With the progressive decline in mortality rates in intensive care units in recent decades, increasing attention has been drawn to the fact that many patients who survive their stay in the intensive care unit develop long-lasting physical, cognitive and psychological impairments, which can last for months or even years after their critical illness. This health problem, known as post-intensive care syndrome, can be alleviated by implementing certain practices during hospitalisation, and its treatment generally requires attention upon discharge from hospital. The stress and trauma associated with the intensive care unit experience can also affect family members in the long term, manifesting as mental health problems known as family post-intensive care syndrome. In this context, pharmacists play a key role in the prevention and treatment of post-intensive care syndrome, integrating into multidisciplinary teams in both the intensive care unit and post-intensive care unit recovery clinics. Their intervention includes comprehensive optimisation of pharmacotherapy, reconciliation, identification and prevention of adverse drug events, and health education for patients and their families.
There is limited literature on the perceptions and practices of nurses in Saudi Arabia related to neonatal palliative care (NPC). This study aimed to assess NPC perceptions and practices among female nurses in Saudi Arabia. This cross-sectional survey study was conducted in Saudi Arabia between May and October 2025. The inclusion criteria for this study were nurses working in neonatal intensive care units in Saudi Arabia, regardless of the level of care provided. Factors associated with higher perception scores were identified using multivariable logistic regression analysis. A total of 170 nurses were included in this study. The majority worked in the governmental sector (148, 87.6%). Most participants reported that their institutions had formal NPC guidelines (142, 83.5%). Perception scores showed a significant difference by nurses' education level (P = .01). Nurses with a bachelor's degree or lower reported a mean score of 85.16 ± 16.64, whereas those with a master's degree or PhD had a mean score of 71.44 ± 31.30 (P-value = .02). Participants aged between 30 and 40 years showed lower odds of attitude (adjusted odds ratio = 0.33, 95% confidence interval: 0.11-1.00, P = .05), which was borderline significant. This study assessed NPC among nurses in neonatal intensive care units in different settings in Saudi Arabia. The results suggested the importance of education in both NPC awareness and practice. Further studies are needed to confirm these findings. Improving nurses' knowledge and skills may lead to better palliative care for neonates and their families.
Multidrug-resistant (MDR) bacterial infections remain a major challenge in intensive care units, leading to prolonged hospitalization and increased mortality. Although several clinical factors have been associated with MDR infections, there is still a lack of practical and individualized predictive tools to facilitate early risk stratification in intensive care unit (ICU) patients. This retrospective single-center study included adult patients admitted to the ICU of Leshan People's Hospital between January 2020 and December 2025 who stayed for at least 48 hours and had complete microbiological records. The primary outcome was the occurrence of MDR bacterial infection, defined as resistance to at least 3 classes of antibiotics confirmed by microbiological culture and susceptibility testing. Patients were randomly divided into a training cohort (70%) and a validation cohort (30%). Univariable and multivariable logistic regression analyses were performed to identify independent risk factors. A nomogram prediction model was constructed based on significant predictors. Model performance was evaluated using receiver operating characteristic curves, area under the curve (AUC), calibration curves, the Hosmer-Lemeshow goodness-of-fit test, decision curve analysis, and internal validation using Bootstrap resampling combined with 10-fold cross-validation. A total of 876 ICU patients were included (mean age: 68.4 ± 14.7 years; 58.2% male), among whom 161 (18.38%) developed MDR bacterial infections. Multivariable logistic regression identified age > 75 years (OR: 3.350, 95% CI: 2.916-3.792), endotracheal intubation (OR: 2.079, 95% CI: 1.740-3.130), ICU stay > 1 week (OR: 3.428, 95% CI: 2.553-4.417), coma (OR: 2.735, 95% CI: 2.000-4.469), and central venous catheterization (OR: 2.438, 95% CI: 1.464-4.295) as independent risk factors. The nomogram demonstrated good discriminative ability, with an AUC of 0.827 in the training cohort and 0.812 in the validation cohort. Internal validation yielded an AUC of 0.820, with a sensitivity of 83.2% and a specificity of 82.8%. Advanced age, invasive procedures, prolonged ICU stay, and impaired consciousness are associated with an increased risk of MDR bacterial infections in ICU patients. The developed nomogram provides a practical tool for individualized risk prediction and may assist clinicians in early identification and targeted preventive strategies. However, due to the retrospective nature of the study, these findings suggest associations but do not establish causality.
