Limited impact of bacterial virulence on early mortality risk factors in Acinetobacter baumannii bacteremia observed in a Galleria mellonella model.

Acinetobacter baumannii (AB) has emerged as a major pathogen in vulnerable and severely ill patients. It remains unclear whether early mortality (EM) due to AB bacteremia is because of worse clinical characteristics of the infected patients or the virulence of the pathogen. In this study, we aimed to investigate the effect of AB virulence on EM due to bacteremia. This retrospective study included 138 patients with AB bacteremia (age: ≥ 18 years) who were admitted to a tertiary care teaching hospital in South Korea between 2015 and 2019. EM was defined as death occurring within 7 days of bacteremia onset. The AB clinical isolates obtained from the patients' blood cultures were injected into 15 Galleria mellonella larvae each, which were incubated for 5 days. Clinical isolates were classified into high- and low-virulence groups based on the number of dead larvae. Patients' clinical data were combined and subjected to multivariate Cox regression analyses to identify the risk factors for EM. In total, 48/138 (34.8%) patients died within 7 days of bacteremia onset. The Pitt bacteremia score was the only risk factor associated with EM. In conclusion, AB virulence had no independent effect on EM in patients with AB bacteremia.

Risk factors for subsequent fractures in hip fracture patients: a nested case-control study.

BACKGROUND: The risk factors for subsequent fractures following an initial hip fracture are not entirely understood. This study examined the clinical characteristics of hip fracture patients to identify potential risk factors associated with a higher risk of experiencing subsequent fractures. METHODS: We conducted a nested case-control study using data from the Chinese PLA General Hospital Hip Fracture Cohort between January 2008 and March 2022. The cases were individuals who experienced subsequent fractures following an initial hip fracture. Each case was matched with up to 2 controls who did not develop subsequent fractures. Important clinical factors were compared across groups, including traditional fracture risk factors and potential risk factors (e.g., comorbidities, falls risk, physical impairment, calcium or vitamin D use, and anti-osteoporosis medications). Conditional logistic regression analyses were used to evaluate the impact of these clinical features as potential risk factors for subsequent fractures. RESULTS: A total of 96 individuals who suffered from subsequent fractures were matched with 176 controls. The median time between the initial hip fracture and the subsequent fracture was 2.1 years. The overall proportion of patients receiving anti-osteoporosis treatment after initial hip fracture was 25.7%. In the multivariable regression analysis, living in a care facility (OR = 3.78, 95%CI: 1.53-9.34), longer hospital stays (OR = 1.05, 95%CI: 1.00-1.11), and falls after discharge (OR = 7.58, 95%CI: 3.37-17.04) were associated with higher odds of subsequent fractures. CONCLUSIONS: This study showed that living in a care facility, longer hospital stays, and falls after discharge may be independent risk factors for repeat fractures following an initial hip fracture. These findings could be used to identify and manage patients at high risk of subsequent fractures.

Risk analysis for subsequent fracture of osteoporotic fractures in Chinese women over age 60: a nationwide cross-sectional study.

Prevention of subsequent fracture is a major public health challenge in the field of osteoporosis prevention and treatment, and older women are at high risk for osteoporotic fractures. This study aimed to examine factors associated with subsequent fracture in older Chinese women with osteoporosis. We collected data on 9212 older female patients with osteoporotic fractures from 580 medical institutions in 31 provinces of China. Higher odds of subsequent fractures were associated with age of 70-79 years (OR 1.218, 95% CI 1.049-1.414), age ≥ 80 (OR 1.455, 95% CI 1.222-1.732), index fracture site was vertebrae (OR 1.472, 95% CI 1.194-1.815) and hip (OR 1.286, 95% CI 1.041-1.590), index fracture caused by fall (OR 1.822, 95% CI 1.281-2.591), strain (OR 1.587, 95% CI 1.178-2.139), no inducement (OR 1.541, 95% CI 1.043-2.277), and assessed as high risk of fracture (OR 1.865, 95% CI 1.439-2.416), BMD T-score ≤ -2.5 (OR 1.725, 95% CI 1.440-2.067), history of surgery (OR 3.941, 95% CI 3.475-4.471) and trauma (OR 8.075, 95% CI 6.941-9.395). Low risk of fall (OR 0.681, 95% CI 0.513-0.904), use of anti-osteoporosis medication (AOM, OR 0.801, 95% CI 0.693-0.926), and women who had received fall prevention health education (OR 0.583, 95% CI 0.465-0.730) associated with lower risk. The areas under the curve of the prediction model was 0.818. The sensitivity was 67.0% and the specificity was 82.0%. The prediction model showed a good ability to predict the risk of subsequent fracture in older women with osteoporotic fractures and are suitable for early self-measurement which may benefit post-fracture management.

