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Typhoid fever is an endemic disease in many low-income and middle-income countries. The 2018 WHO position paper recommends that countries should consider typhoid vaccination in high-risk groups and for outbreak control. To address the typhoid vaccine supply and demand gap, a typhoid Vi polysaccharide-diphtheria toxoid (Vi-DT) conjugate vaccine development effort was undertaken to achieve WHO prequalification and contribute to the global supply of typhoid conjugate vaccine. The main aim of this study was to show immune non-inferiority of the Vi-DT vaccine compared with the WHO prequalified Vi polysaccharide-tetanus toxoid (Vi-TT) conjugate vaccine (Typbar TCV; Bharat Biotech India, Hyderabad, India) in participants of various ages from an endemic country.We did an observer-blind, active-controlled, randomised, non-inferiority, phase 3 trial at four hospitals in Kathmandu, Dhulikhel, Dharan, and Nepalgunj in Nepal. Eligible participants were healthy individuals aged 6 months to 45 years for whom informed consent was obtained, were willing to follow the study procedures and were available for the duration of the study. Patients with an acute or chronic illness that could interfere with interpretation of the study endpoints, or who were involved in any other clinical trial were excluded. Participants were randomly assigned (1:1:1:1) by block randomisation (block size of four and eight), stratified by age (6 months to2 years, 2 years to18 years, and 18 years to 45 years), into one of four groups (A-D). Participants in groups A-C received a single dose (25 μg; 0·5 mL) of Vi-DT test vaccine via intramuscular injection from one of three good manufacturing practice lots (group A received lot 1, group B received lot 2, and group C received lot 3), and those in group D received a single dose (25 μg; 0·5 mL) of the Vi-TT vaccine via intramuscular injection. All participants, site staff (except for those who administered the study vaccines), and those assessing the outcomes were masked to group assignment. The co-primary endpoints were: (1) non-inferiority of immunogenicity of the Vi-DT vaccine (pooled groups A-C) versus the Vi-TT vaccine (group D), measured by the anti-Vi IgG seroconversion rate at 4 weeks after vaccination; and (2) the lot-to-lot consistency of the Vi-DT vaccine, measured by immune equivalence of the anti-Vi IgG geometric mean titre (GMT) at 4 weeks after receipt of the three Vi-DT vaccine lots (lot 1 vs lot 2, lot 1 vs lot 3, and lot 2 vs lot 3). Non-inferiority of the Vi-DT vaccine compared with the Vi-TT vaccine was shown if the lower limit of the 97·5% CI for the difference between the seroconversion rates in Vi-DT vaccine groups A-C combined versus Vi-TT vaccine group D was above the predefined non-inferiority margin of -10%. Lot-to-lot immune equivalence was shown if the upper and lower bounds of the two-sided 99·17% CI around the GMT ratio for each pairwise lot-to-lot comparison was between 0·67 and 1·50, which is the predefined equivalence margin recommended by WHO. The co-primary immunogenicity endpoints were assessed in all randomised participants who had received their assigned vaccine and had completed at least one post-baseline immunogenicity assessment. Safety was descriptively summarised by group and age strata, and was assessed in all participants who had received one dose of the investigational vaccine. The trial is registered with ClinicalTrials.gov, NCT03933098.Between Nov 20, 2019, and March 10, 2020, 1854 individuals were screened, of whom 1800 were enrolled and randomly assigned to groups A-D (450 participants in each group). 1786 (99·2%; 443 in group A, 450 in group B, 447 in group C, and 446 in group D) were included in the immunogenicity assessments at 4 weeks post vaccination, and all 1800 participants were included in the safety analysis. In the immunogenicity analysis, the anti-Vi-IgG seroconversion rate in all age strata was 99·33% (97·5% CI 98·61 to 99·68; 1331 of 1340 participants) in Vi-DT vaccine groups A-C and 98·88% (97·10 to 99·57; 441 of 446) in Vi-TT vaccine group D. The difference in seroconversion rates between Vi-DT vaccine groups A-C combined versus Vi-TT group D was 0·47% (97·5% CI -0·68 to 1·61), indicating non-inferiority of the Vi-DT vaccine. Anti-Vi-IgG GMT ratios at 4 weeks post-vaccination were 1·02 (99·17% CI 0·85 to 1·22) for lot 1 versus lot 2, 1·02 (0·85 to 1·23) for lot 1 versus lot 3, and 1·01 (0·84 to 1·21) for lot 2 versus lot 3, indicating lot-to-lot equivalence according to the predefined, WHO-recommended equivalence margin. The proportion of participants reporting adverse events was similar between Vi-DT vaccine groups A-C and Vi-TT vaccine group D; 260 (19·3%) of 1350 participants in Vi-DT vaccine groups A-C and 115 (25·6%) of 450 in Vi-TT vaccine group D reported solicited adverse events within 7 days after vaccination, and 208 (15·4%) in Vi-DT vaccine groups A-C and 76 (16·9%) in Vi-TT vaccine group D reported unsolicited adverse events within 4 weeks after vaccination. Seven serious adverse events (four [0·3%] participants in Vi-DT vaccine groups A-C and three [0·7%] in Vi-TT vaccine group D), including one death in the Vi-TT vaccine group, were reported during the 24-week follow-up period, none of which were considered related to the investigational product.When administered as a single dose, the Vi-DT test vaccine was safe, immunogenic, and non-inferior to the Vi-TT vaccine at 4 weeks post vaccination. Equivalent immunogenicity of the three lots of Vi-DT vaccine was also shown, supporting the manufacturing process of this vaccine. Once prequalified by WHO, this vaccine could be an option for purchase by UN agencies.The BillMelinda Gates Foundation.For the Nepali translation of the abstract see Supplementary Materials section.

