Objective
No imaging biomarkers are available for the prediction of cardiac events following concurrent chemoradiation therapy (CCRT) for non-small-cell lung cancer (NSCLC). We evaluated whether F-18 ...fluorodeoxyglucose positron emission tomography (FDG PET) early after CCRT, in addition to cardiac dosimetry, could predict late cardiac events in NSCLC.
Methods
We retrospectively enrolled 133 consecutive patients with locally advanced, unresectable stage III NSCLC, who underwent FDG PET early after CCRT and survived at least 6 months. The primary endpoint was cardiac event ≥ grade 2 according to the Common Terminology Criteria for Adverse Events (version 5.0). Myocardial FDG uptake was measured and its association with the risk of cardiac events was evaluated.
Results
FDG PET was performed after a median interval of 11 days of completing CCRT. Overall, 42 (32%) patients experienced cardiac events during a median follow-up of 45 months. The mean heart dose, maximum left ventricular (LV) standardized uptake value (SUV), changes in maximum and mean LV SUV, right ventricular uptake, tumor stage, white blood cell count, and diabetes were associated with cardiac events in univariable analysis. In multivariable analysis, maximum LV SUV (cutoff > 12.84; hazard ratio 95% confidence interval = 2.140 1.140–4.016;
p
= 0.018) was an independent predictor of cardiac events along with the mean heart dose (> 11.1 Gy; 3.646 1.792–7.417;
p
< 0.001) and tumor stage (IIIB; 1.986 1.056–3.734;
p
= 0.033). It remained predictive of cardiac events in those with higher mean heart dose but not in those with lower mean heart dose.
Conclusions
Early FDG PET after CCRT for NSCLC could aid in predicting late cardiac events, especially in patients with higher mean heart dose.
This study aimed to add real-world evidence to the literature regarding the effectiveness and safety of durvalumab consolidation (DC) after concurrent chemoradiotherapy (CCRT) in the treatment of ...unresectable stage III non-small cell lung cancer (NSCLC). Using a hospital-based NSCLC patient registry and propensity score matching in a 2:1 ratio, we conducted a retrospective cohort study of patients with unresectable stage III NSCLC who completed CCRT with and without DC. The co-primary endpoints were 2-year progression-free survival and overall survival. For the safety evaluation, we evaluated the risk of any adverse events requiring systemic antibiotics or steroids. Of 386 eligible patients, 222 patients-including 74 in the DC group-were included in the analysis after propensity score matching. Compared with CCRT alone, CCRT with DC was associated with increased progression-free survival (median: 13.3 vs. 7.6 months, hazard ratioHR: 0.63, 95% confidence intervalCI: 0.42-0.96) and overall survival (HR: 0.47, 95% CI: 0.27-0.82) without an increased risk of adverse events requiring systemic antibiotics or steroids. While there were differences in patient characteristics between the present real-world study and the pivotal randomized controlled trial, we demonstrated significant survival benefits and tolerable safety with DC after the completion of CCRT.
We recruited 50 patients with unresectable stage III NSCLC who received CCRT between March 2020 and March 2021. Durvalumab consolidation (DC) was administered to patients (
= 23) without progression ...after CCRT and programmed death-ligand 1 (PD-L1) ≥ 1%. Blood samples were collected before (C0) and after CCRT (C1) to calculate PBC counts and analyze CTCs. CTCs, isolated by the CD-PRIME
system, exhibited EpCAM/CK+/CD45- phenotype in BioViewCCBS
. At median follow-up of 27.4 months, patients with residual CTC clusters at C1 had worse median PFS than those without a detectable CTC cluster (11.0 vs. 27.8 months,
= 0.032), and this trend was noted only in the DC group (
= 0.034). Patients with high platelets at C1 (PLT
, >252 × 10
/µL) had worse median PFS than those with low platelets (PLT
) (5.9 vs. 17.1 months,
< 0.001). In multivariable analysis, PLT
and residual CTC clusters at C1 were independent risk factors for PFS, and DC group with PLT
and residual CTC clusters at C1 showed the worst median PFS (2.6 months, HR 45.16,
= 0.001), even worse than that of the CCRT alone group with PLT
(5.9 months, HR 15.39,
= 0.001). The comprehensive analysis of CTCs and PBCs before and after CCRT revealed that the clearance of CTC clusters and platelet counts at C1 might be potential biomarkers for predicting survival.