Quantitative and qualitative evaluation of antimicrobial usage: the first step for antimicrobial stewardship.

The identification of antimicrobial use patterns is essential for determining key targets for antimicrobial stewardship interventions and evaluating the effectiveness thereof. Accurately identifying antimicrobial use patterns requires quantitative evaluation, which focuses on measuring the quantity and frequency of antimicrobial use, and qualitative evaluation, which assesses the appropriateness, effectiveness, and potential side effects of antimicrobial prescriptions. This paper summarizes the quantitative and qualitative methods used to evaluate antimicrobials, drawing insights from overseas and domestic cases.

Trends of antibiotic use at the end-of-life of cancer and non-cancer decedents: a nationwide population-based longitudinal study (2006-2018).

Objective: This study aimed to assess the actual burden of antibiotic use among end-of-life (EOL) patients in South Korea and to compare trends between cancer and non-cancer decedents. Design: Population-based mortality follow-back study. Setting: Data from the Korean National Health Insurance Database, covering the period from January1, 2006, to December 31, 2018, provided for research by the National Health Insurance Service (NHIS), were used. Participants: All decedents from 2006 to 2018 were included and categorized as cancer decedents or non-cancer decedents. Methods: Annual antibiotic consumption rates and prescription rates were calculated, and Poisson regression was used to estimate their trends. Results: Overall antibiotic consumption rates decreased slightly among decedents in their final month with a less pronounced annual decrease rate among cancer decedents compared to non-cancer decedents (0.4% vs 2.3% per year, P <.001). Over the study period, although narrow spectrum antibiotics were used less, utilization and prescription of broad-spectrum antibiotics steadily increased, and prescription rates were higher in cancer decedents compared to non-cancer controls. Specifically, carbapenem prescription rates increased from 5.6% to 18.5%, (RR 1.087, 95% CI 1.085-1.088, P <.001) in cancer decedents and from 2.9% to 13.2% (RR 1.115, 95% CI 1.113-1.116, P <.001) in non-cancer decedents. Conclusions: Our findings show that patients at the EOL, especially those with cancer, are increasingly and highly exposed to broad-spectrum antibiotics. Measures of antibiotic stewardship are required among this population.

Synthesis of carboxymethyl chitosan-guar gum-poly(vinylpyrrolidone) ternary blended hydrogels with antibacterial/anticancer efficacy and drug delivery applications.

Biopolymers have the utmost significance in biomedical applications and blending synthetic polymers has shown favorable characteristics versus individual counterparts. The utilization of the blends can be restricted through the use of toxic chemical agents such as initiators or crosslinkers. In this regard, a chemical agent-free ionizing irradiation is a beneficial alternative for preparing the hydrogels for biomedical applications. In this study, carboxymethyl chitosan (CM-CS), guar gum (GG), and poly(vinylpyrrolidone) (PVP) based ternary blends (TB) were crosslinked using various doses of ionizing irradiation to fabricate hydrogels. The prepared hydrogels were characterized for physicochemical properties, swelling analysis, biological assays, and drug delivery applications. Swelling analysis in distilled water revealed that the hydrogels exhibit excellent swelling characteristics. An in vitro cytocompatibility assay showed that the hydrogels have greater than 90% cell viability for the human epithelial cell line and a decreasing cell viability trend for the human alveolar adenocarcinoma cell line. In addition, the prepared hydrogels possessed excellent antibacterial characteristics against gram-positive Staphylococcus aureus (S. aureus) and gram-negative Escherichia coli (E. coli). Finally, the release studies of anti-inflammatory Quercus acutissima (QA) loaded hydrogels exhibited more than 80% release in phosphate-buffered saline (pH = 7.4). These findings suggest that TB hydrogels can be used as suitable carrier media for different release systems and biomedical applications.

