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The clinical outcome of patients affected by Differentiated Thyroid Carcinoma (DTC) and an indeterminate response (IR) after initial therapy is not yet clear. IR includes three different sub-groups of patients: (1) IRTg+ group: Detectable thyroglobulin (Tg), regardless of antithyroglobulin antibodies (TgAb) presence or imaging studies; (2) IRTgAb+ group: Positive TgAb, regardless of Tg levels and nonspecific imaging findings; (3) IRImaging+ group: Nonspecific findings on neck ultrasonography or faint uptake in the thyroid bed on the whole-body scan, negative TgAb, and undetectable Tg. The main aim of this retrospective study was to investigate the dynamic evolution and prognostic role of these patients. From January 2010 to December 2017, 2176 patients who received radioiodine for DTC after total thyroidectomy were included. Two-hundred-eighty-eight patients had IR one year after therapy (187 TgAb+, 76 Tg+, 25 imaging+). After two years, 110 patients (38%) were reclassified as an excellent response and 5 (2%) as an incomplete response; after five years, 221 (77%) achieved an excellent response and 11 (4%) showed an incomplete response. One-year stimulated Tg and nodal disease at diagnosis may predict the final status of the disease. Progression-free survival was significantly shorter in IRTg+ than in IRTgAb+ and IRimaging+ groups. Considering Tg+ patients, a threshold of 3.3 ng/mL is best to predict prognosis.

Our aim was to clarify the optimum pre-ablative thyroid-stimulating hormone (TSH) level for initial radioiodine remnant ablation (RRA) in patients with differentiated thyroid carcinoma (DTC). From December 2015 to May 2019, 689 patients undergone RRA at Nuclear Medicine Department, Second Hospital of Shandong University were included in the study. Patients were categorized by their pre-ablative TSH level grouping of P = 0.036). A pre-ablative TSH level of 30–70 mIU/L was appropriate for patients with DTC to achieve a better response to RRA.

Objective After 131I treatment in patients with differentiated thyroid carcinoma (DTC), we sometimes find a star-shaped intense uptake of 131I on therapeutic whole body scans (Rx-WBS), called star artifacts. Therefore, we analyzed the relevant clinical factors and prognostic value of star artifacts in DTC patients. Methods 809 DTC patients who received 131I treatment were retrospectively evaluated and divided into 2 groups of patients with and without star artifacts. We evaluated the therapeutic response which was divided into excellent response (ER), biochemical incomplete response (BIR), indeterminate response (IR), and structural incomplete response (SIR). Clinical factors for the presence of star artifacts were analyzed. We also compared the rate of ER, BIR, IR, SIR and recurrence rate between group 1 and group 2. Results The major clinical factors included stimulated thyroglobulin (sTg) > 1.8 ng/ml, 24 h radioiodine uptake (RAIU) > 2.2%, and positive 99mTcO4− thyroid imaging for the presence of star artifacts. In patients with sTg levels > 10 ng/ml, patients in group 1 had a higher rate of ablation success and ER than patients in group 2 (80.2% vs 65.6%, P = 0.038, 31.6% vs 13.1%, P = 0.008, respectively) and had a similar rate of BIR, IR, SIR. Recurrence rate was similar between group 1 and group 2 (5.2% vs 3.1%, P = 0.13). Conclusion More remnant thyroid tissue is one of the factors associated with the presence of star artifacts on Rx-WBS. Patients with star artifacts exhibit a better therapeutic response (ER) when sTg levels are >10 ng/ml. However, star artifacts have no effect on the recurrence rate.

Objectives To assess the value of 18F-FDG-PET/CT for detecting recurrent/persistent disease in patients with biochemical incomplete (BIR) or indeterminate response (IR) and to assess the impact of 18F-FDG-PET/CT on the therapeutic management of these patients. Methods The study included patients with BIR, in whom 18F-FDG PET/CT was used within the diagnostic algorithm from our database. Patients with IR referred to our hospital with the 18F-FDG PET/CT already performed were also enrolled. All patients had neck ultrasonography with no structural changes. A change in therapeutic approach was defined as repeat surgery; administration of external beam radiotherapy; and/or the start of systemic therapy. Results Sixty patients (85% women) aged 18–86 years were enrolled in this retrospective study. Of these, 75% had BIR and 25% IR. Increased FDG uptake suggesting locoregional lesions was seen in 40% of patients. Sensitivity, specificity, and diagnostic accuracy of 18F-FDG PET/CT to detect local disease were 95%, 87.5% and 90% respectively. The therapeutic approach was modified in 50% of patients with locoregional lesions. Conclusions Our study confirmed that 18F-FDG-PET/CT is a useful tool for detecting locoregional recurrence in thyroid cancer patients with BIR or IR with conflicting findings in standard diagnostic procedures. In 50% of patients with locoregional lesions, there was an immediate change in the treatment approach.

