Growth rates and histopathological outcomes of small (6-9 mm) colorectal polyps based on CT colonography surveillance and endoscopic removal.

BACKGROUND AND AIMS: The natural history of small polyps is not well established and rests on limited evidence from barium enema studies decades ago. Patients with one or two small polyps (6-9 mm) at screening CT colonography (CTC) are offered CTC surveillance at 3 years but may elect immediate colonoscopy. This practice allows direct observation of the growth of subcentimetre polyps, with histopathological correlation in patients undergoing subsequent polypectomy. DESIGN: Of 11 165 asymptomatic patients screened by CTC over a period of 16.4 years, 1067 had one or two 6-9 mm polyps detected (with no polyps ≥10 mm). Of these, 314 (mean age, 57.4 years; M:F, 141:173; 375 total polyps) elected immediate colonoscopic polypectomy, and 382 (mean age 57.0 years; M:F, 217:165; 481 total polyps) elected CTC surveillance over a mean of 4.7 years. Volumetric polyp growth was analysed, with histopathological correlation for resected polyps. Polyp growth and regression were defined as volume change of ±20% per year, with rapid growth defined as +100% per year (annual volume doubling). Regression analysis was performed to evaluate predictors of advanced histology, defined as the presence of cancer, high-grade dysplasia (HGD) or villous components. RESULTS: Of the 314 patients who underwent immediate polypectomy, 67.8% (213/314) harboured adenomas, 2.2% (7/314) with advanced histology; no polyps contained cancer or HGD. Of 382 patients who underwent CTC surveillance, 24.9% (95/382) had polyps that grew, while 62.0% (237/382) remained stable and 13.1% (50/382) regressed in size. Of the 58.6% (224/382) CTC surveillance patients who ultimately underwent colonoscopic resection, 87.1% (195/224) harboured adenomas, 12.9% (29/224) with advanced histology. Of CTC surveillance patients with growing polyps who underwent resection, 23.2% (19/82) harboured advanced histology vs 7.0% (10/142) with stable or regressing polyps (OR: 4.0; p<0.001), with even greater risk of advanced histology in those with rapid growth (63.6%, 14/22, OR: 25.4; p<0.001). Polyp growth, but not patient age/sex or polyp morphology/location were significant predictors of advanced histology. CONCLUSION: Small 6-9 mm polyps present overall low risk to patients, with polyp growth strongly associated with higher risk lesions. Most patients (75%) with small 6-9 mm polyps will see polyp stability or regression, with advanced histology seen in only 7%. The minority of patients (25%) with small polyps that do grow have a 3-fold increased risk of advanced histology.

Abdominal CT Body Composition Thresholds Using Automated AI Tools for Predicting 10-year Adverse Outcomes.

Background CT-based body composition measures derived from fully automated artificial intelligence tools are promising for opportunistic screening. However, body composition thresholds associated with adverse clinical outcomes are lacking. Purpose To determine population and sex-specific thresholds for muscle, abdominal fat, and abdominal aortic calcium measures at abdominal CT for predicting risk of death, adverse cardiovascular events, and fragility fractures. Materials and Methods In this retrospective single-center study, fully automated algorithms for quantifying skeletal muscle (L3 level), abdominal fat (L3 level), and abdominal aortic calcium were applied to noncontrast abdominal CT scans from asymptomatic adults screened from 2004 to 2016. Longitudinal follow-up documented subsequent death, adverse cardiovascular events (myocardial infarction, cerebrovascular event, and heart failure), and fragility fractures. Receiver operating characteristic (ROC) curve analysis was performed to derive thresholds for body composition measures to achieve optimal ROC curve performance and high specificity (90%) for 10-year risks. Results A total of 9223 asymptomatic adults (mean age, 57 years ± 7 [SD]; 5152 women and 4071 men) were evaluated (median follow-up, 9 years). Muscle attenuation and aortic calcium had the highest diagnostic performance for predicting death, with areas under the ROC curve of 0.76 for men (95% CI: 0.72, 0.79) and 0.72 for women (95% CI: 0.69, 0.76) for muscle attenuation. Sex-specific thresholds were higher in men than women (P < .001 for muscle attenuation for all outcomes). The highest-performing markers for risk of death were muscle attenuation in men (31 HU; 71% sensitivity [164 of 232 patients]; 72% specificity [1114 of 1543 patients]) and aortic calcium in women (Agatston score, 167; 70% sensitivity [152 of 218 patients]; 70% specificity [1427 of 2034 patients]). Ninety-percent specificity thresholds for muscle attenuation for both risk of death and fragility fractures were 23 HU (men) and 13 HU (women). For aortic calcium and risk of death and adverse cardiovascular events, 90% specificity Agatston score thresholds were 1475 (men) and 735 (women). Conclusion Sex-specific thresholds for automated abdominal CT-based body composition measures can be used to predict risk of death, adverse cardiovascular events, and fragility fractures. © RSNA, 2022 Online supplemental material is available for this article. See also the editorial by Ohliger in this issue.

