Unexpected Events Research Articles

Background: Sudden cardiac arrest (SCA) is a critical and unexpected event that disrupts survivors’ physical, psychological, and social well-being. Objective: This study aimed to explore the lived experiences of individuals who survived SCA, focusing on their adaptation processes and the meaning they ascribed to life after the event. Methods: A descriptive phenomenological approach based on Giorgi’s methodology was employed. Twelve individuals who experienced SCA, received an implantable cardioverter defibrillator (ICD), and regularly attended a tertiary hospital outpatient clinic in South Korea participated in this study. Data were collected through semi-structured, face-to-face interviews and continued until theoretical saturation was reached. Thematic analysis was conducted to identify the essential structures of participants’ lived experiences. Results: Participants had a mean age of 50.6 years; eight were male and four were female. All were classified as New York Heart Association class I. Five essential themes were derived: (1) Being brought back at the edge of death —experiencing sudden collapse and revival through emergency care; (2) Living in fragile stability —a paradoxical sense of security coexisting with fear of recurrence; (3) Disruption of everyday life —struggles with physical limitations, social isolation, and an uncertainty about the future; (4) Enduring and striving alone —managing psychological distress while attempting to resume normalcy; and (5) Reframing life through a second chance —developing resilience and new meaning in life. Conclusions: The findings highlight the complex and evolving psychological and social adjustment processes experienced by SCA survivors. Long-term, tailored psychosocial support is essential to promote adaptation and reintegration. This study provides foundational insights to inform patient-centered care strategies in clinical settings.

Introduction: Pulmonary arterial hypertension (PAH) is a progressive disease. Continuous hemodynamic monitoring may help manage more severe PAH. The CardioMEMS HF System, an implantable pulmonary artery pressure (PAP) monitoring device, has shown promise in PAH management. However, its safety in patients with PAH remains undefined. Hypothesis: The use of the CardioMEMS is associated with an acceptable safety profile in patients with PAH. Methods: Adverse event data were combined from the completed CS1-003 (NCT05224531), on-going ARTISAN (NCT05203510), and on-going FIT_PH (NCT04078243) studies. Baseline assessments included demographics, hemodynamics, N-terminal pro B-type natriuretic peptide (NT-proBNP), 6-minute walk test (6MWT), and WHO Functional Class. Safety data were collected throughout each study. Results: At the time of analysis, 129 patients had received a CardioMEMS implant across the CS1-003 (n=25), ARTISAN (n=49), and FIT_PH (n=55) studies. All patients were diagnosed with PAH, with idiopathic, heritable, or drug/toxin-induced etiologies accounting for 81.4% of the cases, and connective tissue disease for 14.7%. The mean age was 54.6 years (range: 19-84), with 73.6% female patients. Most patients (77.5%) were classified as WHO Functional Class III or IV. The pooled means of baseline hemodynamic parameters were as follows: mean PAP of 47.9 mmHg (range: 23–81), mean right atrial pressure of 8.2 mmHg (range: 1–25), pulmonary artery wedge pressure of 10.0 mmHg (range: 1– 16), the cardiac output (CO) of 5.1 L/min (range: 1.3–10.9), and pulmonary vascular resistance of 8.4 Wood Units (range: 2–21). The average of baseline 6MWT was 336 meters (range: 10–930) and mean NT-proBNP was 978.6 ng/L (range: 18-11006). Based on the REVEAL 2.0 or Lite 2 risk scores (mean: 7, range: 2–14), the cohort was categorized at intermediate risk. A total of 71 (55%) patients completed at least 12 months of follow-up. Only five adverse events were reported as possibly related to the CardioMEMS implant procedure, including one serious adverse event. No unexpected adverse events, CardioMEMS device- or system-related adverse events, or sensor failures were reported by study sites throughout each study. Conclusions: The use of CardioMEMS in this combined PAH cohort has demonstrated a favorable safety profile, with few procedure-related adverse events and no enduring consequences. Future studies are warranted to investigate its long-term safety and efficacy in this population.

