Combination of pancreas volume and HbA1c level predicts islet yield in patients undergoing total pancreatectomy and islet autotransplantation

Islet yield is an important predictor of acceptable glucose control after total pancreatectomy with islet autotransplantation (TP-IAT). We assessed if pancreas volume calculated with preoperative MRI could assess islet yield and postoperative outcomes. We reviewed dynamic MRI studies from 154 adult TP-IAT patients (2009-2016), and associations between calculated volumes and digest islet equivalents (IEQs) were tested. In multivariate regression analysis, pancreas volume (P < .001) and preoperative HbA1c levels (P = .009) were independently associated with digest IEQs. The IEQ prediction formula was calculated according to each preoperative HbA1c level, (a) pancreas volume × 5800 for HbA1c ≥ 6.5, (b) pancreas volume × 10 000 for HbA1c ≥5.7/<6.5 and (iii) pancreas volume × 11 400 for HbA1c < 5.7. The formula was internally validated with 28 TP-IAT patients between 2017 and 2018 (r² = .657 and r² = .710 when restricted to 24 patients without prior pancreatectomy). An estimated IEQs/Body Weight (kg) ≥3700 predicted HbA1c ≤6.5 and insulin independence at 1 year after TP-IAT with 77% and 88% sensitivity and 55% and 43% specificity, respectively. The combination of pancreas volume and preoperative HbA1c levels may be useful to estimate islet yield. Estimated IEQs were reasonably sensitive to predict acceptable glucose control at 1 year.     

Diverse p53 gene aberration in hepatocellular carcinoma detected by dual-color fluorescence in situ hybridization

BACKGROUND AND AIM: In order to evaluate loss of the p53 gene more precisely, we performed dual-color fluorescence in situ hybridization (dual-color FISH) for chromosome 17 and p53 gene together with DNA polymorphism analysis of the p53 gene in hepatocellular carcinoma (HCC). METHODS: Dual-color FISH using probes specific for the centromere of chromosome 17 and the p53 gene was performed for 41 HCC and DNA polymorphism analysis was also performed for them. RESULTS: Of the 34 HCC tested by dual-color FISH, 20 had loss of at least one p53 gene (58.8%). In contrast, of the 32 HCC tested by DNA polymorphism analysis, 23 gave informative results, among which only eight had loss of heterozygosity (LOH) of the p53 gene (34.8%). Notably, among 14 cases positive for loss of the p53 gene by dual-color FISH, seven cases were negative for LOH of the p53 gene. Moreover, dual-color FISH revealed that the percentage of cells that lost at least one p53 gene increased as the HCC became less differentiated (P < 0.01), whereas LOH did not reveal any such correlation. CONCLUSIONS: These data suggest that loss of the p53 gene was present in a considerable number of HCC, and diversity of the p53 gene aberration increases with progression of HCC. Dual-color FISH is an effective method for detection of p53 gene aberration, and it can provide new insight into oncogenesis in HCC.     

Effectiveness of combined anticoagulant therapy for extending portal vein thrombosis in Crohn's disease

PURPOSE: Portal vein thrombosis is a rare complication of Crohn's disease, and its precise cause and appropriate treatment are not known. We describe a patient with extending portal vein thrombosis in Crohn's disease who was successfully treated with combined anticoagulant therapy. METHOD: Urokinase and tissue plasminogen activator were administered from a catheter inserted into the superior mesenteric artery, and heparin and a serine protease inhibitor also were given intravenously. RESULTS: On admission, thromboembolic occlusion was observed throughout the entire portal venous system in association with massive ascites and remarkable intestinal edema. After administration of combined anticoagulant therapy, thrombus rapidly decreased in size, and color Doppler ultrasonography showed a gradual increase in portal venous flow. The patient had no recurrence of symptoms while receiving warfarin after resolution of thrombus. CONCLUSION: This case report suggests that combined anticoagulant therapy is effective for patients with severe portal vein thrombosis in Crohn's disease and that color Doppler ultrasonography is useful for evaluation of portal venous flow.     

