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.
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.
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.
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.
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.
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.
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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.
To evaluate an annotation-free deep learning (DL) approach for the image-level detection of periapical bone rarefactions (PBRs) on panoramic radiographs (PRs). A retrospective dataset of 2,527 PRs was classified at the image level based on expert consensus using internationally accepted radiographic criteria. Multiple pretrained convolutional neural network (CNN) and vision transformer (ViT) architectures were evaluated under different modeling strategies, including fine-tuning and attention mechanisms. Model performance was assessed using accuracy, recall, specificity, and F1 score. Inferential comparisons were performed using nonparametric statistical tests. CNN-based models consistently outperformed ViT architectures in binary classification of PBRs. The fine-tuned Xception model achieved the highest overall performance, with an F1-score of 64.7% and low variability across repeated runs. Analyses were restricted to Classes A and B due to class imbalance constraints, then multiclass evaluation was not performed at this stage. Annotation-free DL demonstrated feasibility for binary image-level detection of PBRs on PRs, reducing dependence on labor-intensive spatial annotations while maintaining clinically interpretable behavior. Multiclass classification remains a target for investigation with balanced datasets. The approach supports scalable image-level analysis under clinically realistic conditions, although external validation is still required to confirm generalizability.
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.
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.
BackgroundAcute kidney injury (AKI) is a serious complication in early preterm neonates with severe birth asphyxia, yet its incidence and predictors in this specific population remain incompletely characterised. The effect of caffeine initiation timing on AKI outcomes has not been prospectively examined.MethodsThis prospective observational cohort study enrolled 112 neonates of 28-32 weeks gestational age with severe birth asphyxia admitted to a level III neonatal intensive care unit (NICU) in South India (February-August 2025). AKI was defined by neonatal KDIGO (nKDIGO) criteria. Neonates were categorised according to early (≤6 h) or delayed (>6 h) caffeine initiation; delayed initiation was primarily associated with outborn status and haemodynamic instability at admission. Independent predictors of AKI were identified by multivariate logistic regression with bootstrap confidence intervals.ResultsAKI was diagnosed in 48 of 112 neonates (42.9%; 95% CI 34.1-52.1%). Stage 1 disease predominated (47.9% of AKI cases), with onset in the first 48 h in the majority. On multivariate analysis, early caffeine initiation was independently associated with reduced odds of AKI (aOR 0.22; 95% CI 0.11-0.43; p < 0.001), and cumulative fluid balance at 48 h was associated with increased odds (aOR 6.30 per SD [21.8 ml/kg]; 95% CI 4.27-13.05; p < 0.001). AKI incidence was 24.1% in the early caffeine group versus 60.3% in the delayed group (p < 0.001), with an observed difference in AKI incidence of 36.2%. In-hospital mortality was higher in the AKI group (10.4% vs 0%; p = 0.013).ConclusionsAKI occurred in 42.9% of early preterm neonates with severe birth asphyxia. Early caffeine initiation (≤6 h) was associated with reduced AKI incidence. Positive fluid balance at 48 h was an independent predictor. These findings suggest early caffeine initiation as a potentially modifiable factor associated with reduced AKI risk and identify fluid balance as a clinically relevant early marker in this high-risk population.
Dihydroartemisinin-piperaquine is increasingly used for malaria treatment and chemoprevention in children with HIV co-infection. Its efficacy and safety are associated with piperaquine exposure, which can be compromised by drug-drug interactions with antiretroviral therapy. In a prospective, open-label study, we evaluated the pharmacokinetics of piperaquine following a 3-day standard dihydroartemisinin-piperaquine regimen in malaria-uninfected Ugandan children living with HIV receiving either dolutegravir-, lopinavir/ritonavir-, or efavirenz-based antiretroviral therapies. Children without HIV aged 11-17 and 3-10 years were enrolled as control groups to match (a) the dolutegravir and (b) lopinavir/ritonavir and efavirenz groups, respectively (n = 30 per group). Intensive pharmacokinetic sampling for piperaquine over 42 days was completed. Compared to controls, overall piperaquine exposure, as measured by area under the concentration-time curve from the 3rd dihydroartemisinin-piperaquine dose to 42 days in the dolutegravir group was similar but terminal piperaquine concentrations were reduced by 32% on day 28 (P = 0.02) and 64% on day 42 (P < 0.0001). In contrast, overall piperaquine exposure in the lopinavir/ritonavir group increased by 240% (P < 0.0001), with day 42 concentration increasing by 91% (P < 0.0001), while exposure with efavirenz was reduced by 69% (P < 0.0001), with day 42 concentration reducing by 92% (P < 0.0001). Electrocardiographic monitoring during co-administration with lopinavir/ritonavir identified two transient grade 3 changes that resolved. Efavirenz and lopinavir/ritonavir have opposing effects on piperaquine exposure in children living with HIV, which may impact efficacy and toxicity, respectively, although co-administration in this study did not yield concerning safety findings. Dolutegravir reduced only terminal concentrations significantly, which may shorten the duration of post-treatment chemoprophylaxis.