BackgroundTrials of deep brain stimulation (DBS) to the subcallosal cingulate gyrus (SCG) for treatment-resistant depression (TRD) have yielded mixed results. While open-label studies suggest effectiveness, randomized controlled trials (RCTs) have not consistently supported these findings. The study compared the efficacy of active versus sham SCG stimulation for TRD.MethodsParticipants (n = 35) in a major depressive episode and treatment resistance completed a 6-month double blind, crossover RCT, with an 18-month open-label phase. A Balaam design was applied with participants randomized to 1 of 4 stimulation groups over two 3-month phases. The primary outcome was a change in Hamilton Depression Rating Scale (HDRS) score at 6 months, with response defined as ≥50% reduction in HDRS-17 scores.ResultsWhile all groups showed improvement at 3 and 6 months, no significant differences were found among them. The OFF-OFF group had a numerically lower HDRS-17 score compared to the ON-ON group at the end of the RCT. No unexpected adverse events occurred. During the open-label phase, participants showed sustained reduction in HDRS-17 scores at 12, 18, and 24 months post-implantation, with successive observed-case response rates of 65.7%, 69%, and 73.1%, respectively. Improvements in life functioning were also noted.ConclusionsThis trial represents the largest single-centre, sham-controlled study of SCG DBS for TRD in the literature. Although the RCT showed no significant group differences, most participants achieved response during the open-label phase. Safety outcomes aligned with previous trials. Future RCTs should integrate insights from the past decade of DBS for TRD research to optimize outcomes. Key considerations include selecting DBS contact locations that ensure engagement of critical white matter tracts, employing novel and sufficiently long clinical trial designs to account for the non-specific effects of the DBS procedure, as well as incorporating biomarkers to guide DBS programming.

PurposeWomen with gestational diabetes mellitus (GDM) may experience disordered eating (DE), leading to adverse pregnancy outcomes and compromised mental health. However, in-depth studies in this field are lacking. This study explored the DE experiences among women with GDM, focusing on behavioral characteristics and potential risk factors.Patients and MethodsThis study was a descriptive qualitative study. Using purposive sampling, 23 pregnant women with GDM who had exhibited DE behaviors within the past month were recruited from a maternal and child health hospital in Nanjing, China. Semi-structured interviews were conducted with the participants. Data were analyzed using conventional content analysis.ResultsThree categories of DE experiences among women with GDM were identified: (1) behavioral characteristics; (2) internal drivers; (3) external enablers. DE behaviors in women with GDM primarily included restrictive eating, binge eating, and inappropriate insulin use. These behaviors often formed a vicious cycle: initial excessive restrictive eating led to binge eating due to intense hunger and food cravings, which in turn caused elevated glycemia and prompted impromptu restrictive eating, restarting the cycle. Inappropriate insulin use aimed at maintaining glycemic stability further perpetuated DE. Additionally, the study identified three internal drivers and three external enablers. Excessive risk perception mainly drove restrictive eating, insufficient internal motivation triggered binge eating, and low self-efficacy exacerbated both. Perceived pressure from dietary norms was a key external risk factor for the development of restrictive eating. Permissive messages from family members and disruptions from unexpected social events induced binge eating.ConclusionInternal and external factors led to a restrictive-binge eating cycle in women with GDM, sustained by inappropriate insulin use. Excessive risk perception about hyperglycemia and fetal health existed as unique risk factors. Future studies should be conducted across diverse cultural and geographical contexts to enhance the generalizability of our findings.

ABSTRACT ‘Complex thinking’ has become an essential skill for understanding current societal issues. Complexity, inherent in the living world, is part of our daily lives. Genetics, a complex discipline, occupies an increasing place in our society, notably through free access to online genetic tests. Our research questions the ability of students, at the end of their school journey, across all tracks, to grasp genetics in all its complexity. Is this discipline approached in such a way as to anchor fundamental knowledge essential to awaken the learner to a reality full of unexpected events and uncertainties? A first study examined the misconceptions conveyed by the education frames of reference, school curriculums, and textbooks used by French-speaking Belgian teachers (the prescribed). This analysis highlighted that the prescribed reflects little, if at all, the complexity of genetics and reinforces misconceptions. Two surveys were then conducted in order to analyse the practices of science teachers in the third degree of secondary education in French-speaking Belgium (the taught) and the knowledge of students leaving secondary school (the learned). These surveys reveal that a rather reductionist and deterministic approach, poorly contextualised, insufficiently updated (didactic transposition delay), and little nuanced persists in the teaching of genetics.

