Search

Introduction: Isolated, confined, and extreme (ICE) environments such as found at Antarctic, Arctic, and other remote research stations are considered space-analogs to study the long duration isolation aspects of operational space mission conditions., Methods: We interviewed 24 sojourners that participated in different short/long duration missions in an Antarctic (Concordia, Halley VI, Rothera, Neumayer II) or non-Antarctic (e.g., MDRS, HI-SEAS) station or in polar treks, offering a unique insight based on first-hand information on the nature of demands by ICE-personnel at multiple levels of functioning. We conducted a qualitative thematic analysis to explore how sojourners were trained, prepared, how they experienced the ICE-impact in function of varieties in environment, provided trainings, station-culture, and type of mission., Results: The ICE-environment shapes the impact of organizational, interpersonal, and individual working- and living systems, thus influencing the ICE-sojourners' functioning. Moreover, more specific training for operating in these settings would be beneficial. The identified pillars such as sensory deprivation, sleep, fatigue, group dynamics, displacement of negative emotions, gender-issues along with coping strategies such as positivity, salutogenic effects, job dedication and collectivistic thinking confirm previous literature. However, in this work, we applied a systemic perspective, assembling the multiple levels of functioning in ICE-environments., Discussion: A systemic approach could serve as a guide to develop future preparatory ICE-training programs, including all the involved parties of the crew system (e.g., family, on-ground crew) with attention for the impact of organization- and station-related subcultures and the risk of unawareness about the impact of poor sleep, fatigue, and isolation on operational safety that may occur on location., Competing Interests: SB-C was employed by Oxford Human Performance. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Van Puyvelde, Gijbels, Van Caelenberg, Smith, Bessone, Buckle-Charlesworth and Pattyn.)

Introduction: High fidelity between non-small cell lung cancer (NSCLC) primary tumours and patient-derived tumour xenografts (PDTXs) is of paramount relevance to spur their application. Extensive proteomic and kinomic analysis of these preclinical models are missing and may inform about their functional status, in terms of phosphopeptides and hyperactive signalling pathways., Methods: We investigated tumour xenografts derived from patients with NSCLC to identify hyperactive signalling pathways. Fresh tumour fragments from 81 NSCLC surgical samples were implanted in Nod/Scid/Gamma mice, and engrafted tumours were compared with primary specimens by morphology, immunohistochemistry, gene mutation analyses, and kinase activity profiling. Four different tyrosine and serine/threonine kinase inhibitors were tested against primary tumour and PDTX lysates using the PamGene peptide microarray platform., Results: The engraftment rate was 33%, with successful engraftment being more associated with poor clinical outcomes. Genomic profiles led to the recognition of hotspot mutations, some of which were initially undetected in donor samples. Kinomic analyses showed that characteristics of primary tumours were retained in PDTXs, and tyrosine kinase inhibitors (TKIs) responses of individual PDTX lines were either expected, based on the genetic status, or alternatively defined suitable targets unpredictable by single-genome fingerprints., Conclusions: Collectively, PDTXs mostly resembled their parental NSCLC. Combining genomic and kinomic analyses of tumour xenografts derived from patients with NSCLC, we identified patients' specific targetable pathways, confirming PDTXs as a preclinical tool for biomarker identification and therapeutic algorithm'' improvement., Competing Interests: Conflict of interest statement The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: A van den Berg, Rob Ruijtenbeek, Rik de Wijn and Riet Hilhorst are/were employees of PamGene International BV. All other authors have nothing to declare., (Copyright © 2020 Elsevier Ltd. All rights reserved.)

Machine Learning (ML) has found several applications in spectroscopy, including recognizing minerals and estimating elemental composition. ML algorithms have been widely used on datasets from individual spectroscopy methods such as vibrational Raman scattering, reflective Visible-Near Infrared (VNIR), and Laser-Induced Breakdown Spectroscopy (LIBS). We firstly reviewed and tested several ML approaches to mineral classification from the existing literature, and identified a novel approach for using Deep Learning algorithms for mineral classification from Raman spectra, that outperform previous state-of-the-art methods. We then developed and evaluated a novel method for automatic mineral identification from combining measurements with two complementary spectroscopic methods using Convolutional Neural Networks (CNN) for Raman and VNIR, and cosine similarity for LIBS. Specifically, we evaluated fusing Raman + VNIR, Raman + LIBS or VNIR + LIBS spectra in order to classify minerals. ML methods applied to combined spectral methods presented here are shown to outperform the use of a single data source by a significant margin. Our approach was tested on both open access experimental Raman (RRUFF) and VNIR (USGS, RELAB, ECOSTRESS) libraries, as well as on synthetic LIBS (NIST) spectral libraries. Our cross-validation tests show that multi-method spectroscopy paired with ML paves the way towards rapid and accurate characterization of rocks and minerals. Future solutions combining Deep Learning Algorithms, together with data fusion from multi-method spectroscopy, could drastically increase the accuracy of automatic mineral recognition compared to existing approaches.

