RSV Neutralizing Antibodies Following Nirsevimab and Palivizumab Dosing.

BACKGROUND: Data describing respiratory syncytial virus (RSV) neutralizing antibody (nAb) levels for nirsevimab, a recently approved, extended half-life, anti-RSV fusion protein (F protein) monoclonal antibody, relative to the previous standard of care, palivizumab, have not been reported. METHODS: The MEDLEY trial was a randomized, palivizumab-controlled, phase 2/3 study of nirsevimab during 2 RSV seasons (season 1 and 2) in infants born preterm (≤35 weeks' gestational age; dosed season 1 only) or with congenital heart disease or chronic lung disease of prematurity (dosed seasons 1 and 2). Participants were randomly assigned to receive a single dose of nirsevimab followed by 4 monthly placebo doses, or 5 once-monthly doses of palivizumab. Anti-RSV fusion protein serology (ie, levels of prefusion [pre-F]/postfusion [post-F] conformation antibodies), nirsevimab and palivizumab serum concentrations, and RSV nAbs were measured in participant samples collected at baseline (pre-dose) and days 31, 151, and 361. RESULTS: Serologic data were similar in seasons 1 and 2. Nirsevimab predominately conferred pre-F antibodies, whereas palivizumab conferred pre-F and post-F antibodies. Nirsevimab and palivizumab serum concentrations were highly correlated with nAb levels in both seasons. In season 1, the nAb levels in nirsevimab recipients were highest in day 31 samples and gradually declined but remained 17-fold above baseline at day 361. nAb levels in palivizumab recipients increased incrementally with monthly doses to day 151. nAb levels followed similar patterns in season 2. nAb levels were ∼10-fold higher with nirsevimab compared with palivizumab across both seasons. CONCLUSIONS: Nirsevimab prophylaxis confers ∼10-fold higher and more sustained RSV nAb levels relative to palivizumab.

Effects of intubation and hypoxemia on intraventricular hemorrhage in preterm infants during the first week: An observational study.

BACKGROUND: Preterm infants with intraventricular hemorrhage (IVH) are at a risk of developing neurodevelopmental disabilities. Few studies have examined the effects of oxygen saturation (SpO2) changes and intubation procedures on the risk of IVH. OBJECTIVES: We examined the effects of intubation and the rates of three thresholds of hypoxemia on the occurrence of IVH in preterm infants during their first week in the neonatal intensive care unit (NICU). METHODS: In this prospective observational cohort study, preterm infants with a gestational age (GA) of <37 weeks were included from two Level III NICUs in Taiwan. Continuous electrocardiography was used to monitor SpO2 changes, and cranial ultrasonography was used to monitor IVH. Thresholds of hypoxemia (SpO2 levels of <80 %, <85 %, and <90 %) were screened by digitally sampling data at 10-s intervals. Generalized estimating equations were used with logistic regression to analyze the effects of intubation and the rates of the three thresholds of hypoxemia on the risk of IVH during the first week after birth. RESULTS: In all preterm infants (N = 73), the mean GA was 31.55 weeks, and the mean birth weight was 1508.86 g. Intubation within 3 days of birth, duration of mechanical ventilation and oxygen use, hypoxemia rate, and maternal use of magnesium sulfate before and during delivery were significantly associated with IVH. A multivariate analysis revealed that intubation was a key factor associated with the occurrence of IVH across different thresholds of hypoxemia (p = 0.004). CONCLUSIONS: Although the rate of hypoxemia, duration of mechanical ventilation and oxygen use, and maternal use of magnesium sulfate were significantly associated with IVH, intubation within 3 days of birth was the key factor responsible for increased IVH risk.

The role of geographic distances in green industrial pilot policies evaluation: A sustainability transition perspective.

