Adenovirus expressing nc886, an anti-interferon and anti-apoptotic non-coding RNA, is an improved gene delivery vector.

Recombinant adenovirus (rAdV) vector is the most promising vehicle to deliver an exogenous gene into target cells and is preferred for gene therapy. Exogenous gene expression from rAdV is often too inefficient to induce phenotypic changes and the amount of administered rAdV must be very high to achieve a therapeutic dose. However, it is often hampered because a high dose of rAdV is likely to induce cytotoxicity by activating immune responses. nc886, a 102-nucleotide non-coding RNA that is transcribed by RNA polymerase III, acts as an immune suppressor and a facilitator of AdV entry into the nucleus. Therefore, in this study, we have constructed an rAdV expressing nc886 (AdV:nc886) to explore whether AdV:nc886 overcomes the aforementioned drawbacks of conventional rAdV vectors. When infected into mouse cell lines and mice, AdV:nc886 expresses a sufficient amount of nc886, which suppresses the induction of interferon-stimulated genes and apoptotic pathways triggered by AdV infection. As a result, AdV:nc886 is less cytotoxic and produces more rAdV-delivered gene products, compared with the parental rAdV vector lacking nc886. In conclusion, this study demonstrates that the nc886-expressing rAdV could become a superior gene delivery vehicle with greater safety and higher efficiency for in vivo gene therapy.

Study Design and Protocol for a Randomized Controlled Trial to Assess Long-Term Efficacy and Safety of a Triple Combination of Ezetimibe, Fenofibrate, and Moderate- Intensity Statin in Patients with Type 2 Diabetes and Modifiable Cardiovascular Risk Factors (ENSEMBLE).

Background: Atherogenic dyslipidemia, which is frequently associated with type 2 diabetes (T2D) and insulin resistance, contributes to the development of vascular complications. Statin therapy is the primary approach to dyslipidemia management in T2D, however, the role of non-statin therapy remains unclear. Ezetimibe reduces cholesterol burden by inhibiting intestinal cholesterol absorption. Fibrates lower triglyceride levels and increase high-density lipoprotein cholesterol (HDL-C) levels via peroxisome proliferator- activated receptor alpha agonism. Therefore, when combined, these drugs effectively lower non-HDL-C levels. Despite this, few clinical trials have specifically targeted non-HDL-C, and the efficacy of triple combination therapies, including statins, ezetimibe, and fibrates, has yet to be determined. Methods: This is a multicenter, prospective, randomized, open-label, active-comparator controlled trial involving 3,958 eligible participants with T2D, cardiovascular risk factors, and elevated non-HDL-C (≥100 mg/dL). Participants, already on moderate-intensity statins, will be randomly assigned to either Ezefeno (ezetimibe/fenofibrate) addition or statin dose-escalation. The primary end point is the development of a composite of major adverse cardiovascular and diabetic microvascular events over 48 months. Conclusion: This trial aims to assess whether combining statins, ezetimibe, and fenofibrate is as effective as, or possibly superior to, statin monotherapy intensification in lowering cardiovascular and microvascular disease risk for patients with T2D. This could propose a novel therapeutic approach for managing dyslipidemia in T2D.

The association of shift work and TyG index among male workers in a chemical plant of Korea: a cross-sectional study.

