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Background: While [18F]-fluordeoxyglucose ([18F]FDG) uptake is associated with arterial inflammation, [18F]-sodium fluoride ([18F]NaF) is a marker for arterial micro-calcification. We aimed to investigate the prospective correlation between both PET markers over time and whether they are prospectively ([18F]FDG) and retrospectively ([18F]NaF) related to progression of systemic arterial disease in a longitudinal study in patients with type 2 diabetes mellitus (T2DM). Methods: Baseline [18F]FDG PET/Low Dose (LD) Computed Tomography (CT) scans of ten patients with early T2DM without cardiovascular history (70% men, median age 63 years) were compared with five-year follow-up [18F]NaF/LDCT scans. Systemic activity was expressed as mean target-to-background ratio (meanTBR) by dividing the maximal standardized uptake value (SUVmax) of ten arteries by SUVmean of the caval vein. CT-assessed macro-calcifications were scored visually and expressed as calcified plaque (CP) score. Arterial stiffness was assessed with carotid-femoral pulse wave velocity (PWV). Five-year changes were expressed absolutely with delta (Δ) and relatively with %change. Results: Baseline meanTBR[18F]FDG was strongly correlated with five-year follow-up meanTBR[18F]NaF (r = 0.709, P =.022). meanTBR[18F]NaF correlated positively with ΔCPscore, CPscore at baseline, and follow-up (r = 0.845, P =.002 and r = 0.855, P =.002, respectively), but not with %change in CPscore and PWV. Conclusion: This proof-of-concept study demonstrated that systemic arterial inflammation is an important pathogenetic factor in systemic arterial micro-calcification development. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effect of a two-third re- duction of the scanned length (i.e. 10 cm) on diagnosis of both pulmonary embolism (PE) and alternative diseases. Methods: 247 consecutive patients suspected of acute PE had a CT pulmonary angiography (CTPA) of the thorax (standard length, L). Based on this acquisition, a second set of images was created to obtain a scan length of 10cm caudally to the aortic arch (I). Images were anonymized, randomized and interpreted by two independent readers. The quality of enhancement, the presence of PE and the possible alternative and/or complementary diagnoses were recorded. A McNemar exact test investigated differ- ences in discrepancies between readers and between scan lengths. Results: 57 (23%) patients had an acute PE. Among I sets, PE was missed by both readers in one (1.8%) patient, because the unique clot was localized in a subsegmental artery out of the 10-cm range. There were discrepancies between L and I sets in 9 (3.6%) and 11(4.5%) patients, by Readers 1 and 2 (p = 0.820), respectively. Discrepancies between the readers of L sets and those between both sets were not different regardless of the reader (p> 0.99). There were discrepancies between both sets for alternative and/or complementary diagnoses in 43 (17.2%) patients. Conclusion: Although its performance in diagnosing PE is maintained, CTPA should not be restricted to a range of 10cm centred over the pulmonary hilum, because alternative and/or complementary diagnoses could be missed. Advances in knowledge: (1) A 10-cm CTPA acquisition reduces the radiation dose by two-thirds as compared with a standard one, but does not impair the accuracy for the diagnosis of PE. (2) Significant alternative diagnoses are missed in 17.2% of patients when reducing the acquisition height to 10 cm. [ABSTRACT FROM AUTHOR]

Objective: To compare diagnostic performances of two reduced z-axis coverages to full coverage of the abdomen and pelvis for the diagnosis of acute appendicitis and alternative diseases at unenhanced CT. Methods: This study included 152 adults suspected of appendicitis who were enrolled in two ethical committeeapproved previous prospective trials. Based on scans covering the entire abdomen and pelvis (set L), two additional sets of images were generated, each with reduced z-axis coverages: (1) from the top of the iliac crests to the pubis (set S) and (2) from the diaphragmatic crus to the pubis (set M). Two readers independently coded the visualisation of the appendix, measured its diameter and proposed a diagnosis (appendicitis or alternative). Final diagnosis was based on surgical findings or clinical follow-up. Fisher exact and McNemar tests and logistic regression were used. Results: 46 patients had a definite diagnosis of appendicitis and 53 of alternative diseases. The frequency of appendix visualisation was lower for set S than set L for both readers (89% and 84% vs 95% and 91% by Readers A and B, respectively; p=0.021 and 0.022). The probability of giving a correct diagnosis was lower for set S (68%) than set L (78%; odds ratio, 0.611; p=0.008) for both readers, without significant difference between sets Land M (77%, p=0.771); z-axis coverage being reduced by 25% for set M. Conclusion: Coverage from diaphragmatic crus to pubis, but not focused on pelvis only, can be recommended in adults suspected of appendicitis. Advances in knowledge: In suspected appendicitis, CT-coverage can be reduced from diaphragmatic crus to pubis. [ABSTRACT FROM AUTHOR]

We determined by trichometry the rate of hair growth in ten hirsute patients receiving a combination of cyproterone acetate (CA) 50 mg/daily and ‘Diane’® (CA 2 mg + etbinyl oestradiol 0.05 mg). In two patients there was a prompt and persistent reduction in hair growth; in three the response was less marked, and in the remaining five patients the rate of hair growth fluctuated during therapy. However, there was an overall reduction in hair growth in all but one patient during the 12 months of treatment and all patients noticed that their hair became softer, thinner and lighter in colour. [ABSTRACT FROM AUTHOR]

