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Special Issues
Management of Chronic Critical Illness after Sepsis
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Management of Chronic Critical Illness after Sepsis

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Emergency Medicine".

Deadline for manuscript submissions: closed (15 March 2021) | Viewed by 22179

Special Issue Editors

Prof. Dr. Frederick A. Moore

E-Mail Website
Guest Editor
University of Florida, Gainesville, Florida, USA
Interests: trauma; critical care; sepsis; neutrophils; multiple organ failure; nutrition; phenotypic heterogeneity; persistent inflammation immunosuppression and catabolism syndrome
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Philip A. Efron

E-Mail Website
Guest Editor
University of Florida, Gainesville, FL, USA
Interests: trauma; critical care; sepsis; epigenetics/genetics; inflammation; immunology; immune suppression; leukocytes
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Despite decades of extensive research, sepsis remains a common, costly, and debilitating syndrome. The Surviving Sepsis Campaign (SSC) was initiated in 2004 as an international effort to develop and implement evidence-based care guidelines (EBG). Over the subsequent decade, with widespread early use of the SSC EBG “sepsis bundles”, hospital mortality decreased substantially. However, this tremendous success created a new problem:  A growing epidemic of “sepsis survivors” are now progressing into chronic critical illness (CCI). Increasingly, studies have documented that the majority of CCI patients are discharged to long-term healthcare facilities with severe physical and cognitive disabilities and do not recover. Mortality for this cohort can be 40% and 70% within one and three years of their sepsis, respectively. As a result, the next major challenge in sepsis will be the management of these individuals and their maladies. These include increased cardiovascular events, malnutrition, sepsis recidivism, immobility, neuropathy, and frailty, as well as impaired host cognition and a suboptimal host microbiome. This Special Issue will describe these disorders and discuss potential interventions to minimize risk, maximize recovery, and prevent long-term mortality. These articles will work towards promoting multidisciplinary discussion and aid the focus of future research.

Prof. Dr. Frederick A. Moore
Prof. Dr. Philip A. Efron
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2600 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • Sepsis survivors
  • Chronic critical illness
  • Long-term outcomes
  • Sepsis rehabilitation
  • Sepsis recidivism
  • Immunosuppression
  • Frailty
  • Delirium
  • Malnutrition

Published Papers (5 papers)

