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Data on the pathology of COVID-19 are scarce; available studies show diffuse alveolar damage; however, there is scarce information on the chronologic evolution of COVID-19 lung lesions. The primary aim of the study is to describe the chronology of lung pathologic changes in COVID-19 by using a post-mortem transbronchial lung cryobiopsy approach. Our secondary aim is to correlate the histologic findings with computed tomography patterns. SARS-CoV-2-positive patients, who died while intubated and mechanically ventilated, were enrolled. The procedure was performed 30 min after death, and all lung lobes sampled. Histopathologic analysis was performed on thirty-nine adequate samples from eight patients: two patients (illness duration < 14 days) showed early/exudative phase diffuse alveolar damage, while the remaining 6 patients (median illness duration—32 days) showed progressive histologic patterns (3 with mid/proliferative phase; 3 with late/fibrotic phase diffuse alveolar damage, one of which with honeycombing). Immunohistochemistry for SARS-CoV-2 nucleocapsid protein was positive predominantly in early-phase lesions. Histologic patterns and tomography categories were correlated: early/exudative phase was associated with ground-glass opacity, mid/proliferative lesions with crazy paving, while late/fibrous phase correlated with the consolidation pattern, more frequently seen in the lower/middle lobes. This study uses an innovative cryobiopsy approach for the post-mortem sampling of lung tissues from COVID-19 patients demonstrating the progression of fibrosis in time and correlation with computed tomography features. These findings may prove to be useful in the correct staging of disease, and this could have implications for treatment and patient follow-up.

The regulation of end-of-life decisions has been the subject of intense debate for years, marked by the challenge of reconciling two fundamental ethical principles: preservation of life and individual self-determination. From a legal perspective, numerous court rulings have outlined an evolving framework, highlighting the difficulty of establishing a regulatory approach that balances constitutional rights with ethical values. This study examines key Italian judicial decisions, with a particular focus on recent Constitutional Court rulings regarding end-of-life issues, and discusses the underlying ethical and humanistic perspectives. We aim to explore the key ethical and legal issues arising in the context of end-of-life regulation. Judicial developments demonstrate an increasing recognition of individual self-determination in accessing assisted suicide despite persisting ongoing ambiguities and regulatory gaps. The end-of-life debate underscores the urgency of moving beyond abstract and schematic approaches, favoring a perspective that integrates multidisciplinary expertise and human sensitivity. Ensuring effective access to palliative care and comprehensive social and healthcare systems is essential to alleviate suffering and provide genuine alternatives to assisted suicide.

Background Pulmonary hypertension (PH) frequently complicates acute respiratory distress syndrome (ARDS) and contributes to right ventricular dysfunction and mortality. Veno-venous extracorporeal membrane oxygenation (V-V ECMO) may attenuate PH through improved gas exchange, yet pulmonary pressures often remain elevated. Data on the determinants and prognostic impact of PH in ECMO-supported ARDS are limited. Methods We performed a retrospective observational study of adult ARDS patients receiving V-V ECMO at a tertiary referral center between 2003 and 2024. Only patients monitored with a pulmonary artery catheter were included. Daily hemodynamic, ventilatory, and gas exchange data were prospectively collected. Determinants of mean pulmonary artery pressure (mPAP) were analyzed using a linear mixed-effects model. The association of (1) mPAP on the first day of ECMO and (2) the mPAP trajectory over the first 5 ECMO days—expressed as the patient-specific daily slope—with hospital mortality was assessed using logistic regression before and after adjustment for confounders. Results Among 240 consecutive V-V ECMO patients, 225 had a pulmonary artery catheter and were analyzed. Median age was 51 years, 33% were female. The median mPAP during ECMO was 27 mmHg [23–32], with 91% of measurements exceeding 20 mmHg. Independent determinants of higher mPAP included intrapulmonary shunt fraction, lower venous pH, higher pulmonary artery occlusion pressure, increased PEEP, reduced respiratory system compliance, and longer ECMO duration. In contrast, higher venous partial pressure of oxygen and mixed venous oxygen saturation were associated with lower mPAP. mPAP on the first day of ECMO was not associated with hospital mortality. In contrast, the trajectory of mPAP during the first 5 days was independently associated with mortality (adjusted OR 1.89 per 1-mmHg/day increase, 95% CI 1.33–2.77, p < 0.001). Conclusions Pulmonary hypertension is highly prevalent in ARDS patients on V-V ECMO and reflects underlying disease severity. Early upward trajectories in mPAP, rather than the initial mPAP value, independently predicted higher mortality. Serial pulmonary pressure monitoring may provide relevant prognostic information and help guide management of pulmonary hemodynamics in ECMO-supported ARDS.

