Image Quality and Radiation Dose of CT Coronary Angiography with Automatic Tube Current Modulation and Strong Adaptive Iterative Dose Reduction Three-Dimensional (AIDR3D)

Purpose

To investigate image quality and radiation dose of CT coronary angiography (CTCA) scanned using automatic tube current modulation (ATCM) and reconstructed by strong adaptive iterative dose reduction three-dimensional (AIDR3D).

Methods

Eighty-four consecutive CTCA patients were collected for the study. All patients were scanned using ATCM and reconstructed with strong AIDR3D, standard AIDR3D and filtered back-projection (FBP) respectively. Two radiologists who were blinded to the patients'' clinical data and reconstruction methods evaluated image quality. Quantitative image quality evaluation included image noise, signal-to-noise ratio (SNR), and contrast-to-noise ratio (CNR). To evaluate image quality qualitatively, coronary artery is classified into 15 segments based on the modified guidelines of the American Heart Association. Qualitative image quality was evaluated using a 4-point scale. Radiation dose was calculated based on dose-length product.

Results

Compared with standard AIDR3D, strong AIDR3D had lower image noise, higher SNR and CNR, their differences were all statistically significant (P<0.05); compared with FBP, strong AIDR3D decreased image noise by 46.1%, increased SNR by 84.7%, and improved CNR by 82.2%, their differences were all statistically significant (P<0.05 or 0.001). Segments with diagnostic image quality for strong AIDR3D were 336 (100.0%), 486 (96.4%), and 394 (93.8%) in proximal, middle, and distal part respectively; whereas those for standard AIDR3D were 332 (98.8%), 472 (93.7%), 378 (90.0%), respectively; those for FBP were 217 (64.6%), 173 (34.3%), 114 (27.1%), respectively; total segments with diagnostic image quality in strong AIDR3D (1216, 96.5%) were higher than those of standard AIDR3D (1182, 93.8%) and FBP (504, 40.0%); the differences between strong AIDR3D and standard AIDR3D, strong AIDR3D and FBP were all statistically significant (P<0.05 or 0.001). The mean effective radiation dose was (2.55±1.21) mSv.

Conclusion

Compared with standard AIDR3D and FBP, CTCA with ATCM and strong AIDR3D could significantly improve both quantitative and qualitative image quality.     

Feasibility Study of Using Gemstone Spectral Imaging (GSI) and Adaptive Statistical Iterative Reconstruction (ASIR) for Reducing Radiation and Iodine Contrast Dose in Abdominal CT Patients with High BMI Values

Purpose

To prospectively investigate the effect of using Gemstone Spectral Imaging (GSI) and adaptive statistical iterative reconstruction (ASIR) for reducing radiation and iodine contrast dose in abdominal CT patients with high BMI values.

Materials and Methods

26 patients (weight > 65kg and BMI ≥ 22) underwent abdominal CT using GSI mode with 300mgI/kg contrast material as study group (group A). Another 21 patients (weight ≤ 65kg and BMI ≥ 22) were scanned with a conventional 120 kVp tube voltage for noise index (NI) of 11 with 450mgI/kg contrast material as control group (group B). GSI images were reconstructed at 60keV with 50%ASIR and the conventional 120kVp images were reconstructed with FBP reconstruction. The CT values, standard deviation (SD), signal-noise-ratio (SNR), contrast-noise-ratio (CNR) of 26 landmarks were quantitatively measured and image quality qualitatively assessed using statistical analysis.

Results

As for the quantitative analysis, the difference of CNR between groups A and B was all significant except for the mesenteric vein. The SNR in group A was higher than B except the mesenteric artery and splenic artery. As for the qualitative analysis, all images had diagnostic quality and the agreement for image quality assessment between the reviewers was substantial (kappa = 0.684). CT dose index (CTDI) values for non-enhanced, arterial phase and portal phase in group A were decreased by 49.04%, 40.51% and 40.54% compared with group B (P = 0.000), respectively. The total dose and the injection rate for the contrast material were reduced by 14.40% and 14.95% in A compared with B.

Conclusion

The use of GSI and ASIR provides similar enhancement in vessels and image quality with reduced radiation dose and contrast dose, compared with the use of conventional scan protocol.     

Inhaled Carbon Monoxide Protects against the Development of Shock and Mitochondrial Injury following Hemorrhage and Resuscitation

Aims

Currently, there is no effective resuscitative adjunct to fluid and blood products to limit tissue injury for traumatic hemorrhagic shock. The objective of this study was to investigate the role of inhaled carbon monoxide (CO) to limit inflammation and tissue injury, and specifically mitochondrial damage, in experimental models of hemorrhage and resuscitation.

