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.

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.

Cutaneous Calcified Mass of Foot in Pseudohypoparathyoidism: Case Report.

Soft tissue calcifications frequently appear on imaging studies, representing a prevalent but non-specific discovery, varying from a local reaction without clear cause to suggesting an underlying systemic condition. Because calcifications like these can arise from various causes, an accurate differential diagnosis is crucial. Differential diagnosis entails a methodical assessment of the patient, encompassing clinical presentation, medical history, radiological and pathological findings, and other pertinent factors. Through scrutiny of the patient's medical and trauma history, we can refine potential causes of calcification to vascular, metabolic, autoimmune, neoplastic, or traumatic origins. Furthermore, routine laboratory assessments, including serum levels of calcium, phosphorus, ionized calcium, vitamin D metabolites, and parathyroid hormone (PTH), aid in identifying metabolic etiologies. We describe a rare occurrence of osteoma cutis in a 15-year-old female patient with a history of pseudohypoparathyroidism (PHP) and Albright's hereditary osteodystrophy (AHO). The patient presented with a painful mass on the lateral side of her left foot. The diagnosis was based on medical history, laboratory tests, and imaging, leading to an excisional biopsy and complete pain relief post-surgery. Understanding such rare occurrences and related conditions is crucial for accurate diagnosis and management.

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.

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.

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.

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.

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.

Can DNA Methylation Profiling Classify Histologic Subtypes and Grades in Soft Tissue Sarcoma?

BACKGROUND: A clear classification of the subtype and grade of soft tissue sarcoma is important for predicting prognosis and establishing treatment strategies. However, the rarity and heterogeneity of these tumors often make diagnosis difficult. In addition, it remains challenging to predict the response to chemotherapy and prognosis. Thus, we need a new method to help diagnose soft tissue sarcomas and determine treatment strategies in conjunction with traditional methods. Genetic alterations can be found in some subtypes of soft tissue sarcoma, but many other types show dysregulated gene expression attributed to epigenetic changes, such as DNA methylation status. However, research on DNA methylation profiles in soft tissue sarcoma is still insufficient to provide information to assist in diagnosis and therapeutic decisions. QUESTIONS/PURPOSES: (1) Do DNA methylation profiles differ between normal tissue and soft tissue sarcoma? (2) Do DNA methylation profiles vary between different histologic subtypes of soft tissue sarcoma? (3) Do DNA methylation profiles differ based on tumor grade? METHODS: Between January 2019 and December 2022, we treated 85 patients for soft tissue sarcomas. We considered patients whose specimens were approved for pilot research by the Human Biobank of St. Vincent's Hospital, The Catholic University of Korea, as potentially eligible. Based on this, 41% (35 patients) were eligible; 1% (one patient) was excluded because of gender mismatch between clinical and genetic data after controlling for data quality. Finally, 39 specimens (34 soft tissue sarcomas and five normal samples) were included from 34 patients who had clinical data. All tissue samples were collected intraoperatively. The five normal tissue samples were from muscle tissues. There were 20 female patients and 14 male patients, with a median age of 58 years (range 19 to 82 years). Genomic DNA was extracted from frozen tissue, and DNA methylation profiles were obtained. Genomic annotation of DNA methylation sites and hierarchical cluster analysis were performed to interpret results from DNA methylation profiling. A t-test was used to analyze different methylation probes. Benjamini-Hochberg-adjusted p value calculations were used to account for bias resulting from evaluating thousands of methylation sites. RESULTS: The most common histologic subtypes were liposarcoma (n = 10) and leiomyosarcoma (n = 9). The tumor grade was Fédération Nationale des Centres de Lutte Contre Le Cancer Grades 1, 2, and 3 in 3, 15, and 16 patients, respectively. DNA methylation profiling demonstrated differences between soft tissue sarcoma and normal tissue as 21,188 cytosine-phosphate-guanine sites. Despite the small number of samples, 72 of these sites showed an adjusted p value of < 0.000001, suggesting a low probability of statistical errors. Among the 72 sites, 70 exhibited a hypermethylation pattern in soft tissue sarcoma, with only two sites showing a hypomethylation pattern. Thirty of 34 soft tissue sarcomas were distinguished from normal samples using hierarchical cluster analysis. There was a different methylation pattern between leiomyosarcoma and liposarcoma at 7445 sites. Using the data, hierarchical clustering analysis showed that liposarcoma was distinguished from leiomyosarcoma. When we used the same approach and included other subtypes with three or more samples, only leiomyosarcoma and myxofibrosarcoma were separated from the other subtypes, while liposarcoma and alveolar soft-part sarcoma were mixed with the others. When comparing DNA methylation profiles between low-grade (Grade 1) and high-grade (Grades 2 and 3) soft tissue sarcomas, a difference in methylation pattern was observed at 144 cytosine-phosphate-guanine sites. Among these, 132 cytosine-phosphate-guanine sites exhibited hypermethylation in the high-grade group compared with the low-grade group. Hierarchical clustering analysis showed a division into two groups, with most high-grade sarcomas (28 of 31) separated from the low-grade group and few (3 out of 31) clustered together with the low-grade group. However, three high-grade soft tissue sarcomas were grouped with the Grade 1 cluster, and all of these sarcomas were Grade 2. When comparing Grades 1 and 2 to Grade 3, Grade 3 tumors were separated from Grades 1 and 2. CONCLUSION: We observed a different DNA methylation pattern between soft tissue sarcomas and normal tissues. Liposarcoma was distinguished from leiomyosarcoma using methylation profiling. High-grade soft tissue sarcoma samples showed a hypermethylation pattern compared with low-grade ones. Our findings indicate the need for research using methylation profiling to better understand the diverse biological characteristics of soft tissue sarcoma. Such research should include studies with sufficient samples and a variety of subtypes, as well as analyses of the expression and function of related genes. Additionally, efforts to link this research with clinical data related to treatment and prognosis are necessary. LEVEL OF EVIDENCE: Level III, diagnostic study.

