Polyhexamethylene guanidine phosphate induces pyroptosis via reactive oxygen species-regulated mitochondrial dysfunction in bronchial epithelial cells.

Pyroptosis is a form of programmed cell death characterized by gasdermin (GSDM)-mediated pore formation in the cell membrane, resulting in the release of pro-inflammatory cytokines and cellular lysis. Increasing evidence has shown that pyroptosis is responsible for the progression of various pulmonary disorders. The inhalation of polyhexamethylene guanidine (PHMG) causes severe lung inflammation and pulmonary toxicity; however, the underlying mechanisms are unknown. Therefore, in this study, we investigate the role of pyroptosis in PHMG-induced pulmonary toxicity. We exposed bronchial epithelial cells, BEAS-2B, to PHMG phosphate (PHMG-p) and evaluated cell death type, reactive oxygen species (ROS) levels, and relative expression levels of pyroptosis-related proteins. Our data revealed that PHMG-p reduced viability and induced morphological alterations in BEAS-2B cells. Exposure to PHMG-p induced excessive accumulation of mitochondrial ROS (mtROS) in BEAS-2B cells. PHMG-p activated caspase-dependent apoptosis as well as NLRP3/caspase-1/GSDMD-mediated- and caspase-3/GSDME-mediated pyroptosis through mitochondrial oxidative stress in BEAS-2B cells. Notably, PHMG-p reduced mitochondrial respiratory function and induced the translocation of Bax and cleaved GSDM into the mitochondria, leading to mitochondrial dysfunction. Our results enhanced our understanding of PHMG-p-induced lung toxicity by demonstrating that PHMG-p induces pyroptosis via mtROS-induced mitochondrial dysfunction in bronchial epithelial cells.

Sensory Stimulation-dependent Npas4 Expression in the Olfactory Bulb during Early Postnatal Development.

The development of the olfactory system is influenced by sensory inputs, and it maintains neuronal generation and plasticity throughout the lifespan. The olfactory bulb contains a higher proportion of interneurons than other brain regions, particularly during the early postnatal period of neurogenesis. Although the relationship between sensory stimulation and olfactory bulb development during the postnatal period has been well studied, the molecular mechanisms have yet to be identified. In this study, we used western blotting and immunohistochemistry to analyze the expression of the transcription factor Npas4, a neuron-specific immediate-early gene that acts as a developmental regulator in many brain regions. We found that Npas4 is highly expressed in olfactory bulb interneurons during the early postnatal stages and gradually decreases toward the late postnatal stages. Npas4 expression was observed in all olfactory bulb layers, including the rostral migratory stream, where newborn neurons are generated and migrate to the olfactory bulb. Under sensory deprivation, the olfactory bulb size and the number of olfactory bulb interneurons were reduced. Furthermore, Npas4 expression and the expression of putative Npas4 downstream molecules were decreased. Collectively, these findings indicate that Npas4 expression induced by sensory input plays a role in the formation of neural circuits with excitatory mitral/tufted cells by regulating the survival of olfactory bulb interneurons during the early stages of postnatal development.

Green tea extract suppresses airway inflammation via oxidative stress-driven MAPKs/MMP-9 signaling in asthmatic mice and human airway epithelial cells.

Introduction: The anti-inflammatory effect of green tea extract (GTE) has been confirmed in asthmatic mice, however, the pharmacological mechanism is not fully elucidated. Methods: To investigate the therapeutic efficacy of GTE in asthma and identify specific pathways, murine model of allergic asthma was established by ovalbumin (OVA) sensitization and the challenge for 4 weeks, with oral treatment using GTE and dexamethasone (DEX). Inflammatory cell counts, cytokines, OVA-specific IgE, airway hyperreactivity, and antioxidant markers in the lung were evaluated. Also, pulmonary histopathological analysis and western blotting were performed. In vitro, we established the model by stimulating the human airway epithelial cell line NCI-H292 using lipopolysaccharide, and treating with GTE and mitogen-activated protein kinases (MAPKs) inhibitors. Results: The GTE100 and GTE400 groups showed a decrease in airway hyperresponsiveness and the number of inflammatory cells in the bronchoalveolar lavage fluid (BALF) compared to the OVA group. GTE treatment also reduced interleukin (IL)-13, IL-5, and IL-4 levels in the BALF, and OVA-specific immunoglobulin E levels in the serum compared to those in the OVA group. GTE treatment decreased OVA-induced mucus secretion and airway inflammation. In addition, GTE suppressed the oxidative stress, and phosphorylation of MAPKs, which generally occurs after exposure to OVA. GTE administration also reduced matrix metalloproteinase-9 activity and protein levels. Conclusion: GTE effectively inhibited asthmatic respiratory inflammation and mucus hyperproduction induced by OVA inhalation. These results suggest that GTE has the potential to be used for the treatment of asthma.

