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Background and Aims: The outcome of patients with HCC who achieved complete response (CR) to immune-checkpoint inhibitor (ICI)-based systemic therapies is unclear., Approach and Results: Retrospective study of patients with HCC who had CR according to modified Response Evaluation Criteria in Solid Tumors (CR-mRECIST) to ICI-based systemic therapies from 28 centers in Asia, Europe, and the United States. Of 3933 patients with HCC treated with ICI-based noncurative systemic therapies, 174 (4.4%) achieved CR-mRECIST, and 97 (2.5%) had CR according to RECISTv1.1 (CR-RECISTv1.1) as well. The mean age of the total cohort (male, 85%; Barcelona-Clinic Liver Cancer-C, 70%) was 65.9±9.8 years. The majority (83%) received ICI-based combination therapies. Median follow-up was 32.2 (95% CI: 29.9-34.4) months. One- and 3-year overall survival rates were 98% and 86%. One- and 3-year recurrence-free survival rates were excellent in patients with CR-mRECIST-only and CR-RECISTv1.1 (78% and 55%; 70% and 42%). Among patients who discontinued ICIs for reasons other than recurrence, those who received immunotherapy for ≥6 months after the first mRECIST CR had a longer recurrence-free survival than those who discontinued immunotherapy earlier (p=0.008). Of 9 patients who underwent curative surgical conversion therapy, 8 (89%) had pathological CR (CR-RECISTv1.1, n= 2/2; CR-mRECIST-only, n= 6/7)., Conclusions: Overall survival and recurrence-free survival of patients with CR-mRECIST-only and CR-RECISTv1.1 were excellent, and 6 of 7 patients with CR-mRECIST-only who underwent surgical conversion therapy had pathological CR. Despite potential limitations, these findings support the use of mRECIST in the context of immunotherapy for clinical decision-making. When considering ICI discontinuation, treatment for at least 6 months beyond CR seems advisable., (Copyright © 2024 American Association for the Study of Liver Diseases.)