Background and Aims: Sodium [ 18 F]fluoride (Na [ 18 F]F) positron emission tomography imaging allows detailed visualization of early arterial micro-calcifications. This study aims to investigate atherosclerosis manifested by micro-calcification, macro-calcification, and aortic stiffness in patients with type 2 diabetes mellitus (T2DM) with and without albuminuria and severely decreased kidney function., Methods: A cohort was stratified in four groups (N = 10 per group), based on KDIGO categories (G1-5 A1-3). G1-2A1 non-diabetic controls (median [IQR] estimated glomerular filtration rate (eGFR) in mL/min/1.73 m 2 91 [81-104]), G1-2A1 with T2DM (eGFR 87 [84-93], and albumin-creatinin-ratio (ACR) in mg/mmol 0.35 [0.25-0.75]), G1-2A3 with T2DM (eGFR 85 [60-103], and ACR 74 [62-122], and G4A3 with T2DM (eGFR 19 [13-27] and ACR 131 [59-304])., Results: Na [ 18 F]F femoral artery grading score differed significantly in the groups with the highest Na [ 18 F]F activity in A3 groups with T2DM (G1-2A3 with T2DM 228 [100-446] and G4A3 with T2DM 198 [113-578]) from the lowest groups of the G1-2A1 with T2DM (33 [0-93]) and in G1-2A1 non-diabetic controls (75 [0-200], p = 0.001). Aortic Na [ 18 F]F activity and femoral artery computed tomography (CT)-assessed macro-calcification was increased in G4A3 with T2DM compared with G1-2A1 with T2DM (47.5 [33.8-73.8] vs. 17.5 [8.8-27.5] (p = 0.006) and 291 [170-511] vs. 12.2 [1.41-44.3] mg (p = 0.032), respectively). Carotid-femoral pulse wave velocity (PWV)-assessed aortic stiffness was significantly higher in both A3 groups with T2DM compared with G1-2A1 with T2DM (11.15 and 12.35 vs. 8.86 m/s, respectively (p = 0.009))., Conclusions: This study indicates that the presence of severely increased albuminuria in patients with T2DM is cross-sectionally associated with subclinical arterial disease in terms of micro-calcification and aortic stiffness. Additional decrease in kidney function was associated with advanced macro-calcifications., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)

Purpose of Review: To highlight the importance of biological age in the context of prehabilitation and to present relevant research regarding prehabilitation prior to solid organ transplantation., Recent Findings: Studies on the effect of prehabilitation have been performed in kidney-, lung-, liver-, and heart transplant patient populations. Prior to kidney transplantation, exercise interventions have been shown to improve cardiopulmonary- and physical fitness and result in a decreased length of hospital stay postoperatively. Among lung transplant candidates, various methods of prehabilitation have been studied including home-based, outpatient and in-patient programs, consisting of physical training, psychological support, education, and nutritional interventions. Overall, prehabilitation seems to improve or maintain quality of life and exercise capacity in this patient population. Patients undergoing liver transplantation seem to benefit from prehabilitation as well. Not only does it seem safe and feasible, but significant improvements in aerobic and functional capacity have also been found. Regarding heart transplant candidates, both inpatient and outpatient, supervised prehabilitation programs show promising results with improvements in exercise capacities and quality of life., Summary: Prehabilitation is an effective and safe intervention for improving functional outcomes of solid organ transplant patients. Future studies should evaluate whether prehabilitation translates into improved pre- and post-transplant clinical outcomes., Competing Interests: Conflict of InterestThe authors declare no competing interests., (© The Author(s) 2023.)

Current COVID-19 vaccines are based on prototypic spike sequences from ancestral 2019 SARS-CoV-2 strains. However, the ongoing pandemic is fueled by variants of concern (VOC) escaping vaccine-mediated protection. Here we demonstrate how immunization in hamsters using prototypic spike expressed from yellow fever 17D (YF17D) as vector blocks ancestral virus (B lineage) and VOC Alpha (B.1.1.7) yet fails to fully protect from Beta (B.1.351). However, the same YF17D vectored vaccine candidate with an evolved antigen induced considerably improved neutralizing antibody responses against VOCs Beta, Gamma (P.1) and the recently predominant Omicron (B.1.1.529), while maintaining immunogenicity against ancestral virus and VOC Delta (B.1.617.2). Thus vaccinated animals resisted challenge by all VOCs, including vigorous high titre exposure to the most difficult to cover Beta, Delta and Omicron variants, eliminating detectable virus and markedly improving lung pathology. Finally, vaccinated hamsters did not transmit Delta variant to non-vaccinated cage mates. Overall, our data illustrate how current first-generation COVID-19 vaccines may need to be updated to maintain efficacy against emerging VOCs and their spread at community level., (© 2022. The Author(s).)