Effective detection of unexpected events in wide-area surveillance remains a critical challenge in the development of intelligent monitoring systems. Recent advancements in Narrowband Internet of Things (NB-IoT) and 5G technologies provide a robust foundation to address this issue. This study presents an integrated architecture for real-time event detection and response. The system utilizes the Constrained Application Protocol (CoAP) to transmit encapsulated JPEG images from NB-IoT modules to an Internet of Things (IoT) server. Upon receipt, images are decoded, processed, and archived in a centralized database. Subsequently, image data are transmitted to client applications via WebSocket, leveraging the Message Queuing Telemetry Transport (MQTT) protocol. By performing temporal image comparison, the system identifies abnormal events within the monitored area. Once an anomaly is detected, a visual alert is generated and presented through an interactive interface. The test results show that the image recognition accuracy is consistently above 98%. This approach enables intelligent, scalable, and responsive wide-area surveillance reliably, overcoming the constraints of conventional isolated and passive monitoring systems.

Disclosure: M. Celik Guler: None. R. Meral: None. M. Lightbourne: None. O. Besci: None. A. Neidert: None. M.C. Foss de Freitas: None. R.J. Brown: Pfizer, Inc., Regeneron Pharmaceuticals, Chiesi Farmaceutici, Marea Therapeutics. E.A. Oral: Ionis Pharmaceuticals Inc., Novo Nordisk, Chiesi Farmaceutici, Rhythm Pharmaceuticals, Marea Therapeutics, Rejuvenate Bio, Fractyl, Morphic Medical, Regeneron Pharmaceuticals.Lipodystrophy syndromes (LD) are rare disorders characterized by partial or generalized loss of adipose tissue and significant metabolic disturbances. Metreleptin (ML) remains the cornerstone of treatment for generalized lipodystrophy (GL); however, its efficacy in partial lipodystrophy (PL) can be limited, highlighting the need for alternative or incremental therapies to achieve optimal metabolic control. We hypothesize that combining leptin-based therapies, such as ML or leptin receptor agonists like mibavademab (investigational product), with incretin-based agents may offer a promising therapeutic strategy to enhance metabolic outcomes in this population. We report 6 patients taking ML or mibavademab for clinical or compassionate use in whom incretin-based therapies were added to enhance metabolic control, with outcomes prospectively followed. P1 (25-year-old, congenital generalized lipodystrophy (CGL) type 1, treated with metreleptin for 2.5 years): following the addition of semaglutide for 8 months, HbA1c reduced from 8.7% to 5.6%, BMI from 24.7 to 21.9 kg/m², and triglycerides (TG) from 2261 to 33 mg/dL. P2 (36-year-old, acquired GL, treated with metreleptin for 18 years): after 9 months of tirzepatide treatment, HbA1c reduced from 9.1% to 6.5%, BMI from 19.5 to 17.6 kg/m², and TG from 1240 to 100 mg/dL. P3 (25-year-old, LMNA related GL (with T10I variant), treated with mibavademab for 4 years): after adding dulaglutide for 5 months, HbA1c reduced from 8.9% to 7.3%, with stable BMI (14.4 kg/m²) and no change in TG (265 to 273 mg/dL). P4 (44-year-old, familial partial lipodystrophy type 2 (FPLD2), treated with metreleptin for 3.5 years): after 17 months of tirzepatide therapy, HbA1c reduced from 6.6% to 5.1%, BMI from 18.2 to 16.2 kg/m², and TG from 298 to 104 mg/dL. P5 (23-year-old, atypical PL, previously treated with mibavademab for 5 years and 10 months): Following initiation of tirzepatide for 4 months, there was no change in HbA1c (10.1% to 10.5%) or BMI (27.1 to 27.3 kg/m²) but a 49% reduction in TG (1764 to 895 mg/dL) was observed. P6 (52-year-old, FPLD2, treated with metreleptin for 10 years): initiation of tirzepatide for 5 months led to reductions in HbA1c (6.8% to 5.7%), BMI (26.0 to 21.8 kg/m²), and TG (279 to 127 mg/dL). There were no unexpected adverse events with combination therapy, but patient P5 had an episode of pancreatitis at month 5 due to running out of her insulin and worsening glucose control. In summary, combined leptin-based and incretin-based therapies may enhance metabolic outcomes in lipodystrophy. Future randomized controlled trials are needed to evaluate the efficacy of incretin-based therapies either with or without leptin pathway treatments to confidently determine the extent of benefit of combination therapy in lipodystrophy.Presentation: Sunday, July 13, 2025

