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Background: Transcatheter aortic valve implantation is an established, guideline-endorsed treatment for severe aortic stenosis. Precise sizing of the balloon-expandable Myval transcatheter heart valve (THV) series with the aortic annulus is facilitated by increasing its diameter in 1·5 mm increments, compared with the usual 3 mm increments in valve size. The LANDMARK trial aimed to show non-inferiority of the Myval THV series compared with the contemporary THVs Sapien Series (Edwards Lifesciences, Irvine, CA, USA) or Evolut Series (Medtronic, Minneapolis, MN, USA)., Methods: In this prospective, multinational, randomised, open-label, non-inferiority trial across 31 hospitals in 16 countries (Germany, France, Sweden, the Netherlands, Italy, Spain, New Zealand, Portugal, Greece, Hungary, Poland, Slovakia, Slovenia, Croatia, Estonia, and Brazil), 768 participants with severe symptomatic native aortic stenosis were randomly assigned (1:1) to the Myval THV or a contemporary THV. Eligibility was primarily decided by the heart team in accordance with 2021 European Society of Cardiology guidelines. As per the criteria of the third Valve Academic Research Consortium, the primary endpoint at 30 days was a composite of all-cause mortality, all stroke, bleeding (types 3 and 4), acute kidney injury (stages 2-4), major vascular complications, moderate or severe prosthetic valve regurgitation, and conduction system disturbances resulting in a permanent pacemaker implantation. Non-inferiority of the study device was tested in the intention-to-treat population using a non-inferiority margin of 10·44% and assuming an event rate of 26·10%. This trial is registered with ClinicalTrials.gov, NCT04275726, and EudraCT, 2020-000137-40, and is closed to new participants., Findings: Between Jan 6, 2021, and Dec 5, 2023, 768 participants with severe symptomatic native aortic stenosis were randomly assigned, 384 to the Myval THV and 384 to a contemporary THV. 369 (48%) participants had their sex recorded as female, and 399 (52%) as male. The mean age of participants was 80·0 years (SD 5·7) for those treated with the Myval THV and 80·4 years (5·4) for those treated with a contemporary THV. Median Society of Thoracic Surgeons scores were the same in both groups (Myval 2·6% [IQR 1·7-4·0] vs contemporary 2·6% [1·7-4·0]). The primary endpoint showed non-inferiority of the Myval (25%) compared with contemporary THV (27%), with a risk difference of -2·3% (one-sided upper 95% CI 3·8, p non-inferiority <0·0001). No significant difference was seen in individual components of the primary composite endpoint., Interpretation: In individuals with severe symptomatic native aortic stenosis, the Myval THV met its primary endpoint at 30 days., Funding: Meril Life Sciences., Competing Interests: Declaration of interests NvR reports grant funding and personal fees from Abbott; grants from Philips, Biotronik, and Medtronic; and personal fees from MicroPort, Bayer, and RainMed Medical outside the submitted work. IJA-S reports being a proctor for Medtronic, Boston Scientific, and Meril Life Sciences. AIj reports consulting fees from Meril Life Sciences, Medtronic, Angiocare, Keystone Heart, PulseCath, Salveo, Abbott, Philips, Fysicon, Cardiawave, Pi Medical, and Svelte. DU reports lecture and educational event fees from Medtronic; a lecture fee from and being a proctor for Meril Life Sciences; and being a member of the Medtronic EMEA surgical advisory board. RSH reports grant funding from Bayer; and speaker fees from Amgen, Novartis, and Abbott outside the submitted work. MW reports institutional research funding from Emboline, Meril Life Sciences, Edwards Lifesciences, and TransAortic Medical. MPa reports honoraria from Boston Scientific, Philips, and Abbott. OA reports research grants and lecture fees from and being a proctor for Abbott; and advisory board participation for and support for attending meetings from Meril Life Sciences. W-KK reports honoraria or consultancy