Jonathan Montomoli

Post-translational modifications of human serum albumin (HSA) have been described in patients with liver disease. This prospective cohort study aimed to characterize HSA microheterogeneity in hospitalized patients with alcohol-associated hepatitis (AH) and investigate its clinical relevance. We analyzed HSA isoforms by mass spectrometry in 49 patients with AH (at admission and day 14) and 20 healthy controls. Survival at 30, 90, and 365 days was assessed. Differences in HSA isoform abundance were compared between controls and AH patients, as well as between 90-day survivors and non-survivors. AH patients (69% male, median age 53 years) exhibited a significantly different HSA form profile compared to controls, with a lower amount of native HSA and higher oxidized forms. Native HSA negatively correlated with total HSA concentration (R = −0.47, p < 0.001). The relative amount of native HSA increased non-significantly from admission to day 14, but its estimated concentration increased significantly (8.8 vs. 12.0 g/L, p = 0.005). There were no significant differences in HSA forms between 90-day survivors and non-survivors at admission or day 14. Patients with AH exhibit extensive post-translational modifications of HSA compared to healthy individuals. While HSA forms changed during early hospitalization, they did not significantly correlate with short-term mortality in this cohort.

Objective: Handheld vital microscopy (HVM) enables bedside visualization of the microcirculation, with major improvements from sidestream darkfield (SDF) to incident dark field (IDF) imaging. Although IDF offers high‐resolution images, standard analysis methods require down‐sampling to match SDF's lower field of view (FOV) and pixel density. MicroTools, an automated stabilization and analysis algorithm, has previously been validated for use with SDF image sequences. This study aimed to assess the accuracy and precision of microcirculatory analysis using MicroTools on full‐frame, high‐resolution IDF images. Methods: Image sequences from a previous study were re‐analyzed in both IDF and down‐sampled SDF formats. Microcirculatory parameters—including total vessel density (TVD), functional capillary density, and red blood cell velocity (RBCv)—were compared between formats. MicroTools' new stabilization algorithm was also evaluated against existing algorithms. Results: Full‐frame IDF analysis increased the FOV by 200% and pixel density by 66%, enhancing capillary detection and TVD measurements. RBCv values were lower with IDF images. The updated stabilization algorithm showed performance comparable to prior methods. Conclusions: MicroTools analysis of full‐frame IDF images improved measurement accuracy and vessel detection, with excellent agreement to standard software. Its new stabilization algorithm proved equally robust, supporting broader adoption in clinical research.

Neuroleptic malignant syndrome (NMS) is a rare, life-threatening hypermetabolic reaction to dopamine-antagonist drugs that may progress to profound rhabdomyolysis, extreme hyperkalemia, and cardiac arrest (CA). Evidence guiding extracorporeal cardiopulmonary resuscitation (ECPR) for metabolic or toxic etiologies is scarce, and its use in NMS has not yet been described. We report the case of a 23 year old woman who presented with hyperthermia, severe muscular rigidity and laboratory evidence of NMS. In the emergency-department arrival she developed witnessed asystolic CA, unresponsive to conventional treatment. After a transient return of spontaneous circulation and a second refractory CA, veno-arterial extracorporeal membrane oxygenation (V-A ECMO) was initiated. Continuous hemodiafiltration facilitated rapid correction of extreme hyperkalemia, whereas dantrolene and active cooling normalized core temperature. Valid cardiac activity recovered after 36 hours, allowing ECMO weaning. However, devastating hypoxic-ischemic brain injury led to brain death, which was declared on day 5. Heart and liver procurement for transplantation were successfully performed. To our knowledge, implementation of ECPR in the context of NMS was not previously documented in the literature. Our case suggests that timely V-A ECMO might bridge extreme hyperkalemic arrest to cardiac recovery, offering both a chance of patient survival and, when neurological prognosis is dismal, an opportunity for organ donation.

