Clinical utility of gadobenate dimeglumine in contrast-enhanced MRI of the breast: a review

Breast magnetic resonance imaging (MRI) is considered the technique with the highest sensitivity for breast cancer detection. Gadobenate dimeglumine is a gadolinium-based contrast agent (GBCA) that is specifically approved in Europe for breast MRI and which has the highest r1 relaxivity among all GBCAs for this indication. In order to improve the diagnostic performance of breast MRI, several intra-individual crossover studies have evaluated gadobenate dimeglumine as a possible GBCA for this application. This review focuses on the role and advantages of gadobenate dimeglumine as a contrast agent for breast MRI by describing the unique properties of this agent and by summarizing published studies

Changes in total choline concentration in the breast of healthy fertile young women in relation to menstrual cycle or use of oral contraceptives: a 3-T 1H-MRS study

BACKGROUND: To evaluate changes in total choline (tCho) absolute concentration ([tCho]) in the breast of healthy fertile women in relation to menstrual cycle (MC) or use of oral contraceptives (OC). METHODS: After institutional review board approval, we prospectively evaluated 40 healthy fertile volunteers: 20 with physiological MC, aged 28 ± 3 years (mean ± standard deviation; nOC group); 20 using OC, aged 26 ± 3 years (OC group). Hormonal assays and water-suppressed single-voxel 3-T proton magnetic resonance spectroscopy (1H-MRS) were performed on MC days 7, 14, and 21 in the nOC group and only on MC day 14 in the OC group. [tCho] was measured versus an external phantom. Mann-Whitney U test and Spearman coefficient were used; data are given as median and interquartile interval. RESULTS: All spectra had good quality. In the nOC group, [tCho] (mM) did not change significantly during MC: 0.8 (0.3-2.4) on day 7, 0.9 (0.4-1.2) on day 14, and 0.4 (0.2-0.8) on day 21 (p = 0.963). In the OC group, [tCho] was 0.7 (0.2-1.7) mM. The between-groups difference was not significant on all days (p ≥ 0.411). All hormones except prolactin changed during MC (p ≤ 0.024). In the OC group, [tCho] showed a borderline correlation with estradiol (r = 0.458, p = 0.056), but no correlation with other hormones (p ≥ 0.128). In the nOC group, [tCho] negatively correlated with prolactin (r = -0.587, p = 0.006) on day 7; positive correlation was found with estradiol on day 14 (r = 0.679, p = 0.001). CONCLUSIONS: A tCho peak can be detected in the normal mammary gland using 3-T 1H-MRS. The [tCho] in healthy volunteers was 0.4-0.9 mM, constant over the MC and independent of OC use

Metabolism of glutathione in tumour cells as evidenced by 1H MRS

Abstract1H MRS signals of glutathione and of free glutamate were examined in samples from cultured tumour cells, namely MCF-7 from mammary carcinoma and TG98 from malignant glioma, with the aim of relating signal intensities to aspects of GSH metabolism. Spectra of cells harvested at different cell densities suggest that GSH and glu signal intensities are related to cell density and proliferation and their ratio is dependent on the activity of the γ-glutamyl cysteine synthetase. The hypothesis is confirmed by experiments performed on cells treated with buthionine sulfoximine that inhibits the enzyme activity

Multicenter observational study on the reliability of the HEART score

Objective To rapidly and safely identify the risk of developing acute coronary syndrome in patients with chest pain who present to the emergency department, the clinical use of the History, Electrocardiogram, Age, Risk Factors, and Troponin (HEART) scoring has recently been proposed. This study aimed to assess the inter-rater reliability of the HEART score calculated by a large number of Italian emergency physicians. Methods The study was conducted in three academic emergency departments using clinical scenarios obtained from medical records of patients with chest pain. Twenty physicians, who took the HEART score course, independently assigned a score to different clinical scenarios, which were randomly administered to the participants, and data were collected and recorded in a spreadsheet by an independent investigator who was blinded to the study\u2019s aim. Results After applying the exclusion criteria, 53 scenarios were finally included in the analysis. The general inter-rater reliability was good (kappa statistics [\u3ba], 0.63; 95% confidence interval, 0.57 to 0.70), and a good inter-rater agreement for the high- and low-risk classes (HEART score, 7 to 10 and 0 to 3, respectively; \u3ba, 0.60 to 0.73) was observed, whereas a moderate agreement was found for the intermediate-risk class (HEART score, 4 to 6; \u3ba, 0.51). Among the different items of the HEART score, history and electrocardiogram had the worse agreement (\u3ba, 0.37 and 0.42, respectively). Conclusion The HEART score had good inter-rater reliability, particularly among the high- and low-risk classes. The modest agreement for history suggests that major improvements are needed for objectively assessing this component. Keywords HEART score; HEART pathway; Chest pain; Acute coronary syndrome; Emergency service, hospita