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.

Hypofractionated Partial Breast Irradiation With Intensity-Modulated Radiotherapy in Early Breast Cancer or Carcinoma In Situ: An Investigational Short-Term Analysis.

PURPOSE: This study aimed to analyze the treatment outcomes and adverse effects of moderately hypofractionated partial breast irradiation (PBI) in patients with early breast cancer. METHODS: In total, 473 patients with early breast cancer or carcinoma in situ were diagnosed with Tis or T1N0 disease and underwent PBI following breast-conserving surgery. All histologic tumor types, close surgical margins within 1 mm of the tumor, and multifocal tumors were included in this study. A radiation dose of 50 Gy in 20 fractions was delivered over 4 weeks using intensity-modulated radiotherapy technique. Dosimetric data, recurrence patterns, survival outcomes, and adverse events were retrospectively analyzed. RESULTS: During a median follow-up of 28.9 months, seven patients (1.5%) experienced ipsilateral breast tumor recurrence (IBTR). Two patients had regional recurrence, four patients developed contralateral breast cancer, and no distant metastases were observed. The locoregional recurrence rate in the ipsilateral breast was 1.8%. Two deaths occurred during the follow-up period, but were not attributed to breast cancer. The 2-year disease-free survival and 2-year overall survival rates were was 94.0% and 99.8%, respectively. Acute adverse events occurred in 131 patients (27.1%), and were distributed among all grades, with only two patients (0.4%) experiencing grade 3 events. Late adverse events were noted in 16 patients (3.4%), and were distributed among all grades, including grade 3 events in four patients (0.8%). No grade 4 or 5 events were observed. CONCLUSION: Hypofractionated PBI demonstrated favorable IBTR rates in patients with early breast cancer, with low incidence of acute and late toxicities in the short-term analysis.

MRI-based volumetric tumor parameters before and during chemoradiation predict tumor recurrence and patient survival in locally advanced cervical cancer: a subgroup analysis of a phase II prospective trial.

BACKGROUND: This subgroup analysis of a prospective phase II trial aimed to identify valuable and accessible prognostic factors for overall survival (OS) and progression-free survival (PFS) of patients with locally advanced cervical cancer (LACC). METHODS: Patients with FIGO II to IVA cervical cancer were assessed in this study. All patients underwent concurrent chemoradiotherapy (CCRT) followed by brachytherapy. Tumor parameters based on MRI scans before and during CCRT were evaluated for Overall survival (OS) and Progression-free survival (PFS). RESULTS: A total of 86 patients were included in this analysis with a median follow-up period of 31.7 months. Three-year OS and PFS rates for all patients were 87.1% and 76.5%, respectively. Univariate Cox regression analysis showed that restaging tumor size (rTS) over 2.55 cm (p < 0.001), initial tumor volume (iTV) over 55.99 cc (p < 0.001), downstaging (p = 0.042), and restaging tumor volume (rTV) over 6.25 cc (p = 0.006) were significantly associated with OS. rTS (p < 0.001), iTV (p < 0.001), downstaging (p = 0.027), and rTV (p < 0.001) were identified as significant prognostic factors for PFS. In the stepwise multivariable analysis, only rTS > 2.55 cm showed statistically significant with OS (HR: 5.47, 95% CI 1.80-9.58, p = 0.035) and PFS (HR: 3.83, 95% CI 1.50-11.45; p = 0.025). CONCLUSIONS: Initial tumor size and restaging tumor volume that are easily accessible during radiotherapy provide valuable prognostic information for cervical cancer. MRI-based measurable volumetric scoring system can be readily applied in real-world practice of cervical cancer. CLINICAL TRIAL INFORMATION: This study is a subgroup analysis of prospective trial registered at ClinicalTrials.gov Identifier: NCT02993653.