Characterization of complement C3, C4, and factor B molecules in human bile

We performed molecular analysis of complement components (C3, C4, and factor B) in human bile by sodium dodecyl sulfate-polyarylamide gel electrophoresis (SDS-PAGE) and immunoblotting. Complement C3 was detected as a molecule composed of a 115-kDa α-chain linked to a 70-kDa β-chain by disulfide bonds, and C3 levels ranged from 45 to 650μg/ml (n=15). C4 was detected as a triple chain (98-kDa α-chain, 73-kDa β-chain, and 33-kDa γ-chain) molecule linked by disulfide bonds, and C4 levels ranged from 2.5 to 60μg/ml. Factor B, a component of the alternative pathway, was also detected, as an intact form. Factor B levels ranged from 0.3 to 8.0μg/ml. The sizes and subunit structures of complement components in human bile were compatible with those reported in human serum. The results of a hemolytic assay indicated that complement molecules in human bile were functionally active. These molecules may participate in local immune and inflammatory responses in the biliary tract.     

High-density activation mapping of fractionated electrograms in the atria of patients with paroxysmal atrial fibrillation

BACKGROUND: Areas of complex fractionated atrial electrograms (CFAEs) have been implicated in the atrial substrate of atrial fibrillation (AF). The mechanisms underlying CFAE in humans are not well investigated. OBJECTIVES: The purpose of this study was to investigate the regional activation pattern associated with CFAE using a high-density contact mapping catheter. METHODS: Twenty patients with paroxysmal AF were mapped using a high-density multielectrode catheter. CFAE were mapped at 10 different sites (left atrium [LA]: inferior, posterior, roof, septum, anterior, lateral; right atrium [RA]: anterior, lateral, posterior, septum). Local atrial fibrillation cycle length (AFCL) was measured immediately before and after the occurrence of CFAE, and the longest electrogram duration (CFAEmax) was assessed. RESULTS: Longer electrogram durations were recorded in the LA compared with the RA (CFAEmax 118 +/- 21 ms vs 104 +/- 23 ms, P = .001). AFCL significantly shortened before the occurrence of CFAEmax compared with baseline (LA: 174 +/- 32 ms vs 186 +/- 32 ms, P = .0001; RA: 177 +/- 31 ms vs 188 +/- 31 ms, P = .0001) and returned to baseline afterwards. AFCL shortened by >or=10 ms in 91% of mapped sites. Two different local activation patterns were associated with occurrence of CFAEmax: a nearly simultaneous activation in all spines in 84% indicating passive activation, and a nonsimultaneous activation sequence suggesting local complex activation or reentry. CONCLUSION: Fractionated atrial electrograms during AF demonstrate dynamic changes that are dependent on regional AFCL. Shortening of AFCL precedes the development of CFAE; thus, cycle length is a major determinant of fractionation during AF. High-density mapping in AF may help to differentiate passive activation of CFAE from CFAE associated with an active component of the AF process.     

CHA2DS2-VASc score is a useful-predictor of not prognosis but coronary-arteriosclerosis in chronic atrial-fibrillation compared with CHADS2 score: A two-center study of 320-slice CT,part 2

Background

The aim of this study is to predict the risk of coronary-arteriosclerosis and prognosis in subjects with chronic-atrial-fibrillation (CAF) using the CHADS2 and CHA2DS2-VASc scores by 320-slice-CT and invasive-coronary-angiography (ICA) in a two-center-study.

Methods

53 CAF subjects who underwent 320-slice-CT and ICA within 6-months (43 male; 69 ± 9 years; CHADS2 score 2.2 ± 1.3; CHA2DS2-VASc score 3.5 ± 1.6) in the two-institutes were analyzed. CT and ICA data were transferred to the analysis-center and were analyzed by cardiologists.