Background: Disturbance of circadian rhythms caused by shift work has adverse effects on insulin resistance. Many previous studies have confirmed that shift work and insulin resistance are related using homeostasis model assessment-insulin resistance, one of the insulin resistance indicators. However, the triglycerides and glucose index (TyG index) has recently been studied as an insulin resistance indicator. The aim of this study is to investigate the association of shift work and TyG index, one of the indirect indicators of insulin resistance, using results of health checkups in one workplace. Methods: Based on medical examination data collected in February 2019, a total of 3,794 subjects from one chemical plant in Korea were selected for this study. Cut-off value of TyG index for predicting development of diabetes mellitus (DM) was 4.69. A multiple logistic regression analysis was performed after adjusting for age, employment period, obesity, abdominal obesity, smoking, drinking, physical activity, hypertension, stroke, heart disease. Results: As a result of logistic regression analysis, compared to day workers, odds ratio (OR) with a TyG index above cut-off value for predicting development of DM in shift workers was 1.220 after adjusting for age, employment period, obesity, abdominal obesity, smoking, drinking, physical activity, hypertension, stroke, heart disease (Model 1, OR: 1.276; 95% confidence interval [CI]: 1.099-1.482; Model 2, OR: 1.232; 95% CI: 1.055-1.438; Model 3, OR: 1.220, 95% CI: 1.030-1.444). Conclusions: There was a significant association between shift work and TyG index among male workers in a chemical plant. More research studies on the association between shift work and TyG index are needed in the future.

Extracts of Phlomoides umbrosa Turczaninow alleviate allergic airway inflammation in lipopolysaccharide-stimulated RAW 264.7 cells and ovalbumin-induced hyper-responsiveness mouse model.

Phlomoides umbrosa Turczaninow (PU), a traditional Korean medicinal herb, exhibits osteogenic and anti-inflammatory effects. This research explored the effect of PU extracts on hyperimmune responses within the respiratory tract using lipopolysaccharide-stimulated RAW 264.7 cells and an ovalbumin-induced hyper-responsiveness model. The inflammatory cytokines, protein expression linked to airway inflammation, antioxidant enzyme activity, histopathological observation, and expectorant activity were measured. The results revealed that PU treatment led to a concentration-dependent reduction in Th2 cytokines and the expression of nuclear factor (NF)-κB, phosphatase-tensin homolog, mitogen-activated protein kinase (MAPK), and inducible nitric oxide synthase (iNOS). Simultaneously, antioxidant enzyme activity increased. Furthermore, PU exhibited substantial enhancements in lung tissue condition and expectorant activity relative to the allergic rhinitis-induced group. These findings indicate the potential of PU to mitigate airway inflammation and excessive mucus production by suppressing NF-κB, MAPK, and iNOS pathways. Consequently, PU emerges as a promising anti-inflammatory agent for respiratory tract applications. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-024-01521-3.

Improved Pulmonary Artery Evaluation Using High-Pitch Photon-Counting CT Compared to High-Pitch Conventional or Routine-Pitch Conventional Dual-Energy CT.

OBJECTIVE: Pulmonary CT angiography (CTA) to detect pulmonary emboli can be performed using conventional dual-source CT with single-energy acquisition at high-pitch (high-pitch conventional CT), which minimizes motion artifacts, or routine-pitch, dual-energy acquisitions (routine-pitch conventional DECT), which maximize iodine signal. We compared iodine signal, radiation dose, and motion artifacts of pulmonary CTA between these conventional CT modalities and dual-source photon-counting detector CT with high-pitch, multienergy acquisitions (high-pitch photon-counting CT). METHODS: Consecutive clinically indicated pulmonary CTA exams were collected. CT number/noise was measured from the main to right lower lobe segmental pulmonary arteries using 120 kV threshold low, 120 kV, and mixed kV (0.6 linear blend) images. Three radiologists reviewed anonymized, randomized exams, rating them using a 4- or 5-point Likert scale (1 = worst, and 4/5 = best) for contrast enhancement in pulmonary arteries, motion artifacts in aortic root to subsegmental pulmonary arteries, lung image quality; pulmonary blood volume (PBV) map image quality (for multienergy or dual-energy exams), and contribution to reader confidence. RESULTS: One hundred fifty patients underwent high-pitch photon-counting CT (n = 50), high-pitch conventional CT (n = 50), and routine-pitch conventional DECT (n = 50). High-pitch photon-counting CT had lower radiation dose (CTDIvol: 8.1 ± 2.5 vs 9.6 ± 6.8 and 16.2 ± 8.5 mGy, respectively; P < 0.001), and routine-pitch conventional DECT had significantly less contrast (P < 0.009). CT number and CNR measurements were significantly greater at high-pitch photon-counting CT (P < 0.001). Across readers, high-pitch photon-counting CT demonstrated significantly higher subjective contrast enhancement in the pulmonary arteries compared to the other modalities (4.7 ± 0.6 vs 4.4 ± 0.7 vs 4.3 ± 0.7; P = 0.011) and lung image quality (3.4 ± 0.5 vs 3.1 ± 0.5 vs 3.1 ± 0.5; P = 0.013). High-pitch photon-counting CT and high-pitch conventional CT had fewer motion artifacts at all levels compared to DECT (P < 0.001). High-pitch photon-counting CT PBV maps had superior image quality (P < 0.001) and contribution to reader confidence (P < 0.001) compared to routine-pitch conventional DECT. CONCLUSION: High-pitch photon-counting pulmonary CTA demonstrated higher contrast in pulmonary arteries at lower radiation doses with improved lung image quality and fewer motion artifacts compared to high-pitch conventional CT and routine-pitch conventional dual-energy CT.

