Ventilator-associated pneumonia (VAP) affects up to 20% of critically ill patients and induces significant antibiotic prescription pressure, accounting for half of all antibiotic use in the ICU. VAP significantly increases hospital length of stay and healthcare costs yet is also associated with long-term morbidity and mortality. The diagnosis of VAP continues to present challenges and pitfalls for the currently available clinical, radiological and microbiological diagnostic armamentarium. Biomarkers and artificial intelligence offer an innovative potential direction for ongoing future research. In this Review, we summarise the pathobiological heterogeneity and diagnostic challenges associated with VAP.

Ventilator-associated pneumonia (VAP) is the most prevalent nosocomial infection in the intensive care unit (ICU), accounting for more than 30 % of the overall costs for all healthcare-associated infections. VAP leads to poor outcomes, such as increased duration of mechanical ventilation, prolonged length of ICU stay and increased mortality rates for up to five years after discharge. The pathophysiology of VAP is complex, attributable to the colonisation of abnormal microbiota and micro-aspiration risks associated with mechanical ventilation and critical illness, and thus its prevention and treatment is complex. With the rising prevalence of multidrug resistance infections and antibiotic prescription pressures, the management of VAP is becoming increasingly challenging. The traditional treatment of VAP with intravenous or oral antibiotics is effective; yet inhaled antibiotics may offer a targeted, synergistic and effective alternative. Empirical therapy with broad-spectrum antibiotics are associated with systemic complications and increased pathogenic strains, whilst inhaled antibiotics reduce bystander antimicrobial resistance with fewer systemic side effects. However, large-scale clinical trials have failed to cosnsitently demonstrate the clinical benefits of inhaled antibiotics and thus translation into practice remains controversial. In this review, we summarise the pathophysiology and diagnosis of VAP, underpin the mechanisms of currently available therapies and discuss the potential role of inhaled antibiotics for the prevention and treatment of VAP, with critical discussion of the available evidence.

Background: Major trauma is a significant global health issue. Pneumonia poses an additional risk for morbidity and mortality after major trauma yet identifying pneumonia remains challenging in clinical practice. This systematic review aims to evaluate blood-based biomarkers for pneumonia in major trauma patients. Methods: The search was performed across four databases up to November 18th 2024, including primary studies investigating blood-based biomarkers associated with pneumonia in adults hospitalised after major trauma (PROSPERO CRD42024542059). Risk of bias was assessed using the ROBINS-E tool and meta-analysis was performed of pooled data. Results: Among 20 included studies, with a total of 4316 participants, the pooled mean pneumonia rate was 32.7% (23.5%–43.4%). Seventy biomarkers for post-operative pneumonia were identified, with meta-analysis possible for 12 of the reported biomarkers. At admission interleukin (IL)-6 (standardised mean difference: 1.41 (0.04–2.77), p = 0.04), cytokeratin fragment 21-1 (CYFRA21-1; 0.53 (0.19–0.86), p = 0.002) and leucocyte count (0.28 (0.05–0.50), p = 0.01) were higher in patients who developed pneumonia. During hospitalisation, patients with pneumonia had significantly higher IL-10 (4.42 (3.89–4.95), p > 0.001) and neutrophil oxidative burst capacity (1.52 (0.96–2.09), p > 0.001) at day 1, CYFRA21-1 at day 2 (0.43 (0.10–0.76), p = 0.01), IL-6 at day 3 (3.11 (2.66–3.55), p > 0.001) and day 5 (0.57 (0.05–1.09), p = 0.03) and CRP at day 4 (1.87 (1.51–2.24), p > 0.001), day 5 (1.38 (1.03–1.72), p > 0.001), day 6 (0.74 (0.42–1.06), p > 0.001) and day 7 (0.87 (0.12–1.63), p = 0.02). Across the included studies, 85% exhibited some concerns to very high risk of bias. Conclusions: While we identified potential candidate biomarkers for pneumonia in major trauma patients, the high heterogeneity across trauma populations, clinical diagnostic tools and biomarker testing methods warrants further high-quality studies to confirm their clinical value.

Introduction: Older adults are more likely to acquire the severe manifestation of COVID-19 and the hospitalised survivors experience significant functionality loss. Thus, we aimed to identify the level of functionality in older adults hospitalised due to COVID-19, and the effect of inpatient rehabilitation upon functional recovery. Methods: A search was performed on July 2024, across five databases to retrieve studies assessing functionality in patients during COVID-19 hospitalisation, with or without rehabilitation. Results: At admission, higher functionality was significantly higher for survivors than non survivors (standardized mean difference (SMD): 0.83 [0.56; 1.09]). The effect of inpatient rehabilitation on functionality was tested among 38 arms across studies. Inpatient rehabilitation improved functionality SMD across all indexes (1.47 [1.18; 1.77], P <= 0.001), with greatest effect in the patients >70 years (2.84 [1.74, 3.93], P = 0.006), compared to their counterparts. Conclusion: Hospitalisation due to COVID-19 reduced functionality to a higher extent in older adults above 70 years. Inpatient rehabilitation was effective to improve functionality in both age groups. Protocol registration: PROSPERO CRD42021278619.