Future human missions to the surface of the Moon and Mars will involve scientific exploration requiring new support tools to enable rapid and high quality science decision-making. Here, we describe the PANGAEA (Planetary ANalogue Geological and Astrobiological Exercise for Astronauts) Mineralogical Database developed by ESA (European Space Agency): a catalog of petrographic and spectroscopic information on all currently known minerals identified on the Moon, Mars, and associated with meteorites. The catalog also includes minerals found in the analog field sites used for ESA's geology and astrobiology training course PANGAEA, to broaden the database coverage. The Mineralogical Database is composed of the Summary Catalog of Planetary Analog Minerals and of the Spectral Archive and is freely available in the public repository of ESA PANGAEA. The Summary Catalog provides essential descriptive information for each mineral, including name (based on the International Mineralogical Association recommendation), chemical formula, mineral group, surface abundance on planetary bodies, geological significance in the context of planetary exploration, number of collected VNIR and Raman spectra, likelihood of detection using different spectral methods, and bibliographic references evidencing their detection in extraterrestrial or terrestrial analog environments. The Spectral Archive provides a standard library for planetary in-situ human and robotic exploration covering Visual-Near-Infrared reflective (VNIR) and Raman spectroscopy (Raman). To populate this library, we collected VNIR and Raman spectra for mineral entries in the Summary Catalog from open-access archives and analyzed them to select the ones with the best spectral features. We also supplemented this collection with our own bespoke measurements. Additionally, we compiled the chemical compositions for all the minerals based on their empirical formula, to allow identification using the measured abundances provided by LIBS and XRF analytical instruments. When integrated into an operational support system like ESA's Electronic Fieldbook (EFB) system, the Mineralogical Database can be used as a real-time and autonomous decision support tool for sampling operations on the Moon, Mars and during astronaut geological field training. It provides both robust spectral libraries to support mineral identification from instrument outputs, and relevant contextualized information on detected minerals., Competing Interests: The authors declare that there are no known competing financial interests or personal relatiosnhips that have or could be perceived to have influenced the work reported in this article., (© 2020 Published by Elsevier Inc.)

Renewed interest in human space exploration has highlighted the gaps in knowledge needed for successful long-duration missions outside low-Earth orbit. Although the technical challenges of such missions are being systematically overcome, many of the unknowns in predicting mission success depend on human behavior and performance, knowledge of which must be either obtained through space research or extrapolated from human experience on Earth. Particularly in human neuroscience, laboratory-based research efforts are not closely connected to real environments such as human space exploration. As caves share several of the physical and psychological challenges of spaceflight, underground expeditions have recently been developed as a spaceflight analog for astronaut training purposes, suggesting that they might also be suitable for studying aspects of behavior and cognition that cannot be fully examined under laboratory conditions. Our objective is to foster a bi-directional exchange between cognitive neuroscientists and expedition experts by (1) describing the cave environment as a worthy space analog for human research, (2) reviewing work conducted on human neuroscience and cognition within caves, (3) exploring the range of topics for which the unique environment may prove valuable as well as obstacles and limitations, (4) outlining technologies and methods appropriate for cave use, and (5) suggesting how researchers might establish contact with potential expedition collaborators. We believe that cave expeditions, as well as other sorts of expeditions, offer unique possibilities for cognitive neuroscience that will complement laboratory work and help to improve human performance and safety in operational environments, both on Earth and in space.