BackgroundGBP510 vaccine contains self-assembling, recombinant nanoparticles displaying SARS-CoV-2 spike receptor-binding domains. We report interim phase 3 immunogenicity results for GBP510 adjuvanted with AS03 (GBP510/AS03) compared with ChAdOx1-S (Vaxzevria, AstraZeneca) up to 2 weeks after the second dose, and safety data up to a median of 2.5 months follow-up.MethodsRandomised, active-controlled, observer-blinded, multinational study: Cohort 1 (no history of SARS-CoV-2 infection/COVID-19 vaccination, n=1956) randomised 2:1 to receive two doses of GBP510/AS03 or ChAdOx1-S (immunogenicity and safety); Cohort 2 (regardless of baseline serostatus; n=2080) randomised 5:1 (safety). Primary objectives: demonstrate superiority in geometric mean titre (GMT) and non-inferiority in seroconversion rate (SCR; ≥4-fold rise from baseline) of GBP510/AS03 versus ChAdOx1-S for neutralising antibodies against the ancestral strain by live-virus neutralisation assay. Secondary objectives included assessment of safety and reactogenicity.FindingsAt 2 weeks after the second vaccination, the GMT ratio (GBP510/AS03 / ChAdOx1-S) was 2.93 (95% CI 2.63–3.27), demonstrating superiority (95% CI lower limit >1). The between-group SCR difference of 10.76% (95% CI 7.68–14.32) satisfied the non-inferiority criterion (95% CI lower limit > −5%).The proportion of subjects with adverse events (AEs) after any vaccination was higher with GBP510/AS03 versus ChAdOx1-S for solicited local AEs (56.69% vs 49.20%), but was similar for solicited systemic AEs (51.21% vs 53.51%) and unsolicited AEs (13.27% vs 14.56%). No safety concerns were identified during follow-up for a median 2.5-months after the second vaccination.InterpretationGBP510/AS03 met the superiority criterion for neutralising antibodies and non-inferiority criterion for SCR compared with ChAdOx1-S, and showed a clinically acceptable safety profile.FundingThis work was supported, in whole or in part, by funding from CEPI and the Bill & Melinda Gates Foundation Investments INV-010680 and INV-006462. The Bill & Melinda Gates Foundation supported this project for the generation of IND-enabling data and CEPI supported this clinical study.RESEARCH IN CONTEXTEvidence before this studyImmunobridging has been proposed as an approach for assessing new COVID-19 vaccines by comparing the immunogenicity of candidate vaccines with an active comparator with demonstrated clinical efficacy. We searched PubMed up to 26 October 2022 for immunobridging clinical trials comparing a candidate vaccine with an approved vaccine, using the terms “immunobridging”, “SARS-CoV-2”, “COVID-19”, and “vaccine”. A phase 2/3 study showed that the ChAdOx1 vaccine, manufactured by the Serum Institute of India after technology transfer from Oxford University/AstraZeneca, had a non-inferior immune response compared to the original ChAdOx1 (AZD1222) vaccine. A post hoc analysis of phase 2 data found that MVC-COV1901 vaccine (a protein subunit vaccine developed by Medigen Vaccine Biologics Corporation, Taiwan) was non-inferior to ChAdOx1 (AZD1222) with respect to neutralising antibody titres. A phase 3 study found that VLA2001 (an adjuvanted, inactivated whole-virus vaccine developed by Valneva, Austria) was superior to ChAdOx1 with respect to neutralising antibody titres and non-inferior with respect to seroconversion rates.Added value of this studyThis is the first study comparing the immunogenicity of recombinant SARS-CoV-2 protein nanoparticle vaccine GBP510 adjuvanted with AS03 versus ChAdOx1-S. Interim analysis found that two-dose vaccination with GBP510/AS03 induced stronger neutralising antibody immune responses compared with ChAdOx1-S against the ancestral D614G strain at 2 weeks after the second dose. GBP510/AS03 had an acceptable safety profile during a median 2.5 months of follow-up.Implications of the available evidenceThis interim analysis suggests that GBP510/AS03 induces strong neutralising antibody responses against SARS-CoV-2 ancestral strain and has an acceptable safety profile.

Metastasis of ductal carcinoma of the breast to the thyroid gland is uncommon and usually detected at autopsy. The incidences of metastases to the thyroid have been reported at 3%, and the most common primary malignancy is renal cell carcinoma. We report a rare case of intrathyroid metastatsis of breast ductal carcinoma in a patient who was treated for breast cancer 15 years earlier.

Background: Pneumococcal diseases among children aged 0.35 μg/mL was lower for some serotypes in the GBP411 group than in the comparator group (6B: 20.83% vs. 39.22%, P=0.047 and 19A: 58.33% vs. 90.20%, P97% of the subjects in each group achieved IgG concentrations of ≥0.35 μg/mL for all 12 serotypes. Increased immunogenicity was observed for some serotypes that showed significant intergroup differences after administration of the primary doses but not after the booster dose. We also found no significant intergroup difference in the overall incidence of solicited local adverse events. Furthermore, the overall incidence of solicited systemic adverse events was significantly lower in the GBP411 group than in the comparator vaccine group (79.59% vs. 98.04%; P=0.003).Conclusion: The GBP411 vaccine with a dosing schedule of 2p+1 may be immunogenic and safe for healthy infants.

Highlights • Vi-DT is safe and well tolerated in infants and toddlers aged 6–23 months. • Vi-DT showed >1000-fold higher Geometric Mean Titer (GMT) compared to Placebo. • 100% seroconversion reported in Vi-DT group in all age strata., Background Typhoid fever remains an important public health problem in developing countries and is endemic in many parts of Asia and Africa where the incidence of disease typically peaks in school-aged children. Age restrictions and other limitations of existing oral live-attenuated typhoid and parenteral Vi polysaccharide vaccines have triggered the development of Vi conjugate vaccines with improved immunological properties, use in younger age range, and longer durability of protection. We present the safety, reactogenicity, and immunogenicity data from a Phase II study after a single dose of Vi polysaccharide conjugated to diphtheria toxoid (Vi-DT) conducted in 6–23-month old Filipino children. Methods This is a randomized, observer-blinded Phase II study to assess the immunogenicity, safety and reactogenicity of Vi-DT compared to placebo, conducted in Muntinlupa City, The Philippines. Participants aged 6–23 months were enrolled and randomized to Vi-DT (25 µg) or placebo (0.9% sodium chloride) and evaluated for immunogenicity and overall safety 28 days post vaccination. Results A total of 285 participants were enrolled and age-stratified: 6 to < 9 months, 9–12 months, and 13–23 months. Seventy-six (76) participants received Vi-DT and 19 received placebo per each strata. All participants seroconverted after a single dose of Vi-DT versus 7% of placebo recipients. Anti-Vi IgG GMT was 444.38 [95% CI (400.28; 493.34)] after a single dose of Vi-DT; there was no change in GMT after placebo administration, 0.41 [95% CI (0.33; 0.51), p

