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Proposal of nomograms to predict clinical outcomes in patients with ampulla of Vater cancer based on the Korea-Japan collaborative study
No full textBackground In this study, we aimed to develop and validate a nomogram to predict overall survival (OS) and recurrence-free survival (RFS) in patients who underwent curative resection of ampulla of Vater (AOV) cancer. This is the first study for nomograms in AOV cancer patients using retrospective data based on an international multicenter study. Methods A total of 2007 patients with AOV adenocarcinoma who received operative therapy between 2002 January and 2015 December in Korea and Japan were retrospectively assessed to develop a prediction model. Nomograms for 5-year OS and 3-year RFS were constructed by dividing the patients who received and who did not receive adjuvant therapy after surgery, respectively. Significant risk factors were identified by univariate and multivariate Cox analyses. Performance assessment of the four prediction models was conducted by the Harrell's concordance index (C-index) and calibration curves using bootstrapping. Results A total of 2007 and 1873 patients were collected for nomogram construction to predict 5-year OS and 3-year RFS. We developed four types of nomograms, including models for 5-year OS and 3-year RFS in patients who did not receive postoperative adjuvant therapy, and 5-year OS and 3-year RFS in patients who received postoperative adjuvant therapy. The C-indices of these nomograms were 0.795 (95% confidence interval [CI]: 0.766-0.823), 0.712 (95% CI: 0.674-0.750), 0.804 (95% CI: 0.7778-0.829), and 0.703 (95% CI: 0.669-0.737), respectively. Conclusions This predictive model could help clinicians to choose optimal treatment and precisely predict prognosis in AOV cancer patients.restrictio
Combined Effects of Focused Ultrasound and Photodynamic Treatment for Malignant Brain Tumors Using C6 Glioma Rat Model
Full text linkPurpose: Glioblastoma (GBM) is an intractable disease for which various treatments have been attempted, but with little effect. This study aimed to measure the effect of photodynamic therapy (PDT) and sonodynamic therapy (SDT), which are currently be ing used to treat brain tumors, as well as sono-photodynamic therapy (SPDT), which is the combination of these two.
Materials and Methods: Four groups of Sprague-Dawley rats were injected with C6 glioma cells in a cortical region and treated with PDT, SDT, and SPDT. Gd-MRI was monitored weekly and 18F-FDG-PET the day before and 1 week after the treatment. The acoustic power used during sonication was 5.5 W/cm2 using a 0.5-MHz single-element transducer. The 633-nm laser was illumi nated at 100 J/cm2. Oxidative stress and apoptosis markers were evaluated 3 days after treatment using immunohistochemistry (IHC): 4-HNE, 8-OhdG, and Caspase-3.
Results: A decrease in tumor volume was observed in MRI imaging 12 days after the treatment in the PDT group (p<0.05), but the SDT group showed a slight increase compared to the 5-Ala group. The high expression rates of reactive oxygen species-related factors, such as 8-OhdG (p<0.001) and Caspase-3 (p<0.001), were observed in the SPDT group compared to other groups in IHC.
