Clinical outcomes of holmium laser enucleation of the prostate: A large prospective registry-based patient cohort study under regular follow-up protocol.

PURPOSE: To evaluate the efficacy and safety of holmium laser enucleation of the prostate (HoLEP) in a large prospective cohort of patients with benign prostatic hyperplasia (BPH) through systematic follow-up at a single institution. MATERIALS AND METHODS: Clinical outcomes were analyzed between August 2008 and June 2022. Patients were followed-up at 2 weeks, 3 months and 6 months postoperatively. RESULTS: A total of 3,000 patients (mean age, 69.6±7.7 years) underwent HoLEP. Baseline total International Prostate Symptom Score (IPSS) was 19.3±7.7 and maximum flow rate (Qmax) was 9.4±4.8 mL/s. Mean total prostate volume was 67.7±3.4 mL. Total operation time was 60.7±31.5 minutes, and catheterization time was 1.0 days (range, 1.0-1.0 days). At 6 months postoperatively, the total IPSS decreased to 6.6±5.8 and Qmax increased to 22.2±11.3 mL/s. Complications at 6 months postoperatively included stress urinary incontinence (SUI) in 36 patients (1.9%), urgency urinary incontinence (UUI) in 25 (1.3%), bladder neck contracture (BNC) requiring transurethral incision (TUI) in 16 (0.5%), and urethral stricture in 29 (1.0%). Eleven patients (0.4%) with prostatic fossa stones required stone removal. Sixty-one patients (2.0%) required secondary surgery (transurethral coagulation, 16 [0.5%]; TUI for BNC, 16 [0.5%]; stone removal for prostatic fossa stones, 11 [0.4%]; and endoscopic internal urethrotomy for urethral stricture, 18 [0.6%]). CONCLUSIONS: Mid-term follow-up results after HoLEP in BPH patients showed excellent efficacy and low complication rates. Unlike previous reports, the incidence of SUI and UUI after HoLEP was low, but the occurrence of de novo stone formation in prostatic fossa was notable.

The effect of ADAMTS13 on graft-versus-host disease.

Allogeneic haematopoietic stem cell transplantation (allo-HSCT) can potentially cure malignant blood disorders and benign conditions such as haemoglobinopathies and immunologic diseases. However, allo-HSCT is associated with significant complications. The most common and debilitating among them is graft-versus-host disease (GVHD). In GVHD, donor-derived T cells mount an alloimmune response against the recipient. The alloimmune response involves several steps, including recognition of recipient antigens, activation and proliferation of T cells in secondary lymphoid organs, and homing into GVHD-targeted organs. Adhesion molecules on T cells and endothelial cells mediate homing of T cells into lymphoid and non-lymphoid tissues. In this study, we showed that Von Willebrand factor (VWF), an adhesion molecule secreted by activated endothelial cells, plays an important role in mouse models of GVHD. We investigated the effect of the VWF-cleaving protease ADAMTS13 on GVHD. We found that ADAMTS13 reduced the severity of GVHD after bone marrow transplantation from C57BL6 donor to BALB/C recipient mice. A recombinant VWF-A2 domain peptide also reduced GVHD in mice. We showed that ADAMTS13 and recombinant VWF-A2 reduced the binding of T cells to endothelial cells and VWF in vitro, and reduced the number of T cells in lymph nodes, Peyer's patches and GVHD-targeted organs in vivo. We identified LFA-1 (αLß2) as the binding site of VWF on T cells. Our results showed that blocking T-cell homing by ADAMTS13 or VWF-A2 peptide reduced the severity of the GVHD after allo-HSCT, a potentially novel method for treating and preventing GVHD.

Amyloid-related imaging abnormalities (ARIA) and their radiological, biological and clinical characteristics: a plain language summary.

