-
noglobulin (Ig) supergene family expressed on endothelial cells
such as intercellular adhesion molecule-1 (ICAM-1) [19–22].
1
Correspondence: Centre for Experimental Medicine, Nephrology & Criti-
cal Care, William Harvey Research Institute, Queen Mary, University of
London, Charterhouse Square, London, EC1M 6BQ, UK. E-mail:
c.thiemermann@qmul.ac.uk
Received June 14, 2004; accepted August 3, 2004; doi: 10.1189/
jlb.0604338.
Journal of Leukocyte Biology Volume 76, November 2004 961
So what about those trials?
42. Pharmacogenes
Gene ID Fold Change
drotrecogin alpha
TFPI 1.74
SERPINB2 1.61
CP 1.52
GGCX 1.49
SERPIND1 1.58
SERPINB6 1.82
SERPINE1 1.43
THBD 0.53
F5 0.48
vasopressin
GNG11 1.73
GNG5 1.43
GNAQ 0.58
hydrocortisone
5-LOX 0.34
ANXA1 0.64
norepinephrine
NNMT 1.32
MOXD1 1.42
PharmGKB
This Provisional PDF corresponds to the article as it appeared upon acceptance. Copyedited and
fully formatted PDF and full text (HTML) versions will be made available soon.
Flavocoxid, a dual inhibitor of COX-2 and 5-LOX of natural origin, attenuates the
inflammatory response and protects mice from sepsis
Critical Care 2012, 16:R32 doi:10.1186/1364-8535-16-R32
Alessandra Bitto (abitto@unime.it)
Letteria Minutoli (lminutoli@unime.it)
Antonio David (adavid@unime.it)
Natasha Irrera (nirrera@unime.it)
Mariagrazia Rinaldi (mariagrazia.rinaldi@yahoo.it)
Francesco S Venuti (fsvenuti@unime.it)
Critical Care
This Provisional PDF corresponds to the article as it appeared upon acceptance. Copyedited and
fully formatted PDF and full text (HTML) versions will be made available soon.
Flavocoxid, a dual inhibitor of COX-2 and 5-LOX of natural origin, attenuates the
inflammatory response and protects mice from sepsis
Critical Care 2012, 16:R32 doi:10.1186/1364-8535-16-R32
Alessandra Bitto (abitto@unime.it)
Letteria Minutoli (lminutoli@unime.it)
Critical Care
So what about those trials?
43. MOLECULAR
COMPLEXITY
X
DYNAMIC
CHANGE
(GRO-b), CCL2 (MCP-1), CXCL8 (IL-8) and CXCL10)
maximum 2–4 h after endotoxin administration, consis
early activation of innate immunity. Subsequently, the e
of several members of the nuclear factor kappa/relA
transcription factors (NFKB1, NFKB2, RELA and RELB
their zenith.
The time period 4–6 h after endotoxin injection seemed
the expression of a number of transcription factors was
including both those that initiate and those that limit
immune response. In the former group, these included
transducer and activators of transcription (STAT genes)
cAMP-response element-binding protein (CREB) and
enhancer binding protein (CEBP) gene families. Transcri
tors limiting the innate immune response included sup
cytokine signalling 3 (SOCS3) and IKBK genes. There was a
(4–6 h) in increased mRNA abundance of secreted and m
associated proteins that limit the inflammatory response,
IL1RAP, IL1R2, IL10 and TNFRSF1A. Together, these dat
hensively document the temporal modulation of genes c
the innate immune response in a human model that
from an acute proinflammatory phase to unencumbered
regulation, concluding with full recovery and a normal ph
To further elucidate the global changes during inflamm
subsequent return to homeostasis, we sought to compu
decipher the principal networks involved. The specificity o
tions for each gene was calculated, as defined by the percen
direct connections to other genes showing significant trans
changes. A network pathway was initiated by the gene
highest specificity of connections, and was propagated ac
the descent of the specificity. Individual significant pathw
ified by a statistical likelihood calculation (P , 0.0001) we
to represent the biological processes.
