Antiplatelet drugs may increase the risk for checkpoint inhibitor-related pneumonitis in advanced cancer patients.

BACKGROUND: Immune checkpoint inhibitors (ICIs) are indicated for various cancers and are the mainstay of cancer immunotherapy. They are often associated with ICI-related pneumonitis (CIP), however, hindering a favorable clinical course. Recently, non-oncology concomitant drugs have been reported to affect the efficacy and toxicity of ICIs; however, the association between these drugs and the risk for CIP is uncertain. The aim of this study was to assess the impact of baseline concomitant drugs on CIP incidence in ICI-treated advanced cancer patients. PATIENTS AND METHODS: This was a single-center retrospective study that included a cohort of 511 patients with advanced cancer (melanoma and non-small-cell lung, head and neck, genitourinary, and other types of cancer) treated with ICIs. Univariable analysis was conducted to identify baseline co-medications associated with CIP incidence. A propensity score matching analysis was used to adjust for potential CIP risk factors, and multivariable analysis was carried out to assess the impact of the identified co-medications on CIP risk. RESULTS: Forty-seven (9.2%) patients developed CIP. In these patients, the organizing pneumonia pattern was the dominant radiological phenotype, and 42.6% had grade ≥3 CIP, including one patient with grade 5. Of the investigated baseline co-medications, the proportion of antiplatelet drugs (n = 50, 9.8%) was higher in patients with CIP (23.4% versus 8.4%). After propensity score matching, the CIP incidence was higher in patients with baseline antiplatelet drugs (22% versus 6%). Finally, baseline antiplatelet drug use was demonstrated to increase the risk for CIP incidence regardless of cancer type (hazard ratio, 3.46; 95% confidence interval 1.21-9.86). CONCLUSIONS: An association between concomitant antiplatelet drug use at baseline and an increased risk for CIP was seen in our database. This implies the importance of assessing concomitant medications for CIP risk management.

Comparison of the Antiemetic Effect of Aprepitant/granisetron and Palonosetron Combined with Dexamethasone in Gynecological Cancer Patients Treated with Paclitaxel and Carboplatin Combination Regimen.

A triple antiemetic therapy combining aprepitant (APR) with conventional double antiemetic therapy, including 5-hydroxytryptamine 3 receptor antagonist (5-HT3-RA) and dexamethasone (DEX), is recommended for preventing chemotherapy-induced nausea and vomiting induced by a carboplatin (CBDCA) regimen. However, consensus on the additive effects of APR for gynecological patients on a combined regimen of paclitaxel and CBDCA (TC regimen) has yet to be reached. This retrospective study investigated the antiemetic effects of palonosetron and DEX (PD therapy) and granisetron and DEX with APR (GDA therapy) in patients with gynecologic cancer and who underwent their first TC regimen cycle between April 2017 and March 2020 at the Gunma University Hospital Outpatient Chemotherapy Center. The results showed that the complete response rate of the 92 patients who underwent PD therapy (PD group) and the 46 patients who underwent GDA therapy (GDA group) were both 80.4% (p = 1.000), and the complete control rates of the PD and GDA groups were 78.3% and 80.4%, respectively (p = 0.828), resulting in no significant difference. Furthermore, we observed no significant difference between the PD and GDA groups in the incidence of grade ≥2 nausea, vomiting, and anorexia (nausea: 7.6% vs. 0%, p = 0.095; vomiting: 4.3% vs. 0%, p = 0.301; and anorexia: 9.8% vs. 2.2%, p = 0.164). Concerning adverse events, compared to the PD group, the GDA group showed significantly higher incidence of grade ≥2 malaise (7.6% vs. 19.6%, p = 0.039). Given the lack of difference in the antiemetic effects of PD and GDA therapies, antiemetic therapy should be selected carefully for individual patients by accounting for the incidence of adverse reactions and interactions with APR.

Organic synthesis associated with serpentinization and carbonation on early Mars.