Host-microbe interactions rewire metabolism in a C. elegans model of leucine breakdown deficiency.

In humans, defects in leucine catabolism cause a variety of inborn errors in metabolism. Here, we use Caenorhabditis elegans to investigate the impact of mutations in mccc-1, an enzyme that functions in leucine breakdown. Through untargeted metabolomic and transcriptomic analyses we find extensive metabolic rewiring that helps to detoxify leucine breakdown intermediates via conversion into previously undescribed metabolites and to synthesize mevalonate, an essential metabolite. We also find that the leucine breakdown product 3,3-hydroxymethylbutyrate (HMB), commonly used as a human muscle-building supplement, is toxic to C. elegans and that bacteria modulate this toxicity. Unbiased genetic screens revealed interactions between the host and microbe, where components of bacterial pyrimidine biosynthesis mitigate HMB toxicity. Finally, upregulated ketone body metabolism genes in mccc-1 mutants provide an alternative route for biosynthesis of the mevalonate precursor 3-hydroxy-3-methylglutaryl-CoA. Our work demonstrates that a complex host-bacteria interplay rewires metabolism to allow host survival when leucine catabolism is perturbed.

Ticagrelor monotherapy in ST-elevation myocardial infarction: An individual patient-level meta-analysis from TICO and T-PASS trials.

BACKGROUND: Patients with ST-elevation myocardial infarction (STEMI) tend to be excluded or under-represented in randomized clinical trials evaluating the effects of potent P2Y12 inhibitor monotherapy after short-term dual antiplatelet therapy (DAPT). METHODS: Individual patient data were pooled from randomized clinical trials that included STEMI patients undergoing drug-eluting stent (DES) implantation and compared ticagrelor monotherapy after short-term (≤3 months) DAPT versus ticagrelor-based 12-month DAPT in terms of centrally adjudicated clinical outcomes. The co-primary outcomes were efficacy outcome (composite of all-cause death, myocardial infarction, or stroke) and safety outcome (Bleeding Academic Research Consortium type 3 or 5 bleeding) at 1 year. FINDINGS: The pooled cohort contained 2,253 patients with STEMI. The incidence of the primary efficacy outcome did not differ between the ticagrelor monotherapy group and the ticagrelor-based DAPT group (1.8% versus 2.0%; hazard ratio [HR] = 0.88; 95% confidence interval [CI] = 0.49-1.61; p = 0.684). There was no difference in cardiac death between the groups (0.6% versus 0.7%; HR = 0.89; 95% CI = 0.32-2.46; p = 0.822). The incidence of the primary safety outcome was significantly lower in the ticagrelor monotherapy group (2.3% versus 4.0%; HR = 0.56; 95% CI = 0.35-0.92; p = 0.020). No heterogeneity of treatment effects was observed for the primary outcomes across subgroups. CONCLUSIONS: In patients with STEMI treated with DES implantation, ticagrelor monotherapy after short-term DAPT was associated with lower major bleeding without an increase in the risk of ischemic events compared with ticagrelor-based 12-month DAPT. Further research is necessary to extend these findings to non-Asian patients. FUNDING: This study was funded by Biotronik (Bülach, Switzerland).

