Association of Low-Dose Whole-Body Computed Tomography With Missed Injury Diagnoses and Radiation Exposure in Patients With Blunt Multiple Trauma.

Importance: Initial whole-body computed tomography (WBCT) for screening patients with suspected blunt multiple trauma remains controversial and a source of excess radiation exposure. Objective: To determine whether low-dose WBCT scanning using an iterative reconstruction algorithm does not increase the rate of missed injury diagnoses at the point of care compared with standard-dose WBCT with the benefit of less radiation exposure. Design, Setting, and Participants: This quasi-experimental, prospective time-series cohort study recruited 1074 consecutive patients admitted for suspected blunt multiple trauma to an academic metropolitan trauma center in Germany from September 3, 2014, through July 26, 2015, for the standard-dose protocol, and from August 7, 2015, through August 20, 2016, for the low-dose protocol. Five hundred sixty-five patients with suspected blunt multiple trauma prospectively received standard-dose WBCT, followed by 509 patients who underwent low-dose WBCT. Confounding was controlled by segmented regression analysis and a secondary multivariate logistic regression model. Data were analyzed from January 16, 2017, through October 14, 2019. Interventions: Standard- or low-dose WBCT. Main Outcomes and Measures: The primary outcome was the incidence of missed injury diagnoses at the point of care, using a synopsis of clinical, surgical, and radiological findings as an independent reference test. The secondary outcome was radiation exposure with either imaging strategy. Results: Of 1074 eligible patients, 971 (mean [SD] age, 52.7 [19.5] years; 649 men [66.8%]) completed the study. A total of 114 patients (11.7%) had multiple trauma, as defined by an Injury Severity Score of 16 or greater. The proportion of patients with any missed injury diagnosis at the point of care was 109 of 468 (23.3%) in the standard-dose and 107 of 503 (21.3%) in the low-dose WBCT groups (risk difference, -2.0% [95% CI, -7.3% to 3.2%]; unadjusted odds ratio, 0.89 [95% CI, 0.66-1.20]; P = .45). Adjustments for autocorrelation and multiple confounding variables did not alter the results. Radiation exposure, measured by the volume computed tomography dose index, was lowered from a median of 11.7 (interquartile range, 11.7-17.6) mGy in the standard-dose WBCT group to 5.9 (interquartile range, 5.9-8.8) mGy in the low-dose WBCT group (P < .001). Conclusions and Relevance: Low-dose WBCT using iterative image reconstruction does not appear to increase the risk of missed injury diagnoses at the point of care compared with standard-dose protocols while almost halving the exposure to diagnostic radiation.

Retrospective Analysis and Systematic Review of Isolated Traumatic Dissections of the Celiac Artery.

BACKGROUND: Isolated dissections of the celiac artery (CA) after blunt trauma are rarely described. This retrospective analysis and systematic review analyzes epidemiology, radiologic examinations, patterns of injuries, therapeutic measures, clinical courses, and outcomes. METHODS: Retrospective analysis of polytraumatized patients admitted between 1997 and 2012 to a trauma center level I. Systematic literature search was carried out on pubmed.gov, eurorad.org, and google.com. RESULTS: Isolated traumatic dissections of the CA had an incidence of 0.17% in a retrospective collective (n = 9). Mean age was 31.7 years in 6 male (66.7%) and 3 female (33.3%) patients. Systematic literature search identified 12 primary sources describing 13 males (100%) with a mean age of 41.3 years. Traffic accidents and falls were the most common causes of injury. An intimal flap (77.7%) and a thrombosed false lumen (59.1%) were the most common computed tomographic findings. Twenty-two patients were analyzed, and 16 patients were treated conservatively. The CA was bypassed in 2 symptomatic patients. One patient was treated with a stent. Two patients died because of massive bleeding, and 1 patient died because of liver failure. About 19 discharged patients were asymptomatic on follow-up. Long-term follow-up with magnetic resonance angiography showed stable dissections (n = 1), medium stenosis (n = 1), resolution of the dissection (n = 2), high-grade stenosis of the CA combined with a small pseudoaneurysm (n = 1), or occlusion of the CA with sufficient collateralization (n = 3). Pharmaceutical treatment was individualized with low-molecular-weight heparin, heparin, or warfarin, and acetylicsalicylic acid. CONCLUSIONS: Traumatic CA dissections are mostly caused by traffic accidents and falls. Visceral perfusion should be monitored clinically and radiologically. Beginning visceral ischemia requires early invasive treatment. Endovascular and open surgery are possible options. Benefits of specific pharmaceuticals are still up for debate. Follow-up via magnetic resonance imaging or computed tomography angiography is essential to rule out vascular complications. LEVEL OF EVIDENCE: III (Retrospective therapeutic study and systematic literature review).