Results

Inhaled CO (250 ppm for 30 minutes) protected against mortality in severe murine hemorrhagic shock and resuscitation (HS/R) (20% vs. 80%; P<0.01). Additionally, CO limited the development of shock as determined by arterial blood pH (7.25±0.06 vs. 7.05±0.05; P<0.05), lactate levels (7.2±5.1 vs 13.3±6.0; P<0.05), and base deficit (13±3.0 vs 24±3.1; P<0.05). A dose response of CO (25–500 ppm) demonstrated protection against HS/R lung and liver injury as determined by MPO activity and serum ALT, respectively. CO limited HS/R-induced increases in serum tumor necrosis factor-α and interleukin-6 levels as determined by ELISA (P<0.05 for doses of 100–500ppm). Furthermore, inhaled CO limited HS/R induced oxidative stress as determined by hepatic oxidized glutathione:reduced glutathione levels and lipid peroxidation. In porcine HS/R, CO did not influence hemodynamics. However, CO limited HS/R-induced skeletal muscle and platelet mitochondrial injury as determined by respiratory control ratio (muscle) and ATP-linked respiration and mitochondrial reserve capacity (platelets).

Conclusion

These preclinical studies suggest that inhaled CO can be a protective therapy in HS/R; however, further clinical studies are warranted.     

Heart Rate Variability Analysis in an Experimental Model of Hemorrhagic Shock and Resuscitation in Pigs

Background

The analysis of heart rate variability (HRV) has been shown as a promising non-invasive technique for assessing the cardiac autonomic modulation in trauma. The aim of this study was to evaluate HRV during hemorrhagic shock and fluid resuscitation, comparing to traditional hemodynamic and metabolic parameters.

Methods

Twenty anesthetized and mechanically ventilated pigs were submitted to hemorrhagic shock (60% of estimated blood volume) and evaluated for 60 minutes without fluid replacement. Surviving animals were treated with Ringer solution and evaluated for an additional period of 180 minutes. HRV metrics (time and frequency domain) as well as hemodynamic and metabolic parameters were evaluated in survivors and non-survivors animals.

Results

Seven of the 20 animals died during hemorrhage and initial fluid resuscitation. All animals presented an increase in time-domain HRV measures during haemorrhage and fluid resuscitation restored baseline values. Although not significantly, normalized low-frequency and LF/HF ratio decreased during early stages of haemorrhage, recovering baseline values later during hemorrhagic shock, and increased after fluid resuscitation. Non-surviving animals presented significantly lower mean arterial pressure (43±7vs57±9 mmHg, P<0.05) and cardiac index (1.7±0.2vs2.6±0.5 L/min/m², P<0.05), and higher levels of plasma lactate (7.2±2.4vs3.7±1.4 mmol/L, P<0.05), base excess (-6.8±3.3vs-2.3±2.8 mmol/L, P<0.05) and potassium (5.3±0.6vs4.2±0.3 mmol/L, P<0.05) at 30 minutes after hemorrhagic shock compared with surviving animals.

Conclusions

The HRV increased early during hemorrhage but none of the evaluated HRV metrics was able to discriminate survivors from non-survivors during hemorrhagic shock. Moreover, metabolic and hemodynamic variables were more reliable to reflect hemorrhagic shock severity than HRV metrics.     

Fluctuations of Serum Neuron Specific Enolase and Protein S-100B Concentrations in Relation to the Use of Shunt during Carotid Endarterectomy

Objective

To evaluate the changes in serum neuron specific enolase and protein S-100B, after carotid endarterectomy performed using the conventional technique with routine shunting and patch closure, or eversion technique without the use of shunt.

Materials and Methods

Prospective non-randomized study included 43 patients with severe (>80%) carotid stenosis undergoing carotid endarterectomy in regional anesthesia. Patients were divided into two groups: conventional endarterectomy with routine use of shunt and Dacron patch (csCEA group) and eversion endarterectomy without the use of shunt (eCEA group). Protein S-100B and NSE concentrations were measured from peripheral blood before carotid clamping, after declamping and 24 hours after surgery.

Results

Neurologic examination and brain CT findings on the first postoperative day did not differ from preoperative controls in any patients. In csCEA group, NSE concentrations decreased after declamping (P<0.01), and 24 hours after surgery (P<0.01), while in the eCEA group NSE values slightly increased (P=ns), accounting for a significant difference between groups on the first postoperative day (P=0.006). In both groups S-100B concentrations significantly increased after declamping (P<0.05), returning to near pre-clamp values 24 hours after surgery (P=ns). Sub-group analysis revealed significant decline of serum NSE concentrations in asymptomatic patients shunted during surgery after declamping (P<0.05) and 24 hours after surgery (P<0.01), while no significant changes were noted in non-shunted patients (P=ns). Decrease of NSE serum levels was also found in symptomatic patients operated with the use of shunt on the first postoperative day (P<0.05). Significant increase in NSE serum levels was recorded in non-shunted symptomatic patients 24 hours after surgery (P<0.05).

