Novel Technique for the Identification of Hip Implants Using Artificial Intelligence.

BACKGROUND: The anticipated growth of total hip arthroplasty will result in an increased need for revision total hip arthroplasty. Preoperative planning, including identifying current implants, is critical for successful revision surgery. Artificial intelligence (AI) is promising for aiding clinical decision-making, including hip implant identification. However, previous studies have limitations such as small datasets, dissimilar stem designs, limited scalability, and the need for AI expertise. To address these limitations, we developed a novel technique to generate large datasets, tested radiographically similar stems, and demonstrated scalability utilizing a no-code machine learning solution. METHODS: We trained, validated, and tested an automated machine learning-implemented convolutional neural network to classify 9 radiographically similar femoral implants with a metaphyseal-fitting wedge taper design. Our novel technique uses computed tomography-derived projections of a 3-dimensional scanned implant model superimposed within a computed tomography pelvis volume. We employed computer-aided design modeling and MATLAB to process and manipulate the images. This generated 27,020 images for training (22,957) and validation (4,063) sets. We obtained 786 test images from various sources. The performance of the model was evaluated by calculating sensitivity, specificity, and accuracy. RESULTS: Our machine learning model discriminated the 9 implant models with a mean accuracy of 97.4%, sensitivity of 88.4%, and specificity of 98.5%. CONCLUSIONS: Our novel hip implant detection technique accurately identified 9 radiographically similar implants. The method generates large datasets, is scalable, and can include historic or obscure implants. The no-code machine learning model demonstrates the feasibility of obtaining meaningful results without AI expertise, encouraging further research in this area.

Development of substituted benzimidazoles as inhibitors of human aldehyde dehydrogenase 1A isoenzymes.

Aldehyde dehydrogenase 1A (ALDH1A) isoforms may be a useful target for overcoming chemotherapy resistance in high-grade serous ovarian cancer (HGSOC) and other solid tumor cancers. However, as different cancers express different ALDH1A isoforms, isoform selective inhibitors may have a limited therapeutic scope. Furthermore, resistance to an ALDH1A isoform selective inhibitor could arise via induction of expression of other ALDH1A isoforms. As such, we have focused on the development of pan-ALDH1A inhibitors, rather than on ALDH1A isoform selective compounds. Herein, we report the development of a new group of pan-ALDH1A inhibitors to assess whether broad spectrum ALDH1A inhibition is an effective adjunct to chemotherapy in HGSOC. Optimization of the CM10 scaffold, aided by ALDH1A1 crystal structures, led to improved biochemical potencies, improved cellular efficacy as demonstrated by reduction in ALDEFLUOR signal in HGSOC cells, and substantial improvements in liver microsomal stability. Based on this work we identified two compounds 17 and 25 suitable for future in vivo proof of concept experiments.

The chemotherapeutic CX-5461 primarily targets TOP2B and exhibits selective activity in high-risk neuroblastoma.

Survival in high-risk pediatric neuroblastoma has remained around 50% for the last 20 years, with immunotherapies and targeted therapies having had minimal impact. Here, we identify the small molecule CX-5461 as selectively cytotoxic to high-risk neuroblastoma and synergistic with low picomolar concentrations of topoisomerase I inhibitors in improving survival in vivo in orthotopic patient-derived xenograft neuroblastoma mouse models. CX-5461 recently progressed through phase I clinical trial as a first-in-human inhibitor of RNA-POL I. However, we also use a comprehensive panel of in vitro and in vivo assays to demonstrate that CX-5461 has been mischaracterized and that its primary target at pharmacologically relevant concentrations, is in fact topoisomerase II beta (TOP2B), not RNA-POL I. This is important because existing clinically approved chemotherapeutics have well-documented off-target interactions with TOP2B, which have previously been shown to cause both therapy-induced leukemia and cardiotoxicity-often-fatal adverse events, which can emerge several years after treatment. Thus, while we show that combination therapies involving CX-5461 have promising anti-tumor activity in vivo in neuroblastoma, our identification of TOP2B as the primary target of CX-5461 indicates unexpected safety concerns that should be examined in ongoing phase II clinical trials in adult patients before pursuing clinical studies in children.

Development of 2,5-dihydro-4H-pyrazolo[3,4-d]pyrimidin-4-one inhibitors of aldehyde dehydrogenase 1A (ALDH1A) as potential adjuncts to ovarian cancer chemotherapy.

