Breath sound changes associated with malpositioned endotracheal tubes

Endotracheal tubes (ETTs) are used to establish airway access in patients with ventilatory failure and during general anaesthesia. Tube malpositioning can compromise respiratory function and can be associated with increased morbidity and mortality. Clinical assessment of ETT position normally involves chest auscultation, which is highly skill-dependent and can be misleading. The objective of this pilot study was to investigate breath sound changes associated with ETT malpositioning. Breath sounds were acquired in six human subjects over each hemithorax and over the epigastrium for tracheal, bronchial and oesophageal intubations. When the ETT was in the oesophagus, the acoustic energy ratio between epigastrium and chest surface increased in all subjects (p<0.04). In addition, ETT placement in the right mainstem bronchus decreased the acoustic energy ratio between the left and right hemithoraxes in all subjects (p<0.04). A baseline measurement of this energy ratio was needed for bronchial intubation identification. However, using this ratio after bandpass filtering (200–500 Hz) did not require a baseline value, which would increase the utility of this method for initial ETT placement. These results suggest that computerised analysis of breath sounds may be useful for assessment of ETT positioning. More studies are needed to test the feasibility of this approach further.     

Non-invasive computerised detection of acute coronary occlusion

The goal of this study was to evaluate the role of a computerised, non-invasive ECG method for detecting acute coronary occlusion (ACO). Ninety-five standard ECG leads were recorded, before and during ACO, from 18 patients undergoing balloon angioplasty. ECG amplitude and derivative parameters were calculated for the QRS, ST and T components of the ECG signal, before and during ACO. Results were obtained for each lead. Sensitivity of the standard visual ECG analysis for detecting ACO was 48%, whereas the percentage of conventional ECG changes during baseline was 14%. For the best ECG parameter, the amplitude parameter of the QRS component, sensitivity was 82%, and the percentage of parameter changes during baseline was 20%. The sensitivity for detecting ACO with five of the six ECG parameters studied was greater than that of the standard visual analysis. Ischaemic changes were detected in 4.3±1.6 leads per patient using the amplitude parameter of the QRS component, whereas, with the standard visual analysis, 2.5±2.1 leads demonstrated such changes (p<0.001). Results were then summarized per patient. The standard visual ECG analysis detected ACO in 15 of 18 patients (83%), if at least one lead showed ischaemic changes. The computerised analysis detected ACO in all 18 patients using the same criterion. The sensitivity of the computerised method for detecting ACO in the clinical setting of angioplasty was greater than that of the standard visual analysis. It is suggested that the computerised method may be useful for detecting myocardial ischaemia in other clinical settings of acute myocardial ischaemia.     

Acoustic characteristics of air cavities at low audible frequencies with application to pneumoperitoneum detection

Air accumulations within living organisms are sometimes pathologic. An example is free air within the abdomen from perforation of the intestines (a condition called pneumoperitoneum). The objectives of the described research were to define the acoustic signatures of abdominal air cavities at low frequencies and to investigate the feasibility of using these signatures for pneumoperitoneum diagnosis. The central hypothesis was that low-frequency vibro-acoustic property changes are detectable using broad-band acoustic excitation applied at the abdominal surface. Band-limited white noise (0-3200 Hz) was introduced at the abdominal surface of sedated dogs and response was measured by a surface vibro-acoustic sensor. The transfer function and coherence were estimated from these measurements. The presence of pneumoperitoneum caused increased resonances and anti-resonances (p<0.01). Measures of the latter parameters were proposed and evaluated to quantitatively measure their magnitude. Resonant spectral peaks of more than 3dB were consistent with pneumoperitoneum (p<0.01), and both resonance and anti-resonance increased with condition severity (p<0.03). The data also suggest a possible reduction in the resonant and anti-resonant frequencies with decreasing air cavity volumes (p=0.14) as supported by theoretical predictions. Finally, anti-resonance was also found to be associated with a drop in coherence. These findings suggest that the proposed technique may be useful in the diagnosis of pneumoperitoneum.     

