Monitoring coronavirus disease progression and clinical impact through quantitative viral load testing.

BACKGROUND: The viral load (VL) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-infected individuals is critical for improving clinical treatment strategies, care, and decisions. Several studies have reported that the initial SARS-CoV-2 VL is associated with disease severity and mortality. Cycle threshold (Ct) values and/or copies/mL are often used to quantify VL. However, a multitude of platforms, primer/probe sets of different SARS-CoV-2 target genes, and reference material manufacturers may cause inconsistent interlaboratory interpretations. The first International Standard for SARS-CoV-2 RNA quantitative assays has allowed diagnostic laboratories to transition SARS-CoV-2 VL results into international units per milliliter (IU/mL). The Cobas SARS-CoV-2 Duo quantitative assay provides VL results expressed in IU/mL. MATERIALS AND METHODS: We enrolled 145 and 50 SARS-CoV-2-positive, hospitalized and 50-negative individuals at the Tri-Service General Hospital, Taiwan from January to May 2022. Each participant's electronic medical record was reviewed to determine asymptomatic, mild, moderate, and severe cases. Nasopharyngeal swabs were collected using universal transport medium. We investigated the association of SARS-CoV-2 VL with disease severity using the Cobas SARS-CoV-2 Duo quantitative assay and its functionality in clinical assessment and decision making to further improve clinical treatment strategies. Limit of detection (LOD) was assessed. RESULTS: All 50 SARS-CoV-2-negative samples confirmed negative for SARS-CoV-2, demonstrating 100 % specificity of the Cobas SARS-CoV-2 Duo assay. Patients with severe symptoms had longer hospital stays, and the length of hospital stay (30.56 days on average) positively correlated with the VL (8.22 ± 1.21 log10 IU/mL). Asymptomatic patients had the lowest VL (5.54 ± 2.06 log10 IU/mL) at admission and the shortest hospital stay (14.1 days on average). CONCLUSIONS: VL is associated with disease severity and duration of hospitalization; therefore, its quantification should be considered when making clinical care decisions and treatment strategies. The Cobas SARS-CoV-2 Duo assay provides a commutable unitage IU/mL for interlaboratory interpretations.

The cost-effectiveness of iruplinalkib versus alectinib in anaplastic lymphoma kinase-positive crizotinib-resistant advanced non-small-cell lung cancer patients in China.

Background: Iruplinalkib is a second-generation anaplastic lymphoma kinase (ALK) tyrosine kinase inhibitor (TKI) with efficacy in patients with ALK-positive crizotinib-resistant advanced non-small cell lung cancer (NSCLC), which is independently developed by a Chinese pharmaceutical company. This study examined the cost-effectiveness of iruplinalkib versus alectinib in the Chinese healthcare setting. Methods: A partitioned survival model was developed to project the economic and health outcomes. Efficacy was derived using unanchored matching-adjusted indirect comparison (MAIC). Cost and utility values were obtained from the literature and experts' opinions. Deterministic and probabilistic sensitivity analyses (PSA) were carried out to evaluate the model's robustness. Results: Treatment with iruplinalkib versus alectinib resulted in a gain of 0.843 quality-adjusted life years (QALYs) with incremental costs of $20,493.27, resulting in an incremental cost-effectiveness ratio (ICER) of $24,313.95/QALY. Parameters related to relative efficacy and drug costs were the main drivers of the model outcomes. From the PSA, iruplinalkib had a 90% probability of being cost-effective at a willingness-to-pay threshold of $37,863.56/QALY. Conclusion: Compared to alectinib, iruplinalkib is a cost-effective therapy for patients with ALK-positive crizotinib-resistant advanced NSCLC.

A Na+ channel receptor of FMRFamide in the cephalopod Sepiella japonica: Identification, characterisation, and expression profiling during different stages of gonadal development.