Characteristics of terminal hemimelia: What is the difference between terminal hemimelia and classic fibular hemimelia?

Purpose: Fibular hemimelia has denoted a spectrum of postaxial longitudinal deficiency with fibular aplasia/hypoplasia; the term "terminal hemimelia" is reserved for patients with postaxial longitudinal deficiency having a normal fibula. We aimed to delineate the characteristics of terminal hemimelia. Methods: In total, 30 patients with postaxial longitudinal deficiency who had a normal or hypoplastic fibula and visited our institution between 1992 and 2022 were reviewed. Patients were divided into terminal hemimelia and classic fibular hemimelia groups, and their demographic characteristics and clinical and radiographic findings were compared. Results: Femoral shortening, knee valgus, and tibial spine hypoplasia were less common in terminal hemimelia (n = 13) than in classic fibular hemimelia (n = 17) (p = 0.03, p < 0.001, and p = 0.003, respectively). None of the patients in the terminal hemimelia group exhibited knee instability, whereas 12% of patients with classic fibular hemimelia did. Ball-and-socket ankle and absence of lateral rays were commonly observed in both groups. However, tarsal coalition was observed less frequently in terminal hemimelia (p = 0.004). All terminal hemimelia patients exhibited a painless plantigrade foot without ankle instability. Despite limb-length discrepancy at maturity averaging 40.4 mm for terminal hemimelia and 67.0 mm for classic fibular hemimelia (p < 0.001), patients with terminal hemimelia, except for one, exhibited > 20 mm of limb-length discrepancy. However, 46% of them underwent limb-length equalization procedures, mostly single-stage tibial lengthening, at a mean age of 11.2 years. Conclusion: Terminal hemimelia may present with a milder phenotype than classic fibular hemimelia. It mainly overlaps with the symptoms of fibular hemimelia below the ankle joint and manifests as limb-length discrepancy. However, a considerable number of patients with terminal hemimelia required limb-length equalization procedures, for example single-stage tibial lengthening. Level of evidence: level IV.

Bibliometric analysis of auriculotherapy research trends over the past 20 years.

OBJECTIVES: Auriculotherapy has long been used to treat various diseases. We analyzed and visualized auriculotherapy's geographical distribution, key contributors, and thematic trends over the past 20 years to provide current trends in auriculotherapy field and to offer recommendations for future research directions. DESIGN/SETTING: We searched for relevant studies in the Web of Science between January 10, 2003, and December 31, 2022. A bibliometric analysis was performed using VOSviewer for annual publications, journals, countries, institutions, authors, and keywords. RESULTS: A total of 800 studies were included in the analysis, and the number of studies steadily increased over the 20 examined years. In 2018, there was a noteworthy rise in publications, nearly twice as many as the preceding year. Integrative & complementary medicine was the most researched area, with most articles published in Evidence-Based Complementary and Alternative Medicine. China was the country with the most published research, and the most active organization was Guangzhou University of Chinese Medicine in China, followed by Kyung Hee University in South Korea. The most prolific author was Yeh Mei-ling, who reported the effects of auriculotherapy on dysmenorrhea and smoking cessation. Keyword analysis revealed four clusters: pain, mental health, obesity, and smoking cessation. CONCLUSION: Auriculotherapy research primarily focused on clinical studies related to pain, obesity, smoking cessation, and depression. Future research should place greater emphasis on verifying the mechanisms of auriculotherapy for specific ailments and may require efforts to enhance the robustness of clinical trials. Through visual analysis, our study may serve as a foundational resource, offering valuable insights into the trajectory of auriculotherapy research.

Prolyl hydroxylase inhibition protects against murine MC903-induced skin inflammation by downregulating TSLP.