Water-rock interactions are relevant to planetary habitability, influencing mineralogical diversity and the production of organic molecules. We examine carbonates and silicates in the martian meteorite Allan Hills 84001 (ALH 84001), using colocated nanoscale analyses, to characterize the nature of water-rock reactions on early Mars. We find complex refractory organic material associated with mineral assemblages that formed by mineral carbonation and serpentinization reactions. The organic molecules are colocated with nanophase magnetite; both formed in situ during water-rock interactions on Mars. Two potentially distinct mechanisms of abiotic organic synthesis operated on early Mars during the late Noachian period (3.9 to 4.1 billion years ago).

Molecular identification of fungi microfossils in a Neoproterozoic shale rock.

Precambrian fossils of fungi are sparse, and the knowledge of their early evolution and the role they played in the colonization of land surface are limited. Here, we report the discovery of fungi fossils in a 810 to 715 million year old dolomitic shale from the Mbuji-Mayi Supergroup, Democratic Republic of Congo. Syngenetically preserved in a transitional, subaerially exposed paleoenvironment, these carbonaceous filaments of ~5 µm in width exhibit low-frequency septation (pseudosepta) and high-angle branching that can form dense interconnected mycelium-like structures. Using an array of microscopic (SEM, TEM, and confocal laser scanning fluorescence microscopy) and spectroscopic techniques (Raman, FTIR, and XANES), we demonstrated the presence of vestigial chitin in these fossil filaments and document the eukaryotic nature of their precursor. Based on those combined evidences, these fossil filaments and mycelium-like structures are identified as remnants of fungal networks and represent the oldest, molecularly identified remains of Fungi.

Imperceptible magnetic sensor matrix system integrated with organic driver and amplifier circuits.

Artificial electronic skins (e-skins) comprise an integrated matrix of flexible devices arranged on a soft, reconfigurable surface. These sensors must perceive physical interaction spaces between external objects and robots or humans. Among various types of sensors, flexible magnetic sensors and the matrix configuration are preferable for such position sensing. However, sensor matrices must efficiently map the magnetic field with real-time encoding of the positions and motions of magnetic objects. This paper reports an ultrathin magnetic sensor matrix system comprising a 2 × 4 array of magnetoresistance sensors, a bootstrap organic shift register driving the sensor matrix, and organic signal amplifiers integrated within a single imperceptible platform. The system demonstrates high magnetic sensitivity owing to the use of organic amplifiers. Moreover, the shift register enabled real-time mapping of 2D magnetic field distribution.

Quantitative assessment of outer retinal folds on enface optical coherence tomography after vitrectomy for rhegmatogenous retinal detachment.

We aimed to investigate the possible causes of metamorphopsia for rhegmatogenous retinal detachment (RRD) based on findings of enface optical coherence tomography (OCT). The study was a retrospective, consecutive case series of 33 eyes with macula-off RRD. Metamorphopsia was measured by M-CHARTS and enface OCT images covering a macular area of 6 × 6 mm square obtained at 1, 3, and 6 months postoperatively. Within the outer retinal slabs of enface OCT, multiple lines that looked like folds were delineated in all eyes at month 1, and we succeeded in extracting images of folds by subtracting retinal vessels. We calculated their density by an image-processing technique. The mean M-CHARTS scores were 0.62 ± 0.47 at month 1 and 0.30 ± 0.29 at month 6 (P < 0.001). The fold density was 8.3 ± 4.2 at month 1 and 6.1 ± 3.1 at month 6 (P = 0.0044). The M-CHARTS scores at 6 months were significantly associated with the fold density at 1 month (r = 0.515, P = 0.002). In conclusion, enface OCT visualized the outer retinal folds in eyes that had undergone successful RRD surgery, and a larger number of folds was related to the remaining metamorphopsia.

Robust water desalination membranes against degradation using high loads of carbon nanotubes.