Results

Agatston-calcium-score and frequencies of the presence of various-kinds of plaques and > 50% and > 75% coronary artery stenosis were significantly higher in the subjects with CHA2DS2-VASc score ≥ 3 compared with those with score < 3. However there were no-significant differences in the Agatston-calcium-score and frequencies of the presence of various-kinds of plaques and > 50% and > 75% coronary artery stenosis evaluated by 320-slice CT between the subjects with CHADS2 score ≥ 2 and < 2. Frequency of > 50% coronary artery stenosis by ICA was significantly higher in the subjects with CHA2DS2-VASc score ≥ 3 compared with those with score < 3. However, there were no-significant differences in the frequencies of > 50% and > 75% coronary artery stenosis by ICA between the subjects with CHADS2 score ≥ 2 and < 2. During a mean of 15.9 months, composite rate of cardiac death and heart failure did not differ between subjects with CHADS2 score ≥ 2 and score < 2 and between subjects with CHA2DS2-VASc score ≥ 3 and score < 3.

Conclusions

The CHA2DS2-VASc score is a useful predictor of not prognosis but coronary-arteriosclerosis in subjects with CAF compared with CHADS2 score in this two-center-study.     

Analysis of cardiopulmonary stress during endoscopy: Is unsedated transnasal esophagogastroduodenoscopy appropriate for elderly patients?

BACKGROUND:

Transnasal esophagogastroduodenoscopy (EGD) without sedation has been reported to be safe and tolerable. It has recently been used widely in Japan for the detection of upper gastrointestinal disease. Alternatively, transoral examination using a thin endoscope has also been reported to be highly tolerable.

OBJECTIVE:

To examine the cardiocirculatory effects of transoral versus transnasal EGD in an attempt to determine the most suitable endoscopic methods for patients ≥75 years of age.

METHODS:

Subjects who underwent monitoring of respiratory and circulatory dynamics without sedation during endoscopic screening examinations were enrolled at the New Ooe Hospital (Kyoto, Japan) between April 2008 and March 2009. A total of 165 patients (age ≥75 years) provided written informed consent and were investigated in the present study. Patients were randomly divided into three subgroups: UO group – thin endoscope; SO group – standard endoscope; and UT group – transnasal EGD. Percutaneous arterial blood oxygen saturation, heart rate and blood pressure were evaluated just before EGD and at five time points during EGD. After transnasal EGD, patients who had previously been examined using transoral EGD with a standard endoscope were asked about preferences for their next examination.

RESULTS:

There were no statistical differences in the characteristics among the groups. Percutaneous oxygen saturation in the UT group showed a transient drop compared with the SO and UO groups at the beginning of the endoscopic procedure. Heart rate showed no significant differences among the SO, UO and UT groups; Systolic blood pressure in the UO group was lower immediately after insertion compared with the SO and UT groups. The rate pressure product in the UO group was comparable with that in the UT group during endoscopy, and the SO group showed a continuously higher level than the UO and UT groups. More than one-half (54.4%) of patients were ‘willing to choose transnasal EGD for next examination’.

CONCLUSIONS:

For elderly patients, unsedated transnasal EGD failed to show an advantage over unsedated standard endoscopy. Transoral thin EGD was estimated to be safe and tolerable.     