IUPAC International Chemical Identifier (InChI)-related education and training materials through InChI Open Education Resource (OER).

The IUPAC International Chemical Identifier (InChI) is a structure-based chemical identifier that encodes various aspects of a chemical structure into a hierarchically layered line notation. Because InChI is non-proprietary, open-source, and freely available to everyone, it is adopted in popular chemical information resources and software programs. This paper describes the InChI Open Education Resource (OER) (https://www.inchi-trust.org/oer/), designed to provide educators and other interested parties with resources, training material, and information related to InChI. Currently, the OER contains over 100 materials collected from various sources and provides users with search, filtering, and sorting functionalities to locate specific records. New relevant materials can be suggested by anyone, allowing the scientific community to share and find InChI-related resources. This paper will show how to use the InChI OER tag taxonomy to filter content and demonstrate two resources within the InChI OER; the ChemNames2LCSS Google Sheet and the InChILayersExplorer, an Excel spreadsheet that breaks an InChI into its layers. While the InChI OER is of value to a broader chemistry community, this paper seeks to reach out to chemical educators and provide them with an understanding of InChI and its role in the practice of science.

Current Understanding on Psilocybin for Major Depressive Disorder: A Review Focusing on Clinical Trials.

Previous studies suggested effectiveness of psilocybin in the field of mental health. FDA designated psilocybin as a "breakthrough therapy" for the treatment of treatment-resistant depression (TRD) in 2018. This paper provided a review of psilocybin's potential role in treatment of depression by focusing on published clinical trials. Studies showed that psilocybin, an agonist on 5-HT2A receptors, manifests antidepressant and anxiolytic effects by increasing glutamate transmission, reducing brain inflammation, decreasing default mode network activity. In terms of clinical trials, eleven studies (six open-label and five double blinded randomized clinical trials [DB-RCTs]) trials exploring psilocybin's impact on depression were found. Among open-label studies, a pilot study on TRD patients demonstrated significant reductions in depressive symptoms after two psilocybin sessions. Psilocybin also improved cognitive bias associated with depression. Extension studies confirmed sustained improvements and high remission rates. Among five DB-RCTs, two showed that psilocybin led to significant reductions in anxiety and depression in cancer patients, and the improvements sustained for over six months. In MDD, psilocybin showed rapid reductions in depression, with higher remission rates compared to escitalopram in a DB-RCT. Another DB-RCT showed that psilocybin induced higher decrease in depression around 6 hours after their administrations than placebo. The last DB-RCT showed that in patients with TRD, a single dose of psilocybin 25 mg, but not psilocybin 10 mg, resulted in superior antidepressant effect than psilocybin 1 mg. Overall, psilocybin showed promise in treating depression and anxiety, with notable safety profiles. Further research should explore optimal dosages and long-term effects.

Safety and feasibility of optimized transcranial direct current stimulation in patients with mild cognitive impairment due to Alzheimer's disease: a multicenter study protocol for a randomized controlled trial.

Introduction: Transcranial direct current stimulation (tDCS) may effectively preserve and improve cognitive function in patients with mild cognitive impairment (MCI). Research has shown that Individual brain characteristics can influence the effects of tDCS. Computer three-dimensional brain modeling based on magnetic resonance imaging (MRI) has been suggested as an alternative for determining the most accurate tDCS electrode position based on the patients' individual brain characteristics to enhance tDCS effects. Therefore, this study aims to determine the feasibility and safety of applying tDCS treatment using optimized and personalized tDCS electrode positions in patients with Alzheimer's disease (AD)-induced MCI using computer modeling and compare the results with those of a sham group to improve cognitive function. Method: A prospective active-sham group feasibility study was set to recruit 40 participants, who will be randomized into Optimized-tDCS and Sham-tDCS groups. The parameters for tDCS will be 2 mA (disk electrodes R = 1.5 cm) for 30 min during two sets of 15 sessions (2 weeks of resting period in between), using two electrodes in pairs. Using computer modeling, the tDCS electrode positions of each participant will be personalized. Outcome measurements are going to be obtained at three points: baseline, first post-test, and second post-test. The AD assessment scale-cognitive subscale (ADAS-Cog) and the Korean version of Mini-Mental State Examination (K-MMSE), together with other secondary outcomes and safety tests will be used. Discussion: For the present study, we hypothesize that compared to a sham group, the optimized personalized tDCS application would be effective in improving the cognitive function of patients with AD-induced MCI and the participants would tolerate the tDCS intervention without any significant adverse effects.Clinical trial registration: https://cris.nih.go.kr, identifier [KCT0008918].