What is this summary about? This is a plain language summary of an article published in the journal Brain. People with Alzheimer's disease may receive treatments that target amyloid-ß ­ a protein in the brain that is one of the key characteristics of Alzheimer's disease when it is present in higher levels than normal. This article is about amyloid-related imaging abnormalities (ARIA), which can be adverse events for people with Alzheimer's disease receiving antibody treatments targeting amyloid-ß (known as anti­amyloid-ß antibody treatments). This article also discusses ways to identify and manage ARIA.ARIA are adverse events that happen due to amyloid-ß buildup in the brain or following treatments targeting amyloid-ß. ARIA are identified on MRI scans as swelling or bleeding in the brain, and people with ARIA do not typically have symptoms. In rare cases, ARIA can cause serious symptoms or lead to disability.What are the key takeaways? There are two types of ARIA: ARIA-E (swelling in the brain) and ARIA-H (bleeding in the brain).Presence of an APOE ε4 gene variant and exposure to anti­amyloid-ß antibody treatments are major risk factors for ARIA.With the recent availability in the clinic of antibody treatments targeting amyloid-ß, increased awareness is needed to identify, monitor and manage ARIA effectively.What were the main conclusions reported by the researchers? Uniform detection, monitoring and management of ARIA are essential in patients receiving antibody treatments targeting amyloid-ß. To increase ARIA detection in clinical trials and clinical practice, the authors recommend the implementation of uniform imaging protocols and rigorous reporting standards.

A Novel Deep Learning-based Artificial Intelligence System for Interpreting Urolithiasis in Computed Tomography.

BACKGROUND AND OBJECTIVE: Our aim was to develop an artificial intelligence (AI) system for detection of urolithiasis in computed tomography (CT) images using advanced deep learning capable of real-time calculation of stone parameters such as volume and density, which are essential for treatment decisions. The performance of the system was compared to that of urologists in emergency room (ER) scenarios. METHODS: Axial CT images for patients who underwent stone surgery between August 2022 and July 2023 comprised the data set, which was divided into 70% for training, 10% for internal validation, and 20% for testing. Two urologists and an AI specialist annotated stones using Labelimg for ground-truth data. The YOLOv4 architecture was used for training, with acceleration via an RTX 4900 graphics processing unit (GPU). External validation was performed using CT images for 100 patients with suspected urolithiasis. KEY FINDINGS AND LIMITATIONS: The AI system was trained on 39 433 CT images, of which 9.1% were positive. The system achieved accuracy of 95%, peaking with a 1:2 positive-to-negative sample ratio. In a validation set of 5736 images (482 positive), accuracy remained at 95%. Misses (2.6%) were mainly irregular stones. False positives (3.4%) were often due to artifacts or calcifications. External validation using 100 CT images from the ER revealed accuracy of 94%; cases that were missed were mostly ureterovesical junction stones, which were not included in the training set. The AI system surpassed human specialists in speed, analyzing 150 CT images in 13 s, versus 38.6 s for evaluation by urologists and 23 h for formal reading. The AI system calculated stone volume in 0.2 s, versus 77 s for calculation by urologists. CONCLUSIONS AND CLINICAL IMPLICATIONS: Our AI system, which uses advanced deep learning, assists in diagnosing urolithiasis with 94% accuracy in real clinical settings and has potential for rapid diagnosis using standard consumer-grade GPUs. PATIENT SUMMARY: We developed a new AI (artificial intelligence) system that can quickly and accurately detect kidney stones in CT (computed tomography) scans. Testing showed that this system is highly effective, with accuracy of 94% for real cases in the emergency department. It is much faster than traditional methods and provides rapid and reliable results to help doctors in making better treatment decisions for their patients.

Chip collection of hepatocellular carcinoma based on O2 heterogeneity from patient tissue.

Hepatocellular carcinoma frequently recurs after surgery, necessitating personalized clinical approaches based on tumor avatar models. However, location-dependent oxygen concentrations resulting from the dual hepatic vascular supply drive the inherent heterogeneity of the tumor microenvironment, which presents challenges in developing an avatar model. In this study, tissue samples from 12 patients with hepatocellular carcinoma are cultured directly on a chip and separated based on preference of oxygen concentration. Establishing a dual gradient system with drug perfusion perpendicular to the oxygen gradient enables the simultaneous separation of cells and evaluation of drug responsiveness. The results are further cross-validated by implanting the chips into mice at various oxygen levels using a patient-derived xenograft model. Hepatocellular carcinoma cells exposed to hypoxia exhibit invasive and recurrent characteristics that mirror clinical outcomes. This chip provides valuable insights into treatment prognosis by identifying the dominant hepatocellular carcinoma type in each patient, potentially guiding personalized therapeutic interventions.