IntroductionAfter resuscitation from out of hospital cardiac arrest (OHCA), mechanical ventilation (MV) and respiratory management are fundamental to support patients in the intensive care unit (ICU) and to minimise secondary brain injury. Best practices for MV and association with clinical outcomes in patients with OHCA remain unclear.Methods and analysisThis protocol describes a pre-planned respiratory-focused series of sub-analyses within the Sedation, Temperature and Pressure after Cardiac Arrest and Resuscitation (STEPCARE) trial, an ongoing interventional study evaluating 6-month mortality after randomisation in patients admitted to ICUs following OHCA. The primary aim is to describe real-world ventilator settings and gas-exchange targets during the first 72 hours after ICU admission in patients receiving invasive mechanical ventilation after OHCA. Secondary aims include to estimate the incidence of respiratory complications during ICU stay (eg, ventilator-associated pneumonia, acute respiratory distress syndrome, barotrauma); and to explore the association between early ventilator settings/gas-exchange parameters and 6-month outcomes (mortality and neurological status). Exploratory aim is to characterise weaning and extubation practices, including timing and failure rates.Eligible patients will include adult STEPCARE participants receiving invasive MV after return of spontaneous circulation with available respiratory data recorded within the STEPCARE database.Data collected in the STEPCARE trial that will be analysed include patients’ prehospital characteristics; clinical examination at hospital admission and at ICU admission; ventilator settings and arterial blood gases recorded at predefined time points during ICU stay. In particular: MV setting (mode, tidal volume, positive end-expiratory pressure, fraction of inspired oxygen, tidal volume, mechanical power, plateau/driving pressures), gas-exchange values (arterial partial pressure of oxygen and carbon dioxide, pH, arterial saturation of oxygen), timing of measurements and the occurrence/timing of respiratory complications and weaning outcomes.Ethics and disseminationThe STEPCARE study has been approved by the regional ethics committee at Lund University (Dnr 2022-02425-01, Approved IRB on 2022-06-18) and by all ethics boards in the participating countries. No additional ethical approval is required for this predefined secondary analysis, as no further data collection or interventions will be performed. Findings will be disseminated through publication in peer-reviewed journals and, where appropriate, conference abstracts and presentations. Patients and the public were not involved.ClinicalTrials.govNCT05564754.

This review highlights the pathophysiology and anesthesiologic management of pulmonary complications in minimally invasive cardiac surgery, emphasizing challenges of one-lung ventilation and cardiopulmonary bypass, to improve postoperative respiratory outcomes.

Background Changes in cerebrospinal fluid (CSF) in patients with aneurysmal subarachnoid hemorrhage (aSAH) have not been fully elucidated, yet they are critical and may potentially be associated with the risk of complications. The aim of this study is to characterize the biochemical properties of CSF and examine the temporal changes in aSAH patients with and without post-aSAH complications such as vasospasm and shunt-dependent hydrocephalus. Methods This prospective observational longitudinal cohort study involved collecting CSF and arterial blood samples from SAH patients requiring an external ventricular drain at four different timepoints following the initial event (1–3, 4–7, 8–13, and 14–20 days after aSAH). A control group that comprised patients with idiopathic normal pressure hydrocephalus undergoing CSF sampling was included. Results A total of 20 SAH patients and 20 controls were enrolled. We observed significantly higher levels of hemoglobin (Hb), proteins, lactate, and cell concentrations in the CSF of aSAH patients compared to the control group ( p  < 0.001), with no corresponding differences in serum levels. Furthermore, a progressive decline in CSF Hb, proteins, and cells levels was noted over the days following the hemorrhage ( p  = 0.029, p  = 0.005, and p  = 0.010, respectively). Patients that developed vasospasm exhibited a lower CSF glucose/lactate ratio ( p  < 0.001) and reduced CSF sodium levels ( p  = 0.045), while patients that developed shunt-dependent hydrocephalus exhibited higher plasmatic and CSF glucose levels ( p  = 0.013 and p  = 0.003, respectively) and lower CSF Hb/proteins ratio ( p  < 0.001). Conclusions Patients with aSAH exhibit changes in the biochemical profile of the CSF, which evolve over time following the acute event. Parameters such as CSF glucose/lactate ratio and CSF Hb/proteins ratio could potentially provide valuable insights not only into the pathophysiology of aSAH but also into patient risks of post-hemorrhagic complications, such as vasospasm and hydrocephalus.

