Endovascular stenting of the ascending aorta for visceral malperfusion in a patient with type A aortic dissection.

A type A aortic dissection is a challenging condition for both cardiothoracic and vascular surgeons. Although open surgery remains the gold standard, there is considerable interest in the use of endovascular techniques for patients who present with malperfusion. We present the case of an unstable 55-year-old man with visceral malperfusion from a type A dissection who was stabilized using an endovascular technique as a bridge to open surgery. A bare metal thoracic endograft was used in the ascending aorta to rapidly restore perfusion. This hybrid approach to the problem of malperfusion in type A dissection could be useful for these patients with complicated cases.

Flood Syndrome.

Flood syndrome refers to the exsanguination of ascitic fluid following the spontaneous rupture of an umbilical hernia, and is a rare complication of liver cirrhosis with ascites. In this case report, we describe a 67-year-old patient with Flood syndrome who was initially managed conservatively in a community hospital run by primary care physicians, prior to transfer to a tertiary hospital for specialist surgical review and management. We also performed a literature review of the current treatment modalities to manage this condition.

Association of the FRAIL scale with rehabilitation outcomes in the community hospital setting.

Introduction: Frailty is associated with adverse health outcomes and can be measured using the FRAIL scale. In Singapore, its use has been studied in tertiary hospitals but not in community hospitals. A tool to predict rehabilitation outcomes would allow for better risk stratification and allocation of resources. We aimed to determine whether the FRAIL scale is associated with rehabilitation outcomes in patients admitted to the community hospital setting, where post-acute care and rehabilitation are primarily delivered. Methods: This was a retrospective cohort study. The FRAIL scale was utilised to screen 560 older adults who were admitted to a community hospital for rehabilitation. Data were analysed to determine the relationship between baseline characteristics and frailty status, with rehabilitation outcome measures of absolute functional gain, rehabilitation effectiveness, rehabilitation efficiency, length of stay and discharge destination. Results: The combined score of the FRAIL scale showed significant negative association with absolute functional gain (P < 0.001), rehabilitation effectiveness (P < 0.001) and rehabilitation efficiency (P < 0.001), whereas it was positively associated with increased length of stay (P < 0.05) and a need for continued support in increased care settings (P < 0.001). Individual components of the FRAIL scale, in particular, the 'fatigue', 'ambulation' and 'loss of weight' components, appeared to be highly associated with rehabilitation effectiveness and efficiency, especially among pre-frail patients. Conclusion: The utility of the FRAIL scale as an indicator of frailty status and its association with rehabilitative outcomes in the post-acute care setting were demonstrated. Moreover, the FRAIL scale may better predict the rehabilitative progress of pre-frail patients.

Extended Robotic Pulmonary Resections.

While lung cancer remains the most common cause of cancer-related mortality in the United States, surgery for curative intent continues to be a mainstay of therapy. The robotic platform for pulmonary resection for non-small cell lung cancer (NSCLC) has been utilized for more than a decade now. With respect to more localized resections, such as wedge resection or lobectomy, considerable data exist demonstrating shorter length of stay, decreased postoperative pain, improved lymph node dissection, and overall lower complication rate. There are a multitude of technical advantages the robotic approach offers, such as improved optics, natural movement of the operator's hands to control the instruments, and precise identification of tissue planes leading to a more ergonomic and safe dissection. Due to the advantages, the scope of robotic resections is expanding. In this review, we will look at the existing data on extended robotic pulmonary resections, specifically post-induction therapy resection, sleeve lobectomy, and pneumonectomy. Additionally, this review will examine the indications for these more complex resections, as well as review the data and outcomes from other institutions' experience with performing them. Lastly, we will share the strategy and outlook of our own institution with respect to these three types of extended pulmonary resections. Though some controversy remains regarding the use and safety of robotic surgery in these complex pulmonary resections, we hope to shed some light on the existing evidence and evaluate the efficacy and safety for patients with NSCLC.

Current Novel Advances in Bronchoscopy.

Screening for lung cancer has changed substantially in the past decade since The National Lung Screening Trial. The resultant increased discovery of incidental pulmonary nodules has led to a growth in the number of lesions requiring tissue diagnosis. Bronchoscopy is one main modality used to sample lesions, but peripheral lesions remain challenging for bronchoscopic biopsy. Alternatives have included transthoracic biopsy or operative biopsy, which are more invasive and have a higher morbidity than bronchoscopy. In hopes of developing less invasive diagnostic techniques, technologies have come to assist the bronchoscopist in reaching the outer edges of the lung. Navigational bronchoscopy is able to virtually map the lung and direct the biopsy needle where the scope cannot reach. Robotic bronchoscopy platforms have been developed to provide stability and smaller optics to drive deeper into the bronchial tree. While these new systems have not yet proven better outcomes, they may reduce the need for invasive procedures and be valuable armamentarium in diagnosing and treating lung nodules, especially in the periphery.

