ABO incompatibility is no longer considered a contraindication for adult living donor liver transplantation (ALDLT) due to various strategies to overcome the ABO blood group barrier. We report the ...largest single‐center experience of ABO‐incompatible (ABOi) ALDLT in 235 adult patients. The desensitization protocol included a single dose of rituximab and total plasma exchange. In addition, local graft infusion therapy, cyclophosphamide, or splenectomy was used for a certain time period, but these treatments were eventually discontinued due to adverse events. There were three cases (1.3%) of in‐hospital mortality. The cumulative 3‐year graft and patient survival rates were 89.2% and 92.3%, respectively, and were comparable to those of the ABO‐compatible group (n = 1301). Despite promising survival outcomes, 17 patients (7.2%) experienced antibody‐mediated rejection that manifested as diffuse intrahepatic biliary stricture; six cases required retransplantation, and three patients died. ABOi ALDLT is a feasible method for expanding a living liver donor pool, but the efficacy of the desensitization protocol in targeting B cell immunity should be optimized.
This article presents the clinical results of ABO‐incompatible adult living donor liver transplantation in a single institution.
In order to determine the location of the gamma-ray emission site in blazars, we investigate the time-domain relationship between their radio and gamma-ray emission. Light curves for the brightest ...detected blazars from the first 3 yr of the mission of the Fermi Gamma-ray Space Telescope are cross-correlated with 4 yr of 15 GHz observations from the Owens Valley Radio Observatory 40 m monitoring programme. The large sample and long light-curve duration enable us to carry out a statistically robust analysis of the significance of the cross-correlations, which is investigated using Monte Carlo simulations including the uneven sampling and noise properties of the light curves. Modelling the light curves as red noise processes with power-law power spectral densities, we find that only one of 41 sources with high-quality data in both bands shows correlations with significance larger than 3σ (AO 0235+164), with only two more larger than even 2.25σ (PKS 1502+106 and B2 2308+34). Additionally, we find correlated variability in Mrk 421 when including a strong flare that occurred in 2012 July–September. These results demonstrate very clearly the difficulty of measuring statistically robust multiwavelength correlations and the care needed when comparing light curves even when many years of data are used. This should be a caution. In all four sources, the radio variations lag the gamma-ray variations, suggesting that the gamma-ray emission originates upstream of the radio emission. Continuous simultaneous monitoring over a longer time period is required to obtain high significance levels in cross-correlations between gamma-ray and radio variability in most blazars.
An up‐to‐date map of the Antarctic Circumpolar Current (ACC) fronts is constructed from the latest version of mean dynamic topography (MDT) from satellite altimetry and reveals the narrowest ACC ...width in the Udintsev Fracture Zone (UFZ), with the strongest concentration of the three major ACC fronts within a limited distance as short as 170 km, about 40% narrower than that at Drake Passage. At 144°W, at the entrance of the UFZ, which lies between the Pacific‐Antarctic Ridge (PAR) and its eastwardly offset segment (offset PAR segment), there is a triple confluence of the Subantarctic Front, Polar Front, and Southern ACC Front . Downstream of this longitude, the Subantarctic Front progressively meanders northward over the relatively shallow offset PAR segment before channeling through the Eltanin Fracture Zone, thus diverging from the Polar Front which proceeds through the UFZ. In situ observations from two recent cruises at 144°W confirm the satellite altimetry‐derived frontal circulation in the UFZ region and yield a baroclinic transport relative to the bottom of 113 × 106 m3/s, comparable to that through Drake Passage. The hydrographic sections show no Antarctic bottom water colder than 0.2 °C. Characteristics of major water masses are described, and the implications for their potential downstream modifications at Drake Passage are discussed in terms of the meridional overturning circulation across the ACC. Mesoscale eddy activity with periods shorter than 90 days is predominantly concentrated in the immediate downstream area of the offset PAR segment, suggesting a substantial poleward eddy heat flux there.