Preoperative molecular imaging is paramount to direct surgery in primary hyperparathyroidism (pHPT). We investigated the diagnostic performance of 18 F-fluorocholine ( 18 F-FCH) PET/CT compared with 11 C-methionine ( 11 C-MET) PET/CT for localization of hyperfunctioning parathyroid tissue in patients with pHPT and negative or inconclusive 99m Tc-sestaMIBI ( 99m Tc-MIBI) SPECT findings. Methods: Fifty-eight patients with biochemical evidence of pHPT and negative or inconclusive 99m Tc-MIBI SPECT findings were referred for presurgical detection and localization of hyperfunctioning parathyroid tissue by 11 C-MET and 18 F-FCH PET/CT. The PET/CT results were classified into 3 categories (positive, inconclusive, or negative) based on the nodular aspect of tracer uptake and the visualization of corresponding nodules on CT. The PET/CT results were correlated with the surgical and histopathologic findings, which were used as the gold standard. Results: Fifty-three patients were included for analysis. 18 F-FCH PET/CT was positive in 39 patients (74%), inconclusive in 5 (9%), and negative in 9 (17%), compared with 25 (47%), 12 (23%), and 16 (30%), respectively, for 11 C-MET PET/CT. 18 F-FCH localized 11 additional foci (6 positive and 5 inconclusive), compared with 11 C-MET. Twenty-six patients (sex ratio, 10/16 M/F) underwent surgery, with resection of 31 lesions (22 adenomas, 6 hyperplastic glands, and 3 carcinomas) and 1 normal gland. At follow-up, 21 patients (81%) were considered cured after surgery, whereas 3 patients (12%) had persistence of hypercalcemia. With inconclusive cases being considered negative, 18 F-FCH PET/CT correctly localized 26 lesions in 24 of 26 patients (92%), compared with 16 lesions in 15 of 26 patients (58%) localized by 11 C-MET PET/CT. Per-patient-based sensitivity and positive predictive value were 96% and 96%, respectively, for 18 F-FCH and 60% and 94%, respectively, for 11 C-MET ( P < 0.0001). Per-lesion-based sensitivity and positive predictive value were 84% and 90%, respectively, for 18 F-FCH and 52% and 94%, respectively, for 11 C-MET ( P < 0.0001). Conclusion: In the presence of biochemical evidence of pHPT with negative or inconclusive 99m Tc-MIBI SPECT findings, 18 F-FCH PET/CT performs better than 11 C-MET PET/CT for the detection of pathologic parathyroid tissue, allowing localization of parathyroid adenoma or hyperplasia in 96% of patients., (© 2022 by the Society of Nuclear Medicine and Molecular Imaging.)

Repurposing drugs is a promising strategy to identify therapeutic interventions against novel and re-emerging viruses. Posaconazole is an antifungal drug used to treat invasive aspergillosis and candidiasis. Recently, posaconazole and its structural analog, itraconazole were shown to inhibit replication of multiple viruses by modifying intracellular cholesterol homeostasis. Here, we show that posaconazole inhibits replication of the alphaviruses Semliki Forest virus (SFV), Sindbis virus and chikungunya virus with EC 50 values ranging from 1.4 μM to 9.5 μM. Posaconazole treatment led to a significant reduction of virus entry in an assay using a temperature-sensitive SFV mutant, but time-of-addition and RNA transfection assays indicated that posaconazole also inhibits post-entry stages of the viral replication cycle. Virus replication in the presence of posaconazole was partially rescued by the addition of exogenous cholesterol. A transferrin uptake assay revealed that posaconazole considerably slowed down cellular endocytosis. A single point mutation in the SFV E2 glycoprotein, H255R, provided partial resistance to posaconazole as well as to methyl-β-cyclodextrin, corroborating the effect of posaconazole on cholesterol and viral entry. Our results indicate that posaconazole inhibits multiple steps of the alphavirus replication cycle and broaden the spectrum of viruses that can be targeted in vitro by posaconazole, which could be further explored as a therapeutic agent against emerging viruses., (Copyright © 2021 The Authors. Published by Elsevier B.V. All rights reserved.)

The expanding pandemic of coronavirus disease 2019 (COVID-19) requires the development of safe, efficacious and fast-acting vaccines. Several vaccine platforms are being leveraged for a rapid emergency response 1 . Here we describe the development of a candidate vaccine (YF-S0) for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that uses live-attenuated yellow fever 17D (YF17D) vaccine as a vector to express a noncleavable prefusion form of the SARS-CoV-2 spike antigen. We assess vaccine safety, immunogenicity and efficacy in several animal models. YF-S0 has an excellent safety profile and induces high levels of SARS-CoV-2 neutralizing antibodies in hamsters (Mesocricetus auratus), mice (Mus musculus) and cynomolgus macaques (Macaca fascicularis), and-concomitantly-protective immunity against yellow fever virus. Humoral immunity is complemented by a cellular immune response with favourable T helper 1 polarization, as profiled in mice. In a hamster model 2 and in macaques, YF-S0 prevents infection with SARS-CoV-2. Moreover, a single dose conferred protection from lung disease in most of the vaccinated hamsters within as little as 10 days. Taken together, the quality of the immune responses triggered and the rapid kinetics by which protective immunity can be attained after a single dose warrant further development of this potent SARS-CoV-2 vaccine candidate.