SUMMARYBackgroundVaccination has helped to mitigate the COVID-19 pandemic. Ten traditional and novel vaccines have been listed by the World Health Organization for emergency use. Additional alternative approaches may better address ongoing vaccination globally, where there remains an inequity in vaccine distribution. GBP510 is a recombinant protein vaccine, which consists of self-assembling, two-component nanoparticles displaying the receptor-binding domain (RBD) in a highly immunogenic array.MethodsWe conducted a randomized, placebo-controlled, observer-blinded, phase 1/2 trial to evaluate the safety and immunogenicity of GBP510 (2-doses at a 28-day interval) adjuvanted with or without AS03 in adults aged 19–85 years. The main outcomes included solicited and unsolicited adverse events; anti-SARS-CoV-2 RBD IgG antibody and neutralizing antibody responses; T-cell immune responses.FindingsOf 328 participants who underwent randomization, 327 participants received at least 1 dose of vaccine. Each received either 10 μg GBP510 adjuvanted with AS03 (n = 101), 10 μg unadjuvanted GBP510 (n = 10), 25 μg GBP510 adjuvanted with AS03 (n = 104), 25 μg unadjuvanted GBP510 (n = 51), or placebo (n = 61). Most solicited adverse events were mild-to-moderate in severity and transient. Higher reactogenicity was observed in the GBP510 adjuvanted with AS03 groups compared to the non-adjuvanted and placebo groups. Reactogenicity was higher post-dose 2 compared to post-dose 1, particularly for systemic adverse events. The geometric mean concentrations of anti-SARS-CoV-2-RBD IgG antibody reached 2163.6/2599.2 BAU/mL in GBP510 adjuvanted with AS03 recipients (10 μg/25 μg) by 14 days after the second dose. Two-dose vaccination with 10 μg or 25 μg GBP510 adjuvanted with AS03 induced high titers of neutralizing antibody via pseudovirus (1369.0/1431.5 IU/mL) and wild-type virus (949.8/861.0 IU/mL) assays.InterpretationGBP510 adjuvanted with AS03 was well tolerated and highly immunogenic. These results support further development of the vaccine candidate, which is currently being evaluated in Phase 3.FundingCoalition for Epidemic Preparedness InnovationsRESEARCH IN CONTEXTEvidence before this studyWe searched PubMed for research articles published by December 31, 2021, using the terms “COVID-19” or “SARS-CoV-2,” “vaccine,” and “clinical trial.” In previously reported randomized clinical trials, we found that mRNA vaccines were more immunogenic than adenovirus-vectored vaccines. Solicited adverse events were more frequent and more severe in intensity after the first dose compared to the second dose for adenovirus-vectored vaccines, whereas they increased after the second dose of mRNA or recombinant spike-protein nanoparticle vaccines.Added value of this studyThis is the first human study evaluating the immunogenicity and safety of recombinant SARS-CoV-2 protein nanoparticle with and without adjuvant AS03, designed to elicit functional cross-protective responses via receptor-binding domain (RBD). Both 10 and 25 μg of GBP510 with AS03 formulations were well tolerated with an acceptable safety profile. Potent humoral immune responses against the SARS-CoV-2 RBD were induced and peaked by day 42 (14 days after the second dose). In addition, GBP510 adjuvanted with AS03 elicited a noticeable Th1 response, with production of IFN-γ, TNF-α, and IL-2. IL-4 was inconsistent and IL-5 nearly inexistent response across all groups.Implications of the available evidenceThe results from this phase 1/2 trial indicate that GBP510 adjuvanted with AS03 has an acceptable safety profile with no vaccine-related serious adverse events. Two-dose immunization with GBP510 adjuvanted with AS03 induced potent humoral and cellular immune responses against SARS-CoV-2.

Typhoid fever is a common disease in developing countries especially in the Indian subcontinent and Africa. The available typhoid conjugate vaccines (TCV) have been found to be highly immunogenic in infants and children less than 2 years of age. Many countries are planning to adopt TCV in their routine EPI programs around 9 months of age when measles containing vaccines are given. Therefore, Vi-DT TCV was tested in 9-15 months aged healthy infants in Nepal to demonstrate non-interference with a measles containing vaccine.This was a randomized, open label, phase III study to assess the immune non-interference, safety, and reactogenicity of Vi-DT typhoid conjugate vaccine when given concomitantly with measles, mumps and rubella (MMR) vaccine. A total of 360 participants aged 9-15 months were enrolled and randomized equally into Vi-DT + MMR (180 participants) or MMR alone (180 participants) group and were evaluated for immunogenicity and safety 28 days post vaccination.Using the immunogenicity set, difference between proportions (95% CI) of the Vi-DT + MMR group vs MMR alone group were -2.73% (-8.85, 3.38), -3.19% (-11.25, 4.88) and 2.91% (-3.36, 9.18) for sero-positivity rate of anti-measles, anti-mumps and anti- rubella, respectively. Only the lower bound of the range in difference of the proportions for sero-positivity rate of anti-mumps did not satisfy the non-inferiority criteria as it was above the -10% limit, which may not be of clinical significance. These results were confirmed in the per protocol set. There were no safety concerns reported from the study and both Vi-DT + MMR and MMR alone groups were comparable in terms of solicited and unsolicited adverse events .Results indicated that there is non-interference of MMR vaccine with Vi-DT and Vi-DT conjugate vaccine could be considered as an addition to the EPI schedule among children at risk of contracting typhoid.

Background To evaluate the imaging features, clinical manifestations, and prognosis of patients with thyroid nodule rupture after radiofrequency ablation (RFA). Methods The records of 12 patients who experienced thyroid nodule rupture after RFA at four Korean thyroid centers between March 2010 and July 2017 were retrospectively reviewed. Clinical data evaluated included baseline patient characteristics, treatment methods, initial presenting symptoms, imaging features, treatment, and prognosis. Results The most common symptoms of post-RFA nodule rupture were sudden neck bulging and pain. Based on imaging features, the localization of nodule rupture was classified into three types: anterior, posterolateral, and medial types. The anterior type is the most often, followed by posterolateral and medial type. Eight patients recovered completely after conservative treatment. Four patients who did not improve with conservative management required invasive procedures, including incision and drainage or aspiration. Conclusion Thyroid nodule rupture after RFA can be classified into three types based on its localization: anterior, posterolateral, and medial types. Because majority of thyroid nodule ruptures after RFA can be managed conservatively, familiarity with these imaging features is essential in avoiding unnecessary imaging workup or invasive procedures.

Phase 3, randomized, controlled, multicenter, equivalence trial.Recruitment of participants occurred between 04Februray2020 and 15July2020 at four centers in the Philippines: University of the East - Ramon Magsaysay Memorial Medical Center Inc., Quezon City; University of Philippines Manila - National Institute of Health, Ermita Manila; Asian Hospital and Medical Center, Metro Manila, Philippines Study; and Medical Research Unit, Tropical Disease Foundation, Makati City, Metro Manila, Philippines.1800 adults and children 6-months to 45-years of age.Participants received a single injection of multidose (MD) or single dose (SD) Vi-DT as test vaccines or meningococcal conjugate vaccine as a comparator.To evaluate immune equivalence of SD and MD formulations of Vi-DT, and to assess the safety of both formulations compared with comparator vaccine.Blood draw for immunogenicity was performed at baseline prior to vaccine receipt and at four weeks after vaccination for a subset of participants to determine anti-Vi IgG geometric mean titers (GMT) and seroconversion rates. The primary outcome was comparison of anti Vi-IgG seroconversion and GMT between the two formulations of Vi-DT at 4 weeks following vaccine administration. Immune equivalence of MD and SD formulations was confirmed when the two-tailed 95% confidence interval (CI) of the GMT ratio is within [0.67, 1.5] at a two-sided significance level of 0.05. All participants were followed for safety events for six months after vaccine administration.Participants were randomized to receive SD Vi-DT, MD Vi-DT, or meningococcal conjugate vaccines in 2.5:2.5:1 allocation ratio.Study participants and observers were blinded to treatment assignment.Immune equivalence of SD (n=252) and MD (n=247) formulations was confirmed by anti-Vi IgG GMT ratio of 1.14 (95%CI: 0.91, 1.43) with respective GMTs in the MD and SD groups of 640.62 IU/mL (95%CI: 546.39, 751.11) and 562.57 IU/mL (95%CI: 478.80, 661.00) (The MD and SD formulations of Vi-DT elicited robust and equivalent immune responses following one dose vaccination, and both formulations demonstrated a favorable safety profile.ClinicalTrials.gov: NCT04204096.This study was funded by the BillMelinda Gates Foundation (OPP 1115556).