FMRFamide, a member of the neuropeptide family, is involved in numerous physiological processes. FMRFamide-activated sodium channels (FaNaCs) are a family of non-voltage-gated, amiloride-sensitive, Na+-selective channels triggered by the neuropeptide FMRFamide. In the present study, the full-length cDNA of the FaNaC receptor of Sepiella japonica (SjFaNaC) was cloned. The cDNA of SjFaNaC was 3004 bp long with an open reading frame (ORF) of 1812 bp, encoding 603 amino acid residues with no signal peptide at the N-terminus. Sequence analysis indicated that SjFaNaC shared a high identity with other cephalopods FaNaCs and formed a sister clade with bivalves. The protein structure was predicted using SWISS-MODEL with AcFaNaC as the template. Quantitative real-time PCR (qRT-PCR) revealed that SjFaNaC transcripts were highly expressed in both female and male reproductive organs, as well as in the optic lobe and brain of the central nervous system (CNS). Results of in situ hybridisation (ISH) showed that SjFaNaC mRNA was mainly distributed in the medulla and deep retina of the optic lobe and in both the supraesophageal and subesophageal masses of the brain. Subcellular localisation indicated that the SjFaNaC protein was localised intracellularly and on the cell surface of HEK293T cells. In summary, these findings may lay the foundation for future exploration of the functions of SjFaNaC in cephalopods.

Influence of PhoPQ and PmrAB two component system alternations on colistin resistance from non-mcr colistin resistant clinical E. Coli strains.

BACKGROUND: The current understanding of acquired chromosomal colistin resistance mechanisms in Enterobacterales primarily involves the disruption of the upstream PmrAB and PhoPQ two-component system (TCS) control caused by mutations in the regulatory genes. Interestingly, previous studies have yielded conflicting results regarding the interaction of regulatory genes related to colistin resistance in Escherichia coli, specifically those surrounding PhoPQ and PmrAB TCS. RESULTS: In our study, we focused on two clinical non-mcr colistin-resistant strains of E. coli, TSAREC02 and TSAREC03, to gain a better understanding of their resistance mechanisms. Upon analysis, we discovered that TSAREC02 had a deletion (Δ27-45) in MgrB, as well as substitutions (G206R, Y222H) in PmrB. On the other hand, TSAREC03 exhibited a long deletion (Δ84-224) in PhoP, along with substitutions (M1I, L14P, P178S, T235N) in PmrB. We employed recombinant DNA techniques to explore the interaction between the PhoPQ and PmrAB two-component systems (TCSs) and examine the impact of the mutated phoPQ and pmrB genes on the minimum inhibitory concentrations (MICs) of colistin. We observed significant changes in the expression of the pmrD gene, which encodes a connector protein regulated by the PhoPQ TCS, in the TSAREC02 wild-type (WT)-mgrB replacement mutant and the TSAREC03 WT-phoP replacement mutant, compared to their respective parental strains. However, the expressions of pmrB/pmrA, which reflect PmrAB TCS activity, and the colistin MICs remained unchanged. In contrast, the colistin MICs and pmrB/pmrA expression levels were significantly reduced in the pmrB deletion mutants from both TSAREC02 and TSAREC03, compared to their parental strains. Moreover, we were able to restore colistin resistance and the expressions of pmrB/pmrA by transforming a plasmid containing the parental mutated pmrB back into the TSAREC02 and TSAREC03 mutants, respectively. CONCLUSION: While additional data from clinical E. coli isolates are necessary to validate whether our findings could be broadly applied to the E. coli population, our study illuminates distinct regulatory pathway interactions involving colistin resistance in E. coli compared to other species of Enterobacterales. The added information provided by our study contribute to a deeper understanding of the complex pathway interactions within Enterobacterales.

Cost-Effectiveness Analysis of Fluocinolone Acetonide Intravitreal (FAI) Implant for Chronic Noninfectious Uveitis Affecting the Posterior Segment of the Eye (NIU-PS) in China.

INTRODUCTION: Chronic non-infectious uveitis affecting the posterior segment (NIU-PS), which can be recurrent and persistent for numerous years, mainly affects people of working age and significantly increases the risk of visual impairment. This study aimed to investigate the cost-effectiveness of fluocinolone acetonide intravitreal (FAI) implant in the treatment of patients with chronic NIU-PS from the Chinese healthcare perspective. METHODS: A Markov model with a 2-week cycle was constructed from the perspective of the Chinese healthcare system over a lifetime time horizon. The model consists of four health states: on-treatment, treatment failure, blindness, and death. The outcomes for effectiveness were based on the Chinese real-world study (RWS). Utilities and mortality rates were derived from published literature and standard sources. Costs were determined from the MENET website, prices of medical service items at local providers, published literature, and expert surveys. Outcomes were measured in quality-adjusted life years (QALYs). Sensitivity analyses were performed to account for the impact of uncertainty. RESULTS: It was estimated that in the base case, the FAI implant provided 0.43 incremental QALYs compared with the limited current practice (LCP) at an additional cost of $7503.72 (¥50,575.05), resulting in an incremental cost-effectiveness ratio (ICER) of $17,373.49 (¥117,097.33) per QALY gained. Parameters related to utility emerged as the primary influencers on the outcomes. In probabilistic sensitivity analysis (PSA), considering the willingness-to-pay (WTP) threshold of $19,072 (¥128,547) and $38,145 (¥257,094), the FAI implant had 67.70% and 99.50% probability of being cost-effective, respectively. As demonstrated in the scenario analysis, if the FAI implant aligns its price reduction with the average rate from the 2023 negotiation of the National Reimbursement Drug List (NRDL), it would result in lower costs and represent an absolute advantage. CONCLUSIONS: The FAI implant, which can effectively reduce the recurrence rate and maintain the incremental costs within the WTP limit, is likely to be cost-effective in treating chronic NIU-PS in China.

