Intensive Behavioral Therapy for Obesity Combined with Liraglutide 3.0 mg: A Randomized Controlled Trial.

OBJECTIVE: The Centers for Medicare and Medicaid Services (CMS) covers intensive behavioral therapy (IBT) for obesity. The efficacy, however, of the specific approach has never been evaluated in a randomized trial, as described here. The 1-year trial also assessed whether the addition to IBT of liraglutide 3.0 mg would significantly increase weight loss and whether the provision of meal replacements would add further benefit. METHODS: A total of 150 adults with obesity were randomly assigned to: IBT (IBT-alone), providing 21 counseling visits; IBT combined with liraglutide (IBT-liraglutide); or IBT-liraglutide combined for 12 weeks with a 1,000- to 1,200-kcal/d meal-replacement diet (Multicomponent). All participants received weekly IBT visits in month 1, every-other-week visits in months 2 to 6, and monthly sessions thereafter. RESULTS: Ninety-one percent of participants completed 1 year, at which time mean (± SEM) losses for IBT-alone, IBT-liraglutide, and Muticomponent participants were 6.1 ± 1.3%, 11.5 ± 1.3%, and 11.8 ± 1.3% of baseline weight, respectively. Fully 44.0%, 70.0%, and 74.0% of these participants lost ≥ 5% of weight, respectively. The liraglutide-treated groups were superior to IBT-alone on both outcomes. Weight loss in all three groups was associated with clinically meaningful improvements in cardiometabolic risk factors. CONCLUSIONS: The findings demonstrate the efficacy of IBT for obesity and the potential benefit of adding pharmacotherapy to this approach.

Differential expression of transferrin receptor (TfR) in a spectrum of normal to malignant breast tissues: implications for in situ and invasive carcinoma.

Transferrin receptor (TfR), a type II transmembranous receptor involved in iron uptake, is highly expressed in some cancers. We evaluated the expression of TfR in a spectrum of normal to malignant breast tissues to test the hypothesis that overexpression is associated with malignant transformation. Expression of TfR was studied by immunohistochemistry (CD71-Antibody, Thermo Fisher Scientific, Fremont, CA) for percent positive cells (%) and intensity of staining (0 to 3 score) in normal (n=127), benign (n=172), potentially premalignant and in-situ carcinoma (n=65), and invasive carcinoma (n=38). Normal and benign lesions had significantly lower TfR expression compared with premalignant lesions (atypical hyperplasia and carcinoma in situ) and invasive carcinoma (median %: 0, 10, 50, and 80, respectively; P<0.0001). TfR expression was higher in high-grade ductal carcinoma in situ (DCIS) than in other grades of DCIS (median %: 95 vs 55; P=0.02) and in high-grade invasive carcinoma. Among the latter, medullary carcinoma had the highest expression and there was a trend for invasive lobular carcinoma to have a higher expression than invasive ductal carcinoma. In invasive carcinoma cases, the proportion (%) of cells staining for TfR was inversely correlated with the percentage of estrogen receptor-positive cells, with a decreasing slope on linear regression models. In comparison, the relationship with progesterone receptor was not as well defined and linear regression models revealed close to a flat line. These data show that there is a differential expression of TfR in breast tissues with the highest expression in in-situ and invasive carcinoma and with aggressive phenotypes (higher grade DCIS and lower estrogen receptor positivity in invasive carcinomas). Further studies are indicated to determine whether TfR is an independently significant prognostic marker that may have potential as a therapeutic target in in-situ and invasive breast carcinoma.

B7-h4 expression in a range of breast pathology: correlation with tumor T-cell infiltration.

B7-H4, a member of the B7 family, is involved in the regulation of antigen-specific immune responses. Its expression in a range of breast pathology and correlation to the number of CD3 and CD8 tumor infiltrating T-lymphocytes in invasive carcinomas were explored. The proportion of B7-H4 positive cells, staining pattern, and intensity were evaluated within diagnostic groups (normal and benign lesional, potentially premalignant and in situ carcinoma, and invasive carcinoma) on archival tissue blocks by immunohistochemistry. The proportion and intensity of B7-H4 expression was progressively increased across the major diagnostic groups. There was a significant association between a high proportion of B7-H4 positive cells in invasive ductal carcinomas and decreased number of tumor infiltrating lymphocytes (P=0.002). The cellular distribution of B7-H4 appears altered in the spectrum of normal to malignant breast. Its overexpression may help cancers avoid immune detection.

False-positive D-dimer result in a patient with Castleman disease.

In suspected cases of disseminated intravascular coagulation, concurrent elevation of both fibrin(ogen) degradation products (FDPs) and D-dimer levels aids in confirming the diagnosis. This pattern of results reflects the action of plasmin proteolysis of cross-linked fibrin polymers as well as fibrinogen. We report the case of a patient with human immunodeficiency virus (HIV) and Castleman disease who presented with a high-positive D-dimer level and a negative FDP level in the course of a workup for disseminated intravascular coagulation. This finding suggested the possibility of either a false-positive D-dimer or a false-negative FDP level. To investigate the former, a Western blot was performed on the patient's serum to determine the presence of the D-dimer. No D-dimer band was visualized on the Western blot, confirming the false-positive nature of the D-dimer result. Insufficient quantity of patient serum, however, prevented further investigation into the etiology of this result. The false-positive D-dimer result is likely attributable to interference caused by the patient's Castleman disease-associated monoclonal gammopathy, a phenomenon that has been reported in other immunoassays. As the development of lymphoproliferative disorders is especially common within the HIV population, and hypergammaglobulinemia in Castleman disease is particularly common, clinicians should be aware of this phenomenon when the laboratory findings do not fit the clinical picture. Although it is rare, recognition of potential paraprotein interference in immunoassays will help avoid undertreatment or overtreatment of patients based on erroneous laboratory results.

Plasma cell granuloma of the thyroid with Hashimoto's thyroiditis: report of a rare case.

As only eight cases have been previously reported in the literature, plasma cell granuloma of the thyroid gland is a rare entity. This condition can be confused with a benign or malignant neoplastic thyroid process. In this article, we describe a new case of plasma cell granuloma of the thyroid gland that occurred in a 46-year-old man who also had Hashimoto's thyroiditis. This case represents only the second documented instance of a plasma cell granuloma of the thyroid occurring in the setting of Hashimoto's thyroiditis. Moreover, it is only the second case of a plasma cell granuloma that has been reported in a male.