The bundle studies reported a pooled odds ratio of 0.40, with a 95% confidence interval of 0.28 to 0.57 and an I² of 37%, indicating 60% lower odds of VAP in intervention groups than in comparison groups. When incidence was evaluated relative to time at risk, the incidence-rate ratio was 0.56 (95% CI 0.43–0.73; I² 28%), consistent with a 44% lower VAP rate per unit of patient-time. The incidence-rate difference was −0.0083 (95% CI −0.0127 to −0.0039; I² 38%), corresponding to 8.33 fewer cases per 1,000 mechanical-ventilation days. Leave-one-out analysis did not materially change the pooled bundle estimates, but Doi and funnel plots showed asymmetry, with the largest study having relatively higher effect sizes.

These packages combined clinical and organizational measures rather than applying a uniform intervention. Depending on the unit and study, bundles included hand-hygiene practices, head-of-bed elevation, sterile airway management with closed suction and reduced circuit changes, oral-care protocols, daily readiness-to-wean evaluations, staff education, adherence monitoring, audit and feedback and changes to unit workflow. The breadth of the packages means the pooled estimates cannot identify which practice or implementation feature produced the association. It is also possible that improvements in surveillance, staffing, infection-control practice or other secular changes contributed to the lower pneumonia rates observed after implementation. Several bundle evaluations used before-and-after comparisons, which cannot fully separate an intervention’s effect from changes in neonatal care occurring over the same period.

Oral care produced the clearest evidence among individual preventive approaches. Across 14 oral-care studies, the pooled odds ratio for VAP was 0.53 (95% CI 0.35–0.81), with very low statistical heterogeneity of I² 3%. Twelve of those studies evaluated oropharyngeal therapy with mothers’ own milk, or OPT-MOM, which involves using breast milk to swab the oral and pharyngeal area. In a subgroup analysis, OPT-MOM was associated with an odds ratio of 0.54 (95% CI 0.31–0.93; I² 13%). The overall association remained after four studies without a clearly defined mechanically ventilated at-risk population were removed, producing an odds ratio of 0.47 (95% CI 0.29–0.77). The sensitivity result indicates that the association was not explained solely by those four studies, but it does not remove the broader limitations affecting the oral-care evidence.

That oral-care signal nevertheless carries substantial uncertainty. Most studies were small, the pooled analysis showed signs of publication bias or small-study effects, and the magnitude was not consistent across every methodological subgroup. In the randomized-trial-only subgroup, oral care remained associated with lower VAP odds, at 0.53 (95% CI 0.34–0.83; I² 0%). The estimate was also consistent in studies using Centers for Disease Control and Prevention diagnostic criteria, at 0.35 (95% CI 0.14–0.85; I² 0%), and in studies clearly restricted to ventilated neonates, at 0.47 (95% CI 0.29–0.77; I² 0%). By contrast, estimates were non-significant in some groups defined by gestational age or birth weight, and studies without clear mechanical-ventilation restriction showed a weaker, highly uncertain association of 0.69 (95% CI 0.17–2.78). The evidence assessment therefore rated the certainty for oral care as moderate rather than conclusive.

Individual ventilator-care methods did not lend themselves to pooled analysis because the interventions differed markedly. Three studies examined the interval between ventilator-circuit changes. None found that changing circuits more frequently reduced VAP, and the differing comparisons ranged from every third day versus daily, every seven days versus every two days, and every 14 days versus every seven days. Two studies comparing closed- and open-suction systems found no reduction in VAP with closed suction, although closed suction appeared safe. A modified endotracheal tube with a sanitation port was associated with lower pneumonia incidence in one study, 10% versus 30%, but the finding was not independently replicated. A trial of polymyxin B rather than saline for suction-catheter flushing found no significant difference, and its interpretation was limited by baseline differences and non-random allocation. Overall, the evidence did not support more frequent circuit changes or closed suction as effective standalone measures for reducing neonatal VAP.

Evidence for other approaches was also limited. Two trials examined nursing education programs. One reported better practice scores and markedly different VAP incidence after four infection-control and ventilator-care sessions, while another found no significant change in VAP but a reduction in overall healthcare-associated infections. Two small trials evaluated nebulized 3% hypertonic saline. Both reported lower VAP incidence and shorter ventilation exposure, but the authors judged the evidence low certainty because of small samples, single-center designs and variable protocols. Environmental studies produced mixed results: copper plating and ultraviolet-C treatment reduced healthcare-associated infection rates without a statistically significant VAP effect, while an upper-room ultraviolet germicidal system was associated with fewer VAP episodes, lower tracheal microbial loads and less antibiotic use in one study. These findings describe associations from limited studies rather than establishing the effectiveness of each approach across neonatal intensive care units.

The certainty assessment rated evidence for preventive bundles and oral care as moderate, evidence for ventilator-care strategies and nebulization as low, and evidence for education and environmental interventions as very low to low. The analysis included studies from several countries, with seven conducted in the United States, six in India and five in Egypt. Eighteen of the 34 studies were randomized controlled trials, and 14 used CDC criteria to define VAP. Most enrolled high-risk neonatal groups, particularly preterm and very-low-birth-weight infants, although mechanical-ventilation indications were not reported in 18 studies. Mechanical-ventilation status was not clearly restricted in every included report, so the 6,301 participants should not all be described as ventilated neonates. Study populations ranged from 12 to 1,465 infants, with a mean of 186 per study. Methodological quality scores ranged from 16 to 33 out of 36, with a mean of 25.4, assessed using the Methodological Standards for Epidemiological Research scale.

Several features limit how confidently the results can be applied. In addition to varied bundle composition, studies differed in baseline pneumonia risk, gestational age, birth weight, intervention protocols and diagnostic definitions. This variation could cause the same clinical presentation to be classified differently across studies. Some reports did not clearly restrict enrollment to mechanically ventilated infants or provide an adequately detailed mechanical-ventilation-day denominator, potentially diluting associations with VAP. Nine non-English articles were excluded because reliable translation and detailed extraction were not feasible, and several quality-improvement reports were excluded for lacking extractable VAP data. Most bundle evidence also came from before-and-after evaluations, which are vulnerable to confounding by concurrent changes in care. Finally, few studies assessed long-term outcomes, cost-effectiveness, sustainability, implementation barriers or performance in resource-limited units.

Overall, the synthesis provides a focused meta-analytic assessment of primary prevention interventions for VAP in ventilated neonates, including outcomes adjusted for mechanical-ventilation days. The strongest and most consistent signal was for multicomponent quality-improvement bundles, which were associated with lower odds, lower incidence rates and an absolute reduction of about eight VAP cases per 1,000 mechanical-ventilation days. Oral care was also associated with lower odds, including in trials and studies focused on ventilated infants, but small-study effects, publication bias, inconsistent subgroups and variable VAP definitions limit confidence in the size of that benefit. The authors call for future multicenter studies with standardized VAP definitions, stronger controlled designs, detailed reporting of bundle components and implementation fidelity, and consistent use of mechanical-ventilation-day-adjusted outcomes. Until then, the pooled bundle estimate should be understood as the association with a diverse quality-improvement program, not proof that a particular bundle or individual component is responsible.