Introduction: Bio-repositories are invaluable resources to implement translational cancer research and clinical programs. They represent one of the most powerful tools for biomolecular studies of clinically annotated cohorts, but high quality samples are required to generate reliable molecular readouts and functional studies. The objective of our study was to define the impact of cancer tissue ischemia time on RNA and DNA quality, and for the generation of Patient-Derived Xenografts (PDXs)., Methods: One-hundred thirty-five lung cancer specimens were selected among our Institutional BioBank samples. Associations between different warm (surgical) and cold (ex-vivo) ischemia time ranges and RNA quality or PDXs engraftment rates were assessed. RNA quality was determined by RNA integrity number (RINs) values. Fresh viable tissue fragments were implanted subcutaneously in NSG mice and serially transplanted., Results: RNAs with a RIN>7 were detected in 51% of the sample (70/135), with values of RIN significantly lower (OR 0.08, P = 0.01) in samples preserved for more than 3 hours before cryopreservation. Higher quality DNA samples had a concomitant high RIN. Sixty-three primary tumors (41 adenocarcinoma) were implanted with an overall engraftment rate of 33%. Both prolonged warm (>2 hours) and ex-vivo ischemia time (>10 hours) were associated to a lower engraftment rate (OR 0.09 P = 0.01 and OR 0.04 P = 0.008, respectively)., Conclusion: RNA quality and PDXs engraftment rate were adversely affected by prolonged ischemia times. Proper tissue collection and processing reduce failure rate. Overall, NSCLC BioBanking represents an innovative modality, which can be successfully executed in routine clinical settings, when stringent Standard Operating Procedures are adopted.

Doxorubicin is commonly considered to exert its anti-tumor activity by triggering apoptosis of cancer cells through DNA damage. Recent reports have shown that Doxorubicin elicits a marked heat shock response, and that either inhibition or silencing of heat shock proteins enhance the Doxorubicin apoptotic effect in neuroblastoma cells. In order to investigate whether Doxorubicin may also act through protein modification, we performed a proteomic analysis of ubiquitinated proteins. Here we show that nanomolar Doxorubicin treatment of neuroblastoma cells caused: (a) dose-dependent over-ubiquitination of a specific set of proteins in the absence of measurable inhibition of proteasome, (b) protein ubiquination patterns similar to those with Bortezomib, a proteasome inhibitor, (c) depletion and loss of activity of ubiquitinated enzymes such as lactate dehydrogenase and α-enolase, and (d) a decrease in HSP27 solubility, probably a consequence of its binding to denatured proteins. These data strongly reinforce the hypothesis that Doxorubicin may also exert its effect by damaging proteins., (© 2012 The Authors Journal compilation © 2012 FEBS.)

After several years of planning and preparation, ESA's ISS training programme has become operational. Between 26 August and 6 September, the European Astronaut Centre (EAC) near Cologne gave the first ESA advanced training course for an international ISS astronaut class. The ten astronauts who took part--two from NASA, four from Japan and four from ESA--had begun their advanced training programme back in 2001 with sessions at the Johnson Space Center (JSC) in Houston and at the Japanese Training Centre in Tsukuba. During their stay in Cologne, the ten astronauts participated in a total of 33 classroom lessons and hands-on training sessions, which gave them a detailed overview of the systems and subsystems of the Columbus module, the Automated Transfer Vehicle (ATV), and the related crew operations tasks. They were also introduced to the four ESA experiment facilities to be operated inside the Columbus module. After their first week of training at EAC, the astronauts were given the opportunity to see the flight model of the Columbus module being integrated at the site of ESA's ISS prime contractor, Astrium in Bremen. The second week of training at EAC included hands-on instruction on the Columbus Data Management System (DMS) using the recently installed Columbus Crew Training Facility. In preparation for the first advanced crew training session at EAC, two Training Readiness Reviews (TRR) were conducted there in June and August. These reviews were supported by training experts and astronauts from NASA, NASDA and CSA (Canada), who were introduced to ESA's advanced training concept and the development process, and then analysed and evaluated the training flow, content and instructional soundness of lessons and courses, as well as the fidelity of the training facilities and the skills of the ESA training instructors. The International Training Control Board (ITCB), made up of representatives from all of the ISS International Partners and mandated to control and coordinate all multilateral training for ISS crew and ground-support personnel, testified to ESA's readiness to provide Advanced Training by declaring the EAC TRR successful. The completion of this first training course was therefore a good opportunity for the Astronaut Training Division to assess the status of its training programme. The comments and recommendations of the training experts and the astronauts who took part have been carefully evaluated and the results are being fed back into the ongoing training development process.