Chlorine resistant reverse osmosis (RO) membranes were fabricated using a multi-walled carbon nanotube-polyamide (MWCNT-PA) nanocomposite. The separation performance of these membranes after chlorine exposure (4800 ppm·h) remained unchanged (99.9%) but was drastically reduced to 82% in the absence of MWCNT. It was observed that the surface roughness of the membranes changed significantly by adding MWCNT. Moreover, membranes containing MWCNT fractions above 12.5 wt.% clearly improved degradation resistance against chlorine exposure, with an increase in water flux while maintaining salt rejection performance. Molecular dynamics and quantum chemical calculations were performed in order to understand the high chemical stability of the MWCNT-PA nanocomposite membranes, and revealed that high activation energies are required for the chlorination of PA. The results presented here confirm the unique potential of carbon nanomaterials embedded in polymeric composite membranes for efficient RO water desalination technologies.

Radiological features and metastatic patterns of thymic neuroendocrine tumours.

AIM: To investigate the clinical and image features of thymic neuroendocrine tumours (NETs), and characterise the radiological patterns of recurrence and metastasis on serial imaging studies. MATERIALS AND METHODS: The study included 14 patients (11 males) with a histopathological diagnosis of thymic NETs (one typical carcinoid, eight atypical carcinoid, and five large cell neuroendocrine carcinoma). Preoperative images were assessed for features of primary tumours. Follow-up imaging studies were evaluated for the patterns of metastasis or recurrence. RESULTS: Underlying endocrine or autoimmune disorders were present in four patients (29%), including multiple endocrine neoplasia (MEN) type 1 (n=3) and autoimmune thyroiditis (n=1). On preoperative imaging, the primary tumours were commonly lobulate and heterogeneous, infiltrated the surrounding fat, and showed ≥50% abutment of the mediastinal structures, with the mean longest diameter of 14 cm (range: 4.1-28 cm). No significant differences of preoperative imaging features were noted among histopathological subtypes. Metastasis or recurrence was noted in 11 of the 14 patients (79%). Ten patients developed intrathoracic metastasis or recurrence, involving thoracic lymph nodes (n=7), pleura (n=4), lung (n=4), pericardium (n=4), and local recurrence in the postoperative mediastinum (n=3). Eight of the 11 patients also had extra-thoracic metastasis, involving bone (n=6), abdominal lymph nodes (n=4), liver, pancreas, kidney, adrenal gland, spleen and brain (n=1 for each site). CONCLUSIONS: Thymic NETs presented as a large, lobulate, heterogeneous mass with an infiltrative nature. Metastasis and recurrence were frequent, most commonly involving thoracic lymph nodes, while extra-thoracic metastasis to bones and abdominal lymph nodes were also noted.

Electrochemical microdevices for rapid and on-site determination of the minimum inhibitory concentration of antibiotics.

A tool for rapid selection of appropriate antibiotics may be useful to maximize the benefits of their effectiveness against severe infectious diseases. In this study, we propose a microdevice that works with surface tension-driven sample introduction and impedance measurements for on-site, rapid estimation of suitable antibiotics.

Endogenous analgesic effect of pregabalin: A double-blind and randomized controlled trial.

BACKGROUND: Conditioned pain modulation (CPM) is widely used to measure endogenous analgesia, and a recent study indicated that drugs that act on endogenous analgesia are more effective in individuals with lower CPM. Recent animal studies have indicated that pregabalin activates endogenous analgesia by stimulating the descending pain inhibitory system. The present study examined whether the analgesic effect of pregabalin is greater in individuals with lower original endogenous analgesia using CPM. METHODS: Fifty-nine healthy subjects were randomly assigned to either a pregabalin group or a placebo group, and 50 of them completed the study. CPM was measured before and after pregabalin or placebo administration. The correlation of initial CPM to change in CPM was compared between the pregabalin and placebo groups. RESULTS: Initial CPM was significantly correlated with the change in CPM in the pregabalin group (r = -0.73, p < 0.0001) but not in the placebo group (p = 0.56) (difference in correlation coefficients between groups; p = 0.004). Furthermore, the initial CPM significantly affected the change in CPM in the pregabalin group but not in the placebo group (pregabalin group: adj R2  = 0.51, p < 0.001, y = -0.54x + 2.98; placebo group: p = 0.56, significant difference in regression slopes; p = 0.015). These results indicate that pregabalin has a higher endogenous analgesic effect in individuals with lower original endogenous analgesia. SIGNIFICANCE: The analgesic effect of pregabalin depends on the original endogenous analgesia status. Its effect on conditioned pain modulation (CPM) was stronger for subjects with lower original endogenous analgesia, suggesting that the mechanism of pregabalin involves the improvement of endogenous analgesia.