Subject of Research: Meta-analysis of primary prevention interventions for ventilator-associated pneumonia in neonates receiving mechanical ventilation

Article Title: Primary preventive interventions to reduce ventilator-associated pneumonia in neonatal intensive care units: a meta-analysis

Article References: Elmakaty, I., Karen, O., Kokash, R., Al-Sayegh, N. F., Bacha, K. M., Abdelhady, I., & Gad, A. (2026). Primary preventive interventions to reduce ventilator-associated pneumonia in neonatal intensive care units: a meta-analysis. Pediatric Research. https://doi.org/10.1038/s41390-026-05562-8

Image Credits: AI Generated

DOI: 10.1038/s41390-026-05562-8

Keywords: neonatal intensive care, ventilator-associated pneumonia, quality-improvement bundles, oral care, mechanical ventilation, preventive interventions, systematic review, meta-analysis, neonatal infection, evidence synthesis, Primary, preventive

The episode occurred during the woman’s ninth hospital admission at an intensive care unit in China. She had chronic respiratory dysfunction and type II respiratory failure and required long-term tracheostomy and mechanical ventilation. Her medical history included coronary artery disease, heart failure, Parkinson disease, sequelae of cerebral infarction, diabetes and hypertension. The affected device was a cuffed percutaneous dilatational tracheostomy tube with a 7.0-mm internal diameter and a 10.5-mm external diameter. It had been inserted in March 2021 and last replaced in August 2023.

On the morning of February 26, 2024, an intensive care nurse heard the new leak while the patient was receiving mechanical ventilation. A ventilator alarm sounded at the same time, and displayed tidal volume decreased. Inspection of the external assembly showed that the blue pilot balloon, including its Luer one-way valve, had detached entirely and was no longer present. A residual segment of inflation line nevertheless remained connected to the tracheostomy tube. The combination of physical findings and ventilator changes supported failure of the cuff inflation system rather than an isolated equipment malfunction.

Replacing the tube was considered, but bedside examination by an otolaryngology team identified granulation tissue below the tracheostomy stoma. The surrounding area was clean and had no obvious secretions, yet removal appeared potentially difficult. The specialists warned that exchange could produce bleeding, aspiration, respiratory difficulty or loss of the airway. Chest computed tomography documented post-tracheostomy changes, bronchitis, bilateral pneumonia resembling earlier imaging, bilateral pleural effusions and adjacent incomplete lung expansion, but did not report peri-tracheostomy granulation or airway narrowing. No event-specific bronchoscopy was documented, so the airway-risk assessment was clinical rather than bronchoscopic.

Intensive care and otolaryngology clinicians explained both the consequences of continuing with the failed cuff system and the hazards of immediate exchange to the family. After informed shared decision-making, the team and family chose to defer replacement, retain the existing tube and continue ventilatory support under close observation. The report emphasizes that family preference was not itself the clinical justification. Bridge management was considered temporarily acceptable because the specialist assessment indicated that immediate exchange carried substantial patient-specific risks, while the teams remained prepared to escalate if ventilation or oxygenation could not be maintained.

To obtain temporary access to the cuff, a nurse inserted the needle supplied with a 1-mL syringe into the lumen of the residual inflation line using a 5-mL syringe. Air was introduced incrementally, and after approximately 3 mL had been delivered, the audible leak and ventilator leak alarm were no longer present at that observation. The needle was removed and the residual line occluded with a straight haemostatic clamp to limit air escape. Because both the pilot balloon and one-way valve were absent, the usual cuff-manometer connection did not exist and intracuff pressure could not be measured by the standard method.

The injected volume was specific to this event rather than a target, and it cannot establish that a safe cuff pressure, clinical efficacy or procedural safety had been achieved. A fixed quantity of air cannot reliably be translated into a known pressure across different tube designs and anatomical conditions. The maneuver also did not reconstruct either missing component or restore a durable seal. Its potential hazards include uncontrolled intracuff pressure, overinflation, cuff rupture, damage to the inflation line, inadvertent air loss, loss of positive-pressure ventilation and airway injury. Accordingly, the authors describe the technique as an exceptional bridge for a single high-risk case, not as a recommended bedside procedure.

The available records did not provide a controlled assessment of the intervention. They contained routine hourly observations rather than measurements designed as immediate paired pre- and post-procedure comparisons. At 07:00, oxygen saturation was 99%, heart rate 79 beats per minute, respiratory rate 19 breaths per minute and blood pressure 112/46 mmHg; peak and mean airway pressures were approximately 21 and 11 cmH₂O, respectively, with displayed tidal volume of about 491 mL. The 08:00 ventilator record noted P-SIMV mode, positive end-expiratory pressure of 5 cmH₂O, inspired oxygen fraction of 50%, airway pressures of approximately 20 and 11 cmH₂O and displayed tidal volume of about 466 mL. At 09:00, oxygen saturation was 100% and respiratory rate was 14 breaths per minute. Delivered and exhaled tidal volumes were not recorded as paired measurements, minute ventilation was unavailable, and no arterial blood gases were linked specifically to the failure and intervention.

Intermittent leakage continued through the hospital stay, demonstrating that the bridge did not produce normal or sustained cuff function. On February 29, the patient remained on P-SIMV ventilation with positive end-expiratory pressure of 5 cmH₂O and an inspired oxygen fraction of 50%; oxygen saturation was 100%, but air leakage around the tracheostomy was still recorded. At discharge on March 6, she still required P-SIMV, now with positive end-expiratory pressure of 6 cmH₂O and an inspired oxygen fraction of 60%. Air leakage was described as obvious, with episodic tachypnea and continued sputum production. The defective tube remained in place, and no reliable post-discharge follow-up was available. Because the device was not removed, the investigators could not inspect it or determine why the pilot balloon detached.

The single retrospective case offers no proof that the maneuver is effective, reproducible, safe or generalizable. It lacked intracuff-pressure measurement, event-specific arterial blood gases, paired ventilator measurements and complete complication surveillance. Staff retrospectively recalled that cuff reinflation was commonly needed two to four times daily, usually with about 3 mL of air, but those estimates were not contemporaneous quantified data. The transferable lesson is therefore not the injected volume or needle-and-clamp technique. It is the need to recognize cuff-system failure promptly, combine patient findings with ventilator information and physical inspection, obtain early airway expertise, assess whether exchange is feasible and involve the family in an informed decision. Definitive management still requires replacement of an irreparable tracheostomy tube whenever it can be done safely.