Factors Causing Unintended Sagittal and Axial Alignment Changes in High Tibial Osteotomy: Comparative 3-Dimensional Analysis of Simulation and Actual Surgery.

BACKGROUND: Unintended secondary changes in the posterior tibial slope (PTS) and tibial torsion angle (TTA) may occur after medial open-wedge high tibial osteotomy (MOWHTO). In surgical procedures using patient-specific instruments (PSIs), it is essential to reproduce the PTS and TTA that were planned in simulations. PURPOSE: To analyze the factors causing unintended sagittal and axial alignment changes after MOWHTO. STUDY DESIGN: Case series; Level of evidence, 4. METHODS: Overall, 63 patients (70 knees) who underwent MOWHTO using a PSI between June 2020 and June 2023 were retrospectively reviewed. Preoperative and postoperative computed tomography scans were 3-dimensionally reconstructed. Simulated osteotomy was performed so that the weightbearing line could pass through the target point. A PSI gapper was 3-dimensionally printed to fit the posteromedial corner of the osteotomy gap in the simulated HTO model. After MOWHTO using the PSI gapper, the actual postoperative model was compared with the preoperative or simulation model. This assessment included PTS, TTA, hinge axis, and osteotomy-related parameters. Cortical breakage around the lateral hinge was evaluated to assess stability. RESULTS: The mean PTS and TTA did not change in the simulation. However, significant changes were observed in the actual postoperative PTS and TTA (change, -2.4°± 2.2° and -3.9°± 4.7°, respectively). The PTS was reduced, while the TTA decreased with internal rotation of the distal fragment. The difference in the axial hinge axis angle (AHA) between the simulation and actual surgery was the factor most correlated with the difference in the PTS (r = 0.625; P < .001). In regression analysis, the difference in the AHA was the only factor associated with the difference in the PTS (ß = 0.558; P = .001), and there were no factors that showed any significant associations with the difference in the TTA. In subgroup analyses for the change in the TTA, the correction angle and anterior osteotomy angle were significantly higher in the more internal rotation group (P = .023 and P = .010, respectively). The TTA change was significantly higher in the unstable group with lateral cortical breakage (P = .018). The unstable group was more likely to show an internal rotation of ≥5° (odds ratio, 5.0; P = .007). CONCLUSION: The AHA was associated with a difference in the PTS between the simulation and actual surgery. The change in the TTA was caused by a combination of multiple factors, such as a large correction angle and anterior osteotomy angle, but mainly by instability of the lateral cortical hinge.

Impact of Apolipoprotein E4 on the Locus Coeruleus Functional Connectivity in Preclinical Alzheimer's Disease.

Background: Recent interest has surged in the locus coeruleus (LC) for its early involvement in Alzheimer's disease (AD), notably concerning the apolipoprotein ɛ4 allele (APOE4). Objective: This study aimed to discern LC functional connectivity (FC) variations in preclinical AD subjects, dissecting the roles of APOE4 carrier status and amyloid-ß (Aß) deposition. Methods: A cohort of 112 cognitively intact individuals, all Aß-positive, split into 70 APOE4 noncarriers and 42 carriers, underwent functional MRI scans, neuropsychological assessments, and APOE genotyping. The research utilized seed to voxel analysis for illustrating LC rsFC discrepancies between APOE4 statuses and employed a general linear model to examine the interactive influence of APOE4 carrier status and Aß deposition on LC FC values. Results: The investigation revealed no significant differences in sex, age, or SUVR between APOE4 carriers and noncarriers. It found diminished LC FC with the occipital cortex in APOE4 carriers and identified a significant interaction between APOE4 carrier status and temporal lobe SUVR in LC FC with the occipital cortex. This interaction suggested a proportional increase in LC FC for APOE4 carriers. Additional notable interactions were observed affecting LC FC with various brain regions, indicating a proportional decrease in LC FC for APOE4 carriers. Conclusions: These findings confirm that APOE4 carrier status significantly influences LC FC in preclinical AD, showcasing an intricate relationship with regional Aß deposition. This underscores the critical role of genetic and pathological factors in early AD pathophysiology, offering insights into potential biomarkers for early detection and intervention strategies.