Green industrial policies (GIPs) aim to promote the adoption of green technology within a sustainability framework. While previous evaluations of GIP have focused more on the policy itself and the impacts within the policy boundaries, this paper further introduces the geographical factor to analyze the impact of different spatial geographic distances on implementing GIP. By integrating geographic distances into a spatial difference-in-differences analysis to assess the effects of municipal green industry policies (referred to as green industry pilot policies in this paper) enacted in 11 cities in China from 2006 to 2010, we find that these policies not only improve environmental and economic outcomes in targeted regions but also have spillover effects that may affect neighboring areas negatively, highlighting the importance of geographic considerations. The effectiveness of green industrial policies varies across cities, influenced by local socio-technical systems and regional characteristics such as infrastructure and information technology. These findings suggest that policy impacts are complex and multifaceted, requiring a comprehensive understanding of geographic interdependencies. By incorporating geographic factors, this research contributes to sustainability transition theory by offering insights into the spatial and temporal dynamics of socio-technical systems. The results underscore the need for policymakers to consider spatial-temporal aspects and potential secondary effects on adjacent regions when designing and implementing green industrial policies.

Association of Decreased Enhancement of Nasoseptal Flap on Postoperative Magnetic Resonance Imaging with the Risk of Complication.

Objectives Our objective was to determine if decreased contrast enhancement on postoperative magnetic resonance imaging (MRI) is associated with an increased risk of complication in patients who have undergone nasoseptal flap (NSF) reconstruction. Design/Setting This was a single-institution retrospective study of patients who underwent a first-time endoscopic endonasal approach (EEA) with NSF reconstruction. Participants Patients underwent an EEA to the skull base with NSF reconstruction and received postoperative MRI within 3 weeks of the operation. Main Outcome Measures MR exams were scored on the degree of contrast enhancement at first postoperative MRI. An enhancement score of 4 indicated ≥75% enhancement of the NSF. A score of 3 indicated enhancement ≥50% and <75% enhancement of the NSF. A score of 2 indicated ≥25% and <50% enhancement of the NSF. Complications (e.g., cerebrospinal fluid [CSF] leak, meningitis, empyema, cerebritis, brain abscess, flap necrosis, and flap migration) were retrieved from our institution's skull base database. Logistic regression was used to determine the effect of the MRI enhancement score on the odds of developing a complication. Results Out of 99 patients in the study, six had complications. Patients who underwent NSF reconstruction of skull base defects were found to have 19 times higher odds of complication ( p = 0.007) if they had had an NSF enhancement score of 2 on their postoperative MRI when compared with patients with complete or near complete NSF enhancement (score 4). Conclusion Quantifying NSF enhancement with an MRI may help surgeons better predict which of their patients are at an increased risk of complication.

Continuously tunable single-photon level nonlinearity with Rydberg state wave-function engineering.

Extending optical nonlinearity into the extremely weak light regime is at the heart of quantum optics, since it enables the efficient generation of photonic entanglement and implementation of photonic quantum logic gate. Here, we demonstrate the capability for continuously tunable single-photon level nonlinearity, enabled by precise control of Rydberg interaction over two orders of magnitude, through the use of microwave-assisted wave-function engineering. To characterize this nonlinearity, light storage and retrieval protocol utilizing Rydberg electromagnetically induced transparency is employed, and the quantum statistics of the retrieved photons are analyzed. As a first application, we demonstrate our protocol can speed up the preparation of single photons in low-lying Rydberg states by a factor of up to∼40. Our work holds the potential to accelerate quantum operations and to improve the circuit depth and connectivity in Rydberg systems, representing a crucial step towards scalable quantum information processing with Rydberg atoms.

C-Reactive Protein Induces Immunosuppression by Activating FcγR2B in Pulmonary Macrophages to Promote Lung Metastasis.