To investigate the incidence and the risk factors for occult ipsilateral or contralateral central neck lymph node (LN)metastasis in patients with unilateral papillary thyroid carcinoma (PTC) and a ...clinically negative neck.
Elective central lymph node dissection (CLND) in patients with PTC remains controversial. There have been few prospective studies assessing accurate histopathologic information and predictive factors for the presence of metastasis to the ipsilateral or contralateral central compartment of the neck in patients with PTC and clinically negative neck nodes.
We reviewed a prospective protocol of 111 unilateral PTC patients with clinically node-negative necks who have received total thyroidectomy and elective bilateral CLND from 2005 to 2007. The relationships between LN metastasis to the ipsilateral or contralateral central neck compartment and clinico-pathologic factors such as age, sex, size of primary tumor, perithyroidal invasion, lymphovascular invasion, and capsular invasion were analyzed.
Occult central neck LN metastasis was present in 54.1% (60/111). Of these patients, bilateral central LN metastases were present in 50% (30/60), unilateral ipsilateral central LN metastasis in 43.3% (26/60), and unilateral contralateral central LN metastasis in 6.7% (4/60). In the univariate analysis, the rate of ipsilateral central LN metastasis was significantly higher in male patients, high risk MACIS score, carcinoma with a maximal diameter of greater than 1 cm, and carcinoma with lymphovascular invasion (P < 0.05). The rate of contralateral central LN metastasis was significantly higher in cases of carcinoma with a maximal diameter of greater than 1 cm, lymphovascular invasion or histologically proven metastasis to the ipsilateral central LN (P < 0.05). Multivariate analysis showed that the tumor size was an independent risk factor for the presence of ipsilateral central LN metastasis, and the presence of ipsilateral central LN metastasis was the only independent predictor for the presence of contralateral central LN metastasis.
Unilateral PTC with a maximal diameter of greater than 1 cm is associated with a high rate of ipsilateral central neck LN metastasis. Moreover, ipsilateral central LN metastasis is a potential independent predictor of synchronous contralateral central LN metastasis. These findings suggest that contralateral as well as ipsilateral elective CLND, performed during the initial thyroid operation, may be effective in the management of patients with unilateral PTC having a maximal diameter of greater than 1 cm and ipsilateral central LN metastasis.
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•Electrochemical properties of CNTs treated in various plasma conditions through EIS analysis.•Analysis of the charge transfer resistance by the decrease of roughness and porosity of ...the SWCNT film.•The functionalization procedure promotes larger rate constants on functionalized SWCNT than untreated CNT.•Plasma-treated CNT under optimized treatment showed an enlarged effective area and improved electrocatalytic activity.
In this study, carbon-nanotube (CNT) surfaces were treated with oxygen plasma, and the improvement in surface inertness was analyzed using electrochemical impedance spectroscopy (EIS). Among nanomaterials, CNTs are the most attractive owing to their outstanding properties. However, the chemical inertness of CNT surfaces hinders the widespread implementation of CNTs in bioanalytical applications. Therefore, we present in detail the electrochemical properties of CNTs treated in various plasma conditions. The single-walled carbon nanotube (SWCNT) films were spray-coated onto working electrodes with a three-electrode configuration fabricated on a glass substrate and activated at various plasma conditions. The EIS spectra of the SWCNT film revealed typical porous structure characteristics. As the thickness of the SWCNT film increased by spray coating, the charge-transfer resistance sharply increased owing to the reduction of the effective electrode area caused by the decreased roughness and porosity of the SWCNT film. The Nyquist plots of the plasma-treated SWCNT electrodes featured two semicircular regions at high and intermediate frequencies, as well as one straight line at low frequencies. The plasma-treated SWCNT electrode had a less distinct separation of the second arc and straight line than the untreated SWCNT electrode because the time constant was lowered owing to the diffusion process generated where the charge-transfer reaction occurred. We analyzed the change in the electrodes through EIS, which can identify individual contributions to the total impedance of an electrochemical system.