ABSTRACTChildren often say that possible events are impossible, and only gradually come to see these events as possible. For instance, they often deny that people could do unusual things, like own a pet peacock, or immoral things, like stealing or lying. These possibility denials are surprising. For instance, children have first‐hand experience with the very moral violations they say are impossible. In two experiments (total N = 220), we provide evidence that children's possibility denials can nonetheless be taken at face value and do not merely arise from quirks in how children understand questions about possibility. We do this by showing that these denials also arise in children's judgments of actuality—their judgments about what has actually happened and about which assertions of actual events could be true. In Experiment 1, children aged 4–7 judged whether ordinary, immoral, and improbable events could happen or had ever happened. With both judgments, children mostly responded affirmatively to ordinary events, often responded negatively for immoral events, and mostly responded negatively to improbable ones. In Experiment 2, children aged 5–7 judged if assertions of the three kinds of events could be true, and the same pattern emerged again. Together, these findings show that children's denials of immoral and conceptually improbable events extend beyond their judgments about what is possible and match their inferences about what is actual. These correspondences across judgments suggest that children drew on a single procedure, or set of procedures, for assessing possibility.SummaryWe show that children judge unexpected events as both impossible and nonactual.Four‐ to seven‐year‐olds judged if events could happen, if events had ever happened, and if assertions about events could be true.For all judgments, children often responded negatively to immoral events, and mostly responded negatively to conceptually improbable ones.Children's possibility denials can be taken at face value, and do not reflect quirks in how they respond to questions about possibility.

Academic libraries play a pivotal role in developing strategies to improve access to information, promote literacy, and offer support to students, particularly during unexpected events such as the pandemic. This study aims to identify the sources of information relevant to students' course research and assignments, the challenges they face, and their coping strategies The study employed the quantitative method and purposive sampling to include students who visited the library during the limited in-person classes. The study's findings revealed that students rely heavily on the modules provided by faculty members. The majority of students found the lack of access to physical information resources, such as books, journals, and theses, to be particularly challenging. Based on the results, this study offers direction for developing more effective library services, collection development programs, information literacy programs, and technological solutions.

Abstract Background and Aims Patients on hemodialysis have cardiovascular complications and impairments in physical and postural balance, which contribute to a higher risk of falls. Therefore, this study evaluated the association of physical function and fear of falling with the number of falls over a 12-month period in patients undergoing hemodialysis. Method This 12-month prospective study included patients on regular hemodialysis. Physical function was assessed using gait speed over 15 feet, the Timed Up and Go (TUG) test, the 5-repetition sit-to-stand (5-STS) test, and handgrip strength. Fear of falling was measured using the Falls Efficacy Scale-International (FES-I). Following the initial assessment, the number of falls was monitored monthly for 12 months using a standardized evaluation. A fall was defined as an unexpected event in which the individual came to rest on the ground, floor, or lower level. A univariate negative binomial regression model was used to evaluate the association of the number of falls with physical function, fear of falling, and sociodemographic, clinical, and laboratory data. Variables significantly associated with the number of falls were included as independent variables in a multivariate negative binomial regression model, with the number of falls as the dependent variable. A p-value of <0.05 was considered statistically significant. Results This study included 112 patients (58.7 ± 12.9 years, 56.3% male). The incidence of falls was 31.3%. Falls occurred predominantly on nondialysis day and at the patient’s home. In the multivariate negative binomial regression model, the number of falls was significantly associated with performance in the TUG (OR: 1.37; 95% CI: 1.16–1.62), gait speed (OR: 0.22; 95% CI: 0.06–0.77), handgrip strength (OR: 0.95; 95% CI: 0.91–0.99) and FES-I score (OR: 1.11; 95% CI: 1.06–1.17), after adjustment for potential confounders (age, gender, educational level, body mass index, history of fall, cardiovascular disease and calcium levels). Conclusion The number of falls was associated with physical function and fear of falling in patients undergoing hemodialysis.