Conclusion

Variations of NSE concentrations seemed to be influenced by cerebral perfusion alterations, while protein S-100B values were unaffected by shunting strategy. Routine shunting during surgery for symptomatic carotid stenosis may have the potential to prevent postoperative increase of serum NSE levels, a potential marker of brain injury.     

Improving Image Quality of Bronchial Arteries with Virtual Monochromatic Spectral CT Images

Objective

To evaluate the clinical value of using monochromatic images in spectral CT pulmonary angiography to improve image quality of bronchial arteries.

Methods

We retrospectively analyzed the chest CT images of 38 patients who underwent contrast-enhanced spectral CT. These images included a set of 140kVp polychromatic images and the default 70keV monochromatic images. Using the standard Gemstone Spectral Imaging (GSI) viewer on an advanced workstation (AW4.6,GE Healthcare), an optimal energy level (in keV) for obtaining the best contrast-to-noise ratio (CNR) for the artery could be automatically obtained. The signal-to-noise ratio (SNR), CNR and objective image quality score (1–5) for these 3 image sets (140kVp, 70keV and optimal energy level) were obtained and, statistically compared. The image quality score consistency between the two observers was also evaluated using Kappa test.

Results

The optimal energy levels for obtaining the best CNR were 62.58±2.74keV.SNR and CNR from the 140kVp polychromatic, 70keV and optimal keV monochromatic images were (16.44±5.85, 13.24±5.52), (20.79±7.45, 16.69±6.27) and (24.9±9.91, 20.53±8.46), respectively. The corresponding subjective image quality scores were 1.97±0.82, 3.24±0.75, and 4.47±0.60. SNR, CNR and subjective scores had significant difference among groups (all p<0.001). The optimal keV monochromatic images were superior to the 70keV monochromatic and 140kVp polychromatic images, and there was high agreement between the two observers on image quality score (kappa>0.80).

Conclusions

Virtual monochromatic images at approximately 63keV in dual-energy spectral CT pulmonary angiography yielded the best CNR and highest diagnostic confidence for imaging bronchial arteries.     

Determination of the Optimal Dose Reduction Level via Iterative Reconstruction Using 640-Slice Volume Chest CT in a Pig Model

Aim

To determine the optimal dose reduction level of iterative reconstruction technique for paediatric chest CT in pig models.

Materials and Methods

27 infant pigs underwent 640-slice volume chest CT with 80kVp and different mAs. Automatic exposure control technique was used, and the index of noise was set to SD10 (Group A, routine dose), SD12.5, SD15, SD17.5, SD20 (Groups from B to E) to reduce dose respectively. Group A was reconstructed with filtered back projection (FBP), and Groups from B to E were reconstructed using iterative reconstruction (IR). Objective and subjective image quality (IQ) among groups were compared to determine an optimal radiation reduction level.

Results

The noise and signal-to-noise ratio (SNR) in Group D had no significant statistical difference from that in Group A (P = 1.0). The scores of subjective IQ in Group A were not significantly different from those in Group D (P>0.05). There were no obvious statistical differences in the objective and subjective index values among the subgroups (small, medium and large subgroups) of Group D. The effective dose (ED) of Group D was 58.9% lower than that of Group A (0.20±0.05mSv vs 0.48±0.10mSv, p <0.001).

Conclusions

In infant pig chest CT, using iterative reconstruction can provide diagnostic image quality; furthermore, it can reduce the dosage by 58.9%.     

Sympathetic Activation Does Not Affect the Cardiac and Respiratory Contribution to the Relationship between Blood Pressure and Pial Artery Pulsation Oscillations in Healthy Subjects

Introduction

Using a novel method called near-infrared transillumination backscattering sounding (NIR-T/BSS) that allows for the non-invasive measurement of pial artery pulsation (cc-TQ) and subarachnoid width (sas-TQ) in humans, we assessed the influence of sympathetic activation on the cardiac and respiratory contribution to blood pressure (BP) cc-TQ oscillations in healthy subjects.

Methods

The pial artery and subarachnoid width response to handgrip (HGT) and cold test (CT) were studied in 20 healthy subjects. The cc-TQ and sas-TQ were measured using NIR-T/BSS; cerebral blood flow velocity (CBFV) was measured using Doppler ultrasound of the left internal carotid artery; heart rate (HR) and beat-to-beat mean BP were recorded using a continuous finger-pulse photoplethysmography; respiratory rate (RR), minute ventilation (MV), end-tidal CO₂ (EtCO2) and end-tidal O₂ (EtO2) were measured using a metabolic and spirometry module of the medical monitoring system. Wavelet transform analysis was used to assess the relationship between BP and cc-TQ oscillations.