Subject of Research: Management of pilot-balloon detachment in a ventilator-dependent tracheostomy patient

Article Title: Case report: complete pilot balloon detachment in a ventilator-dependent patient with high-risk tracheostomy exchange

Article References: Lai, X., Huang, Y., Hu, M., & Huang, L. (2026). Case report: complete pilot balloon detachment in a ventilator-dependent patient with high-risk tracheostomy exchange. Frontiers in Medicine, 13, Article 1994056. https://doi.org/10.3389/fmed.2026.1994056

Image Credits: AI Generated

DOI: 10.3389/fmed.2026.1994056

Keywords: tracheostomy, mechanical ventilation, pilot balloon, cuff failure, airway management, case report, intensive care, tracheostomy exchange, airway leak, Case, report, complete

For comparison, they selected 78 children with severe adenovirus pneumonia but without encephalitis or encephalopathy. Because this was a single-center retrospective analysis, the findings describe associations in these hospitalized groups and do not establish the independent effects of treatment or the broader course of adenovirus infection in children. The median age of the children with encephalitis or encephalopathy was 18.0 months, with ages reported as 7.5–37.0 months, and 32 of the 53 children, or 60.4%, were male.

Altered mental status was common: 48 children, or 90.6%, had listlessness, 33, or 62.3%, had dysphoria, and 25, or 47.2%, had hypersomnia. Seven children, representing 13.2% of the group, had seizures. Children with encephalitis or encephalopathy had different laboratory profiles from controls.

Their median leukocyte count was 7.39 × 10^9/L, median procalcitonin concentration was 1.885 ng/mL, and median lactate dehydrogenase concentration was 980.50 U/L. The corresponding differences from the control group were significant, with P values of 0.011, 0.001 and less than 0.001. Nasopharyngeal adenovirus load did not differ significantly between the groups. Leukopenia, hypoproteinemia, liver function impairment, coagulopathy and anemia were also more frequent among children with encephalitis or encephalopathy.

These findings show differences in measured clinical characteristics rather than evidence that any one laboratory abnormality caused the neurological complication. Respiratory support was common in the affected group. Treatment records also showed that 49 children, or 92.45%, received gamma globulin, 28, or 52.83%, received albumin, and 14, or 26.42%, received a blood transfusion.

The study documents treatment use but does not determine whether any of these interventions affected survival or later outcomes. At approximately six months, bronchiolitis obliterans was present in 19 of 50 survivors in the affected group, compared with 9 of 78 controls, or 11.54% (P = 0.001). Overall, the results show a cohort characterized by severe respiratory illness, altered mental status and frequent mechanical ventilation, with generally favorable reported neurological outcomes at six months but a substantial burden of pulmonary sequelae.

The retrospective design, single-center setting and small groups limit causal interpretation and generalization beyond the studied population.

Subject of Research: Six-month clinical and pulmonary outcomes in children with severe adenovirus pneumonia complicated by encephalitis or encephalopathy

Article Title: Clinical characteristics and half-year outcomes of 53 children with severe adenovirus pneumonia complicated with encephalitis or encephalopathy

Article References: Zeng, L., Wei, J., Liu, E., Li, Q., & Zang, N. (2026). Clinical characteristics and half-year outcomes of 53 children with severe adenovirus pneumonia complicated with encephalitis or encephalopathy. BMC Pediatrics. https://doi.org/10.1186/s12887-026-07747-w

Image Credits: AI Generated

DOI: 10.1186/s12887-026-07747-w

Keywords: adenovirus, pediatric pneumonia, encephalitis, encephalopathy, bronchiolitis obliterans, mechanical ventilation, retrospective cohort, child health, Clinical, characteristics, half-year, outcomes

The absolute event rates differed between the databases, underscoring the importance of distinguishing a reproducible relative association from a universal risk estimate. In MIMIC-IV, invasive reintubation within 48 hours occurred in 13.6% of 1,124 extubations with calculated osmolality above 300 mOsm/kg and 10.8% of 1,515 extubations at or below that level, an absolute difference of 2.8 percentage points. In eICU-CRD, the respective rates were 10.5% of 486 extubations and 4.6% of 904, a difference of 5.8 percentage points. The association also persisted when the outcome window was extended to 72 hours, with adjusted risk ratios of 1.25 (1.02–1.52) in MIMIC-IV and 1.53 (1.19–1.97) in eICU-CRD. The replication therefore involved the same exposure definition, outcome definitions, adjustment variables, transformations and analytic plan, rather than a threshold or model selected from the replication dataset.

Calculated serum osmolality was derived from the most recent complete set of sodium, glucose and blood urea nitrogen measurements available within 24 hours before extubation, with no more than two hours separating component collection times. The formula was 2 × sodium + glucose/18 + blood urea nitrogen/2.8, with sodium in millimoles per liter and glucose and blood urea nitrogen in milligrams per deciliter. Median calculated osmolality was 297.5 mOsm/kg in MIMIC-IV and 295.2 mOsm/kg in eICU-CRD; 42.6% and 35.0% of the respective cohorts exceeded 300 mOsm/kg. The investigators emphasized that this calculated value is not interchangeable with directly measured serum osmolality or effective osmolality, which excludes urea. It functions instead as a practical summary combining water–solute balance, glycemic stress and renal or catabolic burden using routinely available laboratory data.

The retrospective cohort included the first eligible extubation in each hospital admission after adults had received invasive mechanical ventilation. Exclusions covered tracheostomy conversion, terminal or palliative extubation, death-related cessation of ventilation and boundaries that could not be classified reliably. Noninvasive ventilation, continuous or bilevel positive airway pressure, high-flow nasal oxygen and standby ventilator modes were not treated as invasive ventilation. Invasive reintubation was tracked throughout the same hospital admission, and noninvasive respiratory support alone did not count as reintubation. Sensitivity analyses addressed planned versus unplanned extubation, potentially procedure-related reintubation, repeated admissions, narrower exposure windows, respiratory severity, fluid balance, renal status and identifiable hypertonic treatment.

Adjustment covered age, sex, ventilation duration, pre-extubation respiratory rate, oxygen saturation, Glasgow Coma Scale score, serum creatinine and vasopressor use during the preceding 24 hours. Missing covariates were handled separately within each database with 30 multiply imputed datasets, and complete-case analyses served as sensitivity checks. Additional respiratory adjustment had little effect within the subsets where PaO2/FiO2 was recorded. For example, in 1,329 MIMIC-IV extubations with 169 reintubations, the risk ratio was 1.47 both before and after adjustment for the oxygenation ratio. In 771 eICU-CRD extubations with 52 events, the corresponding estimates were 1.21 and 1.23, although their confidence intervals included no association. Adjustment for recorded fluid balance, loop-diuretic exposure and creatinine-based acute kidney injury likewise produced little change in the main pattern, but several analyses contained few events and were imprecise.

Exposure shape and biochemical-component analyses suggested that the result was not explained by a single laboratory value. Neighboring thresholds of above 295, 300 and 305 mOsm/kg produced associations in the same direction, although precision varied. An exploratory MIMIC-IV-derived threshold of 301.964 mOsm/kg, applied unchanged to eICU-CRD, corresponded to a risk ratio of 2.04 (1.41–2.96), but bootstrap-derived thresholds had substantial dispersion. Continuous associations differed between databases: each 10-mOsm/kg increase had an adjusted risk ratio of 1.03 (0.96–1.11) in MIMIC-IV and 1.21 (1.06–1.39) in eICU-CRD. Neither restricted cubic spline analysis showed evidence of nonlinearity. Separately modeled sodium, glucose and blood urea nitrogen did not reproduce the categorical association across both databases, while effective osmolality, which excludes urea, showed weaker estimates. The authors consequently interpret 300 mOsm/kg as a pragmatic stratification point rather than a sharply defined biological threshold.