Pneumothorax detection using computerised analysis of breath sounds

The primary objective of the study was to investigate the effects of pneumothorax (PTX) on breath sounds and to evaluate their use for PTX diagnosis. The underlying hypothesis is that there are diagnostic breath sound changes with PTX. An animal model was created in which breath sounds of eight mongrel dogs were acquired and analysed for both normal and PTX states. The results suggested that pneumothorax was associated with a reduction in sound amplitude, a preferential decrease in high-frequency acoustic components and a reduction in sound amplitude variation during the respiration cycle (p<0.01 for each, using the Wilcoxson signed-rank test). Although the use of diminished sound amplitude for PTX diagnosis assumes availability of baseline measurements, this appears unnecessary for high-frequency reduction or sound amplitude changes over the respiratory cycle. Further studies are warranted to test the clinical feasibility of the method in humans.     

Pneumothorax detection using pulmonary acoustic transmission measurements

Pneumothorax is a common clinical condition that can be life threatening. The current standard of diagnosis includes radiographic procedures that can be costly and may not always be readily available or reliable. The objective of this study was to investigate the hypothesis that pneumothorax causes detectable pathognomonic changes in pulmonary acoustic transmission. An animal model was developed whereby 15 mongrel dogs were anaesthetised, intubated and mechanically ventilated. A thoracoscopic trocar was placed into the pleural space for the introduction of air and confirmation of a ∼30% pneumothorax by direct visualisation. Broadband acoustic signals were introduced into the endotracheal tube, while transmitted waves were measured at the chest surface. Pneumothorax was found consistently to lower the pulmonary acoustic transmission in the 200–1200 Hz frequency band, whereas smaller transmission changes occurred at lower frequencies (p<0.0001, sign test). The ratio of acoustic energy between low-(<220 Hz) and high-(550–770 Hz) frequency bands was significantly different in the control and pneumothorax states (p<0.0001, sign test). This implies that pneumothoraces can be reliably detected using pulmonary acoustic transmission measurements in the current animal model. Further studies are needed to investigate the feasibility of using this technique in humans.     

Vascular endothelial growth factor in systemic lupus erythematosus: relationship to disease activity,systemic organ manifestation,and nailfold capillaroscopic abnormalities

Introduction: The aim of the study was to evaluate whether vascular endothelial growth factor (VEGF) serum level is associated with systemic organ involvement, microvascular changes as determined by nailfold capillaroscopy, and disease activity of systemic lupus erythematosus (SLE). Materials and Methods: Serum levels of VEGF were determined by an enzyme-linked immunosorbent assay in 47 SLE patients and in 30 healthy controls. Nailfold capillaroscopy was performed in all patients and healthy subjects. Results: Morphological changes were observed by nailfold capillaroscopy in 45 of 47 (95.7%) SLE patients. Mild capillary changes were found in 16 (34%), moderate in 21 (44.7%), and severe in 8 (17%) SLE patients. All patients with systemic organ involvement showed severe or moderate changes in nailfold capillaroscopy. In comparison with the control group, a higher serum concentration of VEGF in SLE patients was demonstrated (p<0.05). Furthermore, significant differences in VEGF serum concentration between SLE patients with systemic involvement and controls were found (p<0.01). Comparison between patients with active and inactive SLE according to SLEDAI score showed a significantly higher concentration of VEGF in the sera of patients with active SLE (p<0.01). The SLE patients with severe and moderate changes in nailfold capillaroscopy showed significantly higher VEGF serum levels than SLE patients with mild changes (p<0.05) or healthy controls (p<0.01). Moreover, the VEGF serum level correlated significantly with ESR (r=0.580, p<0.0001) and CRP (r=0.512, p<0.005). Conclusions: Our data suggest that VEGF serum level may be a useful marker of disease activity and internal organ involvement in SLE patients. Abnormalities in nailfold capillaroscopy may reflect the extent of microvascular involvement and are associated with systemic manifestation in SLE.     

