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Background: Patient-prosthesis mismatch (PPM) after aortic valve replacement potentially affects the outcome after the operation. This study sought to determine whether PPM has an impact on long-term mortality and reoperation rates., Methods: We included 645 patients who underwent biologic aortic valve replacement between 2000 and 2007. Based on echocardiographic examinations at postoperative month 6, the incidence of PPM was determined according to an indexed effective orifice area <0.85 cm 2 /m 2 . Survival and reoperation status were analyzed during 15 years of follow-up., Results: PPM was present in 256 patients (40%), of whom 175 had moderate PPM and 81 had severe PPM. In multivariable adjusted analysis, survival was not statistically significantly impaired in patients with moderate PPM compared with patients with no PPM, whereas patients with severe PPM showed a marginally significant impairment of survival (hazard ratio [HR], 1.40; 95% CI, 0.99-1.97; P = .054). Risk factors for survival were higher age (HR, 1.12; 95% CI, 1.10-1.14; P < .001), arterial hypertension (HR, 1.78; 95% CI, 1.38-2.31; P < .001), and diabetes mellitus (HR, 1.67; 95% CI, 1.31-2.14; P < .001). In patients with no, moderate, and severe PPM, there were 10.1, 8.5, and 14.8 events of reoperation/1000 patient-years, respectively. The corresponding 10-year cumulative incidence of reoperation was 8.3%, 6.7%, and 12.1%, respectively. In multivariable adjusted analysis, PPM category was not significantly associated with the risk of reoperation (P > .2)., Conclusions: In our study with directly measured effective orifice area, PPM was only marginally related to long-term survival and was not statistically significantly associated with the risk of reintervention., Competing Interests: Disclosures Sabine Bleiziffer reports a relationship with Abbott that includes: speaking and lecture fees; with Boston Scientific Corp that includes: speaking and lecture fees; with Edwards Lifesciences Corporation that includes: speaking and lecture fees; and with Medtronic that includes: speaking and lecture fees. Markus Krane reports a relationship with JOMDD that includes: board membership and consulting or advisory; with Peter Duschek that includes: consulting or advisory; with Evotec that includes: consulting or advisory; with Moderna Inc that includes: consulting or advisory; with Medtronic that includes: speaking and lecture fees; and with Terumo that includes: speaking and lecture fees. The other authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

The identification of TBX5-related regulatory sequences in genes essential for heart development is hampered by the absence of antibodies which allow precipitation of TBX5:DNA complexes. Employing CRISPR/Cas9 technology, we have inserted a FLAG-tag sequence at the end of exon 9 of the TBX5 gene prior to the stop codon by homologous recombination. The translated TBX5-FLAG fusion protein of the three iPSC lines can effectively be precipitated by anti-FLAG antibodies and, thus, allow the detection of specific TBX5-binding sites and their associated genes., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: Contemporary national utilization and comparative safety data of robotic mitral valve repair for degenerative mitral regurgitation compared with nonrobotic approaches are lacking. The study aimed to characterize national trends of utilization and outcomes of robotic mitral repair of degenerative mitral regurgitation compared with sternotomy and thoracotomy approaches., Methods: Patients undergoing intended mitral repair of degenerative mitral regurgitation in The Society of Thoracic Surgeons Adult Cardiac Surgery Database between 2015 and 2021 were examined. Mitral repair was performed in 61,322 patients. Descriptive analyses characterized center-level volumes and outcomes. Propensity score matching separately identified 5540 pairs of robotic vs thoracotomy approaches and 6962 pairs of robotic vs sternotomy approaches. Outcomes were operative mortality, composite mortality and major morbidity, postoperative length of stay, and conversion to mitral replacement., Results: Through the 7-year study period, 116 surgeons across 103 hospitals performed mitral repair robotically. The proportion of robotic cases increased from 10.9% (949 of 8712) in 2015 to 14.6% (1274 of 8730) in 2021. In both robotic-thoracotomy and robotic-sternotomy matched pairs, mortality and morbidity were not significantly different, whereas the robotic approach had lower conversion (1.2% vs 3.1% for robotic-thoracotomy and 1.0% vs 3.7% for robotic-sternotomy), shorter length of stay, and fewer 30-day readmissions. Mortality and morbidity were lower at higher-volume centers, crossing the national mean mortality and morbidity at a cumulative robotic mitral repair case of 40., Conclusions: Robotic mitral repair is a safe and effective approach and is associated with comparable mortality and morbidity, a lower conversion rate, a shorter length of stay, and fewer 30-day readmissions than thoracotomy or sternotomy approaches., (Published by Elsevier Inc.)