Competing-event analyses showed that hyperosmolarity was also associated with death before reintubation within 48 hours. Cause-specific hazard ratios were 1.29 (1.02–1.63) in MIMIC-IV and 1.96 (1.34–2.89) in eICU-CRD, while Fine–Gray subdistribution hazard ratios were 1.34 (1.06–1.69) and 2.03 (1.45–2.86), respectively. For a composite endpoint of reintubation or death, however, the adjusted risk ratios attenuated to 1.09 (0.97–1.23) and 1.42 (1.13–1.78). This pattern indicates that some of the association with reintubation overlaps with a broader association involving mortality. It also reinforces the need to interpret calculated hyperosmolarity as a marker of overall illness severity rather than as an isolated mechanism specific to airway failure.

Secondary prognostic analyses found that calculated hyperosmolarity added little to the transportable accuracy of existing clinical models. In external validation with MIMIC-IV coefficients fixed before transfer to eICU-CRD, the area under the receiver operating characteristic curve increased from 0.5875 for the base model to 0.6074 after adding calculated hyperosmolarity. The numerical difference was 0.0199, but its 95% confidence interval ranged from −0.0327 to 0.0434 and included no improvement. Differences in precision–recall area and Brier score were also small. Original external validation indicated overprediction of absolute risk in eICU-CRD, with observed-to-expected ratios of 0.45 for both the base and osmolality-augmented models. The results support the marker’s value as an adjunctive risk signal, not as a replacement for respiratory mechanics, airway protection, secretion management, neurologic function or other established elements of extubation assessment.

The study has important limitations inherent to retrospective electronic health record research. Residual confounding is possible because cough strength, secretion burden and the rapid shallow breathing index could not be harmonized across databases. The eICU-CRD lacked a comparably reliable field for distinguishing planned from unplanned extubation, while treatment documentation was incomplete, particularly for medication names and high-flow nasal oxygen. Oxygenation and fluid data were available only in selected subsets, acute kidney injury was defined from serum creatinine rather than complete urine-output and kidney-replacement-therapy criteria, and calculated osmolality was not a direct laboratory measurement. Explicit causes of reintubation were recorded for too few events, and post-extubation laboratory sampling was influenced by the opportunity to obtain measurements. With only 93 primary reintubation events in eICU-CRD, some subgroup estimates were especially unstable. Both databases also represent US critical care practice, so replication in contemporary non-US cohorts would be needed to assess broader generalizability. The findings support prospective evaluation of calculated osmolality as a complementary component of extubation assessment, rather than a validated treatment threshold.

Subject of Research: Association of pre-extubation calculated serum hyperosmolarity with early invasive reintubation in critically ill adults

Article Title: Pre-extubation calculated serum osmolality and early invasive reintubation in critically ill adults: a dual-database study with multicenter external replication

Article References: Huang, W., Bian, J., Chen, Y., Huang, B., Liu, C., & Chen, C. (2026). Pre-extubation calculated serum osmolality and early invasive reintubation in critically ill adults: a dual-database study with multicenter external replication. Frontiers in Medicine, 13, Article 1984164. https://doi.org/10.3389/fmed.2026.1984164

Image Credits: AI Generated

DOI: 10.3389/fmed.2026.1984164

Keywords: calculated serum osmolality, extubation, invasive reintubation, critical care, mechanical ventilation, hyperosmolarity, metabolic–renal status, retrospective cohort study, MIMIC-IV, eICU-CRD, Pre-extubation, calculated

Investigators reviewed records from 2,514 unique ICU admissions at a tertiary hospital between August 2024 and August 2025. Candiduria was defined as growth of at least 10,000 colony-forming units per milliliter in a urine culture. It was detected in 371 patients, or 14.8% of the unique admissions, and 296 met the study’s eligibility criteria. Subsequent candidemia was defined as isolation of Candida species from a blood culture within 30 days after candiduria. Patients were grouped according to whether they developed this outcome, and the researchers compared their demographic, clinical, laboratory, treatment and mortality data. They also evaluated the distribution of Candida species and the antifungal susceptibility of bloodstream isolates.

After adjustment in the analysis, documented renal failure was associated with subsequent candidemia with an odds ratio of 2.08, while mechanical ventilation had an odds ratio of 2.23. Each additional point on the Sequential Organ Failure Assessment score was associated with an odds ratio of 1.15, and each additional seven days from ICU admission to candiduria had an odds ratio of 1.29. These results show associations with greater illness severity and longer ICU exposure among patients who already had candiduria; they do not demonstrate that any of these factors caused candidemia.

The primary model combined available variables to distinguish patients who later developed candidemia and achieved an area under the receiver operating characteristic curve of 0.767. Urine erythrocyte count alone had limited discrimination, with an area under the curve of 0.608. The comparison indicates that the multi-variable model was more informative than this urine measurement in the analyzed cohort. It does not establish that the model is sufficiently validated for routine surveillance or individual clinical decisions, and the investigators characterized the results as hypothesis-generating pending external validation.

ICU mortality was 68.6% across the analyzed cohort and 84.7% among patients who developed subsequent candidemia. The study does not establish that candiduria or candidemia caused these deaths. Its retrospective design, single-hospital setting and one-year observation period constrain generalization, while restricting the analysis to patients with candiduria means the findings apply to that selected group rather than to all critically ill adults. The evidence also cannot determine whether urine Candida directly originated the later bloodstream infection. Taken together, the results show that renal failure, mechanical ventilation, higher SOFA scores and longer time between ICU admission and candiduria marked ICU patients with a higher observed likelihood of subsequent candidemia, while leaving the causal role and independent prognostic value of candiduria unresolved.

Subject of Research: Clinical factors associated with subsequent candidemia among adult ICU patients with candiduria

Article Title: Candiduria in intensive care unit: differentiating a benign finding from a warning signal for subsequent candidemia

Article References: Oz, E., Tasdogan, A. M., Ozturk, M., Erinmez, M., & Zer, Y. (2026). Candiduria in intensive care unit: differentiating a benign finding from a warning signal for subsequent candidemia. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14423-y

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14423-y

Keywords: candiduria, candidemia, intensive care, Candida, bloodstream infection, retrospective cohort, renal failure, mechanical ventilation, illness severity, intensive, care, unit

Although practical, structured training in ventilation is described as an important but limited part of critical-care education, opportunities to undertake such training remain restricted. The study therefore evaluated a course designed to combine theoretical instruction with simulation-based practice in managing acute respiratory failure. Because the sample was small and the reported evaluation covered immediate course outcomes, the findings cannot establish whether the gains were sustained or transferred to clinical practice.

Before the intervention, all 17 residents completed a questionnaire containing a standardized 15-item multiple-choice examination. They were subsequently assigned to one of two educational groups: group A received theory-based classes only, while group B received theory-based classes plus practice-based simulation. Skill was assessed through the examination rather than through direct observation of residents managing patients in intensive care, making the measured outcome an assessment of knowledge and skills associated with the course.

