Longitudinal heterogeneity of coronary artery distensibility in plaques related to acute coronary syndrome

Background

How coronary distensibility contributes to stable or unstable clinical manifestations remains obscure. We postulated that the heterogeneous plaque distensibility is associated with unstable clinical presentations in patients with acute coronary syndrome (ACS).

Methods and results

Seventeen and 19 ACS-related and -unrelated lesions, respectively, were visualized using intravascular ultrasound imaging with simultaneous intracoronary pressure recording. Systolic and diastolic lumen cross-sectional areas were measured at the lesion site and at five evenly spaced sites between the proximal and distal reference sites. The coronary distensibility index and stiffness index β were calculated for each site and averaged for each coronary segment. Maximal distensibility index, standard deviation and the difference between maximal and minimal distensibility indices within each segment were significantly higher in the ACS-related than -unrelated plaques (5.6?±?2.3 vs. 3.7?±?1.8, p?p?p?p?=?0.022) than that in ACS-unrelated plaques.

Conclusions

Coronary artery distensibility is longitudinally more heterogeneous in ACS-related than-unrelated plaques, especially between the lesion and the immediate proximal site.     

Selective Imaging of Vascular Endothelial Growth Factor Receptor-1 and Receptor-2 in Atherosclerotic Lesions in Diabetic and Non-diabetic ApoE<Superscript>−/−</Superscript> Mice

Purpose

Plaque vulnerability is associated with inflammation and angiogenesis, processes that rely on vascular endothelial growth factor (VEGF) signaling via two receptors, VEGFR-1 and VEGFR-2. We have recently reported that enhanced uptake of scVEGF-PEG-DOTA/Tc-99m (scV/Tc) single photon emission computed tomography (SPECT) tracer that targets both VEGFR-1 and VEGFR-2, identifies accelerated atherosclerosis in diabetic relative to non-diabetic ApoE^?/? mice. Since VEGFR-1 and VEGFR-2 may play different roles in atherosclerotic plaques, we reasoned that selective imaging of each receptor can provide more detailed information on plaque biology.

Procedures

Recently described VEGFR-1 and VEGFR-2 selective mutants of scVEGF, named scVR1 and scVR2, were site-specifically derivatized with Tc-99m chelator DOTA via 3.4 kDa PEG linker, and their selectivity to the cognate receptors was confirmed in vitro. scVR1 and scVR2 conjugates were radiolabeled with Tc-99m to specific activity of 110 ± 11 MBq/nmol, yielding tracers named scVR1/Tc and scVR2/Tc. 34–40 week old diabetic and age-matched non-diabetic ApoE^?/? mice were injected with tracers, 2–3 h later injected with x-ray computed tomography (CT) contrast agent and underwent hybrid SPECT/CT imaging. Tracer uptake, localized to proximal aorta and brachiocephalic vessels, was quantified as %ID from. Tracer uptake was also quantified as %ID/g from gamma counting of harvested plaques. Harvested atherosclerotic arterial tissue was used for immunofluorescent analyses of VEGFR-1 and VEGFR-2 and various lineage-specific markers.

Results

Focal, receptor-mediated uptake in proximal aorta and brachiocephalic vessels was detected for both scVR1/Tc and scVR2/Tc tracers. Uptake of scVR1/Tc and scVR2/Tc was efficiently inhibited only by “cold” proteins of the same receptor selectivity. Tracer uptake in this area, expressed as %ID, was higher in diabetic vs. non- diabetic mice for scVR1/Tc (p = 0.01) but not for scVR2/Tc. Immunofluorescent analysis revealed enhanced VEGFR-1 prevalence in and around plaque area in diabetic mice.

Conclusions

Selective VEGFR-1 and VEGFR-2 imaging of atherosclerotic lesions may be useful to explore plaque biology and identify vulnerability.

     

Absolute immature platelet counts in the setting of suspected heparin-induced thrombocytopenia may predict anti-PF4-heparin immunoassay testing results

Background

Heparin-induced-thrombocytopenia (HIT) is a disease mediated by antibodies to platelet factor 4 (PF4)-heparin complexes. Immature platelet fraction (%-IPF) and absolute immature platelet count (A-IPC) measure newly-released platelets into circulation and can prove useful in differentiating patients with thrombocytopenic presentations due to consumptive or hypoproduction processes. Therefore, we evaluated utility of A-IPC in a cohort of thrombocytopenic patients suspected of HIT.