Invasive mechanical ventilation (IMV) is crucial for managing acute brain injury (ABI) patients, yet the effects of positive end-expiratory pressure (PEEP) on outcomes are not well understood. This study aimed to evaluate the relationship between PEEP levels and risk of extubation failure as well as intensive care unit (ICU) mortality in ABI patients. This post-hoc analysis of the ENIO study included 1512 ABI patients from the ENIO cohort, excluding those without available data on PEEP at day 1 and who never received an extubation trial. PEEP levels were recorded at days 1, 3, 7, and on the day of extubation. Logistic regression assessed the association between PEEP and extubation failure, while Cox proportional hazards regression analyzed ICU mortality. Among 1154 included patients, extubation failure occurred in 21.2 % and ICU mortality was 3.7 %. Higher median PEEP at days 1, 3, and 7 was independently associated with increased odds ratio (OR) of extubation failure (OR = 1.13; 95 %CI = 1.01–1.26; p = 0.0294). At the time of extubation, higher PEEP was also significantly associated with extubation failure (OR = 1.13; 95 %CI = 1.02–1.25; p = 0.0218) and ICU mortality (Hazard Ratio, HR = 1.38; 95 %CI = 1.12–1.69; p = 0.0026). However, at sensitivity analyses adjusted for acute respiratory distress syndrome (ARDS), PEEP was no longer significantly associated with outcomes, while ARDS itself was an independent predictor of extubation failure. Extubating ABI patients at higher PEEP levels was associated with an increased risk of extubation failure and ICU mortality. However, this association likely reflects underlying respiratory pathology or disease severity. Our findings suggest that PEEP level may serve as a surrogate marker for extubation readiness, rather than a modifiable risk factor, and highlight the need for individualized assessment prior to extubation. •Higher positive end-expiratory pressure (PEEP) levels at the time of extubation were independently associated with increased risk of extubation failure in patients with acute brain injury (ABI).•Median PEEP measured over ICU days 1, 3, and 7 was associated with a higher likelihood of extubation failure.•After adjusting for acute respiratory distress syndrome (ARDS), PEEP was no longer independently associated with outcomes.•Neurological factors—including traumatic brain injury (TBI), preserved visual pursuit, and higher Glasgow Coma Scale motor score—were protective against extubation failure and ICU mortality.•Individualized ventilatory and weaning strategies in ABI patients and question the use of fixed PEEP thresholds are needed.

Despite the lifesaving potential of organ donation, a gap persists between organ demand and availability. Family members of intensive care unit (ICU) patients play a key role in consent for donation, yet factors influencing their decisions are not fully understood. This study assessed the willingness of ICU patients' family members to donate organs and explored associated sociodemographic, clinical, and attitudinal factors. In this cross-sectional single-centered tertiary care center in northern Jordan, 155 adult family members of ICU patients completed a structured questionnaire on demographics, patient variables, knowledge of organ donation and brain death, religious and cultural beliefs, trust in healthcare, and exposure to public campaigns. Baseline characteristics were summarized using descriptive statistics, and between-group comparisons were conducted using chi-square, Student's -test, or Mann-Whitney -test, as appropriate. Firth's penalized logistic regression was used to identify independent predictors of willingness due to small sample size and sparse cell counts. Of 155 participants, 44 (28.4%; 95% CI: 21.9-35.9%) were willing to donate. High trust in the healthcare system was the strongest independent predictor of willingness (OR 7.73; 95% CI: 3.21-19.93; p<0.001), followed by a favorable religious stance toward donation (OR 4.75; 95% CI: 1.99-12.23; p<0.001) and high familiarity with organ donation (OR 2.78; 95% CI: 1.12-6.87; p = 0.028). Willingness to donate organs among family members of ICU patients was primarily influenced by trust in the healthcare system, religious beliefs, and familiarity with organ donation. Context-specific interventions targeting these factors may help improve consent rates in similar settings.

