Background: Sepsis-induced coagulopathy (SIC) and hypoalbuminemia represent distinct yet interrelated manifestations of endothelial dysfunction in sepsis. While both have been individually associated with increased mortality, their combined prognostic value remains unexplored. This study aimed to assess the relationship between the SIC score and serum albumin levels and to evaluate their integrated role in predicting mortality and bleeding risks in septic patients. Methods: We conducted a prospective observational study enrolling adult patients with community-acquired sepsis admitted to an Intermediate Medical Care Unit between January 2023 and June 2024. The primary outcome was 30-day all-cause mortality. The secondary outcome was the occurrence of ISTH-defined major bleeding. Multivariable logistic regression and Net Reclassification Improvement (NRI) analyses were performed to evaluate the predictive value of albumin when added to the SIC score. Results: A total of 413 patients were enrolled; 18.4% had a positive SIC score. The serum albumin and SIC score were inversely correlated (r = −0.189, p < 0.001). Both variables were independently associated with 30-day mortality and major bleeding. The addition of albumin significantly improved the predictive performance of the SIC score (NRI = 0.276 for mortality; NRI = 0.268 for bleeding; both p = 0.003). The cluster analysis identified distinct phenotypes based on albumin and SIC profiles, with differing clinical trajectories and transfusion needs. Conclusions: The combined assessment of the SIC score and serum albumin enhances early risk stratification in sepsis. This dual-parameter approach may support more accurate prognostication and individualized management in septic patients.

Background: In sepsis, albumin homeostasis is altered by capillary leak and recovery mechanisms (synthesis and interstitial–lymphatic return), which are difficult to capture clinically. A joint evaluation of ratio-based escape dynamics and mass-based balance may clarify their temporal interplay in sepsis. Methods: In a prospective longitudinal cohort of 389 sepsis patients admitted to an intermediate medical care unit, serial daily sampling (up to five reassessments; 1897 observations) was used to derive: a transcapillary escape rate (TER)-like index from the hourly percent change in the albumin/hemoglobin ratio and net albumin leakage (NAL) from changes in intravascular albumin mass normalized to plasma volume. Indices were analyzed as continuous measures and by sign-defined combined states. Generalized estimating equations (GEE), patient-level slope analyses, and state-transition analyses were performed. Baseline SOFA and 30-day mortality were explored as effect modifiers. Results: The TER-like index peaked early (median +0.34%/h at day 1) and declined to negative values by day 5 (median −0.07%/h), with the TER-like index > 0 decreasing from 65.3% to 45.8%. NAL was frequently negative and heterogeneous (NAL ≥ 0 in 37.5% of observations). TER-like index and NAL were inversely correlated (ρ = −0.54; p < 0.001). In GEE, the TER-like index was associated with NAL (β = −7.46 g/L per 1%/h; 95% CI −8.69 to −6.22; p < 0.001) with time-varying effects (interaction p < 0.01). The dissociation state (TER-like index ≤ 0 with NAL < 0) increased from 2.3% at day 1 to 22.6% at day 5 (p < 0.001). Conclusions: TER-like index escape dynamics attenuate early; however, net intravascular albumin balance often remains negative, supporting temporal uncoupling between “leak” and recovery. An integrated TER-like/NAL assessment offers a pragmatic framework for the clinical phenotyping of albumin homeostasis using routine laboratory data.

Background: Sepsis remains a leading cause of mortality worldwide, and understanding endothelial damage is crucial for improving patient outcomes. Endothelial dysfunction in sepsis contributes to coagulopathy, increased capillary permeability, and vasoplegia, but the interplay between these processes remains underexplored. The study aims to evaluate the clinical relationship between those factors due to sepsis-induced endothelial damage. Methods: A prospective single-center study on 75 community-acquired septic patients admitted to an Intermediate Care Unit. The Sepsis-Induced Coagulopathy (SIC) score, serum albumin (as a surrogate for capillary leak), and Total Peripheral Resistance Index (TPRI) (as a surrogate for vasoplegia) were assessed. Structural Equation Modeling (SEM) explored the relationship between variables, hypothesizing a common latent factor (endothelial damage). Principal Component Analysis assessed the shared variance among variables. Results: The mean SIC score was 3.4 (SD 1.3), with 44% of patients affected. TPRI and albumin had mean values of 1954 (SD 738) and 2.58 (SD 0.59), respectively, both negatively correlated with SIC: TPRI −0.263 (p = 0.023) and albumin −0.454 (p < 0.001). SEM showed SIC, albumin, and TPRI are associated with a latent factor (endothelial damage), explaining 68% of the variance (CFI = 1.000, RMSEA = 0.000). Albumin was inversely correlated (p = 0.004), and TPRI was significantly associated (p = 0.003). Conclusions: This pilot study suggests that coagulopathy, increased vascular permeability, and vasoplegia may be clinically interrelated manifestations of endothelial injury in sepsis. These findings support the feasibility of modeling a unified pathophysiological construct using accessible bedside data, potentially guiding future individualized approaches in sepsis management.