Key Points
The Antarctic Circumpolar Current is only 170 km wide in the Udintsev Fracture Zone, forming the narrowest circumpolar choke point
First observations of high‐quality hydrography in the Udintsev Fracture Zone show no Antarctic bottom water colder than 0.2 °C
The Udintsev Fracture Zone is a suitable site for a long‐term monitoring of the Antarctic Circumpolar Current
We model the ultraviolet spectra of the Seyfert 1 galaxy NGC 5548 obtained with the Hubble Space Telescope during the 6 month reverberation mapping campaign in 2014. Our model of the emission from ...NGC 5548 corrects for overlying absorption and deblends the individual emission lines. Using the modeled spectra, we measure the response to continuum variations for the deblended and absorption-corrected individual broad emission lines, the velocity-dependent profiles of Ly and C iv, and the narrow and broad intrinsic absorption features. We find that the time lags for the corrected emission lines are comparable to those for the original data. The velocity-binned lag profiles of Ly and C iv have a double-peaked structure indicative of a truncated Keplerian disk. The narrow absorption lines show a delayed response to continuum variations corresponding to recombination in gas with a density of ∼105 cm−3. The high-ionization narrow absorption lines decorrelate from continuum variations during the same period as the broad emission lines. Analyzing the response of these absorption lines during this period shows that the ionizing flux is diminished in strength relative to the far-ultraviolet continuum. The broad absorption lines associated with the X-ray obscurer decrease in strength during this same time interval. The appearance of X-ray obscuration in ∼2012 corresponds with an increase in the luminosity of NGC 5548 following an extended low state. We suggest that the obscurer is a disk wind triggered by the brightening of NGC 5548 following the decrease in size of the broad-line region during the preceding low-luminosity state.
Liquid biopsies including circulating tumor cells (CTCs) and cell-free DNA (cfDNA) have enabled minimally invasive characterization of many cancers, but are rarely analyzed together. Understanding ...the detectability and genomic concordance of CTCs and cfDNA may inform their use in guiding cancer precision medicine. Here, we report the detectability of cfDNA and CTCs in blood samples from 107 and 56 patients with multiple myeloma (MM), respectively. Using ultra-low pass whole-genome sequencing, we find both tumor fractions correlate with disease progression. Applying whole-exome sequencing (WES) to cfDNA, CTCs, and matched tumor biopsies, we find concordance in clonal somatic mutations (~99%) and copy number alterations (~81%) between liquid and tumor biopsies. Importantly, analyzing CTCs and cfDNA together enables cross-validation of mutations, uncovers mutations exclusive to either CTCs or cfDNA, and allows blood-based tumor profiling in a greater fraction of patients. Our study demonstrates the utility of analyzing both CTCs and cfDNA in MM.
Background
In gallbladder cancer, stage T2 is subdivided by tumour location into lesions on the peritoneal side (T2a) or hepatic side (T2b). For tumours on the peritoneal side (T2a), it has been ...suggested that liver resection may be omitted without compromising the prognosis. However, data to validate this argument are lacking. This study aimed to investigate the prognostic value of tumour location in T2 gallbladder cancer, and to clarify the adequate extent of surgical resection.
Methods
Clinical data from patients who underwent surgery for gallbladder cancer were collected from 14 hospitals in Korea, Japan, Chile and the USA. Survival and risk factor analyses were conducted.
Results
Data from 937 patients were available for evaluation. The overall 5‐year disease‐free survival rate was 70·6 per cent, 74·5 per cent for those with T2a and 65·5 per cent among those with T2b tumours (P = 0·028). Regarding liver resection, extended cholecystectomy was associated with a better 5‐year disease‐free survival rate than simple cholecystectomy (73·0 versus 61·5 per cent; P = 0·012). The 5‐year disease‐free survival rate was marginally better for extended than simple cholecystectomy in both T2a (76·5 versus 66·1 per cent; P = 0·094) and T2b (68·2 versus 56·2 per cent; P = 0·084) disease. Five‐year disease‐free survival rates were similar for extended cholecystectomies including liver wedge resection versus segment IVb/V segmentectomy (74·1 versus 71·5 per cent; P = 0·720). In multivariable analysis, independent risk factors for recurrence were presence of symptoms (hazard ratio (HR) 1·52; P = 0·002), R1 resection (HR 1·96; P = 0·004) and N1/N2 status (N1: HR 3·40, P < 0·001; N2: HR 9·56, P < 0·001). Among recurrences, 70·8 per cent were metastatic.
Conclusion
Tumour location was not an independent prognostic factor in T2 gallbladder cancer. Extended cholecystectomy was marginally superior to simple cholecystectomy. A radical operation should include liver resection and adequate node dissection.
