Protecting the Kidney in Liver Transplant Recipients: Practice‐Based Recommendations From the American Society of Transplantation Liver and Intestine Community of Practice

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134132/1/ajt13765_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134132/2/ajt13765.pd

Porphyromonas gingivalis induces CCR5-dependent transfer of infectious HIV-1 from oral keratinocytes to permissive cells

<p>Abstract</p> <p>Background</p> <p>Systemic infection with HIV occurs infrequently through the oral route. The frequency of occurrence may be increased by concomitant bacterial infection of the oral tissues, since co-infection and inflammation of some cell types increases HIV-1 replication. A putative periodontal pathogen, <it>Porphyromonas gingivalis </it>selectively up-regulates expression of the HIV-1 coreceptor CCR5 on oral keratinocytes. We, therefore, hypothesized that <it>P. gingivalis </it>modulates the outcome of HIV infection in oral epithelial cells.</p> <p>Results</p> <p>Oral and tonsil epithelial cells were pre-incubated with <it>P. gingivalis</it>, and inoculated with either an X4- or R5-type HIV-1. Between 6 and 48 hours post-inoculation, <it>P. gingivalis </it>selectively increased the infectivity of R5-tropic HIV-1 from oral and tonsil keratinocytes; infectivity of X4-tropic HIV-1 remained unchanged. Oral keratinocytes appeared to harbor infectious HIV-1, with no evidence of productive infection. HIV-1 was harbored at highest levels during the first 6 hours after HIV exposure and decreased to barely detectable levels at 48 hours. HIV did not appear to co-localize with <it>P. gingivalis</it>, which increased selective R5-tropic HIV-1 <it>trans </it>infection from keratinocytes to permissive cells. When CCR5 was selectively blocked, HIV-1 <it>trans </it>infection was reduced.</p> <p>Conclusion</p> <p><it>P. gingivalis </it>up-regulation of CCR5 increases <it>trans </it>infection of harbored R5-tropic HIV-1 from oral keratinocytes to permissive cells. Oral infections such as periodontitis may, therefore, increase risk for oral infection and dissemination of R5-tropic HIV-1.</p

Validating a novel score based on interaction between ACLF grade and MELD score to predict waitlist mortality

Background and Aim: Among candidates listed for liver transplant (LT), MELD score may not capture acute on chronic liver failure (ACLF) severity. Data on interaction between ACLF and MELD score in predicting waitlist (WL) mortality are scanty. / Methods: UNOS database (01/2002 to 06/2018) on LT listings for adults with cirrhosis and ACLF (without HCC) was analyzed. ACLF grades 1, 2, 3a, and 3b- were defined using modified EASL-CLIF criteria. / Results: Of 18,416 candidates with ACLF at listing (mean age 54 years, 69% males, 63% Caucasians), 90-d WL mortality (patient death or being too sick for LT) was 21.6% (18%, 20%, 25%, and 39% for ACLF grades 1, 2, 3a, and 3b respectively). Fine and Gray regression model identified interaction between MELD and ACLF grade, with higher impact of ACLF at lower MELD score. Other variables included candidate’s age, gender, liver disease etiology, listing MELD, ACLF grade, obesity, and performance status. A score developed using parameter estimates from the interaction model on the derivation cohort (N=9181) stratified the validation cohort (N=9235) to four quartiles Q1 (score 15.50). WL mortality increased with each quartile from 13%, 18%, 23%, and 36% respectively. Observed versus expected deciles on WL mortality in validation cohort showed good calibration (goodness of fit P=0.98) and correlation (R=0.99). / Conclusion: Among selected candidates who are in ACLF at listing, MELD score and ACLF interact in predicting cumulative risk of 90-d WL mortality, with higher impact of ACLF grade at lower listing MELD score. Validating these findings in large prospective studies will support to factor in both MELD and ACLF in prioritizing transplant candidates and allocation of liver grafts

Performance Analysis in Mesh Network-on-Chip Topology by using Multilevel Network Partitioning