Background: Typhoid causes significant mortality among young children in resource-limited settings. Conjugate typhoid vaccines could significantly reduce typhoid-related child deaths, but only one WHO-prequalified typhoid conjugate vaccine exists for young children. To address this gap, we investigated the safety, immunogenicity and dose-scheduling of Vi-DT typhoid conjugate vaccine among children aged 6-23 months. Methods: In this single center, observer blind, phase II trial, participants were randomly assigned (2:2:1) to receive one or two doses of Vi-DT or comparator vaccine. Anti-Vi IgG titer and geometric mean titers (GMT) were determined at 0, 4, 24 and 28 weeks. Data were analyzed using per-protocol and immunogenicity (a subset of intention-to-treat analysis) sets. The trial is registered with ClinicalTrials.gov (NCT03527355). Findings: Between April and July 2018, 285 children were randomized; 114 received one or two doses of Vi-DT while 57 received comparator. 277 completed the study follow-up per protocol; 112 and 110 from single- and two-dose Vi-DT schedules, respectively and 55 from the placebo group were included in the per protocol analysis. Safety profile is satisfactory. Thirteen serious adverse events were reported during the 28-week follow-up, none of which were related to Vi-DT. The seroconversion rate four weeks after the first dose was 100% (95% CI 98·3-100) in Vi-DT recipients and 7·0% (95% CI 2·8-16·7) in comparator recipients (p

To compare the diagnostic performance of ultrasonography (US) and computed tomography (CT) for diagnosing incidentally detected diffuse thyroid disease (DTD) in patients who underwent thyroid surgery using multicenter data. Between July and December 2016, a total of 177 patients who underwent preoperative thyroid US and neck CT, and subsequent thyroid surgery at 4 participating institutions, were reviewed. US and CT images in each case were retrospectively reviewed by a radiologist at each institution, and classified into one of the following four categories based on US and CT features: no DTD; indeterminate; suspicious for DTD; and DTD. The diagnostic accuracy of US and CT were calculated at each institution by comparison with histopathological results. Respective US and CT classifications in the 177 patients were no DTD in 75 and 71, indeterminate in 46 and 34, suspicious for DTD in 28 and 31, and DTD in 28 and 41. Among the histopathological results, 113 patients had normal thyroid parenchyma, 23 had Hashimoto thyroiditis, 36 had non-Hashimoto lymphocytic thyroiditis, and 5 had diffuse hyperplasia. The presence of ≥ 2 US and CT features of DTD, which was classified as suspicious for DTD or DTD, had the largest area under the receiver operating characteristic curve (0.866 and 0.893, respectively), with sensitivity and specificity of 71.9 and 91.2% in US, and 84.4 and 84.1% in CT, respectively. However, there was no statistically significant difference between readers’ experience and their diagnostic performance. US and CT imaging may be helpful for detecting incidental DTD.

This study aimed to compare diagnostic accuracy of real-time and static ultrasonography (US) for differentiating diffuse thyroid disease (DTD) from normal thyroid parenchyma (NTP). At 4 participating institutions, 203 patients underwent real-time thyroid US before thyroid surgery. For static US, the same radiologists retrospectively evaluated US findings on a picture archive and communication system after 4 weeks. In real-time and static US diagnoses, US category included no DTD, indeterminate, suspicious for DTD, and DTD. We investigated the diagnostic accuracy of real-time and static US with a receiver operating characteristic curve analysis using histopathologic results as the reference standard. Histopathologic results exhibited NTP (n = 139), Hashimoto thyroiditis (n = 24), non-Hashimoto lymphocytic thyroiditis (n = 33), and diffuse hyperplasia (n = 7). Of 203 patients, there were significant differences in echogenicity, echotexture, glandular margin, and vascularity of the thyroid gland and US category between NTP and DTD groups in both real-time and static US diagnoses (P < 0.001). The diagnostic indices of real-time and static US were highest when the cutoff criterion was chosen as 1 or more abnormal US features. In addition, US category was the only feature with a significant difference between DTD and NTP groups regardless of the practical experience. The receiver operating characteristic curve analysis showed that real-time US was superior to static US in the diagnostic accuracy; however, there was no significant difference (P = 0.09). In conclusion, real-time and static US can be helpful for detecting incidental DTD by using US classification based on abnormal US features.

The purpose of this multicenter study was to assess the diagnostic accuracy of real-time sonography (US) for differentiating diffuse thyroid disease (DTD) from normal thyroid parenchyma among radiologists blinded to patients' clinical, serologic, and imaging history and to determine the differences in diagnostic accuracy among radiologists from different institutions.From January to March 2017, 214 patients underwent preoperative thyroid US and subsequent thyroid surgery at four participating institutions. Real-time US was performed at each institution by an attending radiologist, who classified US diagnoses into one of the following four categories based on US findings: no DTD, indeterminate, suspicious for DTD, and DTD. The outcomes of US diagnoses were compared with histopathologic results to determine the diagnostic accuracy of real-time US at each institution.Histopathologic results included normal thyroid parenchyma (n = 143), Hashimoto thyroiditis (n = 29), non-Hashimoto lymphocytic thyroiditis (n = 37), and diffuse hyperplasia (n = 5). Normal thyroid parenchyma and DTD exhibited statistically significant differences in echogenicity, echotexture, size, glandular margin, vascularity of thyroid, and US classification. There was positive correlation between US classification and histopathologic results at all institutions for detecting DTD. The highest diagnostic indexes were obtained when the cutoff criterion was suspicious for DTD. There was favorable diagnostic accuracy, with statistically significant differences, at all institutions for the diagnosis of DTD.Real-time US can be helpful for differentiating DTD from normal thyroid parenchyma.

