The incidence of cancer-associated thrombosis has increased in recent years. While the association between venous thromboembolism (VTE) and chemotherapy is well established, there is no clear link between immune checkpoint inhibitors (ICIs) and VTE risk. Many risk assessment models (RAMs) have been developed to identify high-risk patients who need prophylaxis. However, these models are validated in patients undergoing chemotherapy, while they are scarce in those receiving immunotherapy. Moreover, the mechanisms linking ICIs to thrombosis are still a matter of debate. They include the upregulation of pro-inflammatory intracellular pathways, the release of cytokines, the activation of innate immune cells, the release of tissue factors and platelet activation, and the increase in adhesion molecules, thus resulting in the recruitment of agents involved in coagulation. Promising biomarkers are emerging to identify patients undergoing ICIs who are at high risk of developing VTE and need prophylaxis. In this review we investigate the possible causation between cancer-associated thrombosis (CAT) and immunotherapy and the underlying pathophysiological mechanisms. Thus, we suggest the most appropriate therapeutic approaches based on currently available data.

The role of awake prone positioning (aPP) in patients with acute hypoxemic respiratory failure is debated. We performed a systematic review and meta-analysis to evaluate the role of aPP in acute respiratory failure related to COronaVIrus Disease-19 (COVID-19). Studies reporting on the clinical course of patients with acute respiratory failure related to COVID-19 treated or not treated by aPP were included in the systematic review and meta-analysis (ProsperoID: CRD42022333211). The primary study outcome was the composite of in-hospital death or orotracheal intubation; the individual components of the primary outcome were secondary study outcomes. The composite of in-hospital death or orotracheal intubation was available for 6 studies (1884 patients), five randomized and one prospective; a significant reduction in the risk of this outcome was observed in patients treated vs. not treated by aPP (33.5% vs. 39.8%; OR 0.73, 95% CI 0.60–0.89;I²0%). In-hospital death was reported in 34 studies (6808 patients) and occurred in 17.4% vs. 23.5% of patients treated or not treated with aPP (random effect OR 0.60, 95% CI 0.46–0.79;I²59%); orotracheal intubation was observed in 25.8% vs. 32.7% of patients treated or not treated with aPP (27 studies, 5369 patients; random effect OR 0.85, 95% CI 0.56–1.27;I²84%). aPP reduces the risk for death or orotracheal intubation in patients with acute respiratory failure related to COVID-19. Further studies should be conducted to confirm the clinical benefit of aPP outside the ICU.RegistrationProspero ID: CRD42022333211.

Background: Prone positioning (PP) is an established and commonly used lung recruitment method for intubated patients with severe acute respiratory distress syndrome, with potential benefits in clinical outcome. The role of PP outside the intensive care unit (ICU) setting is debated. Objectives: We aimed at assessing the role of PP in death and ICU admission in non-intubated patients with acute respiratory failure related to COronaVIrus Disease-19 (COVID-19) pneumonia. Design: This is a retrospective analysis of a collaborative multicenter database obtained by merging local non-interventional cohorts. Methods: Consecutive adult patients with COVID-19-related respiratory failure were included in a collaborative cohort and classified based on the severity of respiratory failure according to the partial arterial oxygen pressure to fraction of inspired oxygen ratio (PaO₂/FiO₂) and on clinical severity by the quick Sequential Organ Failure Assessment (qSOFA) score. The primary study outcome was the composite of in-hospital death or ICU admission within 30 days from hospitalization. Results: PP was used in 114 of 536 study patients (21.8%), more commonly in patients with lower PaO₂/FiO₂ or receiving non-invasive ventilation and less commonly in patients with known comorbidities. A primary study outcome event occurred in 163 patients (30.4%) and in-hospital death in 129 (24.1%). PP was not associated with death or ICU admission (HR 1.17, 95% CI 0.78–1.74) and not with death (HR 1.01, 95% CI 0.61–1.67) at multivariable analysis; PP was an independent predictor of ICU admission (HR 2.64, 95% CI 1.53–4.40). The lack of association between PP and death or ICU admission was confirmed at propensity score-matching analysis. Conclusion: PP is used in a non-negligible proportion of non-intubated patients with COVID-19-related severe respiratory failure and is not associated with death but with ICU admission. The role of PP in this setting merits further evaluation in randomized studies.