Long-term prediction of algal chlorophyll based on empirical models and the machine learning approach in relation to trophic variation in Juam Reservoir, Korea.

This study analyzed spatiotemporal variation and long-term trends in water quality indicators and trophic state conditions in an Asian temperate reservoir, Juam Reservoir (JR), and developed models that forecast algal chlorophyll (CHL-a) over a period of 30 years, 1993-2022. The analysis revealed that there were longitudinal gradients in water quality indicators along the reservoir, with notable influences from tributaries and seasonal variations in nutrient regimes and suspended solids. The empirical model showed phosphorus was found to be the key determinant of algal biomass, while suspended solids played a significant role in regulating water transparency. The trophic state indices indicated varying levels of trophic status, ranging from mesotrophic to eutrophic. Eutrophic states were particularly observed in zones after the summer monsoons, indicating a heightened risk of algal blooms, which were more prevalent in flood years. The analysis of trophic state index deviation suggested that phosphorus availability strongly influences the reservoir trophic status, with several episodes of non-algal turbidity at each site during Mon. Increases in non-algal turbidity were more prevalent during the monsoon in flood years. This study also highlighted overall long-term trends in certain water quality parameters, albeit with indications of shifting pollution sources towards non-biodegradable organic matter. According to the machine learning tests, a random forest (RF) model strongly predicted CHL-a (R2 = 0.72, p < 0.01), except for algal biomass peaks (>60 µg/L), compared to all other models. Overall, our research suggests that CHL-a and trophic variation are primarily regulated by the monsoon intensity and predicted well by the machine learning RF model.

Long-term clinical impact of early recurrence of atrial tachyarrhythmia after cryoballoon ablation in patients with atrial fibrillation.

INTRODUCTION: The impact of early recurrence of atrial tachyarrhythmia (ERAT) within the 90-day blanking period on long-term outcomes in atrial fibrillation (AF) patients undergoing cryoballoon ablation (CBA) is controversial. This study aimed to assess the relationship between ERAT and late recurrence of atrial tachyarrhythmia (LRAT) post-CBA. METHODS: Utilizing data from a multicenter registry in Korea (May 2018 to June 2022), we analyzed the presence and timing of ERAT (<30, 30-60, and 60-90 days) and its association with LRAT risk after CBA. LRAT was defined as any recurrence of AF, atrial flutter, or atrial tachycardia lasting more than 30 s beyond the 90 days. RESULTS: Out of 2636 patients, 745 (28.2%) experienced ERAT post-CBA. Over an average follow-up period of 21.2 ± 10.3 months, LRAT was observed in 874 (33.1%) patients. Patients with ERAT had significantly lower 1-year LRAT freedom compared to those without ERAT (42.6% vs. 85.5%, p < .001). Multivariate analysis identified ERAT as a potential predictor of LRAT, with a hazard ratio (HR) of 3.98 (95% confidence interval [CI], 3.47-4.57). Significant associations were noted across all examined time frames (HR, 3.84; 95% CI, 3.32-4.45 in <30 days, HR, 5.53; 95% CI, 4.13-7.42 in 30-60 days, and HR, 4.29; 95% CI, 3.12-5.89 in 60-90 days). This finding was consistently observed across all types of AF. CONCLUSION: ERAT during the 90-day blanking period strongly predicts LRAT in AF patients undergoing CBA, indicating a need to reconsider the clinical significance of this period.

Assessment of elimination efficacy on foodborne pathogenic microbes and foulant precipitates using phytic acid and sulfamic acid.