TBX5 is a transcription factor which plays an essential role at different checkpoints during cardiac differentiation. However, regulatory pathways affected by TBX5 still remain ill-defined. We have applied the CRISPR/Cas9 technology using a completely plasmid-free approach to correct a heterozygous causative "loss-of function" TBX5 mutation in an iPSC line (DHMi004-A), that has been established from a patient suffering from Holt-Oram syndrome (HOS). This isogenic iPSC line, DHMi004-A-1, represents a powerful in vitro tool to dissect the regulatory pathways affected by TBX5 in HOS., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

TBX5 is a transcription factor (TF) playing essential role during cardiogenesis. It is well known that TF mutations possibly result in non- or additional binding of the DNA due to conformational changes of the protein. We introduced a Holt-Oram Syndrome (HOS) patient-specific TBX5 mutation c.920&#95;C > A heterozygously in a healthy induced pluripotent stell cell (iPSC) line. This TBX5 mutation results in conformational changes of the protein and displayed ventricular septal defects in the patient itself. Additionally we introduced a FLAG-tag on the TBX5 mutation-carrying allele. The resulting heterozygous TBX5-FLAG iPSC lines are a powerful tool to investigate altered TF activity bonding., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Markus Krane reports a relationship with German Research Foundation that includes: funding grants. Markus Krane reports a relationship with Deutsches Zentrum für Herz-Kreislauf-Forschung that includes: funding grants., (Copyright © 2023 The Author(s). Published by Elsevier B.V. All rights reserved.)

Although TBX5 plays a major role during human cardiogenesis and initiates and controls limb development, many of its interactions with genomic DNA and the resulting biological consequences are not well known. Existing anti-TBX5-antibodies work very inefficiently in certain applications such as ChIP-Seq analysis. To circumvent this drawback, we introduced a FLAG-tag sequence into the TBX5 locus at the end of exon 9 prior to the stop codon by CRISPR/Cas9. The expressed TBX5-FLAG fusion protein can effectively be precipitated by anti-FLAG antibodies. Therefore, these gene-edited iPSC lines represent powerful cellular in vitro tools to unravel TBX5:DNA interactions in detail., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

Background: The long-term outcomes of mitral valve repair by nonresection techniques, such as annuloplasty and chordal replacement, for degenerative mitral valve regurgitation were investigated., Methods: All consecutive patients with degenerative mitral regurgitation who received solely chordal replacement and annuloplasty for mitral valve repair between 2003 and 2010 at the German Heart Center Munich were reviewed. The endpoints of this retrospective study were survival, cumulative incidence of reoperation on the mitral valve, and cumulative incidence of significant recurrent mitral regurgitation., Results: A total of 346 patients were evaluated. The median follow-up period was 10.86 (range, 0.01-15.86) years. The 30-day mortality rate was 0.58% (n = 2 of 346), whereas the 5-year survival was 92.97% ± 1.41%. At 5 years, cumulative incidence of recurrent mitral regurgitation was 6.87% ± 1.57% and cumulative incidence of reoperation on the mitral valve was 3.69% ± 1.05%. Survival at 10 years was 83.35% ± 2.15%. At 10 years, cumulative incidence of recurrent mitral regurgitation was 13.31% ± 2.22% and cumulative incidence of reoperation was 7.84% ± 1.55%. Cox regression analysis identified age, diabetes mellitus, and reduced left ventricular ejection fraction <55% as independent risk factors for death. Left ventricular ejection fraction <55% was revealed as independent risk factor for significant recurrent mitral regurgitation., Conclusions: This study demonstrated excellent long-term outcomes with low incidence of reoperation after mitral valve repair using chordal replacement in a highly selected patient cohort. Our findings emphasized the importance of early intervention in severe degenerative mitral regurgitation, especially in patients with reduced left ventricular ejection fraction., (Copyright © 2023 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Aortic valve replacement is the traditional surgical treatment for aortic valve diseases, yet standardized aortic valve neocuspidization (AVNeo) is a promising alternative that is gaining popularity. The purpose of this article is to review the available published literature of AVNeo using glutaraldehyde-treated autologous pericardium, also known as the Ozaki procedure, including indications, outcomes, potential benefits, and modes of failure for the reconstructed valve., Methods: A comprehensive literature search was performed using keywords related to aortic valve repair, AVNeo, or Ozaki procedure. All articles describing performance of AVNeo were reviewed., Results: Reported early mortality after AVNeo varies from 0% to 5.88%. The largest cohort of patients in the literature includes 850 patients with an inhospital mortality rate of 1.88%. Cumulative incidence of aortic valve reoperation was 4.2% in the largest series. Reoperation was uncommon and mainly due to infective endocarditis or degeneration of the reconstructed valve (most commonly due to aortic valve regurgitation, rather than stenosis)., Conclusions: Aortic valve neocuspidization is a versatile and standardized alternative to aortic valve replacement with a biological prosthesis. Early to midterm outcomes from a number of centers are excellent and demonstrate the safety and durability of the procedure. Long-term outcomes and clinical trial data are necessary to determine which patients benefit the most from this procedure., (Copyright © 2022 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