A High-Affinity Near-Infrared Fluorescent Probe to Target Bombesin Receptors

Purpose

This study aimed to create new optical surgical navigation NIRF probes for prostate and breast cancers.

Procedures

IR800-linker-QWAVGHLM-NH₂ with linker = GSG, GGG, and G-Abz4 were synthesized and characterized. IC₅₀ for bombesin receptors (BBN-R) in PC-3 prostate and T47D breast cancer cells, fluorescence microscopy in PC-3 cells, and NIRF imaging in mice PC-3 tumor xenografts were studied.

Results

GGG, GSG, and G-Abz4 derivatives had IC₅₀ (nM) for BBN-R+ PC-3 cells?=?187?±?31, 56?±?5, and 2.6?±?0.2 and T47D cells?=?383?±?1, 57.4?±?1.2, and 3.1?±?1.1, respectively. By microscopy the Abz4 derivative showed the highest uptake, was competed with by BBN, and had little to no binding to BBN-R? cells. In NIRF imaging the G-Abz4 probe was brighter than GGG probe in BBN-R+ tissues in vivo and tissues, tumors, and tumor slices ex vivo. Uptake could be partially blocked in BBN-R+ pancreas but not visibly in tumor.

Conclusions

Linker choice can dominate peptidic BBN-R binding. The G-Abz4 linker yields a higher affinity and specific BBN-R binder in this series of molecules.     

Effect of transcatheter aortic valve implantation on the ascending aorta’s elasticity

Background

The elastic properties of the ascending aorta were studied before and 1?week after transcatheter aortic valve implantation (TAVI). Previous studies have shown that the distensibility of the ascending aorta was decreased in the early post-operative period after aortic valve replacement. Aortic stiffness is a major moderator of arterio-ventricular coupling and an independent predictor of cardiovascular risk and mortality. We evaluated the effect of TAVI on the elastic properties of the ascending aorta in the early post-operative period.

Methods

Aortic distensibility (AD) and Aortic Stiffness Index (ASI) were evaluated using echocardiographic techniques and brachial artery pressure obtained by sphygmomanometry 2–3?days before and 7–8?days after TAVI.

Results

A total of 30 patients (14 males) were studied with a mean age of 79.9?±?4.7?years and aortic valve area before TAVI of 0.61?±?0.16?cm². Mean arterial pressure decreased significantly after TAVI (from 89.6?±?8.9?mmHg to 83.3?±?10.9?mmHg, p?=?0.004). AD did not change significantly after TAVI (pre: 1.89?±?1.11?cm²/(dynes?×?10⁶), post: 2.05?±?1.50?cm²/(dynes?×?10⁶); p?=?0.813). ASI also remained unchanged (pre: 11.4?±?6.5, post: 15.6?±?14.9; p?=?0.349).

Conclusions

The elastic properties of the ascending aorta did not change significantly in the early post-procedural period after TAVI. This may in part be attributable to the less invasive procedure (compared to aortic valve replacement) which has no effect on vasa vasorum flow.     

Restricted Water Diffusibility as Measured by Diffusion-weighted MR Imaging and Choline Uptake in 11C-Choline PET/CT are Correlated in Pelvic Lymph Nodes in Patients with Prostate Cancer

Purpose

¹¹C-Choline-positron emission tomography (PET)/computed tomography (CT) is increasingly used in patients with prostate cancer. Another promising technique for assessment of tumor biology is diffusion-weighted MR imaging (DWI). The aim of the study was to compare the functional parameters standardized uptake value (SUV) in PET and apparent diffusion coefficient (ADC) value in DWI of lymph nodes in prostate cancer patients.

Procedures

Fourteen patients with prostate cancer underwent DWI at 1.5T and ¹¹C-Choline-PET/CT. ADC values and SUVs of all lymph nodes larger than 5 mm (n?=?55) were compared by using linear regression analysis. Performance of DWI and ¹¹C-Choline PET was assessed by receiver operator characteristic curve analysis using histopathology or clinical follow-up as standard of reference.

Results

ADC values and SUV showed a moderate but highly significant inverse correlation (r?=??0.5144, p?<?0.0001). In lymph nodes with low ADC values, the dispersion of SUV was more pronounced. Moreover, a highly significant difference was observed for mean ADC values and SUV in lymph nodes considered as benign or malignant by follow-up/histopathology (ADC 1.60?±?0.24 vs. 1.09?±?0.23?×?10^?3 mm²/s; SUV 1.82?±?0.57 vs. 4.68?±?03.12; p?<?0.0001, respectively).