BackgroundThere are no definite recommendations on the optimal time of initiating radioactive iodine (RAI) therapy for differentiated thyroid cancer (DTC) patients in current relevant guidelines. This study aimed to investigate the relationship between the timing of initiating radioiodine adjuvant therapy (RAT) and the clinical outcomes based on dynamic follow-ups and assessments in intermediate- to high-risk DTC patients.MethodsA total of 206 patients with intermediate- to high-risk DTC receiving RAT of 150 mCi were retrospectively reviewed. According to the time interval (TI: between thyroidectomy and initial RAT), the patients were divided into 2 groups: Group 1: TI < 3 months (n=148), and Group 2: TI ≥ 3 months (n=58). The RAT therapy response was evaluated as excellent response (ER), indeterminate response (IDR), biochemical incomplete response (BIR), structural incomplete response (SIR). The univariate and multivariate analyses were conducted to screen out factors associated with incomplete response (IR= BIR+SIR). Finally, the prognostic nomogram was used to explain IR rates as a valuable tool in clinical practice.ResultsResponse to initial RAT was significantly different between 2 groups during dynamic follow-ups (all Pvs 63.5, 52.0 vs 73.9, 64.4 vs 80.3, all Pvs 14.9, 36.0 vs 9.7, 12.2 vs 3.9, all PP=0.001), soft tissue invasion (HR: 7.35, 95%CI: 1.624-33.296, P=0.010), higher sTg (HR: 7.21, 95%CI: 1.991-26.075, P=0.003) were manifested to be independent risk factors for IR. The nomogram showed that soft tissue invasion, sTg, and TI were the top 3 contributors to the IR.ConclusionsEarly RAT is associated with greater biochemical response but has no impact on SIR. Delayed initial RAT (≥3 months after thyroidectomy) related to IR in intermediate- to high-risk DTC.

In recent years, the short Synacthen test (SS) has become the most widely used test to assess adrenal reserve. Despite its frequent use, there are still several areas related to the short Synacthen test (SST), which have no consensus including the optimum sampling times, that is, whether a 60 min post-Synacthen administration cortisol is necessary or not. Methodology We performed a retrospective data analysis of 492 SSTs performed on adult patients in a tertiary referral teaching hospital in Ireland. The SSTs were performed in the inpatient and outpatient setting and included patients across all medical disciplines and not exclusively to the endocrinology department. Results 313 patients had 0, 30 and 60 min samples available for analysis. A total of 270/313 (82%) were deemed to pass the test, that is, cortisol ≥500 nmol/L at both 30 and 60 min. Of the 313 patients, 19 (6%) patients had an indeterminate response, cortisol Conclusion Using the 30 min cortisol sample post-Synacthen administration alone identifies clinically relevant adrenal insufficiency in the majority of cases. A small subset of patients have a suboptimal response at 30 min but have a 60 min cortisol concentration above the threshold for a pass. Data regarding the long-term outcomes and management of such patients are lacking and require further study.