A number of mutations in the human TBX5 gene have been described which cause Holt-Oram syndrome, a severe congenital disease associated with abnormalities in heart and upper limb development. We have used a prime-editing approach to introduce a patient-specific disease-causing TBX5 mutation (c.920&#95;C > A) into an induced pluripotent stem cell (iPSC) line from a healthy donor. The resulting iPSC line provides a powerful tool to identify and analyze the biological and molecular impact of this specific TBX5 mutation in comparison to the isogenic control iPSC line during cardiac development., (Copyright © 2022 The Author(s). Published by Elsevier B.V. All rights reserved.)

We generated an induced pluripotent stem cell (iPSC) line from a healthy male 29-year-old proband. Adipose fibroblasts (AFs) were reprogrammed using Sendai virus. Generated iPSCs showed typical stem cell morphology. From passage 9 on, iPSCs were free of virus. Pluripotency in the iPSCs was verified and spontaneous differentiation showed expression of all three germ layers. Karyotyping indicated no anomalies for the generated iPSCs. Many patient-specific iPSCs are generated from subcutaneous fat fibroblasts obtained during surgical procedure. The described control iPSC line was generated equally and therefore serves as an ideal control for adipose-fibroblast-based patient-specific iPSC lines in disease modeling., (Copyright © 2022 The Authors. Published by Elsevier B.V. All rights reserved.)