Background & Aims: Atezolizumab/bevacizumab (atezo/bev) and lenvatinib have demonstrated efficacy as first-line therapies for hepatocellular carcinoma (HCC). However, vascular endothelial growth factor (VEGF) inhibition with these therapies may be associated with the risk of bleeding and thromboembolic events. In this study, we evaluated the efficacy and safety with focus on the bleeding and thromboembolic events of atezo/bev vs . lenvatinib in a large, multicenter real-world population., Methods: This study is based on HCC cohorts from seven centers in Germany and Austria. Incidences of bleeding or thromboembolic events and efficacy outcomes were assessed and compared., Results: In total, 464 patients treated with atezo/bev (n = 325) or lenvatinib (n = 139) were analyzed. Both groups were balanced with respect to demographics, presence of liver cirrhosis, and variceal status. Duration of therapy did not differ between groups. Within 3 months of therapy, bleeding episodes were described in 57 (18%) patients receiving atezo/bev compared with 15 (11%) patients receiving lenvatinib ( p  = 0.07). Variceal hemorrhage occurred in 11 (3%) patients treated with atezo/bev compared with 4 (3%) patients treated with lenvatinib ( p  = 0.99). Thromboembolic events were reported in 19 (6%) of patients in the atezo/bev cohort compared with 5 (4%) patients in the lenvatinib cohort ( p  = 0.37). In addition, incidence of overall bleeding, variceal hemorrhage, and thromboembolic events did not differ significantly in patients who received either atezo/bev or lenvantinib for 6 months., Conclusions: Safety considerations related to bleeding and thromboembolic events may not be helpful in guiding clinical decision-making when choosing between atezo/bev and lenvatinib., Impact and Implications: The inhibition of VEGF by current first-line therapies for HCC, such as atezolizumab/bevacizumab or lenvatinib, may be associated with the risk of bleeding and thromboembolic events. Studies comparing the incidence of these side effects between atezolizumab/bevacizumab and lenvatinib, which are preferred treatments over sorafenib for HCC, are needed. Differences in this side effect profile may influence the choice of first-line therapy by treating physicians. Because no significant differences were observed regarding bleeding or thromboembolic events between both therapies in the present study, we conclude that safety considerations related to these events may not be helpful in guiding clinical decision-making when choosing between atezolizumab/bevacizumab and lenvatinib., Competing Interests: NBK has received reimbursement of meeting attendance fees and travel expenses from EISAI and lecture honoraria from the Falk Foundation and AstraZeneca. UE has received honoraria for lectures from AstraZeneca, the Falk Foundation, Ipsen, and Novartis and travel support from AstraZeneca and Biotest. She has served as an advisory board or steering committee member to AstraZeneca, Bayer, EISAI, and MSD. KB has received honoraria for lectures from Ipsen. MP served as a speaker and/or consultant and/or advisory board member for AstraZeneca, Bayer, Bristol-Myers Squibb, Eisai, Ipsen, Lilly, MSD, and Roche and received travel support from Bayer, Bristol-Myers Squibb, Ipsen, and Roche. BS received grant support from AstraZeneca and Eisai; speaker honoraria from Eisai; and travel support from AbbVie, AstraZeneca, Ipsen and Gilead. OÖ received honorarium from Bayer. MV has received honoraria for her speaker, consultancy, and advisory roles from Amgen, AstraZeneca, Bayer, BMS, EISAI, Ipsen, Lilly, Merck Serono, MSD, Nordic Pharma, Roche, Servier, and Sirtex. SJG has received travel expenses from Gilead and Ipsen. FF has received honoraria for lectures from AstraZeneca, MSD, Pfizer, and Roche and reimbursement of meeting attendance fees and travel expenses from Merck KGaA and Servier. He has served as an advisory board or steering committee member to AstraZeneca, BMS, Eisai, and Roche. ENDT has served as a paid consultant for AstraZeneca, Bayer, BMS, EISAI, Eli Lilly & Co, Pfizer, Ipsen, and Roche. He has received reimbursement of meeting attendance fees and travel expenses from Arqule, AstraZeneca, BMS, Bayer, Celsion, and Roche and lecture honoraria from BMS and Falk Foundation. He has received third-party funding for scientific research from Arqule, AstraZeneca, BMS, Bayer, Eli Lilly, and Roche. AG is an advisory board or steering committee member to AbbVie, Alexion, Bayer, BMS, CSL Behring, Eisai, Falk, Gilead, Heel, Intercept, Ipsen, Merz, MSD, Novartis, Pfizer, Roche, Sanofi-Aventis, and Sequana and a speaker for Advanz. FPR has received honoraria for lectures, consulting activities, and travel support from the Falk Foundation, AbbVie, Gilead, Ipsen, AstraZeneca, Roche and Novartis. All other authors report no conflicts of interest. MM, LSJ, CL, LB, AW, HBL, VZ, LY, JS, IP, MR, FS, and JM have nothing to declare. Please refer to the accompanying ICMJE disclosure forms for further details., (© 2024 The Author(s).)