The concept of a dynamic risk-stratification scheme has been suggested for individualized management of patients with papillary thyroid carcinoma (PTC). However, there is no specified follow-up strategy for patients with an indeterminate response.This study evaluated 403 PTC patients who had an indeterminate response during the first 12-24 months after initial therapy. All patients underwent total thyroidectomy with radioactive iodine remnant ablation. Patients were further classified into three groups based on risk of structural persistence/recurrence: a Tg+ group (detectable thyroglobulin [Tg], regardless of antithyroglobulin antibody [TgAb] or imaging findings; 196 patients), a TgAb+ group (positive results for TgAb with undetectable Tg, regardless of imaging findings; 46 patients), and an Image+ group (nonspecific findings on neck ultrasonography or faint uptake in the thyroid bed on whole-body scan, with undetectable Tg and negative results for TgAb; 161 patients).With a median of 9.6 years (interquartile range 7.7-11.2 years) of follow-up, 56 (14%) PTC patients had structural persistent/recurrent disease: 50 (89%) at locoregional sites and six (11%) at distant sites. The recurrence rate in Tg+, TgAb+, and Image + groups were 26.5%, 8.7%, and 0%, respectively. The median time to detection of structural persistent/recurrent disease from the initial thyroid surgery was 3.7 years (interquartile range 2.5-6.3 years). The optimal cutoff stimulated Tg level to predict structural persistent/recurrent disease was 3.1 ng/mL in the Tg+ group. This classification system revealed higher predictability of structural persistent/recurrent disease than the tumor-node-metastasis staging system and American Thyroid Association risk stratification (proportion of variation explained: 15.7% vs. 2.4% and 0.9%, respectively). Six (3%) patients with distant metastatic disease were all classified in the Tg+ group, and all had lung metastasis.The findings suggest a more individualized follow-up strategy for patients with an indeterminate response. More careful evaluation, including early evaluation of distant metastasis, is necessary in patients with elevated Tg levels. However, for patients testing positive for TgAb or those with only nonspecific imaging findings, regular follow-ups of Tg and TgAb levels and neck ultrasonography are sufficient.

Made available in DSpace on 2022-04-29T08:38:05Z (GMT). No. of bitstreams: 0 Previous issue date: 2021-11-03 Objective: Thyrotropin-stimulated thyroglobulin (STg) after total thyroidectomy is a prognosis marker for differentiated thyroid carcinoma (DTC). As Tg level is influenced by thyrotropin (TSH), perhaps the STg/TSH ratio is also a prognosis marker for these tumours. We aimed to compare STg/TSH ratio and first STg level in differentiated thyroid carcinoma patients for their ability to predict the long-term response to initial treatment. Methods: This retrospective study evaluated data from 181 DTC patients for first (1st) STg and STg/TSH ratio, at 1-3 months post-total thyroidectomy and before iodine-131 therapy, according to response to initial therapy [Excellent/Indeterminate or Incomplete (Biochemical/Structural)] observed at final evaluation, and with the survival time with excellent/indeterminate response. Results: Cases with incomplete response presented higher STg level [225.13 ± 585.26 ng/mL versus (vs) 20.4 ± 192.9 ng/mL; p < 0.001] and STg/TSH ratio (3.01 ± 7.8 vs 0.27 ± 2.58; p < 0.001). Cutoffs of 5 ng/mL for STg and 0.085 for STg/TSH displayed sensitivities of 76.7% and 76.9%, and specificities of 79.2% and 82.6%, respectively, in predicting response to therapy. Values below these cutoffs were associated with longer survival time in excellent/indeterminate response (140.4 vs 15.9 and 144.6 vs 15.9 months, respectively). Conclusion: STg/TSH ratio has a similar performance to the 1st STg in predicting long-term response to initial therapy. Departamento de Clínica Médica Faculdade de Medicina de Botucatu Universidade Estadual Paulista (Unesp) Departamento de Oftalmologia Otorrinolaringologia e Cirurgia de Cabeça e Pescoço Faculdade de Medicina de Botucatu Universidade Estadual Paulista (Unesp) Departamento de Patologia Faculdade de Medicina de Botucatu Universidade Estadual Paulista (Unesp) Departamento de Medicina Nuclear Faculdade de Medicina de Botucatu Universidade Estadual Paulista (Unesp) Departamento de Clínica Médica Faculdade de Medicina de Botucatu Universidade Estadual Paulista (Unesp) Departamento de Oftalmologia Otorrinolaringologia e Cirurgia de Cabeça e Pescoço Faculdade de Medicina de Botucatu Universidade Estadual Paulista (Unesp) Departamento de Patologia Faculdade de Medicina de Botucatu Universidade Estadual Paulista (Unesp) Departamento de Medicina Nuclear Faculdade de Medicina de Botucatu Universidade Estadual Paulista (Unesp)