Conclusion: Our findings show that light with sensitizers can inhibit GBM growth, but not ultrasound. Although SPDT did not show the combined effect in MRI, high oxidative stress was observed in IHC. Further studies are needed to investigate the safety parameters to apply ultrasound in GBM.ope
WNT-modulating gene silencers as a gene therapy for osteoporosis, bone fracture, and critical-sized bone defects
Full text linkTreating osteoporosis and associated bone fractures remains challenging for drug development in part due to potential off-target side effects and the requirement for long-term treatment. Here, we identify recombinant adeno-associated virus (rAAV)-mediated gene therapy as a complementary approach to existing osteoporosis therapies, offering long-lasting targeting of multiple targets and/or previously undruggable intracellular non-enzymatic targets. Treatment with a bone-targeted rAAV carrying artificial microRNAs (miRNAs) silenced the expression of WNT antagonists, schnurri-3 (SHN3), and sclerostin (SOST), and enhanced WNT/b-catenin signaling, osteoblast function, and bone formation. A single systemic administration of rAAVs effectively reversed bone loss in both postmenopausal and senile osteoporosis. Moreover, the healing of bone fracture and critical-sized bone defects was also markedly improved by systemic injection or transplantation of AAV-bound allograft bone to the osteotomy sites. Collectively, our data demonstrate the clinical potential of bone-specific gene silencers to treat skeletal disorders of low bone mass and impaired fracture repair.ope
Photobiomodulation-Based Synergic Effects of Pt-Coated TiO2 Nanotubes and 850 nm Near-Infrared Irradiation on the Osseointegration Enhancement: In Vitro and In Vivo Evaluation
Full text linkAbstract: Photobiomodulation (PBM) therapy is known to have the potential to improve bone regeneration
after implant surgery. However, the combinatory effect of the nanotextured implant and PBM
therapy on osseointegration has not yet been proved. This study evaluated the photobiomodulationbased
synergistic effects of Pt-coated titania nanotubes (Pt-TiO2 NT) and 850 nm near-infrared (NIR)
light on osteogenic performance in vitro and in vivo. The FE-SEM and the diffuse UV-Vis-NIR
spectrophotometer were used to perform the surface characterization. The live-dead, MTT, ALP,
and AR assays were tested to perform in vitro tests. The removal torque testing, the 3D-micro CT,
and the histological analysis were used to conduct in vivo tests. The live-dead and MTT assay
resulted in Pt-TiO2 NTs being biocompatible. The ALP activity and AR assays demonstrated that
the combination of Pt-TiO2 NT and NIR irradiation significantly enhanced osteogenic functionality
(p < 0.05). The results of in vivo test, employing the removal torque testing, the 3D-micro CT, and
histological analysis, showed overall improved outcomes; however, no significant difference was
observed between the control and experimental groups (p > 0.05). Therefore, we confirmed the
possibility of the combination of Pt-TiO2 NT and NIR light as a promising technology for implant
surgery in dentistry.ope
Tenosynovitis of the Hand Caused by Kosakonia cowanii After Being Pricked by a Beanstalk
Full text linkA 77-year-old man with pain in his left hand after being pricked by a beanstalk visited an emergency center. Symptoms and laboratory findings suggested infectious tenosynovitis. Using the Bruker Biotyper (Bruker Daltonics, Germany), Kosakonia cowanii was identified in the swab culture and was confirmed by full-length 16S ribosomal RNA (rRNA) and gyrB sequencing. To the best of our knowledge, this is the first reported case of K. cowanii infection in Korea. Performing only 16S rRNA sequencing was insufficient for accurate identification, and gyrB sequencing or using the Bruker Biotyper (Bruker Daltonics, Germany) confirmed the identification. A positive sorbitol fermentation test can indicate the microorganism to be K. cowanii even if the VITEK 2 system (bioMérieux, France) identifies it as Pantoea spp. Additionally, K. cowanii may be resistant to beta-lactam antibiotics, including cefazolin; therefore, it may be appropriate to use carbapenems, third- or fourth-generation cephalosporins, aminoglycosides, fluoroquinolones, and trimethoprim/sulfamethoxazole. Finally, antibiotic susceptibility testing (AST) should be conducted using a reference method, and Etest AST is unreliable for K. cowanii, especially with beta-lactam/beta-lactamase inhibitors.ope
Clinical significance of anti-NT5c1A autoantibody in Korean patients with inflammatory myopathies