Tools to measure barriers to medication management capacity in older adults: a scoping review.

BACKGROUND: Medication management capacity is a crucial component of medication adherence, particularly among older adults. Various factors, including physical abilities, cognitive functions, sensory capabilities, motivational, and environmental factors, influence older adults' ability to manage medications. It is, therefore, crucial to identify appropriate tools that allow clinicians to determine which factors may impact medication management capacity and, consequently, nonadherence to medications. PURPOSE: 1)To identify tools that measure physical, cognitive, sensory (vision, hearing, touch), motivational, and environmental barriers to medication self-management in older adults, and 2) to understand the extent to which these tools assess various barriers. METHODS: The scoping review was conducted using Arksey and O'Malley's scoping review framework and the PRISMA Extension for Scoping Reviews checklist. In June 2022, the relevant literature was identified by searching PubMed (MEDLINE), Ovid Embase, Ovid IPA, EBSCOhost CINAHL, APA PsycINFO, and Scopus. RESULTS AND DISCUSSION: In total, 7235 studies were identified. Following the removal of duplicates, 4607 articles were screened by title and abstract, of which 4253 did not meet the inclusion criteria. Three reviewers reviewed the full texts of the remaining 354 articles; among them, 41 articles, 4 theses and 1 conference abstract met the inclusion criteria. From the included studies, 44 tools were identified that measured a combination of physical, cognitive, sensory, motivational, and environmental barriers (n=19) or only cognition (n=13), vision (n=5), environmental factors (n=3), auditory (n=1), and motivational factors (n=1). The review also examined the psychometric properties of the identified tools and found that most of them had reported validity and reliability data. Several tools have demonstrated promise in assessing a combination of barriers with validity and reliability. These tools include the Self-Medication Assessment Tool (SMAT), ManageMed Screening (MMS), Self-Medication Risk Assessment Tool (RAT), HOME-Rx revised, and Medication Management Ability Assessment (MMAA). CONCLUSION: This scoping review identified 44 validated tools to measure various challenges that older adults encounter with medication management. However, no tool measures all five barriers (physical, cognitive, sensory, motivational, and environmental) to medication-taking at home. Therefore, utilizing a combination of tools would be most appropriate to measure these different aspects comprehensively. Further research is needed to develop a new comprehensive tool that simultaneously measures various barriers to medication self-management.

Chemical Characterization of Honeysuckle Polyphenols and Their Alleviating Function on Ultraviolet B-Damaged HaCaT Cells by Modulating the Nrf2/NF-κB Signaling Pathways.

Scientific evidence attests that the epidermis receives excessive ultraviolet B (UVB) radiation, triggering the generation of substantial quantities of reactive oxygen species (ROS), which disrupted the delicate equilibrium of oxidation-reduction, leading to oxidative stress and inflammation. The historical use of honeysuckle polyphenols (HPs) has garnered our attention due to their efficacy in inhibiting oxidative damage. In this study, HPs were prepared from honeysuckle flowers employing an ultrasonic-assisted extraction method and quantitatively analyzed by a LC-MS/MS, and the mechanisms underlying HPs' antioxidative and anti-inflammatory effects on a UVB-irradiated HaCaT cell model were systematically investigated. The results showed that HPs had a significant cellular repair effect on UVB-irradiated HaCaT cells (p < 0.001). The mechanism of action indicated that HPs could allow Nrf2 to enter the nucleus by regulating the dissociation of Nrf2 from Keap1, which further increases the activity of downstream proteases (SOD and CAT), increases ROS scavenging, and reduces the intracellular malondialdehyde (MDA) level. In addition, HPs could down-regulate Toll-like receptor 4 (TLR4) and inhibit NF-κB (P65) dissociating from IκBα, resulting in a decrease in NF-κB (P65) entry into the nucleus and a decrease in inflammatory factors (TNF-α, IL-6, and IL-1ß). In addition, four key compounds in HPs, including chlorogenic acid, quercetin, isorhamnetin, and luteolin, were selected to verify the mechanism of HPs repairing UVB damage using molecular docking techniques. The experiment suggested that four key active compounds could effectively occupy the Kelch homologue (Kelch) structural domain of Keap1, competitively bind with Nrf2, and facilitate the promotion of Nrf2 binding, ultimately enhancing the translocation of Nrf2 into the nucleus. In addition, four key active compounds could effectively interact with NF-κB (P65) through hydrogen bonding, van der Waals forces, and electrostatic forces to inhibit its entry into the nucleus. In summary, HPs can effectively repair the damage of HaCaT cells by UVB radiation and can be used to develop health and cosmetic products for the treatment of UV radiation-induced diseases.

