Solving the Organ Shortage Crisis: The 7th Annual American Society of Transplant Surgeons’ State-of-the-Art Winter Symposium

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/73036/1/j.1600-6143.2007.02146.x.pd

Pre-Operative Risk Factors Predict Post-Operative Respiratory Failure after Liver Transplantation

OBJECTIVE: Post-operative pulmonary complications significantly affect patient survival rates, but there is still no conclusive evidence regarding the effect of post-operative respiratory failure after liver transplantation on patient prognosis. This study aimed to predict the risk factors for post-operative respiratory failure (PRF) after liver transplantation and the impact on short-term survival rates. DESIGN: The retrospective observational cohort study was conducted in a twelve-bed adult surgical intensive care unit in northern Taiwan. The medical records of 147 liver transplant patients were reviewed from September 2002 to July 2007. Sixty-two experienced post-operative respiratory failure while the remaining 85 patients did not. MEASUREMENTS AND MAIN RESULTS: Gender, age, etiology, disease history, pre-operative ventilator use, molecular adsorbent re-circulating system (MARS) use, source of organ transplantation, model for end-stage liver disease score (MELD) and Child-Turcotte-Pugh score calculated immediately before surgery were assessed for the two groups. The length of the intensive care unit stay, admission duration, and mortality within 30 days, 3 months, and 1 year were also evaluated. Using a logistic regression model, post-operative respiratory failure correlated with diabetes mellitus prior to liver transplantation, pre-operative impaired renal function, pre-operative ventilator use, pre-operative MARS use and deceased donor source of organ transplantation (p<0.05). Once liver transplant patients developed PRF, their length of ICU stay and admission duration were prolonged, significantly increasing their mortality and morbidity (p<0.001). CONCLUSIONS: The predictive pre-operative risk factors significantly influenced the occurrence of post-operative respiratory failure after liver transplantation

Modulation of apoptosis in human hepatocellular carcinoma (HepG2 cells) by a standardized herbal decoction of Nigella sativa seeds, Hemidesmus indicus roots and Smilax glabra rhizomes with anti- hepatocarcinogenic effects

<p>Abstract</p> <p>Background</p> <p>A standardized poly-herbal decoction of <it>Nigella sativa </it>seeds, <it>Hemidesmus indicus </it>roots and <it>Smilax glabra </it>rhizomes used traditionally in Sri Lanka for cancer therapy has been demonstrated previously, to have anti-hepatocarcinogenic potential. Cytotoxicity, antioxidant activity, anti-inflammatory activity, and up regulation of p53 and p21 activities are considered to be some of the possible mechanisms through which the above decoction may mediate its anti-hepatocarcinogenic action. The main aim of the present study was to determine whether apoptosis is also a major mechanism by which the decoction mediates its anti-hepatocarcinogenic action.</p> <p>Methods</p> <p>Evaluation of apoptosis in HepG2 cells was carried out by (a) microscopic observations of cell morphology, (b) DNA fragmentation analysis, (c) activities of caspase 3 and 9, as well as by (d) analysis of the expression of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) proteins associated with cell death.</p> <p>Results</p> <p>The results demonstrated that in HepG2 cells, the decoction can induce (a) DNA fragmentation and (b) characteristic morphological changes associated with apoptosis (nuclear condensation, membrane blebbing, nuclear fragmentation and apoptotic bodies). The decoction could also, in a time and dose dependent manner, up regulate the expression of the pro-apoptotic gene <it>Bax </it>and down regulate expression of anti-apoptotic <it>Bcl-2 </it>gene (as evident from RT-PCR analysis, immunohistochemistry and western blotting). Further, the decoction significantly (<it>p </it>< .001) enhanced the activities of caspase-3 and caspase-9 in a time and dose dependent manner.</p> <p>Conclusions</p> <p>Overall findings provide confirmatory evidence to demonstrate that the decoction may mediate its reported anti-hepatocarcinogenic effect, at least in part, through modulation of apoptosis.</p

Efficacy of adenovirally expressed soluble TRAIL in human glioma organotypic slice culture and glioma xenografts

Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) selectively induces apoptosis in malignant cells, including gliomas, and is currently in anticancer clinical trials. However, the full-length and tagged forms of TRAIL, unlike the untagged ligand (soluble TRAIL (sTRAIL)), exhibits toxicity against normal cells. Here, we report the generation and testing of an adenovirus (AdsTRAIL) that expresses untagged sTRAIL in an intracranial xenograft model and a human glioma organotypic slice culture model. AdsTRAIL efficiently induced apoptosis in glioma cell lines, including those resistant to sTRAIL, but not in normal human astrocytes (NHAs). It inhibited anchorage-independent glioma growth and exerted a bystander effect in transwell assays. Intratumoral injections of AdsTRAIL in a rodent intracranial glioma model resulted in reduced tumor growth and improved survival compared with Ad-enhanced green fluorescent protein (EGFP)- or vehicle-treated controls without toxicity. Human glioma organotypic slices treated with AdsTRAIL demonstrated apoptosis induction and caspase activation