Dose reduction in whole-body computed tomography of multiple injuries (DoReMI): protocol for a prospective cohort study.

BACKGROUND: Single-pass, contrast-enhanced whole body multidetector computed tomography (MDCT) emerged as the diagnostic standard for evaluating patients with major trauma. Modern iterative image algorithms showed high image quality at a much lower radiation dose in the non-trauma setting. This study aims at investigating whether the radiation dose can safely be reduced in trauma patients without compromising the diagnostic accuracy and image quality. METHODS/DESIGN: Prospective observational study with two consecutive cohorts of patients. SETTING: A high-volume, academic, supra-regional trauma centre in Germany. STUDY POPULATION: Consecutive male and female patients who 1. had been exposed to a high-velocity trauma mechanism, 2. present with clinical evidence or high suspicion of multiple trauma (predicted Injury Severity Score [ISS] ≥16) and 3. are scheduled for primary MDCT based on the decision of the trauma leader on call.Imaging protocols: In a before/after design, a consecutive series of 500 patients will undergo single-pass, whole-body 128-row multi-detector computed tomography (MDCT) with a standard, as low as possible radiation dose. This will be followed by a consecutive series of 500 patients undergoing an approved ultra-low dose MDCT protocol using an image processing algorithm. DATA: Routine administrative data and electronic patient records, as well as digital images stored in a picture archiving and communications system will serve as the primary data source. The protocol was approved by the institutional review board. MAIN OUTCOMES: (1) incidence of delayed diagnoses, (2) diagnostic accuracy, as correlated to the reference standard of a synopsis of all subsequent clinical, imaging, surgical and autopsy findings, (3) patients' safety, (4) radiation exposure (e.g. effective dose), (5) subjective image quality (assessed independently radiologists and trauma surgeons on a 100-mm visual analogue scale), (6) objective image quality (e.g., contrast-to-noise ratio). ANALYSIS: Multivariate regression will be employed to adjust and correct the findings for time and cohort effects. An exploratory interim analysis halfway after introduction of low-dose MDCT will be conducted to assess whether this protocol is clearly inferior or superior to the current standard. DISCUSSION: Although non-experimental, this study will generate first large-scale data on the utility of imaging-enhancing algorithms in whole-body MDCT for major blunt trauma. TRIAL REGISTRATION: Current Controlled Trials ISRCTN74557102.

Quantitative analysis of astrogliosis in drug-dependent humans.