Sympathetic dysfunction as an early indicator of autonomic involvement in Parkinson's disease.

PURPOSE: The specific characteristics of autonomic involvement in patients with early Parkinson's disease (PD) are unclear. This study aimed to evaluate the characteristics of autonomic dysfunction in drug-naïve patients with early-stage PD without orthostatic hypotension (OH) by analyzing Valsalva maneuver (VM) parameters. METHODS: We retrospectively analyzed drug-naïve patients without orthostatic hypotension (n = 61) and controls (n = 20). The patients were subcategorized into early PD (n = 35) and mid-PD (n = 26) groups on the basis of the Hoehn and Yahr staging. VM parameters, including changes in systolic blood pressure at late phase 2 (∆SBPVM2), ∆HRVM3, Valsalva ratio (VR), pressure recovery time, adrenergic baroreflex sensitivity, and vagal baroreflex sensitivity, were assessed. RESULTS: In the early PD group, ∆SBPVM2, a marker of sympathetic function, was significantly lower compared with that in controls (risk ratio = 0.95, P = 0.027). Receiver operating characteristic (ROC) curve analysis showed an optimal cut-off value of -10 mmHg for ∆SBPVM2 [P = 0.002, area under the curve (AUC): 0.737]. VR exhibited an inverse relationship with Unified Parkinson's Disease Rating Scale Part 3 scores in the multivariable regression analysis (VR: P = 0.038, ß = -28.61), whereas age showed a positive relationship (age: P = 0.027, ß = 0.35). CONCLUSION: The ∆BPVM2 parameter of the VM may help detect autonomic nervous system involvement in early-PD without OH. Our results suggest that sympathetic dysfunction is an early manifestation of autonomic dysfunction in patients with PD.

Prevalence and Associations Between Metabolic Syndrome Components and Hyperuricemia by Race: Findings From US Population, 2011-2020.

OBJECTIVE: We explored the trend in prevalence of hyperuricemia and metabolic syndrome in US populations and investigated associations between components of metabolic syndrome and hyperuricemia by race. METHODS: We analyzed data from the four most recent National Health and Nutrition Examination Survey (NHANES) cycles (2011 to March 2020), comprising 10,175 participants. Hyperuricemia is defined as serum urate >7.0 mg/dL (men) or >5.7 mg/dL (women), following the NHANES-III guideline. The definition of metabolic syndrome follows the National Cholesterol Education Program's Adult Treatment Panel III guideline. We estimated the prevalence of metabolic syndrome and hyperuricemia in each cycle and performed subgroup analyses with logistic regression to investigate the patterns of associated components of metabolic syndrome with hyperuricemia. RESULTS: In the most recent cycle (2017 to March 2020), the prevalence of metabolic syndrome was 45.9% and that of hyperuricemia was 20.7%. Over the 2011 to 2020 period, a significant rise in metabolic syndrome prevalence was observed among Hispanic and Asian populations, and the prevalence of hyperuricemia has increased significantly only in the Hispanic population. After adjustment for confounding factors, patients with metabolic syndrome exhibited a higher hyperuricemia in women than in men. Elevated blood pressure was the strongest factor with hyperuricemia. The association was the weakest in the Asian population. Waist circumference was the only significant factor associated with hyperuricemia in the Asian population. CONCLUSION: The prevalence of metabolic syndrome has an increasing pattern, but there was no specific decadal trend in prevalence of hyperuricemia. There is an ethnicity-specific association of metabolic syndrome and hyperuricemia, especially among Asians.

Upper common pathway analysis using late atrial premature depolarization in atrioventricular nodal reentry tachycardia.