Boosted charge separation via Ce2S3 over dual Z-scheme ZnO-Ce2S3-MnO2 core double-shell nanocomposite for the degradation of diverse dye pollutants.

Herein, core double-shell direct dual Z-scheme ZnO-Ce2S3-MnO2 nanocomposite was synthesized via a hydrothermal route along with pure ZnO, Ce2S3, MnO2, and characterized by numerous characterization tools for application in synthetic dyes degradation. The XRD, Raman, and FTIR analyses have confirmed the nanocomposite formation. TEM images exhibited the core double-shell morphology with an average particle diameter of 81 nm and stacking of ZnO, Ce2S3, and MnO2. EDX confirmed the existence of desired elements in the grown composition. The varied oxidation states, presence of defects, and fast charge transfer were also revealed from XPS, PL, and EIS. The ZnO-Ce2S3-MnO2 nanocomposite has an optical energy bandgap of 2.84 eV, capable of decomposing harmful dyes with excellent efficiency, 99.81% MB, 97.62% MO, 88.5% MR, and 58.9% EY in 40 min sunlight exposure. The effect of several operating parameters is also observed and obtained results showed the optimal catalyst dose was 20 mg, pH of 8, and dye concentration of 10 ppm. The scavenger's experiment suggests that •O2- and •OH are the main active radicals in the photodegradation reaction which is also evident in the dual Z-scheme formation. The MnO2 and ZnO layers covered the Ce2S3 (core) and dual Z-scheme formation allows rapid kinetics of redox reaction and provides plenteous channels for transfer of photo-generated charge carriers during photocatalysis. Thus, core double-shell direct dual Z-scheme photocatalysts having inorganic components could be an excellent choice for photocatalysis at the industrial level, particularly for water purification.

Effects of mitral valve disease etiology on the outcomes of mechanical and biological valve replacement: retrospective cohort study.

INTRODUCTION: The choice of an artificial mitral valve (MV) is a crucial clinical decision that affects the long-term survival and quality of life of patients. However, current guidelines recommend selecting MV based on patient age and life expectancy at the time of MV replacement (MVR), without considering the etiology of MV disease. This study aimed to investigate whether MV disease etiology should be considered when choosing a valve for MVR and to evaluate the impact of MV disease etiology on long-term patient survival. METHODS: Using data (2002 to 2018) from Taiwan's National Health Insurance Research Database, we conducted a nationwide retrospective cohort study to compare the biological and mechanical valves in terms of all-cause mortality as the primary outcome. The inverse probability of the treatment weighting method was used to reduce the effects of the confounding factors. The following etiologies were assessed: infective endocarditis (IE), rheumatic heart disease (RHD), ischemic mitral regurgitation (IMR), and degenerative mitral regurgitation (DMR). RESULTS: In patients aged <70 years, it was observed that mechanical valves demonstrated an association with benefits compared to biological valves in the context of survival. In patients with IE aged <72 years, mechanical valves were associated with survival benefits, but not in those with stroke during hospitalization. These valves were also found to be linked with survival advantages for patients with RHD aged <60 years and for those with DMR aged < 72 years. However, no age-dependent effects of valve type on all-cause mortality were observed in patients with IMR. CONCLUSION: The etiology of MV disease appears to be important in the selection of a suitable MV and determination of a cutoff age for mechanical and biological MVR.

Development of a Dyad-Focused Intervention for Stroke Survivors and Their Family Caregivers: A Feasibility Study.