Background: Traumatic brain injury (TBI) is a major cause of death and disability worldwide. Mobilization is defined as the application of assisted movement and physical therapy to hospitalized patients, including progressive exercise and ambulation programs. While early mobilization in the intensive care unit (ICU) has been shown to be a safe and effective intervention to improve patient outcomes in the general ICU cohort, there is currently limited evidence specific to patients with acute TBI. The aim of this service evaluation was to identify current mobilization activity and functional outcomes in patients admitted to the ICU at our institution following an acute TBI. Methods: A single-center retrospective service evaluation was performed for all patients, over 16 years-old, admitted to the ICU at our institution (a Level 1 major trauma center) with an acute TBI between January 2022 and November 2024. Patient demographics, ICU admission details, TBI severity (based on the Glasgow Coma Scale [GCS]) and functional outcomes were extracted. Mobilization outcomes included the timing of the commencement of mobilization (defined as sitting on the edge of the bed or better) and mobilization status, defined using the Manchester Mobility Scale (MMS). Results: The service evaluation included 353 patients, of whom 56.0% had severe TBI (GCS: 3–7). Mobilization was achieved in ICU for 53.0% of patients, with a further 18.1% first mobilized on a hospital ward post-ICU discharge. The first mobilization occurred at a median of 11 days (interquartile range: 6–18) after ICU admission. In patients surviving to ICU discharge, 28.9% had an MMS of 1 (bed-based exercises) at this time, with only 9.1% achieving an MMS of 7 (mobilizing 30 meters or more). Analysis by TBI severity found a significant decline in in-hospital mobilization rates with increasing TBI severity (90.7% vs. 58.4% for mild vs. severe TBI; p < 0.001), with a corresponding increase in the time to the first mobilization (median: 6 vs. 13 days for mild vs. severe TBI; p < 0.001). Conclusion: Acute TBI patients admitted to the ICU at our institution had low rates of mobilization and achieved low levels of mobility at ICU discharge. This service evaluation highlights the need for prospective studies into early mobilization practices in the neurotrauma ICU.

Background: Post-operative pneumonia is a commonly occurring surgical complication associated with poor patient outcomes. This study aimed to synthesise pre-operative and post-operative blood-based biomarkers associated with post-operative pneumonia. Methods: Electronic databases were searched up to April 14th, 2026. Primary studies investigating blood-based biomarkers in adults hospitalised after surgery were included. Meta-analysis was performed using the random effects model to compare pooled data for pneumonia and no-pneumonia groups using standardised mean difference. Risk of bias was assessed using the ROBINS-E tool. Results: Thirty-seven studies ( n = 15,842 patients) were included, with an overall pneumonia rate of 17.8% [15.8–20.0%]. One hundred and fifteen biomarkers were identified. Meta-analysis identified that patients who developed post-operative pneumonia had significantly lower platelet-to-neutrophil ratio ( p < 0.0001), red blood cell count ( p = 0.001), haemoglobin ( p = 0.002), albumin ( p = 0.005) and lymphocyte count ( p = 0.008) and significantly higher monocyte-to-lymphocyte ratio ( p < 0.0001), systemic immune inflammation index ( p < 0.001), systemic inflammatory response index ( p < 0.0001) and blood urea nitrogen ( p = 0.0001) at pre-operative baseline, compared to those without pneumonia. Patients who developed post-operative pneumonia were associated with significantly higher procalcitonin (PCT) at post-operative day one ( p = 0.03), two ( p = 0.0001), three ( p = 0.0004) and six ( p < 0.0001); higher C-Reactive Protein (CRP) at day two ( p = 0.02), four ( p < 0.0001) and five ( p < 0.0001); higher interleukin (IL)-6 at day three ( p = 0.001) and four ( p = 0.0002); and higher white blood cell (WBC) count at day three ( p = 0.01) and day four ( p = 0.001) post-operatively, compared to those without pneumonia. In addition, pre-operative CRP was associated with mortality within the patients who later developed post-operative pneumonia ( r = 0.70, p = 0.0009). Conclusions: The results identify blood-based biomarker signals associated with post-operative pneumonia. However, interpretation is limited by heterogeneous pneumonia definitions and inconsistent reporting of diagnosis timing across studies. The certainty of evidence is therefore limited, and thus these biomarkers cannot currently be used for prediction or diagnosis in clinical practice. Further high‑quality, prospective studies are required to establish clinically meaningful thresholds. Protocol registration: PROSPERO: CRD42024570654.