Disaster response in neonatal intensive care units is particularly complex because care continuity depends on coordinated teamwork, stable infrastructure, and technology-dependent support for highly vulnerable infants. However, qualitative evidence on how nurses experience disaster response in these settings remains limited, especially in the context of the 2023 Türkiye-Syria earthquakes. This study explored how nurses working in neonatal intensive care units experienced disaster response during the earthquakes. Data were collected through semistructured in-depth interviews with 21 nurses and analyzed using descriptive phenomenological analysis. Participants described disaster response not only as a clinical emergency but also as a disruption of the systems supporting coordination, safe neonatal care, and practical preparedness. They reported breakdowns in communication and role clarity, fragility in care when electricity, oxygen delivery, monitoring systems, evacuation planning, and essential supplies became unstable, and a clear gap between general disaster education and unit-specific readiness. Overall, the findings highlight the need for neonatal intensive care-specific disaster preparedness.
Accompanying acute kidney injury (AKI) is an important cause of morbidity and mortality in sepsis patients. Therefore, recognition of AKI is of great importance in the care of critically ill patients. In this study, we aimed to determine the role of the renal angina index (RAI) and tissue perfusion indicators in predicting early AKI and its stage in patients with sepsis. This study was performed prospectively on 40 sepsis patients in the Cukurova University Medical Intensive Care Unit between February 13 and December 1, 2023. Demographic data, clinical characteristics, capillary refill time, RAI, development of AKI, Intensive Care Unit, and 28-day mortality rates were evaluated. RAI (≥10) was found to be higher in patients with AKI and severe AKI (P < .001 and P = .001, respectively). Serum lactate levels at 24, 48, and 72 hours in the AKI group and serum lactate levels at all hours in patients with severe AKI were statistically significantly higher (P < .05). The rate of prolongation in capillary refill time was higher in patients with AKI and severe AKI (P < .05). The best cutoff for the RAI score to predict AKI severity was ≥10 with a 0.961 area under the curve, a sensitivity of 83.33%, and a specificity of 94.12%. A 24-hour lactate value of >2.1 mmol/L showed the best diagnostic performance with an area under the curve of 0.895, a sensitivity of 100%, and a specificity of 79.41%. The RAI score and 24-hour lactate demonstrated strong diagnostic performance in predicting AKI severity, with the RAI score showing superior accuracy. These markers, with high sensitivity and specificity, may serve as valuable tools for early risk assessment and clinical decision-making in AKI management.
Pneumonia causes significant mortality in intensive care unit (ICU) patients, yet traditional culture-based pathogen detection lacks sufficient sensitivity. While bronchoalveolar lavage fluid (BAL) provides optimal diagnostic yield, bronchoscopy is often contraindicated in critically ill patients. This study compares the respiratory microbiome profiles of paired tracheal aspirate (ETA) and BAL samples from pneumonia patients in a tertiary hospital ICU (n=23, November 2019-September 2022). Using 16S rRNA next-generation sequencing, we analyzed microbial diversity (Shannon Index), taxonomic composition, and differential abundance (edgeR). Results showed comparable diversity indices and microbial communities between ETA and BAL samples, with ETA successfully capturing key pneumonia-related microbial signatures. These findings validate ETA as a reliable, less invasive alternative to BAL for respiratory microbiome analysis in critically ill patients, establishing the groundwork for future clinical applications.