Conclusion

These pilot data propose the ADC value in DWI as a new potential imaging biomarker which might provide additional information on tumor pathophysiology compared to the SUV in ¹¹C-Choline PET/CT.     

Axl-Targeted Cancer Imaging with Humanized Antibody h173

Purpose

The tyrosine kinase receptor Axl is overexpressed in various types of cancer and correlated with cancer malignancy. Selective Axl blockade reduces tumor growth and metastasis. The purpose of this study was to examine whether the humanized anti-Axl antibody humanized 173 (h173) labeled with near-infrared fluorescence (NIRF) dye Cy5.5 could be applied as a molecular imaging probe for NIRF imaging of Axl expression in tumor models.

Procedures

NIRF dye Cy5.5 was conjugated to h173 or human normal immunoglobulin G (hIgG) control through amino groups. The resulting probes were evaluated in both A549 (Axl positive) and NCI-H249 (Axl negative) lung cancer xenografts through in vivo NIRF imaging. Ex vivo imaging and probe distribution assay were also carried out to confirm the in vivo imaging results.

Results

After conjugation, binding activity of h173-Cy5.5 was determined to be 97.75 %?±?2.09 % of the unmodified h173. In vitro fluorescence-activated cell sorting (FACS) and fluorescence microscopy analysis validated the specific binding of h173 toward Axl-positive A549 cells. h173-Cy5.5 was then applied to image Axl expression in vivo. In A549 (Axl positive) cancer xenografts, the tumor uptake of h173-Cy5.5 was significantly higher than that of the hIgG-Cy5.5 control (P?<?0.05) at late time points (1, 2, 3, 4, and 7 days). On the contrary, in NCI-H249 (Axl negative) cancer xenografts, the tumor uptake of both hIgG-Cy5.5 and h173-Cy5.5 was low and showed no significant difference (P?>?0.05) at all time points examined. Ex vivo imaging and immunofluorescence staining analysis further validated the in vivo imaging results.

Conclusions

Collectively, all in vitro, in vivo, and ex vivo data suggested that h173-Cy5.5 could serve as a valid probe for Axl-targeted cancer imaging, which could therefore aid in tumor diagnosis, prognosis, and treatment monitoring.     

Intravascular ultrasound elastography analysis of the elastic mechanical properties of atherosclerotic plaque

To assess the elastic mechanical properties of atherosclerotic plaque with different morphological properties by intravascular ultrasound elastography (IVUSE). 30 purebred New Zealand rabbits were fed a high-cholesterol diet; the abdominal aorta endothelium was balloon-injured after 2 weeks; at week 12, 2 plaques with moderate echo from each rabbit were chosen for in situ imaging, and 2 consecutive frames near the end-diastole images in situ were used to construct an IVUS elastogram. Shear strain (SS) and area strain (AS) were greater for eccentric than centripetal plaque (SS: 2.65(2.45)% vs. 1.79?±?0.97%, p?<?0.05; AS: 4.81(4.99)% vs. 3.23?±?1.75%, p?<?0.05) but were lower with low than high plaque burden (SS: 2.14?±?0.37% vs. 3.40?±?0.34%, p?<?0.05; AS: 3.88?±?0.60% vs. 5.81?±?0.54%, p?<?0.05). SS and AS were significantly greater for plaque with negative than no remodeling (SS: 3.98?±?1.53% vs. 1.82(1.40)%, p?<?0.017; AS: 6.94?±?2.24% vs. 2.59(2.87)%, p?<?0.017) and were found correlated with eccentric index and plaque burden (R²?=?0.365 and R²?=?0.359, both p?<?0.05). Plaques associated with eccentricity, high plaque burden and negative remodeling showed greater strain than those with centripetalism, low plaque burden and positive remodeling. Eccentric index and plaque burden may be useful to predict the elastic stability of plaque.     

An optimized set-up for helmet noninvasive ventilation improves pressure support delivery and patient�Cventilator interaction

Objective

To test the effects on mechanical performance of helmet noninvasive ventilation (NIV) of an optimized set-up concerning the ventilator settings, the ventilator circuit and the helmet itself.

Subjects and methods

In a bench study, helmet NIV was applied to a physical model. Pressurization and depressurization rates and minute ventilation (MV) were measured under 24 conditions including pressure support of 10 or 20?cmH₂O, positive end expiratory pressure (PEEP) of 5 or 10?cmH₂O, ventilator circuit with ??high??, ??intermediate?? or ??low?? resistance, and cushion deflated or inflated. In a clinical study pressurization and depressurization rates, MV and patient?Cventilator interactions were compared in six patients with acute respiratory failure during conventional versus an ??optimized?? set-up (PEEP increased to 10?cmH₂O, low resistance circuit and cushion inflated).