The Integrator complex cleaves nascent mRNAs to attenuate transcription.

Cellular homeostasis requires transcriptional outputs to be coordinated, and many events post-transcription initiation can dictate the levels and functions of mature transcripts. To systematically identify regulators of inducible gene expression, we performed high-throughput RNAi screening of the Drosophila Metallothionein A (MtnA) promoter. This revealed that the Integrator complex, which has a well-established role in 3' end processing of small nuclear RNAs (snRNAs), attenuates MtnA transcription during copper stress. Integrator complex subunit 11 (IntS11) endonucleolytically cleaves MtnA transcripts, resulting in premature transcription termination and degradation of the nascent RNAs by the RNA exosome, a complex also identified in the screen. Using RNA-seq, we then identified >400 additional Drosophila protein-coding genes whose expression increases upon Integrator depletion. We focused on a subset of these genes and confirmed that Integrator is bound to their 5' ends and negatively regulates their transcription via IntS11 endonuclease activity. Many noncatalytic Integrator subunits, which are largely dispensable for snRNA processing, also have regulatory roles at these protein-coding genes, possibly by controlling Integrator recruitment or RNA polymerase II dynamics. Altogether, our results suggest that attenuation via Integrator cleavage limits production of many full-length mRNAs, allowing precise control of transcription outputs.

The development and metamorphosis of the indirect developing acorn worm Schizocardium californicum (Enteropneusta: Spengelidae).

BACKGROUND: Enteropneusts are benthic marine invertebrates that belong to the deuterostome phylum Hemichordata. The two main clades of enteropneusts are defined by differences in early life history strategies. In the Spengelidae and Ptychoderidae, development is indirect via a planktotrophic tornaria larva. In contrast, development in the Harrimanidae is direct without an intervening larval life history stage. Most molecular studies in the development and evolution of the enteropneust adult body plan have been carried out in the harrimanid Saccoglossus kowalevskii. In order to compare these two developmental strategies, we have selected the spengelid enteropneust Schizocardium californicum as a suitable indirect developing species for molecular developmental studies. Here we describe the methods for adult collecting, spawning and larval rearing in Schizocardium californicum, and describe embryogenesis, larval development, and metamorphosis, using light microscopy, immunocytochemistry and confocal microscopy. RESULTS: Adult reproductive individuals can be collected intertidally and almost year-round. Spawning can be triggered by heat shock and large numbers of larvae can be reared through metamorphosis under laboratory conditions. Gastrulation begins at 17 h post-fertilization (hpf) and embryos hatch at 26 hpf as ciliated gastrulae. At 3 days post-fertilization (dpf), the tornaria has a circumoral ciliary band, mouth, tripartite digestive tract, protocoel, larval muscles and a simple serotonergic nervous system. The telotroch develops at 5 dpf. In the course of 60 days, the serotonergic nervous system becomes more elaborate, the posterior coeloms develop, and the length of the circumoral ciliary band increases. At the end of the larval stage, larval muscles disappear, gill slits form, and adult muscles develop. Metamorphosis occurs spontaneously when the larva reaches its maximal size (ca. 3 mm), and involves loss and reorganization of larval structures (muscles, nervous system, digestive tract), as well as development of adult structures (adult muscles, tripartite body organization). CONCLUSIONS: This study will enable future research in S. californicum to address long standing questions related to the evolution of axial patterning mechanisms, germ layer induction, neurogenesis and neural patterning, the mechanisms of metamorphosis, the relationships between larval and adult body plans, and the evolution of metazoan larval forms.

Robotic multisegment triangular resections as an alternative to sliding leaflet plasty.

The sliding leaflet plasty of the posterior mitral leaflet is a complex procedure, both lengthy and technically challenging. A simple alternative is desirable, particularly for a minimally invasive approach. We report a distinct substitute to the conventional sliding leaflet plasty that included triangular resections of P2 and P3 using a robot. These multiple triangular resections enabled a successful mitral valve repair with satisfactory clinical and echocardiographic results. Recognizing the complexity of sliding leaflet plasties, we note that multisegment triangular resections seem to be an easy, expeditious, and effective alternative for the posterior leaflet that is readily performed via a robotic endoscopic approach.