The aim of this study was to compare the clinical characteristics, treatments and outcomes of immunocompromised patients with viral severe acute respiratory infections (SARI), to those of immunocompetent patients admitted to an intensive care unit (ICU) across Australia. Retrospective analysis of a prospective, nation-wide, observational registry of 46 ICUs from June 2022 to August 2025. Critically ill adults (age ≥ 18) with laboratory-confirmed viral SARI were included. Immunocompromised status was defined by the presence of any one of the following: chronic immunosuppression, malignant neoplasm, AIDS/HIV, or organ transplantation. Associations between immunocompromised status and in-hospital mortality were evaluated using mixed-effects logistic regression models. Competing risks regression (Fine and Gray models) was used to assess the association between immunocompromised status and risk of hospital discharge within 30 days. Among 4,703 patients with viral SARI who were admitted to ICUs, immunocompromised patients accounted for 908 (19.3%) cases. Immunocompromised patients were older (median age 67 vs. 62 years), more comorbid (31.4% vs. 22.5% with ≥ 3 comorbidities), and more frequently admitted with COVID-19 (51.1% vs. 34.5%); (p < 0.001 for all). Immunocompromised patients received more treatment, including antivirals (67.3% vs. 57.7%), and corticosteroids (81.7% vs. 72%) and had higher in-hospital mortality (22.7% vs. 13.1%); (p < 0.01 for all). After adjusting for demographics, comorbidities, vaccination status (where available), ICU interventions and treatments, immunocompromised status was independently associated with nearly double the odds of in-hospital mortality (adjusted OR 1.93, 95% CI 1.57-2.37). In this study, we found that immunocompromised patients accounted for approximately one-fifth of critically ill viral SARI patients and had nearly twice the odds of in-hospital mortality, when compared to those that were immunocompetent. Targeted public health campaigns and improved treatment strategies may be warranted for this population.
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Empowering children and young people (CYP) to actively participate in research development is essential to ensure impactful outcomes. Meaningful involvement helps researchers to pose relevant questions, design acceptable methodologies, and disseminate findings effectively. However, the inclusion of CYP in research, particularly in paediatric intensive care (PIC), is rarely reported. This is partly due to the challenging PIC environment, and most patient and public involvement and engagement activities (PPIE) focus only on the parents' experience and perspective. The Intensive-Share group was established in Scotland in 2022 to facilitate PPIE activity in PIC research. The group includes family members with a range of lived experiences with the youngest member aged 7 years. They meet regularly to contribute to various aspects of research including research design, study materials and procedures, and public engagement. This article describes the co-production approach adopted in the 'What is data?' Project, which was co-created with researchers based on an idea from the Intensive-Share group. The project aimed to co-develop a short-animated video to explain healthcare data research to CYP in an engaging and accessible format. CYP meaningfully participated in all stages of the project and were integral to its success. Initial evaluations indicated the animation was well-received by families and they self-reported improved understanding of and willingness to participate in research. Co-production with CYP can be resource-intensive and challenging, but this project demonstrated it was feasible and incredibly valuable. Meaningful and authentic involvement challenged the research teams assumptions on inclusive language and the nature and level of involvement CYP preferred. Adopting a broader approach to PPIE in PIC research to include paediatric patients and siblings, perhaps on a national level, could facilitate similar initiatives in research communication and co-production. The open-source animated video is available as a resource to the wider research community to aid communication about paediatric healthcare data research. Actively involving children and young people (CYP) in research development is essential for research to have an impact. CYP can help ensure communication about research is understandable, engaging and addresses what is important to them. However, there are very few reports of involving CYP in developing research information, particularly in paediatric intensive care (PIC). Most examples focus on parents, not on the valuable perspectives of paediatric patients and their siblings. To address this, the Intensive-Share group was established in Scotland in 2022. The group includes families with a range of experiences of PIC. Members meet regularly to contribute to various aspects of research development including project questions, the way projects are carried out (methodology), and sharing research findings with the public. This article shares experiences from the ‘What is data?’ Project which was created through a partnership between researchers and the Intensive-Share group. The project took a co-production approach to develop a short-animated video to help CYP understand how healthcare data is used for research. CYP had important roles in all stages of the project, particularly in ensuring the language in the animation was accessible and relevant. The animation was well-received by families and they reported it improved their understanding of healthcare data research. The project underscores the value of involving CYP in research communication, not just parents, and research teams would benefit from resources to support such initiatives. The animation is an open-source resource to aid researchers communicating with families about healthcare data research.