Results

HGT evoked an increase in BP (+15.9%; P<0.001), HR (14.7; P<0.001), SaO₂ (+0.5; P<0.001) EtO₂ (+2.1; P<0.05) RR (+9.2%; P = 0.05) and MV (+15.5%; P<0.001), while sas-TQ was diminished (-8.12%; P<0.001), and a clear trend toward cc-TQ decline was observed (-11.0%; NS). CBFV (+2.9%; NS) and EtCO₂ (-0.7; NS) did not change during HGT. CT evoked an increase in BP (+7.4%; P<0.001), sas-TQ (+3.5%; P<0.05) and SaO₂(+0.3%; P<0.05). HR (+2.3%; NS), CBFV (+2.0%; NS), EtO₂ (-0.7%; NS) and EtCO₂ (+0.9%; NS) remained unchanged. A trend toward decreased cc-TQ was observed (-5.1%; NS). The sas-TQ response was biphasic with elevation during the first 40 seconds (+8.8% vs. baseline; P<0.001) and subsequent decline (+4.1% vs. baseline; P<0.05). No change with respect to wavelet coherence and wavelet phase coherence was found between the BP and cc-TQ oscillations.

Conclusions

Short sympathetic activation does not affect the cardiac and respiratory contribution to the relationship between BP—cc-TQ oscillations. HGT and CT display divergent effects on the width of the subarachnoid space, an indirect marker of changes in intracranial pressure.     

Morphine-Induced Preconditioning: Involvement of Protein Kinase A and Mitochondrial Permeability Transition Pore

Background

Morphine induces myocardial preconditioning (M-PC) via activation of mitochondrial large conductance Ca²⁺-sensitive potassium (mK_Ca) channels. An upstream regulator of mK_Ca channels is protein kinase A (PKA). Furthermore, mK_Ca channel activation regulates mitochondrial bioenergetics and thereby prevents opening of the mitochondrial permeability transition pore (mPTP). Here, we investigated in the rat heart in vivo whether 1) M-PC is mediated by activation of PKA, and 2) pharmacological opening of the mPTP abolishes the cardioprotective effect of M-PC and 3) M-PC is critically dependent on STAT3 activation, which is located upstream of mPTP within the signalling pathway.

Methods

Male Wistar rats were randomised to six groups (each n = 6). All animals underwent 25 minutes of regional myocardial ischemia and 120 minutes of reperfusion. Control animals (Con) were not further treated. Morphine preconditioning was initiated by intravenous administration of 0.3 mg/kg morphine (M-PC). The PKA blocker H-89 (10 μg/kg) was investigated with and without morphine (H-89+M-PC, H-89). We determined the effect of mPTP opening with atractyloside (5 mg/kg) with and without morphine (Atr+M-PC, Atr). Furthermore, the effect of morphine on PKA activity was tested in isolated adult rat cardiomyocytes. In further experiments in isolated hearts we tested the protective properties of morphine in the presence of STAT3 inhibition, and whether pharmacological prevention of the mPTP-opening by cyclosporine A (CsA) is cardioprotective in the presence of STAT3 inhibition.

Results

Morphine reduced infarct size from 64±5% to 39±9% (P<0.05 vs. Con). H-89 completely blocked preconditioning by morphine (64±9%; P<0.05 vs. M-PC), but H-89 itself had not effect on infarct size (61±10%; P>0.05 vs. Con). Also, atractyloside abolished infarct size reduction of morphine completely (65±9%; P<0.05 vs. M-PC) but had no influence on infarct size itself (64±5%; P>0.05 vs. Con). In isolated hearts STAT3 inhibitor Stattic completely abolished morphine-induced preconditioning. Administration of Stattic and mPTP inhibitor cyclosporine A reduced infarct size to 31±6% (Stat+CsA, P<0.05 vs. Con). Cyclosporine A alone reduced infarct size to 26±7% (CsA P<0.05 vs. Con). In cardiomyocytes, PKA activity was increased by morphine.

Conclusion

Our data suggest that morphine-induced cardioprotection is mediated by STAT3-activation and inhibition of mPTP, with STA3 located upstream of mPTP. There is some evidence that protein kinase A is involved within the signalling pathway.     

Heat Shock Protein 22 (Hsp22) Regulates Oxidative Phosphorylation upon Its Mitochondrial Translocation with the Inducible Nitric Oxide Synthase in Mammalian Heart

Objectives

Stress-inducible heat shock protein 22 (Hsp22) confers protection against ischemia through induction of the inducible isoform of nitric oxide synthase (iNOS). Hsp22 overexpression in vivo stimulates cardiac mitochondrial respiration, whereas Hsp22 deletion in vivo significantly reduces respiration. We hypothesized that Hsp22-mediated regulation of mitochondrial function is dependent upon its mitochondrial translocation together with iNOS.

