Laudański, Krzysztof

Background/Objectives: Treating critically ill patients is complex and often subjective. This study investigates adherence to clinical guidelines for sepsis among different providers. Considering the strengths of the recommendations, we hypothesize that heterogeneity in the decision-making process will be low and independent of provider background and psychological makeup. Methods: This cohort study used two clinical vignettes of sepsis. Providers were given standardized treatment plans for 7 days, and their responses were recorded. Demographical, professional, and psychological (ambiguity tolerance, defensiveness, anxiety due to uncertainty, risk-taking behavior, decision styles, and optimism) variables were acquired. Results: Crystalloids were commonly used in both vignettes. Pressor engagement, especially norepinephrine, increased significantly after the third day. Providers recommended antibiotics and no provider stopped antibiotic therapy. Cluster analysis revealed no differences in therapy implementation among provider types, but some differences existed between the two vignettes. Cluster #1 was characterized by the implementation of early light bundle therapy combined with the use of pressors and a notable enhancement in therapies by the fifth day (Early Cluster). Cluster #2 (Minimalists) involved consistent engagement only in light bundle therapy throughout the treatment period. Cluster #3 (Escalation) comprised providers who rapidly escalated treatment using multiple different modalities. Cluster #3 stood out as most providers were female, non-MD, with significant ICU duties, and enhanced rational thinking. Conclusions: Providers differ in implementation styles of the sepsis treatment standard based on types of therapies selected not studied psychological variables.

The insulin-like growth factor binding protein, acid-labile subunit (IGFALS), plays a crucial role in glucose metabolism and immune regulation, key processes in recovery from surgery. Here, we studied the perioperative serum IGFALS dynamics and explored potential clinical implications. A total of 79 patients undergoing elective cardiac surgery with implementation of cardiopulmonary bypass had their serum isolated at baseline, 24 h, seven days, and three months postoperatively to assess serum concentrations of IGFALS and insulin growth factor 1 (IGF-1). Markers of perioperative injury included troponin I (TnI), high-mobility group box 1 (HMGB-1), and heat shock protein 60 (Hsp-60). Inflammatory status was assessed via interleukin-6 (IL-6) and interleukin-8 (IL-8). Additionally, we measured in vitro cytokine production to viral stimulation of whole blood and monocytes. Surrogates of neuronal distress included neurofilament light chain (NF-L), total tau (τ), phosphorylated tau at threonine 181 (τp181), and amyloid β40 and β42. Renal impairment was defined by RIFLE criteria. Cardiac dysfunction was denoted by serum N-terminal pro-brain natriuretic peptide (NT-proBNP) levels. Serum IGFALS levels declined significantly after surgery and remained depressed even at 3 months. Administration of acetaminophen and acetylsalicylic acid differentiated IGFALS levels at the 24 h postoperatively. Serum IGFALS 24 h post-operatively correlated with production of cytokines by leukocytes after in vitro viral stimulation. Serum amyloid-β1-42 was significantly associated with IGFALS at baseline and 24 h post-surgery Patients discharged home had higher IGFALS levels at 28 days and 3 months than those discharged to healthcare facilities or who died. These findings suggest that IGFALS may serve as a prognostic biomarker for recovery trajectory and postoperative outcomes in cardiac surgery patients.

The immune system’s response to an invading pathogen is the critical determinant in recovery from illness. Here, we hypothesize that the immune response will swiftly follow classical activation and a resolution trajectory in patients with the rapid evolution of symptoms if challenged by a viral pathogen for the first time. Alternatively, a dysregulated response will be signified by a protracted clinical trajectory. Consequently, we enrolled 106 patients during the first wave of COVID-19 and collected their blood within 24 h, 48 h, 7 days, and over 28 days from symptoms onset. The pathogenic burden was measured via serum levels of the S-spike protein and specific immunoglobulin titers against the S and N proteins of SARS-CoV-2. The nonspecific immunological response was gauged using interleukin 6, leukocytosis, and C-reactive protein. Coagulation status was assessed. Several serum biomarkers were used as surrogates of clinical outcomes. We identified four clusters depending on the onset of symptoms (immediate [A], 6 days [B], 12 days [C], and over 21 days [D]). High variability in the S-spike protein in cluster A was present. The corresponding immunoglobulin titer was random. Only procalcitonin differentiated clusters in terms of markers of nonspecific inflammation. Coagulation markers were not significantly different between clusters. Serum surrogates on cardiomyopathy and neuronal pathology exhibited significant variability. Implementation of ECMO or noninvasive ventilation was more prominent in cluster C and D. Interestingly, SOFA or APACHE II scores were not different between nominal (A and B) versus dysregulated clusters (C and D).