Results

In the bench study, all adjustments simultaneously applied (increased PEEP, inflated cushion and low resistance circuit) increased pressurization rate (46.7?±?2.8 vs. 28.3?±?0.6?%, p?<?0.05), depressurization rate (82.9?±?1.9 vs. 59.8?±?1.1?%, p????0.05) and patient MV (8.5?±?3.2 vs. 7.4?±?2.8?l/min, p?<?0.05), and decreased leaks (17.4?±?6.0 vs. 33.6?±?6.0?%, p?<?0.05) compared to the basal set-up. In the clinical study, the optimized set-up increased pressurization rate (51.0?±?3.5 vs. 30.8?±?6.9?%, p?<?0.002), depressurization rate (48.2?±?3.3 vs. 34.2?±?4.6?%, p?<?0.0001) and total MV (27.7?±?7.0 vs. 24.6?±?6.9?l/min, p?<?0.02), and decreased ineffective efforts (3.5?±?5.4 vs. 20.3?±?12.4?%, p?<?0.0001) and inspiratory delay (243?±?109 vs. 461?±?181?ms, p?<?0.005).

Conclusions

An optimized set-up for helmet NIV that limits device compliance and ventilator circuit resistance as much as possible is highly effective in improving pressure support delivery and patient?Cventilator interaction.     

Clinical correlates of endothelial function in chronic heart failure

Objective

There is a close link between heart failure and endothelial dysfunction. Brachial flow-mediated dilation (FMD) is a validated non-invasive measure of endothelial function. The aim of this study was to investigate the clinical correlates of FMD in patients with chronic heart failure (CHF).

Design, setting, patients

We evaluated 60 CHF outpatients (age 62?±?14?years; 49 males, NYHA class 2.2?±?0.7, left ventricular ejection fraction, LVEF, 33?±?8%) taking conventional medical therapy (ACE-inhibitors and/or ARBs 93%, beta-blockers 95%) and in stable clinical conditions.

Main outcome measures

The maximum recovery value of FMD was calculated as the ratio of the change in diameter (maximum-baseline) over the baseline value.

Results

As compared with patients with a higher FMD, those with FMD below the median value (4.3%) were more frequently affected by ischemic cardiopathy (50 vs. 23%; p?=?0.032) and diabetes mellitus (20 vs. 3%; p?=?0.044), had a higher NYHA class (2.5?±?0.5 vs. 1.9?±?0.7; p?<?0.001) and NT-proBNP (2,690?±?3,690 vs. 822?±?1,060; p?=?0.001), lower glomerular filtration rate estimated by Cockcroft-Gault (GFRCG: 63?±?28 vs. 78?±?25; p?=?0.001) and LVEF (29?±?8 vs. 37?±?9; p?=?0.001), as well as more frequently showing a restrictive pattern (40 vs. 7%; p?=?0.002). In a multivariate regression model (R ²?=?0.48; p?<?0.001), FMD remained associated only with the NYHA class (p?=?0.039) and diabetes mellitus (p?=?0.024).

Conclusions

This study demonstrates that a better functional status and absence of diabetes mellitus are associated to higher FMD regardless of the etiology of the cardiac disease.     

Knee area tissue oxygen saturation is predictive of 14-day mortality in septic shock

Purpose

Thenar eminence tissue oxygen saturation (StO₂) was developed to assess organ perfusion. However, mottling, a strong predictor of mortality in septic shock, develops preferentially around the knee. We aimed to evaluate the prognostic value of StO₂ measured around the knee in septic shock patients and compare it to thenar StO₂.

Methods

This was a prospective observational study in a tertiary teaching hospital. All consecutive patients with septic shock were included. Parameters were recorded when vasopressors were started (H0) and every 6?h during 24?h. Their predictive value was assessed on 14-day mortality.

Results

Fifty-two patients were included. SOFA score was 11 (9–15) and SAPS II was 56 (40–72). At 6?h after ICU admission (H6), mean arterial pressure, cardiac index, and central venous pressure were not different between non-survivors and survivors; but non-survivors had higher arterial lactate level (8.8?±?5.0 vs. 2.2?±?1.5?mmol/l, P?P?2 (62?±?20 vs. 72?±?9?%, P?=?0.03). At H6, StO₂ was lower in non-survivors; this difference was not significant for thenar StO₂ (70?±?15 vs. 77?±?12?%, P?=?0.10) but was very pronounced for knee StO₂ (39?±?23 vs. 71?±?12?%, P?2 was associated with a higher mottling score (P?P?R ²?=?0.2), and a lower urinary output (P?=?0.02, R ²?=?0.12).