Increasing HIV Testing Among Sexual and Gender Expansive Men in Kazakhstan: A Stepped-Wedge Randomized Trial of a Community-Level Intervention.

Importance: HIV transmission in Kazakhstan has increased among men who have sex with men (MSM) and transgender and nonbinary people who have sex with men (TSM), driven by low HIV testing rates. Objective: To determine if the PRIDE in HIV Care intervention had a community effect of increasing HIV testing among MSM and TSM in Kazakhstan. Design: We employed a stepped-wedge, cluster-randomized controlled trial with MSM and TSM community members recruited from three cities in Kazakhstan: Almaty, Astana, and Shymkent. We collected serial cross-sectional data where community members completed one assessment between 21 August 2018, and 30 March 2022. Setting: We collected data from 629 MSM and TSM among the study cities. Community respondents were recruited from real-world (e.g., NGOs, bars, clubs) or virtual sites (e.g., social media, apps) where MSM and TSM in each of the three cities were known to frequent. Participants: Eligibility criteria for community respondents were: (1) ≥18 years old; (2) identifying as male at any point in life or being assigned male at birth; (3) having consensual sex with another man in the past 12 months; (4) engaging in binge drinking (i.e., ≥5 drinks in a 2 hour period), illicit use of drugs, or both in the past 90 days; and (5) residing in one of the three study cities. Intervention: The PRIDE in HIV Care intervention is a theory-driven "crowdsourcing and peer-actuated network intervention" designed to amplify community members' successes and resilience via "influencers" who can strengthen and impart benefit to their networks and community. Main outcome measures: Received an HIV test in the prior six months. Results: There was a statistically significant increase in odds of recent HIV testing for every additional month the intervention was implemented in a respondent's city (AOR=1.08, 95% CI=1.05-1.12; p<.001). Conclusions: The PRIDE in HIV Care intervention appears to be efficacious in enacting a community wide increase-i.e., promoted HIV testing among those who did not go through the intervention itself-in HIV testing among MSM and TSM. Trial Registration: This trial is registered with clinicaltrials.gov (NCT02786615). Funding: National Institute on Drug Abuse (NIDA), grant number R01DA040513.

Augmentation of intracranial self-stimulation induced by amphetamine-like drugs in Period circadian regulator 2 knockout mice is associated with intracellular Ca2+ levels.

Over the past decade, new psychoactive substances (NPS) have emerged in the illegal drug market and have continued to attract attention from the international community. Among these, amphetamine-like NPS, classified as stimulants, constitute a significant proportion. However, the pharmacological characteristics and mechanisms underlying addiction to amphetamine-like NPS remain poorly understood. Given that circadian rhythms are linked to the brain stimulation effects of methamphetamine (METH) and amphetamine, we investigated the effects of METH, 1-(4-methoxyphenyl)-N-methylpropan-2-amine (PMMA), and 1-(benzofuran-5-yl)-N-ethylpropan-2-amine (5-EAPB) on intracranial self-stimulation (ICSS) in wild-type (WT) or Period circadian regulator 2 knockout mice. Amphetamine-like drugs increase intracellular Ca2+ levels to provoke dopamine release, so we examined the impact of Per2 knockdown on intracellular Ca2+ levels in PC12 cells to elucidate a potential mechanism underlying NPS-induced ICSS enhancement. Our ICSS results showed that METH and PMMA significantly increased brain stimulation in Per2 knockout mice compared to WT mice. Similarly, METH and PMMA induced higher Ca2+ fluorescence intensity in Per2 knockdown PC12 cells than in control cells. In contrast, 5-EAPB did not produce significant changes in either ICSS or Ca2+ signaling. These findings suggest that Per2 plays a crucial role in the brain stimulation effects of amphetamine-like drugs through the regulation of intracellular Ca2+.