Preoperative assessment of high-risk candidates to predict survival after heart transplantation.

BACKGROUND: Alternate waiting list strategies expand listing criteria for patients awaiting heart transplantation (HTx). We retrospectively analyzed clinical events and outcome of patients listed as high-risk recipients for HTx. METHODS AND RESULTS: We analyzed 822 adult patients who underwent HTx of whom 111 patients met high-risk criteria. Clinical data were collected from medical records and outcome factors calculated for 61 characteristics. Significant factors were summarized in a prognostic score. Age >65 years (67%) and amyloidosis (19%) were the most common reasons for alternate listing. High-risk recipients were older (63.2±10.2 versus 51.4±11.8 years; P<0.001), had more renal dysfunction, prior cancer, and smoking. Survival analysis revealed lower post-HTx survival in high-risk recipients (82.2% versus 87.4% at 1-year; 59.8% versus 76.3% at 5-year post-HTx; P=0.0005). Prior cerebral vascular accident, albumin <3.5 mg/dL, re-HTx, renal dysfunction (glomerular filtration rate <40 mL/min), and >2 prior sternotomies were associated with poor survival after HTx. A prognostic risk score (CARRS [CVA, albumin, re-HTx, renal dysfunction, and sternotomies]) derived from these factors stratified survival post-HTx in high-risk (3+ points) versus low-risk (0-2 points) patients (87.9% versus 52.9% at 1-year; 65.9% versus 28.4% at 5-year post-HTx; P<0.001). Low-risk alternate patients had survival comparable with regular patients (87.9% versus 87.0% at 1-year and 65.9% versus 74.5% at 5-year post-HTx; P=0.46). CONCLUSIONS: High-risk patients had reduced survival compared with regular patients post-HTx. Among patients previously accepted for alternate donor listing, application of the CARRS score identifies patients with unacceptably high mortality after HTx and those with a survival similar to regularly listed patients.

Risk stratification of ambulatory patients with advanced heart failure undergoing evaluation for heart transplantation.

BACKGROUND: Risk stratification of ambulatory heart failure (HF) patients has relied on peak VO(2)<14 ml/kg/min. We investigated whether additional clinical variables might further specify risk of death, ventricular assist device (VAD) implantation (INTERMACS <4) or heart transplantation (HTx, Status 1A or 1B) within 1 year after HTx evaluation. We hypothesized that right ventricular stroke work index (RVSWI), pulmonary capillary wedge pressure (PCWP) and the model for end-stage liver disease-albumin score (MELD-A) would be additive prognostic predictors. METHODS: We retrospectively collected data on 151 ambulatory patients undergoing HTx evaluation. Primary outcomes were defined as HTx, LVAD or death within 1 year after evaluation. RESULTS: Average age in our cohort was 55 ± 11.1 years, 79.1% were male and 39% had an ischemic etiology (LVEF 21 ± 10.5% and peak VO(2) 12.6 ± 3.5 ml/kg/min). Fifty outcomes (33.1%) were observed (27 HTxs, 15 VADs and 8 deaths). Univariate logistic regression showed a significant association of RVSWI (OR 0.47, p = 0.036), PCWP (OR 2.65, p = 0.007) and MELD-A (OR 2.73, p = 0.006) with 1-year events. Stepwise regression showed an independent correlation of RVSWI<5gm-m(2)/beat (OR 6.70, p < 0.01), PCWP>20 mm Hg (OR 5.48, p < 0.01), MELD-A>14 (OR 3.72, p< 0.01) and peak VO(2)<14 ml/kg/min (OR 3.36, p = 0.024) with 1-year events. A scoring system was developed: MELD-A>14 and peak VO(2)<14-1 point each; and PCWP>20 and RVSWI<5-2 points each. A cut-off at≥4 demonstrated a 54% sensitivity and 88% specificity for 1-year events. CONCLUSIONS: Ambulatory HF patients have significant 1-year event rates. Risk stratification based on exercise performance, left-sided congestion, right ventricular dysfunction and liver congestion allows prediction of 1-year prognosis. Our findings support early and timely referral for VAD and/or transplant.

Right atrial lesions do not improve the efficacy of a complete left atrial lesion set in the surgical treatment of atrial fibrillation, but they do increase procedural morbidity.