OBJECTIVES: This study aimed to establish a set of guiding principles for data sharing and harmonization in critical care, focusing on the use of real-world data (RWD) and real-world evidence (RWE) to improve patient outcomes and research efficacy. The principles were developed through a systematic literature review and a modified Delphi process, with the goal of enhancing data accessibility, standardization, and interoperability across critical care settings. DATA SOURCES: Data sources included a comprehensive search of peer-reviewed literature, specifically studies related to the use of RWD and RWE in healthcare, guidelines, best practices, and recommendations on data sharing and harmonization. A total of 8150 articles were initially identified through databases such as MEDLINE and Web of Science, with 257 studies meeting inclusion criteria. STUDY SELECTION: Inclusion criteria focused on publications discussing health-related informatics, recommendations for RWD/RWE usage, data sharing, and harmonization principles. Exclusion criteria ruled out non-human studies, case studies, conference abstracts, and articles published before 2013, as well as those not available in English. DATA EXTRACTION: From the 257 selected studies, 322 statements were extracted. After removing irrelevant definitions and off-topic content, 232 statements underwent content validation and thematic analysis. These statements were then consolidated into 24 candidate guiding principles after rigorous review and consensus-building among the expert panel. DATA SYNTHESIS: A three-phase modified Delphi process was employed, involving a conceptualization group, a review group, and a Delphi group. In phase 1, experts identified key themes and search terms for the systematic review. Phase 2 involved validating and refining the prospective guiding principles, while phase 3 employed a Delphi panel to rate principles on acceptability, importance, and feasibility. This process resulted in 24 guiding principles, with high consensus achieved in rounds 2 and 3 on their relevance and applicability. CONCLUSIONS: The systematic review and Delphi process resulted in 24 guiding principles to improve data sharing and harmonization in critical care. These principles address challenges across the data lifecycle, including generation, storage, access, and usage of RWD and RWE. This framework is designed to promote more effective and equitable data practices, with relevance for the development of artificial intelligence-based decision support tools and clinical research. The principles are intended to guide the responsible use of data science in critical care, with emphasis on ethics and equity, while acknowledging the variability of resources across settings.

OBJECTIVES: To develop the first core Critical Care Data Dictionary (C2D2) with common data elements (CDEs) to characterize critical illness and injuries. DESIGN: Group consensus process using modified Delphi approach. SETTING: Electronic surveys and in-person meetings. SUBJECTS: A multidisciplinary workgroup of clinicians and researchers with expertise in the care of the critically ill and injured. INTERVENTIONS: The Delphi process was divided into domain and CDE portions with each composed of two item generation rounds and one item reduction/refinement rounds. Two in-person meetings augmented this process to facilitate review and consideration of the domains and by panel members. The final set of domains and CDEs was then reviewed by the group to meet the competing criteria of utility and feasibility, resulting in the core dataset. MEASUREMENTS AND MAIN RESULTS: The 23-member Delphi panel was provided 1833 candidate variables for potential dataset inclusion. The final dataset includes 226 patient-level CDCs in nine domains, which include anthropometrics and demographics (8), chronic comorbid illnesses (18), advanced directives (1), ICU diagnoses (61), diagnostic tests (42), interventions (27), medications (38), objective assessments (26), and hospital course and outcomes (5). Upon final review, 91% of the panel endorsed the CDCs as meeting criteria for a minimum viable data dictionary. Data elements cross the lifespan of neonate through adult patients. CONCLUSIONS: The resulting C2D2 provides a foundation to facilitate rapid collection, analyses, and dissemination of information necessary for research, quality improvement, and clinical practice to optimize critical care outcomes. Further work is needed to validate the effectiveness of the dataset in a variety of critical care settings.

OBJECTIVES: Telecritical care (TCC) refers to the delivery of critical care using telehealth technologies. Despite increasing utilization, significant practice variation exists and literature regarding efficacy remains sparse. The Telecritical Care Collaborative Network sought to provide expert, consensus-based best practice recommendations for the design and delivery of TCC. DESIGN: We used a modified Delphi methodology. Following literature review, an oversight panel identified core domains and developed declarative statements for review by an expert voting panel. During three voting rounds, voters agreed or disagreed with statements and provided open-ended feedback, which the oversight panel used to revise statements. Statements met criteria for consensus when accepted by greater than or equal to 85% of voters. SETTING/SUBJECTS: The oversight panel included 18 multidisciplinary members of the TCC Collaborative Network, and the voting panel included 32 invited experts in TCC, emphasizing diversity of discipline, care delivery models, and geography. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: We identified ten core domains: definitions/terminology; care delivery models; staffing and coverage models; technological considerations; ergonomics and workplace safety; licensing, credentialing, and certification; trust and relationship building; quality, safety, and efficiency, research agenda; and advocacy, leading to 79 practice statements. Of 79 original statements, 67 were accepted in round 1. After revision, nine were accepted in round 2 and two in round 3 (two statements were merged). In total, 78 practice statements achieved expert consensus. CONCLUSIONS: These expert consensus recommendations cover a broad range of topics relevant to delivery of TCC. Experts agreed that TCC is most effective when delivered by care teams with specific expertise and by programs with explicit protocols focusing on effective communication, technical reliability, and real-time availability. Interventions should be tailored to local conditions. Although further research is needed to guide future best practice statements, these results provide valuable and actionable recommendations for the delivery of high-quality TCC.

