Diagnostic accuracy,yield, and comparative effectiveness of whole-body computed tomography in blunt trauma: A protocol for systematic review and meta-analysis

Objectives:Controversies emerge over routine performances of whole-body computed tomography (WBCT) in patients with blunt polytrauma. The existing randomized and non-randomized evidence is inconclusive, and during observations of non-trauma, incidental findings, detected by WBCT, have left uncertainty regarding their consequences and optimal management. Additionally, previous meta-analyses have failed to address the limitations of primary studies and issues associated with incidental findings. Therefore, we planned a new systematic review to address these points.Methods:We will search the PubMed, EMBASE, and Cochrane Central databases from inception to December 31, 2020, with no language restriction and perform full-text evaluation of potentially relevant articles. We will include prospective and retrospective studies with a single-gate design that assessed diagnostic accuracy and/or yield of WBCT to detect traumatic injuries, and studies that assessed incidental findings detected by WBCT. Additionally, we will include randomized controlled trials and non-randomized comparative studies that assessed the effectiveness of WBCT against conventional care, including selective computed tomography (CT). Studies of patients of all ages with blunt traumatic injuries, assessed at an emergency department, will be included. Two reviewers will extract data and rate the study validity via standard quality assessment tools. The primary outcome of interest will be reduction in mortality. Our secondary outcomes will include diagnostic accuracy and yield, detection of incidental findings and clinical outcomes associated with these detections, and improvement in other non-mortality clinical outcomes. We will qualitatively assess study, patient, and intervention characteristics and clinical outcomes. If appropriate, we will perform random-effects model meta-analyses to obtain summary estimates. Finally, we will assess the certainty of evidence by the grading the quality of evidence and strength of recommendations.Ethics and dissemination:Ethics approval is not applicable, as this is a secondary analysis of publicly available data. The review results will be submitted for publication in peer-reviewed journals.Prospero registration:CRD42020187852.     

Natural course of the impairment of endothelium-dependent relaxations after balloon endothelium removal in porcine coronary arteries. Possible dysfunction of a pertussis toxin-sensitive G protein

The purposes of the present study were to examine the natural course of the impairment of endothelium-dependent relaxations during a regeneration and tissue repair process after balloon endothelium removal and to elucidate the cellular mechanism(s) underlying it. Twenty-three male Yorkshire pigs underwent balloon endothelium removal along the proximal portion of either the left anterior descending or circumflex coronary artery and were then maintained on a regular chow for 4, 8, 16, or 24 weeks. Endothelium-dependent responses were examined in vitro in rings taken from the control and previously denuded arteries studied in parallel. Morphometric analysis revealed that intimal thickening developed only at the previously denuded area. In the previously denuded arteries with regenerated endothelium, the endothelium-dependent relaxations to UK 14304 (a selective alpha 2-adrenergic agonist), serotonin, and aggregating platelets were impaired 4 weeks after endothelium removal and remained so throughout the study. The endothelium-dependent relaxations to thrombin and adenosine diphosphate became depressed 8 weeks after endothelium removal and those to bradykinin became depressed 16 weeks after endothelium removal, while those to the calcium ionophore A23187 were maintained throughout the study. Endothelium-dependent relaxations to all vasoactive agents were unaltered in the control arteries. In the control arteries, pertussis toxin, an inhibitor of certain G proteins, markedly inhibited the endothelium-dependent relaxations to UK 14304 and serotonin and partially inhibited those to thrombin and aggregating platelets. The responses inhibited by the toxin in control arteries were significantly reduced in the reduced in the previously denuded arteries with regenerated endothelium. The inhibitory effect of pertussis toxin was markedly reduced in those arteries with regenerated endothelium. In quiescent rings, the presence of normal endothelium inhibited the contractions caused by serotonin and aggregating platelets; this endothelium-dependent depression was markedly impaired in the previously denuded arteries throughout the study. Direct relaxation of the coronary smooth muscle to nitric oxide or sodium nitroprusside or direct contraction to KCl or serotonin were comparable between the control and previously denuded arteries. These experiments indicate that endothelium-dependent relaxations progressively worsen after regeneration of the endothelium and that the dysfunction of a pertussis toxin-sensitive G protein partly account for the endothelial dysfunction in the chronic regenerated state.     