The simulation component consisted of four scenarios involving acute exacerbations of chronic lung disease. Residents practiced using high-flow nasal oxygen, non-invasive ventilation and mechanical ventilation under simulated conditions. Following the intervention, skill-assessment scores increased in all three respiratory modalities in group B, which combined classes with simulation.

In group A, increases were reported for high-flow nasal oxygen and non-invasive ventilation, while no increase was reported for mechanical ventilation. Scores did not differ between the three ventilation modalities at baseline or after the intervention. At baseline, senior residents had higher scores than junior residents; after training, higher scores were observed among both senior and junior residents in group B, but among senior residents only in group A.

Course satisfaction was also high. Both junior and senior residents reported gains in confidence and perceived competence, although these were self-reported experiences and were not accompanied by evidence of improved patient outcomes. The results are consistent with the course’s stated aim of strengthening residents’ ability to manage ventilatory support for acute respiratory failure, but the assessment does not establish that the training altered treatment decisions, reduced clinical delays or improved the care received by critically ill patients.

Nor did the study determine whether the score increases remained after participants returned to clinical work or whether the same approach would be useful for other members of the care team. Overall, the study provides measured support for adding structured simulation to respiratory intensive care education. Its clearest finding is that residents who received both theory and practice recorded post-course assessment gains across all three ventilation modalities, while the classroom-only group recorded gains in two.

The authors identified long-term retention, transfer to clinical practice and inter-professional applications as important questions for future work. Until those issues are addressed, the results should be viewed as evidence of immediate assessment gains from a combined ventilation course rather than proof of superior training, durable competence or better patient outcomes.

Subject of Research: Evaluation of a simulation-based ventilation training course for pulmonology residents in respiratory intensive care.

Article Title: Impact of a simulation-based ventilation training course for respiratory intensive care residents

Article References: Artaud-Macari, E., Fresnel, E., Kerfourn, A., Melone, M.-A., Mazellier, N., Roger, P.-A., Lebret, M., Cuvelier, A., Girault, C., Médrinal, C., & Salaün, M. (2026). Impact of a simulation-based ventilation training course for respiratory intensive care residents. BMC Medical Education. https://doi.org/10.1186/s12909-026-10046-8

Image Credits: AI Generated

DOI: 10.1186/s12909-026-10046-8

Keywords: simulation-based medical education, pulmonology residents, respiratory intensive care, acute respiratory failure, mechanical ventilation, non-invasive ventilation, high-flow nasal oxygen, clinical skills training, medical education, Impact, simulation-based, ventilation

ARDS is a clinical syndrome of acute hypoxemic respiratory failure and bilateral lung opacities that develops after direct pulmonary insults such as pneumonia or aspiration, or indirect insults such as sepsis, trauma or pancreatitis. Its Berlin definition helps distinguish it from cardiac failure and fluid overload, but the diagnostic criteria do not capture major differences in the injury to alveolar epithelium, pulmonary endothelium, blood vessels and other organs. Even with lung-protective ventilation, prone positioning and neuromuscular blockade, in-hospital mortality remains about 30% to 40%. A patient classified simply as having ARDS may therefore have very different combinations of inflammation, tissue damage, circulatory strain and mechanical vulnerability.

The central hyperinflammatory and hypoinflammatory framework is generated most often through latent class analysis or related data-driven methods using plasma biomarkers, including interleukin-6, interleukin-8, soluble tumor necrosis factor receptor 1 and angiopoietin-2. Hyperinflammatory patients tend to have greater organ dysfunction, shock and metabolic acidosis, with mortality exceeding 40% in several cohorts. The hypoinflammatory group generally has less systemic inflammation and better survival, although its reported outcomes have not been uniform across studies. Hyperinflammatory status is more common early in critical illness, and longitudinal analyses indicate that some patients transition toward a less inflammatory state. That dynamism argues against relying on a single measurement made at admission and supports reassessment as an illness evolves.

At the tissue level, ARDS begins with disruption of the alveolar-capillary barrier, allowing protein-rich fluid to enter the lungs and impairing gas exchange. Angiopoietin-2, high-mobility group box 1 and receptor for advanced glycation end products are among the mediators linked to endothelial and epithelial injury, while mitochondrial dysfunction in alveolar type II cells may connect oxidative stress with impaired surfactant production, defective fluid clearance and fibrosis. Immune differences are similarly complex. Transcriptomic studies associate the hyperinflammatory state with innate immune activation, granulopoiesis, interferon signaling and stress responses, whereas relatively greater expression of adaptive immune genes has been observed in hypoinflammatory profiles. Metabolic studies also associate the more inflammatory group with lipid dysregulation and a shift toward glycolysis.

Those systemic patterns do not necessarily represent what is happening inside the alveoli. Classifications based on bronchoalveolar lavage fluid overlap only partly with those based on plasma, and one study found no significant differences in local inflammatory mediators between plasma-defined “reactive” and “uninflamed” groups. Bronchoalveolar classifications containing interleukin-6, von Willebrand factor, soluble programmed cell-death receptor 1 and neutrophil percentage have instead correlated closely with oxygenation and ventilatory measures. Lung-microbiome findings likewise show limited concordance with circulating inflammatory classes, even though greater bacterial burden, reduced diversity and gut-associated bacterial translocation have been associated with heightened inflammation. The mismatch means that a patient labeled hypoinflammatory in blood may still have substantial pulmonary injury requiring a different therapeutic strategy.

Respiratory mechanics and imaging reveal another axis of heterogeneity. Machine-learning models using compliance, driving pressure, ventilation ratio and mechanical power distinguish restrictive cases with poor distensibility, gas-exchange impairment and elevated risk of ventilator-induced lung injury from more efficient physiological profiles. Rising ventilation ratio or mechanical power can identify worsening trajectories associated with mortality and fewer ventilator-free days. Computed tomography can separate focal disease, characterized by gravity-dependent consolidation, from diffuse disease with widespread ground-glass opacities or consolidation. Focal lungs tend to be less recruitable and may be harmed by indiscriminate increases in positive end-expiratory pressure, or PEEP, whereas diffuse lungs may recruit and improve oxygenation with higher PEEP or prone positioning. Imaging patterns overlap only weakly with inflammatory biomarker classes, indicating that morphology and systemic biology capture different dimensions of injury.

Circulatory complications introduce further distinctions. Analyses combining echocardiography and hemodynamic data have identified four cardiovascular profiles: normal ventricular function, right ventricular dilation with preserved systolic function, right ventricular dilation with impaired contraction and hyperdynamic left ventricular function. Patients with dilation and systolic impairment had 90-day mortality of 78% in one analysis, while a COVID-19 ARDS cohort reported 73% in the corresponding group. Right ventricular strain may reflect pulmonary hypertension, hypoxic vasoconstriction, microthrombi and elevated intrathoracic pressure. In patients receiving venovenous extracorporeal membrane oxygenation, retrospective classifications have separated “wet,” “dry” and “fibrotic” profiles. The fibrotic group had a more prolonged course and elevated risk of intracranial hemorrhage, but these retrospective associations do not establish that phenotype-based anticoagulation or other interventions improve outcomes.