Influence of Nonenzymatic Glycation in Dentinal Collagen on Dental Caries.

Advanced glycation end-products (AGEs) are generated via nonenzymatic glycation of dentinal collagen, resulting in accumulation of AGEs in dentin tissue. Since accumulated AGEs cause crosslinking between amino acid polypeptides in the collagen molecule and modify mechanical properties of dentinal collagen, the authors assumed that there would be a significant interaction between the generation of AGEs and progression of caries in dentin. To confirm such an interaction, spectroscopic imaging analyses (i.e., nanosecond fluorescence lifetime imaging and second harmonic generation light imaging) were performed in addition to biochemical and electron microscopic analyses in the present study. Seven carious human teeth were fixed in paraformaldehyde and cut longitudinally into 1-mm sections using a low-speed diamond saw for the following analyses. In transmission electron microscopy (TEM) analysis, nondecalcified specimens were embedded in epoxy resin and sliced into thin sections for observation. For the immunohistochemical analysis, the specimens were paraffin embedded after decalcification for 2 wk and sectioned with a microtome. Resultant sections were stained with anti-AGE and anticollagen antibodies. The demineralized specimens were used for spectroscopic analyses without additional treatment. For Western blotting analysis, specimens were separated into carious and sound dentin. Each specimen was homogenized with a bead crusher and an ultrasonic homogenizer and then treated with hydrochloric acid. In carious dentin, the collagen fibers showed an amorphous structure in the TEM image, and the AGEs were localized in the areas of bacterial invasion in the immunostaining image. The total amount of AGEs in carious dentin was higher than in sound dentin in Western blotting. The ultrastructure of type I collagen and total amount of AGEs varied markedly in the dentinal caries region. The fluorescence lifetime was shorter in the carious area than that in the sound areas, indicating an increase of AGEs in the carious area. The increase of AGEs could influence the progression of dentinal caries.

Patterns of metastasis and recurrence in thymic epithelial tumours: longitudinal imaging review in correlation with histological subtypes.

AIM: To determine the patterns of metastasis and recurrence in thymic epithelial tumours based on longitudinal imaging studies, and to correlate the patterns with World Health Organization (WHO) histological classifications. MATERIALS AND METHODS: Seventy-seven patients with histopathologically confirmed thymomas (n=62) and thymic carcinomas (n=15) who were followed with cross-sectional follow-up imaging after surgery were retrospectively studied. All cross-sectional imaging studies during the disease course were reviewed to identify metastasis or recurrence. The sites of involvement and the time of involvement measured from surgery were recorded. RESULTS: Metastasis or recurrence was noted in 24 (31%) of the 77 patients. Patients with metastasis or recurrence were significantly younger than those without (median age: 46 versus 60, respectively; p=0.0005), and more commonly had thymic carcinomas than thymomas (p=0.002). The most common site of involvement was the pleura (17/24), followed by the lung (9/24), and thoracic nodes (9/24). Abdominopelvic involvement was noted in 12 patients, most frequently in the liver (n=8). Lung metastasis was more common in thymic carcinomas than thymomas (p=0.0005). Time from surgery to the development of metastasis or recurrence was shortest in thymic carcinoma, followed by high-risk thymomas, and was longest in low-risk thymoma (median time in months: 25.1, 68.8, and not reached, respectively; p=0.0015). CONCLUSIONS: The patterns of metastasis and recurrence of thymic epithelial tumours differ significantly across histological subgroups, with thymic carcinomas more commonly having metastasis with shorter length of time after surgery. The knowledge of different patterns of tumour spread may contribute to further understanding of the biological and clinical behaviours of these tumours.