C-reactive protein (CRP) is a liver-derived acute phase reactant that is a clinical marker of inflammation associated with poor cancer prognosis. Elevated CRP levels are observed in many types of cancer and are associated with significantly increased risk of metastasis, suggesting that CRP could have pro-metastatic actions. Here, we reported that CRP promotes lung metastasis by dampening the anti-cancer capacity of pulmonary macrophages in breast cancer and melanoma. Deletion of CRP in mice inhibited lung metastasis of breast cancer and melanoma cells without significantly impacting tumor growth compared to wildtype mice. In addition, the lungs of CRP deficient mice were enriched for activated pulmonary macrophages, which could be reduced to the level of wildtype mice by systemic administration of human CRP. Mechanistically, CRP blocked the activation of pulmonary macrophages induced by commensal bacteria in a FcγR2B-dependent manner, thereby impairing macrophage-mediated immune surveillance to promote the formation of a pre-metastatic niche in the lungs of tumor-bearing mice. Accordingly, treatment with specific CRP inhibitors activated pulmonary macrophages and attenuated lung metastasis in vivo. These findings highlight the importance of CRP in lung metastasis, which may represent an effective therapeutic target for patients with advanced solid cancers in clinics.

Evaluating deep learning techniques for identifying tongue features in subthreshold depression: a prospective observational study.

Objective: This study aims to evaluate the potential of using tongue image features as non-invasive biomarkers for diagnosing subthreshold depression and to assess the correlation between these features and acupuncture treatment outcomes using advanced deep learning models. Methods: We employed five advanced deep learning models-DenseNet169, MobileNetV3Small, SEResNet101, SqueezeNet, and VGG19_bn-to analyze tongue image features in individuals with subthreshold depression. These models were assessed based on accuracy, precision, recall, and F1 score. Additionally, we investigated the relationship between the best-performing model's predictions and the success of acupuncture treatment using Pearson's correlation coefficient. Results: Among the models, SEResNet101 emerged as the most effective, achieving an impressive 98.5% accuracy and an F1 score of 0.97. A significant positive correlation was found between its predictions and the alleviation of depressive symptoms following acupuncture (Pearson's correlation coefficient = 0.72, p<0.001). Conclusion: The findings suggest that the SEResNet101 model is highly accurate and reliable for identifying tongue image features in subthreshold depression. It also appears promising for assessing the impact of acupuncture treatment. This study contributes novel insights and approaches to the auxiliary diagnosis and treatment evaluation of subthreshold depression.

Noninvasive Prenatal Genetic Screening of Cell-Free Fetal DNA for Early Prediction of ß-Thalassemia Using Fiber Optic Nanogold-Linked Sorbent Assay.

ß-Thalassemia is a prevalent type of severe inherited chronic anemia, primarily identified in developing countries. The identification of single nucleotide polymorphisms (SNPs) plays a vital role in the early diagnosis of genetic diseases. Here, we reported the development of an amplification-free fiber optic nanogold-linked sorbent assay method using a fiber optic particle plasmon resonance (FOPPR) biosensor for rapid and ultrasensitive detection of SNPs. Herein, MutS protein was selected as the biorecognition capture probe and immobilized on the sensing region to capture the target mutant DNA, which was hybridized with a single-base mismatched single-stranded DNA labeled by a gold nanoparticle (AuNP). The AuNP acts as a signaling agent to be detected by the FOPPR biosensor when it is bound on the fiber core surface. The method effectively differentiates mismatched double-stranded DNA by MutS protein from perfectly matched/complementary dsDNA. It exhibits an impressively low detection limit for the detection of SNPs at approximately 10-16 M using low-cost sensor chips and devices. By determination of the ratio of mutant DNA to normal DNA in cell-free genomic DNA from blood samples, this method is promising for diagnosing ß-thalassemia in fetuses without invasive testing techniques.

Changes in pituitary adenoma patient presentation and outcomes during the COVID pandemic at a Pituitary Center of Excellence.