Although previous studies continuously report an increased risk of hearing loss in diabetes patients, the impact of the disease on the inner ear remains unexplored. Herein, we examine the ...pathophysiology of diabetes-associated hearing impairment and cochlear synaptopathy in a mouse model of diabetes. Male B6.BKS(D)-Leprdb/J (db/db, diabetes) and heterozygote (db/+, control) mice were assigned into each experimental group (control vs. diabetes) based on the genotype and tested for hearing sensitivity every week from 6 weeks of age. Each cochlea was collected for histological and biological assays at 14 weeks of age. The diabetic mice exerted impaired hearing and a reduction in cochlear blood flow and C-terminal-binding protein 2 (CtBP2, a presynaptic ribbon marker) expression. Ultrastructural images revealed severely damaged mitochondria from diabetic cochlea accompanied by a reduction in Cytochrome c oxidase subunit 4 (COX4) and CR6-interacting factor 1 (CRIF1). The diabetic mice presented significantly decreased levels of platelet endothelial cell adhesion molecule (PECAM-1), B-cell lymphoma 2 (BCL-2), and procaspase-9, but not procaspase-8. Importantly, significant changes were not found in necroptotic programmed cell death markers (receptor-interacting serine/threonine-protein kinase 1, RIPK1; RIPK3; and mixed lineage kinase domain-like pseudokinase, MLKL) between the groups. Taken together, diabetic hearing loss is accompanied by synaptopathy, microangiopathy, damage to the mitochondrial structure/function, and activation of the intrinsic apoptosis pathway. Our results imply that mitochondrial dysfunction is deeply involved in diabetic hearing loss, and further suggests the potential benefits of therapeutic strategies targeting mitochondria.
Molecular biology and literature databases represent essential infrastructure for life science research. Effective integration of these data resources requires that there are structured ...cross-references at the level of individual articles and biological records. Here, we describe the current patterns of how database entries are cited in research articles, based on analysis of the full text Open Access articles available from Europe PMC. Focusing on citation of entries in the European Nucleotide Archive (ENA), UniProt and Protein Data Bank, Europe (PDBe), we demonstrate that text mining doubles the number of structured annotations of database record citations supplied in journal articles by publishers. Many thousands of new literature-database relationships are found by text mining, since these relationships are also not present in the set of articles cited by database records. We recommend that structured annotation of database records in articles is extended to other databases, such as ArrayExpress and Pfam, entries from which are also cited widely in the literature. The very high precision and high-throughput of this text-mining pipeline makes this activity possible both accurately and at low cost, which will allow the development of new integrated data services.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To determine the prognostic significance of long-term adjuvant androgen deprivation therapy (A-ADT) over 1 year in achieving undetectable levels of prostate-specific antigen (PSA) less than 0.001 ...ng/mL in prostate cancer patients with high- or very high-risk prostate cancer who underwent radiotherapy (RT).
A total of 197 patients with prostate cancer received RT, with a follow-up of ≥12 months. Biochemical failure was defined as PSA ≥nadir + 2 ng/mL after RT. We analyzed clinical outcomes, including survival, failure patterns, and prognostic factors affecting outcomes.