This study investigates the molecular characteristics of multidrug-resistant Acinetobacter baumannii (MDRAB) clinical isolates with particular emphasis on colistin resistance, biofilm formation, antimicrobial resistance determinants, clonal relatedness, and pmrA gene expression. Twenty MDRAB isolates were collected from intensive care unit patients at Afzalipour Hospital, Kerman, Iran. Antimicrobial susceptibility testing was performed using the broth microdilution method according to the EUCAST 2022 guidelines. Polymerase chain reaction (PCR) was used to detect extended-spectrum β-lactamase (ESBL), carbapenemase, biofilm-associated genes, and class 1 integrons. Clonal relatedness was assessed using Repetitive-element PCR (Rep-PCR), and the pmrA gene (GenBank accession no. MN787072.1) expression analyzed through quantitative RT-PCR (qRT-PCR). The isolates demonstrated high minimum inhibitory concentrations (MICs) particularly against carbapenems. Many isolates showed strong biofilm, while carrying biofilm-associated genes bap, csuE, pgaA, and ompA. Class 1 integrons and the blaCTX-M gene detected in 94% and 65% of isolates, respectively. Colistin-resistant (ColR) isolates shared a distinct Rep-PCR profile (singleton) and harbored both the pmrA and blaCTX-M-15 genes. DNA sequencing and qRT-PCR analysis revealed that, the Q218→K mutation had marginal effect on pmrA gene expression. These findings underscore the urgent need for effective antibiotic stewardship to address rising incidence of carbapenemase-producing, colistin resistance in A. baumannii. Acinetobacter baumannii is a harmful germ commonly found in the environment, like in soil, skin and water. Infections caused by this germ often occur among the people with weak immune systems, especially hospital patients. It can cause many different infections with various symptoms. A. baumannii can cause infections in the blood, urinary tract, lungs (pneumonia) or wounds. In some cases, people can carry the bacteria without being infected, known as carrier. Many strains of this germ have become resistant to antibiotics, making them very hard to treat. This problem is especially serious in Intensive Care Units and needs quick medical action. The Centers for Disease Control and Prevention (CDC) has called infections from this germ a major public health threat. This study looked at how this germ is becoming resistant to colistin, an important antibiotic.
This study aimed to assess the association between early nutritional support - specifically the attainment of predefined energy targets - and the risk of hospital-acquired infections (HAIs) in critically ill neonates. We conducted a retrospective cohort study involving 200 critically ill neonates admitted to a tertiary neonatal intensive care unit between January 2022 and December 2023. Participants were stratified into 2 exposure groups according to the timing of nutritional initiation and adequacy of energy/protein intake during the first postnatal week: an early-adequate nutrition group (n = 92) and a delayed or insufficient nutrition group (n = 108). A multivariable logistic regression model was fitted to evaluate the independent effect of energy target achievement on HAI risk, with additional subgroup and sensitivity analyses to assess robustness. The cohorts were largely comparable at baseline, although birth weight was significantly higher in the early-adequate nutrition group (1605 ± 390 vs 1470 ± 440 g, P = .02). Initiation of nutritional support occurred earlier in the early-adequate group, resulting in significantly greater cumulative energy and protein intake by day 7. The energy target achievement rate was 100% in the early-adequate group, compared with 33.3% in the delayed/insufficient group (P < .001). Throughout the follow-up period, 48 neonates (24.0%) developed HAIs, with a significantly lower incidence observed in the early-adequate nutrition group (15.2% vs 31.5%, P = .008). Quartile-based analysis demonstrated a clear inverse dose-response relationship between energy intake and infection incidence (P for trend = .001). After adjusting for potential confounders, achievement of the energy target (≥60 kcal/kg/d) remained independently associated with reduced HAI risk (adjusted odds ratio = 0.45, 95% confidence interval = 0.22-0.89, P = .02). Subgroup analyses revealed a more pronounced protective effect among very low birth weight infants and those born at <28 weeks' gestation. Sensitivity analyses confirmed the consistency of these findings across alternative energy thresholds (60, 70, and 80 kcal/kg/d). Early attainment of energy targets is independently associated with a reduced incidence of HAIs in critically ill neonates, underscoring the vital role of timely and sufficient nutritional support in mitigating infectious complications in the neonatal intensive care unit setting.
