Objectives: To study the prognostic value of vascular endothelial growth factor (VEGF)-A and its ... more Objectives: To study the prognostic value of vascular endothelial growth factor (VEGF)-A and its receptor VEGFR-1 in localized prostate cancer. Methods: One hundred patients undergoing radical prostatectomy (RP) for clinically localized prostate cancer were prospectively included. Plasma levels of VEGF-A were measured preoperatively. After intervention, tissue microarrays were built from the RP specimens. VEGF-A and VEGFR-1 expressions in prostate cancer tissue were determined using immunochemistry. Then the associations between plasma levels of VEGF-A, VEGF-A and VEGFR-1 expressions in prostate cancer tissue, and the outcome of patients were analyzed. Results: After a median follow-up of 22 months, 14 patients experienced biological recurrence of prostate cancer. There was no correlation between plasma VEGF-A and the risk of recurrence following RP. Moreover, there was no correlation between VEGF-A expression or VEGFR-1 expression in prostate cancer tissue and the risk of recurrence after RP. Conclusions: Plasma levels of VEGF-A, the expression of VEGF-A and that of VEGFR-1 in prostate cancer tissue did not affect patients outcome following RP. VEGF-A and its receptor VEGFR-1 may have no prognostic value in localized prostate cancer. Further studies with longer follow-up are mandatory to confirm these findings.
Objective Stratifying the risk of death in SSc-related interstitial lung disease (SSc-ILD) is a c... more Objective Stratifying the risk of death in SSc-related interstitial lung disease (SSc-ILD) is a challenging issue. The extent of lung fibrosis on high-resolution CT (HRCT) is often assessed by a visual semiquantitative method that lacks reliability. We aimed to assess the potential prognostic value of a deep-learning–based algorithm enabling automated quantification of ILD on HRCT in patients with SSc. Methods We correlated the extent of ILD with the occurrence of death during follow-up, and evaluated the additional value of ILD extent in predicting death based on a prognostic model including well-known risk factors in SSc. Results We included 318 patients with SSc, among whom 196 had ILD; the median follow-up was 94 months (interquartile range 73–111). The mortality rate was 1.6% at 2 years and 26.3% at 10 years. For each 1% increase in the baseline ILD extent (up to 30% of the lung), the risk of death at 10 years was increased by 4% (hazard ratio 1.04, 95% CI 1.01, 1.07, P = 0.004...
Background: RhoA/Rho kinase (ROCK) pathway is important in regulating vascular tone and vascular ... more Background: RhoA/Rho kinase (ROCK) pathway is important in regulating vascular tone and vascular remodelling in pulmonary hypertension (PH). It has been shown to be altered in the bleomycin-induced pulmonary fibrosis (PF) and PH in mice. However, the exact mechanism by which it leads to PF and PH remains to be clarified. Objectives: The present study aimed to assess whether fasudil, a ROCK inhibitor, is able to inhibit PF and PH induced by bleomycin in mice. Methods: Male C57BL/6 mice were randomized into 3 groups: G1 (saline), G2 (bleomycin) and G3 (bleomycin + fasudil). Bleomycin (3.3U/kg) was given intratracheally (day 0) and fasudil (30mg/kg/d) intraperitoneally from day -1 during 21 days. Right ventricular systolic pressure (RVSP) was measured by RV puncture at 7, 14, and 21 days, followed by sacrifice and lung and heart samplings for collagen analysis. Results: Pulmonary fibrosis was present at 7 days, and became more apparent at 14 days. RVSP increased at 14 days, accompanied by right ventricular hypertrophy. Fasudil improved survival, reversed PF and attenuated PH. Conclusions: The efficacy of the ROCK inhibitor, Fasudil, suggests that RhoA/ROCK is involved in causing PF and PH induced by bleomycin in mice.
Previous studies have highlighted a decreased exhaled nitric oxide concentration (FE NO) in diver... more Previous studies have highlighted a decreased exhaled nitric oxide concentration (FE NO) in divers after hyperbaric exposure in a dry chamber or following a wet dive. The underlying mechanisms of this decrease remain however unknown. The aim of this study was to quantify the separate effects of submersion, hyperbaric hyperoxia exposure and decompression-induced bubble formation on FE NO after a wet dive. Healthy experienced divers (n=31) were assigned to either (i) a group making a scuba-air dive (Air dive), (ii) a group with a shallow oxygen dive protocol (Oxygen dive) or (iii) a group making a deep dive breathing a trimix gas mixture (deep-dive). Bubble signals were graded with the KISS score. Before and after each dive FE NO values were measured using a hand-held electrochemical analyzer. There was no change in post-dive values of FE NO values (expressed in ppb=parts per billion) in the Air dive group (15.1 ± 3.6 ppb vs. 14.3 ± 4.7 ppb, n=9, p=0.32). There was a significant decrease in post-dive values of FE NO in the Oxygen dive group (15.6 ± 6 ppb vs. 11.7 ± 4.7 ppb, n=9, p=0.009). There was an even more pronounced decrease in the deep dive group (16.4 ± 6.6 ppb vs. 9.4 ± 3.5 ppb, n=13, p<0.001) and a significant correlation between KISS bubble score >0 (n=13) and percentage decrease in post-dive FE NO values (r=-0.53, p=0.03). Submersion and hyperbaric hyperoxia exposure cannot account entirely for these results suggesting the possibility that, in combination, one effect magnifies the other. A main finding of the present study is a significant relationship between reduction in exhaled NO concentration and dive-induced bubble formation. We postulate that exhaled NO concentration could be a useful index of decompression severity in healthy human divers.