The potential for drug incompatibility and its drivers - A hospital wide retrospective descriptive study.

OBJECTIVE: Drug incompatibility, a significant subset of medication errors, threaten patient safety during the medication administration phase. Despite the undeniably high prevalence of drug incompatibility, it is currently poorly understood because previous studies are focused predominantly on intensive care unit (ICU) settings. To enhance patient safety, it is crucial to expand our understanding of this issue from a comprehensive viewpoint. This study aims to investigate the prevalence and mechanism of drug incompatibility by analysing hospital-wide prescription and administration data. METHODS: This retrospective cross-sectional study, conducted at a tertiary academic hospital, included data extracted from the clinical data warehouse of the study institution on patients admitted between January 1, 2021, and May 31, 2021. Potential contacts in drug pairs (PCs) were identified using the study site clinical workflow. Drug incompatibility for each PC was determined by using a commercial drug incompatibility database, the Trissel's™ 2 Clinical Pharmaceutics Database (Trissel's 2 database). Drivers of drug incompatibility were identified, based on a descriptive analysis, after which, multivariate logistic regression was conducted to assess the risk factors for experiencing one or more drug incompatibilities during admission. RESULTS: Among 30,359 patients (representing 40,061 hospitalisations), 24,270 patients (32,912 hospitalisations) with 764,501 drug prescriptions (1,001,685 IV administrations) were analysed, after checking for eligibility. Based on the rule for determining PCs, 5,813,794 cases of PCs were identified. Among these, 25,108 (0.4 %) cases were incompatible PCs: 391 (1.6 %) PCs occurred during the prescription process and 24,717 (98.4 %) PCs during the administration process. By classifying these results, we identified the following drivers contributing to drug incompatibility: incorrect order factor; incorrect administration factor; and lack of related research. In multivariate analysis, the risk of encountering incompatible PCs was higher for patients who were male, older, with longer lengths of stay, with higher comorbidity, and admitted to medical ICUs. CONCLUSIONS: We comprehensively described the current state of drug incompatibility by analysing hospital-wide drug prescription and administration data. The results showed that drug incompatibility frequently occurs in clinical settings.

Topical dorzolamide for macular holes: A randomised, double-blind, placebo-controlled trial.

BACKGROUND: To assess topical dorzolamide as medical therapy for idiopathic full-thickness macular holes (FTMHs). METHODS: Randomised, double-blinded, placebo-controlled, single-centre clinical trial involving 32 patients with idiopathic small FTMHs (<400 µm $$ \upmu \mathrm{m} $$ ). Participants in both arms used topical dorzolamide 2% or saline thrice daily for 8 weeks with monthly OCT. Those with persisting FTMH underwent vitrectomy with ILM peel and gas tamponade. The primary outcome was the rate of FTMH closure at the end of treatment. RESULTS: Between 6 March 2020 and 16 June 2023, 32 eligible patients were enrolled: 16 participants in each arm. All participants in both groups were included in the final analysis. At the final visit, 3 of 16 (18.8%) patients in both the topical dorzolamide and placebo group demonstrated closure. There was no statistically significant difference in the proportion of FTMH closure between the control and treatment group (p = 1.00), nor statistically significant difference in the mean change in best corrected visual acuity (BCVA; p = 0.909). There was no difference in the change in FTMH diameter between groups (p = 0.225). No serious adverse events were reported in either group. CONCLUSION: Topical dorzolamide was safe but not superior to placebo in the functional and anatomical outcomes of FTMH.