fees from Abbott, Boston Scientific, Edwards Lifesciences, Meril Life Sciences, and Hi-D Imaging; and participation on an advisory board or data and safety monitoring board for Abbott and Boston Scientific. JR reports being a consultant with Medtronic and Qatma; being a proctor for Medtronic; and travel support for attending meetings from Meril Life Sciences, Edwards Lifesciences, Abbott, Medtronic, and Boston Scientific. AT reports a grant from the Fukuda Foundation for Medical Technology. SG reports honoraria or consultancy fees from Biosensors. PWS reports consultancy fees from SMT, Novartis, Meril Life Sciences, Xeltis, and Philips. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: Resolute Onyx polymer-based zotarolimus-eluting stents (ZES) were noninferior in safety and effectiveness to BioFreedom polymer-free biolimus A9-coated stents (DCS) in high-bleeding-risk (HBR) patients treated with 1-month dual antiplatelet therapy (DAPT) followed by single antiplatelet therapy (SAPT) at 1 year., Objectives: This study reports the final 2-year results of the randomized Onyx ONE trial., Methods: The Onyx ONE (A Randomized Controlled Trial With Resolute Onyx in One Month Dual Antiplatelet Therapy (DAPT) for High-Bleeding Risk Patients) trial randomly assigned HBR patients to treatment with ZES or DCS. Following 1-month DAPT, event-free patients received SAPT (either aspirin or a P2Y 12 inhibitor at physician discretion). The primary safety endpoint, a composite of cardiac death, myocardial infarction, or stent thrombosis at 1 year, was determined at 1 year. Rates of primary and secondary endpoints were calculated after final follow-up at 2 years., Results: A total of 1,003 patients were randomly allocated to ZES and 993 patients to DCS. Follow-up was complete in 980 (97.7%) ZES patients and 962 (96.9%) DCS patients at 2 years. The primary safety endpoint occurred in 208 (21.2%) patients in the ZES group and 199 (20.7%) patients in the DCS group (risk difference: 0.5%; 95% CI: -3.1% to 4.2%; P = 0.78) at 2 years without significant differences in individual components of the composite endpoint. The secondary effectiveness endpoint occurred in 217 (22.1%) patients in the ZES group and 202 (21.0%) patients in the DCS group (risk difference: 1.1%; 95% CI: -2.5% to 4.8%; P = 0.54)., Conclusions: Among patients at HBR treated with 1-month DAPT followed by SAPT, the Resolute Onyx polymer-based ZES had similar 2-year outcomes for the primary safety and secondary effectiveness endpoint compared with the BioFreedom polymer-free DCS. (A Randomized Controlled Trial With Resolute Onyx in One Month Dual Antiplatelet Therapy [DAPT] for High-Bleeding Risk Patients [Onyx ONE]; NCT03344653)., Competing Interests: Funding Support and Author Disclosures The Onyx ONE trial was sponsored by Medtronic. Dr Windecker has received research and educational grants to the institution from Abbott, Amgen, AstraZeneca, BMS, Bayer, Biotronik, Boston Scientific, Cardinal Health, CardioValve, CSL Behring, Daiichi-Sankyo, Edwards Lifesciences, Guerbet, InfraRedx, Johnson & Johnson, Medicure, Medtronic, Novartis, Polares, OrPha Suisse, Pfizer, Regeneron, Sanofi, Sinomed, Terumo, and V-Wave; served as an unpaid advisory board member and/or unpaid member of the steering/executive group of trials funded by Abbott, Abiomed, Amgen, AstraZeneca, BMS, Boston Scientific, Biotronik, CardioValve, Edwards Lifesciences, MedAlliance, Medtronic, Novartis, Polares, Sinomed, V-Wave, and Xeltis but has not received personal payments by pharmaceutical companies or device manufacturers; and has served as a member of the steering/executive committee group of several investigator-initiated trials that receive funding by industry without impact on his personal remuneration. Dr Latib has received consulting fees from Medtronic, Abbott Vascular, and Boston Scientific. Dr Kedhi has received speaker honoraria and institutional grants from Medtronic and Abbott Vascular. Dr Kirtane has received institutional funding to Columbia University