Antecedentes
En el cáncer de vesícula biliar, la ubicación del tumor subdivide el estadio T2 en tumores con invasión del lado peritoneal y del lado del hígado (T2a y T2b). Para los tumores que invaden el lado peritoneal (T2a) se sugiere que se puede obviar la resección hepática sin que ello comprometa el pronóstico. Sin embargo, este argumento no ha sido validado. El estudio tuvo como objetivo investigar el valor pronóstico de la localización del tumor en el cáncer de vesícula biliar T2 y establecer la extensión adecuada de la resección quirúrgica.
Métodos
Se recogieron los datos clínicos de pacientes que se sometieron a cirugía por cáncer de vesícula biliar en 14 hospitales de Corea, Japón, Chile y Estados Unidos. Se realizaron análisis de la supervivencia y de los factores de riesgo.
Resultados
Se dispuso de datos de 937 pacientes para ser evaluados. La tasa de supervivencia global libre de enfermedad a los 5 años fue del 70,6%, y las de T2a y T2b del 74,5% y 65,5% (P = 0,028). Con respecto a la resección hepática, la colecistectomía extendida presentó una tasa mejor de supervivencia libre de enfermedad a los 5 años que la colecistectomía simple (73,0% versus 61,5%, P = 0,012). La tasa de supervivencia libre de enfermedad a los 5 años fue marginalmente mejor para la colecistectomía extendida que para la colecistectomía simple tanto en T2a (76,5% versus 66,1%, P = 0,094) como en T2b (68,2% versus 56,2%, P = 0,084). Las tasas de supervivencia libre de enfermedad a los 5 años no fueron diferentes entre la resección hepática en cuña y la segmentectomía S4b+S5 (74,1% versus 71,5%, P = 0,720). En el análisis multivariable, los factores de riesgo independientes para la recidiva fueron la presencia de síntomas (cociente de riesgos instantáneos, hazard ratio, HR 1,52, P = 0,002), la resección R1 (HR 1,96, P = 0,004) y el estadio N1/N2 (N1 HR 3,40, P < 0,001; N2 HR 9,56, P < 0,001). El 70,8% de las recidivas eran metastásicas.
Conclusión
La localización del tumor no fue un factor pronóstico independiente en el cáncer de vesícula biliar T2. La colecistectomía extendida fue marginalmente superior que la colecistectomía simple. La cirugía radical debe incluir una resección hepática y una linfadenectomía adecuada.
This multinational multicentre cohort study was undertaken to investigate the prognostic value of tumour location in T2 gallbladder cancer and to clarify the adequate extent of surgical resection. Although tumour location influenced prognosis, it was not an independent prognostic factor in T2 gallbladder cancer. T2 gallbladder cancer requires extended cholecystectomy including hepatic resection and lymph node dissection, regardless of the location.
challenges current TNM system
Summary
Background
Toluene diisocyanate (TDI) is the most important cause of occupational asthma, but the genetic mechanism of TDI‐induced asthma is still unknown.
Objective
The objective of the ...study was to identify susceptibility alleles associated with the TDI‐induced asthma phenotype.
Methods
We conducted a genome‐wide association study in 84 patients with TDI‐induced asthma and 263 unexposed healthy normal controls using Affymetrix 500K SNPchip. We also investigated the relationships between genetic polymorphisms and transcript levels in Epstein–Barr virus‐transformed lymphoblastoid cell lines from patients with TDI‐induced asthma enrolled in this study.
Results
Genetic polymorphisms of CTNNA3 (catenin alpha 3, alpha‐T catenin) were significantly associated with the TDI‐induced asthma phenotype (5.84 × 10−6 for rs10762058, 1.41 × 10−5 for rs7088181, 2.03 × 10−5 for rs4378283). Carriers with the minor haplotype, HT2 GG, of two genetic polymorphisms (rs10762058 and rs7088181) showed significantly lower PC20 methacholine level (P=0.041) and lower mRNA expression of CTNNA3 than non‐carriers (P=0.040). A genetic polymorphism in the 3′ downstream region of CTNNA3 (rs1786929), as identified by DNA direct sequencing, was significantly associated with the TDI‐induced asthma phenotype (P=0.015 in recessive analysis model) and the prevalence of serum‐specific IgG to cytokeratin 19 (P=0.031).
Conclusion
These findings suggested that multiple genetic polymorphisms of CTNNA3 may be determinants of susceptibility to TDI‐induced asthma.