Doctor shopping trend of patients before undergoing rotator cuff repair in Korea: a multicenter study.

Background: To investigate the doctor shopping trend of patients with rotator cuff tear (RCT) before undergoing surgery and the relevance of the results to the public. Methods: A survey was conducted of 326 patients from 10 hospitals (male, 176; female, 150) who underwent arthroscopic rotator cuff repair (ARCR) for symptomatic RCT between September 2019 and February 2020. A questionnaire was used to obtain data regarding the type of medical care service, medical institutions visited before surgery, number of treatments received, and cost of treatment. Results: A total of 326 patients (87%) received treatment at least once at another medical institution before visiting the hospital where the surgery was performed. Patients visited an average of 9.4 health providers or physicians for shoulder pain before visiting the hospital where surgery was performed. Among the 326 patients, 148 (45%) visited more than two medical institutions and spent an average of 641,983 Korean won (KRW; $466, 50,000-5,000,000 KRW) before surgery. Medical expenses before surgery were proportional to the number of medical institutions visited (P=0.002), symptom duration (P=0.002), and initial visual analog scale (VAS) pain score (P=0.007) but were not associated with gender, age, VAS pain score immediately before surgery, or RCT size. Conclusions: Medical expense before ARCR was associated with the severity of preoperative pain and duration of symptoms. After onset of shoulder symptoms, patients should visit as soon as possible a hospital that has surgeons who specialize in shoulder repair to prevent unnecessary medical expense and proper treatment.

Surgical Results with Low-Grade Arteriovenous Malformations : A Single Center 14-Year Experience.

Objective: Advancements in surgical techniques for cerebral arteriovenous malformation (AVM) underscore its efficacy. Our research aims to showcase the positive outcomes of treating low-grade AVMs surgically, focusing on safety and effectiveness. Methods: We retrospectively reviewed 55 patients (36 males, 19 females, and average age 37.4 years) with Spetzler-Martin (S-M) grade 1 and 2 AVMs who underwent surgical resection between January 2009 and December 2022. Results: In our study, 55 patients with S-M grade 1 and 2 AVMs underwent surgical resection, evenly divided between grades 1 (50.9%) and 2 (49.1%). Intracranial hemorrhage was the primary symptom in 74.5% of cases. Pre-operative Glasgow Coma Scale (GCS) scores revealed 69.1% of patients scored above 13, with 18% below 8. Successful resection was achieved in 87.3%. Postoperatively, 95.5% of ruptured and 90.9% of unruptured AVM patients showed lower or same modified Rankin Scale scores. Poorer outcomes were significantly linked to lower GCS scores and intranidal/flow-related aneurysms through multivariate logistic regression. Postoperative seizures noted in 9 patients, were exclusive to the ruptured AVM group. Conclusion: Our findings indicate surgical resection as a beneficial treatment for low-grade AVMs, yielding high cure rates and positive functional outcomes in both ruptured and unruptured cases. Preoperative GCS scores and the presence of associated aneurysms are predictive of postoperative functional status. Additionally, managing postoperative seizures effectively is key to enhancing prognosis.

Three-Dimensional Integrated Synaptic Devices Based on a Silver-Cluster Conduction Mechanism with High Thermostability.

During the operation of synaptic devices based on traditional conductive filament (CF) models, the formation and dissolution of CFs are usually uncertain. Moreover, when the device is operated for a long time, the CFs may dissolve due to both the Joule heat generated by the device itself and the thermal coupling between the devices. These problems seriously reduce the reliability and stability of the synaptic device. Here, an artificial synapse device based on polyimide-molybdenum disulfide quantum dot (MoS2 QD) nanocomposites is presented. Research has shown that MoS2 QDs doped into the active layer can effectively induce the reduction of Ag ions into Ag atoms, leading to the formation of Ag clusters and thereby achieving control over the growth of the CFs. Therefore, the device is capable of stably realizing various basic synaptic functions. Moreover, the long-term potentiation/long-term depression (LTP/LTD) of this device shows good linearity. In addition, due to the change in the shape of the CFs, the highly integrated devices with a three-dimensional (3D) stacked structure can operate normally even in a high-temperature environment of 110 °C. Finally, the synaptic characteristics of the devices on learning and inference tests show that their recognition rates are approximately 90.75% (room temperature) and 90.63% (110 °C).