Previously, we reported an anti-inflammatory effect of mTORC1 in a mouse model of type 2 skin inflammation. TSLP, one of the epithelial cell-derived cytokines, was upregulated by Raptor deficiency or rapamycin treatment, which was inhibited by dimethyloxalylglycine (DMOG). However, it remains unclear how DMOG regulates TSLP expression and type 2 skin inflammation. In this study, we investigated the protective effect of DMOG on MC903 (calcipotriol)-induced type 2 skin inflammation. Morphological and immunological changes were assessed by H-E staining, flow cytometry and RT-qPCR. DMOG treatment attenuated MC903-induced skin inflammation in a T cell-independent manner. The anti-inflammatory effect of DMOG was accompanied by downregulation of TSLP and IL-33, and supplementation with recombinant TSLP and IL-33 abolished the effect of DMOG. MC903 increased ROS levels in skin tissue, which was prevented by DMOG. Furthermore, the ROS scavenger N-acetylcysteine (NAC) downregulated TSLP and ameliorated MC903-induced skin inflammation, as did DMOG. Finally, the effect of DMOG on ROS and TSLP was reduced by HIF knockdown. These results suggest that DMOG downregulates TSLP and ROS through the HIF pathway, which reduces MC903-induced skin inflammation.

Pandemic Effects on Stability of End-of-Life Preferences and Patient-Surrogate Dyad Congruence.

CONTEXT: Whether a largescale disaster alters people's previous decisions about their end-of-life care is unknown. OBJECTIVES: We examined the effects of a disaster, the COVID-19 pandemic, on stability of end-of-life care preferences among dialysis patients and on patient-surrogate goals-of-care congruence. METHODS: We used a natural experimental design to examine goals-of-care preferences pre- and postexposure to the pandemic during a pragmatic trial testing SPIRIT (sharing patient's illness representations to increase trust), an evidence-based advance care planning (ACP) intervention. There were 151 patient-surrogate dyads who prior to the pandemic lockdown had completed baseline (T1) and postintervention assessments (T2) regarding their goals-of-care preferences in two end-of-life scenarios. Of those 151 dyads, 59 intervention, and 51 usual care dyads consented to be in the present study and completed the goals-of-care tool two additional times, at enrollment (T3) and six months later (T4), along with the COVID stress scale (CSS). Dyad congruence was ascertained by comparing patient and surrogate responses to the goals-of-care tool. RESULTS: There were no changes over time in the proportions of patients who chose comfort-care-only in the goals-of-care tool. The proportion of patients who chose comfort-care-only and dyad congruence were higher in SPIRIT compared to usual care, but there was no interaction between that treatment effect and exposure to the pandemic. CSS was associated with neither patients' preferences nor dyad congruence. CONCLUSIONS: The pandemic alone did not appear to influence patients' goals-of-care preferences or dyad congruence. This finding supports the stability of value-based end-of-life preferences in general, even during a disaster.

Timosaponin A3 Induces Anti-Obesity and Anti-Diabetic Effects In Vitro and In Vivo.

Obesity is a serious global health challenge, closely associated with numerous chronic conditions including type 2 diabetes. Anemarrhena asphodeloides Bunge (AA) known as Jimo has been used to address conditions associated with pathogenic heat such as wasting-thirst in Korean Medicine. Timosaponin A3 (TA3), a natural compound extracted from AA, has demonstrated potential therapeutic effects in various disease models. However, its effects on diabetes and obesity remain largely unexplored. We investigated the anti-obesity and anti-diabetic properties of TA3 using in vitro and in vivo models. TA3 treatment in NCI-H716 cells stimulated the secretion of glucagon-like peptide 1 (GLP-1) through the activation of phosphorylation of protein kinase A catalytic subunit (PKAc) and 5'-AMP-activated protein kinase (AMPK). In 3T3-L1 adipocytes, TA3 effectively inhibited lipid accumulation by regulating adipogenesis and lipogenesis. In a high-fat diet (HFD)-induced mice model, TA3 administration significantly reduced body weight gain and food intake. Furthermore, TA3 improved glucose tolerance, lipid profiles, and mitigated hepatic steatosis in HFD-fed mice. Histological analysis revealed that TA3 reduced the size of white adipocytes and inhibited adipose tissue generation. Notably, TA3 downregulated the expression of lipogenic factor, including fatty-acid synthase (FAS) and sterol regulatory element-binding protein 1c (SREBP1c), emphasizing its potential as an anti-obesity agent. These findings revealed that TA3 may be efficiently used as a natural compound for tackling obesity, diabetes, and associated metabolic disorders, providing a novel approach for therapeutic intervention.