Typhoid fever remains a major public health problem in low- and middle-income countries where children aged 2-14 years bear the greatest burden. Vi polysaccharide is poorly immunogenic in children2 years of age, and protection in adults is modest. The limitations of Vi polysaccharide vaccines can be overcome by conjugation of the Vi to a carrier protein. A typhoid conjugate vaccine composed of Vi polysaccharide conjugated to diphtheria toxoid (Vi-DT) has been developed. The Phase I study results are presented here.This was a randomized, observer-blinded Phase I study to assess the safety and immunogenicity of Vi-DT compared to Vi polysaccharide vaccine, conducted in Manila, Philippines. Participants enrolled in an age de-escalation manner (18-45, 6-17 and 2-5 years) were randomized between Test (Vi-DT, 25 µg) administered at 0 and 4 weeks and Comparator (Vi polysaccharide, Typhim Vi® and Vaxigrip®, Sanofi Pasteur) vaccines.A total of 144 participants were enrolled (48 by age strata, 24 in Test and Comparator groups each). No serious adverse event was reported in either group. Solicited and unsolicited adverse events were mild or moderate in both groups with the exception of a 4-year old girl in Test group with grade 3 fever which resolved without sequelae. All participants in Test group seroconverted after first and second doses of Vi-DT while the proportions in the Comparator group were 97.1% and 97.2%, after first dose of Typhim Vi® and second dose of Vaxigrip®, respectively. Vi-DT showed 4-fold higher Geometric Mean Titers (GMT) compared to Typhim Vi® (adjusted for age strata, p 0.001). No further increase of GMT was detected after the second dose of Vi-DT. Anti-DT IgG seroresponse rates were 81.2% and 84.5% post first and second Vi-DT doses, respectively.Vi-DT vaccine was safe, well-tolerated and immunogenic in participants aged 2-45 years. ClinicalTrials.gov registration number: NCT02645032.

Purpose No previous study using follow-up ultrasonography for evaluating the factors associated with the successful regression of congenital muscular torticollis in young infants has been published. This study aimed to assess clinical factors and sonographic features potentially influencing regression in patients with congenital muscular torticollis. Methods From January 2010 to December 2012, 80 infants underwent neck ultrasonography because of clinical suspicion of congenital muscular torticollis. We statistically analysed the correlation between complete resolution and clinicosonographic findings when complete resolution was defined as no visible lesion on follow-up ultrasonography. Results Of the 80 infants, 61 had congenital muscular torticollis and all were followed up by ultrasonography: 1) 34 underwent physiotherapy, and 27 of them (79.4%) revealed complete resolution in follow-up; 2) 27 did not undergo physiotherapy, and 15 of them (55.6%) showed complete resolution. A statistically significant correlation was found between physiotherapy and complete resolution, but not between complete resolution and patient sex; size, volume, and echogenicity of the lesion; and thickness ratio. Conclusions Physiotherapy was the only factor influencing complete resolution in young infants with congenital muscular torticollis.

Background As there is increased concern over the radiation exposure particularly in adolescents and young adults, computed tomography (CT) dose reduction is needed in the diagnosis of acute appendicitis. Purpose To evaluate the optimal strength of sinogram affirmed iterative reconstruction (SAFIRE) to obtain the best image quality on a 30-mAs applied low-dose CT (LDCT30mAs) and to compare the diagnostic performances of the LDCT30mAs with different SAFIRE strengths with that of the 100-mAs applied LDCT (LDCT100mAs) for the diagnosis of acute appendicitis. Material and Methods A total of 102 consecutive patients (47 men, 55 women; mean age, 41.2 years; range, 15–82 years) with right lower quadrant pain underwent abdominal-pelvic CT, consisting of arterial phase LDCT100mAs and portal venous phase LDCT30mAs under a fixed 120 kV. LDCT30mAs images were reconstructed separately with five strength levels (S1–S5). Two blinded radiologists recorded scores for the subjective image quality of the LDCT30mAs dataset (S0–S5) and confidence scores for the diagnosis of acute appendicitis on each dataset and LDCT100mAs. CT image noise was measured for each set. Results The study population consisted of 58 patients with confirmed appendicitis and 44 without appendicitis. There was no significant difference in diagnostic performance between LDCT100mAs and LDCT30mAs with any strength for both readers (AUC for reader 1, LDCT30mAs with S0–S5 = 0.97, LDCT100mAs = 0.93, P = 0.0936; for reader 2, LDCT30mAs with S0–S5 = 0.96, LDCT100mAs = 0.97, P = 0.128). The measured noise decreased as the strength increased from S0 to S5 (mean, 20.8 > 17.7 > 15.6 > 13.5 > 11.5 > 9.5, P S4 > S5, P Conclusion Although measured noise declined as SAFIRE strength increased, S3 seems optimal for the best subjective image quality on LDCT30mAs. The diagnostic performance of LDCT30mAs with any strength is comparable to that of LDCT100mAs for the diagnosis of acute appendicitis.

Meningiomas arising outside the intracranial compartment are known as extradural meningiomas. Extradural meningiomas are rare conditions, accounting for less than 2% of all meningiomas. Primary intraosseous meningioma is used to describe a subset of extradural meningiomas arising from bone. A 46-year-old woman presented with left exophthalmos. Computed tomography and magnetic resonance images revealed an expansile bony lesion in the orbital lateral wall of the left sphenoid bone. The patient underwent craniotomy for excision of the bony lesion. Pathologic examination revealed an intraosseous meningioma.

The effect of ultrasonography (US)-guided fine-needle aspiration (US-FNA) for the collapse of benign cystic thyroid nodules is still unclear. This study aimed to assess the positive response rate following US-FNA of the cystic component of thyroid cysts and of partially cystic thyroid nodules (PCTNs), and to evaluate the factors influencing the outcome.From June to December 2013, seven radiologists at seven institutions prospectively performed US-FNA on 320 cystic thyroid nodules in 320 patients. Among them, 179 underwent at least one follow-up US examination following US-FNA of the cystic component at each institution by the same radiologist. A variety of factors, including US features of cystic thyroid nodules, the characteristics of the aspirates, and the follow-up US findings, were analyzed.Of 179 cystic thyroid nodules, there were 53 thyroid cysts and 126 PCTNs. Of 179 cystic thyroid nodules, no malignancies were detected. On follow-up US, the mean size reduction rate of the cystic component was 31.9%, and 102 out of 179 thyroid nodules (57.0%) were assigned to the response group. On univariate analysis, the degree of aspiration and time interval between US-FNA and the final follow-up US showed the significant differences between the response and no response groups. On multivariate analysis, the only factor that influenced the outcome was the nodule type. The cystic component's positive response rate after simple aspiration was higher in the thyroid cysts than in the PCTNs.US-FNA may be effective at collapsing the cystic components of benign thyroid cysts and PCTNs.