Emergence of SARS-CoV-2 causing COVID-19 has resulted in hundreds of thousands of deaths. In search for key targets of effective therapeutics, robust animal models mimicking COVID-19 in humans are urgently needed. Here, we show that Syrian hamsters, in contrast to mice, are highly permissive to SARS-CoV-2 and develop bronchopneumonia and strong inflammatory responses in the lungs with neutrophil infiltration and edema, further confirmed as consolidations visualized by micro-CT alike in clinical practice. Moreover, we identify an exuberant innate immune response as key player in pathogenesis, in which STAT2 signaling plays a dual role, driving severe lung injury on the one hand, yet restricting systemic virus dissemination on the other. Our results reveal the importance of STAT2-dependent interferon responses in the pathogenesis and virus control during SARS-CoV-2 infection and may help rationalizing new strategies for the treatment of COVID-19 patients.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) rapidly spread around the globe after its emergence in Wuhan in December 2019. With no specific therapeutic and prophylactic options available, the virus has infected millions of people of which more than half a million succumbed to the viral disease, COVID-19. The urgent need for an effective treatment together with a lack of small animal infection models has led to clinical trials using repurposed drugs without preclinical evidence of their in vivo efficacy. We established an infection model in Syrian hamsters to evaluate the efficacy of small molecules on both infection and transmission. Treatment of SARS-CoV-2-infected hamsters with a low dose of favipiravir or hydroxychloroquine with(out) azithromycin resulted in, respectively, a mild or no reduction in virus levels. However, high doses of favipiravir significantly reduced infectious virus titers in the lungs and markedly improved lung histopathology. Moreover, a high dose of favipiravir decreased virus transmission by direct contact, whereas hydroxychloroquine failed as prophylaxis. Pharmacokinetic modeling of hydroxychloroquine suggested that the total lung exposure to the drug did not cause the failure. Our data on hydroxychloroquine (together with previous reports in macaques and ferrets) thus provide no scientific basis for the use of this drug in COVID-19 patients. In contrast, the results with favipiravir demonstrate that an antiviral drug at nontoxic doses exhibits a marked protective effect against SARS-CoV-2 in a small animal model. Clinical studies are required to assess whether a similar antiviral effect is achievable in humans without toxic effects., Competing Interests: The authors declare no competing interest., (Copyright © 2020 the Author(s). Published by PNAS.)

Objective: The purpose of this study is to investigate the magnitude of differences between attenuation values measured on virtual unenhanced images and true unenhanced images obtained using third-generation dual-source dual-energy CT (DECT)., Subjects and Methods: A total of 83 patients requiring thoracoabdominal CT for cancer workup were included in this prospective study. CT examinations included true unenhanced acquisitions (tube potential, 120 kVp) and arterial and portal phase dual-energy CT (DECT) acquisitions (tube potential, 100 kVp and Sn 150 kVp [where Sn denotes the interposition of a tin filter in the high-energy beam]; tube current-exposure time product, 190 and 95 mAs). Virtual unenhanced images were created using two commercially available DECT postprocessing algorithms, one of which was designed to create liver images (hereafter referred to as VNC1 images) and the other of which was designed to create images of organs containing minor amounts of fat (hereafter referred to as VNC2 images). Attenuation values on the liver, spleen, paraspinal muscles, retroperitoneal fat, renal cortex and medulla, and gallbladder and bladder lumens were measured., Results: The attenuation values of all tissues were significantly different between virtual unenhanced and true unenhanced images (p = < 0.001-0.042), except for the liver and spleen in the portal phase and muscles in both phases. When statistically significant, correlations between these differences and body mass index (weight in kilograms divided by the square of height in meters) depended on the tissue imaged and algorithm used. The percentage of cases in which these differences were 10 HU or greater was 1% for the liver and approximately 5% for the spleen and muscles, regardless of the algorithm and phase, but on VNC1 images it reached approximately 30% for the kidney, 70% for the gallbladder and bladder, and depending on the phase, 40-70% for fat. On VNC2 images, the percentage of cases in which these differences were 20 HU or greater was approximately 90% for fat., Conclusion: Abdominal virtual unenhanced images obtained with third-generation dual-source DECT still should not replace true unenhanced images because of substantial differences in attenuation measurements for fluid, fat, and renal tissues.

Objective: The objective of our study was to evaluate in vivo urinary calculus characterization with third-generation dual-source dual-energy CT (DECT) at reduced versus standard radiation dose., Subjects and Methods: One hundred fifty-three patients requiring unenhanced CT for suspected or known urolithiasis were prospectively included in our study. They underwent two acquisitions at reduced-dose CT (90 kV and 50 mAs ref ; Sn150 kV and 31 mAs ref , where Sn denotes the interposition of a tin filter in the high-energy beam) and standard-dose CT (90 kV and 50 mAs ref ; Sn150 kV and 94 mAs ref ). One radiologist interpreted the reduced-dose examinations before the standard-dose examinations during the same session. Among 103 patients (23 women, 80 men; mean age ± SD, 50 ± 15 years; age range, 18-82 years) with urolithiasis, dedicated DECT software measured the maximal diameter and CT numbers, calculated the DECT number ratio, and labeled with a color code each calculus visualized by the radiologist as uric acid (UA) or non-UA. Volume CT dose index (CTDI vol ) and dose-length product (DLP) were recorded., Results: The radiologist visualized 279 calculi on standard-dose CT and 262 on reduced-dose CT; 17 calculi were missed on reduced-dose CT, all of which were ≤ 3 mm. Among the 262 calculi visualized at both doses, the CT number ratio was obtained with the software for 227 calculi and was not different between the doses (p = 0.093). Among these 262 calculi, 197 were labeled at both doses; 194 of the 197 labeled calculi were labeled with the same color code. Among the 65 remaining calculi, 48 and 61 (all ≤ 5 mm) were not labeled at standard-dose and reduced-dose CT (p = 0.005), respectively. At reduced-dose CT, the mean CTDI vol was 2.67 mGy and the mean DLP was 102.2 mGy × cm., Conclusion: With third-generation dual-source DECT, a larger proportion of calculi ≤ 5 mm are not characterized as UA or non-UA at a reduced dose.