Background: Robotic surgery was introduced in the early 2000s but its use remains limited, particularly in thoracic surgery. Here we compare the first consecutive 185 four-arm robotic procedures carried out in our institution vs. muscle-sparing video-assisted mini-thoracotomy (MSMT), our previous minimally invasive approach for anatomical lung resection., Methods: One hundred and eighty-five consecutive patients undergoing surgery using the four-arm robotic technique between February 2014 and December 2016 were compared to a control historical series of 136 consecutive patients undergoing surgery by MSMT in the same institution. The same senior surgeon performed all surgical procedures. Comparisons between the two groups were performed using the Chi 2 test for qualitative data and the Wilcoxon, Mann-Whitney or Student's t -test for quantitative data., Results: The demographic and clinical characteristics of the patients were similar in the two groups. In the robotic group, median (min-max) length of hospital stay (LOS) was significantly shorter (by 2 days) than in the MSMT group {7 days [3-63] vs. 9 days [5-63], respectively; P<0.0001}. The rate of complications was similar in the two groups, but the complications appeared to be less severe in patients undergoing robotic surgery (switch from Clavien-Dindo grade III and IV to grade II) although further studies are required to confirm this due to the large number of missing data., Conclusions: In a senior thoracic surgery practice, the switch from a minimally invasive technique to robotic surgery was safe and beneficial in patients undergoing anatomical lung resection in terms of LOS and possible complication severity., Competing Interests: Conflicts of Interest: Marion Durand is an official proctor for Intuitive Surgical. The other authors have no conflicts of interest to declare.

Objective: Noninvasive ventilation has been successfully used after thoracic surgery. However, noninvasive ventilation fails in about 20% of patients. The aim of the study was to analyze episodes of noninvasive ventilation failure and to assess possible risk factors, while taking into account the performance of fiberoptic bronchoscopy for secretion management., Methods: From January 2006 to June 2008, the use of noninvasive ventilation was prospectively recorded after thoracic surgery. Data were retrospectively abstracted from charts, including the number of fiberoptic bronchoscopies performed. Risk factors associated with noninvasive ventilation failure were evaluated using logistic regression analysis to estimate odds ratios (ORs) and their 95% confidence intervals (CIs)., Results: During the study period, 664 patients were admitted in the intensive care unit (ICU) after lung resection or pulmonary thromboendarterectomy. A total of 135 patients underwent noninvasive ventilation (20.3%). As many as 40 of these 135 patients needed to be intubated (29.6%) and represented the noninvasive ventilation failure group. Patients with noninvasive ventilation failure had more fiberoptic bronchoscopies performed compared with patients with noninvasive ventilation success: 3 (1-5) versus 1 (0-3); p = 0.0008. Four independent variables were associated with noninvasive ventilation failure during the first 48 h of appliance: increased respiratory rate (OR: 4.17 (1.63-10.67); increased Sequential Organ Failure Assessment (SOFA) score (OR: 3.05 (1.12-8.34); number of fiberoptic bronchoscopies performed (OR: 1.60 (1.01-2.54); and number of hours spent on noninvasive ventilation (OR: 1.06 (1.01-1.11). Nosocomial pneumonia was the leading cause of respiratory complications and occurred in 21 and 6 patients with and without noninvasive ventilation failure, respectively (53% vs 6%; p < 0.0001). Patients in the failure group had a higher mortality rate (20% vs 0%; p < 0.0001)., Conclusions: Noninvasive ventilation failure is associated with higher mortality, but is merely a marker of progression of a more severe disease. This may at least indicate the need for caution in some patients. Interestingly, increased use of fiberoptic bronchoscopies during noninvasive ventilation appliance was identified as a risk factor of failure., (Copyright © 2010 European Association for Cardio-Thoracic Surgery. Published by Elsevier B.V. All rights reserved.)