Full text linkTo explore the clinical significance of anti-cytosolic 5'-nucleoditase 1A (NT5c1A) antibody seropositivity in inflammatory myopathies, we measured anti-NT5c1A antibodies and analyzed their clinical features. Anti-NT5c1A antibodies were measured in the sera of 103 patients with inflammatory myopathies using an enzyme-linked immunosorbent assay. Positivity for anti-NT5c1A antibody was found in 13 (12.6%) of 103 patients with inflammatory myopathy. Anti-NT5c1A antibody was most frequently identified in patients with inclusion body myositis (IBM) (8/20, 40%), followed by dermatomyositis (2/13, 15.4%), immune-mediated necrotizing myopathy (2/28, 7.1%), and polymyositis (1/42, 2.4%). In eight patients with the anti-NT5c1A antibody-seropositive IBM, the median age at symptom onset was 54 years (interquartile range [IQR]: 48-57 years), and the median disease duration was 34 months (IQR: 24-50 months]. Knee extension weakness was greater than or equal to hip flexion weakness in eight (100%) patients, and finger flexion strength was less than shoulder abduction in three (38%) patients. Dysphagia symptoms were found in three (38%) patients. The median serum CK level was 581 IU/l (IQR: 434-868 IU/L]. Clinically significant differences were not found between anti-NT5c1A antibody-seropositive and seronegative IBM groups with respect to gender, age at symptom onset, age at diagnosis, disease duration, serum CK values, presence of other autoantibodies, dysphagia, and the pattern of muscle impairment. Although anti-NT5c1A antibody is known to be associated with IBM, seropositivity has also been noted in non-IBM inflammatory myopathies, and is insufficient to have clinical significance by itself. These findings have important implications for interpreting anti- NT5c1A antibody test results as the first study in Korea. © 2023 Lee et al.ope
Clinical features and molecular genetics associated with brain metastasis in suspected early-stage non-small cell lung cancer
No full textIntroduction: Regarding whether brain magnetic resonance imaging (MRI) should be routine in patients with suspected early-stage lung cancer, guideline recommendations are inconsistent. Therefore, we performed this study to evaluate the incidence of and risk factors for brain metastasis (BM) in patients with suspected early-stage non-small-cell lung cancer (NSCLC).
Methods: A review of the medical charts of consecutive NSCLC patients diagnosed between January 2006 and May 2020 was performed. We identified 1,382 NSCLC patients with clinical staging of T1/2aN0M0 (excluding BM), and investigated the incidence, clinical predictors, and prognosis of BM in the cohort. We also performed RNA-sequencing differential expression analysis using transcriptome of 8 patients, using DESeq2 package (version 1.32.0) with R (version 4.1.0).
Results: Among 1,382 patients, nine hundred forty-nine patients (68.7%) underwent brain MRI during staging, and 34 patients (3.6%) were shown to have BM. Firth’s bias-reduced logistic regression showed that tumor size (OR 1.056; 95% CI 1.009-1.106, p=0.018) was the only predictor of BM, and
pathologic type was not a predictor of BM in our cohort (p>0.05). The median overall survival for patients with brain metastasis was 5.5 years, which is better than previously reported in the literature. RNA-sequencing differential expression analysis revealed the top 10 significantly upregulated genes and top 10 significantly downregulated genes. Among the genes involved in BM, Unc-79 homolog, non-selective sodium leak channel (NALCN) channel complex subunit (UNC79) was the most highly expressed gene in the lung adenocarcinoma tissues from the BM group, and an in vitro assay using A549 cells revealed that the NALCN inhibitor suppressed lung cancer cell proliferation and migration.ope
Differential association between apolipoprotein B and LDL cholesterol and cerebral atherosclerosis according to pre-stroke statin use
No full textBackground and aims: To reduce cardiovascular risk, low-density lipoprotein cholesterol (LDL-C) is the primary target of statin treatment, while apolipoprotein B (ApoB) is secondary. We investigated the association between atherosclerotic stenosis and LDL-C or ApoB levels and whether a difference in association exists according to pre-admission statin use in ischemic stroke patients. Methods: This retrospective cross-sectional study included consecutive patients with acute ischemic stroke or transient ischemic attack who underwent lipid profile and angiographic testing. Patients were categorized into four groups according to stenosis location: normal, extracranial atherosclerotic stenosis (ECAS), intracranial