Improved CT-based Osteoporosis Assessment with a Fully Automated Deep Learning Tool.

Purpose: To develop, test, and validate a deep learning (DL) tool that improves upon a previous feature-based CT image processing bone mineral density (BMD) algorithm and compare it against the manual reference standard. Materials and Methods: This single-center, retrospective, Health Insurance Portability and Accountability Act-compliant study included manual L1 trabecular Hounsfield unit measurements from abdominal CT scans in 11 035 patients (mean age, 58 years ± 12 [SD]; 6311 women) as the reference standard. Automated level selection and L1 trabecular region of interest (ROI) placement were then performed in this CT cohort with both a previously validated feature-based image processing tool and a new DL tool. Overall technical success rates and agreement with the manual reference standard were assessed. Results: The overall success rate of the DL tool in this heterogeneous patient cohort was significantly higher than that of the older image processing BMD algorithm (99.3% vs 89.4%, P < .001). Using this DL tool, the closest median Hounsfield unit values for single-, three-, and seven-slice vertebral ROIs were within 5% of the manual reference standard Hounsfield unit values in 35.1%, 56.9%, and 85.8% of scans; within 10% in 56.6%, 75.6%, and 92.9% of scans; and within 25% in 76.5%, 89.3%, and 97.1% of scans, respectively. Trade-offs in sensitivity and specificity for osteoporosis assessment were observed from the single-slice approach (sensitivity, 39.4%; specificity, 98.3%) to the minimum value of the multislice approach (for seven contiguous slices; sensitivity, 71.3% and specificity, 94.6%). Conclusion: The new DL BMD tool demonstrated a higher success rate than the older feature-based image processing tool, and its outputs can be targeted for higher specificity or sensitivity for osteoporosis assessment.Keywords: CT, CT-Quantitative, Abdomen/GI, Skeletal-Axial, Spine, Deep Learning, Machine Learning Supplemental material is available for this article. © RSNA, 2022.

MC3R links nutritional state to childhood growth and the timing of puberty.

The state of somatic energy stores in metazoans is communicated to the brain, which regulates key aspects of behaviour, growth, nutrient partitioning and development1. The central melanocortin system acts through melanocortin 4 receptor (MC4R) to control appetite, food intake and energy expenditure2. Here we present evidence that MC3R regulates the timing of sexual maturation, the rate of linear growth and the accrual of lean mass, which are all energy-sensitive processes. We found that humans who carry loss-of-function mutations in MC3R, including a rare homozygote individual, have a later onset of puberty. Consistent with previous findings in mice, they also had reduced linear growth, lean mass and circulating levels of IGF1. Mice lacking Mc3r had delayed sexual maturation and an insensitivity of reproductive cycle length to nutritional perturbation. The expression of Mc3r is enriched in hypothalamic neurons that control reproduction and growth, and expression increases during postnatal development in a manner that is consistent with a role in the regulation of sexual maturation. These findings suggest a bifurcating model of nutrient sensing by the central melanocortin pathway with signalling through MC4R controlling the acquisition and retention of calories, whereas signalling through MC3R primarily regulates the disposition of calories into growth, lean mass and the timing of sexual maturation.