Mechanisms involving regulated cell death add both opportunities and cautions. Ferroptosis has been linked to iron accumulation, lipid peroxidation, glutathione depletion and impaired antioxidant defenses in epithelial, endothelial, macrophage and neutrophil compartments. Ferrostatin-1, liproxstatin-1, melatonin and dipyridamole have reduced ferroptosis-related lung injury in various animal and cellular models, and a nonrandomized dipyridamole study included only five patients with moderate-to-severe ARDS. Pyroptosis, especially in alveolar and recruited macrophages, can amplify cytokine release, damage signals and barrier disruption through inflammasome and gasdermin pathways. Human studies have linked these signals with outcomes, but they do not directly demonstrate active pyroptotic death in vivo, and no clinical trial has established that selectively inhibiting it improves ARDS outcomes. Neither process has yet been validated as a separate clinical subphenotype.

Translation depends first on classification tools that are rapid, inexpensive, reproducible and simple enough for bedside use. The review describes simplified models based on small sets of biomarkers and clinical variables, including angiopoietin-2, soluble tumor necrosis factor receptor 1, procalcitonin and bicarbonate, and a two-marker score using interleukin-8 and soluble ST2 among patients receiving high-flow nasal oxygen. These tools require independent, multicenter prospective validation, including assessment of whether they predict treatment response rather than merely prognosis. Prospective randomized trials would need to assign patients with validated subtypes to targeted interventions or standard care, account for transitions between phenotypes and test whether enrichment improves statistical power. Candidate approaches include immunomodulation for hyperinflammatory disease, morphology-guided PEEP, personalized ventilation and targeted prevention of right ventricular failure, but none should be treated as established subtype-specific therapy on the current evidence.

Future systems may combine clinical observations, continuous ventilator data, imaging, blood biomarkers, transcriptomics, proteomics, metabolomics and microbiome measurements. Artificial intelligence could detect nonlinear patterns across these sources, while longitudinal monitoring could create an evolving digital representation of each patient rather than a fixed label. The review cites early multimodal models that combine CT radiomics with clinical information, and ongoing work is collecting ventilator waveforms, imaging and biospecimens to define biologically grounded endotypes. Major obstacles remain, including standardized data collection, transportability between hospitals, interpretability, privacy and prospective clinical validation. The practical advance is thus not a claim that ARDS has already become a precision-medicine disease, but that its traditional diagnostic label can increasingly be decomposed into testable biological and physiological states that might reveal which patients are likely to benefit from which interventions.

Subject of Research: Biological, physiological and imaging-based subphenotypes of acute respiratory distress syndrome

Article Title: Acute respiratory distress syndrome subphenotypes: the translational path from pathobiology to precision medicine

Article References: Shao, H., Bai, T., Zhang, T., Qiao, Y., & Li, Y. (2026). Acute respiratory distress syndrome subphenotypes: the translational path from pathobiology to precision medicine. Frontiers in Pharmacology, 17, Article 1947054. https://doi.org/10.3389/fphar.2026.1947054

Image Credits: AI Generated

DOI: 10.3389/fphar.2026.1947054

Keywords: acute respiratory distress syndrome, ARDS subphenotypes, precision medicine, hyperinflammation, biomarkers, lung inflammation, mechanical ventilation, right ventricular dysfunction, clinical trials, artificial intelligence, Acute, respiratory

The study abstract describes recruitment between November 20, 2024, and July 15, 2025, at four governmental hospitals: Al-Shaheed Al-Sadder Teaching Hospital, Al-Hakeem Teaching Hospital, Al-Zahrawi Surgical Hospital and Child & Maternal Hospital. Participants were selected through non-probability purposive sampling and had to have at least one year of ICU experience and direct involvement in caring for mechanically ventilated patients. Data came from a structured, self-administered questionnaire covering demographic characteristics and 20 knowledge questions, each scored as one point for a correct answer and zero for an incorrect answer.

The largest measured gaps involved forced artificial respiration, for which 90.8% of nurses answered incorrectly; interpretation of high-pressure alarms, with 89.5% incorrect; and prevention of ventilator-associated pneumonia, with 81.6% incorrect. The primary inferential analysis was a hierarchical multiple linear regression using the continuous knowledge score for all 152 participants. Together, personal characteristics, experience-related variables and training-related variables accounted for 48.2% of the variance in knowledge, with an adjusted R² of 0.456. The training block added 0.183 to R², and the block-level change was significant at p < 0.001.

An exploratory binary logistic regression examined the 12 nurses who reached the study’s adequate-knowledge threshold. In that small model, each additional year of ICU experience was associated with an odds ratio of 1.21 for adequate knowledge, while participation in at least five training sessions was associated with an odds ratio of 4.40. The investigators cautioned that the model had approximately three events per predictor, was neither adequately powered nor internally validated, and was therefore exploratory. Its reported correct-classification rate of 82.9% and area under the curve of 0.871 may be optimistic.

The study also used a failure mode and effects analysis-derived Patient-Safety Risk Index, calculated from the same item-level error rates as the knowledge score. Because this index is a severity- and detectability-weighted transformation of those data, its inverse relationship with knowledge is not independent evidence that patients experienced harm. The research did not directly assess patient outcomes, clinical errors, deterioration or deaths. Accordingly, its findings identify measured knowledge deficits and associated training and experience variables among the participating nurses in Amara City, but do not establish the frequency or clinical consequences of unsafe practice. The investigators proposed prospective evaluation of structured simulation-based ventilation training, alarm-management and ventilator-associated pneumonia bundle education, and tier-based clinical decision support; the study itself did not test those interventions or demonstrate clinical benefit.

Subject of Research: Measured mechanical-ventilation knowledge among ICU nurses in four hospitals in Amara City, Iraq

Article Title: Hidden knowledge gaps in mechanical ventilation care: a multicenter study of ICU nurses’ competence and patient safety risks in Iraq

Article References: Arrar, A. A., Radhi, T. A., Hussein, H. A., Hassooni, M. K., Hafedh, M. H., & Saber, A. F. (2026). Hidden knowledge gaps in mechanical ventilation care: a multicenter study of ICU nurses’ competence and patient safety risks in Iraq. BMC Nursing. https://doi.org/10.1186/s12912-026-05371-8

Image Credits: AI Generated

DOI: 10.1186/s12912-026-05371-8

Keywords: mechanical ventilation, ICU nursing, knowledge assessment, patient safety, ventilator alarms, ventilator-associated pneumonia, Iraq, cross-sectional study, Hidden, knowledge, gaps, mechanical

Infants were eligible if they were born at 28 to 32 weeks of gestation, weighed less than 2,500 grams at birth, entered the study neonatal intensive care unit within 24 hours with stable vital signs, and initially received nasogastric or orogastric tube feeding, with or without parenteral nutrition. The investigation took place at the Affiliated Hospital of Shandong Medical and Pharmaceutical University in Binzhou, China, from May 2025 through April 2026. It deliberately enrolled only infants who received a uniformly prepared preterm formula, a design choice intended to reduce variation in feeding type rather than a description of all feeding practices in the unit. The researchers excluded infants with major congenital anomalies or neonatal complications including intraventricular hemorrhage, necrotizing enterocolitis, and sepsis.