There is strong evidence that inhibition of one or more Aldehyde Dehydrogenase 1A (ALDH1A) isoforms may be beneficial in chemotherapy-resistant ovarian cancer and other tumor types. While many previous efforts have focused on development of ALDH1A1 selective inhibitors, the most deadly ovarian cancer subtype, high-grade serous (HGSOC), exhibits elevated expression of ALDH1A3. Herein, we report continued development of pan-ALDH1A inhibitors to assess whether broad spectrum ALDH1A inhibition is an effective adjunct to chemotherapy in this critical tumor subtype. Optimization of the CM39 scaffold, aided by metabolite ID and several new ALDH1A1 crystal structures, led to improved biochemical potencies, improved cellular ALDH inhibition in HGSOC cell lines, and substantial improvements in microsomal stability culminating in orally bioavailable compounds. We demonstrate that two compounds 68 and 69 are able to synergize with chemotherapy in a resistant cell line and patient-derived HGSOC tumor spheroids, indicating their suitability for future in vivo proof of concept experiments.

Management of inferior vena cava thrombosis with the FlowTriever and ClotTriever systems.

OBJECTIVE: Although inferior vena cava (IVC) thrombosis is infrequently encountered, it carries a significant risk of post-thrombotic syndrome and pulmonary embolus. Recent studies show no difference in the incidence of post-thrombotic syndrome in patients with iliofemoral deep venous thrombosis (DVT) treated with pharmacothrombolysis vs anticoagulation alone; however, there is an associated increased risk of bleeding. The treatment of IVC thrombosis is less well-studied and the hemodynamic changes may be more significant with pharmacothrombolysis, although the bleeding risk remains. The ClotTriever and FlowTriever systems remove thrombus from veins without the use of thrombolytics. Our study evaluates outcomes of patients undergoing mechanical thrombectomy for the treatment of IVC thrombosis using the ClotTriever and FlowTriever devices. METHODS: A retrospective chart review was performed to identify consecutive patients who underwent mechanical thrombectomy for the treatment of IVC thrombosis using the ClotTriever and/or FlowTriever systems from November 2018 to January 2020 at four data-sharing institutions. The decision of which device(s) to use was at the discretion of the surgeon. Patient demographics, symptomatology, and imaging characteristics were captured at presentation and follow-up. RESULTS: A total of 15 patients met the inclusion criteria; 10 were male, and the average age was 59 years. The majority of patients were symptomatic at presentation (n = 14), had a prior history of DVT (n = 13), and had a preexisting IVC filter (n = 8). Eleven patients presented with acute onset (<1 week) of symptoms, whereas three patients had subacute (1-4 weeks) symptoms. Most patients had an associated iliofemoral DVT (n = 13) and were treated with both ClotTriever and FlowTriever (n = 8); others were treated with either ClotTriever or FlowTriever alone (n = 5 and n = 2, respectively). Technical success was achieved in all but two patients, one who had a nonocclusive thrombus densely adherent to a preexisting IVC filter and another who had a chronic rubbery clot in the IVC that could not be cleared. No patient required concomitant lytic therapy or a postoperative stay in the intensive care unit. Furthermore, there were no postoperative bleeding events, myocardial infarctions, pulmonary emboli, renal impairments, or deaths. The median length of stay was 3 days (range, 1-37 days). Patients underwent postoperative follow-up (n = 7) as well as extended follow-up (>6 months; n = 8). All patients who achieved technical success were asymptomatic without evidence of reocclusion of the IVC on follow-up imaging. CONCLUSIONS: In our multicenter series of 15 patients, The ClotTriever and FlowTriever showed promise in the treatment of IVC thrombosis without the use of fibrinolytic drugs, with no bleeding events and no requirement for intensive care unit stay.

Interferon-Induced Protein 44 and Interferon-Induced Protein 44-Like Restrict Replication of Respiratory Syncytial Virus.