IMPORTANCE: Transitioning from the hospital to the community poses significant challenges for stroke survivors and their caregivers. OBJECTIVE: To examine the feasibility and preliminary effects of a dyad-focused strategy training intervention. DESIGN: Single-arm trial with data collection at baseline, postintervention, and 3-mo follow-up. SETTING: Rehabilitation settings in Taiwan. PARTICIPANTS: Sixteen stroke survivor-caregiver dyads. INTERVENTIONS: Dyad-focused strategy training was provided to stroke survivor-caregiver dyads twice a week over 6 wk. The training included shared decision-making, goal setting, performance evaluation, strategy development and implementation, and therapeutic guided discovery. OUTCOMES AND MEASURES: Feasibility indicators were Goal Attainment Scaling, Dyadic Relationship Scale, Participation Measure-3 Domains, 4 Dimensions, Activity Measure for Post-Acute Care, Montreal Cognitive Assessment, Trail Making Test, Stroop Color and Word Test, Preparedness for Caregiving Scale, and Zarit Burden Interview. RESULTS: In total, 15 dyads completed all intervention sessions with full attendance. Both stroke survivors and their caregivers demonstrated high engagement and comprehension and reported moderate to high satisfaction with the intervention. From baseline to postintervention, the effects on goal attainment, frequency and perceived difficulty of community participation, executive function, mobility function, and caregiver preparedness were significant and positive. CONCLUSIONS AND RELEVANCE: Our study supports the feasibility and preliminary efficacy of dyad-focused strategy training for stroke survivor-caregiver dyads transitioning from the hospital to the community in Taiwan. Our preliminary evidence indicates that dyads who receive strategy training exhibit advancement toward their goals and experience considerable enhancements in their individual outcomes. Plain-Language Summary: This study addresses the scarcity of interventions catering to both stroke survivors and their caregivers. By demonstrating the feasibility of our dyad-focused intervention, the research offers preliminary evidence that supports the potential advantages of involving both stroke survivors and their caregivers in the intervention process.

Single-Cell RNA Sequencing Reveals HIF1A as a Severity-Sensitive Immunological Scar in Circulating Monocytes of Convalescent Comorbidity-Free COVID-19 Patients.

COVID-19, caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), is characterized by a wide range of clinical symptoms and a poorly predictable disease course. Although in-depth transcriptomic investigations of peripheral blood samples from COVID-19 patients have been performed, the detailed molecular mechanisms underlying an asymptomatic, mild or severe disease course, particularly in patients without relevant comorbidities, remain poorly understood. While previous studies have mainly focused on the cellular and molecular dissection of ongoing COVID-19, we set out to characterize transcriptomic immune cell dysregulation at the single-cell level at different time points in patients without comorbidities after disease resolution to identify signatures of different disease severities in convalescence. With single-cell RNA sequencing, we reveal a role for hypoxia-inducible factor 1-alpha (HIF1A) as a severity-sensitive long-term immunological scar in circulating monocytes of convalescent COVID-19 patients. Additionally, we show that circulating complexes formed by monocytes with either T cells or NK cells represent a characteristic cellular marker in convalescent COVID-19 patients irrespective of their preceding symptom severity. Together, these results provide cellular and molecular correlates of recovery from COVID-19 and could help in immune monitoring and in the design of new treatment strategies.

Host-Pathogen Interactions in K. pneumoniae Urinary Tract Infections: Investigating Genetic Risk Factors in the Taiwanese Population.

BACKGROUND: Klebsiella pneumoniae (K. pneumoniae) urinary tract infections pose a significant challenge in Taiwan. The significance of this issue arises because of the growing concerns about the antibiotic resistance of K. pneumoniae. Therefore, this study aimed to uncover potential genomic risk factors in Taiwanese patients with K. pneumoniae urinary tract infections through genome-wide association studies (GWAS). METHODS: Genotyping data are obtained from participants with a history of urinary tract infections enrolled at the Tri-Service General Hospital as part of the Taiwan Precision Medicine Initiative (TPMI). A case-control study employing GWAS is designed to detect potential susceptibility single-nucleotide polymorphisms (SNPs) in patients with K. pneumoniae-related urinary tract infections. The associated genes are determined using a genome browser, and their expression profiles are validated via the GTEx database. The GO, Reactome, DisGeNET, and MalaCards databases are also consulted to determine further connections between biological functions, molecular pathways, and associated diseases between these genes. RESULTS: The results identified 11 genetic variants with higher odds ratios compared to controls. These variants are implicated in processes such as adhesion, protein depolymerization, Ca2+-activated potassium channels, SUMOylation, and protein ubiquitination, which could potentially influence the host immune response. CONCLUSIONS: This study implies that certain risk variants may be linked to K. pneumoniae infections by affecting diverse molecular functions that can potentially impact host immunity. Additional research and follow-up studies are necessary to elucidate the influence of these risk variants on infectious diseases and develop targeted interventions for mitigating the spread of K. pneumoniae urinary tract infections.