Recent natural and man‐made catastrophes, such as the Fukushima nuclear power plant, flooding caused by Hurricane Katrina, the Deepwater Horizon oil spill, the Haiti earthquake, and the mortgage ...derivatives crisis, have renewed interest in the concept of resilience, especially as it relates to complex systems vulnerable to multiple or cascading failures. Although the meaning of resilience is contested in different contexts, in general resilience is understood to mean the capacity to adapt to changing conditions without catastrophic loss of form or function. In the context of engineering systems, this has sometimes been interpreted as the probability that system conditions might exceed an irrevocable tipping point. However, we argue that this approach improperly conflates resilience and risk perspectives by expressing resilience exclusively in risk terms. In contrast, we describe resilience as an emergent property of what an engineering system does, rather than a static property the system has. Therefore, resilience cannot be measured at the systems scale solely from examination of component parts. Instead, resilience is better understood as the outcome of a recursive process that includes: sensing, anticipation, learning, and adaptation. In this approach, resilience analysis can be understood as differentiable from, but complementary to, risk analysis, with important implications for the adaptive management of complex, coupled engineering systems. Management of the 2011 flooding in the Mississippi River Basin is discussed as an example of the successes and challenges of resilience‐based management of complex natural systems that have been extensively altered by engineered structures.
To cite this article: Kim YH, Yang TY, Park C‐S, Ahn S‐H, Son BK, Kim JH, Lim DH, Jang TY. Anti‐IL‐33 antibody has a therapeutic effect in a murine model of allergic rhinitis. Allergy 2012; 67: ...183–190.
Background: Interleukin (IL)‐33 is involved in the Th2 immune response and could play an essential role in nasal allergy. Therefore, we aimed to investigate the therapeutic potential of anti‐IL‐33 for allergic rhinitis (AR).
Methods: Twenty‐four BALB/c mice were used. In group A (control group, n = 6), mice were sensitized and challenged with saline. Group B ovalbumin (OVA) group, n = 6 mice received intraperitoneal and intranasal OVA challenge. In group C (control IgG group, n = 6), mice were injected intraperitoneally with rabbit control IgG before OVA challenge. In group D (anti‐IL‐33 group, n = 6), anti‐IL‐33 was injected before challenge. We evaluated the number of nose‐scratching events and external morphology; serum total and OVA‐specific IgE; number of eosinophils, neutrophils, and lymphocytes in bronchoalveolar lavage (BAL) fluid; histopathologic examination of nasal cavity; and IL‐4, IL‐5, and IL‐13 in BAL fluid.
Results: Anti‐IL‐33 treatment significantly reduced the nose‐scratching events and ameliorated skin denudation. Serum total and OVA‐specific IgE was significantly decreased in group D. The number of eosinophils in BAL fluid was also significantly decreased. Eosinophilic infiltration in the nasal cavity was significantly decreased in group D. IL‐4, IL‐5, and IL‐13 in BAL fluid were also significantly decreased after treatment.
Conclusions: Anti‐IL‐33 antibody has a therapeutic potential for experimental AR.
Abstract Background Living donor liver transplantation (LDLT) has been the first option for the patients requiring liver transplantation in East Asia because of the scarcity of cadaveric grafts. We ...have performed consecutively more than 300 LDLTs per year, and herein report our methods. Methods In 1997, the first successful adult LDLTs used a left and subsequently a right lobe. However, congestion in the anterior segment of right-lobe grafts prompted us to initiate reconstruction of middle hepatic venous tributaries in 1998. Dual LDLT grafts using 2 left lobes were developed in 2000 to solve graft-size insufficiency and minimize donor risk. The indications for adult LDLT were broadened to near complete obstruction of the portal vein by application of intraoperative cine-portography and portal vein stenting in 2004. ABO-incompatible adult LDLT was initiated in 2008 to overcome the blood group barrier between recipient and donor. Results With various innovations at our institution, 317 LDLTs were performed yearly in 2010 and 2011: 301 in 2010 and 298 in 2011. The most common primary diseases was hepatitis B virus-related liver cirrhosis with or without hepatocellular carcinoma (64.3%). The most common graft types were right hemiliver (82.6%). There has been no donor mortality. ABO-incompatible LDLT cases were 11.0% of the total. In-hospital mortality in 2011 was 2.5% ( n = 8; adult 6, pediatric 2). Conclusion Innovations in operative techniques and perioperative care as well as dedicated team members have made it possible to perform more than 300 LDLTs per year consecutively with excellent outcomes.
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