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Review

10 pages, 229 KiB  
Review
Chronic Critical Illness and PICS Nutritional Strategies
by Martin D. Rosenthal, Erin L. Vanzant and Frederick A. Moore
J. Clin. Med. 2021, 10(11), 2294; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10112294 - 25 May 2021
Cited by 8 | Viewed by 4172
Abstract
The nutritional hallmark of chronic critical illness (CCI) after sepsis is persistent inflammation, immunosuppression, and catabolism syndrome (PICS), which results in global resistance to the anabolic effect of nutritional supplements. This ultimately leaves these patients in a downward phenotypic spiral characterized by cachexia [...] Read more.
The nutritional hallmark of chronic critical illness (CCI) after sepsis is persistent inflammation, immunosuppression, and catabolism syndrome (PICS), which results in global resistance to the anabolic effect of nutritional supplements. This ultimately leaves these patients in a downward phenotypic spiral characterized by cachexia with profound weakness, decreased capacity for rehabilitation, and immunosuppression with the propensity for sepsis recidivism. The persistent catabolism is driven by a pathologic low-grade inflammation with the inability to return to homeostasis and by ongoing increased energy expenditure. Better critical care support systems and advances in technology have led to increased intensive care unit (ICU) survival, but CCI due to PICS with poor long-term outcomes has emerged as a frequent phenotype among ICU sepsis survivors. Unfortunately, therapies to mitigate or reverse PICS-CCI are limited, and recent evidence supports that these patients fail to respond to early ICU evidence-based nutrition protocols. A lack of randomized controlled trials has limited strong recommendations for nutrition adjuncts in these patients. However, based on experience in other conditions characterized by a similar phenotype, immunonutrients aimed at counteracting inflammation, immunosuppression, and catabolism may be important for improving outcomes in PICS-CCI patients. This manuscript intends to review several immunonutrients as adjunctive therapies in treating PICS-CCI. Full article
(This article belongs to the Special Issue Management of Chronic Critical Illness after Sepsis)
11 pages, 934 KiB  
Review
Pathophysiology and Treatment Strategies of Acute Myopathy and Muscle Wasting after Sepsis
by Robert T. Mankowski, Orlando Laitano, Thomas L. Clanton and Scott C. Brakenridge
J. Clin. Med. 2021, 10(9), 1874; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10091874 - 26 Apr 2021
Cited by 14 | Viewed by 4432
Abstract
Sepsis survivors experience a persistent myopathy characterized by skeletal muscle weakness, atrophy, and an inability to repair/regenerate damaged or dysfunctional myofibers. The origins and mechanisms of this persistent sepsis-induced myopathy are likely complex and multifactorial. Nevertheless, the pathobiology is thought to be triggered [...] Read more.
Sepsis survivors experience a persistent myopathy characterized by skeletal muscle weakness, atrophy, and an inability to repair/regenerate damaged or dysfunctional myofibers. The origins and mechanisms of this persistent sepsis-induced myopathy are likely complex and multifactorial. Nevertheless, the pathobiology is thought to be triggered by the interaction between circulating pathogens and impaired muscle metabolic status. In addition, while in the hospital, septic patients often experience prolonged periods of physical inactivity due to bed rest, which may exacerbate the myopathy. Physical rehabilitation emerges as a potential tool to prevent the decline in physical function in septic patients. Currently, there is no consensus regarding effective rehabilitation strategies for sepsis-induced myopathy. The optimal timing to initiate the rehabilitation intervention currently lacks consensus as well. In this review, we summarize the evidence on the fundamental pathobiological mechanisms of sepsis-induced myopathy and discuss the recent evidence on in-hospital and post-discharge rehabilitation as well as other potential interventions that may prevent physical disability and death of sepsis survivors. Full article
(This article belongs to the Special Issue Management of Chronic Critical Illness after Sepsis)
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13 pages, 1110 KiB  
Review
Dysregulated Immunity and Immunotherapy after Sepsis
by Dijoia B. Darden, Lauren S. Kelly, Brittany P. Fenner, Lyle L. Moldawer, Alicia M. Mohr and Philip A. Efron
J. Clin. Med. 2021, 10(8), 1742; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10081742 - 17 Apr 2021
Cited by 34 | Viewed by 4399
Abstract
Implementation of protocolized surveillance, diagnosis, and management of septic patients, and of surgical sepsis patients in particular, is shown to result in significantly increased numbers of patients surviving their initial hospitalization. Currently, most surgical sepsis patients will rapidly recover from sepsis; however, many [...] Read more.
Implementation of protocolized surveillance, diagnosis, and management of septic patients, and of surgical sepsis patients in particular, is shown to result in significantly increased numbers of patients surviving their initial hospitalization. Currently, most surgical sepsis patients will rapidly recover from sepsis; however, many patients will not rapidly recover, but instead will go on to develop chronic critical illness (CCI) and experience dismal long-term outcomes. The elderly and comorbid patient is highly susceptible to death or CCI after sepsis. Here, we review aspects of the Persistent Inflammation, Immunosuppression, and Catabolism Syndrome (PICS) endotype to explain the underlying pathobiology of a dysregulated immune system in sepsis survivors who develop CCI; then, we explore targets for immunomodulatory therapy. Full article