Conclusion

After initial septic shock resuscitation, StO₂ measured around the knee is a strong predictive factor of 14-day mortality.     

20-MHz Ultrasound for Measurements of Flow-Mediated Dilation and Shear Rate in the Radial Artery

A high-frequency scanning system consisting of a 20-MHz linear array transducer combined with a 20-MHz pulsed Doppler probe was introduced to evaluate the degree of radial artery flow-mediated dilation (FMD [%]) in two groups of patients after 5?min of controlled forearm ischemia followed by reactive hyperemia. In group I, comprising 27 healthy volunteers, FMD (mean?±?standard deviation) was 15.26?±?4.90% (95% confidence interval [CI]: 13.32%–17.20%); in group II, comprising 17 patients with chronic coronary artery disease, FMD was significantly less at 4.53?±?4.11% (95% CI: 2.42%–6.64%). Specifically, the ratio FMD/SR (mean?±?standard deviation), was equal to 5.36?×?10^?4?±?4.64?×?10^?4 (95% CI: 3.54?×?10^?4 to 7.18?×?10^?4) in group I and 1.38?×?10^?4?±?0.89?×?10^?4 (95% CI: 0.70?×?10^?4 to 2.06?×?10^?4) in group II. Statistically significant differences between the two groups were confirmed by a Wilcoxon–Mann–Whitney test for both FMD and FMD/SR (p?<0.01). Areas under receiver operating characteristic curves for FMD and FMD/SR were greater than 0.9. The results confirm the usefulness of the proposed measurements of radial artery FMD and SR in differentiation of normal patients from those with chronic coronary artery disease.     

Enlarged Size and Impaired Elastic Properties of the Ascending Aorta are Associated with Endothelial Dysfunction and Elevated Plasma Matrix Metalloproteinase-2 Level in Patients with Bicuspid Aortic Valve

The aim of this study was to test whether enlarged size and impaired elastic properties of the ascending aorta are associated with impaired endothelial function and increases in plasma matrix metalloproteinase (MMP)-2 concentrations in patients with bicuspid aortic valve (BAV) without significant valvular dysfunction. The size and the elasticity of the ascending aorta and the flow-mediated vasodilation (FMD) in the brachial artery in response to hyperemia were evaluated with 2-D echocardiography and high-frequency linear ultrasound in 42 patients with BAV without significant valvular dysfunction and 30 age- and sex-matched healthy controls. In the BAV group, diastolic ascending aortic diameter (AoD) (32.1?±?8.1?mm vs. 25.3?±?3.6?mm, p?<0.001) and aortic stiffness index (8.0?±?5.3 vs. 4.0?±?1.8, p?<0.001) were significantly higher, and aortic strain (7.4?±?3.6% vs. 11.1?±?3.0%, p?<0.001) and aortic distensibility (7.4?±?4.1 × 10^?6cm²/dyn vs. 11.1?±?4.3 × 10^?6cm²/dyn, p?<0.001) were significantly lower than those in the control group. The BAV group also had lower FMD (6.5?±?2.2% vs. 11.9?±?2.7%, p?<0.001) and higher plasma MMP-2 levels (226.7?±?55.0?ng/mL vs. 177.0?±?45.3?ng/mL, p?<0.001) compared with the control group. In the BAV group, AoD, aortic strain, aortic stiffness index and aortic distensibility significantly correlated with FMD and MMP-2 (all p?<0.05). The multivariable linear regression analysis further indicated that FMD and MMP-2 were independently associated with AoD (β?=??1.1, p?=?0.005, and β?=?0.09, p?<0.001, respectively). These findings suggest that enlarged size and impaired elastic properties of the ascending aorta are associated with endothelial dysfunction and elevated plasma MMP-2 level in patients with BAV without significant valvular dysfunction. FMD and plasma MMP-2 level are the significant and independent predictors of dilation of the ascending aorta in patients with BAV.     

