Establishment of an immune-related gene prognostic model for head and neck tumors.

This study aimed to screen the key immune-related genes (IRGs) in head and neck squamous cell carcinoma (HNSC) and construct the IRGs-related prognostic model to predict the overall survival (OS) of patients with HNSC. The RNA-seq data and clinical data were downloaded from The Cancer Genome Atlas database, and IRGs were obtained from the Immunology Database and Analysis Portal. Differentially expressed genes (DEGs) between HNSC and normal samples were identified, followed by integration with IRGs to screen differentially expressed IRGs. After univariate and multivariate proportional hazard regression analyses, an IRG-based risk model was constructed. Meanwhile, data chip of GSE65858 as the validation set to assess the predicted performance of established model. Next, univariate and multivariate Cox regression analyses were performed to identify the independent prognostic factor of HNSC, and the Nomogram model was developed to predict patient outcome. Furthermore, the correlation between immune cell infiltration and risk score was analyzed. A total of 65 differently expressed IRGs associated with prognosis of HNSC were screened, and finally a 26-gene IRG signature was identified to construct a prognostic prediction model. The AUC of ROC curve was 0.750. Survival analysis showed that patients in the high-risk group had a worse prognosis. Independent prognostic analysis showed that risk score could be considered as an independent predictor for HNSC prognosis. Nomogram assessment showed that the model had high reliability for predicting the survival of patients with HNSC in 1, 2, 3 years. Ultimately, the abundance of B cells and CD4+ T cell infiltration in HNSC showed negative correlations with risk score. Our IRG-based prognostic risk model may be used to estimate the prognosis of HNSC patients.

Induced immune tolerance of autoantigen loaded immature dendritic cells in homogenic lupus mice.

This study investigated the induced immune tolerance of autoantigen dendritic cells (imDCs) in homogenic lupus mice to support the use of dendritic cell treatment against autoimmune diseases, such as systemic lupus erythematosus. A lupus mouse was used to model based on in vitro cell culture. An immunohistochemistry assay was used to assess CD8(+), CD4(+) cell ratio in mouse spleen cells. The ratio of CD4(+)CD25(+) cells in mouse spleen lymphocytes was detected by flow cytometry, whereas the kidney was directly measured by immunofluorescence. After the injection of mouse antigen loaded bone marrow-derived antigen imDCs with a homogenetic background, mouse nucleoprotein immune with a homogenetic background was carried out. The results were compared against the simple mouse nucleoprotein immune model with a homogenic background. The 24-h urine protein, serum antinuclear antibody and anti-ds-DNA antibodies of the simple mouse model were lower compared to group S1. The CD4(+)CD25(+) cell percentage of spleen was higher in the simple mouse model compared to group S1. In the spleen, the number of lymphocyte CD8(+) cells declined, whereas the number of CD4(+) cells increased. In conclusion, after autoantigen uptake, imDCs are able to induce immune tolerance to the antigen by reinfusion, which appears to prevent or mitigate systemic lupus erythematosus-like illness.

Rapid assessment of cardiac anatomy and function with a new hand-carried ultrasound device (OptiGo): a comparison with standard echocardiography.

AIMS: The aim of this study was to evaluate image quality and accuracy of a new hand-carried ultrasound device, OptiGo (Agilent Technologies) when compared to standard echocardiography in the setting of a focused examination in the assessment of cardiac anatomy and function. METHODS AND RESULTS: One-hundred and twenty-one patients were prospectively enrolled. Image quality and accuracy in assessment of chamber sizes, left ventricular (LV) wall thickness and contractility, right ventricular (RV) function, mitral and aortic leaflet thickening, mitral annular calcification, pericardial effusion and valvular regurgitation were assessed. Two-dimensional (2D) findings were graded on a four-point scale, except for LV function (six-point) and valvular leaflet opening (two-point). Colour Doppler assessment of valvular regurgitation was graded on a seven-point scale. A one-point difference was considered minor; a two or more point difference was considered major. There was no statistically significant difference in image quality between the two devices. For 2D data, the number of total (minor and major) differences between the hand-carried and standard echocardiograph examinations was significantly greater than the inter-observer variability (14.3% vs 10.7%, P< 0.05), however, major differences alone were not statistically different. For the colour Doppler assessment of regurgitation there was a significant difference between the devices for total (minor and major) differences, (40.0% vs 31.8%,P < 0.007) however, the number of major differences is explained by inter-observer variability. CONCLUSIONS: Image quality and diagnostic accuracy of the hand-carried device, OptiGo, was adequate for the purpose of performing a focused assessment of a limited number of 2D and Doppler parameters for the evaluation of cardiac anatomy and function.