ABSTRACT Sudden loss of consciousness in children is an unexpected event that raises concerns among parents, patients, teachers, and physicians. Although most cases of loss of consciousness in children are benign, some life-threatening conditions can initially manifest as syncope. Therefore, most patients with syncope are hospitalized, and a series of tests are performed in an attempt to elucidate the diagnosis, which is not always successful. This chapter aims to help clinicians plan a Syncope is defined as the sudden loss of consciousness and postural tone resulting from diffuse brain dysfunction due to poor brain perfusion. The syncopal episode is transient and followed by spontaneous recovery of consciousness. Approximately 15 to 25% of children and adolescents between the ages of 8 and 18 experience at least one episode of syncope. Before the age of 6, syncope is uncommon, except in cases of seizures, shortness of breath, and primary cardiac arrhythmias. Syncope is more prevalent in adolescents between 15 and 19 years of age (20 to 50% experience syncope), in girls (twice as many as in boys), and accounts for approximately 2% of pediatric emergency room visits and 1% of total hospitalizations. Pseudosyncope is a transient and apparent loss of consciousness in the absence of actual loss of consciousness. It represents a physical manifestation of internal or psychological stress without changes in vital signs. Keywords: Pediatric Syncope, Syncope, Pediatrics and Syncope, Loss of Consciousness in Syncope.

Abstract Background and Aims Atypical hemolytic uremic syndrome (aHUS) is a rare form of thrombotic microangiopathy (TMA) caused by an uncontrolled complement activation, characterized by microangiopathic hemolytic anemia, thrombocytopenia, and acute kidney injury. Before the availability of treatment with C5 complement inhibitor drugs, the prognosis of aHUS in both pediatric and adult patients was unfavorable despite the use of plasmapheresis or plasma infusion, with a mortality rate during the acute phase of 25%. In fact, the advent of Eculizumab (ECZ), humanized monoclonal antibody directed against the C5 complement factor, has drastically altered the natural history of aHUS, improving prognosis and ensuring rapid recovery of renal function. Although highly effective for the treatment of patients with aHUS since its approval in 2011, ECZ requires intravenous infusions every two weeks, increasing infusion burden, in-hospital visits, patient journey and limiting patients’ and caregivers’ quality of life. Therefore, through targeted modifications of ECZ to enhance antibody recycling, a new anti-C5 monoclonal antibody called Ravulizumab (RVZ) was developed. RVZ presents a optimized halflife in comparison with ECZ, allowing intravenous infusions every 8 weeks. The clinical efficacy and safety of RVZ in adults and pediatric patients with aHUS has been demonstrated in several clinical trials. Although RVZ has been approved for the treatment of aHUS in the United States, Europe, and Japan there is currently no large real-life evidence of the mid- and long-term effects of therapy switch from ECZ to RVZ. Method From June 2023 to January 2025, 15 patients followed at our center for aHUS on ECZ therapy made the switch to RVZ. RVZ was administered via intravenous infusion based on bodyweight. Patients received a first loading infusion of RVZ on day 1, which was 14 days from the last dose of ECZ, followed by maintenance doses administered on day 15 and every 8 weeks thereafter. Patients were followed regularly during follow-up with baseline hematochemical examinations performed on day 1 and then approximately every 8 weeks (preinfusion). t-test for paired data was used to analyze data. Results Patients have a median age of 50.5 (SD 9.4) years and are predominantly female (9 patients). Four patients are on hemodialytic replacement treatment for ESKD, seven patients are on conservative therapy for chronic kidney disease (CKD), and four patients are normal renal function. All patients underwent genetic testing, showing mutations in complement genes in 9 patients. The test was negative in three patients and was still ongoing in three patients. The mean follow-up was 390 (SD 168) days. Baseline and post switch lab values are summarized and compared in Table 1. No patient required hemodialytic treatment at any time during RVZ therapy, and renal function, as measured by eGFR values, remained constant throughout follow-up. No signs of disease recurrence. All patients preserved the same stage of CKD observed at baseline. Throughout the observation period, hematological parameters and indices of hemolysis (platelets, hemoglobin, haptoglobin, LDH) remained stable. Spaghetti Plot image shows the trend of laboratory values for each individual patient. Two adverse events of post-infusion asthenia (unrelated to CPK increase or otherwise) were recorded during follow-up. No other unexpected adverse events were recorded. Conclusion RVZ represents an important therapeutic option for aHUS patients. Long-term treatment with RVZ was well tolerated and associated with stable renal function and hematological parameters. In addition, the reduced infusion frequency of RVZ reduces the therapeutic burden and, as a result, may improve the quality of life for patients and their caregivers.