Preliminary experience with patch-enlarged brachial artery for hemodialysis access

The patency of patch-enlarged (capsule-shaped) brachial arteries for long-term hemodialysis access was evaluated retrospectively. Twelve brachial arteries were patched with polytetrafluoroethylene (PTFE) grafts (standard wall thickness), making 1 x 2 cm aneurysms proximal to the elbow joints in 10 patients (six men with six patches, four women with six patches; patient age: 53 to 76 years, mean age +/- SD: 65.4 +/- 8.5 years) between September 2001 and April 2002. Ten patches were needled for each hemodialysis session as blood-drawing ports. The port's 1-year primary patency rate was 90%, 2-year patency was 70%, and 3-year patency was 70%. Two patches were needled in each hemodialysis session for dialyzed blood infusion access; both clotted within 1 year, with intact vessel continuity. Patch enlargement (capsule-shaped) of the brachial artery with a PTFE graft can be used as a long-term blood-drawing access in selected patients. This novel access may help patients with central vein stenosis or occlusion (which some patients had) and may help patients who have comorbid conditions such as chronic congestive heart failure or liver cirrhosis with ascites.     

Detection and analysis of gastrointestinal sounds in normal and small bowel obstructed rats

This study is aimed at detecting gastrointestinal sounds (GIS) and correlating their characteristics with gastrointestinal (GI) conditions. The central hypotheses are that GIS generation depends on the motility patterns and the mechanical properties of the gut, and that changes in those result in measurable differences in GIS. An animal model which included both healthy rats and those with small bowel obstruction (SBO) was developed. The acoustic bursts, of GIS were detected by amplitude thresholding the signal envelope. Three methods of envelope estimation were proposed and evaluated. Envelope estimation using a Hilbert transform was found to produce the best results in the current application. The duration and dominant frequency of each detected GIS event was estimated and clear differences between healthy and diseased rats were discovered. In the control state, GIS events were found to consistently be of relatively short duration (3–65ms). Although the majority of events in the SBO state had similar short duration, infrequent longer events were also detected and appeared to be pathognomonic. Long duration events (>100 ms) occurred in each of seven obstructed, but in none of 14 non-obstructed, cases (p<0.001). It is concluded that GIS analysis may prove useful in the non-invasive, rapid, and accurate diagnosis of SBO.     

The relationship between Vaspin,Nesfatin-1 plasma levels and presence of fragmented QRS with the severity of coronary atherosclerosis

PurposeDespite continuous efforts to address classical risk factors for atherosclerosis, the battle to control the disease is far from over and atherosclerosis is still a major factor in all-cause mortality. To investigate the relations between early diagnosis and severity of coronary atherosclerosis we examined vaspin and nesfatin-1 levels, and the presence of fragmented QRS (fQRS) in admission electrocardiograms.Materials and methodsWe divided 168 patients into asymptomatic control (18%), <50% coronary artery stenosis (28%), >50% stenosis (31%) and myocardial infarction (MI) (23%) groups. Patients were also evaluated in anatomically significant (>50%stenosis ?+ ?MI) and non-significant atherosclerosis (control+<50%stenosis) groups. Vaspin and nesfatin-1 levels were measured using ELISA methods.ResultsVaspin in MI and >50% stenosis groups was lower than in other groups (p ?< ?0.001). Nesfatin-1 in MI and >50% stenosis groups was lower only than in <50%stenosis group (p0.007). The presence of fQRS was higher in MI and >50% stenosis groups than other groups (p ?< ?0.001). In the anatomically significant atherosclerosis group, vaspin, nesfatin-1 and left ventricular ejection fraction (LVEF) values were lower while Gensini score and the presence of fQRS were higher (for all p ?< ?0.001). Lower vaspin levels and fQRS were related to in-hospital mortality (p ?< ?0.001 and p ?= ?0.02,respectively). Logistic regression analysis showed that male gender, diabetes mellitus, smoking, family history, lower LVEF, lower vaspin and fQRS were defined as independent risk factors for anatomically significant atherosclerosis (p ?= ?0.001).ConclusionsOur results indicate that low vaspin and fQRS were found to be novel independent risk factors for anatomically significant atherosclerosis and were predictors of mortality.     