Study Objective: To assess the value of the global end-diastolic volume (GEDV) evaluated by transpulmonary thermodilution as an indicator of cardiac preload., Design: Prospective clinical study., Setting: Medical ICU of a university hospital (20 beds)., Patients: Thirty-six patients with septic shock., Interventions: Volume loading and dobutamine infusion., Measurements and Results: Hemodynamic parameters were evaluated in triplicate by the transpulmonary thermodilution technique: (1) before and after 66 fluid challenges in 27 patients, and (2) before and after 28 increases in dobutamine infusion rate in 9 patients. Volume loading induced a significant (p < 0.001) increase in central venous pressure (CVP) from 10 +/- 4 to 13 +/- 4 mm Hg, in GEDV index from 711 +/- 164 to 769 +/- 144 mL/m(2), in stroke volume index (SVI) from 36 +/- 12 to 42 +/- 12 mL/m(2), and in cardiac index (CI) from 3.4 +/- 1.1 to 3.9 +/- 1.2 L/min/m(2) (mean +/- SD). Changes in GEDV index were correlated (r = 0.72, p < 0.001) with changes in SVI, while changes in CVP were not. The increase in SVI was > 15% in 32 of 66 instances (positive response). The preinfusion GEDV index was lower (637 +/- 134 mL/m(2) vs 781 +/- 161 mL/m(2), p < 0.001) in the cases of positive response, and was negatively correlated with the percentage increase in GEDV index (r = - 0.65, p < 0.001) and in SVI (r = - 0.5, p < 0.001). Dobutamine infusion induced an increase in SVI (32 +/- 11 mL/m(2) vs 35 +/- 12 mL/m(2), p < 0.05) and in CI (2.8 +/- 0.6 L/min/m(2) vs 3.2 +/- 0.6 L/min/m(2), p < 0.001) but no significant change in CVP (13 +/- 3 mm Hg vs 13 +/- 3 mm Hg) and in GEDV index (823 +/- 221 mL/m(2) vs 817 +/- 202 mL/m(2))., Conclusion: In patients with septic shock, our findings demonstrate that, in contrast to CVP, the transpulmonary thermodilution GEDV index behaves as an indicator of cardiac preload.

The recent discovery that sporadic and familial primary pulmonary hypertension can be associated with germline mutations of genes encoding receptor members of the transforming growth factor-beta family has focused much attention on cytokines and growth factors in pulmonary vascular disorders. Production of several cytokines has been demonstrated in severe pulmonary arterial hypertension, emphasizing the possible influence of inflammatory mechanisms in this condition. Moreover, perivascular inflammatory cell infiltrates composed of macrophages and lymphocytes have been detected in plexiform lesions of primary pulmonary hypertension. Chemokine RANTES is an important chemoattractant for monocytes and T cells. We therefore hypothesize that chemokine RANTES promotes cell recruitment in the lungs of patients displaying severe pulmonary arterial hypertension. Reverse transcriptase polymerase chain reaction demonstrated elevated RANTES mRNA expression in 10 lung samples from patients with severe pulmonary arterial hypertension, as compared with seven control subjects. In situ hybridization and immunohistochemistry confirmed that endothelial cells were the major source of RANTES within the pulmonary artery wall of the patients. Serial sections analysis showed that RANTES expression was associated with CD45+ inflammatory cell infiltrates. These results support the concept that inflammatory mechanisms play a role in the natural history of pulmonary arterial hypertension.

The aim of our study was to evaluate the prognostic value of serum procalcitonine (PCT) assay in adult respiratory infections. Forty-nine patients admitted with pleurisy, community-acquired pneumonia, tuberculosis, infection were included in this prospective study. PCT was assayed on admission and discharge. Biological and clinical parameters of gravity were also evaluated. Twenty patients had elevated PCT of more than 0.50 ng/ml. In 29 patients, PCT was undetectable. The serum PCT level was normal in the patients with tuberculosis, infection, pneumocytosis. PCT did not correlate with the biological and clinical markers of the disease severity but the evolution of PCT correlated with the evolution of C-reactive-protein (r = 0.58, p < 0.05). PCT seems to be an early marker of the evolution of respiratory infections, but it does not help to establish prognosis. Further studies are necessary to assess the potential value of PCT in more severe respiratory infections requiring assisted ventilation.

In our study, the rate of pregnancy by transfer and puncture was not significantly different in unexplained and in tubal infertility, but the mean number of transferred embryos was significantly higher in the first group. To explain these data, we compared the quality of embryos in 32 punctures realized among 29 women with unexplained infertility and in 171 punctures planned among 156 women with tubal infertility. The percentage of embryos with 4 or more blastomeres was significantly lower in the unexplained infertility group than in the pure tubal infertility group.