Morphology of coronary artery lesions assessed by virtual histology intravascular ultrasound tissue characterization and fractional flow reserve

Fractional flow reserve (FFR) is an index of the physiological significance of a coronary stenosis. Patients who have lesions with a FFR of >0.80, even optimally treated with medication, have however a MACE rate ranging from 8 to 21%. Coronary plaques at high risk of rupture and clinical events can be also identified by virtual histology intravascular ultrasound (IVUS-VH) as plaques with high amount of necrotic core (NC) abutting the lumen. Aim of this exploratory study was to investigate whether the geometry and composition of lesions with FFR????0.80 were different from their counterparts. Fifty-five consecutive patients in whom FFR was clinically indicated on a moderate angiographic lesion, received also an imaging investigation on the same lesion with IVUS-VH. Data on plaque geometry and composition was analyzed. Patients were subdivided in two groups according to the value of FFR (> or ??0.80). Lesions with a FFR????0.80 (n?=?17) showed a slightly larger plaque burden than those with FFR?>?0.80 (n?=?38) (54.6?±?0.7% vs. 51.7?±?0.7% P?=?0.1). In addition, they tend to have less content of necrotic core than their counterparts (14.2?±?8% vs. 19.2?±?10.2%, P?=?0.08). No difference was found in the distribution of NC-rich plaques (fibroatheroma and thin-capped fibroatheroma) between groups (82% in FFR????0.80 vs. 79% in FFR?>?0.80, P?=?0.5). Although FFR????0.80 lesions have larger plaque size, they do not differ in composition from the ones with FFR?>?0.80. Further exploration in a large prospective study is needed to study whether the lesions with FFR?>?0.80 that are NC rich are the ones associated with the presence of clinical events at follow-up.     

Longitudinal Changes in Glucose Metabolism of Denervated Muscle after Complete Peripheral Nerve Injury

Purpose

Electrodiagnostic studies can obtain information 2 or 3 weeks after an acute nerve injury. Previous studies have shown increased glucose metabolism in denervated muscles 1 week after injury using 2-deoxy-2-[¹⁸F]fluoro-D-glucose ([¹⁸F]FDG) positron emission tomography (PET). Therefore, this study aimed to evaluate the changes in glucose metabolism in denervated muscles using serial monitoring by [¹⁸F]FDG PET scans.

Procedures

Denervation was induced in eight male Sprague-Dawley rats (aged 7 weeks old) weighing 200–250 g. The right legs of the rats were denervated by resecting the sciatic nerve in the thigh after the initial skin incision. Two rats were sacrificed 1 and 10 weeks after denervation. Skeletal muscles (gastrocnemius and tibialis anterior) were excised from both the right and left legs of the rats. Staining with hematoxylin and eosin, glucose transporter (GLUT)-1, GLUT-4, and hexokinase II was undertaken. PET/computed tomography (CT) scans were performed on the six remaining rats a total of five times at 1, 2, 5, 8, and 10 weeks after denervation. Regions of interest were drawn on integrated PET/CT images to measure the degree of [¹⁸F]FDG uptake in the right and left lower leg muscles. Target-to-background ratios (TBRs) were calculated by dividing the FDG uptake of the lower leg muscles by that of the upper leg muscles.

Results

The TBRs of the denervated muscles were higher than those of the control muscles at both 1 (6.84?±?1.98 vs. 1.18?±?0.11, p?=?0.009) and 2 (4.10?±?2.05 vs. 1.86?±?0.73, p?=?0.0374) weeks after denervation. After 5 (2.18?±?0.78 vs. 1.35?±?0.47, p?=?0.1489), 8 (1.76?±?0.18 vs. 1.69?±?0.18, p?=?0.5127), and 10 (1.76?±?0.52 vs. 1.56?±?0.37, p?=?0.5637) weeks, the difference in the TBRs between the denervated and controls became non-significant.

Conclusions

[¹⁸F]FDG PET can visualize increased glucose metabolism in a denervated muscle early as 1 week after injury. Therefore, PET could be adopted as a noninvasive imaging modality for acute nerve injuries. In addition, [¹⁸F]FDG PET may help to understand the role of the nervous system in the control of peripheral tissues.

     

Influence of patient related factors on number of mesenchymal stromal cells reached after in vitro culture expansion for clinical treatment

Background: Number of stromal cells injected in patients with ischaemic heart disease (IHD) may be of importance for the treatment efficacy, which in turn may be influenced by various patient-related factors. In this study, we investigate whether patient-related factors influence the number of autologous stromal cells reached after in vitro culture expansion for clinical therapy.

Methods: Culture expansion data from 111 patients with IHD treated with autologous stromal cells in three clinical trials were used. We correlated the final cell count after two passages of cultivation with different patient factors.