This research investigated the comparative efficacy of sulfamic acid (SA) and phytic acid (PA), both individually and in combination, for treating potential foodborne pathogens and pre-formed foulants. Pathogens studied included Listeria monocytogenes, E. coli DH5α, Salmonella Typhimurium, Staphylococcus aureus, and vegetative Bacillus cereus, in suspended aqueous solutions, as well as Pseudomonas aeruginosa biofilm on quartz glass surfaces. Inactivation kinetics for Listeria monocytogenes revealed concentration-dependent rate constants (k) of 6.6(±0.2)×10-6 M and 2.8(±0.1)×10-8 M for single treatments of SA and PA, respectively, and ranged from 6.9(±0.3) to 50.7(±2.3)×10-6 M for combined treatments with PA pre-treatment concentrations of 75-758 µM. Observable cellular abnormalities in Listeria monocytogenes, such as membrane vesiculation, chelation, cellular disruption, biomolecule leakage, and lipid peroxidation, were identified after exposure to PA or SA, either individually or in combination. The optimized combined treatment of PA and SA achieved significant removal (i.e., >3-log; 99.9%) of potential foodborne pathogens under simulated food-washing process conditions. Additionally, over 90% descaling efficacy was observed for pre-formed foulants such as CaCO3 precipitates and Pseudomonas aeruginosa biofilm on quartz glass surfaces with the combined treatment. These findings provide novel insights into the versatile utility of PA and SA for optimizing combinational water disinfection systems and addressing (in)organic foulant scaling on surfaces in the food processing industry.

Clinical Significance of Prognostic Nutrition Index in Patients with Crohn's Disease after Primary Bowel Resection.

PURPOSE: Although advancements in medical treatments have been made, approximately half of patients with intestinal Crohn's disease (CD) require intestinal resections during their lifetime. It is well-known that the nutritional status of CD patients can impact postoperative morbidity. The objective of this study was to evaluate the clinical significance of prognostic nutritional index (PNI) in patients with intestinal CD who underwent primary bowel resection. MATERIALS AND METHODS: We retrospectively investigated patients who were diagnosed with CD and underwent intestinal surgery at Severance Hospital between January 2005 and October 2018. The patients were divided into two groups: PNI ≤40 (n=150) and PNI >40 (n=77). We assessed the clinical significance of PNI in terms of the incidence of postoperative infectious complications (PICs) and the postoperative recurrence of CD. RESULTS: The low PNI group had significantly higher rates of infectious complications (32.0% vs. 10.4%, p=0.001) compared to the high PNI group. Multivariable analysis identified low PNI (≤40) and longer operation time (>180 min) as independent risk factors associated with PICs [odds ratio (OR)=2.754, 95% confidence interval (CI)=1.140-6.649, p=0.024; OR=2.986, 95% CI=1.451-6.143, p=0.003]. PICs were significantly associated with surgical recurrence (hazard ratio=2.217, 95% CI=1.064-4.617, p=0.034). CONCLUSION: Preoperative PNI could serve as a predictive factor for PICs in CD patients who undergo intestinal resection. Additionally, PICs are significantly associated with a higher risk of surgical recurrence in CD.

Apolipoprotein E in Alzheimer's disease trajectories and the next-generation clinical care pathway.

Alzheimer's disease (AD) is a complex, progressive primary neurodegenerative disease. Since pivotal genetic studies in 1993, the ε4 allele of the apolipoprotein E gene (APOE ε4) has remained the strongest single genome-wide associated risk variant in AD. Scientific advances in APOE biology, AD pathophysiology and ApoE-targeted therapies have brought APOE to the forefront of research, with potential translation into routine AD clinical care. This contemporary Review will merge APOE research with the emerging AD clinical care pathway and discuss APOE genetic risk as a conduit to genomic-based precision medicine in AD, including ApoE's influence in the ATX(N) biomarker framework of AD. We summarize the evidence for APOE as an important modifier of AD clinical-biological trajectories. We then illustrate the utility of APOE testing and the future of ApoE-targeted therapies in the next-generation AD clinical-diagnostic pathway. With the emergence of new AD therapies, understanding how APOE modulates AD pathophysiology will become critical for personalized AD patient care.