This study validated the dynamic risk stratification (DRS) system with regard to its association with structural recurrence and risk factors associated with non-excellent responses in patients45 years with stage I classical papillary thyroid cancer (PTC).This historical cohort study included 598 patients with stage I classical PTC45 years of age treated with total thyroidectomy followed by radioactive iodine remnant ablation (n = 440), total thyroidectomy without radioactive iodine remnant ablation (n = 23), and thyroid lobectomy alone (n = 135).The median follow-up period was 123 months. Structural recurrence occurred in 4.2% (n = 18/432) of the patients with an excellent response, 17.1% (18/105) of patients with an indeterminate response, 44.7% (17/38) of patients with a biochemically incomplete response, and 82.6% (19/23) of patients with a structurally incomplete response (p 0.001) during the follow-up. The disease-free survival curves of each response showed significant differences (p 0.001). Extensive extrathyroidal extension and extranodal extension were the independent risk factors associated with non-excellent response (p 0.05).DRS may reduce unnecessary additional treatments by reclassifying initial risk estimates of structural recurrence. Furthermore, applying the risk factors associated with non-excellent response to initial therapy may be a more useful and viable surrogate of the risk for structural recurrence in stage I PTC patients45 years of age.

The adequate risk stratification in thyroid carcinoma is crucial to avoid on one hand the overtreatment of low-risk and on the other hand the undertreatment of high-risk patients. The question how to properly assess the risk of relapse has been discussed during recent years and resulted in a substantial change in our approach to risk stratification in differentiated thyroid cancer, proposed by the newest ATA guidelines. First initial risk stratification, based on histopathological data is carried out just after primary surgery. It should be emphasized, that a high quality of histopathological report is crucial for proper risk stratification. Next, during the follow-up, patients are restratified considering their response to treatment applied and classified to one of the following categories: excellent response, biochemical incomplete response, structural incomplete or indeterminate response. This new approach is called dynamic risk stratification as, in contrary to the previous rigid evaluation performed at diagnosis, reflects a real-time prognosis and thereby substantially influences and personalizes disease management. In this review, we raise some unresolved questions, among them the lack of prospective studies, fulfilling evidence-based criteria, necessary to validate this model of risk stratification. We also provided some data concerning the use of dynamic risk stratification in medullary thyroid cancer, not yet reflected in ATA guidelines. In conclusion, dynamic risk stratification allows for better prediction of the risk of recurrence in thyroid carcinoma, what has been demonstrated in numerous retrospective analyses. However, the validation of this approach in prospective studies seems to be our task for near future.

This is a longitudinal study of retrospective data aimed at verifying whether repeated measurements of serum non-stimulated thyroglobulin (Tg) allow the prediction of persistent disease in patients with differentiated thyroid cancer (DTC) and indeterminate response. We examined 145 DTC patients with indeterminate response to therapy followed up for a median time of 68 months. Tg measurements and neck ultrasound (US) were performed every 6–12 months. The changes over time of repeated measurements of basal Tg were analyzed through the multilevel linear regression. Seventy (48.3%) out of 145 patients spontaneously achieved an excellent response, while persistent indeterminate response was observed in 62 (42.7%) patients. The remaining 13 (9.0%) patients had progression: 3/13 with biochemical disease and 10/13 with structural disease. Tg steadily increased in patients with progressive disease (mean percentage change + 27.1% at each follow-up visit), while Tg decreased in patients without any evidence of progression (mean percentage change − 8.8%). This different trend between the two groups was not related to either different values of median TSH at baseline (0.32 vs 0.28 mIU/l, respectively) or to different trend of TSH during follow-up (p = 0.76). Basal Tg values did not increase in three out of ten patients with structural disease that was identified by neck US. The importance of the study is that, in DTC patients with indeterminate response, rising values of unstimulated Tg, independently from the basal levels, may be useful to identify patients with progressive disease. These results are also useful to avoid unnecessary TSH stimulation.