BACKGROUND: Anatomic and electrophysiologic findings suggest that the actual circuit of atrioventricular nodal reentrant tachycardia (AVNRT) involves the perinodal atrium. However, occasional instances in which the atrium is dissociated from the AVNRT have led to the concept of an upper common pathway (UCP). OBJECTIVE: We aimed to assess the prevalence of UCP in AVNRT using a late atrial premature depolarization (LAPD) maneuver. METHODS: Patients who were diagnosed with typical AVNRT by electrophysiologic studies were enrolled. For evaluation of the presence of UCP, an LAPD was given at the coronary sinus ostium (osCS) during AVNRT, and then pacing was repeated incrementally every 10 ms. Electrograms in the earliest retrograde atrial activation site (ERAS) near the proximal His were mapped and recorded during the pacing. Results were interpreted as follows: absence of UCP-an LAPD from the osCS can reset the tachycardia without depolarizing the ERAS; presence of UCP-an LAPD from the osCS can depolarize the ERAS without resetting the tachycardia; and indeterminate-an LAPD from the osCS either resets the ERAS and tachycardia simultaneously or does not reset both. RESULTS: The LAPD maneuver was performed in 126 patients with AVNRT. It demonstrated an absence of UCP in 121 (96.0%) patients and the presence of UCP in 3 (2.4%) patients; the result was indeterminate in 2 (1.6%) patients. CONCLUSION: The LAPD maneuver revealed that the presence of UCP is indicated in only rare cases of AVNRT. In most AVNRT cases, the atrium is involved in the reentry circuit.

The effects of Pycnogenol, a pine bark extract on pulmonary inflammation by Asian sand dust in mice.

Asian sand dust (ASD), also called China dust or yellow dust, mainly occurs in East Asia during spring and autumn. Because ASD enters the body mainly through the respiratory system, it can cause respiratory disorders or worsen underlying diseases. Because of this, it has become an important health concern that threatens the well-being of humans and animals. In this study, we investigated the effects of 15 and 30 mg/kg of Pycnogenol (PYC15 and 30 groups), a pine bark extract, on ASD-induced pulmonary inflammation in mice. We evaluated the inflammatory cell counts, inflammatory cytokines, and matrix-metalloproteinase (MMP)-9 expression in animal models. PYC administration significantly decreased inflammatory cell infiltration into lung tissue; this was accompanied by a reduction in the levels of proinflammatory mediators including interleukin (IL)-1ß (P < 0.01), IL-6 (P < 0.01) and tumour necrosis factor-α (P < 0.01) in bronchoalveolar lavage fluids of ASD-exposed mice (ASD group). Histological analysis revealed that PYC suppressed ASD-induced pulmonary inflammation. Moreover, PYC suppressed the levels of matrix-metalloproteinase (MMP)-9 in the lung tissue of ASD-exposed mice, indicating that PYC reduced ASD-induced pulmonary inflammation by suppressing MMP-9. Together, these results indicate that PYC as the potential to treat ASD-driven pulmonary inflammation.

The posterior tibial slope affects the measurement reliability regarding the radiographic parameter of the knee.

BACKGROUND: Posterior tibial slope (PTS) exhibits considerable variability among individuals and is anticipated to influence the accuracy of radiographic measurements related to the knee. Despite this potential impact, there is a lack of prior research investigating how PTS affects the accuracy of these measurements. Therefore, this study aimed to investigate the effect of PTS on the measurement reliability regarding the radiographic parameter of the knee. METHODS: The medical records of patients who took full-length anteroposterior radiographs of the lower limb between January 2020 and June 2022 were evaluated retrospectively. Radiographic parameters related to the knee joint characteristics such as osteoarthritis grade, hip-knee-ankle angle, weight-bearing line ratio, medial proximal tibial angle (MPTA), lateral distal femoral angle, joint-line convergence angle (JLCA), and PTS were measured. Subjects were classified into 3 groups according to PTS (group A, PTS < 4°; group B, PTS ≥ 4° and < 8°; group C, PTS ≥ 8°), and the measurement reliability for the radiographic variables was compared between groups. The intra- and inter-observer agreements were assessed using the kappa coefficients, intra-class correlation coefficients (ICC), and Bland-Altman plots. RESULTS: A total of 175 limbs (86 patients) were included in this study. As the intra- and inter-observer reliability for PTS ranged over 0.9, grouping was performed based on the average of the measured PTSs. The inter-observer reliability of the MPTA and JLCA decreased as the PTS increased (ICCs for MPTA in Groups A, B, and C: 0.889, 0.796, and 0.790, respectively; ICCs for JLCA in Groups A, B and C: 0.916, 0.859, and 0.843, respectively), whereas there were no remarkable differences in other variables. Similar trends were observed in the comparisons of intra-observer reliability and Bland-Altman plots also showed consistent results. CONCLUSION: The larger the PTS, the lower the measurement reliability regarding the radiographic parameters of the knee that includes the joint line, such as MPTA and JLCA. Given the occasional challenge in accurately identifying the knee joint line in patients with a relatively large PTS, careful measurement of radiographic parameters is crucial and utilizing repetitive measurements for verification may contribute to minimizing measurement errors.