Objectives The purpose of this study was to evaluate characteristic features of juvenile fibroadenoma of the breast on sonography. Methods Our study included 34 juvenile fibroadenomas confirmed by surgical biopsy or sonographically guided 8-gauge vacuum-assisted biopsy in 23 patients (age range, 15-47 years; mean age, 25 years). Sonographic findings of the lesions were analyzed retrospectively by 2 radiologists in consensus according to the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) lexicon. The BI-RADS final assessment category was also established. Results On sonography, all fibroadenomas presented as masses. The mean size was 30 mm. Regarding shape, there were 29 oval, 2 round, and 3 irregular masses. The margins were circumscribed in 24, indistinct in 5, microlobulated in 4, and angular in 1. Regarding echogenicity, 16 masses were hypoechoic, 16 isoechoic, and 2 complex echoic. Posterior acoustic characteristics included posterior acoustic enhancement in 22 masses (65%), posterior shadowing in 1, and no posterior acoustic features in 9; this information was not available in 2. The lesion boundary presented as an abrupt interface in 32 and an echogenic halo in 2. The orientation was parallel in 32 and nonparallel in 2. Calcifications were present in 3 cases and absent in 31. On color Doppler sonography, the masses were usually hypervascular with vessel counts of 5 or more (87%). The BI-RADS final assessment categories were 3 in 24 and 4a in 10. Conclusions The dominant sonographic presentation of juvenile fibroadenoma is a circumscribed oval hypoechoic or isoechoic mass, which resembles that of simple fibroadenoma. Juvenile fibroadenomas frequently show posterior acoustic enhancement and hypervascularity on color Doppler sonography.

This study aimed to assess the diagnostic accuracy of pre-operative ultrasound (US) and computed tomography (CT) for detecting thyroid pyramidal lobe (TPL). A single radiologist prospectively performed thyroid US and retrospectively reviewed neck CT to detect TPLs in 135 consecutive patients scheduled for thyroid surgery. The location, size and superior extent of each TPL and its separation or continuity with the main thyroid gland were assessed by thyroid US, neck CT and surgery. The prevalence of TPLs as diagnosed by thyroid US, neck CT and surgery was 58.5% (79/135), 56.3% (76/135) and 60% (81/135), respectively. We compared US and CT detection of TPLs with surgical data to determine their sensitivity (85.2% and 91.4%), specificity (81.5% and 94.4%), positive (87.3% and 96.1%) and negative (78.6% and 87.9%) predictive values and accuracy (83.7% and 92.6%). For detecting TPLs, both neck CT and thyroid US have good diagnostic value, although neck CT is more accurate than thyroid US.

No study has so far investigated the relationship between aspirate color or degree of aspiration on the success of ethanol ablation (EA) of cystic thyroid nodules. We aimed to evaluate the efficacy of EA of benign cystic thyroid nodules and assess the relevant factors influencing the outcome. Over a 2-year period, 64 benign cystic thyroid nodules in 62 patients were treated with EA. Several factors related to EA efficacy were evaluated, including the cystic component volume, volume and color of aspirates, degree of aspiration, and volume of injected ethanol. In all cases, we performed ultrasound follow-up for at least 12 months after the last EA session to evaluate the collapsed cystic component. The 64 treated nodules had aspirate colors that were red bloody (n = 3), dark bloody (n = 31), brownish (n = 15), greenish-yellow (n = 13), and colorless (n = 2). The degrees of aspiration were scant (n = 8), mild (n = 3), moderate (n = 8), and complete (n = 45). There was successful collapse of the cystic component after initial EA in 52 cases, but a repeat EA was employed in 12 failed cases. Statistical analysis showed that the degree of aspiration and color of aspirates correlated significantly with the success of EA. The results of this study suggest that complete aspiration of cystic contents was the most important factor in the efficacy of EA of benign cystic thyroid nodules, and greenish-yellow contents were closely related to scant or mild aspiration.

Understanding the computed tomography (CT) characteristics of the pyramidal lobe and other thyroid variations and detecting them accurately using preoperative neck CT will minimize unnecessary remnant thyroid tissue after total thyroidectomy in patients with thyroid cancer. The purpose of the present study was to assess the frequency, location, and size of the pyramidal lobe and other thyroid variations using a large-scaled, multicenter study.Neck CT scans for 200 patients were selected from 11 institutions; a total of 2200 patients were included in the study. The patients underwent neck CT for the following reasons: trauma, known thyroid malignancy, cervical lymphadenopathy, palpable neck mass, oropharyngolaryngeal malignancy, vocal cord palsy, postchemotherapy CT follow-up, inflammatory or infectious neck lesion, parathyroid abnormality, and patient request. A single radiologist at each institution retrospectively analyzed 200 neck CT scans. Each radiologist investigated the presence, location, length, volume, and upper end of the pyramidal lobe and its separation or continuity with the main thyroid gland as well as the presence, location, length, and volume of the accessory or ectopic thyroid using a picture archiving and communication system.A pyramidal lobe was present in 44.6% (981/2200) of the patients. The prevalence for the pyramidal lobe at the participating institutions ranged from 28.0% to 55.0% (mean, 44.6%). Pyramidal lobes originating from the left side of the thyroid were most common, and the number of pyramidal lobes showing separation from the main thyroid gland was 90 (9.2%). The mean anteroposterior diameter, transverse diameter, and length of the pyramidal lobe were 2.3, 5.9, and 20.8 mm, respectively. Among both men and women, the most common level of the upper end of the pyramidal lobes was the thyroid cartilage, but there was a significant difference in the frequency of the pyramidal lobe between males and females (p0.0001). The rate of the pyramidal lobe detection in the 2-mm-slice-thickness group was higher than those in the 2.5- and 3-mm groups (p=0.0003).Neck CT is useful for detecting the presence, size, configuration, and location of the pyramidal lobe and other thyroid variations.

Objective: We aimed to assess the adequacy and efficacy of ultrasound (US)-guided fine-needle aspiration (US-FNA) for small solid thyroid nodules (SSTNs) with the largest diameter Study Design: Among 656 SSTNs in 569 patients, each SSTN was classified into 1 of 4 groups according to the largest diameter: 1 mm ≤ group A < 2 mm; 2 mm ≤ group B < 3 mm; 3 mm ≤ group C < 4 mm, and 4 mm ≤ group D < 5 mm. We compared the adequacy and efficacy of US-FNA between these groups using histopathologic results as a reference standard. Results: 571 (87.0%) SSTNs were adequately sampled by US-FNA and 200 of these were histopathologically confirmed. The adequacy of US-FNA for SSTNs varied according to the nodule diameter: the smaller the nodule diameter, the lower the diagnostic adequacy. The diagnostic efficacy of US-FNA for SSTNs showed a significant relationship with nodule size: diagnostic efficacy in groups A and B was lower than in groups C and D. Conclusions: The adequacy of US-FNA for SSTNs tended to decrease with decreased nodule size, and diagnostic efficacy of US-FNA for SSTNs with the largest diameter