Sepsis, acute kidney injury (AKI), and acute respiratory distress syndrome (ARDS) are severe conditions commonly seen in the intensive care unit (ICU). The study was designed to evaluate the influence of single-organ dysfunction (AKI or ARDS) and 2-organ dysfunction (AKI combined with ARDS) on the 30-day mortality risk in patients with sepsis. Data originated from a prospective multicenter cohort involving 18 Chinese ICUs, which enrolled patients with sepsis following ICU admission. Patients were stratified into 4 groups according to their organ status within 7 days of sepsis onset: those who did not develop AKI or ARDS (non-AKI and non-ARDS group), those who developed AKI but not ARDS (AKI and non-ARDS group), those who developed ARDS but not AKI (ARDS and non-AKI group), and those who developed both AKI and ARDS (AKI and ARDS group). The primary endpoint was defined as mortality within 30 days of sepsis diagnosis. Furthermore, a survival analysis was conducted among the 4 groups. A total of 2175 septic patients were eligible, including 273 cases (12.6%) in the non-AKI and non-ARDS group, 435 cases (20.0%) in the AKI and non-ARDS group, 560 cases (25.7%) in the ARDS and non-AKI group, and 907 cases (41.7%) in the AKI and ARDS group. Kaplan-Meier analysis revealed that the survival probabilities of the 4 groups at 30 days after sepsis diagnosis were 85.6%, 70.6%, 58.9%, and 50.8%, respectively (P < .001). Compared with the patients in the non-AKI and non-ARDS group, a landmark analysis showed that the average adjusted hazard ratios for the 30-day mortality risk for the AKI and non-ARDS, ARDS and non-AKI, and AKI and ARDS groups were 2.19 (95% confidence interval [CI]: 1.26-3.82, P = .006), 2.92 (95% CI: 1.73-4.93, P < .001), and 3.09 (95% CI: 1.85-5.15, P < .001), respectively. Septic patients complicated with AKI and ARDS had a poor prognosis, with a 30-day survival rate of only 50.8% after the diagnosis of sepsis.
To compare the clinical outcomes of ultra-fast-track extubation (UFTE), defined as extubation in the operating room or within 1 hour postoperatively, versus fast-track extubation (FTE), defined as extubation within 6 hours in the intensive care unit [ICU]), in adult patients undergoing cardiac surgery. Systematic review and meta-analysis. Studies identified from MEDLINE, Scopus, and the Cochrane Library. Adult patients undergoing cardiac surgery. Comparison of UFTE versus FTE. Twenty studies including nearly 800,000 patients were analyzed. UFTE was associated with lower 30-day mortality (odds ratio [OR], 0.54), shorter ICU length of stay (LOS) (mean difference [MD], -12.27 hours), shorter hospital LOS (MD, -1.19 days), reduced stroke rate (OR, 0.85) and reduced readmission rate (OR, 0.64). Rates of reintubation, reoperation for bleeding, acute kidney injury, pneumonia, and atrial fibrillation were similar. In the minimally invasive cardiac surgery subgroup, UFTE was associated with lower reintubation risk (OR, 0.26), whereas in the coronary artery bypass grafting subgroup, only hospital LOS was reduced. In propensity-matched cohorts, mortality and reintubation were comparable, although ICU and hospital stays remained shorter with UFTE. Meta-regression identified male sex and baseline left ventricular ejection fraction as significant moderators of the mortality effect. UFTE appears safe in selected patients and is associated with improved efficiency and recovery, particularly reduced ICU and hospital LOS. However, the observed mortality benefit is not sustained after adjustment, suggesting an important role of patient selection and perioperative optimization. Prospective randomized trials are required to confirm these findings.