Drug addiction is a chronic, relapsing disease caused by neurochemical and molecular changes in the brain. In this human autopsy study qualitative and quantitative changes of glial fibrillary acidic protein (GFAP)-positive astrocytes in the hippocampus of 26 lethally intoxicated drug addicts and 35 matched controls are described. The morphological characterization of these cells reflected alterations representative for astrogliosis. But, neither quantification of GFAP-positive cells nor the Western blot analysis indicated statistical significant differences between drug fatalities versus controls. However, by semi-quantitative scoring a significant shift towards higher numbers of activated astrocytes in the drug group was detected. To assess morphological changes quantitatively, graph-based representations of astrocyte morphology were obtained from single cell images captured by confocal laser scanning microscopy. Their underlying structures were used to quantify changes in astroglial fibers in an automated fashion. This morphometric analysis yielded significant differences between the investigated groups for four different measures of fiber characteristics (Euclidean distance, graph distance, number of graph elements, fiber skeleton distance), indicating that, e.g., astrocytes in drug addicts on average exhibit significant elongation of fiber structures as well as two-fold increase in GFAP-positive fibers as compared with those in controls. In conclusion, the present data show characteristic differences in morphology of hippocampal astrocytes in drug addicts versus controls and further supports the involvement of astrocytes in human pathophysiology of drug addiction. The automated quantification of astrocyte morphologies provides a novel, testable way to assess the fiber structures in a quantitative manner as opposed to standard, qualitative descriptions.

Activation of the bumetanide-sensitive Na+,K+,2Cl- cotransporter (NKCC2) is facilitated by Tamm-Horsfall protein in a chloride-sensitive manner.

Active transport of NaCl across thick ascending limb (TAL) epithelium is accomplished by Na(+),K(+),2Cl(-) cotransporter (NKCC2). The activity of NKCC2 is determined by vasopressin (AVP) or intracellular chloride concentration and includes its amino-terminal phosphorylation. Co-expressed Tamm-Horsfall protein (THP) has been proposed to interact with NKCC2. We hypothesized that THP modulates NKCC2 activity in TAL. THP-deficient mice (THP(-/-)) showed an increased abundance of intracellular NKCC2 located in subapical vesicles (+47% compared with wild type (WT) mice), whereas base-line phosphorylation of NKCC2 was significantly decreased (-49% compared with WT mice), suggesting reduced activity of the transporter in the absence of THP. Cultured TAL cells with low endogenous THP levels and low base-line phosphorylation of NKCC2 displayed sharp increases in NKCC2 phosphorylation (+38%) along with a significant change of intracellular chloride concentration upon transfection with THP. In NKCC2-expressing frog oocytes, co-injection with THP cRNA significantly enhanced the activation of NKCC2 under low chloride hypotonic stress (+112% versus +235%). Short term (30 min) stimulation of the vasopressin V2 receptor pathway by V2 receptor agonist (deamino-cis-D-Arg vasopressin) resulted in enhanced NKCC2 phosphorylation in WT mice and cultured TAL cells transfected with THP, whereas in the absence of THP, NKCC2 phosphorylation upon deamino-cis-D-Arg vasopressin was blunted in both systems. Attenuated effects of furosemide along with functional and structural adaptation of the distal convoluted tubule in THP(-/-) mice supported the notion that NaCl reabsorption was impaired in TAL lacking THP. In summary, these results are compatible with a permissive role for THP in the modulation of NKCC2-dependent TAL salt reabsorptive function.

Renal Na+-K+-Cl- cotransporter activity and vasopressin-induced trafficking are lipid raft-dependent.

Apical bumetanide-sensitive Na(+)-K(+)-2Cl(-) cotransporter (NKCC2), the kidney-specific member of a cation-chloride cotransporter superfamily, is an integral membrane protein responsible for the transepithelial reabsorption of NaCl. The role of NKCC2 is essential for renal volume regulation. Vasopressin (AVP) controls NKCC2 surface expression in cells of the thick ascending limb of the loop of Henle (TAL). We found that 40-70% of Triton X-100-insoluble NKCC2 was present in cholesterol-enriched lipid rafts (LR) in rat kidney and cultured TAL cells. The related Na(+)-Cl(-) cotransporter (NCC) from rat kidney was distributed in LR as well. NKCC2-containing LR were detected both intracellularly and in the plasma membrane. Bumetanide-sensitive transport of NKCC2 as analyzed by (86)Rb(+) influx in Xenopus laevis oocytes was markedly reduced by methyl-beta-cyclodextrin (MbetaCD)-induced cholesterol depletion. In TAL, short-term AVP application induced apical vesicular trafficking along with a shift of NKCC2 from non-raft to LR fractions. In parallel, increased colocalization of NKCC2 with the LR ganglioside GM1 and their polar translocation were assessed by confocal analysis. Apical biotinylation showed twofold increases in NKCC2 surface expression. These effects were blunted by mevalonate-lovastatin/MbetaCD-induced cholesterol deprivation. Collectively, these findings demonstrate that a pool of NKCC2 distributes in rafts. Results are consistent with a model in which LR mediate polar insertion, activity, and AVP-induced trafficking of NKCC2 in the control of transepithelial NaCl transport.