Coordinate-free analysis of mitral valve dynamics in normal and ischemic hearts.

BACKGROUND: The purpose of this investigation was to study mitral valve 3D geometry and dynamics by using a coordinate-free system in normal and ischemic hearts to gain mechanistic insight into normal valve function, valve dysfunction during ischemic mitral regurgitation (IMR), and the treatment effects of ring annuloplasty. METHODS AND RESULTS: Radiopaque markers were implanted in sheep: 9 in the ventricle, 1 on each papillary tip, 8 around the mitral annulus, and 1 on each leaflet edge midpoint. One group served as a control (n=7); all others underwent flexible Tailor partial (n=5) or Duran complete (n=6) ring annuloplasty. After an 8+/-2-day recovery, 3D marker coordinates were measured with biplane videofluoroscopy before and during posterolateral left ventricular ischemia, and MR was assessed by color Doppler echocardiography. Papillary to annular distances remained constant throughout the cardiac cycle in normal hearts, during ischemia, and after ring annuloplasty with either type of ring. Papillary to leaflet edge distances similarly remained constant throughout ejection. During ischemia, however, the absolute distances from the papillary tips to the annulus changed in a manner consistent with leaflet tethering, and IMR was observed. In contrast, during ischemia in either ring group, those distances did not change from preischemia, and no IMR was observed. CONCLUSIONS: This analysis uncovered a simple pattern of relatively constant intracardiac distances that describes the 3D geometry and dynamics of the papillary tips and leaflet edges from the dynamic mitral annulus. Ischemia perturbed the papillary-annular distances, and IMR occurred. Either type of ring annuloplasty prevented such changes, preserved papillary-annular distances, and prevented IMR.

Contrast echocardiography is superior to tissue harmonics for assessment of left ventricular function in mechanically ventilated patients.

BACKGROUND: Assessment of left ventricular function by echocardiography is frequently challenging in mechanically ventilated patients. We evaluated the potential value of contrast-enhanced imaging and tissue harmonic imaging over standard fundamental imaging for endocardial border detection (EBD) in these patients. METHODS AND RESULTS: Fifty patients underwent standard transthoracic 2D echocardiography and were imaged in fundamental and tissue harmonic modes and subsequently with intravenous contrast (Optison). Two echocardiographers reviewed all studies for ease of visualization of endocardial border segments and scoring of wall motion. EBD for each wall segment was graded from 1 to 4 (1 = excellent EBD). Wall motion was scored by a standard 16-segment model and 1 to 5 scale. Studies were categorized as nondiagnostic if 4 of 6 segments in the apical 4-chamber view were either poorly seen or not seen (EBD score 3 or 4). Quantification of ejection fraction was independently performed offline. Visualization of 68% of all segments improved with contrast echocardiography versus 17% improvement with tissue harmonics compared with fundamental mode. Significant improvement (poor/not seen to good/excellent) occurred in 60% of segments with contrast echocardiography versus 18% with tissue harmonics. A total of 850 segments were deemed poor/not seen, 78% of which improved to good/excellent with contrast echocardiography versus 23% with tissue harmonics. Interobserver agreement on EBD was 64% to 70%. Conversion of nondiagnostic to diagnostic studies occurred in 85% of patients with contrast echocardiography versus 15% of patients with tissue harmonics. Scoring of wall motion with fundamental mode, tissue harmonics, and contrast echocardiography was possible in 61%, 74%, and 95% of individual segments, respectively (P <.001). Wall motion scoring was altered in 17% of segments with contrast echocardiography and in 8% with tissue harmonics. Interobserver agreement on wall motion scoring was 84% to 88%. Contrast echocardiography permitted measurement of ejection fraction 45% (P =.003) more often over fundamental mode versus a 27% (P =.09) increase with tissue harmonics. CONCLUSIONS: Contrast echocardiography is superior to tissue harmonic imaging for EBD, wall motion scoring, and quantification of ejection fraction in mechanically ventilated patients.