Transformer load is a key factor influencing its aging and service life. Accurately predicting load trends is crucial for assisting load redistribution. This study proposes a hybrid model called RIME-VMD-TCN-iTransformer to forecast the trend of transformer load. In this model, RIME (Randomized Improved Marine Predators Algorithm) is employed to enhance decomposition stability, VMD (Variational Mode Decomposition) is used to address the non-stationary characteristics of the load sequence, TCN (Temporal Convolutional Network) extracts local temporal dependencies, and iTransformer (Inverted Transformer) captures global inter-variable correlations. First, the variational mode decomposition algorithm is applied to mitigate the non-stationary characteristics of the signal, followed by the RIME to further enhance the orderliness of the intrinsic mode functions. Subsequently, the TCN-iTransformer model is utilized to predict each intrinsic mode function individually, and the prediction results of all intrinsic mode functions are reconstructed to obtain the final forecast. The findings indicate that the intrinsic mode functions obtained through RIME-VMD exhibit no spectral aliasing and can decompose abrupt time-series signals into stable and regular frequency components. Compared to other hybrid models, the proposed model demonstrates superior responsiveness to changes in time-series trends and achieves the lowest prediction error across various transformer capacity scenarios. These results highlight the model’s superior accuracy and generalization capability in handling abrupt signals, underscoring its potential for preventing unexpected transformer events.

Gravitational-wave (GW) detection has become a significant area of research following the first successful observation by the Laser Interferometer Gravitational-Wave Observatory (LIGO). The detection of signals emerging from binary black hole (BBH) mergers have challenges due to the presence of non-Gaussian and non-stationary noise in observational data. Using traditional matched filtering techniques to detect BBH merging are computationally expensive and may not generalize well to unexpected GW events. As a result, deep learning-based methods have emerged as powerful alternatives for robust GW signal detection. In this study, we propose a novel Transformer-based architecture that introduces energy-aware modulation into the attention mechanism through dual-energy attention masks. In the proposed framework, Q-transform and discrete wavelet transform (DWT) are employed to extract time–frequency energy representations from gravitational-wave signals which are fused into energy masks that dynamically guide the Transformer encoder. In parallel, the raw one-dimensional signal is used directly as input and segmented into temporal patches, which enables the model to leverage both learned representations and physically grounded priors. This proposed architecture allows the model to focus on energy-rich and informative regions of the signal in order to enhance the robustness of the model under realistic noise conditions. Experimental results on BBH datasets embedded in real LIGO noise show that EDAT-BBH outperforms CNN-based and standard Transformer-based approaches, achieving an accuracy of 0.9953, a recall of 0.9950, an F1-score of 0.9953, and an AUC of 0.9999. These findings demonstrate the effectiveness of energy-modulated attention in improving both the interpretability and performance of deep learning models for gravitational-wave signal classification.