Methods and Results

Adenoviruses harboring either the full coding sequence of Hsp22 (Ad-WT-Hsp22) or a mutant lacking a N-terminal 20 amino acid putative mitochondrial localization sequence (Ad-N20-Hsp22) were generated, and infected in rat neonatal cardiomyocytes. Compared to β-Gal control, WT-Hsp22 accumulated in mitochondria by 2.5 fold (P<0.05) and increased oxygen consumption rates by 2-fold (P<0.01). This latter effect was abolished upon addition of the selective iNOS inhibitor, 1400W. Ad-WT-Hsp22 significantly increased global iNOS expression by about 2.5-fold (P<0.01), and also increased iNOS mitochondrial localization by 4.5 fold vs β-gal (P<0.05). Upon comparable overexpression, the N20-Hsp22 mutant did not show significant mitochondrial translocation or stimulation of mitochondrial respiration. Moreover, although N20-Hsp22 did increase global iNOS expression by 4.6-fold, it did not promote iNOS mitochondrial translocation.

Conclusion

Translocation of both Hsp22 and iNOS to the mitochondria is necessary for Hsp22-mediated stimulation of oxidative phosphorylation.     

How Do Urban Indian Private Practitioners Diagnose and Treat Tuberculosis? A Cross-Sectional Study in Chennai

Setting

Private practitioners are frequently the first point of healthcare contact for patients with tuberculosis (TB) in India. Inappropriate TB management practices among private practitioners may contribute to delayed TB diagnosis and generate drug resistance. However, these practices are not well understood. We evaluated diagnostic and treatment practices for active TB and benchmarked practices against International Standards for TB Care (ISTC) among private medical practitioners in Chennai.

Design

A cross-sectional survey of 228 practitioners practicing in the private sector from January 2014 to February 2015 in Chennai city who saw at least one TB patient in the previous year. Practitioners were randomly selected from both the general community and a list of practitioners who referred patients to a public-private mix program for TB treatment in Chennai. Practitioners were interviewed using standardized questionnaires.

Results

Among 228 private practitioners, a median of 12 (IQR 4–28) patients with TB were seen per year. Of 10 ISTC standards evaluated, the median of standards adhered to was 4.0 (IQR 3.0–6.0). Chest physicians reported greater median ISTC adherence than other MD and MS practitioners (score 7.0 vs. 4.0, P<0.001), or MBBS practitioners (score 7.0 vs. 4.0, P<0.001). Only 52% of all practitioners sent >5% of patients with cough for TB testing, 83% used smear microscopy for diagnosis, 33% monitored treatment response, and 22% notified TB cases to authorities. Of 228 practitioners, 68 reported referring all patients with new pulmonary TB for treatment, while 160 listed 27 different regimens; 78% (125/160) prescribed a regimen classified as consistent with ISTC. Appropriate treatment practices differed significantly between chest physicians and other MD and MS practitioners (54% vs. 87%, P<0.001).

Conclusion

TB management practices in India’s urban private sector are heterogeneous and often suboptimal. Private providers must be better engaged to improve diagnostic capacity and decrease TB transmission in the community.     

Vitamin E Attenuates the Progression of Non-Alcoholic Fatty Liver Disease Caused by Partial Hepatectomy in Mice

Background and Aim

The progression of non-alcoholic fatty liver disease (NAFLD) likely involves a ‘multiple hit’ mechanism. We hypothesized that partial hepatectomy, a procedure performed frequently in patients with NAFLD, would accelerate the progression of disease.

Methods

C57BL/6JolaHsd mice were fed a choline-deficient L-amino acid-defined diet (CD-AA) or a choline-sufficient L-amino acid-defined control diet (CS-AA). Part of the mice in the CD-AA group received a diet enriched in vitamin E (~20 mg /day). Two weeks after the start of the diet, mice underwent a partial hepatectomy or a sham operation.

Results

In the CD-AA group, NAFLD activity scores were significantly higher at 7 days after partial hepatectomy compared to the sham operated mice (3.7 ± 1.3 vs. 1.8 ± 0.7; P<0.05). In addition, TBARS, a measure for oxidative stress, in liver tissue of the CD-AA group were significantly higher at day 1, 3 and 7 after partial hepatectomy compared to the sham operated mice (P<0.05). Vitamin E therapy significantly reduced TBARS level at day 7 after partial hepatectomy compared to the CD-AA diet group (P< 0.05). Vitamin E suppletion reduced NAFLD activity score at day 7 after partial hepatectomy compared to the CD-AA group (2.3 ± 0.8 vs. 3.8 ± 1.0; P<0.05).