Ovarian cancer with intestinal wall invasion and hyperamylasemia: a case report.

Numerous studies have suggested a robust association between amylase and ovarian cancer. however, few amylase-producing ovarian cancers have been reported because amylase is a rare product of ovarian cancer. A case of an elderly female patient with an upper abdominal unfitness, intestinal wall along with uterine adnexal invasion, and high serum and urinary amylase is summarized in this article. The patient was initially suspected of having a gastrointestinal tumor. Initial laboratory findings showed markedly significantly raised serum and urinary amylase levels. Imaging showed invasion of the intestinal wall and uterine adnexa, and histology of the specimen taken through the abdominal wall lump and electron colonoscopy showed ovarian cancer. The patient's blood amylase levels decreased to normal after 4 cycles of neoadjuvant chemotherapy with paclitaxel and carboplatin. Following this, she underwent interval debulking surgery, which included total hysterectomy, bilateral adnexectomy, great omentectomy, appendectomy, resection of pelvic and abdominal lesions, and partial rectal resection. Postoperative pathology and immunohistochemistry staining confirmed a diagnosis of high-grade serous ovarian cancer. This case suggests that in female patients, hyperamylasemia may indicate the presence of ovarian cancer. It is necessary to perform a multisite, multipoint histologic examination to identify the tumor's origin in patients with multiple sites of invasion.

Efficacy of cefoperazone/sulbactam for ESBL-producing Escherichia coli and Klebsiella pneumoniae bacteraemia and the factors associated with poor outcomes.

OBJECTIVE: We aimed to assess the efficacy of cefoperazone/sulbactam (CPZ/SUL) in extended-spectrum ß-lactamase (ESBL)-producing Enterobacterales infections and identify factors influencing outcomes. METHODS: This retrospective multicentre study was conducted in Taiwan (January 2015 to December 2020) and examined the efficacy of CPZ/SUL treatment in ESBL-producing Enterobacterales bacteraemia. The minimum inhibitory concentrations (MICs) were determined using agar dilution; ESBL/AmpC genes were detected using polymerase chain reaction. The primary outcome was clinical success, whereas the secondary outcome was 30-day mortality. Clinical success was defined as the complete resolution of clinical signs and symptoms of K. pneumoniae or E. coli infection, with no evidence of persistent or recurrent bacteraemia. The factors influencing outcomes were identified using a multivariate analysis. RESULTS: CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia, with a 30-day mortality rate of 9.1% (10/110). Among 110 ESBL-producing isolates, a high clinical success rate was observed at an MIC of ≤32/32 mg/L. Multivariate analysis revealed that a Charlson comorbidity index (CCI) of ≥6 was associated with lower clinical success [odds ratio (OR): 5.80, 95% confidence interval (CI): 1.15-29.14, P = 0.033]. High Sequential Organ Failure Assessment scores (≥6) were significantly associated with increased 30-day mortality (OR: 14.34, 95% CI: 1.45-141.82, P = 0.023). DISCUSSION: CPZ/SUL demonstrated a clinical success rate of 82.7% (91/110) in treating ESBL-producing Enterobacterales bacteraemia. Treatment success was evident when the CPZ and SUL MIC was ≤32/32 mg/L. Comorbidities (CCI ≥6) were associated with lower clinical success, while disease severity (Sequential Organ Failure Assessment score ≥6) correlated with higher mortality.

Sex Differences in Epidemiological Distribution and Outcomes of Surgical Mitral Valve Disease.