Tristetraprolin Prevents Gastric Metaplasia in Mice by Suppressing Pathogenic Inflammation.

BACKGROUND & AIMS: Aberrant immune activation is associated with numerous inflammatory and autoimmune diseases and contributes to cancer development and progression. Within the stomach, inflammation drives a well-established sequence from gastritis to metaplasia, eventually resulting in adenocarcinoma. Unfortunately, the processes that regulate gastric inflammation and prevent carcinogenesis remain unknown. Tristetraprolin (TTP) is an RNA-binding protein that promotes the turnover of numerous proinflammatory and oncogenic messenger RNAs. Here, we assess the role of TTP in regulating gastric inflammation and spasmolytic polypeptide-expressing metaplasia (SPEM) development. METHODS: We used a TTP-overexpressing model, the TTPΔadenylate-uridylate rich element mouse, to examine whether TTP can protect the stomach from adrenalectomy (ADX)-induced gastric inflammation and SPEM. RESULTS: We found that TTPΔadenylate-uridylate rich element mice were completely protected from ADX-induced gastric inflammation and SPEM. RNA sequencing 5 days after ADX showed that TTP overexpression suppressed the expression of genes associated with the innate immune response. Importantly, TTP overexpression did not protect from high-dose-tamoxifen-induced SPEM development, suggesting that protection in the ADX model is achieved primarily by suppressing inflammation. Finally, we show that protection from gastric inflammation was only partially due to the suppression of Tnf, a well-known TTP target. CONCLUSIONS: Our results show that TTP exerts broad anti-inflammatory effects in the stomach and suggest that therapies that increase TTP expression may be effective treatments of proneoplastic gastric inflammation. Transcript profiling: GSE164349.

Hepatic hemangioendothelioma: CT, MR, and FDG-PET-CT in 67 patients-a bi-institutional comprehensive cancer center review.

OBJECTIVE: To evaluate the imaging features of hepatic epithelioid hemangioendothelioma (HEH) on multiphasic CT, MR, and FDG-PET-CT. METHODS: Bi-institutional review identified 67 adults (mean age, 47 years; 23 M/44 F) with pathologically proven HEH and pretreatment multiphasic CT (n = 67) and/or MR (n = 30) and/or FDG-PET-CT (n = 13). RESULTS: HEHs were multifocal in 88% (59/67). Mean size of the dominant mass was 4.1 cm (range, 1.4-19 cm). The tumors were located in the peripheral, subcapsular regions of the liver in 96% (64/67). Capsular retraction was present in 81% (54/67 cases) and tumors were coalescent in 61% (41/67). HEH demonstrated peripheral ring enhancement on arterial phase imaging in 33% (21/64) and target appearance on the portal venous phase in 69% (46/67). Persistent peripheral enhancement on the delayed phase was seen in 49% (31/63). On MR, multilayered target appearance was seen on the T2-weighted sequences in 67% (20/30) and on the diffusion-weighted sequences in 61% (11/18). Target appearance on hepatobiliary phase of MRI was seen in 57% (4/7). On pre-therapy FDG-PET-CT, increased FDG uptake above the background liver parenchyma was seen in 62% (8/13). CONCLUSION: HEHs typically manifest as multifocal, coalescent hepatic nodules in peripheral subcapsular location, with associated capsular retraction. Peripheral arterial ring enhancement and target appearance on portal venous phase are commonly seen on CT. Similarly, multilayered target appearance correlating with its histopathological composition is typically seen on multiple sequences of MR including T2-weighted, diffusion-weighted, and dynamic contrast-enhanced multiphasic MR. KEY POINTS: • Hepatic epithelioid hemangioendotheliomas manifest on CT and MR as multifocal, coalescent hepatic nodules in peripheral subcapsular location, with associated capsular retraction. • Enhancement pattern on contrast-enhanced CT and MR can vary but peripheral ring enhancement on arterial phase and target appearance on portal venous phase are commonly seen. • Retrospective two-center study showed that cross-sectional imaging may help in the diagnosis.