PURPOSE: The COVID-19 pandemic caused significant disruption to the surgical care of patients. The aim of this study was to analyze the impact of the pandemic on endoscopic endonasal surgery (EES) for patients with a pituitary adenoma. METHODS: Patients from 2015 to 2022 that had EES for a pituitary adenoma were included in this study. Patients were separated into pre-COVID (January 2015-March 2020) and COVID (March 2020-September 2022) groups. Univariate analysis was done using chi-square, fisher exact tests, and t-tests to compare groups. RESULTS: This study included 492 patients that had EES for their pituitary adenoma. There were 314 patients in the pre-COVID group and 178 patients in the COVID group. Patients in the COVID group had a higher risk analysis index (RAI) frailty score (15 ± 10 pre-COVID vs. 20 ± 9 COVID, P < 0.001) and a higher American Society of Anesthesiology (ASA) physical status score (3 or 4) (72.0% pre-COVID vs. 81.9% COVID, P = 0.02). There were significantly more macroadenoma cases (87.6% pre-COVID vs. 94.4% COVID, P = 0.02) and extrasellar surgical approaches (45.2% pre-COVID vs. 61.2% COVID, P < 0.001) during COVID. There was no significant difference in length of stay (LOS) and readmission rates between groups. CONCLUSIONS: Patients that presented during the pandemic tended to be more frail, have more comorbidities, and require additional extrasellar surgical approaches. Despite changes in clinical presentation and operative management, the LOS and readmission rate remained stable during COVID, supporting the safety of this procedure during the recent pandemic.

Peripheral PD-1+NK cells could predict the 28-day mortality in sepsis patients.

Background: Unbalanced inflammatory response is a critical feature of sepsis, a life-threatening condition with significant global health burdens. Immune dysfunction, particularly that involving different immune cells in peripheral blood, plays a crucial pathophysiological role and shows early warning signs in sepsis. The objective is to explore the relationship between sepsis and immune subpopulations in peripheral blood, and to identify patients with a higher risk of 28-day mortality based on immunological subtypes with machine-learning (ML) model. Methods: Patients were enrolled according to the sepsis-3 criteria in this retrospective observational study, along with age- and sex-matched healthy controls (HCs). Data on clinical characteristics, laboratory tests, and lymphocyte immunophenotyping were collected. XGBoost and k-means clustering as ML approaches, were employed to analyze the immune profiles and stratify septic patients based on their immunological subtypes. Cox regression survival analysis was used to identify potential biomarkers and to assess their association with 28-day mortality. The accuracy of biomarkers for mortality was determined by the area under the receiver operating characteristic (ROC) curve (AUC) analysis. Results: The study enrolled 100 septic patients and 89 HCs, revealing distinct lymphocyte profiles between the two groups. The XGBoost model discriminated sepsis from HCs with an area under the receiver operating characteristic curve of 1.0 and 0.99 in the training and testing set, respectively. Within the model, the top three highest important contributions were the percentage of CD38+CD8+T cells, PD-1+NK cells, HLA-DR+CD8+T cells. Two clusters of peripheral immunophenotyping of septic patients by k-means clustering were conducted. Cluster 1 featured higher proportions of PD1+ NK cells, while cluster 2 featured higher proportions of naïve CD4+T cells. Furthermore, the level of PD-1+NK cells was significantly higher in the non-survivors than the survivors (15.1% vs 8.6%, P<0.01). Moreover, the levels of PD1+ NK cells combined with SOFA score showed good performance in predicting the 28-day mortality in sepsis (AUC=0.91,95%CI 0.82-0.99), which is superior to PD1+ NK cells only(AUC=0.69, sensitivity 0.74, specificity 0.64, cut-off value of 11.25%). In the multivariate Cox regression, high expression of PD1+ NK cells proportion was related to 28-day mortality (aHR=1.34, 95%CI 1.19 to 1.50; P<0.001). Conclusion: The study provides novel insights into the association between PD1+NK cell profiles and prognosis of sepsis. Peripheral immunophenotyping could potentially stratify the septic patients and identify those with a high risk of 28-day mortality.

The impacts of percutaneous coronary intervention to treat chronic total occlusion of right coronary artery on the 5-year prognosis: A single-centered retrospective study.