Latitudinal Gradients in Degradation of Marine Dissolved Organic Carbon

Heterotrophic microbial communities cycle nearly half of net primary productivity in the ocean, and play a particularly important role in transformations of dissolved organic carbon (DOC). The specific means by which these communities mediate the transformations of organic carbon are largely unknown, since the vast majority of marine bacteria have not been isolated in culture, and most measurements of DOC degradation rates have focused on uptake and metabolism of either bulk DOC or of simple model compounds (e.g. specific amino acids or sugars). Genomic investigations provide information about the potential capabilities of organisms and communities but not the extent to which such potential is expressed. We tested directly the capabilities of heterotrophic microbial communities in surface ocean waters at 32 stations spanning latitudes from 76°S to 79°N to hydrolyze a range of high molecular weight organic substrates and thereby initiate organic matter degradation. These data demonstrate the existence of a latitudinal gradient in the range of complex substrates available to heterotrophic microbial communities, paralleling the global gradient in bacterial species richness. As changing climate increasingly affects the marine environment, changes in the spectrum of substrates accessible by microbial communities may lead to shifts in the location and rate at which marine DOC is respired. Since the inventory of DOC in the ocean is comparable in magnitude to the atmospheric CO2 reservoir, such a change could profoundly affect the global carbon cycle

Pretransplant Prediction of Posttransplant Survival for Liver Recipients with Benign End-Stage Liver Diseases: A Nonlinear Model

Background: The scarcity of grafts available necessitates a system that considers expected posttransplant survival, in addition to pretransplant mortality as estimated by the MELD. So far, however, conventional linear techniques have failed to achieve sufficient accuracy in posttransplant outcome prediction. In this study, we aim to develop a pretransplant predictive model for liver recipients ’ survival with benign end-stage liver diseases (BESLD) by a nonlinear method based on pretransplant characteristics, and compare its performance with a BESLD-specific prognostic model (MELD) and a generalillness severity model (the sequential organ failure assessment score, or SOFA score). Methodology/Principal Findings: With retrospectively collected data on 360 recipients receiving deceased-donor transplantation for BESLD between February 1999 and August 2009 in the west China hospital of Sichuan university, we developed a multi-layer perceptron (MLP) network to predict one-year and two-year survival probability after transplantation. The performances of the MLP, SOFA, and MELD were assessed by measuring both calibration ability and discriminative power, with Hosmer-Lemeshow test and receiver operating characteristic analysis, respectively. By the forward stepwise selection, donor age and BMI; serum concentration of HB, Crea, ALB, TB, ALT, INR, Na +; presence of pretransplant diabetes; dialysis prior to transplantation, and microbiologically proven sepsis were identified to be the optimal input features. The MLP, employing 18 input neurons and 12 hidden neurons, yielded high predictive accuracy, wit

Effects of magnolol on UVB-induced skin cancer development in mice and its possible mechanism of action

Background Magnolol, a plant lignan isolated from the bark and seed cones of Magnolia officinalis, has been shown to have chemopreventive effects on chemically-induced skin cancer development. The objectives of this investigation are to study the anticarcinogenic effects of magnolol on UVB-induced skin tumor development in SKH-1 mice, a model relevant to humans, and determine the possible role of apoptosis and cell cycle arrest involved in the skin tumor development. Methods UVB-induced skin carcinogenesis model in SKH-1 mice was used for determining the preventive effects of magnolol on skin cancer development. Western blottings and flow cytometric analysis were used to study the effects of magnolol on apoptosis and cell cycle. Results Magnolol pretreated groups (30, 60 μ g) before UVB treatments (30 mJ/cm2, 5 days/week) resulted in 27-55% reduction in tumor multiplicity as compared to control group in SKH-1 mice. Magnolol pretreatment increased the cleavage of caspase-8 and poly-(-ADP-ribose) polymerase (PARP), increased the expression of p21, a cell cycle inhibitor, and decreased the expression of proteins involved in the G2/M phase of cell cycle in skin samples from SKH-1 mice. Treatment of A431 cells with magnolol decreased cell viability and cell proliferation in a concentration dependent manner. Magnolol induced G2/M phase cell cycle arrest in A431 cells at 12 h with a decreased expression of cell cycle proteins such as cyclin B1, cyclin A, CDK4, Cdc2 and simultaneous increase in the expression of Cip/p21, a cyclin-dependent kinase inhibitor. Magnolol induced apoptosis in vivo and in vitro with an increased cleavage of caspase-8 and PARP. Phospho-signal transducers and activators of transcription 3 (Tyr705), B-Raf, p-MEK, and p-AKT were down-regulated, whereas phosphorylation of ERK was induced by magnolol in A431 cells. Conclusions Magnolol pretreatments prevent UVB-induced skin cancer development by enhancing apoptosis, causing cell cycle arrest at G2/M phase, and affecting various signaling pathways. Magnolol could be a potentially safe and potent anticarcinogenic agent against skin cancer