High glycated albumin is associated with early neurological deterioration in patients with acute ischemic stroke.

BACKGROUND: Glycated albumin (GA) is an indicator of glycemic variability over the past 2-4 weeks and has suitable characteristics for predicting the prognosis of ischemic stroke during the acute phase. This study evaluated the association between early neurological deterioration (END) and GA values in patients with acute ischemic stroke (AIS). METHODS: We assessed consecutive patients with AIS between 2022 and 2023 at two large medical centers in Korea. END was defined as an increase of ≥ 2 in the total National Institutes of Health Stroke Scale (NIHSS) score or ≥ 1 in the motor NIHSS score within the first 72 h of admission. We evaluated various glycemic parameters including fasting glucose (mg/dL), hemoglobin A1c (%), and GA (%). RESULTS: In total, 531 patients with AIS were evaluated (median age: 69 years, male sex: 66.3%). In the multivariable logistic regression analysis, GA value was positively associated with END (adjusted odds ratio [aOR] = 3.24, 95% confidence interval [CI]: 1.10-9.50). Initial NIHSS score (aOR = 1.04, 95% CI: 1.01-1.08) and thrombolytic therapy (aOR = 2.06, 95% CI: 1.14-3.73) were also associated with END. In a comparison of the predictive power of glycemic parameters for END, GA showed a higher area under the curve value on the receiver operating characteristic curve than fasting glucose and hemoglobin A1c. CONCLUSIONS: High GA values were associated with END in patients with AIS. Furthermore, GA was a better predictor of END than fasting glucose or hemoglobin A1c.

Artificial intelligence algorithm for neoplastic cell percentage estimation and its application to copy number variation in urinary tract cancer.

Background: Bladder cancer is characterized by frequent mutations, which provide potential therapeutic targets for most patients. The effectiveness of emerging personalized therapies depends on an accurate molecular diagnosis, for which the accurate estimation of the neoplastic cell percentage (NCP) is a crucial initial step. However, the established method for determining the NCP, manual counting by a pathologist, is time-consuming and not easily executable. Methods: To address this, artificial intelligence (AI) models were developed to estimate the NCP using nine convolutional neural networks and the scanned images of 39 cases of urinary tract cancer. The performance of the AI models was compared to that of six pathologists for 119 cases in the validation cohort. The ground truth value was obtained through multiplexed immunofluorescence. The AI model was then applied to 41 cases in the application cohort that underwent next-generation sequencing testing, and its impact on the copy number variation (CNV) was analyzed. Results: Each AI model demonstrated high reliability, with intraclass correlation coefficients (ICCs) ranging from 0.82 to 0.88. These values were comparable or better to those of pathologists, whose ICCs ranged from 0.78 to 0.91 in urothelial carcinoma cases, both with and without divergent differentiation/ subtypes. After applying AI-driven NCP, 190 CNV (24.2%) were reclassified with 66 (8.4%) and 78 (9.9%) moved to amplification and loss, respectively, from neutral/minor CNV. The neutral/minor CNV proportion decreased by 6%. Conclusions: These results suggest that AI models could assist human pathologists in repetitive and cumbersome NCP calculations.

Effect of rosuvastatin versus atorvastatin on new-onset diabetes mellitus in patients treated with high-intensity statin therapy for coronary artery disease: a post-hoc analysis from the LODESTAR randomized clinical trial.