Oxyresveratrol drives caspase-independent apoptosis-like cell death in MDA-MB-231 breast cancer cells through the induction of ROS.

Earlier studies from our laboratory have demonstrated that Oxyresveratrol (OXY), a hydroxyl-substituted stilbene, exhibits potent inhibition of human melanoma cell proliferation. The present study defines a cytotoxic effect of OXY on the highly chemo-resistant, triple-negative human breast cancer cell line MDA-MB-231. OXY-mediated cell death resulted in accumulation of cells at the sub-G1 phase of the cell cycle, induced chromatin condensation, DNA fragmentation, phosphatidylserine externalization and PARP cleavage, indicative of apoptosis. Interestingly, morphology and cell viability studies with the pan-caspase inhibitor, QVD-OPH revealed that OXY-induced cell death was caspase-independent. Docking studies also showed that OXY can bind to the S1 site of caspase-3, and could also exert an inhibitory effect on this executioner caspase. The immunoblot analysis demonstrating the absence of caspase cleavage during cell death further confirmed these findings. OXY was also observed to induce the production of reactive oxygen species, which caused the depolarization of the mitochondrial membrane resulting in translocation of Apoptosis Inducing Factor (AIF) into the nucleus. Pretreatment of the cells with N-Acetyl Cysteine antioxidant prevented cell death resulting from OXY treatment. Thus, OXY initiates ROS-mediated, apoptosis-like cell death, involving mitochondrial membrane depolarization, translocation of AIF into the nucleus, and DNA fragmentation, resulting in caspase-independent cell death in MDA-MB-231 cells. The cytotoxicity manifested by OXY was also observed in 3D cell culture models and primary cells, thereby providing a basis for the utilization of OXY as a novel template for the future design of anticancer therapeutics.

Opportunistic Osteoporosis Screening at Routine Abdominal and Thoracic CT: Normative L1 Trabecular Attenuation Values in More than 20 000 Adults.

Background Abdominal and thoracic CT provide a valuable opportunity for osteoporosis screening regardless of the clinical indication for imaging. Purpose To establish reference normative ranges for first lumbar vertebra (L1) trabecular attenuation values across all adult ages to measure bone mineral density (BMD) at routine CT. Materials and Methods Reference data were constructed from 20 374 abdominal and/or thoracic CT examinations performed at 120 kV. Data were derived from adults (mean age, 60 years ± 12 [standard deviation]; 56.1% [11 428 of 20 374] women). CT examinations were performed with (n = 4263) or without (n = 16 111) intravenous contrast agent administration for a variety of unrelated clinical indications between 2000 and 2018. L1 Hounsfield unit measurement was obtained either with a customized automated tool (n = 11 270) or manually by individual readers (n = 9104). The effects of patient age, sex, contrast agent, and manual region-of-interest versus fully automated L1 Hounsfield unit measurement were assessed using multivariable logistic regression analysis. Results Mean L1 attenuation decreased linearly with age at a rate of 2.5 HU per year, averaging 226 HU ± 44 for patients younger than 30 years and 89 HU ± 38 for patients 90 years or older. Women had a higher mean L1 attenuation compared with men (P < .008) until menopause, after which both groups had similar values. Administration of intravenous contrast agent resulted in negligible differences in mean L1 attenuation values except in patients younger than 40 years. The fully automated method resulted in measurements that were average 21 HU higher compared with manual measurement (P < .004); at intrapatient subanalysis, this difference was related to the level of transverse measurement used (midvertebra vs off-midline level). Conclusion Normative ranges of L1 vertebra trabecular attenuation were established across all adult ages, and these can serve as a quick reference at routine CT to identify adults with low bone mineral density who are at risk for osteoporosis. © RSNA, 2019 Online supplemental material is available for this article. See also the editorial by Smith in this issue.