Background: A wealth of data exists on acceptable mortality and morbidity for valve operations in older patients, yet information documenting quality of life is lacking., Methods: From October 1974 to May 1998, 2,075 patients aged 65 years and older underwent valve replacement using a porcine bioprosthesis. There were 1,126 men (54.3%) and 949 women (45.7%) with a mean age of 73.9 years (range 65 to 104 years)., Results: The elective hospital mortality was 8.5% (158 patients), and urgent/emergent/salvage mortality was 25.8% (54 patients). Follow-up was completed for 1,863 patients (98.2%) and extended from 1 month to 23.0 years (mean 60.8 months) with a cumulative follow-up of 9,442.1 patient-years. At follow-up, surviving patients (n = 849) completed the Short Form-36 Quality of Life Survey. Results showed patients had a more favorable quality of life compared with control subjects matched for age and sex. Functional improvement was significant with 96.3% in New York Heart Association functional class I or II at follow-up. There were 74 valves that failed from all causes (33 aortic and 41 mitral valves). Actuarial freedom from valve failure at 9 years was 94.4%+/-1.1% and at 18 years was 83.7%+/-2.4%., Conclusions: Valve replacement in older patients provides excellent functional improvement, reduces late cardiac events, and enhances quality of life.

The Euromir 95 long-duration mission raised many new crew-support issues for ESA. Previous mission experience indicated the need for increased emphasis on generic tools for astronaut Thomas Reiter. In addition, some possible solutions could be demonstrated to combat Mir's onboard stowage problem. Overall, the mission considerably increased ESA's operational experience, while the experimental introduction of certain items generated a vast number of 'lessons learned' in the crew-support domain. Further experience in this area would enhance Europe's role in the International Space Station's operational phase.

The issue of bioprosthetic valve durability has become of critical importance as the number of elderly patients requiring valve operation has continued to increase. Our previous study showed bioprosthetic valve durability to be in excess of 83% at 13 years for patients 70 years of age and older at the time of implantation. There is limited follow-up data in the literature beyond this time point, however. Accordingly a retrospective analysis was conducted of all patients with bioprosthetic valves who were 70 years of age and over at the time of implantation. From September 1974 to April 1994, 1007 patients 70 years of age and over underwent valve replacement using a porcine bioprosthesis. The patients ranged in age from 70 to 104 years (mean, 75.6 +/- 4.3 years). There were 549 men (54.5%) and 458 women (45.5%). Preoperatively 98.8% of the patients were in New York Heart Association functional class III or IV. Operation was performed as an emergency in 66 patients (6.6%). The hospital mortality was 10.9% (110 patients), with 897 hospital survivors. There were 961 valves at risk. Follow-up extended from 1 month to 18.8 years (mean, 56.6 months). The cumulative follow-up is 4232.3 patient-years. A total of 31 valves failed, 12 in the aortic position and 19 in the mitral position (p < 0.0024). The causes of valve failure have included structural deterioration (16 valves), prosthetic endocarditis (7 valves), nonstructural dysfunction (5 valves), prosthetic thrombosis (1 valve), and other (2 valves).(ABSTRACT TRUNCATED AT 250 WORDS)

The number of patients undergoing valve replacement and concomitant coronary artery bypass grafting (CABG) is increasing. To further evaluate the indications for the use of the porcine bioprosthesis, this retrospective comparative analysis of valve structural deterioration was conducted in patients with and without concomitant CABG. From September 1974 to October 1993, 1,567 patients underwent valve replacement using a porcine xenograft. The series was divided into two groups: patients with isolated valve replacement (VR; n = 876) and those with VR and CABG (VR + CABG; n = 691). Aortic valve replacement was performed in 938 patients, mitral valve in 518, tricuspid in 2, and multiple valve replacement in 109 patients. The mean age for the series was 70.7 years (range, 50 to 104 years). The hospital mortality was 8.8% (138 patients). The hospital mortality for the VR group was 7.4% (65 deaths) and the VR + CABG group, 10.6% (73 deaths) p = 0.0365. There were 1,429 patients discharged from the hospital with 1,489 valves at risk. Follow-up extended from 1 month to 17.9 years with a mean of 66.9 months and was 98.3% complete. The cumulative follow-up was 7,927.1 patient-years. Structural deterioration was found to be significantly greater in the VR group for the age category 50 to 59 years (p = 0.0121) and the 60 to 69 years (p = 0.0230). No significant difference in the rate of structural deterioration was found for the two groups for the age category 70 years and older.(ABSTRACT TRUNCATED AT 250 WORDS)

The expanded use of autografts for aortic valve replacement has focused attention on developing an improved implantation technique with the aim of reducing the incidence of early insufficiency. While the technique for total root replacement with nonstented tissue valves is a proven and established method, it is, however, not generally accepted for use in all clinical circumstances. Through the use of a partial inclusion technique, we propose to modify the standard method of extended aortic root replacement and pedicle coronary implantation. This approach also has the advantage of leaving the recipient aortic root intact. Unlike traditional scalloped subcoronary homograft implantation, it does not enclose the transplanted valve totally within the recipient aorta. Thus, there is preservation of the patient's aorta without distortion of the transplanted valve which occurs when it is forced completely into the closed recipient aortic root. While this partial inclusion method is not as simple as total root replacement, preservation of the recipient root is generally more acceptable to implanting surgeons. Either perfection of this proposed method or the acceptance of a traditional extended aortic root replacement will result in correction of the persistent problem of early aortic insufficiency following the use of autograft valves. Decreasing valve incompetence will have the desired effect of increasing the indication for the use of autografts for aortic valve replacement in young patients.