Selectively reduced expression of thick ascending limb Tamm-Horsfall protein in hypothyroid kidneys.

Hypothyroidism causes major changes in the kidney by affecting its growth, structure, function, and biosynthesis of its specific gene products. As a consequence, the nephron shows a selective hypotrophy in the medullary portion of the thick ascending limb (TAL). Contrastingly, we have shown earlier that the abundance of the major ion transporter of the TAL, the furosemide-sensitive Na-K-2Cl cotransporter (NKCC2) was increased when related to kidney function in the hypothyroid organism. Synthesis of Tamm-Horsfall protein (THP), the most abundant urinary protein produced in the TAL, has been suggested to interfere with TAL function. We therefore studied the localization and synthesis rate of THP in the hypothyroid kidney. We used rats chronically treated with methimazole. Kidneys were processed for western blotting and histochemical evaluation. Morphologically the hypothyroid TAL displayed a selectively reduced epithelial cell height of its medullary portion. This was paralleled by decreased THP immunostaining and mRNA abundance. Western blotting indicated a 40% reduction in renal THP content ( P<0.005), and daily urinary THP excretion was 68% lower than in controls ( P<0.05). T3 substitution restored these parameters. To further confirm that changes were specific for THP and not merely the consequence of reduced kidney growth, the abundance of barttin, another distal tubular protein related to chloride transport, was tested as well. Barttin was increased by 43% in the hypothyroid rats. Together with our previous results showing increased NKCC2 expression in hypothyroidism, these results demonstrate a selective decrease in medullary THP synthesis. We suggest a potential involvement of THP in the renal functional changes associated with hypothyroidism.

Renal expression of sodium transporters and aquaporin-2 in hypothyroid rats.

Hypothyroidism is associated with significant abnormalities in the renal handling of salt and water. To address the involvement of tubular transport proteins in these abnormalities, rats were rendered pharmacologically hypothyroid and the abundance of major tubular transport proteins was assessed by immunoblot and immunohistochemistry. Hypothyroidism resulted in a marked reduction in kidney size and creatinine clearance along with decreased or unchanged total kidney abundance of the transport proteins. Whereas the proximal tubular type 3 Na/H exchanger (NHE3) and type 2 Na-phosphate cotransporter (NaPi2) stood out by their disproportionately reduced abundance, the bumetanide-sensitive type 2 Na-K-2Cl cotransporter (NKCC2) and aquaporin-2 (AQP2) were unaltered in their total kidney abundance despite a markedly lower kidney mass. The latter proteins in fact showed enhanced immunostaining. Decreased NHE3 and NaPi2 expression was most likely due to a combination of triiodo-l-thyronine (T(3)) deficiency along with a reduced glomerular filtration rate. The increased abundance of NKCC2 and AQP2 may have been caused by an increased action of vasopressin since urinary excretion of this hormone was elevated. On the other hand, the thiazide-sensitive Na-Cl cotransporter; the alpha-, beta-, and gamma-subunits of the amiloride-sensitive epithelial Na channel; and the alpha(1)-subunit of Na-K-ATPase showed a moderate decrease in total kidney abundance that was largely proportional to the smaller kidney mass. Although the observed expression of transporters was associated with a balanced renal sodium handling, altered transporter abundance may become functionally relevant if the hypothyroid kidney is challenged by an additional destabilization of the milieu interieur that has previously been shown to result in an inadequate natriuresis and clinical symptoms.