The increasing complexity of System-on-Chips (SoCs) has resulted in the bottlenecking of the system due to scalability problems in the bus system. This leads to the decrement of the performance of future SoCs with more complex circuitries inside them. Network-on-Chips (NoCs) was proposed as one of the solutions to overcome these issues especially regarding the communication between Intellectual Properties (IP) in a chip. The fundamentals in designing NoC include the selection of network topologies, and hence performance optimization is needed to ensure the full advantage of networking is taken. Therefore, multi-level Network Partitioning techniques are proposed to obtain the optimal design of networks based on its performance. The performance of a network is measured by its throughput, average queue size, waiting time and data loss. This technique is applied in a case study using MPEG-4 video application with four famous partitioning algorithms (Linear, Spectral, Tailor-Made and Kerninghan-Lin). Experimental results show that second level of spectral partitioning gives the best performance compared to another network partitioning

Chylous Pericardial Effusion and Tamponade Due to Catheter Induced Superior Vena Caval Obstruction in a Premature Infant

Abstract Chylous pericardial effusion and tamponade in children are rare complications of thoracic duct injury during cardiothoracic surgeries or as a result of superior vena cava (SVC) obstruction. We report a rare case of chylous tamponade in a premature infant as a complication of long standing central venous catheterization resulting in SVC obstruction. Urgent pericardiocentesis and then surgical creation of a pericardial window resulted in complete resolution of the effusion and recovery of the patient. Introduction Central venous catheters (CVCs) are more frequently used in the neonatal intensive care units as the birth rate and survival of premature infants increase. They provide long-standing central venous access for the administration of fluids, medications and nutrition. The most common complications of CVC placement are mechanical dislodgment, perforation, thrombosis, catheter obstruction and sepsis Case Report A thirty-six week gestation premature female infant was born via cesarean section. The pregnancy was complicated with a congenital diaphragmatic hernia and cardiac dextroposition. Postnatal 2-D echocardiogram showed normal cardiac anatomy and function and severe pulmonary hypertension. She required ECMO for the first 8 days of life. Surgical repair of the diaphragmatic hernia was performed at 2 weeks of age. A central venous catheter was needed for the administration of medications and for hyper-alimentation. The CVC was inserted in the SVC via the right internal jugular vein. At 3 months of age, she developed respiratory distress and edema of the upper chest, head and neck. A CXR showed an enlarged cardiac silhouette Journal of Pediatrics &amp; Child Care Figure 1: A chest X-Ray showing an enlarged cardiac silhouette due to pericardial effusion and obliteration of the left costophrenic angle due to pleural effusion

The TWEAK receptor Fn14 is a therapeutic target in melanoma: immunotoxins targeting Fn14 receptor for malignant melanoma treatment.

Fibroblast growth factor-inducible protein 14 (Fn14), the cell surface receptor for tumor necrosis factor-like weak inducer of apoptosis (TWEAK), is overexpressed in various human solid tumor types and can be a negative prognostic indicator. We detected Fn14 expression in ∼60% of the melanoma cell lines we tested, including both B-Raf WT and B-Raf(V600E) lines. Tumor tissue microarray analysis indicated that Fn14 expression was low in normal skin, but elevated in 173/190 (92%) of primary melanoma specimens and in 86/150 (58%) of melanoma metastases tested. We generated both a chemical conjugate composed of the recombinant gelonin (rGel) toxin and the anti-Fn14 antibody ITEM-4 (designated ITEM4-rGel) and a humanized, dimeric single-chain antibody of ITEM-4 fused to rGel (designated hSGZ). Both ITEM4-rGel and hSGZ were highly cytotoxic to a panel of different melanoma cell lines. Mechanistic studies showed that both immunotoxins induced melanoma cell necrosis. In addition, these immunotoxins could upregulate the cellular expression of Fn14 and trigger cell-signaling events similar to the Fn14 ligand TWEAK. Finally, treatment of mice bearing human melanoma MDA-MB-435 xenografts with either ITEM4-rGel or hSGZ showed significant tumor growth inhibition compared with controls. We conclude that Fn14 is a therapeutic target in melanoma and the hSGZ construct appears to warrant further development as a therapeutic agent against Fn14-positive melanoma