Comparison between catheter ablation versus permanent pacemaker implantation as an initial treatment for tachycardia-bradycardia syndrome patients: a prospective, randomized trial.

BACKGROUND: Clinical outcomes after catheter ablation (CA) or pacemaker (PM) implantation for the tachycardia-bradycardia syndrome (TBS) has not been evaluated adequately. We tried to compare the efficacy and safety outcomes of CA and PM implantation as an initial treatment option for TBS in paroxysmal atrial fibrillation (AF) patients. METHODS: Sixty-eight patients with paroxysmal AF and TBS (mean 63.7 years, 63.2% male) were randomized, and received CA (n = 35) or PM (n = 33) as initial treatments. The primary outcomes were unexpected emergency room visits or hospitalizations attributed to cardiovascular causes. RESULTS: In the intention-to-treatment analysis, the rates of primary outcomes were not significantly different between the two groups at the 2-year follow-up (19.8% vs. 25.9%; hazard ratio (HR) 0.73, 95% confidence interval (CI) 0.25-2.20, P = 0.584), irrespective of whether the results were adjusted for age (HR 1.12, 95% CI 0.34-3.64, P = 0.852). The 2-year rate of recurrent AF was significantly lower in the CA group compared to the PM group (33.9% vs. 56.8%, P = 0.038). Four patients (11.4%) in the CA group finally received PMs after CA owing to recurrent syncope episodes. The rate of major or minor procedure related complications was not significantly different between the two groups. CONCLUSION: CA had a similar efficacy and safety profile with that of PM and a higher sinus rhythm maintenance rate. CA could be considered as a preferable initial treatment option over PM implantation in patients with paroxysmal AF and TBS. TRIAL REGISTRATION: KCT0000155.

Dose-toxicity surface histogram-based prediction of radiation dermatitis severity and shape.

Objective.This study aimed to develop a new approach to predict radiation dermatitis (RD) by using the skin dose distribution in the actual area of RD occurrence to determine the predictive dose by grade.Approach.Twenty-three patients with head and neck cancer treated with volumetric modulated arc therapy were prospectively and retrospectively enrolled. A framework was developed to segment the RD occurrence area in skin photography by matching the skin surface image obtained using a 3D camera with the skin dose distribution. RD predictive doses were generated using the dose-toxicity surface histogram (DTH) calculated from the skin dose distribution within the segmented RD regions classified by severity. We then evaluated whether the developed DTH-based framework could visually predict RD grades and their occurrence areas and shapes according to severity.Main results.The developed framework successfully generated the DTH for three different RD severities: faint erythema (grade 1), dry desquamation (grade 2), and moist desquamation (grade 3); 48 DTHs were obtained from 23 patients: 23, 22, and 3 DTHs for grades 1, 2, and 3, respectively. The RD predictive doses determined using DTHs were 28.9 Gy, 38.1 Gy, and 54.3 Gy for grades 1, 2, and 3, respectively. The estimated RD occurrence area visualized by the DTH-based RD predictive dose showed acceptable agreement for all grades compared with the actual RD region in the patient. The predicted RD grade was accurate, except in two patients.Significance. The developed DTH-based framework can classify and determine RD predictive doses according to severity and visually predict the occurrence area and shape of different RD severities. The proposed approach can be used to predict the severity and shape of potential RD in patients and thus aid physicians in decision making.

Staged urethroplasty with groin full-thickness skin graft for managing complex anterior urethral strictures: surgical outcomes and predictive factors.