The linked quadripolar montage for transcranial electric motor-evoked potentials (qTceMEP) consists of four stimulation electrodes: two linked anodes and two linked cathodes. This montage has grown in popularity because it can result in a larger compound muscle action potential amplitude compared with the conventional bipolar montage. Despite the increasing number of centers adopting qTceMEP, no studies have investigated patient safety to date. The aim of this study is to evaluate the safety profile of qTceMEP. A total of 3,806 spine surgeries performed at a single institution using intraoperative transcranial electrical motor-evoked potentials (TceMEP) were reviewed. Among them, 1,196 were performed using bipolar TceMEP, while the remaining 2,610 cases were performed using qTceMEP. The incidence of intraoperative seizure, unexpected cardiac events, bite/oral injuries, and movement-related injuries was compared between the two groups, bipolar TceMEP and qTceMEP. The statistical analysis was performed using MedCalc. No seizure activity, cardiac anomalies, or adverse events related to intracranial and cardiac implant devices were reported in either group. The incidence of intraoperative oral injuries was 0.4% in the bipolar TceMEP group and 0.5% in the qTceMEP group. The difference in the incidence of oral injuries between the two groups was not statistically significant. The use of qTceMEP does not increase or decrease a patient's risk of intraoperative injury. Both bipolar TceMEP and qTceMEP are safe, presenting a small incidence of oral injuries and no other adverse side effects.

PurposeFospropofol disodium for injection (FospropofolFP) is a new water-soluble propofol prodrug for procedural sedation and general anesthesia. This prospective cohort study aimed to characterize the pharmacokinetics and safety of FospropofolFP in subjects with hepatic impairment compared with healthy matched participants during general anesthesia.Patients and MethodsTwenty-three patients were enrolled and divided into three cohorts according to liver function: normal liver function (n = 10), moderate hepatic impairment (n = 10), and severe hepatic impairment (n = 3). They received a single bolus of FospropofolFP 10 mg/kg i.v. Venous blood samples were collected from each patient 14 time points. The plasma concentrations of FospropofolFP and active metabolite propofol were determined by liquid chromatography tandem mass spectrometry (LC-MS/MS). The pharmacokinetic parameters were calculated by non-compantmental analysis (NCA) using Phoenix WinNonlin software.ResultsCompared with matched healthy controls, patients with moderate hepatic impairment exhibited significant reduced exposure and increased elimination for FospropofolFP: the area under the curve (AUC) decreased by approximately 43% and clearance (CL) increased by 60%. The AUC of patients with severe hepatic impairment exhibited a significant decrease by approximately 55%. Notably, propofol (active metabolite) clearance decreased by approximately 15% and 33% in moderate and severe impairment, respectively. Multivariate analysis identified preoperative albumin (ALB) as an independent predictor of FospropofolFP exposure.ConclusionOur study is the first to report altered PK of FospropofolFP in patients with moderate-to-severe hepatic impairment, report a reverse pattern of increased elimination of FospropofolFP and slow elimination of the metabolite propofol, and identify ALB as an independent predictor of FospropofolFP’s PK. No unexpected adverse events related to FospropofolFP were seen in subjects with hepatic impairment after a single dose and that repeated dosing may need further evaluation.

Living donor hepatectomy carries a risk of bleeding, and allogeneic transfusion may cause adverse effects. Autologous blood preparation is therefore considered a safer strategy. While preoperative autologous donation (PAD) is widely used, acute normovolemic hemodilution (ANH) may overcome its limitations and offer a practical alternative. However, evidence supporting ANH in donor surgery remains limited. This study compared the clinical utility of ANH and PAD in living donor hepatectomy. We retrospectively analyzed 60 consecutive cases of living donor right hepatectomy performed between 2017 and 2025. Among them, 58 donors who received either PAD or ANH were compared using 1:2 propensity score matching. Perioperative laboratory values, surgical outcomes, any allogeneic transfusion, and postoperative complications were evaluated. No unexpected intraoperative adverse events or allogeneic transfusions occurred. All ANH donors received autologous reinfusion, compared with only 6.5% of PAD donors. After matching, 27 donors (18 PAD, 9 ANH) were analyzed. Whole blood viscosity was higher in the ANH group. Weight-adjusted intraoperative bleeding was lower (2.6 vs. 4.6 mL/kg, p = .024; q = 0.106) and operative time was shorter (321 vs. 390 min, p = .007; q = 0.077) in the ANH group. Postoperative complication rates were comparable. Area under the curve analysis indicated better preservation of total protein (p = .038) and prothrombin time-international normalized ratio (p = .010) across the perioperative period in the ANH group. ANH maintained transfusion avoidance and donor safety comparable to PAD while improving operative efficiency, supporting ANH as a safe, effective alternative in living donor right hepatectomy.