Aim: To compare the diagnostic accuracy of different radiological criteria used in the assessments of antiangiogenic response in patients with metastatic Renal Cell Carcinoma (RCC). Methods: 44 patients were retrospectively evaluated from January 2007 through September 2014, the patients had histologic diagnosis of RCC, existence of target lesions, in therapy with Sorafenib or Sunitinib assumed continuously for 4 weeks for a total of 6 cycles and went through multiphase CT before and 3 months after the therapy. Results: Out of the 44 patients, 21 had Progression Free Survival (PFS) > 250 days. In this group of patients, all the radiological criteria had high predictive value with slightly higher sensitivity for the RECIST 1.1 criteria (sensitivity 100%). In the remaining group of 23 patients (with PFS < 250 days), RECIST criteria also showed slightly higher specificity values by identifying 9 patients (60.86%) compared with Choi, MASS and SACT who identified respectively 56.52%, 52.17% and 56.52% of the patients as having stable disease or indeterminate response to the therapy. Conclusion: All studied radiological criteria had high predictive value with slightly higher sensitivity results for the RECIST 1.1 criteria.

Papillary thyroid cancer (PTC) patients treated with thyroidectomy and radioiodine remnant ablation (RRA) often have detectable TSH-stimulated thyroglobulin (Tg) levels without localizable disease after primary treatment. To assess the value of repeat stimulated Tg assays in these patients' follow-up, we retrospectively analyzed 86 cases followed in 5 Italian thyroid-cancer referral centers. We enrolled 86 patients with PTCs treated with total/near-total thyroidectomy plus RRA between January 1,1990 and January 31, 2006. In all cases, the initial postoperative visit revealed stimulated serum Tg ≥1 ng/mL, negative Tg antibodies, and no structural evidence of disease. None received empiric radioiodine therapy. Follow-up (median: 9.6 years) included neck ultrasound and basal Tg assays (yearly) and at least 1 repeat stimulated Tg assay. Of the 86 patients analyzed (initial risk: low 63 %, intermediate 35 %, high 2 %), one (1 %) had ultrasound-detected lymph node disease and persistently elevated stimulated Tg levels at 3 years. In 17 (20 %), imaging findings were consistently negative, but the final stimulated Tg levels was still >1 ng/mL (median 2.07 ng/mL, range 1.02-4.7). The other 68 (80 %) appeared disease-free (persistently negative imaging findings with stimulated Tg levels ≤1 ng/mL). Mean intervals between first and final stimulated Tg assays were similar (5.2 and 4.8 years) in subgroups with versus without Tg normalization. Reclassification as disease-free was significantly more common when initial stimulated Tg levels were indeterminate (

Radiation therapy (RT) is the common treatment for painful vertebral bone metastases without paralysis by malignant spinal cord compression. However, no studies have focused on the time course of pain after RT. Then, we investigated the change of pain after RT for painful vertebral bone metastases without paralysis.Participants included 101 patients who received RT for painful vertebral bone metastases without paralysis in our institution between 2012 and 2016. All patients received RT and pain response was evaluated by Numeric Rating Scale (NRS). Follow-up assessments were performed just before the start of RT and every month for six months after RT. Pain response was classified as complete response (CR), partial response (PR), pain progression (PP), and indeterminate response (IR) based on the response criteria of International Bone Metastases Consensus Working Party. Responders were classified as either CR or PR, and non-responders as either PP or IR.Median NRS scores for pain were 5 before RT, decreasing to 0 by one month after RT and remaining zero until last follow-up, representing a significant decrease over time (P 0.001). The rate of responders at each month from one to six months was 93, 96, 95, 100, 98, and 96%, respectively. Multivariate analysis revealed that Spinal Instability Neoplastic Score (SINS) was the only risk factor for response to RT at one month. At one month pain disappeared in 88% of the patients with spinal stability (SINS 7), although pain disappeared 58% of the patients with spinal instability (SINS ≥ 7), which was significant (P = 0.002).Pain decreased significantly over time and 93% of patients were classified as responders as early as one month after RT in patients with painful vertebral bone metastases without paralysis. Pretreatment SINS could be a predictor of pain response to RT.