BACKGROUND: Chronic total occlusions (CTO) occur in about 20% of patients referred for coronary angiography, and right coronary artery (RCA) CTO has been reported in 38-50% of the entire CTO population. Limited data on angiographic and procedural characteristics of RCA-CTO and the risk of adverse cardiac events asks for a detailed study. METHODS: From 2010 to 2013, patients with attempted revascularization of at least one CTO lesion were included and followed up to 5 years after PCI. Eligible patients are assigned to RCA-CTO and non-RCA-CTO groups based on their target vessels. The primary endpoint was major adverse cardiovascular events (MACEs; a composite of all-cause death, myocardial infarction (MI) or rehospitalization for heart failure), and secondary endpoints were cardiac death, target lesion revascularization (TLR) and target vessel revascularization (TVR). RESULTS: The present study included 2659 eligible patients, among which 1285 patients were assigned to the RCA-CTO group, whereas 1374 patients were assigned to the non-RCA-CTO group. Lesions in RCA had longer lesion length, higher J-CTO score, higher rates of severe vessel tortuosity, a higher percentage of Rentrop grade 2-3, and more likely to be re-try lesion than those in LAD or LCX (all P < 0.01). CTO lesions in RCA reached less successful recanalization and post-procedural TIMI 3 flow (all <0.01). Multivariate Cox analysis revealed that RCA-CTO was not associated with primary outcome MACEs. Besides MACEs, RCA-CTO was also not associated with cardiac death, but was significantly associated with TLR and TVR (adjusted HR: 1.37 [95% CI:1.07-1.76], P = 0.01; adjusted HR: 1.43 [95% CI:1.13-1.82], P = 0.003). CONCLUSION: RCA-CTO lesions, which had more complex angiographic features, independently contributed to TLR and TVR but not to MACEs or cardiac death in the 5 years of follow-up.

Betaine and I-LG may have a predictive value for ATB: A causal study in a large European population.

PURPOSE: To analyze the causal relationship between 486 human serum metabolites and the active tuberculosis (ATB) in European population. METHODS: In this study, the causal relationship between human serum metabolites and the ATB was analyzed by integrating the genome-wide association study (GWAS). The 486 human serum metabolites were used as the exposure variable, three different ATB GWAS databases in the European population were set as outcome variables, and single nucleotide polymorphisms were used as instrumental variables for Mendelian Randomization. The inverse variance weighting was estimated causality, the MR-Egger intercept to estimate horizontal pleiotropy, and the combined effects of metabolites were also considered in the meta-analysis. Furthermore, the web-based MetaboAnalyst 6.0 was engaged for enrichment pathway analysis, while R (version 4.3.2) software and Review Manager 5.3 were employed for statistical analysis. RESULTS: A total of 21, 17, and 19 metabolites strongly associated with ATB were found in the three databases after preliminary screening (P < 0.05). The intersecting metabolites across these databases included tryptophan, betaine, 1-linoleoylglycerol (1-monolinolein) (1-LG), 1-eicosatrienoylglycerophosphocholine, and oleoylcarnitine. Among them, betaine (I2 = 24%, P = 0.27) and 1-LG (I2 = 0%, P = 0.62) showed the lowest heterogeneity among the different ATB databases. In addition, the metabolic pathways of phosphatidylethanolamine biosynthesis (P = 0.0068), methionine metabolism (P = 0.0089), betaine metabolism (P = 0.0205) and oxidation of branched-chain fatty acids (P = 0.0309) were also associated with ATB. CONCLUSION: Betaine and 1-LG may be biomarkers or auxiliary diagnostic tools for ATB. They may provide new guidance for medical practice in the early diagnosis and surveillance of ATB. In addition, by interfering with phosphatidylethanolamine biosynthesis, methionine metabolism, betaine metabolism, oxidation of branched-chain fatty acids, and other pathways, it is helpful to develop new anti-tuberculosis drugs and explore the virulence or pathogenesis of ATB at a deeper level, providing an effective reference for future studies.