Correlative near-infrared light and cathodoluminescence microscopy using Y2O3:Ln, Yb (Ln = Tm, Er) nanophosphors for multiscale, multicolour bioimaging.

This paper presents a new correlative bioimaging technique using Y2O3:Tm, Yb and Y2O3:Er, Yb nanophosphors (NPs) as imaging probes that emit luminescence excited by both near-infrared (NIR) light and an electron beam. Under 980 nm NIR light irradiation, the Y2O3:Tm, Yb and Y2O3:Er, Yb NPs emitted NIR luminescence (NIRL) around 810 nm and 1530 nm, respectively, and cathodoluminescence at 455 nm and 660 nm under excitation of accelerated electrons, respectively. Multimodalities of the NPs were confirmed in correlative NIRL/CL imaging and their locations were visualized at the same observation area in both NIRL and CL images. Using CL microscopy, the NPs were visualized at the single-particle level and with multicolour. Multiscale NIRL/CL bioimaging was demonstrated through in vivo and in vitro NIRL deep-tissue observations, cellular NIRL imaging, and high-spatial resolution CL imaging of the NPs inside cells. The location of a cell sheet transplanted onto the back muscle fascia of a hairy rat was visualized through NIRL imaging of the Y2O3:Er, Yb NPs. Accurate positions of cells through the thickness (1.5 mm) of a tissue phantom were detected by NIRL from the Y2O3:Tm, Yb NPs. Further, locations of the two types of NPs inside cells were observed using CL microscopy.

Wireless EEG patch sensor on forehead using on-demand stretchable electrode sheet and electrode-tissue impedance scanner.

A wireless electroencephalogram (EEG) sensor using a stretchable electrode sheet and electrode-tissue impedance measurement module is presented herein. The sensor can be attached to the forehead using biocompatible gel with the electrode sheet. The sensor is compactly designed for 3 cm × 9 cm × 6 mm with weight of 12 g. Impedance scanning circuit is also proposed to evaluate the skin surface condition before EEG measurements. We developed the impedance scanning board for 3 cm × 5 cm × 3 mm, with weight of 5.6 g. Results show that the proposed system demonstrates a promising performance in diagnosing the Alzheimer's disease using frequency domain analysis.

Trends in psychological distress and alcoholism after The Great East Japan Earthquake of 2011.

AIMS: Many studies have shown that natural disasters affect mental health; however, longitudinal data on post-disaster mental health problems are scarce. The aims of our study were to investigate the trend in psychological distress and alcoholism after The Great East Japan Earthquake and tsunami in north eastern Japan, in March 2011. METHODS: A longitudinal study was conducted using annual health check data for the general population, in the city of Higashi-Matsushima, which was affected by the high impact of tsunami. In 2012 and 2013, the Kessler Psychological Distress Scale and the CAGE questionnaire (for screening for alcoholism) were used to assess psychological distress and prevalence of alcoholism. RESULTS: Of 11,855 total eligible residents, 2192 received the annual check in 2012 and 2013. The prevalence of mental illness and the mean score of alcoholism tendency increased during the follow-up period. The majority of respondents (43.8%) with baseline serious mental illness (SMI) continued to have SMI at follow-up; only 16.7% reported recovering. Older age, female sex, and severity of home damage predicted higher psychological distress, while male sex was a risk factor for alcoholism at follow-up. CONCLUSIONS: Psychological distress deteriorated 2 years after the huge natural disaster, compared with 1 year after the disaster. Long-term mental health care is needed for those affected by natural disasters, particularly those who have suffered loss.