Clinical outcome in the Marfan syndrome with ascending aortic dilatation followed annually by echocardiography.

This study reviewed the utility of echocardiography in following patients with the Marfan syndrome for whom cardiovascular complications, especially aortic root dilatation, dissection and rupture, are the major causes of morbidity and mortality. We conclude that echocardiography can be used to follow asymptomatic patients with the Marfan syndrome.

The nerve-electrode interface of the cochlear implant: current spread.

One of the fundamental facets of the cochlear implant that must be understood to predict accurately the effect of an electrical stimulus on the auditory nerve is the nerve-electrode interface. One aspect of this interface is the degree to which current delivered by an electrode spreads to neurons distant from it. This paper reports a direct mapping of this current spread using recordings from single units from the cat auditory nerve. Large variations were seen in the degree to which the different units are selective in responding to electrodes at different positions within the scala tympani. Three types of units could be identified based on the selectiveness of their response to the different electrodes in a linear array. The first type of unit exhibited a gradual increase in threshold as the stimulating site was moved from more apical to more basal locations within the scala tympani. The second type of unit exhibited a sharp local minimum, with rapid increases in threshold in excess of 6 dB/mm in the vicinity of the minimum. At electrode sites distant from the local minima the rate of change of the threshold approached that of the first type of units. The final type of unit also demonstrated a gradual change in threshold with changing electrode position, however, two local minima, one apical and one basal, could be identified. These three types are hypothesized to correspond to units which originate apical to the electrode array, along the electrode array and basal to the electrode array.

New real-time interactive cardiac magnetic resonance imaging system complements echocardiography.

OBJECTIVES: We conducted an initial clinical trial of a newly developed cardiac magnetic resonance imaging (CMRI) system. We evaluated left ventricular (LV) function in 85 patients to compare the clinical utility of the CMRI system with echocardiography, the current noninvasive gold standard. BACKGROUND: Conventional CMRI systems require cardiac-gating and respiratory compensation to synthesize a single image from data acquired over multiple cardiac cycles. In contrast, the new CMRI system allows continuous real-time dynamic acquisition and display of any scan plane at 16 images/s without the need for cardiac gating or breath-holding. METHODS: A conventional 1.5T Signa MRI Scanner (GE, Milwaukee, Wisconsin) was modified by the addition of an interactive workstation and a bus adapter. The new CMRI system underwent clinical trial by testing its ability to evaluate global and regional LV function. The first group (A) consisted of 31 patients with acceptable echocardiography image quality. The second group (B) consisted of 31 patients with suboptimal echocardiography image quality. The third group (C) consisted of 29 patients with severe lung disease or congenital cardiac malformation who frequently have suboptimal echo study. Two independent observers scored wall motion and image quality using the standard 16-segment model and rank-order analysis. RESULTS: CMRI evaluation was complete in less than 15 min. In group A, no significant difference was found between ECHO and CMRI studies (p = NS). In group B, adequate visualization of wall segments was obtained 38% of the time using ECHO and 97% of the time using CMRI (p < 0.0001). When grouped into coronary segments, adequate visualization of at least one segment occurred in 18 of 30 patients (60%) with ECHO and in all 30 patients (100%) with CMRI (p < 0.0001). In group C, adequate visualization of the wall segments was obtained in 58% (CI 0.53-0.62) of the time using echocardiography and 99.7% (CI 0.99-1.0) of the time using CMRI (p < 0.0001). CONCLUSIONS: The new CMRI system provides clinically reliable evaluation of LV function and complements suboptimal echocardiography. In comparison with the conventional CMRI, the new CMRI system significantly reduces scan time, patient discomfort and associated cost.