Adherence to postresection colorectal cancer surveillance at National Cancer Institute-designated Comprehensive Cancer Centers.

Guidelines recommend surveillance after resection of colorectal cancer (CRC), but rates of adherence to surveillance are variable and have not been studied at National Cancer Institute (NCI)-designated Comprehensive Cancer Centers. The aim of this study was to determine rates of adherence to standard postresection CRC surveillance recommendations including physician visits, carcinoembryonic antigen (CEA), computed tomography (CT), and colonoscopy after CRC resection at three NCI-designated centers. Data on patients with resected CRC from 2010 to 2017 were reviewed. Adherence to physician visits was defined as having at least two visits within 14 months after surgical resection. CEA adherence was defined as having at least four CEA levels drawn within 14 months. CT and colonoscopy adherence were defined as completing each between 10 and 14 months from surgical resection. Chi-square test and logistic regression analyses were performed for overall adherence and adherence to individual components. A total of 241 CRC patients were included. Overall adherence was 23%. While adherence to physician visits was over 98%, adherence to CEA levels, CT, and colonoscopy were each less than 50%. Center was an independent predictor of adherence to CEA, CT, and/or colonoscopy. Stage III disease predicted CT adherence, while distance traveled of 40 miles or less predicted colonoscopy adherence. Overall adherence to postresection CRC guideline-recommended care is low at NCI-designated centers. Adherence rates to surveillance vary by center, stage, and distance traveled for care. Understanding factors associated with adherence is critical to ensure CRC patients benefit from postresection surveillance.

Pulmonary Intraparenchymal Blood Patching Decreases the Rate of Pneumothorax-Related Complications following Percutaneous CT-Guided Needle Biopsy.

PURPOSE: To investigate whether an autologous intraparenchymal blood patch (IPB) reduces the rate of pneumothorax-related complications associated with computed tomography (CT)-guided lung biopsies. MATERIALS AND METHODS: This study included 834 patients: 482 who received an IPB and 352 who did not. Retrospective review was performed of all CT-guided lung biopsies performed at a single institution between August 2006 and September 2013. Patients were excluded if no aerated lung was crossed. The rate of pneumothorax, any associated intervention (eg, catheter placement, aspiration), chest tube placement, and chest tube replacement requiring hospital admission were compared by linear and multiple regression analysis. RESULTS: Patients who received an IPB had a significantly lower rate of pneumothorax (145 of 482 [30%] vs 154 of 352 [44%]; P < .0001), pneumothorax-related intervention (eg, catheter aspiration, pleural blood patch, chest tube placement; 43 of 482 [8.9%] vs 85 of 352 [24.1%]; P < .0001), and chest tube placement along with other determinants requiring hospital admission (18 of 482 [3.7%] vs 27 of 352 [7.7%]; P < .0001). No complications related to the IPB were noted in the study group. CONCLUSIONS: Autologous IPB placement is associated with a decreased rate of pneumothorax and associated interventions, including chest tube placement and hospital admission, after CT-guided lung biopsies, with no evidence of any adverse effects. These results suggest that an IPB is safe and effective and should be considered when aerated lung is traversed while performing a CT-guided lung biopsy.

Enhanced stability of tristetraprolin mRNA protects mice against immune-mediated inflammatory pathologies.