Objective. The purpose of this study was to differentiate between high-grade and non-high-grade ductal carcinoma in situ (DCIS) of the breast on sonography. Methods. From October 2003 to August 2009, 76 DCIS lesions in 73 women who underwent sonography and mammography were included in this study. Lesions were confirmed by mastectomy, breast-conserving surgery, or surgical biopsy. Images were analyzed by 2 radiologists with consensus and were correlated with histologic grades. Results. Of the 76 lesions, 44 were classified as high--grade and 32 as non-high-grade DCIS. Fifty-seven lesions (75.0%) were identified on sonography, which revealed a mass in 30 cases, microcalcifications in 20, ductal changes in 4, and architectural distortion in 3. All cases with false-negative findings on sonography (n = 19) showed microcalcifications on mammography On sonography, masses were more frequently found in non-high-grade (62.5%) than high-grade DCIS (22.7%; P < .01). No significant difference was seen in the sonographic features of masses between high-grade and non-high-grade DCIS. Microcalcifications were more common in high-grade (43.2%) than non-high-grade (3.1 %) DCIS (P= .02). Most sonographically visible microcalcifications had associated findings such as ductal changes (n = 11), a mass (n = 7), or a hypoechoic area (n = 5). The detection rate of microcalcifications on sonography was higher in high-grade (62.9%) than non-high-grade DCIS (25.0%; P=.023). Conclusions. Microcalcifications with associated ductal changes (11 of 31 [35.5%]) were the most common sonographic findings in high-grade DCIS. An irregular hypoechoic mass with an indistinct and microlobulated margin (13 of 26 [50.0%]) was the most frequent finding in non-high-grade DCIS.

We report a case of mastitis showing bizarre calcifications in a systemic lupus erythematosus (SLE) patient. A 34-year-old woman had suffered from SLE for 12 years. Initial mammogram showed global asymmetry and extensive linear branching casting calcifications with ductal distribution in the left breast; the image had the appearance of a ductogram. Sonogram showed multiple calcifications without formation of a mass in the left breast. At 5-year follow-up, mammogram revealed large, coarsely conglomerated calcifications in the left breast. The clinical and radiological diagnosis of lupus mastitis was made.

Fibromatosis refers to an extra-abdominal desmoid tumor or aggressive fibromatosis. Breast fibromatosis can develop in association with the capsule around a breast implant, although reports of cases of fibromatosis associated with breast implants are rare. As the demand for breast augmentation has increased, it is important to understand the diseases associated with breast implants. In the present report, we describe a case of breast fibromatosis that developed adjacent to a breast implant and demonstrated a relatively well-defined border even though it invaded the surrounding structures. We also explore the specific imaging features for diagnosing breast fibromatosis in association with implants by reviewing previous literature.

We aimed to assess the validity of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system in patients with papillary thyroid carcinoma (PTC) by evaluating the relationships between clinicopathologic factors and TNM stage using histopathological specimens and electronic medical records. We enrolled 733 consecutive patients who had undergone thyroid surgery for PTC between 2010 and 2013. Clinical data were obtained from electronic medical records. TNM stages, multifocality, and bilaterality were analyzed after review of histopathological specimens by applying the AJCC TNM staging system. Multiple statistical analyses were performed to evaluate the correlation between the AJCC TNM staging system and the clinicopathologic factors. Of the 733 patients, there were T stage including T1a (46.9 %, 344/733), T1b (12.6 %, 92/733), T2 (2.0 %, 15/733), T3 (38.1 %, 279/733), T4a (0.4 %, 3/733), and T4b (0 %, 0/733), N stage including N0 (58.9 %, 432/733), N1a (24.3 %, 178/733), and N1b (16.8 %, 123/733), and multiplicity including multifocality (31.1 %, 228/733) and bilaterality (23.7 %, 174/733). There was a significant association between the PTC primary tumor size and T stage, N stage, multifocality, and bilaterality (p < 0.0001). Multifocality, bilaterality, and the presence of nodal metastasis were most frequently seen in patients with T3 stage (p < 0.0001). In multivariate logistic regression analyses, T and N stages were independent predictors of multiple PTCs. The PTC primary tumor size had a significant association with the T and N stages of the AJCC TNM staging system, and these factors were independent predictors of multifocality and bilaterality.

Objective To compare the diagnostic performance of adaptive statistical iterative reconstruction applied low-dose computed tomography (CT) (LDCT) with that of the standard-dose CT (SDCT) for local recurrence in patients with stomach cancer. Methods Seventy-nine consecutive patients who had undergone surgical resection for stomach cancer were enrolled. To monitor recurrence, SDCT (120 kilovolt peak [kVp], 200mAs) had been performed. The LDCT (120 kVp, 100 mA s) was taken, and images were reconstructed with 4 levels of adaptive statistical iterative reconstruction (ASIR) blending (0%, 30%, 50%, and 70%). Two blinded radiologists recorded the diagnostic confidence scores for local recurrence in each data set using a 5-point scale. Endoscopic biopsy results served as the reference standard. Receiver operating characteristic (ROC) curve analysis was used to calculate the diagnostic performance. Results The diagnostic performance of LDCT with variable ASIR blending ratios was comparable to that of SDCT (area under ROC curve, 0.727-0.734, 0.687, respectively, P > 0.05). Conclusions The diagnostic performance of ASIR applied LDCT is comparable to that of SDCT.

Growth hormone and insulin are the primary determinants for cytochrome P450 2E1 (CYP2E1) expression. The role of glucose on the induction of CYP2E1 by hypophysectomy and on the restorative effect by growth hormone was investigated in the rat liver. Western and Northern blot analyses revealed that hypophysectomy induced CYP2E1 by 5-fold at 1–4 weeks, relative to control, with a concomitant increase in CYP2E1 mRNA. Hypophysectomized rats (HXR) showed a 20% reduction in the plasma glucose level. Hypophysectomy-induced increase in the CYP2E1 mRNA was completely abolished by glucose feeding in drinking water (10%) for 7 days. Treatment of HXR with hGH (2 I.U./kg, twice a day, for 7 days) inhibited the increases in CYP2E1 protein and mRNA levels with restoration of the plasma glucose level. In contrast to the effect of human growth hormone (hGH) on CYP2E1 in HXR with free access to foods, CYP2E1 expression failed to be restored by hGH in starving HXR. However, glucose feeding of starving HXR abolished the induction of CYP2E1. Effects of hypophysectomy and hGH treatment were studied in streptozotocin-induced diabetic rats. Insulin, but not hGH, prevented an increase in CYP2E1 mRNA in diabetic rats. The hepatic CYP2E1 induction in hypophysectomized diabetic rats was inhibited by hGH treatment, indicating that the hGH effect on CYP2E1 expression did not involve insulin production. These results provide evidence that the induction of hepatic CYP2E1 by hypophysectomy may result from reduced glucose utilization, and that the effect of hGH on CYP2E1 expression may be mediated with enhanced glucose utilization, but not with insulin production.

