Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study.

Importance Definitions of sepsis and septic shock were last revised in 2001. Considerable advances have since been made into the pathobiology (changes in organ function, morphology, cell biology, biochemistry, immunology, and circulation), management, and epidemiology of sepsis, suggesting the need for reexamination. Objective To evaluate and, as needed, update definitions for sepsis and septic shock. Process A task force (n = 19) with expertise in sepsis pathobiology, clinical trials, and epidemiology was convened by the Society of Critical Care Medicine and the European Society of Intensive Care Medicine. Definitions and clinical criteria were generated through meetings, Delphi processes, analysis of electronic health record databases, and voting, followed by circulation to international professional societies, requesting peer review and endorsement (by 31 societies listed in the Acknowledgment). Key Findings From Evidence Synthesis Limitations of previous definitions included an excessive focus on inflammation, the misleading model that sepsis follows a continuum through severe sepsis to shock, and inadequate specificity and sensitivity of the systemic inflammatory response syndrome (SIRS) criteria. Multiple definitions and terminologies are currently in use for sepsis, septic shock, and organ dysfunction, leading to discrepancies in reported incidence and observed mortality. The task force concluded the term severe sepsis was redundant. Recommendations Sepsis should be defined as life-threatening organ dysfunction caused by a dysregulated host response to infection. For clinical operationalization, organ dysfunction can be represented by an increase in the Sequential [Sepsis-related] Organ Failure Assessment (SOFA) score of 2 points or more, which is associated with an in-hospital mortality greater than 10%. Septic shock should be defined as a subset of sepsis in which particularly profound circulatory, cellular, and metabolic abnormalities are associated with a greater risk of mortality than with sepsis alone. Patients with septic shock can be clinically identified by a vasopressor requirement to maintain a mean arterial pressure of 65 mm Hg or greater and serum lactate level greater than 2 mmol/L (>18 mg/dL) in the absence of hypovolemia. This combination is associated with hospital mortality rates greater than 40%. In out-of-hospital, emergency department, or general hospital ward settings, adult patients with suspected infection can be rapidly identified as being more likely to have poor outcomes typical of sepsis if they have at least 2 of the following clinical criteria that together constitute a new bedside clinical score termed quickSOFA (qSOFA): respiratory rate of 22/min or greater, altered mentation, or systolic blood pressure of 100 mm Hg or less. Conclusions and Relevance These updated definitions and clinical criteria should replace previous definitions, offer greater consistency for epidemiologic studies and clinical trials, and facilitate earlier recognition and more timely management of patients with sepsis or at risk of developing sepsis.

https://jamanetwork.com/journals/jama/articlepdf/2492881/jsc160002.pdf

The Third International Consensus Definitions for Sepsis and Septic Shock (Sepsis-3)

The lion's share of bacteria in various environments cannot be cloned in the laboratory and thus cannot be sequenced using existing technologies. A major goal of single-cell genomics is to complement gene-centric metagenomic data with whole-genome assemblies of uncultivated organisms. Assembly of single-cell data is challenging because of highly non-uniform read coverage as well as elevated levels of sequencing errors and chimeric reads. We describe SPAdes, a new assembler for both single-cell and standard (multicell) assembly, and demonstrate that it improves on the recently released E+V-SC assembler (specialized for single-cell data) and on popular assemblers Velvet and SoapDeNovo (for multicell data). SPAdes generates single-cell assemblies, providing information about genomes of uncultivatable bacteria that vastly exceeds what may be obtained via traditional metagenomics studies. SPAdes is available online ( http://bioinf.spbau.ru/spades ). It is distributed as open source software.

SPAdes, a new genome assembly algorithm and its applications to single-cell sequencing ( 7th Annual SFAF Meeting, 2012)

tion’, implying that most patients ‘should’ receive a particular action. In contrast, level 2 guidelines are essentially ‘suggestions’ and are deemed to be ‘weak’ or discretionary, recognising that management decisions may vary in different clinical contexts. Each recommendation was further graded from A to D by the quality of evidence underpinning them, with grade A referring to a high quality of evidence whilst grade D recognised a ‘very low’ evidence base. The overall strength and quality of the supporting evidence is summarised in table 1 . The guidelines focused on 4 key domains: (1) AKI definition, (2) prevention and treatment of AKI, (3) contrastinduced AKI (CI-AKI) and (4) dialysis interventions for the treatment of AKI. The full summary of clinical practice statements is available at www.kdigo.org, but a few key recommendation statements will be highlighted here.

/pdf/kdigo-clinical-practice-guidelines-for-acute-kidney-injury-27tybolw7l.pdf

KDIGO clinical practice guidelines for acute kidney injury.