and/or the Cardiovascular Research Foundation from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, ReCor Medical, and Neurotronic (in addition to research grants, institutional funding includes fees paid to Columbia University and/or the Cardiovascular Research Foundation for consulting and/or speaking engagements in which Dr Kirtane controlled the content); has served as a consultant for IMDS; and has received travel expenses/meals from Medtronic, Boston Scientific, Abbott Vascular, Abiomed, CSI, CathWorks, Siemens, Philips, ReCor Medical, Chiesi, OpSens, Zoll, and Regeneron. Dr Kandzari has received institutional research or grant support from Abbott Vascular, Biotronik, Boston Scientific, Cardiovascular Systems, Orbus Neich, Medtronic, and Ablative Solutions; and has received personal consulting honoraria from Cardiovascular Systems, Magenta Medical, and Medtronic. Dr Mehran has received institutional research grants from Abbott Laboratories, Abiomed, Applied Therapeutics, AstraZeneca, Bayer, Beth Israel Deaconess, Bristol Myers Squibb, CERC, Chiesi, Concept Medical, CSL Behring, DSI, Medtronic, Novartis Pharmaceuticals, and OrbusNeich; has received consulting fees from Abbott Laboratories, Boston Scientific, CardiaWave, Chiesi, Cine-Med Research, Janssen Scientific Affairs, Medscape/WebMD, Medtelligence (Janssen Scientific Affairs), Roivant Sciences, Sanofi, and Siemens Medical Solutions; has received consultant fees paid to the institution from Abbott Laboratories and Bristol Myers Squibb; has served on the advisory board, with funding paid to the institution, for Spectranetics/Philips/Volcano Corp; has a spouse who has served as a consultant for Abiomed, The Medicines Company, Merck; Equity <1% from Claret Medical, Elixir Medical, Applied Therapeutics, and STEL; has received Data Safety and Monitoring Board Membership fees paid to the institution from Watermark Research Partners; has served as a consultant (no fee) for Idorsia Pharmaceuticals and Regeneron Pharmaceuticals; and has served as an Associate Editor for the American College of Cardiology and the American Medical Association. Dr Price has received consulting fees and speaker honoraria from AstraZeneca, Abbott Vascular, Boston Scientific, and Medtronic; and has received consulting fees from Acutus, Baylis Medical, and W.L. Gore. Dr Simon has received honoraria for serving as a course director (<$10,000) from Medtronic. Dr Worthley has received institutional grant or research support from Abbott and Biotronik. Dr Zaman has received consulting fees from Abbott, Boston Scientific, Medtronic, Meril, SMT, and Terumo. Dr Petrov has received consulting, proctor, or speaker fees from Medtronic, Edwards, Philips, Cardiatis, Boehringer Ingelheim, Servier, and Pfizer. Dr Mylotte has received consulting fees from Medtronic, Boston Scientific, and MicroPort. Dr Moreno has received lecture or consulting fees from Medtronic, Biosensors, Abbott Vascular, Boston Scientific, Terumo, and Braun. Dr Pasupati has received consulting, proctor, or speaker fees from Medtronic, Edwards, Boston Scientific, JenaValve, BioExcel, Boehringer Ingelheim, and Pfizer. Dr Kim has received research grants through Seoul National University Hospital from Abbott, Medtronic, Biotronik, B. Braun, and Daiichi-Sankyo; and has received lecture and consulting fees from Edwards Lifesciences, Medtronic, Novartis, Pfizer, Daiichi-Sankyo, AmGen, AstraZeneca, and Boehringer Ingelheim. Dr Tie has received speaker fees from Boehringer Ingelheim, outside the submitted work. Dr Hur has received research grants from Boston Scientific and Terumo. Dr Marx has received an honorarium for Clinical Events Committee membership from the Cardiovascular Research Foundation. Dr Ali has received institutional grant support from Abiomed, Acist Medical, Abbott, Boston Scientific, Cardiovascular Systems, Philips, and Opsens Medical; has received consulting or advisory fees from Amgen and Boston Scientific; has received speaker honoraria from AstraZeneca; and owns equity in Shockwave Medical. Ms. Parke and Dr Lung are employees of Medtronic. Dr Stone has received speaker honoraria from Cook, Infraredx, Valfix, TherOx, Robocath, HeartFlow, Ablative Solutions, Vectorious, Miracor, Neovasc, Abiomed, Ancora, Elucid Bio, Occlutech, CorFlow, Apollo Therapeutics, Impulse Dynamics, Reva, Vascular Dynamics, Shockwave, V-Wave, Cardiomech, and Gore; and owns equity or options in Ancora, Cagent, Applied Therapeutics, the Biostar family of funds, SpectraWave, Orchestra Biomed, Aria, Cardiac Success, Valfix, and the MedFocus family of funds. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Small vessel diameter is associated with higher risk of target lesion revascularization (TLR) after percutaneous coronary intervention (PCI). The COMBO sirolimus-eluting biodegradable-polymer stent has a proprietary anti-CD34 antibody layer to enhance homogeneous endothelialization, which may be advantageous in treating small vessels., Objective: We examined for differences in 1-year clinical outcomes after PCI by maximum implanted stent diameter from the COMBO collaboration., Methods: The COMBO collaboration (n = 3614) is a patient-level pooled dataset of patients undergoing PCI with COMBO stents in the MASCOT and REMEDEE multicenter registries. Stent diameter was available in 3590 (99.3%) patients. We compared patients receiving COMBO stents <3 mm versus ≥3 mm. The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, target vessel-myocardial infarction (TV-MI) or clinically driven TLR. Secondary outcomes included stent thrombosis (ST). Adjusted outcomes were assessed using Cox regression methods., Results: The study included 792 (22%) patients with small stents <3 mm and 2798 (78%) patients with large stents ≥3 mm. Small stent patients included more women with lower body mass index and higher prevalence of diabetes but similar prevalence of acute coronary syndrome. Risk of 1-year TLF was similar in small and large stent groups (4.4% vs. 3.8%, HR 1.12, 95% CI 0.74-1.72, p = 0.58). There were no differences in the rates of cardiac death (1.7% vs. 1.5%, p = 0.74), TV-MI (1.4% vs. 1.2%, p = 0.58) or TLR (2.7% vs. 2.1%, p = 0.31). Definite or probable ST occurred in 1.3% of the small stent and 0.7% of the large stent PCI patients, p = 0.14, HR 2.13, 95% CI 0.93-5.00, p = 0.07., Conclusions: One-year ischemic outcomes after COMBO PCI were similar irrespective of stent diameter in this all-comers international cohort., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background: The COMBO drug-eluting stent combines sirolimus-elution from a biodegradable polymer with an anti-CD34+ antibody coating for early endothelialization., Objective: We investigated for geographical differences in outcomes after percutaneous coronary intervention (PCI) with the COMBO stent among Asians and Europeans., Methods: The COMBO Collaboration is a pooled patient-level analysis of the MASCOT and REMEDEE registries of all-comers undergoing attempted COMBO stent PCI. The primary outcome was 1-year target lesion failure (TLF), composite of cardiac death, target vessel myocardial infarction (TV-MI) and target lesion revascularization (TLR)., Results: This study included 604 Asians (17.9%) and 2775 Europeans (82.1%). Asians were younger and included fewer females, with a higher prevalence of diabetes mellitus but lower prevalence of other comorbidities than Europeans. Asians had a higher prevalence of ACC/AHA C type lesions and received longer stent lengths. More Asians than Europeans were discharged on clopidogrel (86.5% vs 62.8%) rather than potent P2Y 12  inhibitors. One-year TLF occurred in 4.0% Asians and 4.1% of Europeans, p = 0.93. The incidence of cardiac death was higher in Asians (2.8% vs. 1.3%, p = 0.007) with similar rates of TV-MI (1.5% vs. 1.2%, p = 0.54) and definite stent thrombosis (0.3% vs. 0.5%, p = 0.84) and lower incidence of TLR than Europeans (1.0% vs. 2.5%, p = 0.025). After adjustment, differences for cardiac death and TLR were no longer significant., Conclusions: In the