Small Intercondylar Notch Size Is Not Associated with Poor Surgical Outcomes of Anatomical Single-Bundle Anterior Cruciate Ligament Reconstructions.

Background: Although many studies have been conducted on the association between the intercondylar notch size and the risk of anterior cruciate ligament (ACL) injury, few studies have examined its relationship with the condition after surgical treatment. Therefore, this study aimed to investigate the surgical outcomes of anatomical single-bundle ACL reconstruction according to intercondylar notch volumes. Methods: Medical records of patients who underwent anatomical single-bundle ACL reconstruction using a tibialis anterior allograft between 2015 and 2019 were retrospectively reviewed. For each sex, eligible patients were classified into two groups based on their percentile of intercondylar notch volumes, which were measured using postoperative three-dimensional computed tomography images (group S, ≤ 50th percentile of included patients; group L, > 50th percentile of included patients). Additional grouping was performed based on the group's percentiles of normalized values of intercondylar notch volumes to body heights. Between-group comparative analyses were performed on the perioperative data and surgical outcomes in both objective and subjective aspects. Results: One hundred patients were included in the study. For male patients, there were no differences in the overall surgical outcomes between groups, whereas group L showed a significantly greater knee anteroposterior (AP) laxity than group S at the final follow-up (p = 0.042 for the side-to-side differences [SSD] at the maximum manual force). Similarly, there were no differences in the female patients in the overall surgical results between the groups, whereas group L showed a significantly greater knee AP laxity at the final follow-up (p = 0.020 for the SSD at 134 N; p = 0.011 for the SSD at the maximum manual force). Additional analyses based on the normalized values of the intercondylar notch volume showed consistent results for male patients, and additional grouping for female patients was identical to the existing grouping. Conclusions: The surgical outcomes of anatomical single-bundle ACL reconstruction in patients with relatively small intercondylar notch volumes were comparable to those with large notch volumes, but rather showed favorable outcomes in postoperative knee AP laxity.

Nicotinamide adenine dinucleotide phosphate oxidase 2 deletion attenuates polyhexamethylene guanidine-induced lung injury in mice.

Inhalation of polyhexamethylene guanidine phosphate (PHMG) can cause pulmonary fibrosis. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) are enzymes that produce reactive oxygen species, which may be involved in tissue damage in various lung diseases. To investigate whether the Nox2 isoform of Nox is involved in the progression of PHMG-induced lung damage, we studied the contribution of Nox2 in PHMG-induced lung injury in Nox2-deficient mice. We treated wild-type (WT) and Nox2 knockout mice with a single intratracheal instillation of 1.1 mg/kg PHMG and sacrificed them after 14 days. We analyzed lung histopathology and the number of total and differential cells in the bronchoalveolar lavage fluid. In addition, the expressions of cytokines, chemokines, and profibrogenic genes were analyzed in the lung tissues. Based on our results, Nox2-deficient mice showed less PHMG-induced pulmonary damage than WT mice, as indicated by parameters such as body weight, lung weight, total cell count, cytokine and chemokine levels, fibrogenic mediator expression, and histopathological findings. These findings suggest that Nox2 may have the potential to contribute to PHMG-induced lung injury and serves as an essential signaling molecule in the development of PHMG-induced pulmonary fibrosis by regulating the expression of profibrogenic genes.

Allogeneic umbilical cord blood-derived mesenchymal stem cell implantation versus microdrilling combined with high tibial osteotomy for cartilage regeneration.

This study compared cartilage regeneration outcomes in knee osteoarthritis (OA) using allogeneic human umbilical cord blood-derived mesenchymal stem cell (hUCB-MSC) implantation and microdrilling with high tibial osteotomy (HTO). Fifty-four patients (60 knees) were included: 24 (27 knees) in the hUCB-MSC group and 30 (33 knees) in the microdrilling group. Both groups showed significant improvements in pain and functional scores at 6, 12, and 24 months compared to baseline. At 24 months, the hUCB-MSC group had significantly improved scores. Arthroscopic assessment at 12 months revealed better cartilage healing in the hUCB-MSC group. In subgroup analysis according to the defect site, hUCB-MSC implantation showed superior cartilage healing for anterior lesions. In conclusion, both treatments demonstrated effectiveness for medial OA. However, hUCB-MSC implantation had better patient-reported outcomes and cartilage regeneration than microdrilling. The study suggests promising approaches for cartilage restoration in large knee defects due to OA.