Outcomes of 1½- or 2-ventricle conversion for patients initially treated with single-ventricle palliation

ObjectiveAs outcomes for the Fontan procedure have improved, it has become more difficult to select between a single-ventricle repair or biventricular repair for patients with complex anatomy and 2 ventricles. However, late complications after the Fontan procedure remain a concern. Our strategy, which has favored an aggressive preferential approach for biventricular repair in these patients, has also been applied to patients initially treated on a single-ventricle track elsewhere.MethodsNine patients (4 male patients) who had previously undergone the Fontan procedure (n = 3) or bidirectional cavopulmonary shunting (n = 6) with intent for a later Fontan procedure were referred to our center for complex 1½- or 2-ventricle repair over the last 10 years. Indications for conversion in these patients were protein-losing enteropathy (n = 2), pulmonary arteriovenous malformation (n = 1), and preference for biventricular anatomy (n = 6). The conversion mainly consisted of takedown of the Fontan procedure or bidirectional cavopulmonary shunt connection, reconstruction of 1 or both of venae cavae, creation of an intraventricular pathway for left ventricular output, and placement of a right ventricle–pulmonary artery conduit (Rastelli-type operation).ResultsFive patients underwent 1½-ventricle repair, and 4 had complete biventricular repair. Median cardiopulmonary bypass and aortic crossclamp times were 202 minutes (range, 169–352 minutes) and 129 minutes (range, 100–168 minutes), respectively. There were 2 early deaths and 1 late death. At a median follow-up of 27 months (range, 3.3–99.8 months), all survivors are in New York Heart Association class I.ConclusionsPatients initially treated with intent to perform single-ventricle palliation can be converted to 1½- or 2-ventricle physiology with acceptable outcomes

Biventricular repair for aortic atresia or hypoplasia and ventricular septal defect

AbstractObjective: Aortic valve atresia or hypoplasia can present with a ventricular septal defect and a normal mitral valve and left ventricle. These patients may be suitable for biventricular repair, although the optimal initial management strategy remains unknown. Methods: From January 1991 through March 1999, 20 patients with aortic atresia or hypoplasia and ventricular septal defect underwent operation with the intent to achieve biventricular repair. Aortic atresia was present in 7 patients, and aortic valve hypoplasia was present in 13 patients. Among those patients with aortic hypoplasia, Z-scores of the aortic valve anulus ranged from –8.8 to –2.7. Associated anomalies included interrupted aortic arch (n = 12 patients), coarctation (n = 6 patients), aortopulmonary window (n = 1 patient), and heterotaxia (n = 1 patient). Nine patients were staged with an initial Norwood procedure followed by biventricular repair in 8 patients. One patient awaits biventricular repair after a Norwood procedure. The conditions of 11 patients were corrected with a single procedure. Results: Among the 9 patients who underwent staged repair, there were no deaths after the Norwood procedure and 1 death after biventricular repair. For the 11 patients who underwent a primary biventricular repair, there was 1 early death and 2 late deaths from noncardiac causes. Follow-up ranged from 1 to 85 months (mean, 28 months). Actuarial survival for the entire group was 78% ± 10% at 5 years and was not significantly different between staged repair (89%) and primary biventricular repair (73%). Conclusions: Both primary and staged biventricular repair for patients with aortic atresia or hypoplasia and ventricular septal defect may be performed with good late survival. Refinements in technique of conduit insertion and arch reconstruction have resulted in primary biventricular repair becoming our preferred approach. (J Thorac Cardiovasc Surg 1999;118:648-54

Early Surgical Morbidity and Mortality in Adults with Congenital Heart Disease: The University of Michigan Experience