Prevalence and Risk Factors of Age-Related Macular Degeneration in South Korea: Korea National Health and Nutrition Examination Survey.

PURPOSE: To evaluate the prevalence and risk factors of age-related macular degeneration (AMD) in the Korean population. METHODS: In this cross-sectional study based on the Korea National Health and Nutrition Examination Survey (2017-2020) data 13,737 participants aged ≥ 40 years with assessable fundus images were included. The prevalence and risk factors of AMD were evaluated. The prevalence of early AMD, geographic atrophy (GA), and neovascular AMD were also assessed. Logistic regression analyses were used to identify risk factors. RESULTS: The prevalence (95% confidence interval [CI]) of AMD was 13.94% (13.15-14.72). The prevalence (95% CI) of early AMD, GA, and neovascular AMD was 13.07% (12.29-13.85), 0.26% (0.17-0.35), and 0.61% (0.47-0.75), respectively. The prevalence increased with age; it was 3.61%, 11.33%, 20.31%, 31.37%, and 33.98% in participants in their 40s, 50s, 60s, 70s, and ≥ 80 years, respectively. In multivariate analysis, AMD was positively associated with older age (p < 0.001; odds ratio [OR], 1.08; 95% CI, 1.07-1.09), male sex (p = 0.014; OR, 1.27; 95% CI, 1.05-1.53), and lower degree of education (p < 0.001; OR, 1.36 (for junior high school graduates); 95% CI, 1.12-1.65). CONCLUSIONS: AMD was detected in approximately one-third of individuals aged ≥ 70 years, thus indicating that AMD is a common disease among older Koreans. Regular fundus examinations in populations with risk factors for AMD as well as education on methods to prevent or delay AMD progression, such as the Mediterranean diet, are necessary.

N6-methyladenosine-modified circ_104797 sustains cisplatin resistance in bladder cancer through acting as RNA sponges.

BACKGROUND: Bladder cancer (BCa) ranks among the predominant malignancies affecting the urinary system. Cisplatin (CDDP) remains a cornerstone therapeutic agent for BCa management. Recent insights suggest pivotal roles of circular RNA (circRNA) and N6-methyladenosine (m6A) in modulating CDDP resistance in BCa, emphasizing the importance of elucidating these pathways to optimize cisplatin-based treatments. METHODS: Comprehensive bioinformatics assessments were undertaken to discern circ_104797 expression patterns, its specific interaction domains, and m6A motifs. These findings were subsequently corroborated through experimental validations. To ascertain the functional implications of circ_104797 in BCa metastasis, in vivo assays employing CRISPR/dCas13b-ALKBH5 were conducted. Techniques, such as RNA immunoprecipitation, biotin pull-down, RNA pull-down, luciferase reporter assays, and western blotting, were employed to delineate the underlying molecular intricacies. RESULTS: Our investigations revealed an elevated expression of circ_104797 in CDDP-resistant BCa cells, underscoring its pivotal role in sustaining cisplatin resistance. Remarkably, demethylation of circ_104797 markedly augmented the potency of cisplatin-mediated apoptosis. The amplification of circ_104797 in CDDP-resistant cells was attributed to enhanced RNA stability, stemming from an augmented m6A level at a distinct adenosine within circ_104797. Delving deeper, we discerned that circ_104797 functioned as a microRNA reservoir, specifically sequestering miR-103a and miR-660-3p, thereby potentiating cisplatin resistance. CONCLUSIONS: Our findings unveil a previously uncharted mechanism underpinning cisplatin resistance and advocate the potential therapeutic targeting of circ_104797 in cisplatin-administered patients with BCa, offering a promising avenue for advanced BCa management.