OBJECTIVE: Some have suggested the superiority of biatrial versus left atrial lesions. We sought to analyze our experience. METHODS: We retrospectively reviewed 305 consecutive patients from 2007 to 2011. Rhythm success was defined as freedom from atrial fibrillation (AF) or flutter determined by 12-lead electrocardiograms at 3-month intervals. Lesions sets were pulmonary vein isolation (PVI), left-extended (PVI + mitral valve annulus [MV] lesion ± left atrial appendage lesion [LAA]) or biatrial-extended (right atrial ablation + PVI + MV ± LAA). RESULTS: The success rates of PVI, left-extended, and biatrial-extended lesions were as follows: at 3 months, 56.7%, 74.7%, and 79.4% (P = .003); at 6 months, 56.9%, 72.9%, and 74.6% (P = .02); at 9 months, 54.6%, 72.5%, and 83.3% (P < .001); and at 12 months, 52.6%, 76.1%, and 80.0% (P < .001). Biatrial lesions had a higher rate of pacemaker placement than did left atrial lesions (16.5% vs 7.5%; P = .02). When we grouped patients by left lesion (PVI, PVI + MV, PVI + MV + LAA) irrespective of right atrial ablation, success was as follows: 3 months, 57.9%, 71.1%, and 87.8% (P < .01); 6 months, 58.1%, 71.6%, and 77.6% (P = .03); 9 months, 55.9%, 71.3%, and 89.6% (P < .01); and 12 months, 54.1%, 74.7%, and 83.7% (P < .01). CONCLUSIONS: PVI is associated with lower rhythm success than an extended left atrial lesion set. The addition of a right atrial lesion to an extended left atrial lesion set does not improve efficacy, but it does increase the rate of pacemaker placement for sinus dysfunction. Adding an LAA lesion may confer additional efficacy when added to a lesion set that includes PVI + MV.

An original model to predict Intensive Care Unit length-of stay after cardiac surgery in a competing risk framework.

BACKGROUND: The aim of the study is to design a specific Intensive Care Unit length-of-stay risk model based on the preoperative factors and surgeries utilizing modeling strategies for time-to-event data in a prospective observational clinical study. METHODS: From January 2004 to April 2011 data on 3861 consecutive heart surgery patients were prospectively collected. ICU length of stay was analyzed as a time-to-event variable in a competing risk framework with death as competing risk. RESULTS: The median ICU-LOS was one day. All factors considered but gender was included in the multivariable modeling. In the final model, factors that mostly affected time-to-discharge from ICU were critical preoperative state (Relative Risk 0.41; 95% Confidence Interval: 0.29-0.58), emergency (0.41; 0.32-0.53), poor left ventricular dysfunction (0.50; 0.44-0.57) and serum creatinine>200 µmol/L (0.54; 0.46-0.65). Most of the predictors had a time-dependent effect that decreased in the first fifteen days and was constant thereafter. After the plateau, the risk profile was changed as most of the factors were no longer significant, Conversely, the time-to-ICU death model included only two variables, critical perioperative state and serum creatinine>200 µmol/L, with a constant RR of 9.1 and 3.37 respectively. CONCLUSIONS: ICU-LOS can be predicted by preoperative data and type of surgeries. The derived ICU-LOS prediction model is dynamic and most predictors have an effect that decreases with time. The algorithm can preoperatively predict ICU-LOS curves and could have a major role in the decision making-behavior of clinicians, resources' allocation and maximization of care for high-risk patients.

Serial echocardiography using tissue Doppler and speckle tracking imaging to monitor right ventricular failure before and after left ventricular assist device surgery.

OBJECTIVES: This study aimed to investigate the utility of serial tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE) for monitoring right ventricular failure (RVF) after left ventricular assist device (LVAD) surgery. BACKGROUND: RVF post-LVAD is a devastating adverse event. METHODS: The authors prospectively studied 68 patients undergoing elective LVAD surgery. Echocardiograms were performed within 72 h before and 72 h after surgery. RVF was pre-specified as: 1) the need for salvage right ventricular assist device (RVAD); or 2) persistent need for inotrope and/or pulmonary vasodilator therapy 14 days after surgery. Patients were classified as Group RVF or Group Non-RVF. RESULTS: A total of 24 patients (35.3%) met criteria for RVF. Preoperative TDI-derived S' was lower and RV E/E' ratio was higher (3.7 ± 0.6 cm/s vs. 4.7 ± 0.9 cm/s, 12.0 ± 2.3 vs. 10.0 ± 2.5, both p < 0.001, respectively), and the absolute value of RV longitudinal strain (RV-strain) obtained from STE was lower (-12.6 ± 3.3% vs. -16.2 ± 4.3%, p < 0.001) in Group RVF vs. Group Non-RVF. Echo parameters within 72 h after surgery showed higher RV-E/E', (13.9 ± 4.6 vs. 10.1 ± 3.0, p < 0.001) and lower RV-strain (-11.8 ± 3.5% vs. -16.7 ± 4.4%, p < 0.001) in Group RVF vs. Group Non-RVF. Preoperative S'<4.4 cm/s, RV-E/E'>10 and RV-strain < -14% discriminated patients who developed RVF at day 14 with a predictive accuracy of 76.5%. When we included postoperative RV-E/E' and RV-strain, the predictive accuracy increased to 80.9%, with a sensitivity of 66.7% and a specificity of 88.7%. CONCLUSIONS: Serial echocardiograms using TDI and STE before and soon after LVAD surgery may aid in identifying need to initiate targeted RVF specific therapy in this population.