Conclusion

Partial hepatectomy accelerates the progression of NAFLD. Disease progression induced by partial hepatectomy is substantially attenuated by vitamin E.     

Reduced Radiation Exposure for Face Transplant Surgical Planning Computed Tomography Angiography

Objective

To test the hypothesis that wide area detector face transplant surgical planning CT angiograms with simulated lower radiation dose and iterative reconstruction (AIDR3D) are comparable in image quality to those with standard tube current and filtered back projection (FBP) reconstruction.

Materials and Methods

The sinograms from 320-detector row CT angiography of four clinical candidates for face transplantation were processed utilizing standard FBP, FBP with simulated 75, 62, and 50% tube current, and AIDR3D with corresponding dose reduction. Signal-to-noise ratio (SNR) and contrast-to-noise ratio (CNR) were measured at muscle, fat, artery, and vein. Image quality for each reconstruction strategy was assessed by two independent readers using a 4-point scale.

Results

Compared to FBP, the median SNR and CNR for AIDR3D images were higher at all sites for all 4 different tube currents. The AIDR3D with simulated 50% tube current achieved comparable SNR and CNR to FBP with standard dose (median muscle SNR: 5.77 vs. 6.23; fat SNR: 6.40 vs. 5.75; artery SNR: 43.8 vs. 45.0; vein SNR: 54.9 vs. 55.7; artery CNR: 38.1 vs. 38.6; vein CNR: 49.0 vs. 48.7; all p-values >0.19). The interobserver agreement in the image quality score was good (weighted κ = 0.7). The overall score and the scores for smaller arteries were significantly lower when FBP with 50% dose reduction was used. The AIDR3D reconstruction images with 4 different simulated doses achieved a mean score ranging from 3.68 to 3.82 that were comparable to the scores from images reconstructed using FBP with original dose (3.68–3.77).

Conclusions

Simulated radiation dose reduction applied to clinical CT angiography for face transplant planning suggests that AIDR3D allows for a 50% reduction in radiation dose, as compared to FBP, while preserving image quality.     

Shank Muscle Strength Training Changes Foot Behaviour during a Sudden Ankle Supination

Background

The peroneal muscles are the most effective lateral stabilisers whose tension braces the ankle joint complex against excessive supination. The purpose of this study was to identify the morphological and biomechanical effects of two machine-based shank muscle training methods.

Methods

Twenty-two healthy male recreationally active sports students performed ten weeks of single-set high resistance strength training with 3 training sessions per week. The subjects conducted subtalar pronator/supinator muscle training (ST) with the right leg by using a custom-made apparatus; the left foot muscles were exercised with machine-based talocrural plantar and dorsiflexor training (TT). Muscle strength (MVIC), muscle volume and foot biomechanics (rearfoot motion, ground reaction forces, muscle reaction times) during a sudden ankle supination were recorded before and after the intervention.

Results

Compared to TT, ST resulted in significantly higher pronator (14% vs. 8%, P<0.01) and supinator MVIC (25% vs. 12%, P<0.01). During sudden foot inversions, both ST and TT resulted in reduced supination velocity (-12%; P<0.01). The muscle reaction onset time was faster after the training in peroneus longus (PL) (P<0.01). Muscle volume of PL (P<0.01) and TA (P<0.01) increased significantly after both ST and TT.

Conclusion

After both ST and TT, the ankle joint complex is mechanically more stabilised against sudden supinations due to the muscle volume increase of PL and TA. As the reduced supination velocities indicate, the strength training effects are already present during free-fall. According to a sudden ankle supination in standing position, both machine-based dorsiflexor and pronator strength training is recommended for enhancing the mechanical stability of the ankle.     

Elevated Plasma CXCL12α Is Associated with a Poorer Prognosis in Pulmonary Arterial Hypertension

Rationale

Recent work in preclinical models suggests that signalling via the pro-angiogenic and pro-inflammatory cytokine, CXCL12 (SDF-1), plays an important pathogenic role in pulmonary hypertension (PH). The objective of this study was to establish whether circulating concentrations of CXCL12α were elevated in patients with PAH and related to mortality.

Methods

Plasma samples were collected from patients with idiopathic pulmonary arterial hypertension (IPAH) and PAH associated with connective tissue diseases (CTD-PAH) attending two pulmonary hypertension referral centres (n = 95) and from age and gender matched healthy controls (n = 44). Patients were subsequently monitored throughout a period of five years.