Heterogeneous distribution of trastuzumab in HER2-positive xenografts and metastases: role of the tumor microenvironment

Most HER2-positive metastatic breast cancer patients continue to relapse. Incomplete access to all target HER2-positive cells in metastases and tumor tissues is a potential mechanism of resistance to trastuzumab. The location of locally bound trastuzumab was evaluated in HER2-positive tissues in vivo and as in vivo xenografts or metastases models in mice. Microenvironmental elements of tumors were related to bound trastuzumab using immunohistochemical staining and include tight junctions, vasculature, vascular maturity, vessel patency, hypoxia and HER2 to look for correlations. Trastuzumab was evaluated alone and in combination with bevacizumab. Dynamic contrast-enhanced magnetic resonance imaging parameters of overall vascular function, perfusion and apparent permeability were compared with matched histological images of trastuzumab distribution and vascular patency. Trastuzumab distribution is highly heterogeneous in all models examined, including avascular micrometastases of the brain and lung. Trastuzumab distributes well through the extravascular compartment even in conditions of high HER2 expression and poor convective flow in vivo. Microregional patterns of trastuzumab distribution in vivo do not consistently correlate with vascular density, patency, function or maturity; areas of poor trastuzumab access are not necessarily those with poor vascular supply. The number of vessels with perivascular trastuzumab increases with time and higher doses and dramatically decreases when pre-treated with bevacizumab. Areas of HER2-positive tissue without bound trastuzumab persist in all conditions. These data directly demonstrate tissue- and vessel-level barriers to trastuzumab distribution in vivo that can effectively limit access of the drug to target cells in brain metastases and elsewhere.     

Dynamics of the sounds caused by partially occluded femoral arteries in dogs

Previous studies have indicated that partially occluded arteries produce sounds due to turbulence. If these sounds from the coronary arteries could be detected externally, they would provide a simple approach to the detection of coronary artery disease. To confirm the hypothesis that coronary stenosis produces detectable acoustic correlates, sounds caused by a controlled occlusion of the femoral artery of dogs were detected and analyzed using both the fast Fourier transform (FFT) and the autoregressive (AR) methods. The femoral artery was chosen, since its size and flow approximate those of coronary arteries in humans. The poles of the AR spectra and the power ratios of different sections of the FFT and AR spectra were used to differentiate the degree of the stenosis. The results showed that high frequency acoustical power between 200 and 800 Hz is associated with the turbulence produced by the partially occluded femoral arteries of the dogs. Using the AR method, high acoustic power above 200 Hz increased when the degree of the occlusions increased. The poles and power ratios of the AR spectra differed according to the degree of stenosis. However, the high frequency acoustical power above 200 Hz did not increase above the 85% occlusion.     

Changes in hemostasis parameters in nonfatal methicillin‐sensitive Staphylococcus aureus bacteremia complicated by endocarditis or thromboembolic events: a prospective gender‐age adjusted cohort study

The aim of this study was to examine the changes in hemostasis parameters in endocarditis and thromboembolic events in nonfatal methicillin‐sensitive Staphylococcus aureus bacteremia (MS‐SAB) – a topic not evaluated previously. In total, 155 patients were recruited and were categorized according to the presence of endocarditis or thromboembolic events with gender‐age adjusted controls. Patients who deceased within 90 days or patients not chosen as controls were excluded. SAB management was supervised by an infectious disease specialist. Patients with endocarditis (N = 21), compared to controls (N = 21), presented lower antithrombin III at day 4 (p < 0.05), elevated antithrombin III at day 90 (p < 0.01), prolonged activated partial thromboplastin time at days 4 and 10 (p < 0.05), and enhanced thrombin–antithrombin complex at day 4 (p < 0.01). Thromboembolic events (N = 8), compared to controls (N = 34), significantly increased thrombin–antithrombin complex at day 4 (p < 0.05). In receiver operating characteristic analysis, the changes in these hemostasis parameters at day 4 predicted endocarditis and thromboembolic events (p < 0.05). No differences in hemoglobin, thrombocyte, prothrombin fragment, thrombin time, factor VIII, D‐dimer or fibrinogen levels were observed between cases and controls. The results suggest that nonfatal MS‐SAB patients present marginal hemostasis parameter changes that, however, may have predictability for endocarditis or thromboembolic events. Larger studies are needed to further assess the connection of hemostasis to complications in SAB.     