Tristetraprolin (TTP) is an inducible, tandem zinc-finger mRNA binding protein that binds to adenylate-uridylate-rich elements (AREs) in the 3'-untranslated regions (3'UTRs) of specific mRNAs, such as that encoding TNF, and increases their rates of deadenylation and turnover. Stabilization of Tnf mRNA and other cytokine transcripts in TTP-deficient mice results in the development of a profound, chronic inflammatory syndrome characterized by polyarticular arthritis, dermatitis, myeloid hyperplasia, and autoimmunity. To address the hypothesis that increasing endogenous levels of TTP in an intact animal might be beneficial in the treatment of inflammatory diseases, we generated a mouse model (TTPΔARE) in which a 136-base instability motif in the 3'UTR of TTP mRNA was deleted in the endogenous genetic locus. These mice appeared normal, but cultured fibroblasts and macrophages derived from them exhibited increased stability of the otherwise highly labile TTP mRNA. This resulted in increased TTP protein expression in LPS-stimulated macrophages and increased levels of TTP protein in mouse tissues. TTPΔARE mice were protected from collagen antibody-induced arthritis, exhibited significantly reduced inflammation in imiquimod-induced dermatitis, and were resistant to induction of experimental autoimmune encephalomyelitis, presumably by dampening the excessive production of proinflammatory mediators in all cases. These data suggest that increased systemic levels of TTP, secondary to increased stability of its mRNA throughout the body, can be protective against inflammatory disease in certain models and might be viewed as an attractive therapeutic target for the treatment of human inflammatory diseases.

Sources of sport confidence, imagery type and performance among competitive athletes: the mediating role of sports confidence.

AIM: This study explored the mediating role of sport confidence upon (1) sources of sport confidence-performance relationship and (2) imagery-performance relationship. METHODS: Participants were 157 competitive athletes who completed state measures of confidence level/sources, imagery type and performance within one hour after competition. RESULTS: Among the current sample, confirmatory factor analysis revealed appropriate support for the nine-factor SSCQ and the five-factor SIQ. Mediational analysis revealed that sport confidence had a mediating influence upon the achievement source of confidence-performance relationship. In addition, both cognitive and motivational imagery types were found to be important sources of confidence, as sport confidence mediated imagery type- performance relationship. CONCLUSION: Findings indicated that athletes who construed confidence from their own achievements and report multiple images on a more frequent basis are likely to benefit from enhanced levels of state sport confidence and subsequent performance.

Primary hepatic angiosarcoma: multi-institutional comprehensive cancer centre review of multiphasic CT and MR imaging in 35 patients.

OBJECTIVE: To assess the imaging features of primary hepatic angiosarcoma on multiphasic CT and MR. METHODS: Multi-institutional review identified 35 adults (mean age, 57.1 years; 22M/13F) with pathologically proven hepatic angiosarcoma and pretreatment multiphasic CT (n = 33) and/or MR (n = 7). RESULTS: Multifocal hepatic involvement was seen in all 35 cases, with at least 10 lesions in 74.3% (26/35). Mean size of the dominant mass was 8.9 ± 4.7 cm (range, 2.6-20 cm). Individual nodules were typically circumscribed. Arterial-phase foci of hypervascular enhancement without washout were seen in 89.7% (26/29). Heterogeneously expanding foci of enhancement generally followed blood pool in 88.6% (31/35). Progressive centripetal (n = 16) or diffuse "flash-fill" (n = 4) enhancement pattern resembling cavernous haemangiomas predominated in 20 cases, whereas a "reverse haemangioma" centrifugal pattern predominated in 11 cases. Rapid interval growth was seen in 24 (96.0%) of 25 cases with serial imaging. Vascular invasion was not seen in any case. Underlying cirrhotic morphology was seen in 42.3% (15/35). CONCLUSION: Primary hepatic angiosarcomas typically manifest as aggressive multifocal tumors containing small heterogeneous hypervascular foci that progressively expand and follow blood pool. The appearance can mimic cavernous haemangiomas, but distinction is generally possible. In the setting of cirrhosis, lack of tumour washout and vascular invasion argue against multifocal hepatocellular carcinoma. KEY POINTS: • Hepatic angiosarcoma manifests on CT and MR as rapidly progressive multifocal tumours • Multiphasic imaging demonstrates hypervascular foci that progressively expand and follow blood pool • Enhancement pattern can resemble cavernous haemangiomas or show a "reverse" centrifugal pattern • Lack of tumour washout of hypervascular lesions argues against multifocal hepatocellular carcinoma • Careful assessment of the cross-sectional imaging findings may suggest the diagnosis.

Salmonella subtypes with increased MICs for azithromycin in travelers returned to The Netherlands.