Cellular intrinsic immunity, mediated by the expression of an array of interferon-stimulated antiviral genes, is a vital part of host defense. We have previously used a bioinformatic screen to identify two interferon-stimulated genes (ISG) with poorly characterized function, interferon-induced protein 44 (IFI44) and interferon-induced protein 44-like (IFI44L), as potentially being important in respiratory syncytial virus (RSV) infection. Using overexpression systems, CRISPR-Cas9-mediated knockout, and a knockout mouse model, we investigated the antiviral capability of these genes in the control of RSV replication. Overexpression of IFI44 or IFI44L was sufficient to restrict RSV infection at an early time postinfection. Knocking out these genes in mammalian airway epithelial cells increased levels of infection. Both genes express antiproliferative factors that have no effect on RSV attachment but reduce RSV replication in a minigenome assay. The loss of Ifi44 was associated with a more severe infection phenotype in a mouse model of infection. These studies demonstrate a function for IFI44 and IFI44L in controlling RSV infection.IMPORTANCE RSV infects all children under 2 years of age, but only a subset of children get severe disease. We hypothesize that susceptibility to severe RSV necessitating hospitalization in children without predefined risk factors is, in part, mediated at the antiviral gene level. However, there is a large array of antiviral genes, particularly in the ISG family, the mechanism of which is poorly understood. Having previously identified IFI44 and IFI44L as possible genes of interest in a bioinformatic screen, we dissected the function of these two genes in the control of RSV. Through a range of overexpression and knockout studies, we show that the genes are antiviral and antiproliferative. This study is important because IFI44 and IFI44L are upregulated after a wide range of viral infections, and IFI44L can serve as a diagnostic biomarker of viral infection.

Quality of life after pharmacomechanical catheter-directed thrombolysis for proximal deep venous thrombosis.

BACKGROUND: After deep venous thrombosis (DVT), many patients have impaired quality of life (QOL). We aimed to assess whether pharmacomechanical catheter-directed thrombolysis (PCDT) improves short-term or long-term QOL in patients with proximal DVT and whether QOL is related to extent of DVT. METHODS: The Acute Venous Thrombosis: Thrombus Removal with Adjunctive Catheter-Directed Thrombolysis (ATTRACT) trial was an assessor-blinded randomized trial that compared PCDT with no PCDT in patients with DVT of the femoral, common femoral, or iliac veins. QOL was assessed at baseline and 1 month, 6 months, 12 months, 18 months, and 24 months using the Venous Insufficiency Epidemiological and Economic Study on Quality of Life/Symptoms (VEINES-QOL/Sym) disease-specific QOL measure and the 36-Item Short Form Health Survey (SF-36) physical component summary (PCS) and mental component summary general QOL measures. Change in QOL scores from baseline to assessment time were compared in the PCDT and no PCDT treatment groups overall and in the iliofemoral DVT and femoral-popliteal DVT subgroups. RESULTS: Of 692 ATTRACT patients, 691 were analyzed (mean age, 53 years; 62% male; 57% iliofemoral DVT). VEINES-QOL change scores were greater (ie, better) in PCDT vs no PCDT from baseline to 1 month (difference, 5.7; P = .0006) and from baseline to 6 months (5.1; P = .0029) but not for other intervals. SF-36 PCS change scores were greater in PCDT vs no PCDT from baseline to 1 month (difference, 2.4; P = .01) but not for other intervals. Among iliofemoral DVT patients, VEINES-QOL change scores from baseline to all assessments were greater in the PCDT vs no PCDT group; this was statistically significant in the intention-to-treat analysis at 1 month (difference, 10.0; P < .0001) and 6 months (8.8; P < .0001) and in the per-protocol analysis at 18 months (difference, 5.8; P = .0086) and 24 months (difference, 6.6; P = .0067). SF-36 PCS change scores were greater in PCDT vs no PCDT from baseline to 1 month (difference, 3.2; P = .0010) but not for other intervals. In contrast, in femoral-popliteal DVT patients, change scores from baseline to all assessments were similar in the PCDT and no PCDT groups. CONCLUSIONS: Among patients with proximal DVT, PCDT leads to greater improvement in disease-specific QOL than no PCDT at 1 month and 6 months but not later. In patients with iliofemoral DVT, PCDT led to greater improvement in disease-specific QOL during 24 months.

Very long-term outcome in resected and non-resected patients with temporal lobe epilepsy with medial temporal lobe sclerosis: A multiple case-study.