Intravenous fluids are commonly used to resuscitate cardiac surgery patients in the operating room and ICU, assuming they expand the intravascular compartment. However, the quantitative information for their distribution and shift between the tissue compartments is still lacking. This study aimed to assess how administered fluids distribute across compartments and their effects on micro- and macrocirculation during the long term of cardiac surgery. Thirty-three consecutive patients undergoing major cardiac surgery were prospectively enrolled. Information regarding the body fluid distribution [total body water (TBW), extracellular water (ECW), intracellular water (ICW)], sublingual microcirculation total vessel density (TVD), per-fused vessel density (PVD), and proportion of perfused vessel (PPV)], and hemodynamics were collected before surgery (T0), on the day of discharge from the intensive care unit (T1), and on the third day at the ward (T3). Correlations of the changes in microcirculatory and macrocircula-tory parameters were determined by linear regression. Twenty-four patients were included in the analysis with available data. Body weight significantly increased from 86.0 ± 13.6 kg to 91.6 ± 13.3 kg at T1 and decreased to 87.8 ± 12.9 kg at T3 (p< 0.001). While TBW and ECW varied in parallel with body weight, ICW showed a continuous decrease throughout the study process. TVD, PVD, and PPV significantly decreased at T1, then increased at T3, but all remained lower than baseline (p< 0.001 for TVD and PVD, p= 0.034 for PPV). A cut-off point of a 5% increase in body weight predicted a 10% decrease in TVD with a sensitivity of 0.833 and specificity of 0.666. Besides, a cut-off point of a 4% increase in body weight predicted a 10% decrease in PVD with a sensitivity of 0.94 and specificity of 0.75. Administering fluid during operation and intensive care stay significantly reduces ICW and causes microcirculatory disturbances in cardiac surgery patients. Long-term microcirculation disturbances correlate with ECW and TBW in these patients.

Idiopathic Systemic Capillary Leak Syndrome (ISCLS) is a poorly understood paroxysmal permeability disorder. This study aimed to characterize the clinical features and severity markers of ISCLS in critically and non-critically ill patients. We analyzed prospectively and retrospectively collected data on ISCLS cases from the Italian IRIS-CLS Registry (January 1995–December 2023). A total of 124 acute episodes were identified in 32 patients; 61 episodes in 26 patients having complete records were included in the analysis. Monoclonal gammopathy was found in 20/23 adults but was absent in all three pediatric patients, who exhibited IgA deficiency instead. At admission, patients presented with hypotension (systolic arterial pressure 87 mmHg [80–105]), tachycardia (110 bpm [96–130]), and hemoconcentration (hematocrit 57% [48–62.7]). ICU admission was required in 70.5%, and cardiac involvement occurred in 49.2% of episodes. Fluid volume infused correlated positively with rhabdomyolysis severity, and the need for renal replacement therapy was more frequent in patients receiving ≥ 3 L. No pharmacologic treatment was effective during the crises. Mortality was 9.8% per episode, and the day-1 Sequential Organ Failure Assessment score was a predictor of death (p = 0.0181). Immunoglobulin prophylaxis reduced attack frequency from 0.67 (0.4–1.07) to 0.4 (0.1–0.52) per year (p = 0.033). Two adults (8.7%) developed multiple myeloma during follow-up. This study provides a comprehensive overview of ISCLS in both critically and non-critically ill patients. We highlight clinical-biochemical-instrumental red-flags and emphasize the need for increased awareness and early recognition since effective treatments for acute shock remain elusive.

Administration of supplemental oxygen is a life-saving treatment in critically ill patients. Still, optimal dosing remains unclear during sepsis. The aim of this post-hoc analysis was to assess the association between hyperoxemia and 90-day mortality in a large cohort of septic patients. This is a post-hoc analysis of the Albumin Italian Outcome Sepsis (ALBIOS) randomized controlled trial (RCT). Patients with sepsis who survived the first 48 h since randomization were included and stratified into two groups according to their average PaO₂ levels during the first 48 h (PaO_{2 0-48 h}). The cut-off value was established at 100 mmHg (average PaO_{2 0-48 h} >100 mmHg: hyperoxemia group; PaO_{2 0-48h}≤100: normoxemia group). The primary outcome was 90-day mortality. 1632 patients were included in this analysis (661 patients in the hyperoxemia group, 971 patients in the normoxemia group). Concerning the primary outcome, 344 (35.4%) patients in the hyperoxemia group vs. 236 (35.7%) in the normoxemia group had died within 90 days from randomization (p = 0.909). No association was found after adjusting for confounders (HR 0.87; CI [95%] 0.736-1.028, p = 0.102) or after excluding patients with hypoxemia at enrollment, patients with lung infection or including post-surgical patients only. Conversely, we found an association between lower risk of 90-day mortality and hyperoxemia in the subgroup including patients who had the lung as primary site of infection (HR 0.72; CI [95%] 0.565-0.918). Mortality at 28 days, ICU mortality, incidence of acute kidney injury, use of renal replacement therapy, days to suspension of vasopressor or inotropic agents, and resolution of primary and secondary infections did not differ significantly. Duration of mechanical ventilation and length of stay in ICU were significantly longer in patients with hyperoxemia. In a post-hoc analysis of a RCT enrolling septic patients, hyperoxemia as average PaO₂>100 mmHg during the first 48 h was not associated with patients' survival.