An updated immunosenescence exploration in healthy Chinese donors: circular elevated PD-1 on T cell and increased Ki67 on CD8+ T cell towards aging.

Immunosenescence is a process of immune dysfunction that occurs along with aging. Many studies have focused on the changes of different lymphocyte subsets in diseases and immune aging. However, the fluctuation in the number and phenotype of lymphocyte subset caused by aging have not been comprehensively analyzed, especially the effects of new indicators such as PD-1 and Ki67 in peripheral blood have been rarely reported. We further investigated the humoral and cellular immune parameters of 150 healthy donors over 18 years old. Age was associated with decreased CD4+CD45RA+CD62L+ T cells, decreased CD4+CD45RA+CD31+ T cells, and increased memory CD4+ or CD8+ T cells, dominated by male CD8+ T cells. The loss of CD28 expression on T cells and the transverse trend of activated CD38 and HLA-DR were also related to the increased age. In addition, CD8+ T cells in men were more prominent in activation indicators, and the difference between the old and young groups was obvious. CD4+CD25+CD127- T cells percentage tended to decrease with age and did not differ significantly between gender. Interestingly, we found that age was positively associated with PD-1+ T cells and showed significant age-related variability in men. Similarly, the percentage of CD8+ki-67+ also showed an increasing trend, with significant differences between the young group and other elderly groups in males. Our findings can provide immunological clues for future aging research, offering new insights for clinical monitoring and prevention of certain diseases.

A methodological study on the identification of ecological security change processes and zoning control strategies -- Based on the perspective of sustainable development.

Ecological security (ES) is a crucial indicator for assessing the sustainable development of a region. Currently, most studies on ES primarily focus on process analysis, and the integration of environmental variability into the development of tailored control strategies for regions with varying ecological quality is overlooked. Therefore, in this study, we identified regional ES change processes, employed an optimized system to calculate the ecological security index (ESI), and identified ecological corridors (ECs) through the Minimum Constrained Resource (MCR) model to determine zoning strategies for typical arid regions, using the Ningxia region in the Yellow River Basin of China as an example. The findings showed that (1) from 2006 to 2020, the ESI values of most regions were between 0.2 and 0.4, with small but consistent increases in the ESI values over the years. (2) The proportion of regions with high ES ratings increased by 9.08 % across all districts and counties, and the center of gravity of ES shifted in a north-south and east-west direction. (3) The ESI exhibited a strong positive spatial correlation, characterized by spatial diffusion and spillover effects in most regions. (4) The ECs were predominantly distributed in a north-south direction, involving a total of 20 districts and counties. Based on the principles of sustainable development, we developed a model for the dynamic identification and zoning control of regional ES, aiming to provide a practical framework for effective ecological restoration and protection measures. Additionally, the strategies and methodologies presented in this study serve as important references for similar regions worldwide to facilitate the zoning control of ES, highlighting the broader significance and applicability of the study.

Comparative analysis of corneal parameters in simple myopic anisometropia using Scheimpflug technology.