COMBO collaboration, although 1-year TLF was similar regardless of geography, Asians experienced higher rates of cardiac death and lower TLR than Europeans, while incidence of TV-MI and ST was similar in both regions. Adjusted differences did not reach statistical significance. CLINICALTRIAL., Gov Identifier-Numbers: NCT01874002 (REMEDEE Registry), NCT02183454 (MASCOT registry)., Competing Interests: Declaration of competing interest Dr. Mehran has received institutional research grant support from Eli Lilly/Daiichi-Sankyo Inc., AstraZeneca, The Medicines Company, Bristol-Myers Squibb, OrbusNeich, Beth Israel Deaconess, and Bayer; has served as a consultant for Boston Scientific, Cardiovascular Systems Inc., Medscape, and Shanghai BraccoSine Pharmaceutical; has received institutional advisory board funding from Bristol-Myers Squibb; has received institutional funding from Claret Medical; owns equity in Claret Medical and Elixir Medical; has served on the executive committee for Janssen Pharmaceuticals and Osprey Medical; has served on the data safety monitoring board for Watermark Research Partners; and has a spouse who has served as a consultant for Abiomed and the Medicines Company. Dr. Kala has served as a consultant for Boston Scientific; has received research support from AstraZeneca, Novartis, Zoll; has served on advisory board for Astra Zeneca, Bayer, Medtronic and Boston Scientific. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: The COMBO stent (OrbusNeich Medical, Ft. Lauderdale, Florida) is a new-generation bio-engineered drug eluting stent, combining an abluminal coating of a bioabsorbable polymer matrix for sustained release of sirolimus and luminal anti-CD34 coating for endothelial progenitor cell capture and rapid endothelialization., Methods: The Multinational Abluminal Sirolimus Coated BiO-Engineered StenT (MASCOT) registry was a prospective post-marketing study conducted from June 2014-May 2017 across 60 centers globally. Patients were eligible if COMBO stent implantation was attempted, and they received dual antiplatelet therapy (DAPT) per local guidelines. Follow-up was conducted by trained research staff at 1, 6 and 12 months by phone or clinic visit to capture clinical events and DAPT cessation events. The primary endpoint was 1-year target lesion failure (TLF), composite of cardiac death, non-fatal myocardial infarction not clearly attributable to a non-target vessel, or ischemia-driven target lesion revascularization., Results: A total of 2614 patients were enrolled over the study period with 96.7% completion of 1-year follow-up. The mean age of enrolled patients was 62.9 ± 11.2 years and 23.0% were female. Diabetes mellitus was present at baseline in 33.5%. A total of 56.1% patients underwent PCI for acute coronary syndrome (ACS). The 1-year primary endpoint of TLF occurred in 3.4% patients (n = 88). Definite stent thrombosis occurred in 0.5% patients (n = 12)., Conclusion: The MASCOT post marketing registry provides comprehensive safety and efficacy outcomes following contemporary PCI using the novel COMBO stent in an all-comer population. This platform is associated with low rates of 1-year TLF and ST. CLINICALTRIALS., Gov Identifier: NCT02183454., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Patients with severe aortic stenosis present frequently (∼50%) with concomitant obstructive coronary artery disease. Current guidelines recommend combined surgical aortic valve replacement (SAVR) and coronary artery bypass grafting (CABG) as the preferred treatment. Transcatheter aortic valve implantation (TAVI) and fractional flow reserve (FFR)-guided percutaneous coronary intervention (PCI) represent a valid treatment alternative. We aimed to test the non-inferiority of FFR-guided PCI plus TAVI versus SAVR plus CABG in patients with severe aortic stenosis and complex coronary artery disease., Methods: This international, multicentre, prospective, open-label, non-inferiority, randomised controlled trial was conducted at 18 tertiary medical centres