PURPOSE: To investigate the very long-term (i.e., ≥15 years) seizure, cognitive and psycho-social outcomes in resected patients (RP) with TLE compared to control patients not having undergone epilepsy surgery. METHODS: We applied a multiple case-study design including three non-resected patients (NRP) who were compared to a group of six RP. The latter were matched to the NRP according to clinical-demographic data. Outcome measures were various seizure, cognitive, and psycho-social variables. RESULTS: Patients were 56-72 years old. Seizure and AED outcome was more favourable among RP. RP reported better self-perceived overall health but higher subjective memory complaints. Upon formal neuropsychological testing, RP presented with lower verbal memory scores. Very long-term memory decline was evident in left-sided RP with good baseline memory scores, while RP with lower baseline performance, right-sided RP and NRP remained stable. Seizure-freedom had remarkable effects on the relationship between objective and subjective outcome: seizure-free patients, in general, subjectively reported the best psychosocial and cognitive outcome - irrespective of neuropsychological test results. CONCLUSION: Our study suggests positive effects of TLE surgery in the very long-term course of ≥15 years postoperatively. Long-term seizure-freedom appears to have the strongest impact on patients' subjectively perceived psycho-social and cognitive outcome and may even outweigh actual memory disturbances and/or decline. Overall, our data do not support the assumption of a generally accelerated cognitive decline in patients with TLE.

Quantitative electroencephalography supports diagnosis of natalizumab-associated progressive multifocal leukoencephalopathy.

Long-term treatment of multiple sclerosis with natalizumab (NTZ) carries the risk of a devastating complication in the form of an encephalopathy caused by a reactivation of a latent John Cunningham virus infection (progressive multifocal leucoencephalopathy, PML). Early diagnosis is associated with considerably better prognosis. Quantitative EEG as an objective, rater-independent technique provides high sensitivity (88%) and specificity (82%) for the diagnosis of NTZ-PML. Combination of diagnostic modalities addressing static morphological (brain MRI) as well as functional (EEG) pathologic changes may improve risk management programmes.

Structure-Based Optimization of a Novel Class of Aldehyde Dehydrogenase 1A (ALDH1A) Subfamily-Selective Inhibitors as Potential Adjuncts to Ovarian Cancer Chemotherapy.

Aldehyde dehydrogenase (ALDH) activity is commonly used as a marker to identify cancer stem-like cells. The three ALDH1A isoforms have all been individually implicated in cancer stem-like cells and in chemoresistance; however, which isoform is preferentially expressed varies between cell lines. We sought to explore the structural determinants of ALDH1A isoform selectivity in a series of small-molecule inhibitors in support of research into the role of ALDH1A in cancer stem cells. An SAR campaign guided by a cocrystal structure of the HTS hit CM39 (7) with ALDH1A1 afforded first-in-class inhibitors of the ALDH1A subfamily with excellent selectivity over the homologous ALDH2 isoform. We also discovered the first reported modestly selective single isoform 1A2 and 1A3 inhibitors. Two compounds, 13g and 13h, depleted the CD133+ putative cancer stem cell pool, synergized with cisplatin, and achieved efficacious concentrations in vivo following IP administration. Compound 13h additionally synergized with cisplatin in a patient-derived ovarian cancer spheroid model.

Phosphorylation of a constrained azacyclic FTY720 analog enhances anti-leukemic activity without inducing S1P receptor activation.

The frequency of poor outcomes in relapsed leukemia patients underscores the need for novel therapeutic approaches. The Food and Drug Administration-approved immunosuppressant FTY720 limits leukemia progression by activating protein phosphatase 2A and restricting nutrient access. Unfortunately, FTY720 cannot be re-purposed for use in cancer patients due to on-target toxicity associated with S1P receptor activation at the elevated, anti-neoplastic dose. Here we show that the constrained azacyclic FTY720 analog SH-RF-177 lacks S1P receptor activity but maintains anti-leukemic activity in vitro and in vivo. SH-RF-177 was not only more potent than FTY720, but killed via a distinct mechanism. Phosphorylation is dispensable for FTY720's anti-leukemic actions. However, chemical biology and genetic approaches demonstrated that the sphingosine kinase 2 (SPHK2)-mediated phosphorylation of SH-RF-177 led to engagement of a pro-apoptotic target and increased potency. The cytotoxicity of membrane-permeant FTY720 phosphonate esters suggests that the enhanced potency of SH-RF-177 stems from its more efficient phosphorylation. The tight inverse correlation between SH-RF-177 IC50 and SPHK2 mRNA expression suggests a useful biomarker for SH-RF-177 sensitivity. In summary, these studies indicate that FTY720 analogs that are efficiently phosphorylated but fail to activate S1P receptors may be superior anti-leukemic agents compared to compounds that avoid cardiotoxicity by eliminating phosphorylation.