Results

CXCL12α concentrations were elevated in PAH groups compared to controls (P<0.05) and receiver-operating-characteristic analysis showed that plasma CXCL12α concentrations discriminated patients from healthy controls (AUC 0.80, 95% confidence interval 0.73-0.88). Kaplan Meier analysis indicated that elevated plasma CXCL12α concentration was associated with reduced survival (P<0.01). Multivariate Cox proportional hazards model showed that elevated CXCL12α independently predicted (P<0.05) earlier death in PAH with a hazard ratio (95% confidence interval) of 2.25 (1.01-5.00). In the largest subset by WHO functional class (Class 3, 65% of patients) elevated CXCL12α independently predicted (P<0.05) earlier death, hazard ratio 2.27 (1.05-4.89).

Conclusions

Our data show that elevated concentrations of circulating CXCL12α in PAH predicted poorer survival. Furthermore, elevated circulating CXCL12α was an independent risk factor for death that could potentially be included in a prognostic model and guide therapy.     

Impact of Mitochondrial Ca2+-Sensitive Potassium (mBKCa) Channels in Sildenafil-Induced Cardioprotection in Rats

Background

Mitochondrial large-conductance Ca²⁺-sensitive potassium (mBK_Ca) channels are involved in myocardial ischemic preconditioning. Their role in sildenafil-induced cardioprotection is unknown. We investigated whether sildenafil-induced acute cardioprotection is mediated by activation of mBK_Ca channels in the rat heart in vitro.

Methods

Male Wistar rats (n = 8 per group) were randomized and anesthetized with pentobarbital (90 mg/kg). Hearts were isolated, mounted on a Langendorff system and perfused with Krebs-Henseleit buffer at a constant pressure of 80 mmHg. Hearts underwent 30 min of global ischemia followed by 60 min of reperfusion. At the end of the experiments infarct size was determined by TTC staining. In the control group rats were not further treated. Sildenafil (3 μM) was administered over 10 min before the beginning of ischemia. The mBK_Ca channel inhibitor paxilline (1 μM) was administered with and without sildenafil before the onset of ischemia. The pathway underlying sildenafil-induced cardioprotection was further investigated with the protein kinase G blocker KT5823 (1 μM). Myocardial cGMP concentration was measured by ELISA. Data (mean±SD) were analysed with a one and two-way analysis of variance as appropriate.

Results

In control animals infarct size was 52±8%. Sildenafil increased cGMP concentration and reduced infarct size to 35±6% (P<0.05 vs. control). Paxilline and KT5823 completely blocked sildenafil-induced cardioprotection (paxilline+sildenafil: 50±8%, KT5823+sildenafil: 45±8%; both P<0.05 vs. sildenafil). Functional heart parameters and coronary flow were not different between the study groups.

Conclusion

This study shows that in male rats protein kinase G-dependent opening of mBK_Ca channels plays a pivotal role in sildenafil-induced cardioprotection.     

Brown Adipose Tissue Activation Is Inversely Related to Central Obesity and Metabolic Parameters in Adult Human

Background

Recent studies have shown that adult human possess active brown adipose tissue (BAT), which might be important in affecting obesity. However, the supporting evidence on the relationship between BAT and central obesity and metabolic profile in large population based studies is sparse.

Methodology/Principal Findings

We studied 4011 (2688 males and 1323 females) tumor-free Chinese adults aged 18-89 for BAT activities, visceral/subcutaneous fat areas (VFA/SFA), waist circumferences (WC) and metabolic parameters. We found that the prevalence of BAT was around 2.7% in our study participants, with a significant sexual difference (5.5% in the females vs. 1.3% in the males; p<0.0001). BAT detection was increased in low temperature and declined in elderly subjects. The BAT positive subjects had lower BMI (P<0.0001), less SFA (P<0.01), VFA (P<0.0001), WC (P<0.0001), lower fasting glucose and triglyceride levels (both P<0.01) and increased HDL cholesterol concentrations (P<0.0001), compared with the BAT negative subjects. Robust logistic regression revealed that after adjustment for covariates (including age, sex, BMI, VFA, SFA and WC), age and BMI in the males (0.92 [95%CI, 0.88-0.96] and 0.84 [95% CI, 0.75-0.96], both P ≤0.008) while age and VFA in the females (0.87 [95%CI, 0.83-0.91] and 0.98 [95%CI, 0.97-0.99], respectively, P<0.05) were independently associated with detectable BAT.

Conclusions/Significance

Our data suggest that decreased amount of active BAT might be associated with accumulation of visceral fat content and unfavorable metabolic outcomes.     

Effectiveness of Ureteroscopy-Assisted Retrograde Nephrostomy (UARN) for Percutaneous Nephrolithotomy (PCNL)

Objective

To determine the impact of ureteroscopy-assisted retrograde nephrostomy (UARN) during percutaneous nephrolithotomy (PCNL).