Background Previous studies in β-thalassaemia have shown that thalidomide is effective in reducing transfusion volume and is safe for short-term therapy of 6 months or less. The aim of this prospective study was to investigate long-term benefits and side effects of thalidomide in the treatment of transfusion-dependent β-thalassaemia (TDT) in children. Methods We analyzed the data from children and adolescents with TDT enrolled in a single-arm prospective study. The overall response rate, the incidence of discontinuation due to adverse events, the effect on height growth, and the effect on nerve conduction velocity were analyzed when patients received thalidomide for up to 1 year, or until unacceptable toxicity during the extended follow-up. The Kruskal-Wallis H test, one-way ANOVA, the Cochran-Mantel-Haenszel Chi-square test, and others were used for analysis. Results The overall response rate was 82.9%. The most common grade 3–4 adverse events were abdominal pain, haemolysis, and leukocytopenia/neutropenia. Of the 73 patients who underwent nerve conduction velocity assessment during treatment for more than 12 months, 12 patients developed polyneuropathy and 26 developed motor neuropathy. The standard deviation scores (SDS) of height in major responders were significantly improved (−1.57, 95% CI (−1.95, −1.18)) at the end of 12 to 18-month treatment (p < 0.001). 64% of patients showed improvement in SDS of height. Conclusion Thalidomide is associated with long-term benefits in growth and transfusion burden. A minority of patients required prolonged therapy beyond 6 months to achieve a response. Neuropathy and unexpected adverse events prevent the long-term use of thalidomide in children with thalassaemia and close monitoring is needed. (chictr.org.cn identifiers: ChiCTR2000034998)

BackgroundObinutuzumab is the first glycosylated type II anti-CD20 monoclonal antibody for the treatment of lymphocytic leukemia and follicular lymphoma. This research aimed to identify significant and unexpected adverse events (AEs) associated with obinutuzumab by utilizing data from the US Food and Drug Administration’s Adverse Event Reporting System (FAERS) and the Japanese Adverse Drug Event Report (JADER) databases, with the intention of providing a reference for the safe and rational clinical use of the drug.Research design and methodsThe reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian confidence propagation neural network (BCPNN), and empirical Bayesian geometric average (EBGM) were employed to analyze the AEs of obinutuzumab using the registration data from the FAERS and JADER databases spanning from 2013 to 2025.ResultsThe study screened 7,868 and 1,584 AE reports related to obinutuzumab from the FAERS and JADER databases, respectively. These AEs involved 198 and 39 risk signals, respectively, and were associated with 16 and 8 system organ classes. In the analysis of the top 30 preferred terms, 19 and 15 risk signals in the FAERS and JADER databases, respectively, were not documented in the drug instruction. Moreover, when obinutuzumab is used for tumor indications, the frequency and signal strength of AEs related to infection and infusion-related reaction (IRR) are higher than those when it is used for non-tumor indications.ConclusionThe results of signal mining indicate that more attention should be paid to the risks of obinutuzumab-related AEs. Strengthening clinical medication monitoring is necessary to mitigate the impact of AEs on patients’ prognosis and quality of life.

Abstract Firms with multiple pieces of information can disclose the information concurrently (bundled disclosure) or sequentially (unbundled disclosure). This paper examines the pricing implications of (un)bundled disclosure in a rational expectations equilibrium model. The model considers a firm whose liquidating cash flow consists of two components. Some investors possess private information about one component (e.g., earnings) and all investors are uninformed about the other component (e.g., unexpected events). We analyze three disclosure policies. In bundled disclosure, both cash flow components are disclosed concurrently; in unbundled disclosure, the informed cash flow component is disclosed early, and the uninformed component is disclosed later; and in alternative unbundled disclosure, the uninformed component is disclosed early, and the informed component later. We find that the disclosure policy influences the cost of capital prior to any disclosure through a risk allocation effect and a price informativeness effect. Unbundled disclosure results in a lower cost of capital compared to bundled disclosure, as it improves risk allocation and enhances the informativeness of the stock price prior to any disclosure. However, for alternative unbundled disclosure, the cost of capital can be higher or lower than that of the other disclosure policies. This is because late disclosure of the informed cash flow component alters investors' risk exposure to the noisy supply of shares, thereby influencing the risk allocation and price informativeness effects.