Home parenteral nutrition (HPN) in patients with post-bariatric surgery complications.

BACKGROUND & AIMS: Obesity is a worldwide health problem. Bariatric surgery (BS) is becoming one of the most commonly used methods for fighting obesity and its associated comorbidities. However, current BS techniques can be associated with early or late complications that may require nutritional support. The aim of this retrospective observational study was to determine the indications and outcomes for patients on Home parenteral nutrition (HPN) due to post-bariatric surgery complications. METHODS: A specific questionnaire was designed by the ESPEN HAN/CIF working group and submitted to HPN centers. This questionnaire included: patient demographics, type of surgery, BMI before surgery and at start of HPN, indications for HPN including technical and nutritional complications (early within 2 months after surgery or late), outcome, PN regimen, and HPN complications. Patients were retrospectively included from January 2008 to June 2014. RESULTS: Eighteen HPN centers responded to the survey. A total of 2880 HPN patients were treated during the study period, 77 of whom had BS (65 females; mean age 51 ± 7 years); gastric bypass was performed in 69% of the patients; mean BMI was 44.4 before surgery and 23.2 at the start of HPN. Indications for HPN were early complications in 17 cases and late complications in 60 cases. Early complications were mostly anastomotic leakage/fistula; late complications were hypoalbuminemia, and vitamin and trace element deficiencies. Out of 77 patients, 16 needed a surgical re-intervention, 29 were weaned off HPN, and 6 died (no HPN-related deaths). During the HPN period, 58% of the patients were re-hospitalized and central venous complications were observed in 41%. Diabetes mellitus was described in 17/77 patients. HPN was supportive in 60 patients and exclusive in 17 patients (mean caloric intake: 23 ± 6 kcal/k BW/day and 1.2 g/kBW/day). Only 7/77 patients resumed their professional activities on HPN. CONCLUSIONS: This is the largest observational multicenter study describing the use of HPN in patients with post-BS complications. Severe hypoalbuminemia is a major late complication. Rates of re-hospitalization and CVC infection were high. HPN may be a "bridge therapy" before surgical revision after BS. The high mortality rate reflects the complexity of these cases.

Ethylene-vinyl alcohol copolymer endobiliary obliteration of hepatic segments in a patient with isolated bile leaks.

A 54-year-old woman with a symptomatic giant hepatic hemangioma underwent an extended left hepatic trisegmentectomy complicated by 250-350 mL/d postoperative bilious drainage. After 5 months of therapy, drainage was unabated, and the patient was no longer a surgical candidate. Sinography revealed three distinct isolated bile duct leaks involving segments 6, 7, and 8. Endobiliary segmentectomy was achieved by obliterating the isolated systems with ethylene-vinyl alcohol copolymer (Onyx; ev3, Plymouth, Minnesota) during three fluoroscopic procedures. Bilious leaks were successfully eliminated, and compensatory hypertrophy of noninvolved liver occurred. At 2 years from the last embolization procedure, the patient remained asymptomatic with no bilious leak.

[Rapid detection of a depressive disorder in persons with epilepsy. Validation of a German version of the NDDI-E]. / Schnelle Erkennung einer depressiven Störung bei Menschen mit Epilepsie. Validierung einer deutschsprachigen Version des NDDI-E.

The prevalence of psychiatric disorders in people with epilepsy is high. Depression and anxiety disorders are especially frequent. These comorbid disorders are, however, easily overlooked. The neurological disorders depression inventory for epilepsy (NDDI-E) was developed and validated as a screening instrument with six questions. The aim of the present study was to validate a German version of the NDDI-E. After translation into German and back translation into English, the NDDI-E was presented to 144 patients at the Bethel Epilepsy Center. The Beck depression inventory II (BDI-II), the revised symptom check list by Derogatis (SCL-90-R) and the state-trait anxiety inventory (STAI) were also used. The patients were examined using the mini international neuropsychiatric interview plus (MINI Plus). The German version of the NDDI-E proved to be valid, internally consistent and easy to use.

Characterization and cytotoxic activity of sulfated derivatives of polysaccharides from Agaricus brasiliensis.