Of 245 enrolled infants, 27 were excluded before oral feeding began because their condition worsened, they were transferred, or treatment was withdrawn, while five were lost during follow-up. The final cohort had a mean gestational age of 30.7 weeks and a mean oral-feeding-ability score that rose from 22.03 with a standard deviation of 2.95 on the first day after initiation to 34.41 with a standard deviation of 3.67 on Day 14. Generalized estimating equations, which accounted for correlation among repeated measurements, confirmed a significant overall increase across the five assessment points. The assessments occurred on Days 1, 3, 7, 10, and 14, with each daily score calculated from three scheduled feeding sessions.

Feeding ability was measured with the Chinese version of the Oral Feeding Ability Scale for Preterm Infants, a 23-item instrument covering pre-feeding condition, sucking, swallowing, and physiological stability during feeding. Each item was scored from 0 to 2, producing a total range of 0 to 46, with higher scores indicating greater ability. The scale’s internal consistency in this population was reported as acceptable, with a Cronbach’s alpha of 0.784. Because no validated score thresholds classify feeding ability into clinically defined categories, researchers analyzed the totals as a continuous variable. A session could still be scored when sucking or swallowing could not be elicited, in which case a zero was recorded for the affected dimension rather than excluding the observation.

Latent class growth modeling was used to determine whether infants followed different longitudinal patterns hidden by the group average. Models containing one through five classes were compared using information criteria, class separation, statistical tests, parsimony, clinical interpretability, and class size. The three-class solution was selected because it produced lower Akaike, Bayesian, and sample-size-adjusted Bayesian information criteria than the two-class model, while the Vuong–Lo–Mendell–Rubin and bootstrap likelihood-ratio tests supported the addition of a third class. Entropy was 0.949, indicating good separation, although the two-class model had a slightly higher value of 0.987. Models with four and five classes were not adopted because the additional classes were very small and the VLMR test did not support them.

The high-start rapid-rise group contained 67 infants and began with an estimated score of about 26. Its trajectory rose to approximately 28 on Day 3, 32 on Day 7, 36 on Day 10, and 38 on Day 14. The 95 infants in the moderate-start accelerated catch-up group started near 21, then reached roughly 23, 26, 30, and 34 at the successive assessments. The low-start slow-rise group consisted of 51 infants. Its estimated score was about 20 initially, dipped slightly to 19 on Day 3, and then increased to 23, 26, and 30. Thus, the low-start group remained below the other two throughout follow-up, even though its trajectory ultimately turned upward. The researchers described the slight early dip as consistent with, but not proof of, immature coordination of sucking, swallowing, and breathing.

Univariate comparisons identified six characteristics that varied significantly across trajectory groups: gestational age at birth, birth weight, postmenstrual age when oral feeding began, mechanical ventilation, illness severity as measured by the Neonatal Medical Index, and pre-feeding behavioral state. Multinomial logistic regression then examined whether these variables were independently associated with group membership, using the high-start rapid-rise group as the reference. Compared with that group, lower gestational age and lower birth weight were associated with membership in both less favorable groups. The low-arousal and moderate-arousal behavioral categories were also associated with the moderate-start catch-up group. For the low-start slow-rise group, the analysis additionally found associations with later oral-feeding initiation, mechanical ventilation, and a Neonatal Medical Index score of at least 4.

Some regression estimates were large but imprecise. Relative to the high-start group, the low-start group had an odds ratio of 2.258 for each additional week of postmenstrual age at feeding initiation, 4.875 for mechanical ventilation, and 5.497 for an NMI score of at least 4. Low arousal had an odds ratio of 50.908 and moderate arousal 16.056 for membership in the low-start group, but the confidence intervals were extremely wide: 7.889 to 328.497 and 3.280 to 78.611, respectively. These magnitudes should therefore not be treated as stable risk estimates. Sparse cells contributed to the uncertainty; only four infants in the low-start group had been mechanically ventilated, and only four were classified as high arousal before feeding. The authors explicitly characterized the findings as associative and hypothesis-generating rather than predictive.

Several design features limit how far the results can be generalized. Oral feeding began only after infants reached at least 32 weeks of postmenstrual age, had stable vital signs, and had been weaned from mechanical ventilation for more than 48 hours. Nevertheless, the low-start group began oral feeding at a later median postmenstrual age than the other groups, which likely reflected a more adverse clinical profile rather than greater developmental maturity. The unit used scheduled oral feeding attempts under a protocol that did not primarily follow behavioral cues, and it also used side-lying positioning and a specific preterm formula. The trajectories may therefore reflect interactions between infant readiness and this feeding protocol, not maturation alone, and their frequencies may differ in neonatal units using predominantly cue-based practices.

Other important information was unavailable. Follow-up stopped on Day 14, so the study did not determine whether trajectory classes predicted time to full oral feeding, postmenstrual age at full feeding, length of hospital stay, or later growth and development. Ventilation history was recorded only as a binary variable; ventilation duration, bronchopulmonary dysplasia, and respiratory support at feeding initiation were not measured. Actual daily enteral and parenteral intake, feeding interruptions, parenteral-nutrition indications, and subsequent weight gain were also not recorded, so the prescribed nutritional targets could not be treated as observed exposure. Pre-feeding state was averaged across all five assessment days rather than measured only at initiation, and illness severity was assessed at discharge. Formal inter-rater reliability testing was absent, the behavioral categories were created operationally without external validation, and the study excluded medically complex and human-milk-fed infants. Larger multicenter cohorts with longer follow-up and prospective nutritional measurements are therefore needed to determine whether the three patterns reproduce elsewhere and add clinical value beyond information available when oral feeding begins.

Subject of Research: Longitudinal oral-feeding trajectories and associated clinical factors in preterm infants

Article Title: Three distinct trajectories of early oral feeding ability in preterm infants and their associated clinical factors

Article References: Tang, X., Zhu, Y., Wu, Y., Sun, S., Zhou, M., & Yu, X. (2026). Three distinct trajectories of early oral feeding ability in preterm infants and their associated clinical factors. Frontiers in Pediatrics, 14, Article 1924274. https://doi.org/10.3389/fped.2026.1924274

Image Credits: AI Generated

DOI: 10.3389/fped.2026.1924274

Keywords: preterm infants, oral feeding, feeding ability, latent class growth modeling, neonatal intensive care, gestational age, illness severity, mechanical ventilation, behavioral state, prospective cohort, Three, distinct

The research team, led by investigators affiliated with Southern Illinois University School of Medicine, Wayne State University School of Medicine, and collaborating institutions, mined the TriNetX database, a federated network of de-identified electronic health records spanning the years 2006 to 2026. They identified adults with a stroke diagnosis who required invasive mechanical ventilation within 48 hours of stroke onset and who had documented pulse oximetry readings in that same early window. Patients were classified as receiving a restrictive oxygenation strategy if every recorded peripheral oxygen saturation, or SpO₂, value fell between 92 and 96 percent, and as receiving a liberal strategy if all values were at or above 97 percent. Anyone whose readings straddled both ranges or dipped below 92 percent was excluded, a deliberately strict rule designed to create two cleanly separated, non-overlapping exposure groups.