across Europe. Patients (aged ≥70 years) with severe aortic stenosis and complex coronary artery disease, deemed feasible for percutaneous or surgical treatment according to the on-site Heart Team, were randomly assigned (1:1) to FFR-guided PCI plus TAVI or SAVR plus CABG according to a computer-generated sequence with random permuted blocks sizes stratified by site. The primary endpoint was a composite of all-cause mortality, myocardial infarction, disabling stroke, clinically driven target-vessel revascularisation, valve reintervention, and life-threatening or disabling bleeding at 1 year post-treatment. The trial was powered for non-inferiority (with a margin of 15%) and if met, for superiority. The primary and safety analyses were done per an intention-to-treat principle. This trial is registered with ClinicalTrials.gov (NCT03424941) and is closed., Findings: Between May 31, 2018, and June 30, 2023, 172 patients were enrolled, of whom 91 were assigned to the FFR-guided PCI plus TAVI group and 81 to the SAVR plus CABG group. The mean age of patients was 76·5 years (SD 3·9). 118 (69%) of 172 patients were male and 54 (31%) patients were female. FFR-guided PCI plus TAVI resulted in favourable outcomes for the primary endpoint (four [4%] of 91 patients) versus SAVR plus CABG (17 [23%] of 77 patients; risk difference -18·5 [90% CI -27·8 to -9·7]), which was below the 15% prespecified non-inferiority margin (p non-inferiority <0·001). FFR-guided PCI plus TAVI was superior to SAVR plus CABG (hazard ratio 0·17 [95% CI 0·06-0·51]; p superiority <0·001), which was driven mainly by all-cause mortality (none [0%] of 91 patients vs seven (10%) of 77 patients; p=0·0025) and life-threatening bleeding (two [2%] vs nine [12%]; p=0·010)., Interpretation: The TCW trial is the first trial to compare percutaneous treatment versus surgical treatment in patients with severe aortic stenosis and complex coronary artery disease, showing favourable primary endpoint and mortality outcomes with percutaneous treatment., Funding: Isala Heart Centre and Medtronic., Competing Interests: Declaration of interests EKe reports institutional research grants from Abbott Vascular Laboratories and Medtronic and proctor or lecture fees from Abbott Vascular. RSH reports lecture fees from Abbott Vascular, Amgen, Novartis, Edwards Lifesciences, and Meril. DvG reports lecture fees from Cardiovasculair Onderwijs Instituut. GA reports lecture fees from Medtronic, Abbott, and Meril Life, patents planned for Tdaflo, and being a data and safety monitoring board member for Vivasure. IJA-S reports proctor, lecture, and consultant fees from Medtronic, Boston Scientific, Meril Life, and Products&Features. MA reports institutional research grants from Edwards, Abbott, Medtronic, and LSI, and proctor, lecture, and consultant fees from Edwards Lifesciences, Abbott, Medtronic, Boston, Zoll, and BBraun. GB reports a consulting grant from Medtronic. LC reports consulting fees from Medtronic, Abbott, JenaValve, Edwards Lifesciences, BostonScientific, PiCardia, MicroPort, VenusMedtech, 4C Medical, Smartcanula, MicroInterventions, and Neovasc, support for attending meetings or travel (or both) from Medtronic, Abbott, JenaValve, Edwards Lifesciences, and BostonScientific, and being a data and safety monitoring board member for Medtronic, Abbott, and JenaValve. LvG reports proctor fees from Edwards Lifesciences and support for attending meetings or travel (or both) from Edwards Lifesciences, Corcym, and Atricure. WW reports lecture fees from Medtronic and is a data safety monitoring board member for Medtronic. VV reports consulting fees from Medtronic. JS reports lecture fees from Abiomed. EL reports institutional research grants from Abbott. LN-F reports consulting fees from Abbot, Edwards Lifesciences, and Boston, and proctor, lecture, and consultant fees from Abbott, Edwards Lifesciences, Medtronic, and Boston. All other authors declare no competing interests., (Copyright © 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.)