The Holt-Oram syndrome (HOS) is a rare autosomal dominant disorder, mostly based on mutations in the TBX5 gene. Patients show malformation of at least one upper limb along with congenital heart defects. The established induced pluripotent stem cell (iPSC) line was generated from a patient displaying pronounced and typical features of HOS and carrying a single-nucleotide change c.920&#95;C>A leading to an amino acid change from proline to threonine at amino acid position 85, which appeared de novo. Adipose fibroblasts from the patient were reprogrammed using Sendai virus. Pluripotency of the iPSCs was fully demonstrated., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: Aortic valve neocuspidization (AVNeo) for trileaflet aortic valve reconstruction using autologous pericardium (Ozaki procedure) offers an alternative treatment modality to overcome drawbacks of conventional prosthetic aortic valve replacement., Methods: Between October 2016 and April 2019, 103 patients underwent surgery. Mean follow-up was 426 ± 270 days. Aortic stenosis was the leading diagnosis in 80 patients (77.7%) and aortic regurgitation in 23 (22.3%), respectively. Mean age was 54.0 ± 16.4 years (range, 13.8-78.5). A bicuspid valve was found in 81 patients (78.6%). Transthoracic echocardiography was performed at discharge and at 6 to 12 months after surgery. During AVNeo surgery valve sizing for an Abbott/St Jude Trifecta bioprosthesis (virtually implanted Trifecta bioprosthesis; St Jude Medical, St Paul, MN) was performed to compare pressure gradients and effective orifice area with published data., Results: Trileaflet aortic valve reconstruction was achieved in all patients. In 38 patients neocommissures were created (36.9%). Mean cross-clamp time was 135 ± 20 minutes. Four patients underwent reoperation; the overall freedom from reoperation was 96.1%. Echocardiographic 6- to 12-months follow-up after surgery was available in 93.8% of patients and did not show any change in hemodynamic parameters compared with discharge. Comparison between AVNeo and virtually implanted Trifecta Bioprosthesis revealed a significantly lower mean pressure gradient (8.5 ± 3.7 mm Hg vs 10.2 ± 2.0 mm Hg, P < .001) and higher mean effective orifice area (2.2 ± 0.7 cm 2 vs 2.1 ± 0.4 cm 2 , P = .037) for AVNeo., Conclusions: AVNeo shows low reoperation rates after surgery within the first 2 years. The hemodynamic performance is excellent, and the effective orifice area and mean pressure gradient remain stable within the first year., (Copyright © 2021 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objective: Effective mentorship may be an opportunity to mitigate career de-prioritization, improve stress management, and bolster professional growth. Relatively few studies address specific challenges that occur for general surgery trainees. We conducted a focus group-based investigation to determine facilitators/barriers to effective mentorship among general surgery residents, who are intending to pursue an academic career., Design: A semistructured focus group study was conducted to explore residents' attitudes and experiences regarding (1) needs for mentorship, (2) barriers to identifying mentors, and (3) characteristics of successful mentor-mentee interactions. Subjects self-identified and were characterized as either "Mentored" or "Nonmentored." Transcriptions were independently reviewed by 3 coders. Inter-rater reliability between the coders was evaluated by calculating Cohen's kappa for each coded item., Setting: General surgery residents from 2 academic tertiary hospitals, University of Pittsburgh Medical Center, and University of Washington, participated., Participants: Thirty-four general surgery trainees were divided into 8 focus groups., Results: There were no gender-based differences in mentoring needs among residents. Barriers to establishing a relationship with a mentor, such as lack of exposure to faculty, and time and determination on the part of both mentor and mentee, were exacerbated by aspects of surgical culture including gender dynamics, criticism, and hierarchy. Successful relationships between mentee and mentor were perceived to require personal/professional compatibility and a feeling that the mentor is invested in the mentee, while conflicts of interest and neglect detracted from a successful relationship., Conclusions: Our investigations demonstrate the importance of surgical hierarchy and culture in facilitating interpersonal interactions with potential mentors. Further studies will be necessary to determine how best to address these barriers., (Copyright © 2018 Association of Program Directors in Surgery. Published by Elsevier Inc. All rights reserved.)

Background: Artificial chord implantation has become one of the most applied techniques for mitral valve repair (MVR). Many techniques have been described, with the goal of optimizing neochord implantation. A new annuloplasty device designed to simplify the determination of the appropriate neochord length has been recently introduced. We describe our initial experience with this new device., Methods: The semirigid device is equipped with removable loops on the posterior aspect of the ring. Neochords are tied to the loops, which are subsequently removed. The device was implanted in 47 symptomatic patients from January 2015 to August 2016 through a median sternotomy in 33 patients (70.2%) and a right anterolateral minithoracotomy in 14 (29.8%). The cause of mitral valve insufficiency was degenerative in all patients, and most patients presented with isolated prolapse of the posterior leaflet. Before and after cardiopulmonary bypass, all patients underwent evaluation with transesophageal echocardiography, and transthoracic echocardiography was performed at discharge., Results: A median of 2 neochords were implanted (minimum, 1; maximum, 6). Mean cardiopulmonary bypass time and aortic cross-clamp times were 141.7 ± 32.3 and 104.8 ± 28.5 minutes for combined and 133 ± 53.9 and 98.3 ± 41.6 minutes for isolated MVR. At discharge, echocardiography revealed no or only mild mitral insufficiency in 45 patients (mean gradient, 2.9 ± 1.3 mm Hg)., Conclusions: This new annuloplasty ring facilitated determination of appropriate neochord length and was used to successfully treat different degenerative pathologies affecting both leaflets. This new device simplified length determination of the neochords., (Copyright © 2018 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Objectives: This study sought to analyze health-related quality-of-life (HrQoL) outcomes of patients undergoing transcatheter aortic valve replacement (TAVR) based on data from GARY (German Aortic Valve Registry)., Background: Typically, patients currently referred for and treated by TAVR are elderly with a concomitant variable spectrum of multiple comorbidities, disabilities, and limited life expectancy. Beyond mortality and morbidity, the assessment of HrQoL is of paramount importance not only to guide patient-centered clinical decision-making but also to judge this new treatment modality in this high-risk patient population., Methods: In 2011, 3,875 patients undergoing TAVR were included in the GARY registry. HrQoL was prospectively measured using the EuroQol 5 dimensions questionnaire self-complete version on paper at baseline and 1 year., Results: Complete follow-up EuroQol 5 dimensions questionnaire evaluation was available for 2,288 patients (transvascular transcatheter aortic valve replacement [TAVR-TV]: n = 1,626 and transapical TAVR [TAVR-TA]: n = 662). In-hospital mortality was 5.9% (n = 229) and the 1-year mortality was 23% (n = 893). The baseline visual analog scale score for general health status was 52.6% for TAVR-TV and 55.8% for TAVR-TA and, in parallel to an improvement in New York Heart Association functional class, improved to 59.6% and 58.5% at 1 year, respectively (p < 0.001). Between baseline and 1 year, the number of patients reporting no complaints increased by 7.8% (TAVR-TV) and by 3.5% within the mobility dimension, and by 14.1% (TAVR-TV) and 9.2% within the usual activity dimension, whereas only moderate changes were found for the self-care, pain or discomfort, and anxiety or depression dimensions. In a multiple linear regression analysis several pre- and post-operative factors were predictive for less pronounced HrQoL benefits., Conclusions: TAVR treatment led to improvements in HrQoL, especially in terms of mobility and usual activities. The magnitude of improvements was higher in the TAVR-TV group as compared to the TAVR-TA group. However, there was a sizable group of patients who did not derive any HrQoL benefits. Several independent pre- and post-operative factors were identified being predictive for less pronounced HrQoL benefits., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