Purpose: This study aims to investigate the differences in binocular corneal parameters and their interrelation with binocular biometric parameters asymmetry in patients with simple myopic anisometropia, thereby elucidating the influence of myopia process on various corneal parameters. Methods: In this cross-sectional study, 65 patients with anisometropia in monocular myopia were included. They were divided into low anisometropia group: 3.00D<Δ spherical equivalent (SE)≤-1.00D (Δ represents the difference between the two eyes, i.e., myopic data minus emmetropic data) and high anisometropia group: ΔSE ≤ -3.00D. Corneal and ocular biometric parameters were measured using Pentacam, Corvis ST, and IOL Master 700. Statistical analyses focused on the binocular corneal parameters asymmetry, using the contralateral emmetropia as a control. Results: The mean age of participants was 18.5 ± 1.3 years, with the average SE for myopia and emmetropia being -2.93 ± 1.09D and -0.16 ± 0.41D, respectively. The central corneal thickness (CCT), flat keratometry (Kf), keratometry astigmatism (Ka), total corneal aberration (6 mm) (TOA), surface variance index (ISV), vertical asymmetry index (IVA), stress-strain index (SSI), and first applanation stiffness parameter (SPA1) and ambrosia relational thickness-horizontal (ARTh) showed significant differences between anisometropic fellow eyes (p < 0.05). There were significant differences in ΔIVA, Δ the difference between the mean refractive power of the inferior and superior corneas (I-S), Δ deviation value of Belin/Ambrósio enhanced ectasia display (BAD-D), Δ deformation amplitude ratio max (2 mm) (DAR)and Δ tomographic biomechanical index (TBI) (p < 0.05) in two groups. Asymmetry of corneal parameters was correlated with asymmetry of ocular biometric parameters. Anisometropia (ΔSE) was positively correlated with ΔIVA (r = 0.255, p = 0.040), ΔBAD-D (r = 0.360, p = 0.006), and ΔSSI (r = 0.276, p = 0.039) and negatively correlated with ΔDAR (r = -0.329, p = 0.013) in multiple regression analysis. Δ mean keratometry (Km), Δ anterior chamber depth (ACD), and Δ biomechanically corrected intraocular pressure (bIOP) were also associated with binocular corneal differences. Conclusion: Compared to contralateral emmetropia, myopic eyes have thinner corneas and smaller corneal astigmatism. Myopic corneas exhibit relatively more regular surface morphology but are more susceptible to deformation and possess marginally inferior biomechanical properties. In addition, there is a certain correlation between anisometropia and corneal parameter asymmetry, which would be instrumental in predicting the development of myopia.

Comprehensive Summary of Safety Data on Nirsevimab in Infants and Children from All Pivotal Randomized Clinical Trials.

BACKGROUND: Nirsevimab is approved in the US for the prevention of respiratory syncytial virus (RSV) lower respiratory tract disease in neonates and infants during their first RSV season and in children aged ≤24 months who remain vulnerable to severe RSV disease through their second RSV season. We summarize a pre-specified analysis of nirsevimab safety data from three randomized controlled trials: Phase 2b (NCT02878330; healthy infants born ≥29 to <35 weeks' gestational age [wGA]); Phase 3 MELODY (NCT03979313; healthy infants born ≥35 wGA); and Phase 2/3 MEDLEY (NCT03959488; infants with congenital heart disease [CHD] and/or chronic lung disease of prematurity [CLD] or born ≤35 wGA). METHODS: Participants (randomized 2:1) received a single intramuscular dose of nirsevimab or comparator (placebo, Phase 2b/MELODY; 5× once-monthly palivizumab, MEDLEY) before their first RSV season (recipients < 5 kg, nirsevimab 50 mg; ≥5 kg, nirsevimab 100 mg). In MEDLEY, children with CHD/CLD continued to a second RSV season: first-season nirsevimab recipients received nirsevimab 200 mg; first-season palivizumab recipients were re-randomized 1:1 to receive nirsevimab 200 mg or 5× once-monthly palivizumab. RESULTS: The incidence, severity, and nature of AEs were similar across treatments (nirsevimab, n = 3184; placebo, n = 1284; palivizumab, n = 304). Most AEs were mild to moderate in severity, with ≥98% unrelated to treatment. AEs of special interest occurred infrequently (<1%): no anaphylaxis or thrombocytopenia were treatment-related, and no immune complex disease was reported. Deaths (incidence < 1.0%) were all unrelated to treatment. CONCLUSIONS: A single dose per season of nirsevimab for the prevention of RSV disease had a favorable safety profile, irrespective of wGA or comorbidities.

Retrospective Analysis of Adverse Factors Impacting Medicine Logistics.