Feasibility of laser-targeted photoocclusion of the choriocapillary layer in rats

Purpose. A new method, laser-targeted photoocclusion, was developed to occlude choroidal neovascularization while minimizing damage to the overlying retina. The ability to occlude normal choriocapillary layer in rats was evaluated as a first test of die feasibility of treating choroidal neovascularization with this method. Method. A photosensitive agent, aluminum phdialocyanine tetrasulfonate, encapsulated in heat-sensitive liposomes, was administered intravenously along with carboxyfluorescein liposomes. A low-power argon laser (retinal power density of 5.7 W/cm 2 ) locally released a photosensitizer bolus, monitored by the simultaneous release of carboxyfluorescein. A diode laser (operating at 675 nm with a retinal power density of 0.27 W/cm 2 ) activated the photosensitizer with its release. Results. Vessels in the choriocapillary layer were occluded at day 3 after laser treatment and remained unchanged during die 30-day follow-up. Larger choroidal vessels and retinal capillaries remained perfused. Control experiments excluded possible effects of heat or activation of free photosensitizer. Pilot histologic studies showed no damage to the retinal pigment epithelium. Conclusions. Laser-targeted photoocclusion caused selective occlusion of normal choriocapillaries while sparing overlying retinal pigment epithelium and retinal vessels. The method has potential as a treatment of choroidal neovascularization diat may minimize iatrogenic loss of vision. Invest Ophthalmol Vis Sci. 1997;38:2702-2710 Age-related macular degeneration (ARMD) is one of the leading causes of severe loss of vision in people more than 50 years old. &quot; 3 Choroidal neovascularization (CNV), which occurs in ARMD, is often treated by laser photocoagulation. However, the thermal damage and the scarring of large macular areas can caus

Power Optimization for Mesh Network-on-Chip Architecture: Multilevel Network Partitioning Approach

This paper presents a power optimization for mesh Network-on-Chip (NoC) architecture by using Multilevel Network Partitioning approach. Power consumption is reduced by re-dividing the large networks into few smaller partitions. This approach assigns excessively communicated Intellectual Property (IP) cores into the same portion that result the minimal average inter-core distance. The efficiency of this methodology is verified through a System-on-Chip (SoC) application known as Video Object Plan Decoder (VOPD). Experimental results show a promising improvement of 16.59% in the power consumption

Serum Biomarker Signature Is Predictive of the Risk of Hepatocellular Cancer in Patients With Cirrhosis

BACKGROUND: Inflammatory and metabolic biomarkers have been associated with hepatocellular cancer (HCC) risk in phases I and II biomarker studies. We developed and internally validated a robust metabolic biomarker panel predictive of HCC in a longitudinal phase III study. METHODS: We used data and banked serum from a prospective cohort of 2266 adult patients with cirrhosis who were followed until the development of HCC (n=126). We custom designed a FirePlex immunoassay to measure baseline serum levels of 39 biomarkers and established a set of biomarkers with the highest discriminatory ability for HCC. We performed bootstrapping to evaluate the predictive performance using C-index and time-dependent area under the receiver operating characteristic curve (AUROC). We quantified the incremental predictive value of the biomarker panel when added to previously validated clinical models. RESULTS: We identified a nine-biomarker panel (P9) with a C-index of 0.67 (95% CI 0.66 to 0.67), including insulin growth factor-1, interleukin-10, transforming growth factor β1, adipsin, fetuin-A, interleukin-1 β, macrophage stimulating protein α chain, serum amyloid A and TNF-α. Adding P9 to our clinical model with 10 factors including AFP improved AUROC at 1 and 2 years by 4.8% and 2.7%, respectively. Adding P9 to aMAP score improved AUROC at 1 and 2 years by 14.2% and 7.6%, respectively. Adding AFP L-3 or DCP did not change the predictive ability of the P9 model. CONCLUSIONS: We identified a panel of nine serum biomarkers that is independently associated with developing HCC in cirrhosis and that improved the predictive ability of risk stratification models containing clinical factors