PURPOSE: To describe outcomes of staged-urethroplasty in complex anterior urethral strictures using full-thickness-skin-graft (FTSG) harvested from the hairless groin area, and to identify factors influencing successful outcomes. METHODS: Through retrospective chart review, we identified a total of 67 men who underwent the first-stage operation (grafting) using groin-FTSG for staged-urethroplasty to treat complex anterior urethral strictures unsuitable for one-stage urethroplasty. Among these, 59 underwent the second-stage operation (tubularization) at a median duration of 5.1-months after grafting. Patients were assessed for outcomes as scheduled after tubularization outcomes were analyzed only for 48 patients for whom ≥ 1-year follow-up data after tubularization were available. Their mean follow-up duration was 27.1 months. Success was defined as achieving physiologic voiding without requiring further procedures. RESULTS: Median stricture-length was 5.5 cm in all 67 patients. After grafting, neourethral-opening-narrowing occurred in 18. Partial graft-loss occurred in 8, of whom only 3 underwent re-grafting. The percentage of patients who achieved successful outcomes was 81.3%. Improvements in maximum-urine-flow-rate and post-void-residual-urine-volume were maintained until the last follow-up visit. A urethrocutaneous-fistula occurred in one patient, while meatal-stenosis occurred in two. On multivariate-regression-analysis, the presence of neourethral-opening-narrowing was the only predictor of non-success after tubularization. Furthermore, the presence of hypertension, longer stricture-length, and a history of prior direct-vision-internal-urethrotomy were predictors of the occurrence of neourethral-opening-narrowing. CONCLUSION: Staged-urethroplasty using groin-FTSG is well worth considering as a useful therapeutic option for complex anterior urethral strictures, with an acceptable success rate and low morbidity. The absence of neourethral-opening-narrowing after the first-stage operation leads to success.

Bio-electrochemical degradation of carbamazepine (CBZ): A comprehensive study on effectiveness, degradation pathway, and toxicological assessment.

Recent attention on the detrimental effects of pharmaceutically active compounds (PhACs) in natural water has spurred researchers to develop advanced wastewater treatment methods. Carbamazepine (CBZ), a widely recognized anticonvulsant, has often been a primary focus in numerous studies due to its prevalence and resistance to breaking down. This study aims to explore the effectiveness of a bio-electrochemical system in breaking down CBZ in polluted water and to assess the potential harmful effects of the treated wastewater. The results revealed bio-electro degradation process demonstrated a collaborative effect, achieving the highest CBZ degradation compared to electrodegradation and biodegradation techniques. Notably, a maximum CBZ degradation efficiency of 92.01% was attained using the bio-electrochemical system under specific conditions: Initial CBZ concentration of 60 mg/L, pH level at 7, 0.5% (v/v) inoculum dose, and an applied potential of 10 mV. The degradation pathway established by identifying intermediate products via High-Performance Liquid Chromatography-Mass Spectrometry, revealed the complete breakdown of CBZ without any toxic intermediates or end products. This finding was further validated through in vitro and in vivo toxicity assays, confirming the absence of harmful remnants after the degradation process.

Inverse design of Bézier curve-based mechanical metamaterials with programmable negative thermal expansion and negative Poisson's ratio via a data augmented deep autoencoder.

Controlling stress and deformation induced by thermo-mechanical stimulation in high-precision mechanical systems can be achieved by mechanical metamaterials (MM) exhibiting negative thermal expansion (NTE) and negative Poisson's ratio (NPR). However, the inverse design of MM exhibiting a wide range of arbitrary target NTEs and NPRs is a challenging task due to the low design flexibility of analytical methods and parametric studies based on numerical simulation. In this study, we propose Bézier curve-based programmable chiral mechanical metamaterials (BPCMs) and a deep autoencoder-based inverse design model (DAIM) for the inverse design of BPCMs. Through iterative transfer learning with data augmentation, DAIM can generate BPCMs with a curved rib shape inaccessible with the Bézier curve, which improves the inverse design performance of the DAIM in the data sparse domain. This approach decreases the mean absolute error of NTE and NPR between the inverse design target and the numerical simulation results of inverse designed BPCMs on the data-sparse domain by 79.25% and 83.33% on average, respectively. A 3D-printed BPCM is validated experimentally and exhibits good coincidence with the target NTE and NPR. Our proposed BPCM and the corresponding inverse design framework enable the inverse design of BPCMs with NTE in the range of -1100 to 0 ppm K-1 and NPR in the range of -0.6 to -0.1. Furthermore, programmable thermal deformation modes with a fixed Poisson's ratio are realized by combining various inverse designed BPCM unit cells. BPCMs and the DAIM for their inverse design are expected to improve the mechanical robustness of high-precision mechanical systems through tunable modulation of thermo-mechanical stimulation.