Measures of Patient and Surrogate Preparedness for End-of-Life Decision-Making.

CONTEXT: Reliable and valid measures are critical in accurately assessing outcomes of advance care planning interventions (ACP) for end-of-life (EOL) decision-making. OBJECTIVES: To develop measures of preparedness for EOL decision-making for patients with end-stage renal disease and their surrogates (an exemplar population). METHODS: In this 3-phase study, Phases 1 and 2 included a cross-discipline concept analysis of the preparedness construct, item generation for patient and surrogate scales (82 items), evaluation of content validity and readability, cognitive interviewing, and item reduction. In phase 3, the retained 26 patient and 25 surrogate items were administered to 426 patients and 426 surrogates during a multisite trial of an ACP intervention versus care-as-usual and evaluated internal consistency, 2-week test-retest reliability, and construct validity. RESULTS: Scales were reduced to 20 patient and 19 surrogate items during phase 3. Cronbach's alphas were 0.86 (patient) and 0.90 (surrogate). There was a strong correlation between preparedness at baseline and two weeks for both scales (r = 0.66-0.69, P < 0.001). Confirmatory factor analysis and item-response analyses suggested unidimensionality. A significant correlation was shown between patient preparedness and patient decisional conflict (r = -0.53, P < 0.001), and surrogate preparedness and surrogate decision-making confidence (r = 0.44, P < 0.001). Among those who received the ACP intervention, the effect size of change was medium: Cohen's d = 0.54, P < 0.001 for patients and d = 0.57, P < 0.001 for surrogates. CONCLUSIONS: The preparedness scales demonstrated strong psychometric properties. Future studies should examine scale performance in other populations.

Risk Factors for Coronary Artery Complications After Prosthetic Pulmonary Valve Implantation in Patients With Congenital Heart Disease.

BACKGROUND: Coronary artery complications (CACs) in patients who undergoing prosthetic pulmonary valve implantation for congenital heart disease can lead to fetal outcomes. However, the incidence of and risk factors for CACs in these patients remain unknown.Methods and Results: A retrospective cohort study was conducted on patients who underwent cardiac computed tomography or invasive coronary angiography after prosthetic pulmonary valve implantation at Seoul National University Hospital from June 1986 to May 2021. Among 341 patients, 25 (7.3%) were identified with CACs, and 2 of them died. Among the patients with CACs, congenital coronary anomalies and an interarterial course of the coronary artery were identified in 11 (44%) and 18 (72%) patients, respectively. Interarterial and intramural courses of the coronary artery were associated with a 4.4- and 10.6-fold increased risk of CACs, respectively. Among patients with tetralogy of Fallot and pulmonary atresia, the aortic root was rotated further clockwise in patients with coronary artery compression compared to those without it (mean [±SD] 128.0±19.9° vs. 113.5±23.7°; P=0.024). The cut-off rotation angle of the aorta for predicting the occurrence of coronary artery compression was 133°. CONCLUSIONS: Perioperative coronary artery evaluation and prevention of CACs are required in patients undergoing prosthetic pulmonary valve implantation, particularly in those with coronary artery anomalies or severe clockwise rotation of the aortic root.

State of the science of sexual health among older cancer survivors: an integrative review.

PURPOSE: Sexual health is important for quality of life among older (≥65 years) cancer survivors. Yet, little is known about the extent to which their sexual health has been studied. METHODS: In this integrative review, PubMed, PsycINFO, CINAHL, and Web of Science were searched for data-based articles of sexual health among older cancer survivors. Using a matrix, study characteristics, including cancer types and areas of sexual health, were categorized. RESULTS: The sample included 82 articles (81 studies). The areas of sexual health were categorized into sexual function, body image, sexual function-related distress, sexual health-related quality of life, sexual activity, sexual enjoyment, and sexual desire. Most targeted prostate cancer (n = 56, 69.1%) and studied sexual function, e.g., erectile function (n = 53, 94.6%). Body image (n = 16, 19.8%) was next frequently studied, targeting women with breast cancer. Measures to assess areas of sexual health, largely unstandardized, varied widely. Generally, older cancer survivors reported negative changes in sexual function and other areas during and after cancer treatment. CONCLUSIONS: Studies of sexual health among older cancer survivors have been focused primarily on prostate cancer, male, and sexual function. Together with the lack of standardized sexual health measures validated for older adults, this narrow research focus contributes to the limited body of knowledge regarding sexual health among older cancer survivors. IMPLICATIONS FOR CANCER SURVIVORS: Given that cancer and cancer treatment affect both men and women and many aspects of sexual health beyond functioning, broadening the scope of sexual health and cancer type is warranted for future research.