To determine whether individualized heparin dosing guided by a heparin dose-response (HDR) curve is noninferior to conventional weight-based dosing in achieving target activated clotting time (ACT) of ≥480 seconds before cardiopulmonary bypass (CPB) and to compare total heparin and protamine requirements, postoperative blood loss, and transfusion needs in children younger than 14 years undergoing cardiac surgery with cardiopulmonary bypass support. Single-center, prospective, double-blinded, randomized controlled trial. Cardiothoracic operating theaters and intensive care unit of a tertiary care hospital in India. Pediatric (<14 years) patients undergoing elective cardiac surgery with CPB support. The HDR group received an initial test dose of 100 IU/kg of heparin, and an individualized ACT dose-response curve was constructed to determine the dose required to target an ACT of 480 seconds. Controls received standard 400 IU/kg of heparin. Protamine was given post-CPB per protocol in both groups. In this noninferiority trial, HDR-guided anticoagulation was assessed against conventional weight-based dosing for first-pass attainment of ACT ≥480 seconds before CPB. Target ACT was achieved in 72.2% (26/36) of HDR patients versus 83.3% (30/36) of controls (p = 0.396). Although HDR was associated with lower heparin exposure (260 v 420 IU/kg; p < 0.001) and protamine use (4.1 v 4.8 mg/kg; p = 0.002), as well as reduced 24-hour blood loss (5.2 v 6.5 mL/kg; p = 0.03) and packed red blood cell transfusion (6.8 v 8.2 mL/kg; p = 0.04), it did not demonstrate superior first-attempt ACT attainment. HDR-guided heparinization reduced heparin and protamine exposure and was associated with less bleeding and transfusion, but it did not improve first-pass ACT attainment. Because ACT is an imperfect surrogate for anticoagulant adequacy in children on CPB, these findings should be interpreted as ACT-guided dosing data rather than proof of equivalent anticoagulation. Larger multicenter studies with mechanistic and clinical endpoints are needed to confirm these results.
Tubo-ovarian abscess is a severe form of pelvic inflammatory disease that is typically caused by ascending polymicrobial infections in sexually active women. However, it is extremely rare in sexually inactive women, and its pathogenesis in such cases remains poorly understood. Atopic dermatitis is associated with impaired skin barrier function and increased susceptibility to Staphylococcus aureus bacteremia. Here, we present a rare case of septic shock due to a ruptured ovarian abscess caused by S. aureus in a sexually inactive woman with atopic dermatitis. A 44-year-old Japanese woman with no history of sexual intercourse presented with a prolonged fever lasting 4 weeks. Six weeks before admission, she developed pruritic blisters between the right index and middle fingers due to atopic dermatitis, which subsequently ruptured. Seventeen days before referral, she had watery diarrhea and was diagnosed with enteritis at a clinic. Persistent symptoms raised suspicion for viral hepatitis based on elevated C-reactive protein levels and mild liver dysfunction. Subsequently, the patient developed recurrent high-grade fever and lower abdominal pain. Imaging revealed a large pelvic abscess with ascites, and she was transferred to our hospital. On arrival, she was in septic shock, with a blood pressure of 80/40 mmHg and a pulse rate of 125 bpm. A ruptured left ovarian abscess arising from an infected mature cystic teratoma was diagnosed, and emergency laparoscopic surgery was performed. The procedure revealed severe intraperitoneal inflammation with purulent ascites. S. aureus was isolated from both blood cultures and abscess contents. Postoperatively, the patient underwent intensive care management for septic shock and acute kidney injury, gradually recovering with appropriate antibiotic therapy. She was discharged without complications and remained recurrence-free at the 1-year follow-up. No gastrointestinal or gynecological source of infection was identified despite extensive evaluation, raising the possibility of a hematogenous route of infection. The patient's atopic dermatitis may have contributed to increased susceptibility to S. aureus bacteremia through skin blistering, potentially resulting in bacterial seeding of the ovary. This case underscores the diagnostic challenges associated with atypical ovarian abscesses and highlights the importance of including them in the differential diagnosis of atypical, prolonged fever and abdominal symptoms, even in sexually inactive women, particularly those with atopic dermatitis.
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.
Yellow rust (YR) is a major threat to both bread and durum wheat production, often causing substantial yield losses. Conventional visual scoring of YR severity, while widely adopted, is labor-intensive, time-consuming, and prone to human error. In this study, we evaluated the predictability (PA), defined as the correlation between predicted and observed values, using genomic and phenomic data for YR severity under multiple prediction scenarios in two biparental wheat populations (bread and durum). YR scoring was conducted on two dates, with YR severity visually assessed while unmanned aerial vehicle (UAV)-based high-throughput phenotyping (HTP) data were collected using a multispectral camera. HTP data were processed to extract spectral wavelengths and vegetation indices (VIs), and all lines were also genotyped using SNP arrays. We tested a diverse set of models, including parametric, machine learning, and deep learning approaches. PA increased markedly when HTP-derived data were used compared with genomic markers alone. For example, support vector regression (SVR) improved from 0.35 (markers only) to 0.87 (wavelengths only). However, integrating genomic and phenomic data did not yield further improvements, as models often plateaued when using HTP-derived features alone. Cross-crop prediction demonstrated promising generalization across bread and durum wheat, achieving PA values up to 0.83. For this last task, best linear unbiased prediction (BLUP) and multilayer perception (MLP) consistently provided robust performance across scenarios. These findings highlight the strong potential of UAV-based HTP for rapid, scalable, and accurate prediction of YR severity in wheat. While genomics retains broad utility for breeding, the practical integration of phenomics and AI-driven prediction pipelines will ultimately depend on breeding program strategies, resources, and objectives.