Results: There was a significant relation between body mass index (BMI) and the number of adipose derived stromal cells (ASCs) reached after culture expansion and for all patients included into the three studies (r?=?0.375, p?=?.019 and r?=?0.200, p?=?.036, respectively). Moreover, there was a significantly higher number of ASCs reached in patients with hypertension compared to those without hypertension and for all patients overall (68.8?±?39.6?×?10⁶ vs. 39.1?±?23.6?×?10⁶, p?=?.020 and 62.0?±?55.0?×?10⁶ vs. 29.0?±?19.3?×?10⁶, p?<?.001, respectively). The same tendency was seen with bone marrow derived mesenchymal stromal cells (MSCs) in patients with hypertension compared to those without hypertension (58.4?±?61.8?×?10⁶ vs. 22.6?±?13.3?×?10⁶, p?<?.001) and in males compared to females (56.4?±?61.5?×?10⁶ vs. 30.9?±?27.9?×?10⁶, p?=?.041). Moreover, a significant negative correlation between left ventricular ejection fraction and number of MSCs was found (r?=??0.287, p?=?.017).

Conclusions: Patient related factors such as BMI, hypertension and gender may influence the number of MSCs reached after in vitro culture expansion.     

Near-Infrared Fluorescence Imaging of Non-Hodgkin’s Lymphoma CD20 Expression Using Cy7-Conjugated Obinutuzumab

Purpose

Obinutuzumab is the first fully humanized and glycoengineered monoclonal antibody (mAb) directly targeting CD20 antigen, which is expressed on B cell lymphocytes and the majority of non-Hodgkin’s lymphoma (NHL). This study aims to design a diagnostic molecular probe, Cy7-Obinutuzumab (Cy7-Obi), in which Cy7 is a near-infrared fluorescent dye. This probe is used to noninvasively image CD20 antigen expressed in NHL cells.

Procedures

Cy7-Obi probe was synthesized through nucleophilic substitution reaction between NHS-Cy7 and obinutuzumab. After purification, the conjugate was fully characterized by a series of methods. The immunoreactivity and molecular specificity of the probe were confirmed using flow cytometry and in vitro microscopy on Raji (CD20-positive) cells. For in vivo imaging, Cy7-Obi probe (1 nmol) was injected intravenously in severe combined immunodeficiency (SCID) mice bearing Raji tumors which overexpress CD20 (n?=?3) and was imaged with near-infrared fluorescence (NIRF) at 6, 9, 12, 24, 60, and 96 h post-probe injection. For pre-block, obinutuzumab (3.25 mg) was injected intravenously in tumor-bearing mice 6 h before the administration of Cy7-Obi probe.

Results

The synthesized Cy7-Obi probe in this paper mimics obinutuzumab in both structure and function. Flow cytometry analysis of the probe and obinutuzumab on Raji cells showed minor difference in binding affinity/specificity with CD20. The probe showed significant fluorescence signal when it was examined on Raji cells using in vitro microscopy. The fluorescence signal can be blocked by pretreatment with obinutuzumab. The probe Cy7-Obi also showed high tumor uptake when it was examined by in vivo optical imaging on Raji tumor-bearing mice. The tumor uptake can be blocked by pretreatment with obinutuzumab (n?=?3, p?in vivo imaging results were also confirmed by ex vivo imaging of dissected organs. Finally, the probe Cy7-Obi has shown excellent tumor targeting and specificity through immunofluorescence analysis.

Conclusions

We have shown that humanized Cy7-Obi probe can be used for NIRF imaging successfully. The probe may be an effective and noninvasive diagnostic molecular probe capable of tracking CD20 overexpression in NHL.     

Effects of a 12-week home-based exercise program on the level of physical activity, insulin, and cytokines in colorectal cancer survivors: a pilot study

Purpose

The purposes of this study are to examine (1) the feasibility and efficacy of two different home-based exercise protocols on the level of physical activity (PA), and (2) the effect of increased PA via home-based exercise program on biomarkers of colorectal cancer.

Methods

Seventeen patients (age 55.18 ± 13.3 years) with stage II–III colorectal cancer completed the 12-week home-based exercise program. Subjects were randomized into either casually intervened home-based exercise group (CIHE) or intensely intervened home-based exercise group (IIHE). The primary outcome was the level of PA. Furthermore, insulin, homeostasis model assessment of insulin resistance, insulin-like growth factor axis, and adipocytokines were measured.