Acute kidney injury (AKI) is a complex disorder for which currently there is no accepted definition. Having a uniform standard for diagnosing and classifying AKI would enhance our ability to manage these patients. Future clinical and translational research in AKI will require collaborative networks of investigators drawn from various disciplines, dissemination of information via multidisciplinary joint conferences and publications, and improved translation of knowledge from pre-clinical research. We describe an initiative to develop uniform standards for defining and classifying AKI and to establish a forum for multidisciplinary interaction to improve care for patients with or at risk for AKI. Members representing key societies in critical care and nephrology along with additional experts in adult and pediatric AKI participated in a two day conference in Amsterdam, The Netherlands, in September 2005 and were assigned to one of three workgroups. Each group's discussions formed the basis for draft recommendations that were later refined and improved during discussion with the larger group. Dissenting opinions were also noted. The final draft recommendations were circulated to all participants and subsequently agreed upon as the consensus recommendations for this report. Participating societies endorsed the recommendations and agreed to help disseminate the results. The term AKI is proposed to represent the entire spectrum of acute renal failure. Diagnostic criteria for AKI are proposed based on acute alterations in serum creatinine or urine output. A staging system for AKI which reflects quantitative changes in serum creatinine and urine output has been developed. We describe the formation of a multidisciplinary collaborative network focused on AKI. We have proposed uniform standards for diagnosing and classifying AKI which will need to be validated in future studies. The Acute Kidney Injury Network offers a mechanism for proceeding with efforts to improve patient outcomes.

Acute Kidney Injury Network: report of an initiative to improve outcomes in acute kidney injury

Associations between different sedatives and ventilator-associated events, length-of-stay, and mortality in mechanically ventilated patients.

Sepsis is the subject of intense interest for clinicians, policy makers, patients, and researchers. Stakeholders around the world are striving to improve sepsis awareness and quality of care. The Surviving Sepsis Campaign, World Sepsis Day, and mandatory reporting rules are but a few examples of ongoing initiatives. All sepsis stakeholders need accurate data on sepsis incidence, characteristics, outcomes, and whether these are changing over time. Without these it is almost impossible to plan appropriately or to know whether our efforts to prevent sepsis and improve care are bearing fruit. The most common source for sepsis surveillance is hospital discharge codes. Their advantages include widespread availability and low cost. At first blush they also appear relatively straightforward to analyze. On closer inspection, however, they are fraught with subtleties and uncertainties. There are two prevailing strategies to identify sepsis using diagnosis codes: 1) identify patients with explicit codes for severe sepsis and septic shock, or 2) seek patients with concurrent discharge codes for infection and organ dysfunction, the so-called “implicit” method. The second strategy has obvious limitations. Investigators have proposed at least 5 different sets of infection and diagnosis codes to identify sepsis. Not surprisingly, different methods suggest very different sepsis rates [1]. Moreover, simultaneous infection and organ dysfunction codes at discharge do not reliably imply that organ dysfunction was due to infection. Explicit sepsis codes also have their limitations. They were only added to the International Classification of Disease (ICD9-CM) lexicon in 2002. Despite the passage of almost 15 years since their release, clinicians and coders are still becoming familiar with them and only gradually introducing them into practice. A recent study in Critical Care by Bouza et al. elucidated the uptake rate of explicit diagnosis codes using data from the Spanish national hospital discharge database for the years 2006-2011 [2]. They queried the database for sepsis using the explicit and one implicit strategy in a mutually exclusive fashion. The fraction of total cases assigned explicit codes rose from 51 % in 2006 to 64 % in 2011. Patients assigned explicit codes were sicker than patients with implicit codes alone: almost twice as many had mechanical ventilation codes and ten times as many had cardiovascular dysfunction codes. The in-hospital mortality rate for patients with explicit codes was almost double that of patients with implicit codes alone (55 % vs 29 %). This study has important implications for stakeholders trying to understand sepsis epidemiology through codebased analyses. It is clear that one cannot consider cases identified using explicit codes interchangeably with those identified through implicit codes. It is also clear that tracking sepsis using explicit codes alone provides an incomplete and changing picture of the septic population. One might wonder, however, whether it’s feasible to track sepsis adequately using the combined population of patients with either explicit or implicit codes? To answer this question we need to understand more about the reliability of explicit and implicit codes. Do all * Correspondence: mklompas@partners.org Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, 401 Park Street, Suite 401, Boston, MA 02215, USA Department of Medicine, Brigham and Women’s Hospital, Boston, MA, USA

https://dash.harvard.edu/bitstream/handle/1/29739077/5139029.pdf?sequence=1

Sepsis and the theory of relativity: measuring a moving target with a moving measuring stick.