Milk of calcium located in the breast is typically a benign entity. However, carcinoma may incidentally arise adjacent to or even within milk of calcium. Consequently, the characteristics of all observed calcific particles should be carefully analyzed. In this study, we report a case of carcinoma presented as malignant microcalcifications mixed within milk of calcium in a breast.

Core needle biopsy (CNB) has been suggested as a complementary diagnostic method to fine-needle aspiration in patients with thyroid nodules. Many recent CNB studies have suggested a more advanced role for CNB, but there are still no guidelines on its use. Therefore, the Task Force Committee of the Korean Society of Thyroid Radiology has developed the present consensus statement and recommendations for the role of CNB in the diagnosis of thyroid nodules. These recommendations are based on evidence from the current literature and expert consensus.

Background: There has been no study to compare the diagnostic accuracy of an experienced radiologist with a trainee in nasal bone fracture. Objectives: To compare the diagnostic accuracy between conventional radiography and computed tomography (CT) for the identification of nasal bone fractures and to evaluate the interobserver reliability between a staff radiologist and a trainee. Patients and Methods: A total of 108 patients who underwent conventional radiography and CT after acute nasal trauma were included in this retrospective study. Two readers, a staff radiologist and a second-year resident, independently assessed the results of the imaging studies. Results: Of the 108 patients, the presence of a nasal bone fracture was confirmed in 88 (81.5%) patients. The number of non-depressed fractures was higher than the number of depressed fractures. In nine (10.2%) patients, nasal bone fractures were only identified on conventional radiography, including three depressed and six non-depressed fractures. CT was more accurate as compared to conventional radiography for the identification of nasal bone fractures as determined by both readers (P

The aim of this study was to assess the adequacy and efficacy of ultrasonography (US)-guided fine-needle aspiration cytology (US-FNAC) with one-sampling technique (only one specimen through a single needle pass was obtained during the procedure on each thyroid nodule in each study patient) for the cytological diagnosis of thyroid nodules. In this study, US-FNAC techniques, including "free two-hand," "mixed sampling," "flipping-extraction," and "single-needle-pass" procedures were used to collect thyroid cells from July 2007 to June 2009. The cytopathology results and patients' complications were reviewed retrospectively. Of the 1456 thyroid-nodule samples obtained from 977 patients (1.49 per patient), the incidence of adequate and inadequate samplings was 88.5% (1289/1456) and 11.5% (167/1456), respectively. After thyroid surgery in 396 patients, 568 nodules were confirmed as 353 papillary thyroid carcinomas including one diffuse sclerosing variant, five follicular thyroid carcinomas, three medullary thyroid carcinomas, one anaplastic thyroid carcinoma, one metastatic renal cell carcinoma, two poorly differentiated carcinomas, 17 follicular adenomas, two nodular thyroiditis, two pseudonodules related to thyroiditis, and 182 cases of nodular hyperplasia. Sensitivity, specificity, positive predictive value, negative predictive value, accuracy, false-negative rate, and false-positive rate for the US-FNAC were 94.3%, 91.9%, 96.2%, 88.3%, 93.6%, 3.9%, and 2.6%, respectively. There were no significant patients' complications, but 87 patients (8.9%) reported mild pain during or after the procedure. This study showed a good adequacy and efficacy of US-FNAC for thyroid nodules despite one-sampling.

Background: Triolein emulsion embolization into the carotid artery depicts reversible increased vascular permeability that can promote the effect of chemotherapy or can reduce the amount of chemotherapeutic drugs for equivalent effectiveness. Purpose: To establish the minimum dosage of 0.5% triolein for studying vascular permeability changes in a triolein emulsion model. Material and Methods: Sixty-six cats were divided into six groups based on the amount of emulsified triolein (0.5%) infused into the carotid artery: group 1 ( n=12, 6 ml/kg), group 2 ( n=12, 4.5 ml/kg), group 3 ( n=12, 3 ml/kg), group 4 ( n=10, 1.5 ml/kg), group 5 ( n=10, 1 ml/kg), and group 6 ( n=10, 3 ml/kg of saline (control group)). T1-weighted, T2-weighted, and post-contrast T1-weighted MRI was performed 2 h after the infusion of the triolein emulsion. Contrast enhancement ratios (CERs) were obtained with pre- and post-contrast T1-weighted images in the ipsilateral and contralateral hemispheres. Signal intensity ratios (SIRs) of the ipsilateral and contralateral hemispheres were evaluated on T2-weighted images. After removal of the brain tissues, edema ratios in the ipsilateral and contralateral hemispheres were obtained from wet versus dry brain weights. Data were statistically evaluated by analysis of variance, followed by the Tukey honestly significant difference test to compare the difference in the mean CER of the ipsilateral and contralateral hemispheres, mean SIR on T2-weighted image, and mean edema ratio between each group when overall significance was attained. Results: In the ipsilateral hemispheres, the difference in the CER between the control group and groups 1 ( P=0.004), 2 ( P=0.043), and 3 ( P=0.008) were statistically significant. The difference in the CERs between the triolein emulsion groups was not statistically significant ( P>0.05). The T2-weighted SIRs were significantly different between the control group and groups 1 ( P=0.027) and 2 ( P=0.004). However, the edema ratios of all doses in the triolein emulsion groups showed no significant differences compared with the control group. Conclusion: The minimum dosage of 0.5% triolein emulsion to achieve increased vascular permeability in the hemisphere in cat brains appears to be 3 ml/kg. This minimum dosage of triolein emulsion can be useful for acquiring basic data in further studies of vascular permeability changes in a triolein emulsion model.

Background: When a palpable breast mass is detected, a biopsy is usually performed even if the mass reveals probably benign morphologic features on imaging, as there is relatively little data reporting the outcome of such breast masses. Purpose: To determine the negative predictive value for sonographic evaluation of palpable breast masses with probably benign morphology, and to assess whether follow-up may be an acceptable alternative to immediate biopsy. Material and Methods: Of the 1399 sonograms of palpable masses from January 2004 to September 2005, there were 397 patients with masses of probably benign morphology. This study included 274 of these patients (age range 12–64 years, mean age 34 years) with 312 palpable masses that were pathologically confirmed by fine-needle aspiration ( n=7), ultrasound (US)-guided core needle biopsy ( n=180), or surgical biopsy ( n=125). The false-negative rate, negative predictive value (NPV), and 95% confidence interval (CI) were calculated using the SPSS statistical software package for Windows, version 12.0. A P value Results: Of the 312 masses, there were 310 benign lesions and two malignancies, resulting in a false-negative rate of 0.6% (NPV 99.4%, P value=0.0432, 95% CI 0.0–1.5%). Conclusion: The negative predictive value of sonography for palpable breast masses with probably benign morphology is high (99.4%). Therefore, short-term imaging follow-up can be an acceptable alternative to immediate biopsy, similar to the management of nonpalpable probably benign lesions (BI-RADS category 3).