Objectives.  To review early surgical outcomes in a contemporary series of adults with congenital heart disease (CHD) undergoing cardiac operations at the University of Michigan, and to investigate possible preoperative and intraoperative risk factors for morbidity and mortality. Methods.  A retrospective medical record review was performed for all patients ≥18 years of age who underwent open heart operations by a pediatric cardiothoracic surgeon at the University of Michigan Congenital Heart Center between January 1, 1998 and December 31, 2004. Records from a cohort of pediatric patients ages 1–17 years were matched to a subset of the adult patients by surgical procedure and date of operation. Results.  In total, 243 cardiac surgical operations were performed in 234 adult patients with CHD. Overall mortality was 4.7% (11/234). The incidence of major postoperative complications was 10% (23/234) with a 19% (45/23) minor complication rate. The most common postoperative complication was atrial arrhythmias in 10.8% (25/234). The presence of preoperative lung or liver disease, prolonged cardiopulmonary bypass and aortic cross clamp times, and postoperative elevated inotropic score and serum lactates were significant predictors of mortality in adults. There was no difference between the adult and pediatric cohorts in terms of mortality and morbidity. Conclusions.  The postoperative course in adults following surgery for CHD is generally uncomplicated and early survival should be expected. Certain risk factors for increased mortality in this patient population may include preoperative presence of chronic lung or liver dysfunction, prolonged cardiopulmonary bypass and aortic cross-clamp times, and postoperative elevated inotropic score and serum lactate levels.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/75596/1/j.1747-0803.2008.00170.x.pd

Breaking the In Vitro Alveolar Type II Cell Proliferation Barrier while Retaining Ion Transport Properties

Alveolar type (AT)I and ATII cells are central to maintaining normal alveolar fluid homeostasis. When disrupted, they contribute to the pathogenesis of acute lung injury (ALI) and acute respiratory distress syndrome. Research on ATII cells has been limited by the inability to propagate primary cells in vitro to study their specific functional properties. Moreover, primary ATII cells in vitro quickly transdifferentiate into nonproliferative “ATI-like” cells under traditional culture conditions. Recent studies have demonstrated that normal and tumor cells grown in culture with a combination of fibroblast (feeder cells) and a pharmacological Rho kinase inhibitor (Y-27632) exhibit indefinite cell proliferation that resembled a “conditionally reprogrammed cell” phenotype. Using this coculture system, we found that primary human ATII cells (1) proliferated at an exponential rate, (2) established epithelial colonies expressing ATII-specific and “ATI-like” mRNA and proteins after serial passage, (3) up-regulated genes important in cell proliferation and migration, and (4) on removal of feeder cells and Rho kinase inhibitor under air–liquid interface conditions, exhibited bioelectric and volume transport characteristics similar to freshly cultured ATII cells. Collectively, our results demonstrate that this novel coculture technique breaks the in vitro ATII cell proliferation barrier while retaining cell-specific functional properties. This work will allow for a significant increase in studies designed to elucidate ATII cell function with the goal of accelerating the development of novel therapies for alveolar diseases

Oncological Outcomes of Patients with High-Volume mCRPC. Results from a Longitudinal Real-Life Multicenter Cohort

Simple Summary Metastatic prostate cancer (PCa) may occur as progression after local therapy with curative intent or may be metastatic as newly onset. Approximately 5% of PCa present with metastatic stage at the time of diagnosis. Therapeutic management differs widely according to the site of metastases, the sensitivity to hormonal treatments and the volume of disease. We reported survival outcomes of patients with high-volume metastatic castration-resistant PCa (mCRPC) treated with ARTA in a chemo-naive setting compared to patients treated with chemotherapy as first-line from a longitudinal real-life multicenter series. In our population of 88 high-volume-disease mCRPC patients, we showed that survival probabilities are comparable between first-line ARTA and upfront chemotherapy-treated cohorts. Therefore, regardless tumor burden, novel antiandrogens can be useful treatment options and could be considered as first-line in order to postpone the use of more toxic treatments such as chemotherapy, in the case of significant disease progression.Abstract Registrative trials recommended the use of upfront chemotherapy in high-volume metastatic prostate cancer. We reported survival outcomes of patients with high-volume mCRPC treated with ARTA in a chemo-naive setting compared to patients treated with chemotherapy as first-line from a longitudinal real-life multicenter series. We retrospectively collected data on mCRPC patients treated at six centers. The dataset was queried for high-volume disease (defined as more than 6 bone lesions or bulky nodes >= 5 cm). We compared the main clinical features of chemo-naive versus chemo-treated patients. The Mann-Whitney U test and Chi-squared test were used to compare continuous and categorial variables, respectively. The Kaplan-Meier method was used to compare differences in terms of progression-free survival (PFS), cancer specific survival (CSS) and overall survival (OS) in an upfront ARTA or chemo-treated setting. Survival probabilities were computed at 12, 24, 48, and 60 months. Out of 216 patients, 88 cases with high-volume disease were selected. Sixty-nine patients (78.4%) received upfront ARTA, while 19 patients received chemotherapy as the first-line treatment option. Forty-eight patients received Abiraterone (AA), 21 patients received Enzalutamide (EZ) as the first-line treatment. The ARTA population was older (p = 0.007) and less likely to receive further lines of treatment (p = 0.001) than the chemo-treated cohort. The five-year PFS, CSS and OS were 60%, 73.3%, and 72.9%, respectively. Overall, 28 patients (31.8%) shifted after their first-line therapy to a second-line therapy: EZ was prescribed in 17 cases, AA in seven cases and radiometabolic therapy in four patients. Sixteen cases (18.2%) developed significant progression and were treated with chemotherapy. At Kaplan-Meyer analysis PFS, CSS and OS were comparable for upfront ARTA vs chemo-treated patients (log rank p = 0.10, p = 0.64 and p = 0.36, respectively). We reported comparable survival probabilities in a real-life series of high-volume mCRPC patients who either received upfront ARTA or chemotherapy. Patients primarily treated with chemotherapy were younger and more likely to receive further treatment lines than the upfront ARTA cohort. Our data support the use of novel antiandrogens as first line treatment regardless tumor burden, delaying the beginning of a more toxic chemotherapy in case of significant disease progression

