Minimally invasive mitral valve replacement: Port-access technique, feasibility, and myocardial functional preservation

AbstractObjective: This experiment examined the feasibility of minimally invasive port-access mitral valve replacement via a 2.5 cm incision. Methods: The study evaluated valvular performance and myocardial functional recovery in six mongrel dogs after port-access mitral valve replacement with a St. Jude Medical prosthesis (St. Jude Medical, Inc., St. Paul, Minn.). Femoro-femoral cardiopulmonary bypass and a balloon catheter system for myocardial protection with cardioplegic arrest (Heartport, Inc., Redwood City, Calif.) were used. The mitral valve was replaced through a 2.5 cm port in the left side of the chest, and the animals were weaned from bypass. Cardiac function was measured before and at 30 and 60 minutes after bypass. Left ventricular pressure and electrical conductance volume were used to calculate changes in load-independent indexes of ventricular function. Results: Each procedure was successfully completed. Recovery of left ventricular function was excellent at 30 and 60 minutes after bypass compared with the prebypass values for elastance (30 minutes = 4.04 ± 0.97 and 60 minutes = 4.27 ± 0.57 vs prebypass = 4.45 ± 0.96; p = 0.51) and for preload recruitable stroke work (30 minutes = 76.23 ± 4.80 and 60 minutes = 71.21 ± 2.99 vs prebypass = 71.23 ± 3.75; p = 0.45). Preload recruitable work area remained at 96% and 85% of baseline at 30 and 60 minutes (p = not significant). In addition, transesophageal echocardiography demonstrated normal prosthetic valve function, as well as normal regional and global ventricular wall motion. Autopsy revealed secure annular-sewing apposition and normal leaflet motion. Conclusions: These results suggest that minimally invasive mitral valve replacement using percutaneous cardiopulmonary bypass with cardioplegic arrest is technically reproducible, achieves normal valve placement, and results in complete cardiac functional recovery. Minimally invasive mitral valve replacement is now feasible, and clinical trials are indicated. (J Thorac Cardiovasc Surg 1997; 113:1022-31

Urban agriculture, civil interfaces and moving beyond difference: the experiences of plot holders in Dublin and Belfast

Recent literature suggests that a “shared politics of place” attained through joint activities fosters social integration and provides people with a means to practise co-operation [Baumann, G., 1996. Contesting culture: discourses of identity in multi-ethnic London. Cambridge: Cambridge University Press; Sanjek, R., 1998. The future of us all: race & neighbourhood policies in New York City. Ithaca, NY: Cornell University Press; Sennett, R., 2012. Together: the rituals, pleasures and politics of cooperation. UK: Penguin]. Such a “shared politics of place” is most likely to occur in the context of public space conceptualised broadly as “the setting for everyday spatial behaviour of individuals and communities, emphasizing ordinary activities of citizens” [Lownsbrough, H. and Beunderman, J., 2007. Equally spaced? Public space and interaction between diverse communities. London: Demos, p. 8]. Here we explore one element of such public space – urban agriculture sites – with a view to identifying the extent to which a “shared politics of place” can be created and nurtured among the cultivating citizenry. The paper draws on data collected on allotment gardening sites in two urban contexts: Dublin (Ireland) and Belfast (Northern Ireland) over the period 2009–2013. We demonstrate the centrality of allotment cultivation to the generation of solidarity, mutuality and trust among participating citizens. Individuals engaging in allotment gardening in both Dublin and Belfast create and sustain civil interfaces – dismantling barriers, exchanging knowledge, challenging stereotypes, generating empathy and getting on with the business of simply getting on with their lives. The modus operandi of allotment gardening is predicated on a willingness to disregard social and ethno-national categorisations while on site. This is not to deny that such differences exist and persist, but allotments offer a “space of potential” where those differences are, at least for a time, rendered less salient

Predictors of Radiotherapy Induced Bone Injury (RIBI) after stereotactic lung radiotherapy