Background and Aims: Both a high dietary sodium and high phosphate load are associated with an increased cardiovascular risk in patients with chronic kidney disease (CKD), and possibly also in non-CKD populations. Sodium and phosphate are abundantly present in processed food. We hypothesized that (modulation of) dietary sodium is accompanied by changes in phosphate load across populations with normal and impaired renal function., Methods and Results: We first investigated the association between sodium and phosphate load in 24-h urine samples from healthy controls (n = 252), patients with type 2 diabetes mellitus (DM, n = 255) and renal transplant recipients (RTR, n = 705). Secondly, we assessed the effect of sodium restriction on phosphate excretion in a nondiabetic CKD cohort (ND-CKD: n = 43) and a diabetic CKD cohort (D-CKD: n = 39). Sodium excretion correlated with phosphate excretion in healthy controls (R = 0.386, P < 0.001), DM (R = 0.490, P < 0.001), and RTR (R = 0.519, P < 0.001). This correlation was also present during regular sodium intake in the intervention studies (ND-CKD: R = 0.491, P < 0.001; D-CKD: R = 0.729, P < 0.001). In multivariable regression analysis, sodium excretion remained significantly correlated with phosphate excretion after adjustment for age, gender, BMI, and eGFR in all observational cohorts. In ND-CKD and D-CKD moderate sodium restriction reduced phosphate excretion (31 ± 10 to 28 ± 10 mmol/d; P = 0.04 and 26 ± 11 to 23 ± 9 mmol/d; P = 0.02 respectively)., Conclusions: Dietary exposure to sodium and phosphate are correlated across the spectrum of renal function impairment. The concomitant reduction in phosphate intake accompanying sodium restriction underlines the off-target effects on other nutritional components, which may contribute to the beneficial cardiovascular effects of sodium restriction. (f) Registration numbers: Dutch Trial Register NTR675, NTR2366., (Copyright © 2016. Published by Elsevier B.V.)

Purpose: Focal areas of FDG uptake may occur at the bronchial stump following curative lobectomy for non-small-cell lung carcinoma (NSCLC), even in the absence of suspicious CT changes. The purpose of our study was to investigate the significance of such PET/CT findings., Methods: FDG-PET/CT scans performed in 54 patients after lobectomy for NSCLC were reviewed. The presence of focal areas of FDG uptake at the bronchial stump, associated CT abnormalities, SUVmax, and normalized SUV (SUVnorm = SUVmax/mean liver SUV) were recorded. Final diagnosis was based on biopsy or imaging follow-up., Results: Focal areas of FDG uptake at the bronchial stump were detected in 30 patients (56 %). Mean SUVmax was 4.0 ± 1.9 (range; 2.2-12.1) and mean SUVnorm was 1.8 ± 0.8 (range; 0.9-4.5). Biopsy showed recurrence in two patients. In these patients, SUVnorm was respectively 4.4 and 4.5 (with SUVmax of 8.8 and 12.1), whereas SUVnorm was lower than 4.0 in those without recurrence, with mean SUVnorm of 1.6 ± 0.5 (range; 0.9-3.4) and mean SUVmax of 3.6 ± 0.9 (range; 2.2-5.8). The CT component of the PET/CT revealed ill-defined peribronchial soft tissue opacity only in both patients with recurrence., Conclusion: FDG uptake at the bronchial stump is a frequent finding after pulmonary lobectomy. Moderate levels of FDG uptake (i.e., SUVnorm < 4.0) without corresponding abnormal CT findings might be a dual criterion for diagnosing benign post-surgical changes.

Objective: The purpose of this study was to investigate the nature of FDG-avid and non-FDG-avid lesions detected at colonoscopy in patients presenting with incidental focal colonic FDG uptake at PET/CT., Materials and Methods: Among 9073 patients who underwent PET/CT over a 4-year period, 82 patients without a history of colonic disease had focal colonic FDG uptake and underwent colonoscopy. In consensus, a radiologist and a nuclear physician read images from these PET/CT examinations. They recorded the location of focal FDG uptake in the colon and associated CT abnormalities and measured maximum standardized uptake value (SUVmax) and metabolic volume (MV). Readings were performed twice--first without and second with knowledge of lesion location at colonoscopy. The final diagnosis was based on colonoscopic findings and histopathologic results categorized into benign, premalignant, or malignant., Results: One hundred seven foci of colonic FDG uptake at PET/CT and 150 lesions at colonoscopy were detected. Among 107 foci of FDG uptake, 65 (61%) corresponded to a lesion at colonoscopy (true-positive findings), and 42 (39%) did not (false-positive findings). Among 150 lesions found at colonoscopy, 85 (57%) were not FDG avid (false-negative findings). The MV of true-positive findings was lower than that of false-positive findings (4.0 ± 0.4 cm(3) vs 6.2 ± 0.7 cm(3); p = 0.006), but SUVmax did not differ (7.4 ± 0.5 vs 7.7 ± 0.5; p = 0.649). Considering the histopathologic categories of the lesions and the false-positive findings, there was no difference in SUVmax (p = 0.103), but MV was lower in premalignant lesions than in false-positive findings (p = 0.005)., Conclusion: Focal colonic FDG uptake may indicate the presence of a benign, pre-malignant, or malignant lesion. Subsequent colonoscopy should not be restricted to the colonic site of FDG uptake.