atherosclerotic stenosis (ICAS), or ECAS + ICAS. Subgroup analyses were performed by pre-admission statin use. Results: Of the 6338 patients included, 1980 (31.2%) were in the normal group, 718 (11.3%) in the ECAS group, 1845 (29.1%) in the ICAS group, and 1795 (28.3%) in the ECAS + ICAS group. Both LDL-C and ApoB levels were associated with every location of stenosis. A significant interaction was found between pre-admission statin use and LDL-C level (p for interaction <0.05). LDL-C was associated with stenosis only in statin-naïve patients, whereas ApoB was associated with ICAS, with or without ECAS, in both statin-naïve and statin-treated patients. ApoB also showed a consistent association with symptomatic ICAS in both statin-treated and statin-naïve patients, whereas LDL-C did not. Conclusions: ApoB was consistently associated with ICAS, particularly symptomatic stenosis, in both statin-naïve and statin-treated patients. The close association between ApoB levels and residual risk in statin-treated patients could be partially explained by these results. © 2023 Elsevier B.V.restrictio
Combination Moderate-Intensity Statin and Ezetimibe Therapy for Elderly Patients With Atherosclerosis
No full textBackground: The routine use of high-intensity statins should be considered carefully in elderly patients because of their higher risk of intolerance or adverse events. Objectives: We evaluated the impact of moderate-intensity statin with ezetimibe combination therapy compared with high-intensity statin monotherapy in elderly patients with atherosclerotic cardiovascular disease (ASCVD). Methods: In this post hoc analysis of the RACING (RAndomized Comparison of Efficacy and Safety of Lipid-lowerING With Statin Monotherapy Versus Statin/Ezetimibe Combination for High-risk Cardiovascular Diseases) trial, patients were stratified by age (≥75 years and <75 years). The primary endpoint was a 3-year composite of cardiovascular death, major cardiovascular events, or nonfatal stroke. Results: Among the 3,780 enrolled patients, 574 (15.2%) were aged ≥75 years. The rates of the primary endpoint were not different between the moderate-intensity statin with ezetimibe combination therapy group and the high-intensity statin monotherapy group among patients aged ≥75 years (10.6% vs 12.3%; HR: 0.87; 95% CI: 0.54-1.42; P = 0.581) and those <75 years (8.8% vs 9.4%; HR: 0.94; 95% CI: 0.74-1.18; P = 0.570) (P for interaction = 0.797). Moderate-intensity statin with ezetimibe combination therapy was associated with lower rates of intolerance-related drug discontinuation or dose reduction among patients aged ≥75 years (2.3% vs 7.2%; P = 0.010) and those <75 years (5.2% vs 8.4%; P < 0.001) (P for interaction = 0.159). Conclusions: Moderate-intensity statin with ezetimibe combination therapy showed similar cardiovascular benefits to those of high-intensity statin monotherapy with lower intolerance-related drug discontinuation or dose reduction in elderly patients with ASCVD having a higher risk of intolerance, nonadherence, and discontinuation with high-intensity statin therapy. (RAndomized Comparison of Efficacy and Safety of Lipid-lowerING With Statin Monotherapy Versus Statin/Ezetimibe Combination for High-risk Cardiovascular Diseases [RACING Trial]; NCT03044665) © 2023 American College of Cardiology Foundationrestrictio
Subjective Cognitive Complaints in Cognitively Normal Patients With Parkinson's Disease: A Systematic Review
Full text linkSubjective cognitive complaints (SCCs) refer to self-perceived cognitive decline and are related to objective cognitive decline. SCCs in cognitively normal individuals are considered a preclinical sign of subsequent cognitive impairment due to Alzheimer’s disease, and SCCs in cognitively normal patients with Parkinson’s disease (PD) are also gaining attention. The aim of this review was to provide an overview of the current research on SCCs in cognitively normal patients with PD. A systematic search found a lack of consistency in the methodologies used to define and measure SCCs. Although the association between SCCs and objective cognitive performance in cognitively normal patients with PD is controversial, SCCs appear to be predictive of subsequent cognitive decline. These findings support the clinical value of SCCs in cognitively normal status in PD; however, further convincing evidence from biomarker studies is needed to provide a pathophysiological basis for these findings. Additionally, a consensus on the definition and assessment of SCCs is needed for further investigations. © 2023 The Korean Movement Disorder Society. All rights reserved.ope