BACKGROUND: Mitral valve (MV) disease is the most common form of valvular heart disease. Findings that indicate women have a higher risk for unfavorable outcomes than men remain controversial. This study aimed to determine the sex-based differences in epidemiological distributions and outcomes of surgery for MV disease.Methods and Results: Overall, 18,572 patients (45.3% women) who underwent MV surgery between 2001 and 2018 were included. Outcomes included in-hospital death and all-cause mortality during follow up. Subgroup analysis was conducted across different etiologies, including infective endocarditis (IE), degenerative, ischemic, and rheumatic mitral pathology. The overall MV repair rate was lower in women than in men (20.5% vs. 30.6%). After matching, 6,362 pairs (woman : man=1 : 1) of patients were analyzed. Women had a slightly higher risk for in-hospital death than men (10.8% vs. 9.8%; odds ratio [OR]: 1.11, 95% confidence interval [CI]: 0.99-1.24; P=0.075). Women tended to have a higher incidence of de novo dialysis (9.8% vs. 8.6%; P=0.022) and longer intensive care unit stay (8 days vs. 7.1 days; P<0.001). Women with IE had poorer in-hospital outcomes than men; however, there were no sex differences in terms of all-cause mortality. CONCLUSIONS: Sex-based differences of MV intervention still persist. Although long-term outcomes were comparable between sexes, women, especially those with IE, had worse perioperative outcomes than men.

Mitral Valve Repair vs. Replacement by Different Etiologies　- A Nationwide Population-Based Cohort Study.

BACKGROUND: When mitral valve (MV) surgery is indicated, repair is preferred over replacement; however, this preference is not supported by evidence from clinical trials. Furthermore, the benefits of MV repair may not be universal for all etiologies of MV disease.Methods and Results: This study identified a total of 18,428 patients who underwent MV repair (n=4,817) or MV replacement (n=13,611) during 2001-2018 from Taiwan's National Health Insurance Research Database. These patients were classified into 4 etiologies: infective endocarditis (IE, n=2,678), rheumatic heart disease (RHD, n=4,524), ischemic mitral regurgitation (IMR, n=3,893), and degenerative mitral regurgitation (DMR, n=7,333). After propensity matching, all-cause mortality during follow-up was lower among patients receiving MV repair than among patients receiving MV replacement in the IE, IMR, and DMR groups (hazard ratio [HR]=0.72, 95% confidence interval [CI]: 0.55-0.93; HR=0.82, 95% CI: 0.73-0.92; and HR 0.73, 95% CI: 0.64-0.84, respectively). However, in the RHD group, the MV reoperation rate was higher after MV repair than after MV replacement (subdistribution HR=1.91, 95% CI: 1.02-3.55). CONCLUSIONS: In comparison with MV replacement, MV repair was associated with a lower late mortality in patients with IE, IMR, and DMR, and a higher risk of reoperation in patients with RHD.

Quantifying stakeholders' preference for implantable medical devices in China: a discrete choice experiment.

OBJECTIVES: This study aims to gain insight into each attribute as presented in the value of implantable medical devices, quantify attributes' strength and their relative importance, and identify the determinants of stakeholders' preferences. METHODS: A mixed-methods design was used to identify attributes and levels reflecting stakeholders' preference toward the value of implantable medical devices. This design combined literature reviewing, expert's consultation, one-on-one interactions with stakeholders, and a pilot testing. Based on the design, six attributes and their levels were settled. Among 144 hypothetical profiles, 30 optimal choice sets were developed, and healthcare professionals (decision-makers, health technology assessment experts, hospital administrators, medical doctors) and patients as stakeholders in China were surveyed. A total of 134 respondents participated in the survey. Results were analyzed by mixed logit model and conditional logit model. RESULTS: The results of the mixed logit model showed that all the six attributes had a significant impact on respondents' choices on implantable medical devices. Respondents were willing to pay the highest for medical devices that provided improvements in clinical safety, followed by increased clinical effectiveness, technology for treating severe diseases, improved implement capacity, and innovative technology (without substitutes). CONCLUSIONS: The findings of DCE will improve the current evaluation on the value of implantable medical devices in China and provide decision-makers with the relative importance of the criteria in pricing and reimbursement decision-making of implantable medical devices.

Endovascular Management of Post-Irradiated Carotid Blowout Syndrome in Patients with Lower Neck Cancers.