The response evaluation criteria in patients with Hodgkin lymphoma (HL) were designed for the assessment of chemotherapy and targeted molecular agents. We investigated the accuracy of 3-mo 18F-FDG PET/CT for the identification of HL patients responding to immune-checkpoint blockade by anti-programmed death 1 antibodies (anti-PD1). We also reported the frequency of new immune patterns of response and progression. Methods: Retrospectively, we recruited consecutive HL patients treated by anti-PD1 (pembrolizumab or nivolumab) at Gustave Roussy from 2013 to 2015. 18F-FDG PET/CT and contrast-enhanced CT scans were acquired every 3 mo. We recorded the best overall response according to the International Harmonization Project Cheson 2014 criteria and LYmphoma Response to Immunomodulatory therapy Criteria (LYRIC) (2016 revised criteria). Patients achieving an objective response at any time during the anti-PD1 treatment were classified as responders. Results: Sixteen relapsed or refractory classic HL patients were included. The median age was 39 y (age range, 19-69 y). The median previous lines of therapy was 6 (range, 3-13). The mean follow-up was 22.6 mo. Nine of 16 patients (56%) achieved an objective response. Two deaths occurred due to progressive disease at 7 mo. 18F-FDG PET/CT detected all responders at 3 mo and reclassified best overall response in 5 patients compared with CT alone. A decrease in tumor metabolism and volume (SUVmean, metabolic tumor volume) and increase in healthy splenic metabolism at 3 mo were observed in responders (area under the curve > 0.85, P < 0.04). Five of 16 patients (31%) displayed new imaging patterns related to anti-PD1; we observed 2 transient progressions consistent with indeterminate response according to the LYRIC (2016) (IR2b at 14 mo and IR3 at 18 mo) and 3 patients with new lesions associated with immune-related adverse events. Conclusion: Three-month 18F-FDG PET/CT scans detected HL patients responding to anti-PD1. New patterns were encountered in 31% of patients, emphasizing the need for further evaluation in larger series and close collaboration between imaging and oncology specialists on a per-patient basis.

Background The two interferon-γ release assays such as QuantiFERON-TB Gold / In-Tube (QFT-TB) and T-SPOT.TB-are useful tools for the rapid diagnosis of tuberculosis (TB) but can yield indeterminate test results (ITRs). While some studies have identified risk factors for ITRs in the QFT-TB test, there have been few such studies for the T-SPOT.TB test. The aim of this study was to investigate the risk factors associated with ITRs in the T-SPOT.TB test. Materials and Methods From April 2008 to August 2010, all patients with suspected extrapulmonary tuberculosis (E-TB) were enrolled in a tertiary hospital in Korea. ITR was defined as < 20 spots in the positive control well or > 10 spots in the negative control well. Results Out of a total of 368 patients, 32 (8.7%, 95% CI, 6.0% to 11.7%) had ITRs in their T-SPOT.TB tests. The ITRs were due to a low mitogen response in 13 (40.6%) patients and to a high nil response in the other 19 (59.4%) patients. Statistical analysis revealed that old age, underlying diseases, immunosuppressive treatment, lymphopenia, and clinical manifestations of E-TB were not significantly associated with ITRs. Conclusions Indeterminate results in the T-SPOT.TB test are not affected by age, underlying disease, immunosuppressive treatment, lymphopenia, or clinical manifestations of E-TB, which are known risk factors for indeterminate results in the QFT-TB test.

Radiation therapy (RT) is an effective method of palliating painful bone metastases and can improve function and reduce analgesic requirements. In advanced cancer patients, quality of life (QOL) is the primary outcome of interest over traditional endpoints such as survival. The purpose of our study was to compare bone metastasis-specific QOL scores among patients who responded differently to palliative RT.Patients receiving RT for bone metastases across 6 countries were prospectively enrolled from March 2010-January 2011 in a trial validating the QLQ-BM22 and completed the QLQ-BM22 and the core measure (QLQ-C30) at baseline and after 1 month. Pain scores and analgesic intake were recorded, and response to RT was determined according to the latest published guidelines. The Kruskal-Wallis nonparametric and Wilcoxon rank sum tests compared changes in QOL among response groups. A Bonferroni-adjusted P.003 indicated statistical significance.Of 79 patients who received palliative RT, 59 were assessable. Partial response, pain progression, and indeterminate response were observed in 22, 8, and 29 patients, respectively; there were no patients with a complete response. Patients across all groups had similar baseline QOL scores apart from physical functioning (patients who progressed had better initial functioning). One month after RT, patients who responded had significant improvements in 3 of 4 QLQ-BM22 domains (painful site, P.0001; painful characteristic, P.0001; and functional interference, P.0001) and 3 QLQ-C30 domains (physical functioning, P=.0006; role functioning, P=.0026; and pain, P.0001). Patients with progression in pain had significantly worse functional interference (P=.0007) and pain (P=.0019).Patients who report pain relief after palliative RT also have better QOL with respect to bone metastasis-specific issues. The QLQ-BM22 and QLQ-C30 are able to discriminate among patients with varying responses and are recommended for use in future bone metastasis clinical trials.