Validation of a new test that assesses functional performance of the upper extremity and neck (FIT-HaNSA) in patients with shoulder pathology

<p>Abstract</p> <p>Background</p> <p>There is a lack of standardized tests that assess functional performance for sustained upper extremity activity. This study describes development of a new test for measuring functional performance of the upper extremity and neck and assesses reliability and concurrent validity in patients with shoulder pathology.</p> <p>Methods</p> <p>A series of developmental tests were conducted to develop a protocol for assessing upper extremity tasks that required multi-level movement and sustained elevation. Kinematics of movement were investigated to inform subtask structure. Tasks and test composition were refined to fit clinical applicability criteria and pilot tested on 5 patients awaiting surgery for shoulder impingement and age-sex matched controls. Test-retest reliability was assessed on 10 subjects. Then a cohort of patients with mild to moderate (n = 17) shoulder pathology and 19 controls (17 were age-sex matched to patients) were tested to further validate the Functional Impairment Test-Hand, and Neck/Shoulder/Arm (FIT-HaNSA) by comparing it to self-reported function and measured strength. The FIT-HaNSA, DASH and SPADI were tested on a single occasion. Impairments in isometric strength were measured using hand-held dynamometry. Discriminative validity was determined by comparing scores to those of age-sex matched controls (n = 34), using ANOVA. Pearson correlations between outcome measures (n = 41) were examined to establish criterion and convergent validity.</p> <p>Results</p> <p>A test protocol based on three five-minute subtasks, each either comprised of moving objects to waist-height shelves, eye-level shelves, or sustained manipulation of overhead nuts/bolts, was developed. Test scores for the latter 2 subtasks (or total scores) were different between controls as compared to either surgical-list patients with shoulder impingement or a variety of milder shoulder pathologies (p < 0.01). Test 1 correlated the highest with the DASH (r = -0.83), whereas Test 2 correlated highest with the SPADI (r = -0.76).</p> <p>Conclusion</p> <p>Initial data suggest the FIT-HaNSA provides valid assessment of impaired functional performance in patients with shoulder pathology. It discriminates between patients and controls, is related to self-reported function, and yet provides distinct information. Longitudinal testing is warranted.</p

Intraperitoneal drain placement and outcomes after elective colorectal surgery: international matched, prospective, cohort study

Despite current guidelines, intraperitoneal drain placement after elective colorectal surgery remains widespread. Drains were not associated with earlier detection of intraperitoneal collections, but were associated with prolonged hospital stay and increased risk of surgical-site infections.Background Many surgeons routinely place intraperitoneal drains after elective colorectal surgery. However, enhanced recovery after surgery guidelines recommend against their routine use owing to a lack of clear clinical benefit. This study aimed to describe international variation in intraperitoneal drain placement and the safety of this practice. Methods COMPASS (COMPlicAted intra-abdominal collectionS after colorectal Surgery) was a prospective, international, cohort study which enrolled consecutive adults undergoing elective colorectal surgery (February to March 2020). The primary outcome was the rate of intraperitoneal drain placement. Secondary outcomes included: rate and time to diagnosis of postoperative intraperitoneal collections; rate of surgical site infections (SSIs); time to discharge; and 30-day major postoperative complications (Clavien-Dindo grade at least III). After propensity score matching, multivariable logistic regression and Cox proportional hazards regression were used to estimate the independent association of the secondary outcomes with drain placement. Results Overall, 1805 patients from 22 countries were included (798 women, 44.2 per cent; median age 67.0 years). The drain insertion rate was 51.9 per cent (937 patients). After matching, drains were not associated with reduced rates (odds ratio (OR) 1.33, 95 per cent c.i. 0.79 to 2.23; P = 0.287) or earlier detection (hazard ratio (HR) 0.87, 0.33 to 2.31; P = 0.780) of collections. Although not associated with worse major postoperative complications (OR 1.09, 0.68 to 1.75; P = 0.709), drains were associated with delayed hospital discharge (HR 0.58, 0.52 to 0.66; P &lt; 0.001) and an increased risk of SSIs (OR 2.47, 1.50 to 4.05; P &lt; 0.001). Conclusion Intraperitoneal drain placement after elective colorectal surgery is not associated with earlier detection of postoperative collections, but prolongs hospital stay and increases SSI risk