OBJECTIVE: Lower neck cancers (LNCs) include specific tumour types and have some different vascular supply or collaterals from other head and neck cancers. This prospective study evaluated the outcome of endovascular management of post-irradiated carotid blowout syndrome (PCBS) in patients with LNC by comparing reconstructive management (RE) and deconstructive management (DE). METHODS: This was a single centre, prospective cohort study. Patients with LNC complicated by PCBS between 2015 and 2021 were enrolled for RE or DE. RE was performed by stent graft placement covering the pathological lesion and preventive external carotid artery (ECA) embolisation without balloon test occlusion (BTO). DE was performed after successful BTO by permanent coil or adhesive agent embolisation of the internal carotid artery (ICA) and ECA to common carotid artery, or ICA occlusion alone if the pathological lesion was ICA only. Cross occlusion included the proximal and distal ends of the pathological lesion in all patients. Re-bleeding events, haemostatic period, and neurological complications were evaluated. RESULTS: Fifty-nine patients (mean age 58.5 years; 56 male) were enrolled, including 28 patients undergoing RE and 31 patients undergoing DE. Three patients originally grouped to DE were transferred to RE owing to failed BTO. The results of RE vs. DE were as follows: rebleeding events, 13/28 (46%) vs. 10/31 (32%) (p = .27); haemostatic period, 9.4 ± 14.0 months vs. 14.2 ± 27.8 months (p = .59); neurological complication, 4/28 (14%) vs. 5/31 (16%) (p = .84); and survival time, 11.8 ± 14.6 months vs. 15.1 ± 27.5 months (p = .61). CONCLUSION: No difference in rebleeding risk or neurological complications was observed between the DE and RE groups. RE could be used as a potential routine treatment for PCBS in patients with LNC.

Impaired cerebral interstitial fluid dynamics in cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy, caused by cysteine-altering variants in NOTCH3, is the most prevalent inherited cerebral small vessel disease. Impaired cerebral interstitial fluid dynamics has been proposed as one of the potential culprits of neurodegeneration and may play a critical role in the initiation and progression of cerebral small vessel disease. In the present study, we aimed to explore the cerebral interstitial fluid dynamics in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy and to evaluate its association with clinical features, imaging biomarkers and disease severity of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy. Eighty-one participants carrying a cysteine-altering variant in NOTCH3, including 44 symptomatic cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy patients and 37 preclinical carriers, and 21 age- and sex-matched healthy control individuals were recruited. All participants underwent brain MRI studies and neuropsychological evaluations. Cerebral interstitial fluid dynamics was investigated by using the non-invasive diffusion tensor image analysis along the perivascular space method. We found that cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy patients exhibited significantly lower values of diffusion tensor image analysis along the perivascular space index comparing to preclinical carriers and healthy controls. For the 81 subjects carrying NOTCH3 variants, older age and presence of hypertension were independently associated with decreased diffusion tensor image analysis along the perivascular space index. The degree of cerebral interstitial fluid dynamics was strongly related to the severity of cerebral small vessel disease imaging markers, with a positive correlation between diffusion tensor image analysis along the perivascular space index and brain parenchymal fraction and negative correlations between diffusion tensor image analysis along the perivascular space index and total volume of white matter hyperintensity, peak width of skeletonized mean diffusivity, lacune numbers and cerebral microbleed counts. In addition, diffusion tensor image analysis along the perivascular space index was a significant risk factor associated with the development of clinical symptoms of stroke or cognitive dysfunction in individuals carrying NOTCH3 variants. In cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy patients, diffusion tensor image analysis along the perivascular space index was significantly associated with Mini-Mental State Examination scores. Mediation analysis showed that compromised cerebral interstitial fluid dynamics was not only directly associated with cognitive dysfunction but also had an indirect effect on cognition by influencing brain atrophy, white matter disruption, lacunar lesions and cerebral microbleeds. In conclusion, cerebral interstitial fluid dynamics is impaired in cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy and its disruption may play an important role in the pathogenesis of cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy. Diffusion tensor image analysis along the perivascular space index may serve as a biomarker of disease severity for cerebral autosomal dominant arteriopathy with subcortical infarcts and leucoencephalopathy.

Organic-Inorganic Hybrid Ferroelectric and Antiferroelectric with Afterglow Emission.

Luminescent ferroelectrics are holding exciting prospect for integrated photoelectronic devices due to potential light-polarization interactions at electron scale. Integrating ferroelectricity and long-lived afterglow emission in a single material would offer new possibilities for fundamental research and applications, however, related reports have been a blank to date. For the first time, we here achieved the combination of notable ferroelectricity and afterglow emission in an organic-inorganic hybrid material. Remarkably, the presented (4-methylpiperidium)CdCl3 also shows noticeable antiferroelectric behavior. The implementation of cationic customization and halogen engineering not only enables a dramatic enhancement of Curie temperature of 114.4 K but also brings a record longest emission lifetime up to 117.11 ms under ambient conditions, realizing a leapfrog improvement of at least two orders of magnitude compared to reported hybrid ferroelectrics so far. This finding would herald the emergence of novel application potential, such as multi-level density data storage or multifunctional sensors, towards the future integrated optoelectronic devices with multitasking capabilities.