Antimicrobial susceptibility was analyzed for 354 typhoidal Salmonella isolates collected during 1999-2012 in the Netherlands. In 16.1% of all isolates and in 23.8% of all isolates that showed increased MICs for ciprofloxacin, the MIC for azithromycin was increased. This resistance may complicate empirical treatment of enteric fever.

Retrospective study of alemtuzumab vs ATG-based conditioning without irradiation for unrelated and matched sibling donor transplants in acquired severe aplastic anemia: a study from the British Society for Blood and Marrow Transplantation.

This retrospective national study compared the use of alemtuzumab-based conditioning regimens for hematopoietic SCT (HSCT) in acquired severe aplastic anemia with antithymocyte globulin (ATG)-based regimens. One hundred patients received alemtuzumab and 55 ATG-based regimens. A matched sibling donor (MSD) was used in 87 (56%), matched unrelated donor (MUD) in 60 (39%) and other related or mismatched unrelated donor (UD) in 8 (5%) patients. Engraftment failure occurred in 9% of the alemtuzumab group and 11% of the ATG group. Five-year OS was 90% for the alemtuzumab and 79% for the ATG groups, P=0.11. For UD HSCT, OS of patients was better when using alemtuzumab (88%) compared with ATG (57%), P=0.026, although smaller numbers of patients received ATG. Similar outcomes for MSD HSCT using alemtuzumab or ATG were seen (91% vs 85%, respectively, P=0.562). A lower risk of chronic GVHD (cGVHD) was observed in the alemtuzumab group (11% vs 26%, P=0.031). On multivariate analysis, use of BM as stem cell source was associated with better OS and EFS, and less acute and cGVHD; young age was associated with better EFS and lower risk of graft failure. This large study confirms successful avoidance of irradiation in the conditioning regimens for MUD HSCT patients.

The sunny side of lime.

A 26-year-old woman was affected with a maculopapular rash because of a jellyfish sting on her right leg while surfing in Indonesia. A locally-prepared liniment was applied on the affected skin. She presented with hyperpigmented linear tracks that she noted a few days later.

Anacardic acid inhibits the catalytic activity of matrix metalloproteinase-2 and matrix metalloproteinase-9.

Cashew nut shell liquid (CNSL) has been used in traditional medicine for the treatment of a wide variety of pathophysiological conditions. To further define the mechanism of CNSL action, we investigated the effect of cashew nut shell extract (CNSE) on two matrix metalloproteinases, MMP-2/gelatinase A and MMP-9/gelatinase B, which are known to have critical roles in several disease states. We observed that the major constituent of CNSE, anacardic acid, markedly inhibited the gelatinase activity of 3T3-L1 cells. Our gelatin zymography studies on these two secreted gelatinases, present in the conditioned media from 3T3-L1 cells, established that anacardic acid directly inhibited the catalytic activities of both MMP-2 and MMP-9. Our docking studies suggested that anacardic acid binds into the MMP-2/9 active site, with the carboxylate group of anacardic acid chelating the catalytic zinc ion and forming a hydrogen bond to a key catalytic glutamate side chain and the C15 aliphatic group being accommodated within the relatively large S1' pocket of these gelatinases. In agreement with the docking results, our fluorescence-based studies on the recombinant MMP-2 catalytic core domain demonstrated that anacardic acid directly inhibits substrate peptide cleavage in a dose-dependent manner, with an IC50 of 11.11 µM. In addition, our gelatinase zymography and fluorescence data confirmed that the cardol-cardanol mixture, salicylic acid, and aspirin, all of which lack key functional groups present in anacardic acid, are much weaker MMP-2/MMP-9 inhibitors. Our results provide the first evidence for inhibition of gelatinase catalytic activity by anacardic acid, providing a novel template for drug discovery and a molecular mechanism potentially involved in CNSL therapeutic action.

The peroral pneumocolon revisited: a valuable fluoroscopic and CT technique for ileocecal evaluation.