Machine perfusion technology has redefined donor and recipient criteria for liver transplantation. Despite increasing adoption, data regarding graft and recipient factors associated with unsuccessful normothermic machine perfusion (NMP) outcomes remain limited. The Organ Procurement and Transplantation Network database was used to retrospectively identify adult patients undergoing deceased donor liver transplantation with NMP preservation between January 10, 2021, and December 31, 2024. Populations were stratified by 1-year graft status, with donor and recipient factors compared. Logistic regression identified factors independently associated with NMP graft failure, and center analyses assessed program-level impacts. Among 4928 NMP cases, 398 (8.1%) experienced 1-year graft failure. They were more frequently admitted to the intensive care unit (ICU) at transplant (21.1% vs. 10.6%, p < 0.001) and had more complex abdominal histories, including higher rates of TIPS(17.0% vs. 12.0%), prior abdominal surgery (64.1% vs. 54.7%), and prior liver transplant (10.3% vs. 3.4%) (all p < 0.01). Regression analysis identified increased odds of graft failure with MELD score 35 (aOR 2.10 [1.21-3.63]), low recipient functional status (aOR 2.05 [1.31-3.21]), and prior abdominal surgery (aOR 1.33 [1.01-1.76]). Alcohol-associated liver disease (aOR 0.36 [0.23-0.56]) was the only factor conferring a protective effect. Centers with higher-than-expected standardized NMP graft failure rates were higher-volume programs with low-risk case mixes; no centers had persistently high standardized failure rates throughout the study period. Recipient factors, particularly those conferring surgical complexity, are more significantly associated with NMP graft failure than donor factors. Despite increased adoption of perfusion technologies to mitigate donor and operative risk, transplant provider clinical judgment remains critical for optimizing recipient-donor matching and outcomes.
Intra-abdominal hypertension (IAH) may reduce the diagnostic accuracy of the passive leg raising (PLR) test for predicting fluid responsiveness, with unclear mechanisms. The reliability of the end-expiratory occlusion (EEO) test and mini-fluid challenge in IAH remains unknown. This study explored the mechanisms underlying PLR impairment and assessed the accuracy of EEO and mini-fluid challenge in detecting fluid responsiveness in patients with and without IAH. In this prospective study in two intensive care units (ICUs), we included ventilated patients with IAH ("IAH + "; intra-abdominal pressure [IAP] ≥ 12 mmHg) and without ("IAH-"), all monitored via transpulmonary thermodilution and receiving a 500-mL fluid challenge. Patients consecutively underwent a 1‑minute PLR, a 15‑second EEO, and a 1‑minute mini-fluid challenge of 100 mL, with cardiac index (CI) changes recorded during each maneuver. Following the mini-fluid challenge, the remaining 400 mL were infused over 14 min, and a ≥ 15% increase in CI was used to define fluid responders. The transmural pressure of the inferior vena cava was estimated by the central venous pressure (CVP) - IAP gradient. We included 88 patients, 44 IAH- (25 fluid responders and 19 non-responders) and 44 IAH + (22 responders and 22 non-responders). Baseline IAP was 9 ± 2 mmHg in IAH- and 17 ± 3 mmHg in IAH + (p < 0.001). In IAH- responders, CI increased by 19 ± 11% during PLR and 31 ± 17% after volume expansion, with PLR positive in 24/25 responders. In IAH + responders, CI increased by 6 ± 7% during PLR (p < 0.001 vs. IAH-) and 30 ± 18% after volume expansion (p = 0.907 vs. IAH-). The AUROC of the PLR for detecting fluid responsiveness was 0.96 (0.87-1.00) in IAH- and 0.71 (0.56-0.87) in IAH + (p = 0.009 vs. IAH-). Among IAH + , there were 16 false negatives and 6 true positives for PLR, both with negative baseline CVP-IAP gradients. During PLR, the gradient reversed in true-positives (from -2.4 ± 4.0 to + 2.2 ± 2.7 mmHg, p = 0.014), whereas it remained negative in false-negatives (from -6.3 ± 3.7 to -1.4 ± 3.4 mmHg, p < 0.001). AUROC between IAH- and IAH + was similar for either the EEO test (0.95 [0.87-1.00] vs. 0.89 [0.80-0.97], p = 0.332) or mini-fluid challenge (0.94 [0.87-1.00] vs. 0.90 [0.79-1.00], p = 0.514). In patients with IAH, the limited diagnostic value of PLR for fluid responsiveness may be related to persistently negative CVP-IAP gradients in false-negative cases, whereas EEO and mini-fluid challenge remain reliable alternatives.