Factors Considered by Experienced Urologists when Selecting Alpha-Blockers for Patients with Lower Urinary Tract Symptoms or Benign Prostatic Hyperplasia according to Age.

INTRODUCTION: The objectives of the study were to examine the opinions of urology specialists on whether there are actual differences in efficacy among α1-blockers and to identify the factors that should be considered when prescribing these medications according to age. METHODS: We surveyed 50 South Korean urology specialists with over 3 years of clinical experience in secondary or tertiary hospitals in July-August 2021. The survey covered urologists' demographics, awareness of α1-blocker prescription differences, and key factors in α1-blocker selection based on LUTS severity and patient age. RESULTS: Overall, 82% of the respondents believed that there were differences in the efficacy of α1-blockers in actual practice according to age. Over 90% of the respondents agreed on the need for head-to-head comparison studies to compare the effects of different α1-blockers. Regardless of the severity of LUTS, urologists prioritize cardiovascular side effects when prescribing α1-blockers to patients aged ≥70 years. Further, 19% of the urologists prioritized ejaculatory side effects for mild-to-moderate LUTS and 9% for severe LUTS (p < 0.001). CONCLUSIONS: This study shows that head-to-head studies comparing the efficacy of different α1-blockers are highly valuable for the real-world clinical application of α1-blockers. Notably, urologists prioritize cardiovascular and ejaculatory side effects in older and younger patients while prescribing α1-blockers, respectively.

Correlation between Thalamocortical Tract and Default Mode Network with Consciousness Levels in Hypoxic-Ischemic Brain Injury Patients: A Comparative Study Using the Coma Recovery Scale-Revised.

BACKGROUND The thalamocortical tract (TCT) links nerve fibers between the thalamus and cerebral cortex, relaying motor/sensory information. The default mode network (DMN) comprises bilateral, symmetrical, isolated cortical regions of the lateral and medial parietal and temporal brain cortex. The Coma Recovery Scale-Revised (CRS-R) is a standardized neurobehavioral assessment of disorders of consciousness (DOC). In the present study, 31 patients with hypoxic-ischemic brain injury (HI-BI) were compared for changes in the TCT and DMN with consciousness levels assessed using the CRS-R. MATERIAL AND METHODS In this retrospective study, 31 consecutive patients with HI-BI (17 DOC,14 non-DOC) and 17 age- and sex-matched normal control subjects were recruited. Magnetic resonance imaging was used to diagnose HI-BI, and the CRS-R was used to evaluate consciousness levels at the time of diffusion tensor imaging (DTI). The fractional anisotropy (FA) values and tract volumes (TV) of the TCT and DMN were compared. RESULTS In patients with DOC, the FA values and TV of both the TCT and DMN were significantly lower compared to those of patients without DOC and the control subjects (p<0.05). When comparing the non-DOC and control groups, the TV of the TCT and DMN were significantly lower in the non-DOC group (p<0.05). Moreover, the CRS-R score had strong positive correlations with the TV of the TCT (r=0.501, p<0.05), FA of the DMN (r=0.532, p<0.05), and TV of the DMN (r=0.501, p<0.05) in the DOC group. CONCLUSIONS This study suggests that both the TCT and DMN exhibit strong correlations with consciousness levels in DOC patients with HI-BI.

Development of a multiplex Loop-Mediated Isothermal Amplification (LAMP) for the diagnosis of bacterial periprosthetic joint infection.