Heterogeneity of endothelium-dependent and endothelium-independent responses to aggregating platelets in porcine pulmonary arteries

Experiments were designed to determine the endothelium-dependent and endothelium-independent responses to aggregating platelets in porcine pulmonary arteries. Isolated rings with and without endothelium from large (5-7-mm-diameter) and small (2-3-mm-diameter) pulmonary arteries were suspended in modified Krebs-Ringer bicarbonate solution bubbled with 95% O2-5% CO2 in the presence of indomethacin. Aggregating platelets caused relaxations in rings with endothelium but contractions in rings without endothelium, both of which were significantly larger in small versus large pulmonary artery rings. Serotonin and ADP caused concentration-dependent endothelium-augmented relaxations that were unaffected by ketanserin. Methiothepin, but not apyrase, significantly decreased the platelet-induced endothelium-dependent relaxations; the residual relaxation was abolished when rings were incubated with methiothepin, apyrase, and theophylline but was unaffected if apyrase was absent, indicating that ADP is responsible for the residual relaxation caused by aggregating platelets. Quiescent rings, with and without endothelium, contracted in a dose-dependent manner to norepinephrine and histamine but not to serotonin or vasopressin. The contraction to aggregating platelets was blocked by methiothepin, pyrilamine, and diphenhydramine but was unaffected by phentolamine, ketanserin, or incubation of the platelets with dazoxiben. These data indicate that, in large and small porcine pulmonary arteries, serotonin and ADP are the major contributors to the endothelium-dependent relaxation caused by aggregating platelets, while histamine appears to be responsible for the contraction that platelets cause in rings without endothelium.     

Endothelium-dependent inhibition of ergonovine-induced contraction is impaired in porcine coronary arteries with regenerated endothelium

The inhibitory effects of the endothelium against ergonovine-induced contraction were examined in isolated porcine coronary arteries under normal conditions and after endothelial regeneration. Endothelium-dependent responses were examined in vitro in normal Yorkshire pigs (n = 16) and in pigs that had undergone balloon endothelium removal of the left anterior descending coronary artery (LAD) 4 weeks before the study (n = 10). The presence of a complete endothelial lining was confirmed histologically. In rings from normal arteries contracted with prostaglandin F2 alpha in the presence of indomethacin and ketanserin (a 5-HT2-serotonergic blocker), ergonovine caused endothelium-dependent relaxations. They were attenuated by rauwolscine (an alpha 2-adrenergic blocker), inhibited by methiothepin (a combined 5-HT1- and 5-HT2-serotonergic blocker) or by pertussis toxin (an inhibitor of several G proteins) and abolished by oxyhemoglobin (a selective inactivator of endothelium-derived relaxing factor). In quiescent rings from normal arteries, ergonovine caused contractions that were inhibited by the presence of the endothelium; this endothelium-dependent inhibition was abolished by oxyhemoglobin. The direct contractions were not affected by prazosin (an alpha 1-adrenergic blocker), rauwolscine, 6-hydroxydopamine (an agent causing chemical sympathetectomy), or diphenhydramine (an H1-histaminergic blocker) but were inhibited by ketanserin. In rings with regenerated endothelium contracted with prostaglandin F2 alpha, the endothelium-dependent relaxations to ergonovine were reduced significantly and were not inhibited by pertussis toxin. In quiescent rings with regenerated endothelium, the endothelium-dependent inhibition of ergonovine-induced contraction was less.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of dietary supplementation with cod-liver oil on endothelium-dependent responses in porcine coronary arteries

To study the effect of dietary supplementation with fish oil on endothelium-dependent responses, Yorkshire pigs were maintained on a normal diet or on a low (0.6 ml/kg/day) or a high (1.0 ml/kg/day) dose of cod-liver oil for 4 weeks. Endothelium-dependent responses were examined in vitro in rings of proximal left anterior descending coronary arteries taken from control and treated animals studied in parallel. Endothelium-dependent relaxations in response to bradykinin, serotonin, adenosine diphosphate, and thrombin were facilitated in arteries from treated but not in those from control animals, whereas the relaxations in response to A23187 were unaltered. The facilitated relaxations were not altered by indomethacin but significantly inhibited by methylene blue. Aggregating platelets from control and treated pigs induced comparable, facilitated endothelium-dependent relaxations in rings taken from treated pigs. The platelet-induced contractions were significantly reduced in rings with endothelium taken from treated pigs, and they were comparable in rings without endothelium in both groups. Aggregating platelets from control and treated pigs released comparable amounts of serotonin and thromboxane A2. Endothelium-dependent relaxations induced by arachidonic acid and eicosapentaenoic acid were unaltered, whereas transient endothelium-dependent contractions induced by arachidonic acid were significantly reduced by the treatment with cod-liver oil. Relaxations to sodium nitroprusside or isoproterenol,and contractions to potassium chloride or serotonin were not different in rings without endothelium from control or treated pigs. These results indicate that dietary supplementation with cod-liver oil facilitates endothelium-dependent relaxations and inhibits endothelium-dependent contractions in porcine coronary arteries.     