Global water resources affected by human interventions and climate change

Humans directly change the dynamics of the water cycle through dams constructed for water storage, and through water withdrawals for industrial, agricultural, or domestic purposes. Climate change is expected to additionally affect water supply and demand. Here, analyses of climate change and direct human impacts on the terrestrial water cycle are presented and compared using a multimodel approach. Seven global hydrological models have been forced with multiple climate projections, and with and without taking into account impacts of human interventions such as dams and water withdrawals on the hydrological cycle. Model results are analyzed for different levels of global warming, allowing for analyses in line with temperature targets for climate change mitigation. The results indicate that direct human impacts on the water cycle in some regions, e.g., parts of Asia and in the western United States, are of the same order of magnitude, or even exceed impacts to be expected for moderate levels of global warming (+2 K). Despite some spread in model projections, irrigation water consumption is generally projected to increase with higher global mean temperatures. Irrigation water scarcity is particularly large in parts of southern and eastern Asia, and is expected to become even larger in the future.Terrestrial water fluxes are affected by both climate and direct human interventions, e.g., dam operations and water withdrawals. Climate change is expected to alter the water cycle and will subsequently impact water availability and demand. Several hydrologic modeling studies have focused on climate change impacts on discharge in large river basins or global terrestrial areas under naturalized conditions using a single hydrologic model forced with multiple climate projections (1, 2). Recently, hydrological projections from eight global hydrological models (GHMs) were compared (3). In many areas, there was a large spread in projected runoff changes within the climate–hydrology modeling chain. However, at high latitudes there was a clear increase in runoff, whereas some midlatitude regions showed a robust signal of reduced runoff. The study also concluded that the choice of GHM adds to the uncertainty for hydrological change caused by the choice of atmosphere–ocean general circulation models (hereafter called GCMs) (3). Expected runoff increases in the north and decreases in parts of the middle latitudes have been found also when analyzing runoff from 23 GCMs (4).These studies focused on the naturalized hydrological cycle, i.e., the effects of direct human interventions were not taken into account. However, in many river basins humans substantially alter the hydrological cycle by constructing dams and through water withdrawals. Reservoir operations alter the timing of discharge, although mean annual discharge does not necessarily change much. A study with the water balance model (WBM) showed that the impact of human disturbances, i.e., dams and water consumption, in some river basins is equal to or greater than the impact of expected climate changes on annual runoff over the next 40 y (5). Also, rising water demands are found to outweigh global warming in defining the state of global water systems in the near future (6). Water for irrigation is the largest water use sector, currently accounting for about 70% of global water withdrawals and nearly 90% of consumptive water use (7). A recent synthesis of simulations from seven GHMs found that irrigation water consumption currently amounts to 1,250 km³⋅y⁻¹ (±25%) and that considerable differences among models appear in the spatiotemporal patterns of water consumption (8).Direct comparisons of the climate impact and human intervention modeling studies can be difficult given that the setups are not identical, i.e., the input forcing data and climate models vary. Also, because of the uncertainty of model-specific results, a multimodel approach is preferable in impact modeling studies (3, 9). This approach is similar to assessments performed within the climate community. Here, multimodel results on current and future water availability and consumption at the global scale from the Water Model Intercomparison Project (WaterMIP) within the European Union Water and Global Change (EU WATCH) project (9, 10), and Inter-Sectoral Impact Model Intercomparison Project (ISI-MIP) (11) are presented. (Information on how to get access to WaterMIP and ISI-MIP simulation results can be found at www.eu-watch.org and www.isi-mip.org, respectively.) Results from these two projects are synthesized to obtain a large ensemble of impact model results. The integration of results from the different projects is achieved by extracting impacts for time periods of global mean temperature (GMT) increases of 2 and 3 K from the simulations, largely following the method of Tang and Lettenmaier (4). The advantage of this approach is that it allows presenting results in a way that is in line with temperature targets used in climate mitigation discussions.Other studies have focused on future water scarcity using results from WaterMIP and ISI-MIP, but have analyzed changes of naturalized runoff only (3, 12). We here aim to fill this knowledge gap by comparing the different impacts from climate change and direct human impacts and analyzing their interplay. The models included take into account water withdrawals and consumption in different sectors; for more information, see Models and Data and Supporting Information, SI Models and Data. The objectives of this study are to (i) assess the relative contribution of anthropogenic impacts and climate change to river basin scale water fluxes, and (ii) identify areas where climate change can be expected to cause substantial changes in water consumption and water scarcity, focusing on water for irrigation. The effects of future changes in irrigated areas or irrigation practices are not taken into account, and only dams that currently exist are included in the analyses. In this paper, simulations considering man-made reservoirs, water withdrawals, and water consumption are referred to as human impact simulations, whereas the simulations without these disturbances are referred to as naturalized simulations. The results are mainly presented in a way intended to give an overview of impacts at larger spatial scales (river basin and country levels). However, some finer-scale results are included to reveal effects that can be concealed at coarse spatial scales.