Objectives: To study the prognostic value of vascular endothelial growth factor (VEGF)-A and its ... more Objectives: To study the prognostic value of vascular endothelial growth factor (VEGF)-A and its receptor VEGFR-1 in localized prostate cancer. Methods: One hundred patients undergoing radical prostatectomy (RP) for clinically localized prostate cancer were prospectively included. Plasma levels of VEGF-A were measured preoperatively. After intervention, tissue microarrays were built from the RP specimens. VEGF-A and VEGFR-1 expressions in prostate cancer tissue were determined using immunochemistry. Then the associations between plasma levels of VEGF-A, VEGF-A and VEGFR-1 expressions in prostate cancer tissue, and the outcome of patients were analyzed. Results: After a median follow-up of 22 months, 14 patients experienced biological recurrence of prostate cancer. There was no correlation between plasma VEGF-A and the risk of recurrence following RP. Moreover, there was no correlation between VEGF-A expression or VEGFR-1 expression in prostate cancer tissue and the risk of recurrence after RP. Conclusions: Plasma levels of VEGF-A, the expression of VEGF-A and that of VEGFR-1 in prostate cancer tissue did not affect patients outcome following RP. VEGF-A and its receptor VEGFR-1 may have no prognostic value in localized prostate cancer. Further studies with longer follow-up are mandatory to confirm these findings.
Objective Stratifying the risk of death in SSc-related interstitial lung disease (SSc-ILD) is a c... more Objective Stratifying the risk of death in SSc-related interstitial lung disease (SSc-ILD) is a challenging issue. The extent of lung fibrosis on high-resolution CT (HRCT) is often assessed by a visual semiquantitative method that lacks reliability. We aimed to assess the potential prognostic value of a deep-learning–based algorithm enabling automated quantification of ILD on HRCT in patients with SSc. Methods We correlated the extent of ILD with the occurrence of death during follow-up, and evaluated the additional value of ILD extent in predicting death based on a prognostic model including well-known risk factors in SSc. Results We included 318 patients with SSc, among whom 196 had ILD; the median follow-up was 94 months (interquartile range 73–111). The mortality rate was 1.6% at 2 years and 26.3% at 10 years. For each 1% increase in the baseline ILD extent (up to 30% of the lung), the risk of death at 10 years was increased by 4% (hazard ratio 1.04, 95% CI 1.01, 1.07, P = 0.004...
Background: RhoA/Rho kinase (ROCK) pathway is important in regulating vascular tone and vascular ... more Background: RhoA/Rho kinase (ROCK) pathway is important in regulating vascular tone and vascular remodelling in pulmonary hypertension (PH). It has been shown to be altered in the bleomycin-induced pulmonary fibrosis (PF) and PH in mice. However, the exact mechanism by which it leads to PF and PH remains to be clarified. Objectives: The present study aimed to assess whether fasudil, a ROCK inhibitor, is able to inhibit PF and PH induced by bleomycin in mice. Methods: Male C57BL/6 mice were randomized into 3 groups: G1 (saline), G2 (bleomycin) and G3 (bleomycin + fasudil). Bleomycin (3.3U/kg) was given intratracheally (day 0) and fasudil (30mg/kg/d) intraperitoneally from day -1 during 21 days. Right ventricular systolic pressure (RVSP) was measured by RV puncture at 7, 14, and 21 days, followed by sacrifice and lung and heart samplings for collagen analysis. Results: Pulmonary fibrosis was present at 7 days, and became more apparent at 14 days. RVSP increased at 14 days, accompanied by right ventricular hypertrophy. Fasudil improved survival, reversed PF and attenuated PH. Conclusions: The efficacy of the ROCK inhibitor, Fasudil, suggests that RhoA/ROCK is involved in causing PF and PH induced by bleomycin in mice.
Previous studies have highlighted a decreased exhaled nitric oxide concentration (FE NO) in diver... more Previous studies have highlighted a decreased exhaled nitric oxide concentration (FE NO) in divers after hyperbaric exposure in a dry chamber or following a wet dive. The underlying mechanisms of this decrease remain however unknown. The aim of this study was to quantify the separate effects of submersion, hyperbaric hyperoxia exposure and decompression-induced bubble formation on FE NO after a wet dive. Healthy experienced divers (n=31) were assigned to either (i) a group making a scuba-air dive (Air dive), (ii) a group with a shallow oxygen dive protocol (Oxygen dive) or (iii) a group making a deep dive breathing a trimix gas mixture (deep-dive). Bubble signals were graded with the KISS score. Before and after each dive FE NO values were measured using a hand-held electrochemical analyzer. There was no change in post-dive values of FE NO values (expressed in ppb=parts per billion) in the Air dive group (15.1 ± 3.6 ppb vs. 14.3 ± 4.7 ppb, n=9, p=0.32). There was a significant decrease in post-dive values of FE NO in the Oxygen dive group (15.6 ± 6 ppb vs. 11.7 ± 4.7 ppb, n=9, p=0.009). There was an even more pronounced decrease in the deep dive group (16.4 ± 6.6 ppb vs. 9.4 ± 3.5 ppb, n=13, p<0.001) and a significant correlation between KISS bubble score >0 (n=13) and percentage decrease in post-dive FE NO values (r=-0.53, p=0.03). Submersion and hyperbaric hyperoxia exposure cannot account entirely for these results suggesting the possibility that, in combination, one effect magnifies the other. A main finding of the present study is a significant relationship between reduction in exhaled NO concentration and dive-induced bubble formation. We postulate that exhaled NO concentration could be a useful index of decompression severity in healthy human divers.
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Papers by A. Dinh-xuan