BACKGROUND: Periprosthetic joint infection (PJI) is one of the most serious and debilitating complications that can occur after total joint arthroplasty. Therefore, early diagnosis and appropriate treatment are important for a good prognosis. Recently, molecular diagnostic methods have been widely used to detect the causative microorganisms of PJI sensitively and rapidly. The Multiplex Loop-Mediated Isothermal Amplification (LAMP) method eliminates the complex temperature cycling and delays caused by temperature transitions seen in polymerase chain reaction (PCR) methods, making it faster and easier to perform compared to PCR-based assays. Therefore, this study developed a multiplex LAMP assay for diagnosing bacterial PJI using LAMP technology and evaluated its analytical and clinical performance. METHODS: We developed a multiplex LAMP assay for the detection of five bacteria: Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus agalactiae, Pseudomonas aeruginosa, and Escherichia coli, frequently observed to be the causative agents of PJI. The method of analytical sensitivity and cross-reactivity were determined by spiking standard strains into the joint synovial fluid. The analytical sensitivity of the multiplex LAMP assay was compared with that of a quantitative real-time PCR (qPCR) assay. Clinical performance was evaluated using 20 joint synovial fluid samples collected from patients suspected of having bacterial PJI. RESULTS: The analytical sensitivity of the gram-positive bacterial multiplex LAMP assay and qPCR were 105/104 CFU/mL, 103/103 CFU/mL, and 105/104 CFU/mL against S. agalactiae, S. epidermidis, and S. aureus, respectively. For P. aeruginosa and E. coli, the analytical sensitivity of the multiplex LAMP and qPCR assays were 105/104 and 106/104 CFU/mL, respectively. The multiplex LAMP assay detects target bacteria without cross-reacting with other bacteria, and exhibited 100% sensitivity and specificity in clinical performance evaluation. CONCLUSIONS: This multiplex LAMP assay can rapidly detect five high-prevalence bacterial species causing bacterial PJI, with excellent sensitivity and specificity, in less than 1 h, and it may be useful for the early diagnosis of PJI.

Targeting pyruvate dehydrogenase kinase 1 overcomes EGFR C797S mutation-driven osimertinib resistance in non-small cell lung cancer.

Osimertinib, a selective third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), effectively targets the EGFR T790M mutant in non-small cell lung cancer (NSCLC). However, the newly identified EGFR C797S mutation confers resistance to osimertinib. In this study, we explored the role of pyruvate dehydrogenase kinase 1 (PDK1) in osimertinib resistance. Patients exhibiting osimertinib resistance initially displayed elevated PDK1 expression. Osimertinib-resistant cell lines with the EGFR C797S mutation were established using A549, NCI-H292, PC-9, and NCI-H1975 NSCLC cells for both in vitro and in vivo investigations. These EGFR C797S mutant cells exhibited heightened phosphorylation of EGFR, leading to the activation of downstream oncogenic pathways. The EGFR C797S mutation appeared to increase PDK1-driven glycolysis through the EGFR/AKT/HIF-1α axis. Combining osimertinib with the PDK1 inhibitor leelamine helped successfully overcome osimertinib resistance in allograft models. CRISPR-mediated PDK1 knockout effectively inhibited tumor formation in xenograft models. Our study established a clear link between the EGFR C797S mutation and elevated PDK1 expression, opening new avenues for the discovery of targeted therapies and improving our understanding of the roles of EGFR mutations in cancer progression.

Dexmedetomidine as an effective alternative tool for heart rate control in atrial fibrillation during general anesthesia-A case report.

Atrial fibrillation (AF) is a common arrhythmia requiring effective heart rate (HR) management. Conventional therapies may not always achieve the desired HR control during intraoperative conditions. We present two cases of AF patients in whom dexmedetomidine, an alpha-2 receptor agonist, was utilized during surgery when conventional treatments proved ineffective. In Case 1, a 65-year-old male with multiple comorbidities underwent surgery. Despite receiving intraoperative medications for AF, his HR remained uncontrolled. Dexmedetomidine successfully stabilized his HR without complications. In Case 2, a 75-year-old male with heart disease experienced a sudden HR surge during surgery, which remained uncontrolled despite conventional treatment. Dexmedetomidine effectively managed his HR, ensuring a safer surgical course. While the primary indication of dexmedetomidine is not arrhythmia management, this case report suggests its potential in challenging cases. Further research is needed to explore its therapeutic role in tachyarrhythmia management and establish appropriate dosing strategies.