The peroral pneumocolon represents a time-honored but somewhat forgotten and underutilized technique for improved ileocecal evaluation at small bowel fluoroscopy. The peroral pneumocolon entails fluoroscopically guided gaseous insufflation per rectum following the arrival of barium at the cecum at conventional small bowel follow-through examination. In most cases, high-quality double contrast evaluation of the terminal ileum can be achieved, often superior to enteroclysis examination for this critical location. The peroral pneumocolon improves diagnostic confidence, including assessment of disease activity, and may result in a reversal of the diagnostic impression. This simple procedure will be discussed and a spectrum of fluoroscopic findings with CT and endoscopic correlation will be provided to demonstrate the added yield of this technique in the evaluation of known or suspected Crohn's disease. Application of the pneumocolon technique to CT for combined small and large bowel evaluation ("CT coloenterography") will also be discussed, which represents an attractive new option for investigating inflammatory bowel disease and other bowel-related conditions. Through the use of automated low-pressure carbon dioxide delivery per rectum, supplemented by IV glucagon for relaxation of the ileocecal valve, a CT-based pneumocolon examination may prove to be a useful hybrid technique for bowel evaluation in the future.

CT-guided lung biopsies: pleural blood patching reduces the rate of chest tube placement for postbiopsy pneumothorax.

OBJECTIVE: The objective of our study was to determine whether pleural blood patching reduces the need for chest tube placement and hospital admission for pneumothorax complicating CT-guided percutaneous lung biopsy. MATERIALS AND METHODS: We reviewed 463 CT-guided lung biopsies performed between August 2006 and March 2010 to determine whether intervention for pneumothorax was required and patient outcome. Intervention was categorized as simple aspiration, aspiration and intrapleural blood patching, or chest tube placement and hospital admission. The technique for pleural blood patching consisted of complete pneumothorax aspiration, immediate placement of up to 15 mL of peripheral autologous blood into the pleural space, and positioning the patient in the ipsilateral decubitus position for 1 hour after the procedure. RESULTS: Intervention for pneumothorax was necessary in 45 of 463 patients (9.7%) and 19 of 463 patients (4.1%) required chest tube placement. Pleural blood patching as a method to treat a postbiopsy pneumothorax and avoid further intervention was associated with a significantly higher success rate than simple aspiration: 19 of 22 (86.4%) vs seven of 15 (46.7%) (odds ratio = 7.2, p = 0.03), respectively. CONCLUSION: Aspiration with intrapleural blood patching is superior to simple aspiration to treat pneumothorax associated with CT-guided lung biopsy. Pleural blood patching reduces the need for chest tube placement and hospital admission in this patient population.

Zinc finger protein tristetraprolin interacts with CCL3 mRNA and regulates tissue inflammation.

Zinc finger protein tristetraprolin (TTP) modulates macrophage inflammatory activity by destabilizing cytokine mRNAs. In this study, through a screen of TTP-bound mRNAs in activated human macrophages, we have identified CCL3 mRNA as the most abundantly bound TTP target mRNA and have characterized this interaction via conserved AU-rich elements. Compared to the wild-type cells, TTP(-/-) macrophages produced higher levels of LPS-induced CCL3. In addition, the plasma level of CCL3 in TTP(-/-) mice was markedly higher than that in wild-type mice. To determine the in vivo significance of TTP-regulated CCL3, we generated CCL3(-/-)TTP(-/-) double-knockout mice. Along with decreased proinflammatory cytokines in their paw joints, there were significant functional and histologic improvements in the inflammatory arthritis of TTP(-/-) mice when CCL3 was absent, although cachexia, reflecting systemic inflammation, was notably unaffected. Furthermore, the marked exacerbation of aortic plaque formation caused by TTP deficiency in the APOE(-/-) mouse model of atherosclerosis was also rescued by disrupting CCL3. Taken together, our data indicate that the interaction between TTP and CCL3 mRNA plays an important role in modulating localized inflammatory processes in tissues that are dissociated from the systemic manifestations of chronic inflammation.