Background. Encapsulating peritoneal sclerosis (EPS) is a rare but serious complication of peritoneal dialysis (PD). Besides the endothelial-to-mesenchymal transition (EMT), recently peritoneal adipocytes emerged as a potential source of fibrosis. We performed immunohistochemistry to approach EMT and to localize peritoneal adipocytes in peritoneal biopsies from PD-related EPS patients. Material and Methods. We investigated tissue expression of podoplanin, cytokeratin AE1/AE3 (mesothelium), calretinin (adipocytes), alpha-smooth muscle actin [α-SMA] (mesenchymal cells), interstitial mononuclear cell inflammation, and neoangiogenesis (CD3, CD4, CD8, CD20, CD68, and CD31 immunostainings, resp.). Results. Three patients (1 man/2 women; 17, 64, and 39 years old, resp.) developed EPS after 21, 90, and 164 months of PD therapy. In patients with EPS, we observed (1) loss of AE1/AE3 cytokeratin+ mesothelial cells without any evidence of migration into the interstitium, (2) disappearance of adipose tissue, (3) diffuse infiltration of calretinin+ cells in the areas of submesothelial fibrosis with a huge number of α-SMA and calretinin+ fusiform cells, and (4) increased vascular density. Conclusion. We report that the involvement of EMT in peritoneal fibrosis is difficult to demonstrate and that the calretinin+ adipocytes might be an underestimated component and a new source of myofibroblasts in peritoneal remodeling during PD-related EPS.

Objective: The purpose of this study was to describe the unenhanced CT appearance of the appendix in adults with cystic fibrosis., Subjects and Methods: Among adults with cystic fibrosis undergoing follow-up at our hospital, 71 patients (35 women, 36 men; mean age, 33 years; range, 18-59 years) without a history of appendectomy or current abdominal pain were prospectively included in this study and underwent unenhanced abdominopelvic MDCT. Two readers coded visualization of the appendix, measured the diameter of the appendix, and described the attenuation of its contents in relation to the intestinal wall. They also coded the presence of colonic wall redundancy, pancreatic fatty replacement, and cirrhosis. Lung transplant status and CFTR gene mutations were recorded. Analysis of variance, linear regression analysis, Student t test, and Pearson test were used., Results: The appendix was detected in all patients. The mean diameter was recorded as 10.6 ± 3.5 mm. The mean diameter was larger when the appendix contained hyperattenuating material (p = 0.001). There was no association between diameter and the other coded CT findings (p = 0.076-0.466), transplant status (p = 0.788), or CFTR mutation (p = 0.078). In 75% of the patients, the appendix contained hyperattenuating material with a higher proportion in homozygous ΔF508 mutation (p = 0.029) without any significant effect of the other CT features (p = 0.056-0.392), or transplant status (p = 1.000)., Conclusion: The appendix is larger in adults with cystic fibrosis than in those without it and appears hyperattenuating at unenhanced CT in 75% of patients, more commonly in those with ΔF508 homozygous mutation.

We present the case of a man with a bicuspid aortic valve who presented with persistent fever. Blood cultures yielded Neisseria gonorrhoeae, and the diagnosis of infected mycotic aneurysm was confirmed by detection of the bacterial genome in the aortic wall. The patient was cured with surgery and intravenous ceftriaxone.

Mycobacterium fortuitum is a ubiquitous, rapidly growing nontuberculous mycobacterium (NTM). It is the most commonly reported NTM in peritoneal dialysis (PD) associated peritonitis. We report a case of a 52-year-old man on PD, who developed refractory polymicrobial peritonitis necessitating PD catheter removal and shift to hemodialysis. Thereafter, M. fortuitum was identified in the PD catheter culture and in successive cultures of initial peritoneal effluent and patient was treated with amikacin and ciprofloxacin for six months with a good and sustained clinical response. Months after completion of the course of antibiotics, the patient successfully returned to PD. To our knowledge, this is the first reported case of M. fortuitum peritonitis in the field of polymicrobial PD peritonitis. It demonstrates the diagnostic yield of pursuing further investigations in cases of refractory PD peritonitis. In a systematic review of the literature, only 20 reports of M. fortuitum PD peritonitis were identified. Similar to our case, a delay in microbiological diagnosis was frequently noted and the Tenckhoff catheter was commonly removed. However, the type and duration of antibiotic therapy varied widely making the optimal treatment unclear.

Objective: The objective of this study was to prospectively investigate the influence of oral, IV, and oral and IV contrast media on the information provided by MDCT at standard and simulated low radiation doses in adults suspected of having acute appendicitis., Subjects and Methods: One hundred thirty-one consecutive patients (80 women, 51 men; age range, 18-87 years; mean age, 37 years) suspected of having appendicitis were randomly assigned to either ingest or not ingest iodinated contrast material. Thereafter, all patients underwent IV unenhanced and enhanced abdominopelvic MDCT with a 4 x 2.5 mm collimation at 120 kVp and 100 mAs(eff). Dose reduction corresponding to 30 mAs(eff) was simulated. Two radiologists independently read scans during separate sessions, assessed appendix visualization, and proposed a diagnosis (i.e., appendicitis or an alternative diagnosis). The final diagnosis was based on either surgical findings or clinical follow-up. Data were analyzed by factorial analysis of multiple correspondences followed by an ascending hierarchic classification method., Results: Factorial analysis and ascending hierarchic classification revealed that, in terms of diagnostic correctness, reader influence predominated over the influence of IV and oral contrast media use and radiation dose but that correctness was also influenced by the patient's sex (p = 0.048) and was lower in cases of alternative diseases (p < 0.001). Visualization of the appendix depended predominantly on the reader rather than on the use of IV, oral, or oral and IV contrast agents or on radiation dose., Conclusion: Diagnostic correctness is much more influenced by the reader than by the use of contrast medium (oral, IV, or both) or of simulated low-radiation-dose technique.