Magnetic resonance observation of cartilage repair tissue (MOCART) 2.0 for the evaluation of retropatellar autologous chondrocyte transplantation and correlation to clinical outcome

BackgroundMatrix-associated chondrocyte transplantation (MACT) has become an established treatment option for cartilage defects.ObjectiveThree objectives were defined: first, to evaluate retropatellar cartilage grafts using Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) 2.0 score; second, to determine whether clinical outcome correlates with specific parameters or overall results; third, to screen those parameters for their ability to predict a clinical outcome of Delta IKDC ≥ 20 as a threshold for good clinical response at 12 months.Methods38 patients were included of whom all underwent retropatellar MACT. MRI was performed 3, 6 and 12 months postoperatively. The clinical status was determined using International Knee Documentation Committee Subjective Form (IKDC). Correlations of MOCART 2.0 parameters and Delta IKDC scores were quantified by nonparametric Spearman’s R. Those parameters with significant correlations (p < 0.05) were screened for their ability to predict a clinical outcome of Delta IKDC ≥ 20 at 12 months.ResultsSignificant correlations were identified for the parameters MOCART total _{6 months} (p < 0.05), Surface _{6 months} (p < 0.05), Surface _{12 months} (p < 0.05), Structure _{6 months} (p < 0.01), Structure _{12 months} (p < 0.05), Subchondral changes _{3 months} (p < 0.0001), Subchondral changes _{6 months} (p < 0.05) and Subchondral changes _{12 months} (p < 0.05). Among all MRI score parameters, Subchondral changes _{3 months} achieved the highest accuracy of 0.76 (0.62–0.86) in predicting Delta IKDC ≥ 20 after 12 months.ConclusionSome of the MOCART 2.0 parameters show significant correlation with Delta IKDC scores in the postoperative course after retropatellar MACT, which seems to depend on the time interval between surgery and MRI acquisition.     

Development of in vivo tissue-engineered microvascular grafts with an ultra small diameter of 0.6 mm (MicroBiotubes): acute phase evaluation by optical coherence tomography and magnetic resonance angiography

Biotubes, i.e., in vivo tissue-engineered connective tubular tissues, are known to be effective as vascular replacement grafts with a diameter greater than several millimeters. However, the performance of biotubes with smaller diameters is less clear. In this study, MicroBiotubes with diameters <1 mm were prepared, and their patency was evaluated noninvasively by optical coherence tomography (OCT) and magnetic resonance angiography (MRA). MicroBiotube molds, containing seven stainless wires (diameter 0.5 mm) covered with silicone tubes (outer diameter 0.6 mm) per mold, were embedded into the dorsal subcutaneous pouches of rats. After 2 months, the molds were harvested with the surrounding capsular tissues to obtain seven MicroBiotubes (internal diameter 0.59 ± 0.015 mm, burst pressure 4190 ± 1117 mmHg). Ten-mm-long MicroBiotubes were allogenically implanted into the femoral arteries of rats by end-to-end anastomosis. Cross-sectional OCT imaging demonstrated the patency of the MicroBiotubes immediately after implantation. In a 1-month follow-up MRA, high patency (83.3 %, n = 6) was observed without stenosis, aneurysmal dilation, or elongation. Native-like vascular structure was reconstructed with completely endothelialized luminal surfaces, mesh-like elastin fiber networks, regular circumferential orientation of collagen fibers, and α-SMA-positive cells. Although the long-term patency of MicroBiotubes still needs to be confirmed, they may be useful as an alternative ultra-small-caliber vascular substitute.     

