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.

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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

OBJECTIVES
Syndromic surveillance can help identify the onset, location, affected populations, and trends in infectious diseases quickly and efficiently. We developed an electronic medical record-based surveillance algorithm for COVID-19-like illness (CLI) and assessed its performance in 5 Massachusetts medical practice groups compared with statewide counts of confirmed cases.


MATERIALS AND METHODS
Using data from February 2020 through November 2022, the CLI algorithm was implemented in sites that provide ambulatory and inpatient care for about 25% of the state. The initial algorithm for CLI was modeled on influenza-like illness: an International Classification of Diseases, Tenth Revision, Clinical Modification (ICD-10-CM) diagnosis code for COVID-19 and an ICD-10-CM diagnosis code suggesting severe lower respiratory tract infection or ≥1 ICD-10-CM diagnosis code for upper or lower respiratory tract infection plus fever. We generated weekly counts of CLI cases and patients with ≥1 clinical encounter and visually compared trends with those of statewide laboratory-confirmed cases.


RESULTS
The initial algorithm tracked well with the spring 2020 wave of COVID-19, but the components that required fever did not clearly detect the November 2020-January 2021 surge and identified <1% of weekly encounters as CLI. We revised the algorithm by adding more mild symptoms and removing the fever requirement; this revision improved alignment with statewide confirmed cases through spring 2022 and increased the proportion of encounters identified as CLI to about 2% to 6% weekly. Alignment between CLI trends and confirmed COVID-19 case counts diverged again in fall 2022, likely because of decreased COVID-19 testing and increases in other respiratory viruses.


PRACTICE IMPLICATIONS
Our work highlights the importance of using a broad definition for COVID-19 syndromic surveillance and the need for surveillance systems that are flexible and adaptable to changing trends and patterns in disease or care.

Syndromic Surveillance for COVID-19, Massachusetts, February 2020-November 2022: The Impact of Fever and Severity on Algorithm Performance.

Many hospitals have stopped or are considering stopping universal admission testing for SARS-CoV-2. We discuss reasons why admission testing should still be part of a layered system to prevent hospital-acquired SARS-CoV-2 infections during times of significant community transmission. These include the morbidity of SARS-CoV-2 in vulnerable patients, the predominant contribution of presymptomatic and asymptomatic people to transmission, the high rate of transmission between patients in shared rooms, and data suggesting surveillance testing is associated with fewer nosocomial infections. Preferences of diverse patient populations, particularly the hardest hit communities, should be surveyed and used to inform prevention measures. Hospitals' ethical responsibility to protect patients from serious infections should predominate over concerns about costs, labor, and inconvenience. We call for more rigorous data on the incidence and morbidity of nosocomial SARS-CoV-2 infections and more research to help determine when to start, stop, and restart universal admission testing and other prevention measures.

In Support of Universal Admission Testing for SARS-CoV-2 During Significant Community Transmission.

Dear Editor, We thank Martin-Loeches et al. [1] for their thoughtful comments on our systematic review and meta-analysis evaluating the accuracy of clinical signs and symptoms for the diagnosis of ventilator-associated pneumonia (VAP) in critically ill adults [2]. We agree with many of the points expressed by the authors, and indeed noted many of the same concerns within our manuscript, leading us to rate the quality of evidence supporting the diagnostic accuracy of each sign or symptom as “low” or “very low.” We agree that histopathology is an imperfect reference standard for diagnosis of VAP, due to both the potential for sampling error as well as interobserver variability between pathologists [3]. That being said, what other reference standard is there to choose that is associated with less uncertainty? Clinical consensus, quantitative cultures, radiological readings, and diagnostic criteria are also all prone to similar if not greater variation due to differences in measurement approaches and interpretation [3–5]. We believe histology is the best reference standard available among an admittedly very imperfect set of options. We also agree with Martin-Loeches and colleagues that in actual practice, clinicians are more likely to use a combination of clinical signs rather than any single finding in isolation. We were unable to perform a meta-analysis on combinations of findings because no two studies evaluated the accuracy of the same combinations of findings in the same fashion. We therefore did the next best thing which was to report the results of each of the individual studies evaluating the accuracy of combinations of findings (summarized in Table 3 of our paper). Martin-Loeches and colleagues rightly point out that ventilator-associated event (VAE) criteria were not designed for clinical diagnosis, but rather for surveillance alone [6]. We agree. The reason we mentioned VAE was not to suggest that it might serve as a substitute for clinical diagnostic criteria for VAP, but rather to indicate how the limitations of clinical diagnostic criteria led Centers for Disease Control and Prevention to seek a different strategy for measuring quality of care for ventilated patients. Finally, Martin-Loeches and colleagues note the interconnections between ventilator-associated tracheobronchitis (VAT) and VAP. This was beyond the scope of our review, as we focused on VAP alone rather than VAT, although we suspect that many of the same limitations we documented for the common clinical criteria used to diagnose VAP may also apply to using these same signs to diagnose VAT. All told, we continue to recommend caution when trying to diagnose VAP given the limited association between common diagnostic criteria, both alone and in combination, with histologically confirmed pneumonia. In practice, clinicians have little choice but to use these clinical signs to manage patients, but we continue to recommend tempering them with diagnostic humility, thoughtful use of cross-sectional imaging, calibrating treatment decisions to patients’ severity of illness, and continually reassessing the appropriateness of a diagnosis for or against VAP in light of a patient’s clinical trajectory and response to treatment.

/pdf/a-way-toward-ventilator-associated-lower-respiratory-tract-4k5bwwz816.pdf

Michael Klompas

Papers

Syndromic Surveillance for COVID-19, Massachusetts, February 2020-November 2022: The Impact of Fever and Severity on Algorithm Performance.

In Support of Universal Admission Testing for SARS-CoV-2 During Significant Community Transmission.

A way toward ventilator-associated lower respiratory tract infection research: reply.

The Association Between Time-to-Antibiotics and Mortality in Sepsis Is Sensitive to Four Common Biases in Observational Studies