Objective: The purposes of this study were to investigate whether readers' interpretations are reproducible and whether readers are confident in identifying a normal appendix with CT and to assess the influence of patient characteristics and IV contrast enhancement on visualization of the appendix., Subjects and Methods: One hundred two patients without a history of abdominal surgery underwent unenhanced and contrast-enhanced CT for the evaluation of cancer. Three radiologists with varying degrees of experience read scans twice in separate sessions. They were asked to identify the appendix, to score their confidence in identification, and to mark the appendix on the images. Intraabdominal fat volume was measured with a computer-assisted method. Independent experts compared the readers' markings and indicated whether the findings were reproducible., Results: Reproducibility differed significantly between reading sessions (p < 0.001) and readers (p = 0.003). On the images of 71% of the patients, there was perfect intrareader and interreader agreement with statistically significant and positive influences of patient body mass index (p = 0.005) and intraabdominal fat volume (p = 0.001). Contrast enhancement influenced intrareader reproducibility only for the reader who made less-reproducible interpretations (p = 0.033). Intrareader and interreader agreement in categorizing confidence in identification of the appendix ranged from fair to good (kappa = 0.221-0.620). Confidence was not influenced by contrast enhancement (p = 0.433-0.953), body mass index, or intraabdominal fat volume (p = 0.058-0.798)., Conclusion: Reproducibility in identifying a normal appendix is reader dependent. Perfect intrareader and interreader agreement in marking the appendix occurs approximately 70% of the time and increases with patient body mass index and intraabdominal fat volume. Contrast enhancement does not influence the rate of identification of the appendix or reader confidence but may influence the reproducibility of findings.

Purpose: To compare standard-dose and simulated low-dose multidetector computed tomography (CT) in patients suspected of having lumbar disk herniation., Materials and Methods: The institutional review board approved the research protocol with a waiver of patient informed consent. Sixty consecutive patients underwent multidetector CT with four detector rows at 1 mm collimation at 140 kVp, with tube current-time product adapted to body mass index (BMI): 200 (BMI< 22 kg/m(2)), 300 (BMI > or =22 to <30 kg/m(2)), and 400 effective mAs (BMI > or =30 kg/m(2)). Simulated doses at 65%, 50%, 35%, and 20% of the dose were used for acquisition. During two separate sessions, three independent radiologists coded each of three caudal disks as normal, bulging, or herniated and graded canal and foramen compromise. Median numbers of discrepancies between the standard and reduced doses were compared with Friedman and Wilcoxon tests. Agreements within and between readers were evaluated through kappa statistics., Results: Dose reduction had no effect on a reader's ability to identify bulging disks (P = .128) and left and right foramen compromises (P = .413 and .665, respectively). However, for normal disks (P = .002), herniated disks (P = .004), and canal compromise (P = .002), dose reduction did have a significant effect. For normal disks and canal compromise, a reduction dose effect was not detected at 65% (P = .121 and .250, respectively) but appeared at 50% (P = .004 and .008, respectively). For herniation, a dose reduction effect was detected at 35% (P = .031). Agreements within and between readers ranged from poor to excellent and tended to decrease with dose reduction., Conclusion: For patients suspected of having lumbar disk herniation, tube charge settings could be reduced to 65% of the standard dose adapted to the BMI.

Purpose: To prospectively compare the diagnostic performance of ultrasonography (US) and unenhanced multi-detector row computed tomography (CT) in patients suspected of having acute appendicitis by using surgery or clinical follow-up as the reference standard., Materials and Methods: The institutional review board approved the research protocol. Written informed consent was obtained from all patients or, for those who were adolescents, from their parents. Ninety-four patients (59 female and 35 male patients) aged 16-81 years (mean, 38 years) who were suspected of having acute appendicitis underwent both US and unenhanced multi-detector row CT of the entire abdomen. The examinations were performed within 1-2 hours of each other. US and CT images were obtained and prospectively interpreted by a different radiologist from a group of abdominal radiologists or a group of residents and general radiologists. Radiologists proposed an overall diagnosis and an alternative diagnosis. Data from US and CT were compared, and the definite diagnosis was established with surgical findings (n = 40) or results of clinical follow-up (n = 54) as the reference standard. Comparisons were made for each group of radiologists and the patient's age, body mass index (BMI), and sex. Proportion comparisons were made by using the Pearson chi2 test or the Fisher exact test. Continuous variables were compared between groups with the Mann-Whitney U test., Results: Thirty patients had definite appendicitis. The sensitivity, specificity, positive and negative predictive values, and accuracy were not significantly different between US and CT or between groups of radiologists (P values ranged from .389 to >.99), regardless of the patient's BMI (P values ranged from .073 to >.99). Misclassifications were compared with the definite alternative diagnosis and were not significantly different between US and CT or between groups of radiologists (P = .061-.592), regardless of patient age (P = .875) or sex (P = .151 and >.99 for male and female patients, respectively). The frequency of inconclusive examinations, however, was significantly higher with US than with CT, regardless of radiologist experience (P = .020 and <.001, respectively)., Conclusion: Although the diagnostic performances of US and multi-detector row CT are comparable, more inconclusive images were obtained with US.