远红外线治疗仪联合多磺酸黏多糖乳膏在自体动静脉内瘘狭窄术后的应用

目的:观察远红外线治疗仪联合多磺酸黏多糖乳膏在自体动静脉内瘘狭窄术后的应用效果。方法:选取行自体动静脉内瘘狭窄术患者115例,简单随机法分为对照组57例和观察组58例。对照组术后内瘘处涂抹多磺酸黏多糖乳膏,而观察组在内瘘处涂抹多磺酸黏多糖乳膏基础上采用远红外线治疗仪进行红外线照射。比较两组术后并发症、内瘘及术后半年内血管通路通畅情况,比较两组炎症因子的差异。结果:观察组和对照组累计并发症分别为2例和8例。治疗前,两组炎症因子水平比较无显著差异（P>0.05）,治疗后,两组炎症因子水平均下降,观察组上述指标下降程度大于对照组（P<0.05）。治疗前,两组内瘘情况比较,差异无统计学意义（P>0.05）,治疗后,两组内瘘血管内径增粗、血流量升高,内瘘血管峰值流速下降,观察组内瘘血管内径、血流量及血管峰值流速改善程度大于对照组（P<0.05）。两组术后1、3、6个月时血管通路通畅率比较无显著差异（P>0.05）。结论:远红外线治疗仪联合多磺酸黏多糖乳膏可减少自体动静脉内瘘狭窄术后应激炎症反应,改善内瘘血管内径和血流量,降低并发症。     

Preliminary experience with a cuffed ePTFE graft for hemodialysis vascular access

The purpose of this study was to determine graft patency and blood flow rates in recipients of a new cuffed ePTFE graft (Venaflo graft) used for hemodialysis access. A pilot study was conducted with 12 (7 men, 5 women) consecutive patients (age range, 36-76 yr; mean, 65 yr). All patients were recipients of a new cuffed PTFE graft placed for hemodialysis access. Seven were high risk because of a prior history of clotted hemodialysis accesses (1-6; mean, 3.3). Blood flow rates were determined by ultrasound dilution technique at 3 month intervals. One year and 2 year overall graft patency rates were 90.9% and 68.2%, respectively. One graft (high risk, six prior grafts) was lost to thrombosis in the first year; two grafts (one high risk, four prior grafts) were lost to thrombosis in the second year of follow-up. No graft thrombosis resulted from stenosis at the graft-vein anastomosis. Blood flow rates ranged from 550 to 2,110 ml/min (mean, 1,086 ml/min; n = 8) when first measured 3 months after graft placement. Similar flow rates were observed at 12 months (mean, 1,043 ml/min; n = 7) and 24 months (mean, 1,014 ml/min; n = 4) in grafts available for comparison. Dialysis flow rates in excess of 350 ml/min were possible with all patent grafts. A cuffed ePTFE graft provided stable blood flow and satisfactory graft patency during 2 years of follow-up, even in high risk patients with a prior history of vascular access thrombosis.     

Noninvasive acoustical detection of coronary artery disease using the adaptive line enhancer method

Previous studies have indicated that heart sounds may contain information which is useful in the detection of occluded coronary arteries. Specifically, previous work based on analysing heart sounds recorded during the diastolic portion of the cardiac cycle, when blood flow through the coronary arteries is maximum, has shown that additional frequency components are present in patients with coronary artery disease. To further explore the application of advanced signal processing techniques to the noninvasive detection of coronary artery disease, a new signalprocessing approach is presented using adaptive line enhancing (ALE) and spectral estimation of diastolic heart sounds taken from recordings made at the patient's bedside. This approach comprises two cascaded processes. In the first the ALE method is used to enhance the diastolic heart sounds and eliminate background noise. In the second process, either autoregressive (AR) or autoregressive moving average (ARMA) spectral methods are used to estimate the model parameters. Model parameters (the power spectral density (PSD) functions and the poles of the AR or ARMA method) were used to diagnose patients as diseased or normal. Results showed that normal and abnormal recordings were correctly identified in 39 of 43 cases using the new method. These results also confirm that high-frequency energy above 400 Hz is associated with coronary stenosis.     