Our global representation of the inflammatory respons
toxin, shown in Fig. 3a, comprises a network of 1,556 gene
interactions. This network consists of a subset of 1,214 ge
responsive to in vivo endotoxin administration, and 342 a
Vol 437|13 October 2005|doi:10.1038/nature03985 Vol 437|13 October 2005|doi:10.1038/nature0398
46. ster cohesiveness between whole blood and leukocyte iso-
s, with whole blood-derived data yielding significantly
her average silhouette widths (median values 0.28 and
9 respectively, P ¼ 0.002). In the specific task of forming
(median values 0.21 for whole blood vs 0.16 for isola
P ¼ 0.13). The lack of statistical significance in these analy
may in part be due to a loss of statistical power in this sma
subset of studies.
IG. 3. Principal components analysis (PCA) representations of gene expression data yielding clusters with differing average silhouette wid
shapes of the points reflect the cluster assignment as determined by the partitioning around medoids (PAM) clustering algorithm used in the analysis. F
pes represent sepsis cases while open shapes are control samples, which in the case of the two studies shown were non-septic ICU patients. The left p
ws gene expression data derived from neutrophil RNA (GSE6535) that results in overlapping clusters, while the right panel shows gene expression
ved from whole blood RNA (GSE32707) that results in more cohesive clusters. These differences are reflected in the average silhouette widths (0.16 fo
rophil-derived data vs 0.48 for whole blood-derived data). Clustering of whole blood data revealed a distinct subset of controls, whereas sepsis and coMaslove & Marshall (2016), Shock, 293(3)
STANDARDS & METHODS
Sp 94% vs 78%
Avg. Sil (k=2) 0.41 vs 0.29
47. • Phase II RCT examining the effects of bovine
lactoferrin in preventing nosocomial infection
in the ICU
• Over 100 patients enrolled at 4 centres in
Canada
• Time series gene expression data from a
subset of ~ 80 patients
PREVAIL
Day 28
Baseline
Day 3
Day 7
Day 14
Day 21
62. HR
RR
SpO2
ABPm
ABPd
ABPs
NBPm
NBPd
NBPs
0 5000 10000 15000 20000
Number of measurements
Vitalsign
Non−terminal zeros
Terminal zeros, not assoc. with death
Terminal zeros assoc. with death
HR
RR
SpO2
ABP
NBP
0 50000 100000 150000
Number of VSDs
Vitalsign
Insufficient data
Sufficient data with gaps
Sufficient data with no gaps
0
50000
100000
150000
ABP NBP
vital sign
count
Errors
No errors
numberofmeasurements
Maslove et al. Critical Care Medicine 2016, (In press)
74. ICU DISEASES ARE SYNDROMIC.
SUBTYPES ABOUND.
DATA = DISTINCTION.
DATA ABOUND.
Precision
diagnosis
75. similar patients. The solid and dashed lines are the mean and 95% confidence
en training data homogeneity and size is apparent; as the number of similar patients in
t a rapid rate thanks to increasing training data size but starts to degrade gradually due
er the receiver operating characteristic curve; AUPRC: area under the precision-
Personalized Mortality Prediction
Lee, Maslove, Dubin. PLOS One (2015)
PATIENT
SIMILARITY
Fig 1. Mortality prediction performance of death counting among similar patients. The solid and dashed lines are the mean and 95% confidence
intervals, respectively, from 10-fold cross-validation. A trade-off between training data homogeneity and size is apparent; as the number of similar patients in
the training data increases, predictive performance improves initially at a rapid rate thanks to increasing training data size but starts to degrade gradually due
to decreasing homogeneity within the training data. AUROC: area under the receiver operating characteristic curve; AUPRC: area under the precision-
recall curve.
doi:10.1371/journal.pone.0127428.g001
Personalized Mortality Prediction
76. All High SOFA Low SOFA
0.00
0.25
0.50
0.75
0.00
0.25
0.50
0.75
0.00
0.25
0.50
0.75
0.00
0.25
0.50
0.75
CCUCSRUMICUSICU
AUPRC AUROC AUPRC AUROC AUPRC AUROC
Areaundercurve
Score
Custom
SAPS
Lee, Maslove. J Intensive Care Med (2015)
LOCAL
DATA
78. ACKNOWLEDGEMENTS
Dr. J. Gordon Boyd
Dr. John Muscedere
Dr. Joon Lee
Michael Wood
Victoria Tolls
Usman Raza
Miranda Hunt
Nicole O’Callahagn
Ilinca Georgescu
david.maslove@queensu.ca
www.conduitlab.org