Efficient protective activity of a planar catechin analogue against radiation-induced apoptosis in rat thymocytes

About two thirds of biological damage due to low linear energy transfer (LET) radiation, such as X-rays and the plateau region of heavy-ion beams, is known to be caused by the hydroxyl radical (˙OH), the most powerful reactive oxygen species (ROS), generated via ionisation and excitation of water molecules. Thus, compounds having an efficient scavenging activity against ROS are expected to exhibit a radioprotective activity. A planar catechin analogue, where an isopropyl fragment was introduced into the catechol ring of (+)-catechin, showed an efficient protective effect against X-ray induced apoptosis in rat thymocytes compared to (+)-catechin. The planar catechin scavenged 2,2-diphenyl-1-picrylhydrazyl radicals (DPPH˙) solubilised in water by β-cyclodextrin about 10-fold faster than (+)-catechin in phosphate buffer (0.1 M, pH 7.4) at 298 K. Furthermore, the experimental log P value of the planar catechin (1.22) is reported to be significantly larger than that of (+)-catechin (0.44). The higher radical-scavenging activity and lipophilicity of the planar catechin than those of (+)-catechin may contribute in part to the higher protective activity against X-ray-induced apoptosis in rat thymocytes.

A planar catechin analogue showed a significant higher protective activity against X-ray induced apoptosis in rat thymocytes than (+)-catechin.     

Alcohol-induced sinus bradycardia and hypotension in patients with syncope.

We observed 2 cases of repeated episodes of syncope after alcohol ingestion. Both patients were light drinkers and had carotid sinus hypersensitivity. In both cases, alcohol loading tests repeatedly induced sinus bradycardia and hypotension 1.0-1.5 hours after drinking alcohol. Atropine was effective in improving symptoms. A loading test using a glucose solution of equivalent osmolarity and volume was negative. Acute alcohol ingestion usually increases heart rate with variable effects on blood pressure. However, our 2 cases exhibited unusual alcohol-induced sinus bradycardia and hypotension, suggesting a paradoxical increase in parasympathetic activity and/or decrease in sympathetic activity.     

Role of nitric oxide in regulation of coronary blood flow in response to increased metabolic demand in dogs with pacing-induced heart failure

The role of endothelium-derived nitric oxide (NO) in the metabolic control of coronary blood flow (CBF) in heart failure (HF) is poorly understood, so the present study investigated the effects of inhibitors of NO synthesis on the response of CBF to changes in myocardial oxygen consumption (MVO2) in dogs with HF produced by rapid ventricular pacing and in control dogs. The CBF, MVO2, and other hemodynamic parameters were measured in anesthetized animals. Before infusion of Nomega-nitro-L-arginine methyl ester (L-NAME), the increases in CBF and MVO2 during pacing tachycardia were not significantly different between the control and HF dogs. Intracoronary infusion of L-NAME did not alter the responses of CBF or MVO2 to pacing tachycardia in the control dogs, but in the HF dogs, it reduced the CBF response to pacing tachycardia without altering the tachycardia-induced changes in MVO2. Intracoronary infusion of L-arginine reversed the effect of L-NAME. These results suggest that in HF dogs NO contributes to the regulation of CBF in response to an increased metabolic demand.     

Echocardiographic Changes in Patients Implanted With a Fully Magnetically Levitated Left Ventricular Assist Device (Heartmate 3)

Background

The Heartmate 3 (HM3) is a Conformiteé Européenne mark–approved left ventricular (LV) assist device (LVAD) with fully magnetically levitated rotor and features consisting of a wide range operational speeds, wide flow paths, and artificial pulse. We performed a hemodynamic-echocardiographic speed optimization evaluation in HM3-implanted patients to achieve optimal LV- and right ventricular (RV) shape.