Paradoxical embolism of a shotgun pellet.

Paradoxical embolism of a projectile from the venous to arterial system is a rare occurrence, which can cause diagnostic confusion. We present a case of venous embolism of a shotgun pellet from the left upper extremity to the noncoronary sinus of the aortic valve across a secundum-type atrial septal defect. Prevention of distal embolism of the pellet was presumably a result of its containment by flow vortices created within the sinuses of Valsalva.

Native tissue harmonic imaging improves endocardial border definition and visualization of cardiac structures.

BACKGROUND: The purpose of this study was to examine the impact of native tissue harmonic imaging on endocardial border definition, wall motion scoring, and visualization of intracardiac structures. METHODS AND RESULTS: For wall motion analysis, 60 consecutive patients underwent standard transthoracic echocardiograms in both harmonic and fundamental modes. Three experienced echocardiographers reviewed each echocardiogram. Endocardial border definition for each wall segment was graded from 1 to 4 (1 = excellent endocardial definition). Wall motion was scored by using a standard 16-segment model and 1 to 5 scale. For visualization of cardiac structures, 50 consecutive patients were studied. Two experienced interpreters reviewed each echocardiogram for both normal and abnormal structures by using the following scoring scale: (1) harmonic is much better than fundamental, (2) harmonic is slightly better than fundamental, (3) harmonic and fundamental are equivalent, (4) fundamental is slightly better than harmonic, and (5) fundamental is much better than harmonic. Visualization of 64% (95% confidence interval [CI] 0.61 to 0.66) of all segments improved in harmonic mode, with 26% (95% CI 0.24 to 0.29) improving from poor/not seen to good/excellent. Of 444 segments deemed poor/not seen, visualization of 312 (70%) (95% CI 0.66 to 0.75) improved to good/excellent with harmonic mode. Of these 312 segments, 55% comprised the lateral and anterior walls on apical views. Interobserver agreement on endocardial border definition was 82% to 86%. Scoring of wall motion was altered in 171 of 1075 (16%) of segments by harmonic mode. This was significantly greater than the interobserver disagreement, which was only 10% (p<0.002). Mitral valve chordae and papillary muscles were visualized slightly/much better with harmonic mode in 40 of 50 echocardiograms. Left atrial boundaries were seen slightly/much better in harmonic mode in 29 of 50 studies. Abnormal structures were seen slightly/much better in harmonic mode in 12 of 14 cases. CONCLUSIONS: Native tissue harmonic imaging has significant impact on endocardial border definition and wall motion scoring and improves the visualization of both normal and abnormal cardiac structures.

Forward-looking catheters.

Current intravascular ultrasound catheters provide a cross-sectional view of the blood vessel that limits their ability to visualize severely stenosed or occluded vessels. Forward-looking ultrasound catheters can overcome these limitations. Development of a practical forward-looking ultrasound catheter requires solutions to address the need for improved lateral resolution and depth of penetration presented by the forward-looking format. Methods are also needed to generate the forward-looking scan within the space constraints of a catheter. New developments using mechanical scanning methods suggest that a practical device appears achievable. Two-dimensional, as well as three-dimensional imaging, may be possible. Early efforts towards a phased array scanner have also begun.

Role of compensatory enlargement and shrinkage in transplant coronary artery disease. Serial intravascular ultrasound study.