The optimal level of positive end–expiratory pressure (PEEP) during minimally invasive abdominal surgery is uncertain. Intraoperative ventilation with individualized high PEEP and recruitment maneuvers can be used to keep the driving pressure (ΔP) low, but can also lead to hypotension. In addition, the resulting ΔP and feasibility of individualized high PEEP in minimally invasive abdominal surgery is unclear. Planned interim analysis on safety and feasibility of ‘Driving Pressure During General Anesthesia for Minimally Invasive Abdominal Surgery’ (GENERATOR), an ongoing randomized clinical trial that compares individualized high PEEP, titrated to the lowest ΔP, with a standard low PEEP ventilation strategy with respect to postoperative pulmonary complications. The primary endpoint for this analysis was the proportion of patients with intraoperative hypotension. Secondary endpoints were other intraoperative complications, ventilation variables and feasibility parameters. From December 2023 to July 2024, 181 patients were enrolled. Data for analysis were available for 177 patients, of which 87 patients were randomized to individualized high PEEP and 90 to standard low PEEP. Intraoperative hypotension was similar between the individualized high PEEP vs standard low PEEP group (11.5 vs 11.1 %, relative risk ratio 1.0 [95 % CI 0.5–2.4], p = 1.00), while vasopressor use was higher in the intervention group. The median difference in ΔP between both groups was 6 cm H2O. Protocol compliance was 81.6 % in the individualized high PEEP group vs 97.8 % in the standard low PEEP group; most instances of non–compliance in the individualized high PEEP group concerned a level of PEEP that was too high. In minimally invasive abdominal surgery, a ventilation strategy using individualized high PEEP was not associated with a higher incidence of hypotension, but did show an increased use of vasopressors. The intervention was highly feasible, and led to a lower ΔP. These interim findings warrant confirmation in the main analysis of GENERATOR. This research was funded by ZonMW, grant number 10390012110091. •Individualized high PEEP ventilation is feasible in minimally invasive abdominal surgery.•Intraoperative hypotension is similar between individualized high PEEP and standard low PEEP.•Vasopressors were used in higher doses with individualized high PEEP compared to standard low PEEP.•Driving pressure was lower with individualized high PEEP compared to standard low PEEP.

Background Ventilator-associated bacterial pneumonia (VABP) is a common infection in critically ill patients in intensive care units (ICU), with attributable mortality of up to 13%, and its etiological diagnosis remains challenging. Materials and methods We conducted a multicenter, prospective, observational study within the MULTI-SITA platform to assess the impact on relevant clinical and antimicrobial stewardship outcomes of the use of a molecular syndromic panel (BIOFIRE® FILMARRAY® Pneumonia plus ), in addition to a standard approach based on culture. The primary outcome measure was 30-day mortality from VABP onset. Results Overall, 237 patients with VABP were included in the study. In multivariable analysis, SOFA score (hazard ratio [HR] 1.13, 95% confidence interval [CI] 1.04–1.22, p = 0.003), previous isolation of carbapenem-resistant Pseudomonas aeruginosa (HR 3.02, 95% CI 1.25–7.32, p = 0.015), and solid neoplasm (HR 2.15, 95% CI 1.12–4.14, p = 0.022) were associated with increased mortality, while no association was registered for the molecular syndromic panel performed (HR 1.07, 95% CI 0.59–1.93, p = 0.825). In secondary analyses, use of the molecular syndromic panel resulted in more events of either de-escalation or initiation of appropriate antibiotic therapy at day 1 from VABP onset in comparison with a standard approach based on culture only (41.3% vs. 27.8%, p = 0.041). Conclusion The use of a molecular syndromic panel in patients with VABP was able to impact antibiotic decisions, without an unfavorable effect on mortality. Further study is necessary to assess the long-term effects in terms of antimicrobial stewardship of molecular syndromic panels-based antibiotic treatment decisions.