Extracorporeal pressure monitoring and the detection of vascular access stenosis

Prospective monitoring of static venous pressure is an established tool to detect outflow stenoses in a vascular access. However, with this method it is not possible to identify vascular stenoses which are localized between the arterial and venous dialysis needle. We describe a new approach based on both static arterial and venous extracorporeal pressures. Pressure data of 9 dialysis patients with normal vascular access function and 9 patients with stenotic access were analyzed. Extracorporeal pressure was found to depend on the position of the heart relative to the extracorporeal blood circuit. All patients with venous outflow stenoses had an elevated ratio of arterial and venous intra-access pressure to mean arterial pressure. In case of access stenosis between arterial and venous needle the ratio of venous pressure to mean arterial pressure was normal, and only the arterial pressure ratio was elevated. We conclude that combined arterial and venous intraaccess pressure measurement normalized by mean blood pressure detects venous stenosis as well as stenosis between the arterial and venous dialysis needle. To minimize the rate of access thrombosis both arterial and venous intra-access pressure should be monitored.     

Serum tissue inhibitor of metalloproteinase 1 (TIMP-1) and vascular endothelial growth factor A (VEGF-A) are associated with prognosis in esophageal cancer patients

PurposeThe matrix metalloproteinases, tissue inhibitors of metalloproteinases and angiogenesis contribute to growth and spread of cancer. We investigated the correlation between pretreatment serum levels of tissue inhibitor of metalloproteinase 1 (TIMP-1) and vascular endothelial growth factor A (VEGF-A), and clinicopathologic features and survival in patients with esophageal cancer (EC).Material/MethodsSerum TIMP-1 and VEGF-A were measured by enzyme-linked immunosorbent assay (ELISA) in 89 patients with EC, and 30 healthy controls.ResultsSerum TIMP-1 and VEGF-A levels were significantly higher in patients with esophageal carcinoma than in the control group (p=0.001 and p<0.001, respectively). High levels of TIMP-1 were associated with histological type (p<0.001), tumor depth (p<0.001), stage (p<0.001) and lymph node metastases (p=0.001). Subgroup analysis showed that tumor size (p<0.001), tumor depth (p<0.001), stage (p<0.001), lymph node metastases (p=0.002), distant metastases (p=0.009) and resectability (p=0.003), were correlated with an elevated level of VEGF-A. Patients with elevated levels of TIMP-1 and VEGF-A had a significantly lower overall survival (p=0.02 and p=0.048, respectively), and disease-free survival (TIMP-1, p<0.001).ConclusionHigh serum levels of TIMP-1 and VEGF-A were found to be associated with tumor progression and unfavorable prognosis in patients with EC.     

Readily available tissue-engineered vascular grafts

Autologous or synthetic vascular grafts are used routinely for providing access in hemodialysis or for arterial bypass in patients with cardiovascular disease. However, some patients either lack suitable autologous tissue or cannot receive synthetic grafts. Such patients could benefit from a vascular graft produced by tissue engineering. Here, we engineer vascular grafts using human allogeneic or canine smooth muscle cells grown on a tubular polyglycolic acid scaffold. Cellular material was removed with detergents to render the grafts nonimmunogenic. Mechanical properties of the human vascular grafts were similar to native human blood vessels, and the grafts could withstand long-term storage at 4 °C. Human engineered grafts were tested in a baboon model of arteriovenous access for hemodialysis. Canine grafts were tested in a dog model of peripheral and coronary artery bypass. Grafts demonstrated excellent patency and resisted dilatation, calcification, and intimal hyperplasia. Such tissue-engineered vascular grafts may provide a readily available option for patients without suitable autologous tissue or for those who are not candidates for synthetic grafts.