BACKGROUND: Compensatory enlargement of the vessel wall has been described in the early stages of native atherosclerosis. Whether compensatory enlargement plays a role in transplant coronary artery disease is not known. The objective of this study was to determine, by use of serial intravascular ultrasound (IVUS), whether compensatory dilation occurs in transplant coronary artery disease over time. METHODS AND RESULTS: Seventy-five heart transplant recipients with 151 matched coronary segments were selected for the presence of intimal disease progression as detected by serial IVUS examinations 1 to 3 years apart. Intimal disease progression was defined as a > 10% increase in intimal area (IA). IVUS catheter location in follow-up studies was verified angiographically in relation to branch vessels. Luminal area (LA) and total vessel area (TA) were measured at each site. Intimal area (IA = TA-LA) was calculated. Changes in IA (delta IA) and TA (delta TA) between baseline and follow-up IVUS were compared: delta IA, 2.9 +/- 0.2 mm2: delta TA, 2.7 +/- 0.4 mm2. A remodeling index (RI) was defined as RI = delta TA/delta IA. Three subgroups could be distinguished: over compensation (RI > I), partial compensation (RI 0 to 1), and no compensation or shrinkage (RI < or = 0). Seventy-four segments (49%) showed overcompensation, 44 (29%) showed partial compensation, and 33 (22%) showed no compensation or shrinkage. CONCLUSIONS: In this study, serial IVUS shows that early after cardiac transplantation, a large proportion of the coronary segments with progression of intimal thickening have compensatory dilation of the vessel wall. However, a substantial number of coronary segments (22%) show no compensatory dilation or shrinkage. The progressive luminal narrowing in transplant patients may be due in part to vessel shrinkage or the lack of compensatory dilation over time.

A forward-viewing intravascular ultrasound catheter suitable for intracoronary use.

Current intravascular ultrasound (IVUS) catheters provide a transverse cross-sectional view of the blood vessel, thus limiting their ability to visualize severely stenosed or occluded vessels. Forward-viewing IVUS devices can overcome these limitations. Previously described forward-viewing IVUS catheters are mechanically complex, making them too bulky for use in coronary arteries. A new design for small-forward viewing IVUS catheters was developed. Using this design, flexible 5-Fr (1.6 mm diameter) and 8-Fr (2.6 mm diameter) prototype catheters up to 110 cm long, suitable for intravascular work, were constructed. Imaging of cadaver arterial segments was performed using these prototype catheters. Structures such as branches and plaque and features such as calcium were well seen with these catheters. Correlation of lumen dimensions measured with the IVUS catheters and by histology (HIST) was excellent: IVUS = 1.06 x HIST - 1.45 mm, r2 = 0.98. This new technology holds promise as a tool for guiding intravascular interventions.

Are heart-lung transplant recipients protected from developing transplant coronary artery disease? A case-matched intracoronary ultrasound study.

BACKGROUND: Accelerated coronary artery disease is a major cause of mortality in heart transplant recipients; however, it does not appear to play a major role in the clinical outcome of heart-lung transplant recipients. The purpose of this study was to determine whether the incidence and severity of transplant coronary artery disease as detected by intracoronary ultrasound in heart-lung transplant recipients are less than those encountered in heart transplant recipients. METHODS AND RESULTS: We studied the left anterior descending coronary artery with the use of intracoronary ultrasound imaging in 22 heart-lung transplant recipients at the time of their routine annual coronary angiogram. Twenty-two heart transplant recipients were case matched for number of years after transplant at ultrasound study, recipient age, donor age, and diagnosis of nonischemic cardiomyopathy. Mean intimal area, intimal index, Stanford class, and incidence of at least moderate disease (Stanford class > or = 3) were measured and calculated in each group and then compared between the two groups. Mean intimal area (1.6 +/- 2.5 versus 3.8 +/- 2.8 mm2), mean intimal index (0.07 +/- 0.10 versus 0.22 +/- 0.14), mean Stanford class (1.7 +/- 1.0 versus 2.7 +/- 1.2), and incidence of Stanford class > or = 3 (14% versus 45%) were significantly lower in the heart-lung transplant recipient group. CONCLUSIONS: The incidence and severity of transplant coronary artery disease are much less in patients receiving heart-lung transplants than in those receiving heart transplants alone.

Prediction of angiographic disease by intracoronary ultrasonographic findings in heart transplant recipients.