Results

Both CIHE and IIHE program significantly increased the level of PA at 12 weeks compared to its level at baseline (CIHE, 10.00?±?8.49 vs. 46.07?±?45.59; IIHE, 12.08?±?11.04 vs. 35.42?±?27.42 MET hours per week). Since there was no difference in PA change between groups (p?=?0.511), the data was combined in analyzing the effects of increased PA on biomarkers. Increase in PA significantly reduced insulin (6.66?±?4.58 vs. 4.86?±?3.48 μU/ml, p?=?0.006), HOMA-IR (1.66?±?1.23 vs. 1.25?±?1.04, p?=?0.017), and tumor necrosis alpha-α (TNF-α 4.85?±?7.88 vs. 2.95?±?5.38 pg/ml, p?=?0.004), and significantly increased IGF-1 (135.39?±?60.15 vs. 159.53 ng/ml, p?=?0.007), IGF binding protein (IGFBP)-3 (2.67?±?1.48 vs. 3.48?±?1.00 ng/ml, p?=?0.013), and adiponectin (6.73?±?3.07 vs. 7.54?±?3.96 μg/ml, p?=?0.015).

Conclusion

CIHE program was as effective as IIHE program in increasing the level of PA, and the increase in PA resulted in significant change in HOMA-IR, IGF-1 axis, TNF-α, and adiponectin levels in stage II–III colorectal cancer survivors.     

Influence of tube potential on quantitative coronary plaque analyses by low radiation dose computed tomography: a phantom study

Previous studies have shown that employing the low dose computed tomography (CT) technique based on low tube potential reduces the radiation dose required for the coronary artery examination protocol. However, low tube potential may adversely influence the CT number of plaque composition. Therefore, we aimed to determine whether quantitative atherosclerotic plaque analysis by a multi-slice, low radiation dose CT protocol using 80 kilovolts (kV) yields results comparable to those of the standard 120 kV protocol. Artificial plaque samples (n?=?17) composed of three kinds of plaque were scanned at 120 and 80 kV. Relative low-density and medium-density plaque component volumes obtained by three protocols (80 kV, 60 Hounsfield units [HU] threshold; 120 kV, 60 HU threshold; and 80 kV, 82 HU threshold) were compared. Using the 60 HU threshold, relative volume of the low-density plaque component obtained at 80 kV was lower than that obtained at 120 kV (27?±?3% vs. 51?±?5%, P?<?0.001), whereas relative volume of the medium-density plaque component obtained at 80 kV was higher than that obtained at 120 kV (73?±?3% vs. 48?±?5%, P?<?0.001). By contrast, no significant difference in relative volume obtained at 80 kV (82 HU threshold) versus 120 kV (60 HU threshold) was observed for either low-density (52?±?5% vs. 51?±?5%) or medium-density (48?±?5% vs. 48?±?5%) plaque component. Low tube potential may affect the accuracy of quantitative atherosclerotic plaque analysis. For our phantom test, 82 HU was the optimal threshold for scanning at 80 kV.     

Patterns of physical activity participation across the cancer trajectory in colorectal cancer survivors

Purpose

The purpose of the present study was to explore the participation in physical activity (PA) by colorectal cancer survivors across cancer trajectories and based on selected demographic and medical variables.

Methods

A total of 431 participants were surveyed individually at the Shinchon Severance Hospital, Seoul, Korea, to determine their PA levels before diagnosis, during treatment and after completion of cancer treatment.

Results

Percentage of survivors meeting American College of Sports Medicine guideline significantly reduced from 27 % before diagnosis to 10 % during treatment due to reduced strenuous intensity PA (28.8?±?106.2 vs 11.8?±?95.9 min, p?=?0.042), while total PA and mild intensity PA did not change. Total (187.2?±?257.7 vs. 282.6?±?282.0 min, p?<?0.001) and mild (99.1?±?191.5 vs. 175.1?±?231.2 min, p?<?0.001) intensity PA significantly increased after the completion of treatments compared with their PA level before diagnosis. Further analyses showed that age (more vs. equal or less than 60 years) and chemotherapy (chemotherapy vs. no chemotherapy) significantly influenced the level of physical activity (p?=?0.004). Survivors who were older or received chemotherapy increased their total PA and mild intensity PA after the completion of treatment more than those who did not receive chemotherapy.

Conclusions

The level and the pattern of physical activity by colorectal cancer survivors differed across cancer trajectories, which were significantly influenced by age and adjuvant chemotherapy.