Background: Medicine logistics, particularly cryogenic storage, maintains pharmaceutical efficacy and safety. Ensuring seamless transportation and storage prevents spoilage, degradation, or contamination, safeguarding patient health. Objective: This study aimed to analyze the relationships among the components of the medication cold chain logistics system using grey relational analysis (GRA). Additionally, we utilized GRA to construct an adjacency matrix, facilitating a comprehensive understanding of the interdependencies within the system. Methods: Data from pertinent indices spanning 2021 and 2022 were utilized to conduct a quantitative analysis using GRA. This analysis aimed to identify the most influential elements affecting the growth of pharmaceutical cold chain logistics in a specific location. The negative aspects of the medication cold chain logistics system in particular areas were examined by assessing the grey relationship grades between various components and the medicine cold chain logistics system in those regions. Results: The analysis revealed significant insights into the correlated risk factors impacting medicine logistics operations. Through an examination of the financial status and operational processes of medicine logistics assets, four categories of risks were identified, encompassing transportation, storage, distribution, and quality management. These categories were established by analyzing the most significant risk factors across these operational domains. Additionally, GRA was employed to assess the factors influencing medicine logistics. The study found a strong relationship between key parameters, such as transportation risk and site facilities and equipment, and the growth of the pharmaceutical logistics sector. Operation risk emerged as the least influential factor, while site facilities and equipment, transportation risk, and operation risk demonstrated substantial influence on the region's medical logistics sector growth. Conclusion: This study provides important recommendations to improve medicine logistics, aiming to mitigate adverse effects and elevate inventory management. Implementation can enhance efficiency and safety in the medicine supply chain, benefiting patient care and public health.

Self-Assessed Educational Needs of Chinese Pediatric Clinicians Regarding Pediatric Palliative Care: A Cross-Sectional Investigation.

BACKGROUND: An important first step in enhancing professional palliative care training is to investigate the educational needs of pediatric clinicians in this field. The aims of this research were to analyze the extent of end-of-life care experience of Chinese pediatric clinicians and identify the differing educational needs of physicians and nurses as well as associated impact factors. METHODS: A cross-sectional descriptive survey via a structural questionnaire was used in this research. RESULTS: In total, 187 clinicians, comprising 52 physicians and 135 nurses, participated in this study. The topics "pain management", "symptom management", and "discussing the prognosis with family members" were the most expressed educational needs among both physicians and nurses. Compared to nurses, physicians placed greater emphasis on the importance of "communication" and "pain and symptom management" (p < 0.05). Clinicians with more extensive end-of-life care experience more strongly felt the importance of learning about pain management and communication regarding end-of-life care (p < 0.05). CONCLUSIONS: Research showed that the education currently provided to pediatric clinicians does not meet their distinctive needs. Future palliative care education must be a continuing multi-level, interdisciplinary program and different education should be provided to physicians and nurses based on their respective needs.

Neuroimaging with Rotterdam Scoring System and long-term outcomes in severe traumatic brain injury patients.

PURPOSE: The Rotterdam Scoring System (RSS) attempts to prognosticate early mortality and early functional outcome in patients with traumatic brain injury (TBI) based on non-contrast head computed tomography (CT) imaging findings. The purpose of this study was to identify the relationship between RSS scores and long-term outcomes in patients with severe TBI. METHODS: Consecutively treated patients with severe TBI enrolled between 2008 and 2011, in the prospective, observational, Brain Trauma Research Center database were included. The Glasgow Outcome Scale (GOS) was used to measure long-term functional outcomes at three, six, 12, and 24 months. GOS scores were categorized into favorable (GOS = 4-5) and unfavorable (GOS = 1-3) outcomes. RSS scores were calculated at the time of image acquisition. RESULTS: Of the 89 patients included, 74 (83.4%) were male, 81 (91.0%) were Caucasian, and the mean age of the cohort was 41.9 ± 18.5 years old. Patients with an RSS score of 3 and lower were more likely to have a favorable outcome with increased survival rates than patients with RSS scores greater than 3. CONCLUSIONS: The RSS score determined on the head CT scan acquired at admission in a cohort of patients with severe TBI correlated with long-term survival and functional outcomes up to two years following injury.