Adaptive Gap-Tunable Surface-Enhanced Raman Spectroscopy.

Gap plasmon (GP) resonance in static surface-enhanced Raman spectroscopy (SERS) structures is generally too narrow and not tunable. Here, we present an adaptive gap-tunable SERS device to selectively enhance and modulate different vibrational modes via active flexible Au nanogaps, with adaptive optical control. The tunability of GP resonance is up to ∼1200 cm-1 by engineering gap width, facilitated by mechanical bending of a polyethylene terephthalate substrate. We confirm that the tuned GP resonance selectively enhances different Raman spectral regions of the molecules. Additionally, we dynamically control the SERS intensity through the wavefront shaping of excitation beams. Furthermore, we demonstrate simulation results, exhibiting the mechanical and optical properties of a one-dimensional flexible nanogap and their advantage in high-speed biomedical sensing. Our work provides a unique approach for observing and controlling the enhanced chemical responses with dynamic tunability.

Implantation of hUCB-MSCs generates greater hyaline-type cartilage than microdrilling combined with high tibial osteotomy.

PURPOSE: To compare the outcomes of treating large cartilage defects in knee osteoarthritis using human allogeneic umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) implantation or arthroscopic microdrilling as a supplementary cartilage regenerative procedure combined with high tibial osteotomy (HTO). METHODS: This 1-year prospective comparative study included 25 patients with large, near full-thickness cartilage defects (International Cartilage Repair Society grade ≥ IIIB) in the medial femoral condyles and varus malalignment. Defects were treated with hUCB-MSC implantation or arthroscopic microdrilling combined with HTO. The primary outcomes were pain visual analogue scale and International Knee Documentation Committee subjective scores at 12, 24 and 48 weeks. Secondary outcomes included arthroscopic, histological and magnetic resonance imaging assessments at 1 year. RESULTS: Fifteen and 10 patients were treated via hUCB-MSC implantation and microdrilling, respectively. Baseline demographics, limb alignment and clinical outcomes did not significantly differ between the groups. Cartilage defects and total restored areas were significantly larger in the hUCB-MSC group (7.2 ± 1.9 vs. 5.2 ± 2.1 cm2, p = 0.023; 4.5 ± 1.4 vs. 3.0 ± 1.6 cm2, p = 0.035). The proportion of moderate-to-strong positive type II collagen staining was significantly higher in the hUCB-MSC group compared to that in the microdrilled group (93.3% vs. 60%, respectively). Rigidity upon probing resembled that of normal cartilage tissue more in the hUCB-MSC group (86.7% vs. 50.0%, p = 0.075). Histological findings revealed a higher proportion of hyaline cartilage in the group with implanted hUCB-MSC (p = 0.041). CONCLUSION: hUCB-MSC implantation showed comparable clinical outcomes to those of microdrilling as supplementary cartilage procedures combined with HTO in the short term, despite the significantly larger cartilage defect in the hUCB-MSC group. The repaired cartilage after hUCB-MSC implantation showed greater hyaline-type cartilage with rigidity than that after microdrilling. LEVEL OF EVIDENCE: Level II, Prospective Comparative Cohort Study.

Comparison of High- and Low-Dose Rivaroxaban Regimens in Elderly East Asian Patients With Atrial Fibrillation.