Acid-inhibitory effects of vonoprazan 20 mg compared with esomeprazole 20 mg or rabeprazole 10 mg in healthy adult male subjects--a randomised open-label cross-over study.

BACKGROUND: Proton pump inhibitors (PPIs) are widely used for the treatment of acid-related diseases. Vonoprazan is a member of a new class of acid suppressants; potassium-competitive acid blockers. Vonoprazan may thus be an alternative to PPIs. AIM: To evaluate efficacy, rapidity and duration of acid-inhibitory effects of vonoprazan vs. two control PPIs, esomeprazole and rabeprazole, in 20 healthy Japanese adult male volunteers with CYP2C19 extensive metaboliser genotype. METHODS: In this randomised, open-label, two-period cross-over study, vonoprazan 20 mg and esomeprazole 20 mg (Study V vs. E) or rabeprazole 10 mg (Study V vs. R) were orally administered daily for 7 days. Primary pharmacodynamic endpoint was gastric pH over 24 h measured as percentage of time pH ≥3, ≥4 and ≥5 (pH holding time ratios; HTRs) and mean gastric pH. RESULTS: Acid-inhibitory effect (pH4 HTR) of vonoprazan was significantly greater than that of esomeprazole or rabeprazole on both Days 1 and 7; Day 7 difference in pH4 HTR for vonoprazan vs. esomeprazole was 24.6% [95% confidence interval (CI): 16.2-33.1] and for vonoprazan vs. rabeprazole 28.8% [95% CI: 17.2-40.4]. The Day 1 to Day 7 ratio of 24-h pH4 HTRs was >0.8 for vonoprazan, compared with 0.370 for esomeprazole and 0.393 for rabeprazole. Vonoprazan was generally well tolerated. One vonoprazan subject withdrew due to a rash which resolved after discontinuation. CONCLUSIONS: This study demonstrated a more rapid and sustained acid-inhibitory effect of vonoprazan 20 mg vs. esomeprazole 20 mg or rabeprazole 10 mg. Therefore, vonoprazan may be a potentially new treatment for acid-related diseases.

Correlative cathodoluminescence and near-infrared fluorescence imaging for bridging from nanometer to millimeter scale bioimaging.

Correlative light and electron microscopy (CLEM) is one attractive method of observing biological specimens because it combines the advantages of both light microscopy (LM) and electron microscopy (EM). In LM, specimens are fully hydrated, and molecular species are distinguished based on the fluorescence colors of probes. EM provides both high-spatial-resolution images superior to those obtained with LM and ultrastructural information of cellular components. The combination of LM and EM gives much more information than either method alone, which helps us to analyze cellular function in more detail.We propose a Y2O3:Tm,Yb phosphor nanoparticle which allows upconversion luminescence (UCL) imaging with near-infrared (NIR) light excitation and cathodoluminescence (CL) imaging [1], where the light emission induced by an electron beam is called cathodoluminescence (CL). Due to electron beam excitation, the spatial resolution of CL microscopy is on the order of nanometers [2,3]. Upconversion is a process in which lower energy, longer wavelength excitation light is transduced to higher energy, shorter wavelength emission light. So far, in LM observation for CLEM, ultraviolet (UV) or visible light has been used for excitation. However, UV and visible light have limited ability to observe deep tissue regions due to absorption, scattering, and autofluorescence. On the other hand, NIR light does not suffer from these problems. Rare-earth-doped upconversion nanophosphors have been applied to biological imaging because of the advantages of NIR excitation [4].We investigated the UCL and CL spectra of Y2O3:Tm,Yb nanophosphors. Y2O3:Tm,Yb nanophosphors that emit visible and near-infrared UCL under 980nm irradiation and blue CL via electron beam excitation. To confirm bimodality of our nanophosphors, correlative UCL/CL images of the nanophosphors were obtained for the same region. The nanophosphors were poured onto a P doped Si substrate (Fig. 1(a)) and were irradiated with 980 nm NIR CW laser light or an electron beam. Fig. 1(b) shows the UCL image of the nanophosphors under 980 nm NIR CW laser irradiation, UCL spots were observed, but the individual nanophosphors in each spot were difficult to distinguish in the UCL image. On the other hand, the edges and the gap between the nanophosphors were clearly distinguished in the CL image (Fig. 1(c)), showing that the spatial-resolution of CL imaging was enough higher than that of UCL image. We believe that upconversion phosphors of the type described here will allow the realization of new CLEM imaging techniques covering the nanometer to millimeter scale, i.e., the molecular to in vivo scale.jmicro;63/suppl_1/i29/DFU073F1F1DFU073F1Fig. 1.(a) SEM and correlative (b) UCL (intensity of 980 nm NIR CW laser 8 mW) and (c) CL images of Y2O3:Tm,Yb nanophosphors in same region (accelerating voltage 3 kV, exposure time 100 ms/pixel).