<p>Abstract</p> <p>Background</p> <p>The purpose of this study was to identify clinical and dosimetric factors associated with radiotherapy induced bone injury (RIBI) following stereotactic lung radiotherapy.</p> <p>Methods</p> <p>Inoperable patients with early stage non-small cell lung cancer, treated with SBRT, who received 54 or 60 Gy in 3 fractions, and had a minimum of 6 months follow up were reviewed. Archived treatment plans were retrieved, ribs delineated individually and treatment plans re-computed using heterogeneity correction. Clinical and dosimetric factors were evaluated for their association with rib fracture using logistic regression analysis; a dose-event curve and nomogram were created.</p> <p>Results</p> <p>46 consecutive patients treated between Oct 2004 and Dec 2008 with median follow-up 25 months (m) (range 6 – 51 m) were eligible. 41 fractured ribs were detected in 17 patients; median time to fracture was 21 m (range 7 – 40 m). The mean maximum point dose in non-fractured ribs (n = 1054) was 10.5 Gy ± 10.2 Gy, this was higher in fractured ribs (n = 41) 48.5 Gy ± 24.3 Gy (p < 0.0001). On univariate analysis, age, dose to 0.5 cc of the ribs (D_0.5), and the volume of the rib receiving at least 25 Gy (V₂₅), were significantly associated with RIBI. As D_0.5 and V₂₅ were cross-correlated (Spearman correlation coefficient: 0.57, p < 0.001), we selected D_0.5 as a representative dose parameter. On multivariate analysis, age (odds ratio: 1.121, 95% CI: 1.04 – 1.21, p = 0.003), female gender (odds ratio: 4.43, 95% CI: 1.68 – 11.68, p = 0.003), and rib D_0.5 (odds ratio: 1.0009, 95% CI: 1.0007 – 1.001, p < 0.0001) were significantly associated with rib fracture.</p> <p>Using D_0.5, a dose-event curve was constructed estimating risk of fracture from dose at the median follow up of 25 months after treatment. In our cohort, a 50% risk of rib fracture was associated with a D_0.5 of 60 Gy.</p> <p>Conclusions</p> <p>Dosimetric and clinical factors contribute to risk of RIBI and both should be included when modeling risk of toxicity. A nomogram is presented using D_0.5, age, and female gender to estimate risk of RIBI following SBRT. This requires validation.</p

Comparative Analysis of Acinetobacters: Three Genomes for Three Lifestyles

Acinetobacter baumannii is the source of numerous nosocomial infections in humans and therefore deserves close attention as multidrug or even pandrug resistant strains are increasingly being identified worldwide. Here we report the comparison of two newly sequenced genomes of A. baumannii. The human isolate A. baumannii AYE is multidrug resistant whereas strain SDF, which was isolated from body lice, is antibiotic susceptible. As reference for comparison in this analysis, the genome of the soil-living bacterium A. baylyi strain ADP1 was used. The most interesting dissimilarities we observed were that i) whereas strain AYE and A. baylyi genomes harbored very few Insertion Sequence elements which could promote expression of downstream genes, strain SDF sequence contains several hundred of them that have played a crucial role in its genome reduction (gene disruptions and simple DNA loss); ii) strain SDF has low catabolic capacities compared to strain AYE. Interestingly, the latter has even higher catabolic capacities than A. baylyi which has already been reported as a very nutritionally versatile organism. This metabolic performance could explain the persistence of A. baumannii nosocomial strains in environments where nutrients are scarce; iii) several processes known to play a key role during host infection (biofilm formation, iron uptake, quorum sensing, virulence factors) were either different or absent, the best example of which is iron uptake. Indeed, strain AYE and A. baylyi use siderophore-based systems to scavenge iron from the environment whereas strain SDF uses an alternate system similar to the Haem Acquisition System (HAS). Taken together, all these observations suggest that the genome contents of the 3 Acinetobacters compared are partly shaped by life in distinct ecological niches: human (and more largely hospital environment), louse, soil

Genetic landscape of pediatric acute liver failure of indeterminate origin.

BACKGROUND AIMS Pediatric acute liver failure (PALF) is a life-threatening condition. In Europe, main causes are viral infections (12-16%) and inherited metabolic diseases (14-28%). Yet, in up to 50% of cases the underlying etiology remains elusive, challenging clinical management, including liver transplantation. We systematically studied indeterminate PALF cases referred for genetic evaluation by whole-exome sequencing (WES), and analyzed phenotypic and biochemical markers, and the diagnostic yield of WES in this condition. METHODS With this international, multicenter observational study, patients (0-18 y) with indeterminate PALF were analyzed by WES. Data on the clinical and biochemical phenotype were retrieved and systematically analyzed. RESULTS In total, 260 indeterminate PALF patients from 19 countries were recruited between 2011 and 2022, of whom 59 had recurrent PALF (RALF). WES established a genetic diagnosis in 37% of cases (97/260). Diagnostic yield was highest in children with PALF in the first year of life (46%), and in children with RALF (64%). Thirty-six distinct disease genes were identified. Defects in NBAS (n=20), MPV17 (n=8) and DGUOK (n=7) were the most frequent findings. When categorizing, most frequent were mitochondrial diseases (45%), disorders of vesicular trafficking (28%) and cytosolic aminoacyl-tRNA synthetase deficiencies (10%). One-third of patients had a fatal outcome. Fifty-six patients received liver transplants. CONCLUSION This study elucidates a large contribution of genetic causes in PALF of indeterminate origin with an increasing spectrum of disease entities. The high proportion of diagnosed cases and potential treatment implications argue for exome or in future rapid genome sequencing in PALF diagnostics