This case series discusses the nursing care and clinical outcomes of 3 pediatric patients with febrile infection-related epilepsy syndrome (FIRES) and acute-phase complications, focusing on critical care interventions such as seizure management, respiratory support, and nutritional therapy. Three male patients, aged 10, 5, and 7, presented with altered consciousness, seizures, and recurrent fever. Diagnostic tests, including magnetic resonance imaging, electroencephalogram (EEG), and cerebrospinal fluid analysis, revealed abnormal EEG findings, suspected meningeal inflammation, and cerebrospinal fluid abnormalities. All patients were diagnosed with FIRES, accompanied by acute neurological deterioration, supported by EEG and magnetic resonance imaging. All patients required intensive care unit mechanical ventilation. Two underwent tracheostomy during prolonged ventilator dependence, whereas 1 was extubated to low-flow nasal oxygen after approximately 14 days without tracheostomy. Seizure management included anticonvulsants and a ketogenic diet, with individualized adjustments according to clinical response. Multidisciplinary care involved specialists in neurology, respiratory medicine, and rehabilitation. Short-term outcomes differed. One tracheostomized patient was later decannulated and discharged clinically improved, with recovery of communication, oral intake, and independent ambulation. The non-tracheostomized patient remained off invasive ventilation but continued inpatient neurologic and nutritional management, while the other tracheostomized patient still required ventilatory and neurologic management in the latest available record. Coordinated multidisciplinary nursing, early nutritional planning, and structured monitoring may help organize acute-phase FIRES care while supporting individualized respiratory, seizure, and complication management.
Sepsis-associated delirium (SAD) is a life-threatening complication in the intensive care unit (ICU). Although sleep disturbances are common in sepsis, their relationship with SAD remains poorly understood. We investigated the link between sleep disturbances, melatonin dysregulation, and SAD. In this prospective cohort study, we longitudinally assessed 99 patients with sepsis. Sleep quality was evaluated using the Richards-Campbell Sleep Questionnaire (RCSQ) and melatonin concentration, and multivariable logistic analysis, propensity score matching (PSM), inverse probability weighting (IPW), mixed-effects models, Bayesian, and mediation analysis to adjust for confounding factors to evaluate the relationship of melatonin with sleep disorder and SAD. Sleep disorders preceded SAD onset with a duration-dependent effect (P < 0.001) and were associated with a 1.45-7.69-fold higher risk of delirium (P < 0.05) across multivariable logistic analysis, PSM, IPW and Bayesian analysis. Lower melatonin concentrations were correlated with worse multidimensional sleep impairment (β = 7.65-13.10, all P < 0.05), particularly impaired sleep continuity (β = 9.81) and poorer overall sleep quality (β = 13.10). Patients with SAD exhibited biphasic melatonin suppression: initial decline coinciding with sleep disturbances (P < 0.001), followed by further reduction during active delirium episodes (P < 0.005), independent of sedation exposure (P > 0.05). Mediation analysis demonstrated substantial mediating effects of melatonin concentrations measured at sleep disturbance onset (ADE = 0.60, P < 0.001), and melatonin reduction occurring alongside sleep disturbances was associated with SAD development [average causal mediation effects (ACME) =  - 0.110, P = 0.024]. This study provides preliminary evidence that disrupted sleep patterns and altered melatonin secretion may contribute to the development of SAD in ICU patients. While our findings support melatonin not only as a risk factor for sleep disruption and SAD, but also as a biologically plausible candidate linking sleep disruption to SAD, the potential influence of other factors underscores the need for further research to confirm this relationship.