BACKGROUND: The impact of rosuvastatin versus atorvastatin on new-onset diabetes mellitus (NODM) among patients treated with high-intensity statin therapy for coronary artery disease (CAD) remains to be clarified. This study aimed to evaluate the risk of NODM in patients with CAD treated with rosuvastatin compared to atorvastatin in the randomized LODESTAR trial. METHODS: In the LODESTAR trial, patients with CAD were randomly assigned to receive either rosuvastatin or atorvastatin using a 2-by-2 factorial randomization. In this post-hoc analysis, the 3-year incidence of NODM was compared between rosuvastatin and atorvastatin treatment in the as-treated population with high-intensity statin therapy as the principal population of interest. RESULTS: Among 2932 patients without diabetes mellitus at baseline, 2377 were included in the as-treated population analysis. In the as-treated population with high-intensity statin therapy, the incidence of NODM was not significantly different between the rosuvastatin and atorvastatin groups (11.4% [106/948] versus 8.8% [73/856], hazard ratio [HR] = 1.32, 95% confidence interval [CI] = 0.98 to 1.77, P = 0.071). When the risk of NODM with rosuvastatin versus atorvastatin was assessed according to the achieved low-density lipoprotein cholesterol (LDL-C) level, the risk of NODM began to increase at a LDL-C level below 70 mg/dL. The incidence of NODM was significantly greater in the rosuvastatin group than it was in the atorvastatin group when the achieved LDL-C level was < 70 mg/dL (13.9% versus 8.0%; HR = 1.79, 95% CI 1.18 to 2.73, P = 0.007). CONCLUSIONS: Among CAD patients receiving high-intensity statin therapy, the incidence of NODM was not significantly different between rosuvastatin and atorvastatin. However, a drug effect of the statin type on NODM was observed when the achieved LDL-C level was < 70 mg/dL. TRIAL REGISTRATION: ClinicalTrials.gov, Identifier: NCT02579499.

Efficacy of ferric carboxymaltose or darbepoetin alfa for chemotherapy-induced anemia in patients with esophagogastric or pancreaticobiliary cancer: a retrospective comparative study.

Background: Esophagogastric and pancreaticobiliary cancers are associated with chronic blood loss, poor nutrition, and surgical interventions that interfere with iron absorption. Patients with these cancers often have a higher incidence of chemotherapy-induced anemia (CIA) than patients with other malignancies. Objectives: To investigate the efficacy of intravenous iron or erythropoietin-stimulating agents (ESA) for CIA treatment in patients with esophagogastric or pancreaticobiliary cancer. Design: Retrospective, comparative chart review of patients with esophagogastric or pancreaticobiliary cancer who received ferric carboxymaltose (FCM), or darbepoetin alfa (DA), and myelosuppressive chemotherapy at Chungbuk National University Hospital between June 2018 and December 2022. Methods: To assess the efficacy of FCM or DA over time, data on hemoglobin (Hb) levels were collected from the time of administration of FCM or DA (baseline) until 6 months post-baseline, when available. Results: In total, 214 patients (124 in the FCM and 90 in the DA group) were included in the analysis. The FCM group had a higher maximum Hb level and Hb changes for 3 months (mean ± standard deviation) following FCM or DA administration from baseline than the DA group (11.3 ± 1.5 versus 10.9 ± 1.2 g/dL, p = 0.02 and 2.0 ± 1.4 versus 1.5 ± 1.1 g/dL, p = 0.004, respectively). The FCM group had a higher proportion of Hb responders than the DA group (83.9% versus 68.9%, p = 0.013). Based on multivariable analysis, only the CIA treatment group was a significant factor for Hb response (odds ratio = 2.06, 95% confidence interval = 1.05-4.06, p = 0.036). Conclusion: Both FCM and DA are effective, and FCM showed a higher Hb response than DA for CIA treatment in patients with esophagogastric or pancreaticobiliary cancer. Therefore, further randomized controlled trials should determine the optimal treatment for CIA in patients with these cancers undergoing myelosuppressive chemotherapy.