Purpose: To prospectively compare low- and standard-dose unenhanced multi-detector row computed tomography (CT) in patients suspected of having acute appendicitis., Materials and Methods: Ninety-five consecutive patients underwent two unenhanced multi-detector row CT examinations with 4 x 2.5-mm collimation, 120 kVp, and 30 and 100 effective mAs. Two radiologists independently read the images obtained at each dose during two sessions. Readers recorded visualization of the appendix and presence of gas in its lumen, appendicolith, periappendiceal fat stranding, cecal wall thickening, and abscess or phlegmon to measure the diameter of the appendix and to propose diagnosis (appendicitis or alternative). Data were compared according to dose and reader, with definite diagnosis established on basis of surgical findings (n = 37) or clinical follow-up. chi(2) tests and logistic regression were used. Measurement agreements were assessed with Cohen kappa statistics., Results: Twenty-nine patients had a definite diagnosis of appendicitis. No difference was observed between the frequency of visualization of the appendix (P =.874) neither in its mean diameter (P =.101-.696, according to readers and sessions) nor in the readers' overall diagnosis (P =.788) at each dose. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of each sign were not different between doses. Fat stranding, appendicolith, and diameter were the most predictive signs, regardless of dose, yielding approximately 90% of correct diagnoses. The ability to propose a correct alternative diagnosis was not influenced by the dose., Conclusion: Low-dose unenhanced multi-detector row CT has similar diagnostic performance as standard-dose unenhanced multi-detector row CT for the diagnosis of acute appendicitis., (Copyright RSNA, 2004)

Purpose: To validate lung attenuation measurements for quantifying extravascular lung water in oleic acid-induced pulmonary edema, compare subjective assessment with attenuation measurements, and compare this permeability-type pulmonary edema with hydrostatic-type pulmonary edema., Materials and Methods: Thin-section computed tomography (CT) and pulmonary hemodynamic examinations were performed sequentially in six dogs before and after intravenous administration of 0.08 mg of oleic acid per kilogram of body weight. Extravascular lung water and pulmonary capillary pressure were measured. Results were compared with those reported in a canine model of hydrostatic edema., Results: Oleic acid induced a progressive increase in extravascular lung water without a change in capillary pressure, which indicated pure permeability-type edema. Ground-glass opacification was detected as soon as extravascular lung water increased. Lung attenuation was highly correlated to extravascular lung water (r = 0.76, P<.001), as in hydrostatic edema, but was characterized by an almost absent gravitational gradient., Conclusion: Thin-section CT is sensitive for early detection and quantification of oleic acid-induced pulmonary edema in a canine model. Different from early canine hydrostatic edema, which is characterized by a gravitational gradient, early oleic acid-induced pulmonary edema in a supine dog is characterized by nearly homogeneous distribution, except for ventral sparing.

Congenital anomalies of the thoracic veins are infrequent but important developmental disorders. Anomalies of the systemic thoracic veins usually are asymptomatic but may be associated with other more serious cardiovascular abnormalities and complicate their management. We present a case of a vertical vein consisting in an abnormal venous drainage from the left upper pulmonary lobe to the superior vena cava, resulting in a non cyanotic shunt.

Computed tomography, and particularly high-resolution computed tomography, allows a detailed exploration of the pulmonary parenchyma. We discuss here work on the use of this technique in the diagnosis and quantification of pulmonary emphysema. We stress first the subjective quantification then the objective approach based on specific software. We summarize our work which has demonstrated. 1) that the relative surface with density below -950 Hounsfield units and measured on millimetric tomographic slices obtained at the end of maximal inspiration is a valuable measurement of the extent of the macroscopic emphysema and reflects the microscopic emphysema; 2) that subjective quantification overestimates minimally extensive emphysema and shows important intra- and inter-operator variability; 3) that indexes derived from computed tomographic images acquired at the end of expiration reflect more the obstructive syndrome than emphysematous destruction; 4) that age and the size of the lungs influence computed tomographic measurements while hyperinflation appears to have no effect. Finally, we present an example of recent work applying the computed tomographic technique.

Purpose: To compare subjective visual grading of pulmonary emphysema with macroscopic morphometry and computed tomographic (CT) densitometry., Materials and Methods: In 62 consecutive patients who underwent thinsection CT before surgical lung resection, emphysema was objectively quantified with computer-assisted macroscopic morphometry and CT densitometry. The percentage of lung macroscopically occupied by emphysema was compared with the percentage occupied on CT scans by pixels with attenuation values lower than a predefined threshold (CT densitometry). Three readers with varying degrees of expertise subjectively graded emphysema with visual assessment at two reading sessions. Data from objective quantification and subjective grading were analyzed with correlation coefficients, and interobserver and intraobserver agreement were calculated., Results: Subjective grading of emphysema showed less agreement with the macroscopic reference standard results (r = 0.439-0.505; P < .05) than with objective CT densitometric results (r = 0.555-0.623; P < .001). The 95% CIs for the intercepts of the linear regression lines were suggestive of systematic subjective overestimation of emphysema by all three readers. Interobserver agreement was moderate (kappa = 0.431-0.589). Intraobserver agreement was good to excellent (kappa = 0.738-0.936). The expertise of individual readers did not substantially influence results., Conclusion: Systematic overestimation and moderate interobserver agreement may compromise subjective visual grading of emphysema, which suggests that subjective visual grading should be supplemented with objective methods to achieve precise, reader-independent quantification of emphysema.

The clinical course and management of a 37-year-old woman with systemic lupus erythematosus (SLE) who developed atlanto-axial subluxation as an acute transient phenomenon are presented. The musculoskeletal manifestations of SLE and their pathogenesis are discussed in relation to this manifestation.