There are limited data available on interferon-γ release assay (IGRA) performance in children up to 5 years of age, with documented exposure to active tuberculosis (TB). The aim of this study was to evaluate (1) the influence of infectivity of adult source cases on test results, (2) the impact of age, and (3) the level of agreement, between IGRA and tuberculin skin test (TST) results. A total of 142 Bacille Calmette-Guerin-vaccinated children up to 5 years of age were investigated because of a history of exposure to active TB. QuantiFERON-TB Gold In-Tube IGRA (QFT) and TST assays were performed. Test results were significantly influenced by positive finding of cavitary lesions (QFT, odds ratio [OR] = 6.15 ; TST, OR = 7.48) and positive acid-fast bacilli (QFT, OR = 4.01 ; TST, OR = 4.47) in active TB contacts. QFT resulted in 1 indeterminate response (0.7%), attributable to low mitogen. There was no evidence for age having any effect on QFT performance. The 2 tests showed a moderate overall concordance (89% ; κ = 0.591) at a TST cutoff value of ≥10 mm. Association of positive QFT and TST results with risk factors for infection in child contacts (presence of cavitary lesions and acid-fast bacilli smear positivity in index cases) suggests that both the tests have good diagnostic accuracy. However, there was significant discord between results of the 2 tests that could not be definitively resolved. Thus, in a high-risk population of children up to 5 years of age, both tests (QFT and TST) should be performed and the child should be considered infected if either or both tests are positive.

The confusion/non-consequential thinking explanation proposed by Newstead, Girotto, and Legrenzi (1995) for poor performance on Wason's THOG problem (a hypothetico-deductive reasoning task) was examined in three experiments with 300 participants. In general, as the cognitive complexity of the problem and the possibility of non-consequential thinking were reduced, correct performance increased. Significant but weak facilitation (33-40% correct) was found in Experiment 1 for THOG classification instructions that did not include the indeterminate response option. Substantial facilitation (up to 75% correct) was obtained in Experiment 2 with O'Brien et al.'s (1990) one-other-THOG classification instruction. In Experiment 3, a revised version of O'Brien et al.'s pre-test problem format also led to substantial facilitation, even with the use of the standard three-choice THOG classification instruction. These findings are discussed in terms of Newstead et al.'s theoretical proposal and possible attentional factors.

That children are more likely develop a severe form of TB is reflective of the differences in the maturational stages of their immune systems, but a paucity of data is available about how this system matures and what the relationship of these developmental immune deficiencies are with infection. Maturational deficiencies in the adaptive and innate immune systems in infants and young children may result in immature macrophage and DC function; Th1-type responses to pathogens; and a propensity to develop Th2-type CD4 T-cells in response to immunogens. In vitro responses of two groups of TST positive children at risk for TB were examined by comparing Enzyme-Linked ImmunoSorbent Assay (ELISA)-based IGRAs with clinical and TST findings. Age-related changes in the immune capacity for specific and mitogen-induced IFN-γ production was also examined in these two groups. In the original guidelines for the use of QFT-G, the US Centers for Disease Control and Prevention recommended that additional studies were needed, especially in children under five years of age, both to establish the validity of the assay as a diagnostic tool in the younger age group and to compare the accuracy of the test with the TST for diagnosing active and latent TB. Of TST positive US children, 10 of the 196 (5%) were found to be QFT-G positive; nine had an indeterminate response; of the 130 children from the Philippines who had been immunized with BCG, 115 were TST positive, and seven were also QFT-G positive. In BCG immunized children, all were TST positive and BCG-immunized and because of a presumptive diagnosis of TB, all had received anti-TB therapy; of the 30 children, 14 (47%) were found to be QFT-G-IT positive and one had an indeterminate response. For the study of variations in age-related immune capacity, the capacity of IFN-γ production was measured in various age groups of children in response to specific TB peptides (ESAT-6, CFP-10 and TB7.7) as well as to mitogen in amounts used in the QFT-G and the QFT-G-IT assay kits that had been provided. Both studies suggest that ELISA QFT-G and QFT-G-IT assays are useful for diagnosing TB in children and that adequate IFN-γ production was observed in all children in both groups following lymphocyte stimulation by either purified TB peptides or mitogen including those less than 5 years of age.