BACKGROUND: In the Rivaroxaban Once-daily oral direct factor Xa inhibition Compared with vitamin K antagonism for prevention of stroke and Embolism Trial in Atrial Fibrillation (ROCKET AF) trial, rivaroxaban 20 mg was the on-label dose, and the dose-reduction criterion for rivaroxaban was a creatinine clearance of < 50 mL/min. Some Asian countries are using reduced doses label according to the J-ROCKET AF trial. The aim of this study was to assess the safety and efficacy of a high-dose rivaroxaban regimen (HDRR, 20/15 mg) and low-dose rivaroxaban regimen (LDRR, 15/10 mg) among elderly East Asian patients with atrial fibrillation (AF) in real-world practice. METHODS: This study was a multicenter, prospective, non-interventional observational study designed to evaluate the efficacy and safety of rivaroxaban in AF patients > 65 years of age with or without renal impairment. RESULTS: A total of 1,093 patients (mean age, 72.8 ± 5.8 years; 686 [62.9%] men) were included in the analysis, with 493 patients allocated to the HDRR group and 598 patients allocated to the LDRR group. A total of 765 patients received 15 mg of rivaroxaban (203 in the HDRR group and 562 in the LDRR group). There were no significant differences in the incidence rates of major bleeding (adjusted hazard ratio [HR], 0.64; 95% confidential interval [CI], 0.21-1.93), stroke (adjusted HR, 3.21; 95% CI, 0.54-19.03), and composite outcomes (adjusted HR, 1.13; 95% CI, 0.47-2.69) between the HDRR and LDRR groups. CONCLUSION: This study revealed the safety and effectiveness of either dose regimen of rivaroxaban in an Asian population for stroke prevention of AF. Considerable numbers of patients are receiving LDRR therapy in real-world practice in Asia. Both regimens were safe and effective for these patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04096547.

Effects of concurrent cartilage procedures on cartilage regeneration in high tibial osteotomy: a systematic review.

PURPOSE: This systematic review aimed to evaluate the effects of concurrent cartilage procedures on cartilage regeneration when performed alongside high tibial osteotomy (HTO). MATERIALS AND METHODS: The systematic review followed the guidelines outlined in the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA). A comprehensive search was conducted on databases including PubMed, Embase, Cochrane Library, and Google Scholar, covering articles published until August 31, 2023. RESULTS: Sixteen studies (1277 patients) revealed that HTO, with or without concurrent cartilage procedures, leads to cartilage regeneration based on the International Cartilage Repair Society (ICRS) grade during second-look arthroscopy. No concurrent procedure showed improvement in ICRS grade (mean difference: - 0.80 to - 0.49). Microfracture (mean difference: - 0.75 to - 0.22), bone marrow aspirate concentrate (BMAC) (mean difference: - 1.37 to - 0.67), and human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) (mean difference: - 2.46 to - 1.81) procedures also demonstrated positive outcomes. Clinical outcome assessments for each cartilage procedure were also improved during postoperative follow-up, and no specific complications were reported. CONCLUSIONS: HTO with or without concurrent cartilage procedures promotes cartilage regeneration observed during second-look arthroscopy, with improved clinical outcomes. Future randomized controlled trials on the same topic, along with subsequent meta-analyses, are necessary for conclusive findings.

Automated analysis of knee joint alignment using detailed angular values in long leg radiographs based on deep learning.

Malalignment in the lower limb structure occurs due to various causes. Accurately evaluating limb alignment in situations where malalignment needs correction is necessary. To create an automated support system to evaluate lower limb alignment by quantifying mechanical tibiofemoral angle (mTFA), mechanical lateral distal femoral angle (mLDFA), medial proximal tibial angle (MPTA), and joint line convergence angle (JLCA) on full-length weight-bearing radiographs of both lower extremities. In this retrospective study, we analysed 404 radiographs from one hospital for algorithm development and testing and 30 radiographs from another hospital for external validation. The performance of segmentation algorithm was compared to that of manual segmentation using the dice similarity coefficient (DSC). The agreement of alignment parameters was assessed using the intraclass correlation coefficient (ICC) for internal and external validation. The time taken to load the data and measure the four alignment parameters was recorded. The segmentation algorithm demonstrated excellent agreement with human-annotated segmentation for all anatomical regions (average similarity: 89-97%). Internal validation yielded good to very good agreement for all the alignment parameters (ICC ranges: 0.7213-0.9865). Interobserver correlations between manual and automatic measurements in external validation were good to very good (ICC scores: 0.7126-0.9695). The computer-aided measurement was 3.44 times faster than was the manual measurement. Our deep learning-based automated measurement algorithm accurately quantified lower limb alignment from radiographs and was faster than manual measurement.