Of the 17,207 patients who met the inclusion criteria, 2,366 had restrictive oxygenation profiles and 14,841 had liberal profiles before any statistical adjustment. Because patients who end up on conservative oxygen protocols often differ systematically from those kept at higher saturations—older, sicker, with more cardiopulmonary disease—the researchers used propensity score matching, a statistical technique that pairs patients with similar baseline characteristics. The model accounted for age, sex, race and ethnicity, body mass index, a Glasgow Coma Scale score of nine or below, and a long list of comorbidities including hypertension, ischemic heart disease, heart failure, atrial fibrillation, chronic obstructive pulmonary disease, pneumonia, and shock. After matching, 2,350 patients remained in each group, and all measured covariates were well balanced, with standardized mean differences below 0.1.

The results were striking. In the matched cohort, restrictive oxygenation during the first 48 hours of ventilation was associated with a 13 percent higher hazard of death at one month, with a hazard ratio of 1.13 and a 95 percent confidence interval of 1.03 to 1.23, a statistically significant finding with a p-value of 0.008. The association persisted at three months, with a hazard ratio of 1.11 and a confidence interval of 1.02 to 1.20. Kaplan–Meier survival curves, which track survival over time, visibly separated between the two groups in the combined stroke population, indicating that the mortality gap emerged early and persisted through the follow-up period.

When the investigators split the population by stroke subtype, the picture became more nuanced. In the acute ischemic stroke subgroup, built from 1,214 restrictive and 7,463 liberal patients before matching, restrictive oxygenation was associated with a 26 percent higher hazard of death at one month (hazard ratio 1.26, 95 percent confidence interval 1.11 to 1.43) and a 22 percent higher hazard at three months (hazard ratio 1.22, 95 percent confidence interval 1.08 to 1.37). In the intracerebral hemorrhage subgroup, however, the corresponding hazard ratios—1.09 at one month and 1.11 at three months—had confidence intervals that crossed one, meaning no statistically significant difference could be detected. The authors note that the hemorrhagic subgroup was smaller, with 728 patients per arm after matching, so limited statistical power may have masked a real effect; notably, the point estimates trended in the same direction as those seen in ischemic stroke.

The biology behind these findings is grounded in the peculiar physiology of the acutely injured brain. In the first two days after an ischemic stroke, cerebral autoregulation—the mechanism that normally keeps blood flow constant across swings in blood pressure—is often impaired. Surrounding the core of dead tissue lies the penumbra, a zone of hypoperfused but still viable brain that depends precariously on whatever oxygen the circulation delivers. Even modest reductions in arterial oxygen content could, in theory, tip penumbral tissue into irreversible infarction, extending the damage and worsening outcomes. A restrictive saturation target of 92 to 96 percent, while safe for many critically ill patients, may leave less reserve for this vulnerable tissue than a liberal target of 97 percent or above.

Yet the push toward conservative oxygen in intensive care has its own logic. Excess oxygen generates reactive oxygen species, drives oxidative stress, and can cause cerebral vasoconstriction, and randomized trials in general ICU populations—including ICU-ROX and the Oxygen-ICU trial—have explored whether tighter oxygen control reduces harm. The new study suggests that extrapolating those protocols to stroke patients may be misguided. The authors point to post-hoc analyses of ICU-ROX as a telling parallel: among ventilated patients with acute brain pathologies other than hypoxic-ischemic encephalopathy, 180-day mortality was numerically higher under conservative oxygen (34.5 percent versus 26.9 percent), a heterogeneity considered plausible enough to be formalized as a prespecified hypothesis in the ongoing Mega-ROX Brains trial, which is randomizing brain-injured patients to conservative or liberal oxygenation targets.

Among the secondary outcomes, one result stood out as counterintuitive: patients in the restrictive group were significantly less likely to undergo tracheostomy within 30 days, at 8.5 percent versus 13.1 percent in the liberal group, a risk ratio of 0.653 with a p-value below 0.001. The authors caution that this pattern may reflect survivorship bias—patients who die early cannot receive a tracheostomy—or may be shaped by unmeasured factors such as the reasons for intubation, the trajectory of neurological recovery, and goals-of-care discussions that could not be captured in the database. Ventilator-associated pneumonia, by contrast, showed no significant difference between groups, with event rates of 0.6 percent and 0.89 percent, though the very low number of events limited statistical power.

The study’s observational design imposes important caveats. Because oxygenation was observed rather than allocated, residual confounding by unmeasured variables cannot be excluded, and the association cannot be read as proof of causation. Stroke severity measures such as infarct volume, hematoma size, and detailed neurological examinations were not available in the federated record network and could not be incorporated into the matching model. The exposure was defined by documented pulse oximetry readings rather than continuous arterial oxygen measurements, so the analysis reflects oxygenation strategy rather than precise quantification of hyperoxemia or hypoxemia. The two saturation thresholds are also adjacent, making the contrast between groups relatively narrow, and follow-up was limited to three months.

Even with those limitations, the sheer size of the cohort and the rigor of the matching make this one of the most pointed challenges yet to the assumption that conservative oxygen targets are universally safe. The authors frame their findings as hypothesis-generating rather than practice-changing, but the implication is hard to ignore: the first 48 hours of mechanical ventilation may represent a modifiable window in stroke care, and the optimal saturation target may differ between an ischemic brain starved of blood flow and a hemorrhagic brain compressed by expanding blood. As stroke remains a leading cause of death and disability worldwide, the authors argue that disease-specific randomized trials—rather than broad ICU-wide oxygen protocols—are urgently needed to determine whether liberal oxygenation genuinely protects the penumbra, or whether individualized titration can balance the competing risks of hypoxemia and oxygen toxicity in this uniquely vulnerable population.

Subject of Research: Oxygen saturation targets and short-term mortality in mechanically ventilated stroke patients

Article Title: Association of liberal versus restrictive oxygen saturation targets with mortality in mechanically ventilated stroke patients: a multicenter retrospective propensity-matched analysis

Article References: Ghafarian, A., Saad, J., Wajahath, M., Ghafarian, M., Saasouh, W., Saleh, K., Nasser, M., Badami, A., Shahait, A. D., & Loggini, A. (2026). Association of liberal versus restrictive oxygen saturation targets with mortality in mechanically ventilated stroke patients: a multicenter retrospective propensity-matched analysis. Frontiers in Neurology, 17, 1840183. https://doi.org/10.3389/fneur.2026.1840183

Image Credits: AI Generated

DOI: 10.3389/fneur.2026.1840183

Keywords: stroke, mechanical ventilation, oxygen saturation, acute ischemic stroke, intracerebral hemorrhage, mortality, propensity score matching, critical care, neurocritical care, TriNetX, hyperoxia, ventilator-associated pneumonia