MESP1 represents an essential transcription factor to guarantee coordinated cardiac development. The expression of MESP1 is thought to be the first sign that a cell has been committed to the cardiac lineage. We analyzed the coding sequence of MESP1 in 215 patients with congenital heart disease. Our results show that the sequence of exon 1 is highly variable with up to seven alterations in individual samples. Five base pair positions (c.157&#95;G>C A53P, rs6496598; c.174&#95;A>C P58P, rs28377352; c.182&#95;T>G L61R, rs28368490; c.669&#95;C>G F223L, rs2305440; c.687&#95;T>G P229P, rs2305441) are particularly variable. In almost half of the samples a 12 base pair insertion after position 55 (c.165&#95;166insGTGCCGAGCCCC P55insVPSP, rs71934166) coding for VPSP was detected which was strongly correlated with the appearance of further amino acid changes (c.157&#95;G>C A53P, c.182&#95;T>G L61R, c.669&#95;C>G F223L). Two missense mutations (c.33&#95;G>C E11D, rs190259690; c.528&#95;A>T T176S) were detected in two patients but were absent in the controls. The assessment of the biological activity of altered MESP1 proteins in a luciferase reporter assay showed an enhanced activity of the c.33&#95;G>C E11D mutation and a reduction of the insertion without an accompanying change of c.182&#95;T>G L61R. The modified biological properties of mutated MESP1 proteins might be associated with the appearance of certain pathological phenotypes of congenital heart disease., (Copyright © 2013 Elsevier Masson SAS. All rights reserved.)

