Sepsis: New Insights into Diagnosis and Treatment

Dear Colleagues,

Sepsis represents a life-threatening condition with a huge impact on health care costs. Further, Sepsis is a “time-dependent” disease; the outcome is highly influenced by the prompt detection and efficiency of the management, even from the very “first hour”. Due to the centrality of the complex interactions between the infectious insult and the host's immune response, a deeper understanding of the mechanisms involved in the dysregulation host response is mandatory.

Interestingly, It is now clear that the individual genomic profile is partly responsible for the interindividual variability of the clinical evolution of sepsis. In light of this evidence, immunomorinitoring and immunotherapy have gained increasing recognition in recent decades. Unfortunately, until now, evidence has not supported the extensive introduction of adjuvant therapy in current clinical practice.

In this Special Issue, we invite researchers and clinicians to submit their work, including original clinical research studies, meta-analyses, and systematic reviews, that will provide additional insight on the diagnosis and treatment of septic shock.

Prof. Dr. Francesco Forfori
Dr. Etrusca Brogi
Guest Editors

Manuscript Submission Information

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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.

• sepsis and sepsis subphenotypes
• adjuvant therapy
• blood purification strategies
• immunomonitoring and immunotherapy
• the microbiome in sepsis
• crosstalk in multi-organ failure (MOF)
• ultrasound in sepsis (POCUS)
• sepsis-induced coagulophaty and DIC
• antibiotic therapy
• multimodal approaches to surgical source control

Title: Personalized approaches to patients with abdominal sepsis
Authors: Massimo Sartelli; Federico Coccolini
Affiliation: Department of Surgery, Macerata Hospital, 62100 Macerata, Italy General, Emergency and Trauma Surgery Department, Pisa University Hospital, 56124 Pisa, Italy

Title: AI and Sepsis: Predictive Power and Clinical Impact
Authors: Elena Giovanna Bignami; Michele Berdini; Matteo Panizzi; Tania Domenichetti; Francesca Bezzi; Simone Allai; Tania Damiano; Valentina Bellini
Affiliation: Anesthesiology, Critical Care and Pain Medicine Division, Department of Medicine and Surgery, University of Parma, Viale Gramsci 14, 43126 Parma, Italy.
Abstract: Sepsis is one of the leading causes of mortality in hospital settings, and early diagnosis is a crucial challenge to improve clinical outcomes. Artificial intelligence (AI) is emerging as a valuable resource to address this defiance, with numerous investigations exploring its application to predict and diagnose sepsis early, as well as personalize its treatment. Machine learning (ML) models, in particular, are able to use clinical data collected from hospital computer systems to identify patients at risk of sepsis hours before the onset of symptoms. Background/Objectives: Over the past decades, ML and other AI tools have been explored extensively in sepsis, with mod-els developed for early detection, diagnosis, prognosis, and even real-time management of treatment strategies. This article provides an overview of the use of AI in sepsis management, review-ing the main studies and several methodologies used to assess its strengths, limitations, and future potential applications. Methods: This narrative review was crafted by including the studies considered the most significant and relevant about the application of ML models in the management of sepsis, published and available in literature in the last 5 years, in order to obtain an up-dated overview of the current state of the art. Results: This review aims to examine and highlight the key strengths and limitations in the use of AI for sepsis management, based on significant experiences. The scientific literature presents mixed outcomes: while some studies demonstrate improvements in mortality rates and clinical management, others highlight challenges, such as a high incidence of false positives and the lack of external validation.

Title: Immunomodulations in pediatric sepsis: a narrative review
Authors: G. Bottari et al.
Affiliation: Children Hospital Bambino Gesu, Rome (Italy)
Abstract: Sepsis remains a significant cause of mortality and morbidity among pediatric patients. Moreover, the actual numbers are likely underestimated due to insufficient data. The definition of sepsis has recently been revised. Previously, it was defined as the simultaneous presence of infection and Systemic Inflammatory Response Syndrome (SIRS). In January 2024, new criteria for pediatric sepsis, known as "Phoenix," were developed by an International Task Force. According to Sepsis-3 and the latest pediatric sepsis definitions, sepsis should not be regarded as a uniform inflammatory process. Instead, it varies from patient to patient, following diverse immune-inflammatory pathways. This underscores the need for therapies tailored to individual patients and their specific medical conditions, rather than a one-size-fits-all approach. It's crucial to recognize that translational research on sepsis in the coming decade will focus on “immune-modulation” as signficant therapeutic opportunity. A thorough understanding of immune-therapies in pediatric sepsis is now imperative for pediatric intensivist extending beyond standard care. We have examined in this narrative review the current literature on medical therapies for pediatric sepsis, analyzing those that have gained the most scientific support, despite the limited number of pediatric studies and the reliance on adult protocols. We first explored the role of Intravenous Immunoglobulins (IVIG). Some studies indicate that IVIG administration improves survival rates and reduces the length of hospitalization, especially for IgM-enriched immunoglobulins, although few studies suggest the opposite. The use of corticosteroids remains controversial, even though some studies link their use to better outcomes. Additionally, there is evidence supporting a personalized approach to corticosteroid use, tailored to the immune profile of each patient. Monoclonal antibodies, such as rhIL-1ra, anti-IL-6, and JAK inhibitors, have shown promising results, but further research is needed to validate their use in pediatric sepsis. Immuno-stimulating agents, such as G-CSF, IL-7, and IFN-γ, have been proposed, but studies on their effectiveness provide conflicting results, highlighting the need for more detailed analyses. Finally, we also considered extracorporeal blood purification techniques for their potential benefits, particularly given the recognition of the importance of "organ cross-talk" and multiple organ dysfunction syndrome during sepsis.