Biochemical failure-free survival (BCFFS), clinical failure-free survival, distant metastasis-free survival, cancer-specific survival, and overall survival (OS) rates at 5 years were 91.1%, 95.4%, 96.9%, 99.5%, and 89.1%, respectively. Administration of long-term A-ADT significantly predicted favorable BCFFS (p = 0.027) and OS (p < 0.001) in multivariate analysis. Nadir PSA ≤0.001 ng/mL was an independent prognostic factor for BCFFS (p = 0.006) and OS (p = 0.021). The use of long-term A-ADT significantly affected nadir PSA ≤0.001 ng/mL (p < 0.001). The patients with A-ADT for 1 year or longer had better BCFFS or OS than those for less than 1 year or those without A-ADT (p < 0.001). The best prognosis was demonstrated in patients treated with long-term A-ADT and nadir PSA ≤0.001 ng/mL in BCFFS (p < 0.001).
The addition of long-term A-ADT over 1 year to RT demonstrated good treatment outcomes in patients with locally advanced prostate cancer. Achieving a nadir PSA value ≤0.001 ng/mL using combination therapy with RT and A-ADT is a powerful clinical predictor of treatment outcomes.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
In this study, we analyzed the morphological changes and molecular structure changes on the surface of single-walled carbon nanotube (SWCNT) films during oxygen plasma (O2) etching of SWCNT surfaces ...formed by the spray method and analyzed their potential use as electrochemical electrodes. For this purpose, a SWCNT film was formed on the surface of a glass substrate using a self-made spray device using SWCNT powder prepared with DCB as a solvent, and SEM, AFM, and XPS analyses were performed as the SWCNT film was O2 plasma etched. SEM images and AFM measurements showed that the SWCNT film started etching after about 30 s under 50 W of O2 plasma irradiation and was completely etched after about 300 s. XPS analysis showed that as the O2 plasma etching of the SWCNT film progressed, the sp2 bonds representing the basic components of graphite decreased, the sp3 bonds representing defects increased, and the C–O, C=O, and COO peaks increased simultaneously. This result indicates that the SWCNT film was etched by the O2 plasma along with the oxygen species. In addition, electrochemical methods were used to verify the damage potential of the remaining SWCNTs after O2 plasma etching, including cyclic voltammetry, Randles plots, and EIS measurements. This resulted in a reversible response based on perfect diffusion control in the cyclic voltammetry, and an ideal linear curve in the Randles plot of the peak current versus square root scan rate curve. EIS measurements also confirmed that the charge transfer resistance of the remaining SWCNTs after O2 plasma etching is almost the same as before etching. These results indicate that the remaining SWCNTs after O2 plasma etching do not lose their unique electrochemical properties and can be utilized as electrodes for biosensors and electrochemical sensors. Our experimental results also indicate that the ionic conductivity enhancement by O2 plasma can be achieved additionally.
Purpose: This study was conducted to verify the validity and reliability of the Functional Independence Measure for Children (WeeFIM) for children with cerebral palsy by verifying the construct ...validity, difficulty, suitability, and cultural differences using Rasch analysis. Methods: From May 1, 2015, to February 27, 2020, 105 children with cerebral palsy aged 6 months–95 months (7 years and 11 months old) from Hospital Y located in Korea were included. In WeeFIM, 18 items were divided into 3 areas: Self-care 8 items, Motor 5 items, and Cognition 5 items. Analysis and separation reliability were analyzed. Results: In the Self-care area, the Grooming item and in the Motor area, the Transfer (Tub, Shower) item were judged as inappropriate items, and the order of difficulty was arranged without excluding the unsuitable items. In Self-acre, the most difficult item was Bathing, the easiest items were Eating and Bladder management, and the separation reliability was .87, the most difficult item in Motor was Stair, and the easiest item was Locomotion, and the separation reliability was .99. In Cognition, the most difficult item was Problem Solving, the easiest item was Communication, and the separation reliability was .95. Conclusion: The reliability and validity of WeeFIM was verified for children with cerebral palsy by applying Rasch Analysis. In future research, it is thought that additional research should be conducted by dividing the children by age and type so that they can be generalized.
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