Link between automated coronary calcium volumes from intravascular ultrasound to automated carotid IMT from B-mode ultrasound in coronary artery disease population.

AIM: Establishing relationship between coronary calcium volumes from Intravascular Ultrasound (IVUS) and automated carotid intima-media thickness (cIMT) helps in understanding the genetic nature of atherosclerosis disease. In this research, we have quantified the detected calcium from IVUS video frames and associated a relationship between coronary calcium volumes computed and automated cIMT from B-mode ultrasound. METHODS: Coronary calcium volume is computed from IVUS and auto cIMTs are computed using B-mode ultrasound. An automated computer based application is developed and tested on 100 patient volumes (an average of 2549 frames per volume) to calculate lesion area and normalized coronary calcium volume. We use an integrated approach for volume computation which is based on lesion area per frame. We have measured the normalized volume from the calcium detected video frames using proposed integration method. The cIMT of 100 carotids were measured with novel and dedicated automated software analysis (AtheroEdge™ from AtheroPoint™ LLC, Roseville, CA, USA). RESULTS: The computer-based coronary calcium volume (from IVUS) showed a correlation coefficient with respect to cIMT for left and right carotids as 9.1% and 13.9%, respectively. CONCLUSION: Coronary calcium volume computed from IVUS and auto cIMT are moderately correlated. The association between auto cIMT (right side) vs. computer-based coronary calcium volume (IVUS) is stronger than the association between auto cIMT (left side) vs. computer-based coronary calcium volume.

Tropomyosin-related receptor kinase B at the invasive front and tumour cell dedifferentiation in gastric cancer.

BACKGROUND: Tropomyosin-related receptor kinase B (TrkB) promotes proliferation and invasion, relating to poor prognosis of various malignancies. We examined the role of TrkB at the invasive front of gastric cancer (GC) and its association with tumour cell dedifferentiation and tumour budding. METHODS: Immunoreactive TrkB was evaluated at the tumour centre and margin using whole-tissue sections of 320 GC patients. Tumour cell dedifferentiation was defined as higher histologic grade at the tumour margin than the surface or tumour centre. Tumour budding was also scored on cytokeratin-stained sections. RESULTS: Sixty-five patients (20%) showed higher TrkB expression at the invasive front (TrkB expression was higher at the tumour margin than tumour centre). It was significantly associated with several aggressive phenotypes in the full cohort (n=320). It showed a prognostic significance in test subgroup (n=98) and was identified as an independent prognostic factor (HR=2.09; 95% CI: 1.26-3.53) by multivariate analysis in validation subgroup (n=222). Twenty-one patients showed tumour cell dedifferentiation. In predominantly differentiated tumour, higher TrkB at the invasive front was significantly associated with tumour budding rather than tumour cell dedifferentiation. CONCLUSIONS: Assessment of immunoreactive TrkB at the invasive front by whole-tissue sections provides prognostic information for GC patients.