Agaricus brasiliensis cell-wall polysaccharides isolated from fruiting body (FR) and mycelium (MI) and their respective sulfated derivatives (FR-S and MI-S) were chemically characterized using elemental analysis, TLC, FT-IR, NMR, HPLC, and thermal analysis. Cytotoxic activity was evaluated against A549 tumor cells by MTT and sulforhodamine assays. The average molecular weight (Mw) of FR and MI was estimated to be 609 and 310 kDa, respectively. FR-S (127 kDa) and MI-S (86 kDa) had lower Mw, probably due to hydrolysis occurring during the sulfation reaction. FR-S and MI-S presented ~14% sulfur content in elemental analysis. Sulfation of samples was characterized by the appearance of two new absorption bands at 1253 and 810 cm(-1) in the infrared spectra, related to S=O and C-S-O sulfate groups, respectively. Through (1)H and (13)C NMR analysis FR-S was characterized as a (1→6)-(1→3)-ß-D-glucan fully sulfated at C-4 and C-6 terminal and partially sulfated at C-6 of (1→3)-ß-D-glucan moiety. MI-S was shown to be a (1→3)-ß-D-gluco-(1→2)-ß-D-mannan, partially sulfated at C-2, C-3, C-4, and C-6, and fully sulfated at C-6 of the terminal residues. The combination of high degree of sulfation and low molecular weight was correlated with the increased cytotoxic activity (48 h of treatment) of both FR-S (EC50=605.6 µg/mL) and MI-S (EC50=342.1 µg/mL) compared to the non-sulfated polysaccharides FR and MI (EC50>1500 µg/mL).

Endoscopic vein harvest of the lesser saphenous vein in the supine position: a unique approach to an old problem.

OBJECTIVES: To obtain a suitable conduit from the lesser (short) saphenous system for use in coronary artery bypass surgery. We wanted to perform this while the patient was in the supine position as to not disrupt the standard operation, and at the same time, utilizing the endoscopic vein harvest technique with its obvious abilities to decrease vein harvest morbidity. We also theorized that through endoscopic techniques instead of the open technique we could harvest greater lengths of conduit, thus providing quality vein segments for additional grafts if needed. METHODS: We were able to perform endoscopic vein harvest while in the supine position with one unique centrally located incision that has not been previously described. RESULTS: The lesser saphenous vein harvested in the described technique provided excellent conduit for our patients that were conduit poor. The endoscopic technique allowed increased length of harvested segments, by giving us the ability to travel under the gastrocnemius muscle with minimal morbidity as opposed to the open technique, where the traditional endpoint is the aforementioned muscle. Conduits were harvested successfully from 14 of 16 candidates. No wound infections or healing problems were experienced. Neurovascular integrity was maintained in all patients. CONCLUSIONS: Endoscopic vein harvest of the lesser saphenous vein with the patient in the supine position is safe, effective and affords conduits for a unique subset of patients undergoing coronary artery bypass grafting.

IL-6 regulates exercise and training-induced adaptations in subcutaneous adipose tissue in mice.

AIM: The aim of this study was to test the hypothesis that IL-6 regulates exercise-induced gene responses in subcutaneous adipose tissue in mice. METHODS: Four-month-old male IL-6 whole body knockout (KO) mice and C57B wild-type (WT) mice performed 1 h of treadmill exercise, where subcutaneous adipose tissue (AT) was removed either immediately after, 4 h or 10 h after exercise as well as from mice not running acutely. Moreover, AT was sampled at resting conditions after 5 weeks of exercise training. RESULTS: AT leptin mRNA decreased immediately after a single running exercise bout in both genotypes and returned to baseline within 10 h of recovery in IL-6 KO mice, but not WT mice. Leptin mRNA content decreased in WT and increased in IL-6 KO mice with training, but without significant alterations in leptin protein. Acute exercise induced a decrease in the AT TNFα mRNA content in WT, but not in IL-6-KO mice, while training lowered resting levels of TNFα mRNA in both genotypes. In addition, an exercise-induced decline in AT PPARγ mRNA content was absent in IL-6 KO mice and in line training increased PPARγ mRNA only in IL-6 KO mice. CONCLUSION: The present findings indicate a role of IL-6 in regulating exercise- and training-induced leptin and PPARγ expression in adipose tissue. In addition, while IL-6 is required for TNF-α mRNA reduction in response to acute exercise, IL-6 does not appear to be mandatory for anti-inflammatory effects of exercise training in adipose tissue.

Evaluation of optimal acquisition duration or injected activity for pediatric 18F-FDG PET/CT.