Thousands of years of breeding and agronomic change have pushed genetic change into increasingly narrow corridors. The approach has worked effectively, but gains are slowing and much genetic variance expected from heritability estimates is not readily found. We propose that breeding constraints, the practical demands that make crops useful, force genetic exploration onto curved, lower-dimensional surfaces within the larger landscape of possibility. In crops, these constraints arise jointly from genetic choices and management decisions about fertilizer, sowing density, weed and pest control, irrigation and harvest logistics, which together define the range of environments in which genotypes are routinely grown. These constraints may hide certain classes of gene interactions from breeding programmes, creating an additive appearance where the underlying biology may remain epistatic. Selection moves by additive steps, but on a curved, constrained surface: the speed looks additive, but the long-term path follows the geometry of the constraints. This framework particularly applies to major crop species subjected to intensive directional selection over many generations for stable agricultural requirements, the context where constraint-based filtering of genetic variance is most pronounced. When selection has had less opportunity to impose its effects and gene interactions are weak, this geometric filtering may be less consequential. But when epistatic effects shape fitness, constraints could hide substantial genetic potential behind these boundaries. This Perspective suggests potential escape routes from current plateaus: strategic wide crosses, transgene combinations and targeted edits that access genetic variance currently excluded by constraints.
Gastrointestinal nematodes remain a major challenge in high-risk stocker cattle, impacting performance, health, and animal welfare. Routine blanket deworming combined with intensive grazing systems has accelerated anthelmintic resistance, threatening long-term parasite control. Sustainable management requires integrating diagnostics, refugia-based strategies, concomitant anthelmintic therapy, and improved nutrition and stress management. Adoption is limited by knowledge gaps and behavioral barriers. Developing cattle health and production data infrastructure, improving stakeholder collaboration, and implementing practical, evidence-based recommendations are essential to preserve anthelmintic efficacy and support long-term productivity in stocker cattle systems.
This study aimed to evaluate the effect of the peripheral perfusion index (PPI)-based goal-directed fluid resuscitation strategy for reducing the incidence of acute skin failure (ASF) in elderly critically ill patients. We conducted a prospective, randomized, parallel-controlled study by enrolling 216 elderly critically ill patients who required early active fluid resuscitation from January 2025 to December 2025. They were randomly assigned to 2 categories: PPI-guided and conventional resuscitation groups. The intervention group considered PPI ≥1.4 as an additional resuscitation endpoint with conventional macrohemodynamic goals. Based on routine indicators, the control group received fluid management only. Our primary outcome comprised the incidence of ASF within 7 days of intensive care unit admission. Secondary outcomes included time to ASF onset, resuscitation quality indicators, organ function, and long-term prognosis. Data were analyzed according to the intention-to-treat principle. Our study involved 204 patients (103 intervention and 101 control). The intervention group (14.6%, 15/103) experienced a significantly reduced 7-day incidence of ASF compared with the control group (29.7%, 30/101, P = .009). However, the median time to ASF onset was prolonged in the intervention group (5.2 days vs 3.1 days, log-rank P = .012). Regarding the resuscitation quality, the intervention group demonstrated a higher 6-hour lactate clearance rate (28.5% ± 12.3% vs 21.8% ± 14.1%, P = .001) and reduced cumulative positive fluid balance at 72 hours (+1250 ± 980 mL vs +1850 ± 1100 mL, P < .001). The 28-day all-cause mortality between the groups remained nonsignificant. A PPI-based goal-directed fluid resuscitation strategy significantly reduces the risk of ASF in elderly critically ill patients, improves early perfusion marker assessments, and optimizes fluid management. This noninvasive, bedside monitoring approach provides a new clinical rationale for protecting skin health in critically ill patients.