Background: Aortic valve repair is associated with fewer long-term valve-related complications as compared with valve replacement, and repair is being performed increasingly. A current problem is the lack of a geometric annuloplasty ring to facilitate reconstruction. This paper describes the first clinical application of such a device designed to permanently restore physiologic annular size and geometry during aortic valve repair., Methods: Based on mathematical studies of human cadaver valves, as well as computed tomography angiographic analyses of awake patients with normal valves, a three-dimensional annuloplasty ring has been developed, consisting of low-profile, one-piece titanium construction and Dacron cloth covering. The ring design incorporates 2:3 elliptical base geometry and 10-degree outwardly flaring subcommissural posts., Results: Appropriately sized rings were implanted in 5 patients with severe aortic insufficiency due to annular dilation and anatomic leaflet defects. The rings restored annular geometry and facilitated leaflet repairs in all patients. Each recovered excellent valve function with minimal residual leak. All patients convalesced uneventfully, were discharged within 7 days after surgery, and continue with stable valve function as long as 6 months after implantation., Conclusions: Initial clinical application of a geometric aortic annuloplasty ring was associated with excellent device performance and perhaps better repairs. Further clinical series and patient follow-up should identify potential benefits of the device, including improved applicability and stability of aortic valve repair., (Copyright © 2013 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: The radial artery (RA) is known as an atherosclerosis-prone vessel in contrast to the atherosclerosis-resistant internal thoracic artery (ITA). The purpose of the present study was to compare the gene expression profile of these arteries from the same patient in order to identify genes involved in atherogenesis or intimal hyperplasia., Methods: Paired specimens of RA and ITA (n=6) were analyzed by histomorphometry and whole genome microarray. The microarray data underwent pathway analysis to identify biological networks. Laser microdissection (LMD) was used to identify the cellular expression of candidate genes in the intimal or medial layer of the ITA and RA., Results: Histomorphometric analyses revealed a significantly higher degree of intimal hyperplasia in the RA compared to the ITA. 552 genes were differentially expressed in the ITA and RA. qRT-PCR confirmed a significant up-regulation of six anti-apoptotic genes. p21 (11.8-fold, p=0.011), CCL2 (5.4-fold, p=0.034), SOCS3 (7.2-fold, p=0.002), IER3 (4.1-fold, p=0.048), MCL-1 (2.6-fold, p=0.025) and IL-6 (17.8-fold, p=0.046) were up-regulated in the ITA. LMD confirmed that cells of the intimal layer of the ITA consistently expressed higher levels of all six candidate genes than those of the RA., Conclusions: Microarray analysis and qRT-PCR identified significantly up-regulated genes in the ITA involved in an anti-apoptotic network. LMD revealed a higher expression of all anti-apoptotic genes in the intimal area of the ITA. These genes may play an important role in protecting the intima of the ITA from developing hyperplasia and atherosclerosis., (Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.)

Background: Patients aged 80 years and older who require cardiac surgical procedures are an increasing population and usually present with considerable comorbidity. Detailed operative risk stratification versus long-term survival and quality of life after surgery is mandatory., Methods: A retrospective analysis was performed on 1,003 patients aged 82.3 years (range, 80 to 94 years) who underwent aortic valve replacement (n = 303), coronary artery bypass grafting (n = 403), or aortic valve replacement with coronary artery bypass grafting (n = 297) between 1987 and 2006. Preoperative data, operative outcome, long-term survival, and predictors for early and late mortality were analyzed. Furthermore, the Short Form 36 Health Status questionnaire was used to evaluate the quality of life., Results: Overall in-hospital mortality was 7.1%. Overall actuarial survival at 1, 5, and 10 years was 81.6% ± 1.2%, 60.4% ± 1.9%, and 23.3% ± 2.6% (mean survival time, 6.25 ± 0.2 years) and showed no significant difference compared with an age- and sex-matched general population. Multivariate analysis showed that preoperative creatinine concentration greater than 1.3 mg/dL (p < 0.001), preoperative atrial fibrillation (p < 0.005), and postoperative prolonged ventilation (p < 0.001) were independent predictors for poor long-term survival. The physical health summarized score of the Short Form 36 Health Status questionnaire was significantly increased in the study population compared with a German standard population aged 80 years and older (p < 0.05)., Conclusions: Despite an increased operative mortality, octogenarians showed a considerable quality of life and an excellent long-term survival. To further improve surgical outcome in octogenarians, patient selection should be done with consideration of the identified independent preoperative risk factors., (Copyright © 2011 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Symptomatic heart failure is a complex clinical syndrome with a poor prognosis. Many efforts have been made to develop new therapeutic strategies to improve prognosis associated with heart failure. In this context, different stem cell populations for cardiac regenerative therapy have been examined recently. Here we discuss the potential strategies for using stem cells in cardiac regenerative therapy and the barriers that remain before an effective cell-based cardiac regenerative therapy can be employed clinically.