Since the advent of homograft aortic valve replacement surgery in the early 1960s, this procedure has been plagued by early aortic insufficiency. This problem has not been observed with total aortic root replacement. From September 1985 to April 1991, a modified method was used in 25 of 39 consecutive patients having aortic root replacement--seven having autografts, 30 having homografts, and two having xenografts. This technique is a new approach for implanting unstented valves in the aortic position. It decreases the probability of early failure resulting from technical malalignment of the valve during implantation. Further, it avoids the need to destroy the recipient aortic root. Whether the valve being used is an autograft, homograft, or xenograft, this method standardizes the insertion technique regardless of the anatomy or disease. Salient features of the method include the following: a longitudinal aortotomy to the aortic anulus in the midportion of the noncoronary sinus; a proximal interrupted suture line with the valve oriented in the anatomic position; and circumferential running monofilament side-to-side approximation of the donor coronary ostia to the recipient coronary ostia. The two anterior commissures are left untethered by nonclosure of the recipient aortotomy. Preliminary results have been impressive, with follow-up ranging from 1 to 3 years in 30 of these patients. Postoperative aortic insufficiency was significant in only two cases. There has been no progression of aortic insufficiency detectable by diastolic murmur or echocardiogram. Late complications have been minimal, and the overall clinical results have been excellent.

From July, 1972, to April, 1976, 54 consecutive patients over the age of 70 years underwent valve replacement at Tampa General Hospital. Twenty-one patients had isolated aortic valve replacement (Group 1), 14 had isolated mitral valve replacement (Group 2), and 19 had combined procedures that included at least 1 valve replacement (Group 3). There was 1 operative death (in Group 1), and another patient (Group 3) died three weeks post-operatively, resulting in an early mortality of 3.7%. Follow-up of the 52 hospital survivors from one to forty-one months reveals 2 additional deaths for a late mortality of 3.8%. Cardiac status improved noticeably in the surviving 50 patients. The data suggests that with current techniques, complex intracardiac procedures can be performed safely with acceptable operative mortality and a satisfactory prognostic outlook in elderly patients.

Resection of the ascending aorta with or without aortic valve replacement requires prolonged interruption of myocardial blood flow. Profound local cardiac hypothermia was used in 8 patients, 5 of whom had simultaneous aortic valve replacement. Three patients with acute dissections were encountered, one with cardiac tamponade secondary to intrapericardial rupture. The duration of aortic cross-clamp time varied from 43 to 122 minutes. There were no complications related to the cooling technique. There were no operative or hospital deaths. One patient died of myocardial infarction at 6 weeks. These results coupled with the experience of others suggest that coronary perfusion during periods of obligatory anoxia in unnecessary. Local cardiac hypothermia offers a satisfactory alternative for myocardial protection during prolonged aortic crossclamping.

Local deep hypothermia was utilized as the sole method of myocardial protection in 113 consecutive aortic valve replacements. Thirty-six patients had simultaneous revascularization, mitral valve replacement, tricuspid valve replacement, or a combination of these. In follow-up for as long as 36 months there have been 3 hospital deaths (2.6%), all occurring in the group having isolated aortic valve replacement. No hospital deaths occurred among patients undergoing a combined procedure.

From August, 1972, to May, 1974, 52 consecutive aortic valves were replaced with the Björk-Shiley tilting-disc prosthesis. The hospital mortality was zero. Patients ranged in age from 14 to 77 years, and 19 patients had simultaneous correction of associated cardiac lesions. Using techniques of low flow and local deep hypothermia, aortic valve replacement can be accomplished with little risk even in patients with associated coronary arteriosclerosis. Coronary artery perfusion is unnecessary and often hazardous. Follow-up periods vary from one to twenty-one months. Forty-nine patients are alive and substantially improved.