BACKGROUND: Intracoronary ultrasonography has proven to be a more sensitive test than angiography for the detection of intimal thickening in transplant recipients. However, the prognostic significance of the intimal thickening detected by intracoronary ultrasonography has not been proven. METHOD: During a 1-year period, 70 transplant recipients without angiographically apparent coronary artery disease underwent intracoronary ultrasonography examination. For each intracoronary ultrasonography study an intimal index, defined as the ratio of the plaque area to the area within the media, was measured for the most diseased segment imaged. The subsequent annual follow-up angiograms of these 70 patients were reviewed for the development of visually apparent coronary artery disease. The time since transplantation for the 70 patients without angiographically apparent coronary artery disease ranged from 1 to 15 years, with a mean of 4.2 years an median of 3.9 years. Mean duration of angiographic follow-up was 2.0 years (range 1 to 3 years). RESULTS: Angiographically apparent coronary artery disease developed on follow-up angiograms in 13 of the 70 patients, with a mean time to development of 1.5 years. Four of 46 patients (9%) with an intimal index < 0.3 subsequently had angiographically apparent coronary artery disease, whereas of 25 patients (36%) with an intimal index > or = 0.3 subsequently had angiographically apparent coronary artery disease. Odds ratio for future angiographically apparent coronary artery disease between patients with an intimal index > or = and intimal index < 0.3 was 5.9 (p < 0.01 by Fisher's Exact test). In a subgroup of 22 patients more than 5 years after transplantation at the time of intracoronary ultrasonography, 12 had an intimal index < 0.3 and 10 had an intimal index > or = 0.3. In this subgroup none of the 12 patients with an intimal index < 0.3 had angiographically apparent coronary artery disease and only 1 of the 10 with an intimal index > or = 0.3 had angiographically apparent coronary artery disease (difference not significant). CONCLUSIONS: The presence of moderate to severe intimal thickening by intracoronary ultrasonography is predictive of the future development of angiographically apparent coronary artery disease among patients more than 1 year and less than 5 years after transplantation. This same degree of intimal thickening may not carry the same prognostic significance among patients greater than 5 years after transplantation without the development of angiographically apparent coronary artery disease.

[A study on relationship between balance of serum lipoprotein and the phlegm damp-blood stasis syndrome differentiation of coronary heart diseases].

75 patients were divided into A,B and C group. The LDL-C was 2.97 +/- 0.67, 4.05 +/- 0.38 and 5.25 +/- 0.98 mmol/L respectively (P > 0.01); but comparing group A or B with the normal group (D), it had no significant difference (P > 0.05). An abnormal coronary arteriography (CAG) was found in the group A in 62.1% and the group B in 57.6% (P > 0.05), while the group C in 84.6% (P < 0.01). There was unusual serum lipoprotein electrophoretogram (SLPG) in group A 75.9%, group B 84.8% and group C 100%, but it had no change in group D (P < 0.001). Five types of Syndrome Differentiation about the Phlegm damp and blood stasis (PDBS) could be found in the group A,B and C. The incidence (51.5%-55.2%) and abnormality of the SLPG (66.7%-92.5%) and CAG (68.8%-100%) of PDBS type were the highest among them. 82.7% CHD patient's clinical comprehensive diagnosis was in accordance with the SLPG and that of the CAG were 64.0%. As to the abnormal SLPG, the sensitivity and rate of coincidence of CAG was 91.7% and 69.3% (P < 0.05-0.01) respectively. The Syndrome Differentiation of PDBS was valuable in differentiating CHD. The SLPG is a good criterion for the study of CHD in TCM.

A method for evaluating the selectivity of electrodes implanted for nerve simulation.

The scale of stimulating electrodes possible for use in functional electrical stimulation to restore motor and sensory function is rapidly approaching that of individual neurons. Although the electrodes may approach the dimensions of single nerve cells, it is unclear if the region of excitation elicited by each electrode will be correspondingly small. Previous techniques for evaluating this have either been tedious or have lacked the resolution necessary. This paper describes a method that uses the refractory interaction of the compound action potentials elicited by a stimulus pulse pair, along with high-resolution recording of those potentials, to achieve measurements of the selectivity of stimulation down to the scale of a few axon diameters. The feasibility of this technique is demonstrated in sciatic nerves of frogs (Rana Catesbiana) acutely implanted with a sapphire electrode array.