Hepatic dysfunction and survival after orthotopic heart transplantation: application of the MELD scoring system for outcome prediction.

BACKGROUND: The prevalence of heart failure (HF) is rising and the only corrective treatment is cardiac transplantation. Advanced HF is associated with congestive hepatopathy and progressive functional and ultrastructural changes of the liver. We hypothesized that hepatic dysfunction is associated with impaired clinical outcome after heart transplantation. METHODS: Data of 617 adult patients (75% men, mean age 53 ± 12 years, mean BMI 25 ± 4, mean ejection fraction 19 ± 9%) undergoing orthotopic heart transplantation (OHT) were analyzed retrospectively. Deviation from institutional normal ranges was used to define abnormal liver function. Standard Model for End-stage Liver Disease (MELD) scores were calculated and a modified MELD score with albumin replacing INR (modMELD) was created to eliminate the confounding effects of anti-coagulation. RESULTS: Before OHT, AST, ALT and total bilirubin were elevated in 20%, 18% and 29% of the population, respectively. Total protein and albumin were decreased in 25% and 52% of the population, respectively. By 2 months post-transplantation, percentages of individuals with pathologic values decreased significantly, except for ALT, total protein and albumin, all of which took longer to normalize. Individuals with a higher pre-transplantation MELD or modMELD score had worse outcome 30 days post-transplant and reduced long-term survival over a 10-year follow-up. CONCLUSIONS: In this large, single-center retrospective study, we demonstrated the dynamics of liver dysfunction after cardiac transplantation and that elevated MELD scores indicating impaired liver function are associated with poor clinical outcome after OHT. Thus, pre-operative liver dysfunction has a significant impact on survival of patients after cardiac transplantation.

Cardiac transplantation in over 2000 patients: a single-institution experience from Columbia University.

Since 1977, the cardiac transplantation program at Columbia has performed 2143 heart transplant operations with a current 1-year survival rate of approximately 87% and a 5-year survival rate of approximately 76%, representing the largest single-institution experience in North America. Over three decades of experience in the selection of donors and recipients has permitted us to expand eligibility limits and relax conventional exclusion criteria, allowing us to transplant high-risk donors and medically complex recipients with excellent results. Increasing use of mechanical support is being seen to bridge candidates to cardiac transplantation. Recipient characteristics, rather than those of the donor, substantially impact outcome following OHT and use of extended-criteria donors helps to alleviate the ongoing donor shortage; but this scarcity of donor hearts remains the major obstacle to the growth of transplantation. During the last decade, substantial improvements have been made in the areas of immunosuppression, treatment of rejection, and handling of sensitized recipients. Frequent causes of late mortality such as graft rejection, infection and TCAD, have been significantly diminished in the modern area of immune manipulation but remain major causes of death and barriers to long-term survival.

Towards prediction and prioritization of disease genes by the modularity of human phenome-genome assembled network.

Empirical clinical studies on the human interactome and phenome not only illustrates prevalent phenotypic overlap and genetic overlap between diseases, but also reveals a modular organization of the genetic landscape of human disease, providing new opportunities to reduce the complexity in dissecting the phenotype-genotype association. We here introduce a network-module based method towards phenotype-genotype association inference and disease gene identification. This approach incorporates protein-protein interaction network, phenotype similarity network and known phenotype-genotype associations into an assembled network. We then decomposes the resulted network into modules (or communities) wherein we identified and prioritized the disease genes from the candidates within the loci associated with the query disease using a linear regression model and concordance score. For the known phenotype-gene associations in the OMIM database, we used the leave-one-out validation to evaluate the feasibility of our method, and successfully ranked known disease genes at top 1 in 887 out of 1807 cases. Moreover, applying this approach on 850 OMIM loci characterized by an unknown molecular basis, we propose high-probability candidates for 81 genetic diseases.