The long-term fate of 434 consecutive patients operated on between 1968 and 1971 was assessed. All patients were followed up for more than 60 months after operation (mean 70.7 months). Of the initial 434 patients, 98 died 0 to 74 (mean 31.1) months postoperatively. Of the 336 survivors, 152 reentered the hospital and underwent standardized clinical assessment. Angina was lessened in 93.4 percent (255 of 273) and absent in 51.3 percent (140 of 273) of these patients. Of patients under 65 years of age, 79.2 percent (152 of 192) were still working. Treadmill exercise tests performed in 107 patients showed an ischemic response in 44.9 percent (48 of 107) and an indeterminate response in 9.3 percent (10 of 107). The duration of the exercise, maximal pulse rate and double product all correlated well with the completeness of revascularization. In 176 patients with 256 grafts evaluated angiographically, the patency rate was 86.3 percent (221 of 256), and 94.3 percent of patients (166 of 176) had at least one patent graft. The average crude annual attrition rate after the first year was 2.3 percent per year, which approximates that of the general U.S. population after correction for age and sex. In the next 677 consecutive patients the survival rate after 5 years was 91.4 percent (including 4.7 percent operative mortality rate) compared with the survival rate of a similar normal population of 92.7 percent. The operative mortality rate of 7.1 percent in this early experience has been reduced to less than 2 percent in current experience. These results suggest that the coronary bypass procedure provides sustained symptomatic relief and may prolong life.

Twenty-nine of 33 steroid-dependent asthmatic patients received 18 months of therapy with beclomethasone dipropionate. Only four of 29 subjects required concurrent oral therapy with steroids. Twenty-six of 29 patients noted a marked improvement in their asthma; three of 29 described an indeterminate response. A statistically significant improvement in many of the symptoms, the plasma cortisol level, the first-second forced expiratory volume, and the forced expiratory flow at 50 percent of the observed forced vital capacity was present only at the end of three months of therapy with beclomethasone dipropionate. Steroid-withdrawal symptoms, particularly those related to the nose and sinuses, were initially troublesome but decreased with the passage of time. No oropharyngeal fungal infections were observed. At a dose below the hypothalamic-pituitary-adrenal suppressive level, therapy with beclomethasone dipropionate appears to be safe and effective for treating patients with steroid-dependent asthma.

The coronary bypass procedure has gained widespread acceptance as a highly effective form of treatment for angina pectoris. There is also evidence that it prolongs life in patients with three vessel or left main coronary stenosis. We have been particularly interested in the late results of coronary bypass in regard to relief of symptoms and prolongation of life and have therefore determined the fate of 1578 consecutive patients after coronary bypass with followup beyond 5 years in all cases. An initial study was made of clinical, treadmill and angiographic results in 434 patients operated upon between 1968 and 1971. (Lawrie et al. 1977). All patients were followed up for more than 60 months after operation (mean 70.7 months). Of the initial 434 patients, 98 died 0 to 74 (mean 31.1 months) post-oper-atively. Of the 336 survivors, 152 reentered the hospital and underwent standardized clinical assessment. Angina was lessened in 93.4 percent (255 of 273) and absent in 51.3 percent (140 of 273) of these patients. Of patients under 65 years of age, 79.2 percent (152 of 192) were still working. Treadmill exercise tests performed in 107 patients showed an ischemic response in 44.9 percent (48 of 107) and an indeterminate response in 9.3 percent (10 of 107). The duration of the exercise, maximal pulse rate and double product all correlated well with the completeness of revasculariza-tion.