Genetic landscape of pediatric acute liver failure of indeterminate origin

BACKGROUND AND AIMS: Pediatric acute liver failure (PALF) is a life-threatening condition. In Europe, the main causes are viral infections (12%-16%) and inherited metabolic diseases (14%-28%). Yet, in up to 50% of cases the underlying etiology remains elusive, challenging clinical management, including liver transplantation. We systematically studied indeterminate PALF cases referred for genetic evaluation by whole-exome sequencing (WES), and analyzed phenotypic and biochemical markers, and the diagnostic yield of WES in this condition. APPROACH AND RESULTS: With this international, multicenter observational study, patients (0-18 y) with indeterminate PALF were analyzed by WES. Data on the clinical and biochemical phenotype were retrieved and systematically analyzed. RESULTS: In total, 260 indeterminate PALF patients from 19 countries were recruited between 2011 and 2022, of whom 59 had recurrent PALF. WES established a genetic diagnosis in 37% of cases (97/260). Diagnostic yield was highest in children with PALF in the first year of life (41%), and in children with recurrent acute liver failure (64%). Thirty-six distinct disease genes were identified. Defects in NBAS (n=20), MPV17 (n=8), and DGUOK (n=7) were the most frequent findings. When categorizing, the most frequent were mitochondrial diseases (45%), disorders of vesicular trafficking (28%), and cytosolic aminoacyl-tRNA synthetase deficiencies (10%). One-third of patients had a fatal outcome. Fifty-six patients received liver transplantation. CONCLUSIONS: This study elucidates a large contribution of genetic causes in PALF of indeterminate origin with an increasing spectrum of disease entities. The high proportion of diagnosed cases and potential treatment implications argue for exome or in future rapid genome sequencing in PALF diagnostics

Proceedings of the 3rd Biennial Conference of the Society for Implementation Research Collaboration (SIRC) 2015: advancing efficient methodologies through community partnerships and team science

It is well documented that the majority of adults, children and families in need of evidence-based behavioral health interventionsi do not receive them [1, 2] and that few robust empirically supported methods for implementing evidence-based practices (EBPs) exist. The Society for Implementation Research Collaboration (SIRC) represents a burgeoning effort to advance the innovation and rigor of implementation research and is uniquely focused on bringing together researchers and stakeholders committed to evaluating the implementation of complex evidence-based behavioral health interventions. Through its diverse activities and membership, SIRC aims to foster the promise of implementation research to better serve the behavioral health needs of the population by identifying rigorous, relevant, and efficient strategies that successfully transfer scientific evidence to clinical knowledge for use in real world settings [3]. SIRC began as a National Institute of Mental Health (NIMH)-funded conference series in 2010 (previously titled the “Seattle Implementation Research Conference”; $150,000 USD for 3 conferences in 2011, 2013, and 2015) with the recognition that there were multiple researchers and stakeholdersi working in parallel on innovative implementation science projects in behavioral health, but that formal channels for communicating and collaborating with one another were relatively unavailable. There was a significant need for a forum within which implementation researchers and stakeholders could learn from one another, refine approaches to science and practice, and develop an implementation research agenda using common measures, methods, and research principles to improve both the frequency and quality with which behavioral health treatment implementation is evaluated. SIRC’s membership growth is a testament to this identified need with more than 1000 members from 2011 to the present.ii SIRC’s primary objectives are to: (1) foster communication and collaboration across diverse groups, including implementation researchers, intermediariesi, as well as community stakeholders (SIRC uses the term “EBP champions” for these groups) – and to do so across multiple career levels (e.g., students, early career faculty, established investigators); and (2) enhance and disseminate rigorous measures and methodologies for implementing EBPs and evaluating EBP implementation efforts. These objectives are well aligned with Glasgow and colleagues’ [4] five core tenets deemed critical for advancing implementation science: collaboration, efficiency and speed, rigor and relevance, improved capacity, and cumulative knowledge. SIRC advances these objectives and tenets through in-person conferences, which bring together multidisciplinary implementation researchers and those implementing evidence-based behavioral health interventions in the community to share their work and create professional connections and collaborations