Venous thromboembolism (VTE) is common in patients with coronavirus disease-2019 (COVID-19). The optimal heparin regimen remains unknown and should balance thromboembolic and bleeding risks. The aim of this study was to evaluate the efficacy and safety of standard or higher heparin regimens for the prevention of VTE in patients hospitalized due to COVID-19. We performed a systematic literature search; studies reporting on hospitalized patients with COVID-19 who received standard heparin prophylaxis vs. high (intermediate or therapeutic) heparin regimens were included if outcome events were reported by treatment group and more than 10 patients were included. Primary study outcome was in-hospital VTE. Secondary study outcomes were major bleeding (MB), all-cause death, fatal bleeding and fatal pulmonary embolism. Overall, 33 studies (11,387 patients) were included. Venous thromboembolic events occurred in 5.2% and in 8.2% of patients who received heparin prophylaxis with at high-dose or standard-dose, respectively (RR 0.71, 95% CI 0.55–0.90, I2 48.8%). MB was significantly higher in patients who received high- compared to the standard-dose (4.2% vs 2.2%, RR 1.94, 95% CI 1.47–2.56, I2 18.1%). Sub-analyses showed a slight benefit associated with high-dose heparin in patients admitted to non-intensive care unit (ICU) but not in those to ICU. No significant differences were observed for mortality outcomes. Heparin prophylaxis at high-dose reduces the risk of VTE, but increased the risk of MB compared to the standard-dose. No clinical benefit for heparin high-dose was observed for ICU setting, but its role in the non-ICU deserves further evaluation. PROSPERO registration number: CRD42021252550.

Early fluid resuscitation reduces mortality in patients with sepsis or septic shock, but excessive fluid administration may prolong hospitalization and increase complications. Several non-invasive strategies have been proposed to guide fluid resuscitation, yet their comparative efficacy remains uncertain. We systematically searched PubMed and EMBASE through June 2025 to identify randomized controlled trials evaluating non-invasive strategies to guide fluid resuscitation in adult patients with sepsis or septic shock. Pairwise and network meta-analyses were conducted to assess short-term mortality. Length of stay (LOS) in intensive care unit (ICU) was also analyzed. 20 RCTs (2.435 patients) were included. In pairwise meta-analyses, lactate clearance-guided resuscitation was associated with reduced short-term mortality compared to ScvO₂ (RR 0.81, 95% CI 0.65–1.00; I ² = 0%). No significant difference in mortality was observed between capillary refill time versus lactate clearance (RR 0.82; 95% CI 0.65–1.04; I ² = 0%), passive leg-raising plus stroke volume versus usual care (RR 0.91, 95% CI 0.67–1.23; I ² = 14%), echocardiography versus usual care (RR 0.72, 95% CI 0.32–1.61; I ² = 70%), and inferior vena cava collapsibility versus usual care (RR 0.75, 95% CI 0.52–1.09; I ² = 19%). In network meta-analysis, none of the assessed strategies to guide fluid resuscitation reduced mortality compared to usual care. Heterogeneity was moderate. Non-invasive dynamic parameters—lactate clearance, along with capillary refill time and inferior vena cava collapsibility assessment—are promising, bedside-available tools for guiding fluid resuscitation in patients with sepsis or septic shock. Their broader use in clinical practice may be warranted, pending confirmation from high-quality studies.

Background Prone positioning (PP) is an established and commonly used lung recruitment method for intubated patients with severe acute respiratory distress syndrome, with potential benefits in clinical outcome. The role of PP outside the intensive care unit (ICU) setting is debated. We aimed at describing the use and potential benefits of PP in non-intubated patients with acute respiratory failure related to COronaVIrus Disease-19 (COVID-19)-pneumonia. Methods Consecutive adult patients with COVID-19-related respiratory failure were included in a prospective collaborative cohort and classified based on the severity of respiratory failure by the partial arterial oxygen pressure to fraction of inspired oxygen ratio (PaO2/FiO2) and on clinical severity by the quick Sequential Organ Failure Assessment (qSOFA) score. Primary study outcome was the composite of in-hospital death or ICU admission within 30 days from hospitalization. Results PP was used in 114 of 536 study patients (21.8%), more commonly in patients with lower PaO2/FiO2 or receiving non-invasive ventilation and less commonly in patients with known comorbidities. A primary study outcome event occurred in 163 patients (30.4%) and was in-hospital death in 129 (24.1%). PP was not associated with death or ICU admission (HR 1.15, CI 95% 0.78-1.72) and not with death (HR 1.03, CI 95% 0.62-1.69); PP was an independent predictor of ICU admission (HR 2.55, 95%CI 1.50-4.32). The severity of respiratory failure and non-invasive ventilation were independent predictors of death or ICU admission at 30 days. The lack of association between PP and death or ICU admission was confirmed at propensity score matching analysis.Conclusion PP is used in a not negligible proportion of non-intubated patients with COVID-19-related severe respiratory failure and is not associated with death but with ICU admission. The role of PP in this setting requires evaluation in randomized studies.