Background: The benefit of cardiac surgery in octogenarians is well described. Today, nearly every second patient who undergoes cardiac surgery is older than 70 years. The time between primary cardiac surgery and reoperation is 7 to 13 years. Therefore, in the future we can expect to see an increasing number of reoperations in octogenarians., Methods: We studied 71 patients (41 male) with a mean age of 83 +/- 2.8 years, who underwent cardiac reoperation between 1994 and 2006. These patients were compared with 71 octogenarians who underwent primary cardiac operation. Patients were matched for age, sex, year of operation, and surgical procedure. Demographic profiles, operative data, long-term survival, and quality of life by the Short-Form 36-Item Health Survey questionnaire were analyzed., Results: Average time between previous operation and reoperation was 10.8 +/- 5.6 years (range: 1.7 to 30.6). The 30-day mortality rate was 14.7% in the reoperation group and 8.5% (p = 0.43) in the control group. Actuarial survival at 1, 3, and 6 years was 71% +/- 5.5%, 60.5% +/- 6.1%, and 30% +/- 8.1% for patients who underwent cardiac reoperation; and 77.2% +/- 5%, 58.3% +/- 6.3%, and 36.3% +/- 7.8% for matched octogenarians who underwent primary cardiac surgery (p = 0.68). No significant differences were found between groups regarding the physical health summarized score (40.7 +/- 9.4 versus 39.1 +/- 10; p = 0.55) and the mental health summarized score (51.9 +/- 10.9 versus 48 +/- 12.9; p = 0.24) of the Short-Form 36-Item Health Survey questionnaire., Conclusions: Octogenarians exhibit a similar long-term survival and quality of life after primary and redo cardiac surgery. Therefore, cardiac reoperation should not be a contraindication per se in octogenarians.

Sternal dehiscence after median sternotomy can be a challenging problem in case of multiple fractures or infection. For sternal refixation, the principles of rigid plate and screw osteosynthesis gained from orthopedic surgery have been recommended by several authors. We present a new system for sternal reconstruction consisting of reconstruction plates, steel cables, and cannulated screws.

This paper describes a new and easy to handle reusable minifermenter for high-density culture of hybridoma and other cells. The culture apparatus is composed of two modules: a 40 ml disposable cell culture and antibody production chamber (the 'production module') and a 550 ml medium reservoir (the 'supply module'). The two modules are separated from each other by a dialysis membrane allowing passage of low molecular mass nutrients and metabolites. The monoclonal antibodies are produced and enriched in the production module. The outer part of this module is made from a thin gas-permeable silicone rubber membrane allowing exchange of gases (oxygen and carbon dioxide). To start the culture, the cells are injected into the production module through ports in the silicone rubber which are equipped with Luer Lock connectors. Samples can be removed in the same way. For culturing, the minifermenter is rolled on a roller apparatus in a carbon dioxide-supplied incubator. Depending on the individual properties of the hybridoma cells cultured, cell densities of more than 10 x 10(6) (in some cases up to 35 x 10(6)) cells per ml and monoclonal antibody concentrations of several mg per ml can be obtained in the new minifermenter. On average, 61 mg (range: 9-159 mg) could be produced within 1-4 weeks. In terms of their properties the monoclonal antibodies produced in the new modular minifermenter were indistinguishable from antibodies prepared from ascitic fluid or from the supernatant of conventional stationary culture. The culture method is a useful alternative to the in vivo production method in mice. In addition, it represents a completely new, inexpensive and easy to handle general solution to the problem of culturing cells in high density and obtaining cellular products in high concentrations.

This paper describes the construction and application of a low-cost roller bottle-like culture appliance in which hybridoma cells can be cultivated in high density in dialysis tubing. The appliance facilitates the simultaneous culture of up to four cell lines yielding 50 ml culture volume of each. Samples for follow-up analysis of the cultures can easily be taken when needed through sample ports. In order to obtain high cell densities (at least 10(7) cells/ml), high cell viability (at least 50%) and high antibody yield (at least 1.0 mg/ml) the bottle is rolled at a speed of 4-6 rpm and is gassed continuously by a micropump driven by rechargeable NiCd batteries fixed to the culture flask. Depending on the individual properties of the hybridoma lines tested, the cells may be cultured for 1-2 weeks, and cell densities of up to 30 x 10(6) cells/ml with viabilities of approximately 50% and monoclonal antibodies in concentrations of up to 2.8 mg/ml may be obtained. In their properties the monoclonal antibodies produced by this in vitro procedure are indistinguishable from those prepared in the form of conventional stationary culture supernatant or of ascitic fluid. Specific antibody content is within the same range as in ascitic fluid. Consequently, the monoclonal antibodies can be purified in one step, e.g., by ion exchange chromatography from the culture supernatant. Therefore, the newly developed culture device and the culture method described is a useful alternative to ascites production in live mice.