(This article belongs to the Special Issue Management of Chronic Critical Illness after Sepsis)
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20 pages, 1255 KiB  
Review
Lipid and Lipoprotein Dysregulation in Sepsis: Clinical and Mechanistic Insights into Chronic Critical Illness
by Grant Barker, Christiaan Leeuwenburgh, Todd Brusko, Lyle Moldawer, Srinivasa T. Reddy and Faheem W. Guirgis
J. Clin. Med. 2021, 10(8), 1693; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10081693 - 14 Apr 2021
Cited by 31 | Viewed by 4473
Abstract
In addition to their well-characterized roles in metabolism, lipids and lipoproteins have pleiotropic effects on the innate immune system. These undergo clinically relevant alterations during sepsis and acute inflammatory responses. High-density lipoprotein (HDL) plays an important role in regulating the immune response by [...] Read more.
In addition to their well-characterized roles in metabolism, lipids and lipoproteins have pleiotropic effects on the innate immune system. These undergo clinically relevant alterations during sepsis and acute inflammatory responses. High-density lipoprotein (HDL) plays an important role in regulating the immune response by clearing bacterial toxins, supporting corticosteroid release, decreasing platelet aggregation, inhibiting endothelial cell apoptosis, reducing the monocyte inflammatory response, and inhibiting expression of endothelial cell adhesion molecules. It undergoes quantitative as well as qualitative changes which can be measured using the HDL inflammatory index (HII). Pro-inflammatory, or dysfunctional HDL (dysHDL) lacks the ability to perform these functions, and we have also found it to independently predict adverse outcomes and organ failure in sepsis. Another important class of lipids known as specialized pro-resolving mediators (SPMs) positively affect the escalation and resolution of inflammation in a temporal fashion. These undergo phenotypic changes in sepsis and differ significantly between survivors and non-survivors. Certain subsets of sepsis survivors go on to have perilous post-hospitalization courses where this inflammation continues in a low grade fashion. This is associated with immunosuppression in a syndrome of persistent inflammation, immunosuppression, and catabolism syndrome (PICS). The continuous release of tissue damage-related patterns and viral reactivation secondary to immunosuppression feed this chronic cycle of inflammation. Animal data indicate that dysregulation of endogenous lipids and SPMs play important roles in this process. Lipids and their associated pathways have been the target of many clinical trials in recent years which have not shown mortality benefit. These results are limited by patient heterogeneity and poor animal models. Considerations of sepsis phenotypes and novel biomarkers in future trials are important factors to be considered in future research. Further characterization of lipid dysregulation and chronic inflammation during sepsis will aid mortality risk stratification, detection of sepsis, and inform individualized pharmacologic therapies. Full article
(This article belongs to the Special Issue Management of Chronic Critical Illness after Sepsis)
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16 pages, 954 KiB  
Review
Cardiovascular and Renal Disease in Chronic Critical Illness
by Tyler J. Loftus, Amanda C. Filiberto, Tezcan Ozrazgat-Baslanti, Saraswathi Gopal and Azra Bihorac
J. Clin. Med. 2021, 10(8), 1601; https://0-doi-org.brum.beds.ac.uk/10.3390/jcm10081601 - 09 Apr 2021
Cited by 5 | Viewed by 3467
Abstract
With advances in critical care, patients who would have succumbed in previous eras now survive through hospital discharge. Many survivors suffer from chronic organ dysfunction and induced frailty, representing an emerging chronic critical illness (CCI) phenotype. Persistent and worsening cardiovascular and renal disease [...] Read more.
With advances in critical care, patients who would have succumbed in previous eras now survive through hospital discharge. Many survivors suffer from chronic organ dysfunction and induced frailty, representing an emerging chronic critical illness (CCI) phenotype. Persistent and worsening cardiovascular and renal disease are primary drivers of the CCI phenotype and have pathophysiologic synergy, potentiating one another and generating a downward spiral of worsening disease and clinical outcomes manifest as cardio-renal syndromes. In addition to pharmacologic therapies (e.g., diuretics, beta adrenergic receptor blockers, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, and blood pressure control), special consideration should be given to behavioral modifications that avoid the pitfalls of polypharmacy and suboptimal renal and hepatic dosing, to which CCI patients may be particularly vulnerable. Smoking cessation, dietary modifications (e.g., early high-protein nutrition and late low-sodium diets), and increased physical activity are advised. Select patients benefit from cardiac re-synchronization therapy or renal replacement therapy. Coordinated, patient-centered care bundles may improve compliance with standards of care and patient outcomes. Given the complex, heterogeneous nature of cardiovascular and renal disease in CCI and the dismal long-term outcomes, further research is needed to clarify pathophysiologic mechanisms of cardio-renal syndromes in CCI and develop targeted therapies. Full article
(This article belongs to the Special Issue Management of Chronic Critical Illness after Sepsis)
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