1930 www.ccmjournal.org November 2017 • Volume 45 • Number 11 Septic shock is rapidly becoming critical care’s last remaining bastion for unrestrained antibiotic prescribing. Just about every other area of critical care is moving toward using antibiotics more parsimoniously. Recent studies and guidelines attest to the feasibility of waiting for diagnostic data before prescribing antibiotics for ICU patients without septic shock, the fact that many severe respiratory infections are caused by viruses rather than bacteria, the fact that many sepsis-like syndromes in the ICU are not infections, the relative paucity of drug-resistant organisms even among patients with “healthcare-associated” infections, the safety of shortening treatment courses for patients with established infections, and the futility of antibiotic prophylaxis in noninfectious inflammatory conditions (1–10). By contrast, the latest treatment guidelines for septic shock advise more antibiotics rather than less. They suggest that treating septic shock with two antibiotics, both active against a patient’s known or suspected pathogens, for “several days” is likely to be clinically useful. They recommend continuing combination therapy with two active agents until there is clinical improvement and/or evidence of infection resolution, regardless of when susceptibility results return (11). This aggressive recommendation bears contemplation. What is the origin of the enduring perception that septic shock requires sustained double coverage? Is this recommendation supported by current literature? How in practice should we be treating patients with Gram-negative septic shock? Three reasons for double covering Gram negatives have been proposed: 1) to increase the probability that at least one agent will be active against the patient’s infecting pathogen(s), 2) to prevent the emergence of antibiotic-resistant pathogens, and 3) to increase the efficiency of pathogen clearance by taking advantage of additive or synergistic effects between multiple agents drawn from different classes. The quality of evidence supporting these claims varies. There are moderate data that combination therapy is more likely to include an active agent, conflicting data on whether combination therapy decreases or increases selection for resistant organisms, and in vitro data showing that combinations of antibiotics can be synergistic, antagonistic, or neutral (12–17). Recommendations in favor of combination therapy can be traced to observational studies from the 1970s, 1980s, and 1990s that documented lower mortality rates in patients with Gram-negative bacteremia treated with two antibiotics rather than one, particularly among patients infected with Pseudomonas aeruginosa (18–22). A landmark meta-analysis published in 2004 summarized the papers published to that point: no differences in mortality rates with two agents versus one for Gram-negative bacteremia in general, but a 50% decrease in the odds of death when treating Pseudomonas bacteremia with two agents rather than one (23). This finding, however, has not stood the test of time. The five studies included in the 2004 meta-analysis were observational case series at high risk of bias. The studies themselves reported significant differences between patients treated with combination therapy versus those treated with monotherapy. In the largest case series, for example, patients treated with monotherapy were more likely to have nosocomial infections and to require critical care compared with those who received combination therapy (19). More recent case series that rigorously adjusted for potential confounders report no differences in mortality rates or time to shock resolution with combination versus monotherapy and indeed more frequent kidney injury when the second agent is an aminoglycoside (24–27). Likewise, updated meta-analyses published in 2013 and 2014 reported that combination therapy does not confer a survival benefit for patients with sepsis in general nor for patients with Pseudomonas bacteremia in particular (15, 28). It should also be noted that we lack good data on the potential harms associated with antibiotic prescribing, including Clostridium difficile infection, drug adverse effects, and cultivation of antibiotic resistance. These gaps in our knowledge make it that much more difficult to recommend sustained combination therapy. More recently, Kumar et al (29, 30) reawakened interest in the potential advantages of combination therapy by hypothesizing that the benefits of dual coverage may be limited to patients with septic shock. They reasoned that patients in septic shock are at increasing risk of death with every passing moment in shock and that it is critical to clear their infections as quickly as possible. They proposed that two antibiotics with Copyright © 2017 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved. DOI: 10.1097/CCM.0000000000002678 1Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA. 2Department of Medicine, Brigham and Women’s Hospital, Boston, MA. Dr. Klompas’ institution received funding from the Centers for Disease Control and Prevention. For information regarding this article, E-mail: mklompas@bwh.harvard.edu Monotherapy Is Adequate for Septic Shock Due to Gram-Negative Organisms

Monotherapy Is Adequate for Septic Shock Due to Gram-Negative Organisms.

Background: Our institution had an outbreak of multi-drug-resistant Acinetobacter (MDRA) in 2011. We analyzed the costs of responding to this outbreak from the hospital's perspective. Methods: We estimated retrospectively the excess costs associated with an MDRA outbreak response at a major academic medical center, including the costs of staffing, supplies, administrative time, deep cleaning, and environmental testing. Differences in mean costs before and during the 2011 MDRA outbreak were analyzed using the Student t-test. Results: The overall excess cost incurred during the outbreak response was $371,079 in 2011 U.S. dollars. The largest contributors were the extra resources needed to staff and clean the two intensive care units (ICUs) (78%). In the general surgery ICU, the mean weekly cost of nursing during the outbreak was $13,276 more for regular hours (+15%; p < 0.01) than in the pre-outbreak period and $2,682 more for overtime hours (+86%; p = 0.02). In the trauma ICU, the cost was $20,746...

Michael Klompas

Papers

Associations between different sedatives and ventilator-associated events, length-of-stay, and mortality in mechanically ventilated patients.

Sepsis and the theory of relativity: measuring a moving target with a moving measuring stick.

Monotherapy Is Adequate for Septic Shock Due to Gram-Negative Organisms.

The Cost of Responding to an Acinetobacter Outbreak in Critically Ill Surgical Patients.

Association of Omicron vs Wild-type SARS-CoV-2 Variants With Hospital-Onset SARS-CoV-2 Infections in a US Regional Hospital System.