Hereditary neuropathy with liability to pressure palsies (HNPP) is an autosomal dominant demyelinating neuropathy characterized by an increased susceptibility to peripheral nerve injury from trauma, compression, or shear forces. Patients with this condition are unique, necessitating distinct considerations for anesthesia and surgical teams. This review describes the etiology, prevalence, clinical presentation, and management of HNPP and presents contemporary evidence and recommendations for optimal care for HNPP patients in the perioperative period. While the incidence of HNPP is reported at 7–16:100,000, this figure may be an underestimation due to underdiagnosis, further complicating medicolegal issues. With the subtle nature of symptoms associated with HNPP, patients with this condition may remain unrecognized during the perioperative period, posing significant risks. Several aspects of caring for this population, including anesthetic choices, intraoperative positioning, and monitoring strategy, may deviate from standard practices. As such, a tailored approach to caring for this unique population, coupled with meticulous preoperative planning, is crucial and requires a multidisciplinary approach.

This research analyzes immunological response patterns to SARS-CoV-2 infection in blood and urine in individuals with serum cotinine-confirmed exposure to nicotine. Samples of blood and urine were obtained from a total of 80 patients admitted to hospital within 24 h of admission (tadm), 48 h later (t48h), and 7 days later (t7d) if patients remained hospitalized or at discharge. Serum cotinine above 3.75 ng/mL was deemed as biologically significant exposure to nicotine. Viral load was measured with serum SARS-CoV-2 S-spike protein. Titer of IgG, IgA, and IgM against S- and N-protein assessed specific antiviral responses. Cellular destruction was measured by high mobility group box protein-1 (HMGB-1) serum levels and heat shock protein 60 (Hsp-60). Serum interleukin 6 (IL-6), and ferritin gauged non-specific inflammation. The immunological profile was assessed with O-link. Serum titers of IgA were lower at tadm in smokers vs. nonsmokers (p = 0.0397). IgM at t48h was lower in cotinine-positive individuals (p = 0.0188). IgG did not differ between cotinine-positive and negative individuals. HMGB-1 at admission was elevated in cotinine positive individuals. Patients with positive cotinine did not exhibit increased markers of non-specific inflammation and tissue destruction. The blood immunological profile had distinctive differences at admission (MIC A/B↓), 48 h (CCL19↓, MCP-3↓, CD28↑, CD8↓, IFNγ↓, IL-12↓, GZNB↓, MIC A/B↓) or 7 days (CD28↓) in the cotinine-positive group. The urine immunological profile showed a profile with minimal overlap with blood as the following markers being affected at tadm (CCL20↑, CXCL5↑, CD8↑, IL-12↑, MIC A/B↑, GZNH↑, TNFRS14↑), t48h (CCL20↓, TRAIL↓) and t7d (EGF↑, ADA↑) in patients with a cotinine-positive test. Here, we showed a distinctive immunological profile in hospitalized COVID-19 patients with confirmed exposure to nicotine.

The release of danger signals from tissues in response to trauma during cardiac surgery creates conditions to reprogram the immune system to subsequent challenges posed by pathogens in the postoperative period. To demonstrate this, we tested immunoreactivity before surgery as the baseline (tbaseline), followed by subsequent challenges during the acute phase (t24h), convalescence (t7d), and long-term recovery (t3m). For 108 patients undergoing elective heart surgery, whole blood was stimulated with lipopolysaccharide (LPS), Influenza A virus subtype N2 (H3N2), or the Flublok™ vaccine to represent common pathogenic challenges. Leukocytosis, platelet count, and serum C-reactive protein (CRP) were used to measure non-specific inflammation. Cytokines were measured after 18 h of stimulation to reflect activation of the various cell types (activated neutrophils–IL-8; activated T cells-IL-2, IFNγ, activated monocyte (MO)-TNFα, IL-6, and deactivated or atypically activated MO and/or T cells–M-CSF, IL-10). IL-2 and IL-10 were increased at t7d, while TNFα was suppressed at t24h when LPS was utilized. Interestingly, M-CSF and IL-6 production was elevated at seven days in response to all stimuli compared to baseline. While some non-specific markers of inflammation (white cell count, IL-6, and IL-8) returned to presurgical levels at t3m, CRP and platelet counts remained elevated. We showed that surgical stimulus reprograms leukocyte response to LPS with only partial restoration of non-specific markers of inflammation.