Validation of a new risk stratification system-based management for methicillin-resistant Staphylococcus aureus bacteraemia: analysis of a multicentre prospective study.

PURPOSE: Distinguishing between complicated and uncomplicated Staphylococcus aureus bacteraemia (SAB) is therapeutically essential. However, this distinction has limitations in reflecting the heterogeneity of SAB and encouraging targeted diagnostics. Recently, a new risk stratification system for SAB metastatic infection, involving stepwise approaches to diagnosis and treatment, has been suggested. We assessed its applicability in methicillin-resistant SAB (MRSAB) patients. METHODS: We retrospectively analysed data of a 3-year multicentre, prospective cohort of hospitalised patients with MRSAB. We classified the patients into three risk groups: low, indeterminate, and high, based on the new system and compared between-group management and outcomes. RESULTS: Of 380 patients with MRSAB, 6.3% were classified as low-, 7.6% as indeterminate-, and 86.1% as high-risk for metastatic infection. No metastatic infection occurred in the low-, 6.9% in the indeterminate-, and 19.6% in the high-risk groups (P < 0.001). After an in-depth diagnostic work-up, patients were finally diagnosed as 'without metastatic infection (6.3%)', 'with metastatic infection (17.4%)', and 'uncertain for metastatic infection (76.3%)'. 30-day mortality increased as the severity of diagnosis shifted from 'without metastatic infection' to 'uncertain for metastatic infection' and 'with metastatic infection' (P = 0.09). In multivariable analysis, independent factors associated with metastatic complications were suspicion of endocarditis in transthoracic echocardiography, clinical signs of metastatic infection, Pitt bacteraemia score ≥ 4, and persistent bacteraemia. CONCLUSIONS: The new risk stratification system shows promise in predicting metastatic complications and guiding work-up and management of MRSAB. However, reducing the number of cases labelled as 'high-risk' and 'uncertain for metastatic infection' remains an area for improvement.

MALAT1 promotes FOXA1 degradation by competitively binding to miR-216a-5p and enhancing neuroendocrine differentiation in prostate cancer.

OBJECTIVES: Prostate cancer (PC) is a leading cause of cancer-related death in males worldwide. Neuroendocrine differentiation (NED) is a feature of PC that often goes undetected and is associated with poor patient outcomes. Long non-coding RNAs (lncRNAs), microRNAs (miRNAs/miRs), and messenger RNAs (mRNAs) play important roles in the development and progression of PC. METHODS: In this study, we used transcriptome sequencing and bioinformatics analysis to identify key regulators of NED in PC. Specifically, we examined the expression of PC-related lncRNAs, miRNAs, and mRNAs in PC cells and correlated these findings with NED phenotypes. RESULTS: Our data revealed that metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) and zinc finger protein 91 (ZFP91) were upregulated in PC, while miR-216a-5p was down-regulated. Ectopic expression of MALAT1 induced NED and promoted malignant phenotypes of PC cells. Furthermore, we found that MALAT1 competitively bound to miR-216a-5p, upregulated ZFP91, and promoted the degradation of forkhead box A1 (FOXA1), a key gene involved in NED of PC. CONCLUSION: Taken together, these results suggest that MALAT1 plays an oncogenic role in NED and metastasis of PC via the miR-216a-5p/ZFP91/FOXA1 pathway. Our study highlights the potential of targeting this pathway as a novel therapeutic strategy for PC.