Water dynamics in Shewanella oneidensis at ambient and high pressure using quasi-elastic neutron scattering

Quasielastic neutron scattering (QENS) is an ideal technique for studying water transport and relaxation dynamics at pico- to nanosecond timescales and at length scales relevant to cellular dimensions. Studies of high pressure dynamic effects in live organisms are needed to understand Earth’s deep biosphere and biotechnology applications. Here we applied QENS to study water transport in Shewanella oneidensis at ambient (0.1 MPa) and high (200 MPa) pressure using H/D isotopic contrast experiments for normal and perdeuterated bacteria and buffer solutions to distinguish intracellular and transmembrane processes. The results indicate that intracellular water dynamics are comparable with bulk diffusion rates in aqueous fluids at ambient conditions but a significant reduction occurs in high pressure mobility. We interpret this as due to enhanced interactions with macromolecules in the nanoconfined environment. Overall diffusion rates across the cell envelope also occur at similar rates but unexpected narrowing of the QENS signal appears between momentum transfer values Q = 0.7–1.1 Å−1 corresponding to real space dimensions of 6–9 Å. The relaxation time increase can be explained by correlated dynamics of molecules passing through Aquaporin water transport complexes located within the inner or outer membrane structures

Individual patient data meta-analysis of self-monitoring of blood pressure (BP-SMART): a protocol.

INTRODUCTION: Self-monitoring of blood pressure is effective in reducing blood pressure in hypertension. However previous meta-analyses have shown a considerable amount of heterogeneity between studies, only part of which can be accounted for by meta-regression. This may be due to differences in design, recruited populations, intervention components or results among patient subgroups. To further investigate these differences, an individual patient data (IPD) meta-analysis of self-monitoring of blood pressure will be performed. METHODS AND ANALYSIS: We will identify randomised trials that have compared patients with hypertension who are self-monitoring blood pressure with those who are not and invite trialists to provide IPD including clinic and/or ambulatory systolic and diastolic blood pressure at baseline and all follow-up points where both intervention and control groups were measured. Other data requested will include measurement methodology, length of follow-up, cointerventions, baseline demographic (age, gender) and psychosocial factors (deprivation, quality of life), setting, intensity of self-monitoring, self-monitored blood pressure, comorbidities, lifestyle factors (weight, smoking) and presence or not of antihypertensive treatment. Data on all available patients will be included in order to take an intention-to-treat approach. A two-stage procedure for IPD meta-analysis, stratified by trial and taking into account age, sex, diabetes and baseline systolic BP will be used. Exploratory subgroup analyses will further investigate non-linear relationships between the prespecified variables. Sensitivity analyses will assess the impact of trials which have and have not provided IPD. ETHICS AND DISSEMINATION: This study does not include identifiable data. Results will be disseminated in a peer-reviewed publication and by international conference presentations. CONCLUSIONS: IPD analysis should help the understanding of which self-monitoring interventions for which patient groups are most effective in the control of blood pressure