Giant cell arteritis is often referred to in the context of polymyalgia rheumatica with temporal artery involvement. There are, however, more malignant forms of presentation of this necrotizing arteritis involving either the great vessels of the aorta or, occasionally, the pulmonary arteries. Our case relates to giant cell arteritis presenting as pulmonary artery obstruction in a patient without polymyalgia rheumatica or extensive aortic or proximal great vessel involvement.

From July 1972 through July 1983, 360 consecutive patients 70 years of age and older (mean age 74.1; range 70-88 years) underwent 362 valve replacement procedures. There were 122 isolated aortic valve replacements (33.7%; Group I); 70 isolated mitral valve replacements (19.3%; Group II); and 170 patients had combined procedures (47.0%; Group III), which included the replacement of at least one valve. Eighteen patients (5.0%) had previous cardiac surgery. Thirty-two patients (8.8%) were operated as emergencies. Three hundred and thirty-two (86.5%) of all valves implanted were porcine heterografts. Pre-operatively, over one-half (53.6%) of the patients were in New York Heart Association Functional Class IV. The overall hospital mortality was 13.8% (50 patients). The aortic valve mortality was 11.5%, the mitral valve mortality was 15.7%, and the combined procedures 14.7%. The follow-up period for hospital survivors (312 patients) extended from 2 weeks to 127.2 months, with a mean of 38.7 months or a total of 1,006 patient-years. The long term survival computed up to six years shows a 65 +/- 3.8% (standard error of the mean) for the entire group. The aortic valve group survival was 71 +/- 5.6%; the mitral valve group 60 +/- 8.2%; and the combined procedures group was 64 +/- 5.3%. Postoperative functional improvement was significant with 71.8% of the survivors in Class I and 19.6% in Class II. Based on these results, advanced age can no longer be considered a deterrant to cardiac surgery. The porcine heterograft appears to be the valve substitute of choice for this age group.(ABSTRACT TRUNCATED AT 250 WORDS)

From November, 1972, through December, 1986, 219 consecutive patients 70 years of age and older with aortic stenosis (AS) underwent aortic valve replacement. One hundred seven of them had isolated pure AS, and 112 had AS and coronary artery disease (AS + CAD). The mean age of the AS group was 75.4 years (range, 70 to 88 years) and of the AS + CAD group, 74.8 years (range, 70 to 86 years). The mean aortic valve gradient in the AS group was 87.7 +/- 30.6 mm Hg and in the AS + CAD group, 68.0 +/- 51.3 mm Hg (p less than 0.001). Hospital mortality for the AS group was 12.1% (13 patients) and for the AS + CAD group, 8.9% (10 patients). The long-term survival at seven years was 77.2 +/- 5.5% (+/- the standard error of the mean) for the AS group and 57.0 +/- 6.9% for the AS + CAD group (p less than 0.006). Postoperative assessment reveals substantial functional improvement. These early and long-term favorable results provide a much needed reference point when valvuloplasty is being considered. Aortic valve replacement is the treatment of choice in elderly patients with symptomatic AS.

In a series of 130 patients undergoing aortic valve replacement, 20 had the ascending aorta enlarged with a Dacron patch. Eight of these required division of the annulus with extension of the incision inferiorly to the anterior leaflet of the mitral valve. The resulting separation of the annulus allowed a larger size valve to be inserted. Glutaraldehyde-fixed procine heterografts were used in all patients having the annulus enlarged. No deaths occurred in those patients having annular enlargement, and the post-operative studies show no evidence of mitral valve dysfunction.

Replacement of the aortic valve can be accomplished with ease and safety in most instances. The presence of a small aortic root, however, remains a problem in that both mechanical and stent-mounted tissue valves produce higher resting gradients in the smaller sizes. To avoid this, a technique has been developed to enlarge the aortic annulus. In a series of 253 patients undergoing aortic valve replacement, 22 required division of the aortic annulus. Extension of the incision inferiorly to the anterior leaflet of the mitral valve and a resulting separation of the annulus facilitated implantation of a larger valve. The resulting defect is obliterated with a woven Dacron patch. Hemodynamic data obtained on 12 patients who had recatheterization one to ten months postoperatively disclosed an average resting transvalvular gradient of 13.5 mm Hg. This procedure has been used successfully in combined aortic and mitral valve replacement and heart block has not occurred. Based upon encouraging follow-up studies of the Hancock glutaraldehyde-stabilized porcine heterograft, we use this prosthesis in patients with annular diameters of less than 25 mm. Our experience suggests that enlargement of the aortic annulus is necessary in a significant number of patients undergoing aortic valve replacement.