Background: The agents etoposide and carboplatin are active against ovarian cancer and display synergistic anti-tumor activity in animal tumor models. The objective of these two phase II trials was to determine the efficacy and toxicity of the combination of etoposide with carboplatin in previously treated and untreated patients with ovarian cancer., Patients and Methods: Etoposide (100 mg/m2) was administered as a one-hour infusion on three consecutive days and carboplatin (400 mg/m2) as a 30-minute infusion on day 2 of each monthly scheduled cycle. In 20 patients, previously treated with cisplatin-containing regimens, a total of 102 cycles was applied as salvage therapy (ST) and in 27 patients, a total of 168 cycles as first-line therapy (FLT)., Results: ST yielded 2 complete remissions (CR) and one partial remission (PR); in 7 patients, no evidence of disease (NED) and in 6 patients, no change (NC) were observed. The progression-free intervals (PFI) lasted a median 7.0 months (range < 2-14 months). FLT resulted in 7 CR (4 of them pathologically (p) verified), 11 NED (1 pNED), 3 PR (1 pPR) and 6 NC. The objective response rate was 63% (95% confidence interval: 36-89%). PFI lasted a median 8.0 months (range 3-25+ months); median survival had not been reached at the time of evaluation. Thrombocytopenia (WHO grade 4) was the limiting toxicity., Conclusions: Although not fulfilling the expectations of synergistic activity as shown in preclinical models, the combination of etoposide with carboplatin is an active and feasible therapy regimen in the out-patient management of ovarian cancer.

Serum C-reactive protein (CRP) and alpha 1-acid glycoprotein (AAG) levels were studied in 188 patients undergoing heart operations with cardiopulmonary bypass. Mediastinitis or osteomyelitis of the sternum or both developed in 10 patients on postoperative day 4 to 13 (median, day 9). The mean CRP levels on day 2 were lower in patients with later deep sternal wound infection (9.1 +/- 1.5 mg/dl [mean +/- standard error]) compared with patients without major infections (14.0 +/- 0.8 mg/dl; p = 0.103 [univariate logistic regression]). AAG levels on day 2 reacted in a similar manner, yielding 78.2 +/- 5.5 mg/dl and 100.9 +/- 2.7 mg/dl, respectively (p = 0.0004). No correlation was found between CRP or AAG and duration of cardiopulmonary bypass, number of blood transfusions, or total protein levels on day 2. The white blood cell count (WBC) on day 2 was 13.1 +/- 1.7 X 10(3)/microliter for patients with infection and 9.7 +/- 0.3 for those without infection. Multivariate logistic regression analysis revealed that AAG, WBC, and CRP on day 2 were significant risk factors sufficiently predicting the probability of a deep sternal infection. After adjustment for these three variables, other variables (age, sex, total protein on day 2, diabetes mellitus, type of operation, duration of cardiopulmonary bypass, length of operation, repeat thoracotomy for bleeding, number of blood transfusions on the day of operation, intraaortic balloon pumping, reoperation, emergency operation, and surgeon's professional status) were not of additional significance. The goodness of fit of the statistical model was confirmed by a high correspondence between predicted and observed cases of deep sternal infection.(ABSTRACT TRUNCATED AT 250 WORDS)

Risk factors for severe bacterial infections, that is, deep sternal wound infection, pneumonia, septicemia, and prosthetic valve endocarditis, were evaluated in 246 consecutive patients undergoing valve replacement (N = 84) or aortocoronary bypass operation (N = 162). Multiple logistic regression analysis was applied to determine the ability of putative risk factors to predict infection. The risk factors considered were age, sex, diabetes mellitus, duration of cardiopulmonary bypass (CPB), duration of operation, amount of blood restored on the day of operation, repeat thoracotomy for bleeding, intraaortic balloon pumping, reoperation, emergency operation, and the professional status of the surgeon. Severe infections occurred in similar frequency after valve replacement (8/84; 9.5%) and aortocoronary bypass (11/162; 6.8%). For patients who had a bypass procedure, repeat thoracotomy was the only factor significantly associated with infection (p = 0.0004). However, the classification analysis revealed that this variable alone is too unspecific for a reliable prediction. Univariate analysis indicated that restoration of more than 2,500 ml of blood (p = 0.0001), reoperation (p = 0.0821), duration of operation (p = 0.0061), duration of CPB (p = 0.0318), and intraaortic balloon pumping (p = 0.0281) were associated with infection following valve replacement. A model with three variables emerged from the multiple logistic regression: after correction for blood restoration, reoperation, and duration of CPB, no other variable was of additional predictive value. For patients who underwent valve replacement, the model performed well in predicting complications. The classification analysis revealed a high correspondence between observed and predicted instances of infection: it correctly predicted 75% of the patients with infection and 96% of those without infection.(ABSTRACT TRUNCATED AT 250 WORDS)