Background: Intravascular albumin mass represents the total quantity of albumin circulating within the bloodstream and may serve as a physiologically relevant marker of vascular integrity and fluid distribution in sepsis. While low serum albumin levels are acknowledged as prognostic indicators, dynamic assessments based on albumin mass remain insufficiently explored in patients outside the intensive care unit. Objectives: To describe the temporal changes in intravascular albumin mass in patients with community-acquired sepsis and to examine its relationship with fluid balance and thirty-day mortality. Methods: This prospective observational study encompassed 247 adults diagnosed with community-acquired sepsis who were admitted to a high-dependency hospital ward specializing in acute medical care. The intravascular albumin mass was calculated daily for a duration of up to five days, utilizing plasma albumin concentration and estimated plasma volume derived from anthropometric and hematologic data. Net albumin leakage was defined as the variation in intravascular albumin mass between consecutive days. Fluid administration and urine output were documented to ascertain cumulative fluid balance. Repeated-measures statistical models were employed to evaluate the associations between intravascular albumin mass, fluid balance, and mortality, with adjustments made for age, comorbidity, and clinical severity scores. Results: The intravascular albumin mass exhibited a significant decrease during the initial five days of hospitalization and demonstrated an inverse correlation with the cumulative fluid balance. A greater net leakage of albumin was associated with a positive fluid balance and elevated mortality rates. Furthermore, a reduced intravascular albumin mass independently predicted an increased risk of mortality at thirty days. Conclusions: A reduction in intravascular albumin mass may suggest ineffective fluid retention and the onset of capillary leak syndrome. This parameter holds promise as a clinically valuable, non-invasive indicator for guiding fluid resuscitation in cases of sepsis.

Background: Sepsis is a heterogeneous syndrome in which patients with similar clinical presentations at admission may exhibit markedly different treatment responses and outcomes, suggesting that comparable macroscopic features can conceal profoundly distinct perfusion and hemodynamic states. Aim: This study aimed to characterize the hemodynamic profile of patients with community-acquired sepsis, assess its correlation with macro-hemodynamic indices, compare fluid responders with non-responders, and explore the prognostic value of early identification of a feature consistent with distributive shock. Methods: A prospective observational pilot study was conducted in the Intermediate Medical Care Unit (IMCU) of Ospedale Alto Vicentino (Santorso, Italy), September 2024–May 2025. 115 consecutive adults with community-acquired sepsis underwent NICaS^® bioimpedance assessment at IMCU admission. Sepsis was diagnosed at IMCU admission as suspected/confirmed infection plus an acute increase in total Sequential Organ Failure Assessment (SOFA) ≥ 2 points. Hemodynamic indices were analyzed in relation to the Sequential Organ Failure Assessment (SOFA) score and mean arterial pressure (MAP), fluid responsiveness, and 30-day mortality. Results: Hemodynamics were heterogeneous across patients and within SOFA strata. SOFA showed no correlation with SV, SI, CO, or CI; weak inverse associations for TPR (r = −0.198, p = 0.034) and TPRI (r = −0.241, p = 0.009) were observed. MAP did not correlate with SV, SI, CO, or CI, but correlated positively with TPR (r = 0.461) and TPRI (r = 0.547) and with CPI (ρ = 0.550), all p < 0.001. A distributive profile was present in 21.7% (25/115), increasing with higher SOFA (p = 0.033); only 20% of those with this profile had MAP < 65 mmHg at admission. Fluid non-responders (27.8%) had lower resistance and higher CI (4.1 vs. 3.4 L/min/m²; p = 0.015). The distributive profile was not associated with 30-day mortality (log-rank p = 0.808). Conclusions: In IMCU patients with community-acquired sepsis, macro-indices (SOFA, MAP) correlate poorly with the underlying hemodynamic state. Early noninvasive profiling reveals within-SOFA circulatory heterogeneity and may support operational, individualized resuscitation strategies; these pilot findings are hypothesis-generating and warrant prospective interventional testing.

Background: Delirium is an under-recognized complication in hospitalized acute care patients, associated with worse outcomes including increased length of stay, higher ICU admission rates and greater mortality. Although screening tools exist for early diagnosis, the absence of admission-based tools limits early risk stratification and timely prevention strategies. Aim: To identify early risk factors for delirium development in IMCU patients and quantify its prognostic role on 30-day mortality. Methods: In this prospective single-center study, 651 consecutive IMCU patients without delirium at admission were enrolled. Admission variables were analyzed using multivariable logistic regression and Classification and Regression Tree (CART) analysis to identify clinically relevant risk phenotypes. The association between delirium and 30-day mortality was assessed in adjusted models. Results: Delirium developed in 18.6% of patients within 96 h. Key independent risk factors included age (OR 1.04), male sex (OR 1.75), alcohol use disorder (OR 3.59), cognitive impairment (OR 3.35), COPD (OR 1.68), NEWS (OR 1.18), and need for NIV (OR 3.83). CART analysis identified NIV as the dominant early discriminator, followed by cognitive vulnerability and acute severity. 30-day mortality was significantly higher in patients with delirium (22.3% vs. 9.8%, p = 0.001). Delirium remained an independent risk factor after adjustment (OR 2.53). CART analysis further corroborates delirium as a significant determinant, enhancing prognostic stratification beyond its role as a mere surrogate of disease severity. Conclusions: Admission-level clinical variables and exploratory CART analysis identified clinically interpretable delirium risk phenotypes in IMCU patients. Delirium was independently associated with increased 30-day mortality. These findings provide a preliminary framework for future validation studies and development of IMCU-specific risk-stratification approaches.