Materials and Methods

From April 2009 to September 2011, a total of 50 patients underwent PCNL for large renal stones (stone burden >2 cm). We performed UARN in the Galdakao-modified Valdivia position for 27 patients (UARN PCNL) and ultrasonography-assisted percutaneous nephrostomy in the prone position for 23 patients (prone PCNL).

Results

UARN PCNL significantly improved the stone-free rate (81.5% vs 52.2%) and the rate of residual stones (<4 mm, 92.6% vs 65.2%, P<0.05). The median length of the operation was significantly shorter for UARN PCNL, at 160 min, compared to 299 min for prone PCNL (P<0.001). There was one intraoperative complication in prone PCNL, namely a hemorrhage that resulted in stopping the initial treatment, but it was cured conservatively. The postoperative complications included a high grade fever that persisted for three days in two UARN PCNL patients (7.4%) and six prone PCNL patients (26.1%). The Clavien grading scores showed significantly lower postoperative complications for UARN PCNL compared to prone PCNL.

Conclusion

UARN is associated with a higher stone-free rate, shorter operation time, and fewer complications during PCNL than prone PCNL.     

Improvement of Image Quality and Diagnostic Performance by an Innovative Motion-Correction Algorithm for Prospectively ECG Triggered Coronary CT Angiography

Objective

To investigate the effect of a novel motion-correction algorithm (Snap-short Freeze, SSF) on image quality and diagnostic accuracy in patients undergoing prospectively ECG-triggered CCTA without administering rate-lowering medications.

Materials and Methods

Forty-six consecutive patients suspected of CAD prospectively underwent CCTA using prospective ECG-triggering without rate control and invasive coronary angiography (ICA). Image quality, interpretability, and diagnostic performance of SSF were compared with conventional multisegment reconstruction without SSF, using ICA as the reference standard.

Results

All subjects (35 men, 57.6 ± 8.9 years) successfully underwent ICA and CCTA. Mean heart rate was 68.8±8.4 (range: 50–88 beats/min) beats/min without rate controlling medications during CT scanning. Overall median image quality score (graded 1–4) was significantly increased from 3.0 to 4.0 by the new algorithm in comparison to conventional reconstruction. Overall interpretability was significantly improved, with a significant reduction in the number of non-diagnostic segments (690 of 694, 99.4% vs 659 of 694, 94.9%; P<0.001). However, only the right coronary artery (RCA) showed a statistically significant difference (45 of 46, 97.8% vs 35 of 46, 76.1%; P = 0.004) on a per-vessel basis in this regard. Diagnostic accuracy for detecting ≥50% stenosis was improved using the motion-correction algorithm on per-vessel [96.2% (177/184) vs 87.0% (160/184); P = 0.002] and per-segment [96.1% (667/694) vs 86.6% (601/694); P <0.001] levels, but there was not a statistically significant improvement on a per-patient level [97.8 (45/46) vs 89.1 (41/46); P = 0.203]. By artery analysis, diagnostic accuracy was improved only for the RCA [97.8% (45/46) vs 78.3% (36/46); P = 0.007].

Conclusion

The intracycle motion correction algorithm significantly improved image quality and diagnostic interpretability in patients undergoing CCTA with prospective ECG triggering and no rate control.     

Media Coverage,Journal Press Releases and Editorials Associated with Randomized and Observational Studies in High-Impact Medical Journals: A Cohort Study

Background

Publication of clinical research findings in prominent journals influences health beliefs and medical practice, in part by engendering news coverage. Randomized controlled trials (RCTs) should be most influential in guiding clinical practice. We determined whether study design of clinical research published in high-impact journals influences media coverage.

Methods and Findings

We compared the incidence and amount of media coverage of RCTs with that of observational studies published in the top 7 medical journals between 1 January 2013 and 31 March 2013. We specifically assessed media coverage of the most rigorous RCTs, those with >1000 participants that reported ‘hard’ outcomes. There was no difference between RCTs and observational studies in coverage by major newspapers or news agencies, or in total number of news stories generated (all P>0.63). Large RCTs reporting ‘hard’ outcomes did not generate more news coverage than small RCTs that reported surrogate outcomes and observational studies (all P>0.32). RCTs were more likely than observational studies to attract a journal editorial (70% vs 46%, P = 0.003), but less likely to be the subject of a journal press release (17% vs 50%, P<0.001). Large RCTs that reported ‘hard’ outcomes did not attract an editorial more frequently than other studies (61% vs 58%, P>0.99), nor were they more likely to be the subject of a journal press release (14% vs 38%, P = 0.14).

Conclusions

The design of clinical studies whose results are published in high-impact medical journals is not associated with the likelihood or amount of ensuing news coverage.