UNLABELLED: Pediatric (18)F-FDG dosing and acquisition durations are generally based on coarse extrapolation from adult guidelines. This study sought to determine whether shorter acquisition durations or a lower (18)F-FDG injected activity could be used for pediatric (18)F-FDG PET/CT examinations while maintaining diagnostic utility. Reduction of overall scan time potentially reduces motion artifacts, improves patient comfort, and decreases length of sedation. Alternatively, decreased (18)F-FDG dose minimizes radiation risk. METHODS: Fourteen whole-body (18)F-FDG PET/CT examinations were performed on 13 patients (weight, 13-109 kg; age range, 1-23 y) with a weight-based injected activity (5.3 MBq/kg [0.144 mCi/kg]), fixed acquisition durations (3 min/field of view [FOV] if < 22 kg, 5 min/FOV if > 22 kg), and list-mode acquisition. For each examination, the list-mode data were truncated to form multiple datasets with shorter acquisition durations down to a minimum of 1 min/FOV (i.e., 1, 2, 3, 4, and 5 min/FOV data were formed from single 5 min/FOV acquisition). Fifty-six image volumes were generated, randomized, and reviewed in a masked manner with corresponding CT image volumes by 5 radiologists. Overall, subjective adequacy and objective lesion detection accuracy by body region were evaluated. RESULTS: All examinations with maximum acquisition duration were graded as adequate and were used as the reference standard for detection accuracy. For patients less than 22 kg, 1 of the 3 PET/CT examinations was graded as inadequate for clinical tasks when acquisition duration was reduced to 2 min/FOV, and all examinations were graded as inadequate when reduced to 1 min/FOV. For patients more than 22 kg, all 3-5 min/FOV studies were graded as adequate, and 2 of the 9 studies were graded as inadequate for 2 min/FOV studies. Lesion detection accuracy was perfect for acquisition times between 3 min/FOV and 5 min/FOV for all regions of the body. However, lesion detection became less accurate when imaging acquisition time was reduced more than 40%. CONCLUSION: Evaluation of image volumes generated from simulated shorter acquisition durations suggests that imaging times for larger patients (>22 kg) can be reduced from 5 min/FOV to 3 min/FOV without a loss of diagnostic utility. Using decreased acquisition times as a surrogate for (18)F-FDG dose, (18)F-FDG dose can be reduced by approximately 40% when all patients were scanned for 5 min/FOV.

Longitudinal quality of life assessment of patients with hepatocellular carcinoma after primary transarterial chemoembolization.

PURPOSE: To determine the effects of primary chemoembolization on the health-related quality of life (HRQOL) of patients with hepatocellular carcinoma (HCC). MATERIALS AND METHODS: Single-center prospective data collection with longitudinal analysis of HRQOL scores obtained via the Short Form-36 (SF-36) assessment tool was performed before and during serial chemoembolization procedures in 73 patients with HCC. Baseline HRQOL scores were evaluated for significant (P < .05) change within the total patient population during 4, 8, and 12 months of treatment, and separately within a subset of 23 patients who underwent three or more chemoembolization procedures. RESULTS: Patients had decreased pretreatment baseline scores within all eight scales of the SF-36 compared with healthy age-adjusted norms. Within the total population, mental health scores improved after 4 months of chemoembolization (rate of change, 5.6; P = .05; n = 48), but no significant change was present at 8 or 12 months. Subset patients experienced improvements of mental health scores after the first (score change, 13; P = .008; n = 21) and second procedures (score change, 12.2; P = .002; n = 23) and improvements of bodily pain scores (score change, 9.9; P = .047; n = 21) after the initial procedure. Vitality scores worsened (score change, -7.8; P = .044; n = 21) in the subset after the first chemoembolization. CONCLUSIONS: Patients with HCC are likely to perceive improved mental health during the first 4 months of primary treatment with chemoembolization. In addition, if patients ultimately undergo more than two procedures, they are likely to perceive improved mental health during the first two sessions, with decreased bodily pain during the initial session. Patient-perceived vitality will likely worsen after the initial procedure.

Usefulness of multimodality cardiac imaging in the diagnosis of a right atrial angiosarcoma.

A 78-year-old woman presented with progressive dyspnea and atrial flutter and was found to have a right atrial mass. Multimodality cardiac imaging was useful in further characterizing this mass, which was ultimately diagnosed after biopsy as a low-grade angiosarcoma.