Multicenter observational study on the reliability of the HEART score

Objective To rapidly and safely identify the risk of developing acute coronary syndrome in patients with chest pain who present to the emergency department, the clinical use of the History, Electrocardiogram, Age, Risk Factors, and Troponin (HEART) scoring has recently been proposed. This study aimed to assess the inter-rater reliability of the HEART score calculated by a large number of Italian emergency physicians. Methods The study was conducted in three academic emergency departments using clinical scenarios obtained from medical records of patients with chest pain. Twenty physicians, who took the HEART score course, independently assigned a score to different clinical scenarios, which were randomly administered to the participants, and data were collected and recorded in a spreadsheet by an independent investigator who was blinded to the study’s aim. Results After applying the exclusion criteria, 53 scenarios were finally included in the analysis. The general inter-rater reliability was good (kappa statistics [κ], 0.63; 95% confidence interval, 0.57 to 0.70), and a good inter-rater agreement for the high- and low-risk classes (HEART score, 7 to 10 and 0 to 3, respectively; κ, 0.60 to 0.73) was observed, whereas a moderate agreement was found for the intermediate-risk class (HEART score, 4 to 6; κ, 0.51). Among the different items of the HEART score, history and electrocardiogram had the worse agreement (κ, 0.37 and 0.42, respectively). Conclusion The HEART score had good inter-rater reliability, particularly among the high- and low-risk classes. The modest agreement for history suggests that major improvements are needed for objectively assessing this component

1H NMR spectroscopy of glioblastoma stem-like cells identifies alpha-aminoadipate as a marker of tumor aggressiveness

Patients suffering from glioblastoma multiforme (GBM) face a poor prognosis with median survival of about 14months. High recurrence rate and failure of conventional treatments are attributed to the presence of GBM cells with stem-like properties (GSCs). Metabolite profiles of 42 GSC lines established from the tumor tissue of adult GBM patients were screened with 1H NMR spectroscopy and compared with human neural progenitor cells from human adult olfactory bulb (OB-NPCs) and from the developing human brain (HNPCs). A first subset (n=12) of GSCs exhibited a dramatic accumulation of the metabolite α-aminoadipate (αAAD), product of the oxidation of α-aminoadipic semialdehyde catalyzed by the ALDH7A1 aldehyde dehydrogenase (ALDH) family in lysine catabolism. αAAD was low/not detectable in a second GSC subset (n=13) with the same neural metabolic profile as well as in a third GSC subset (n=17) characterized by intense lipid signals. Likewise, αAAD was not detected in the spectra of OB-NPCs or HNPCs. Inhibition of mitochondrial ATP synthase by oligomycin treatment revealed that the lysine degradative pathway leading to αAAD formation proceeds through saccharopine, as usually observed in developing brain. Survival curves indicated that high αAAD levels in GSCs significantly correlated with poor patient survival, similarly to prostate and non-small-cell-lung cancers, where activity of ALDH7A1 correlates with tumor aggressiveness

Exploiting the 2-Amino-1,3,4-thiadiazole Scaffold To Inhibit <i>Trypanosoma brucei </i>Pteridine Reductase in Support of Early-Stage Drug Discovery

Pteridine reductase-1 (PTR1) is a promising drug target for the treatment of trypanosomiasis. We investigated the potential of a previously identified class of thiadiazole inhibitors of Leishmania major PTR1 for activity against Trypanosoma brucei (Tb). We solved crystal structures of several TbPTR1-inhibitor complexes to guide the structure-based design of new thiadiazole derivatives. Subsequent synthesis and enzyme- and cell-based assays confirm new, mid-micromolar inhibitors of TbPTR1 with low toxicity. In particular, compound 4m, a biphenyl-thiadiazole-2,5-diamine with IC50 = 16 μM, was able to potentiate the antitrypanosomal activity of the dihydrofolate reductase inhibitor methotrexate (MTX) with a 4.1-fold decrease of the EC50 value. In addition, the antiparasitic activity of the combination of 4m and MTX was reversed by addition of folic acid. By adopting an efficient hit discovery platform, we demonstrate, using the 2-amino-1,3,4-thiadiazole scaffold, how a promising tool for the development of anti-T. brucei agents can be obtained

The Loss of the p53 Activator HIPK2 Is Responsible for Galectin-3 Overexpression in Well Differentiated Thyroid Carcinomas

Background: Galectin-3 (Gal-3) is an anti-apoptotic molecule involved in thyroid cells transformation. It is specifically overexpressed in thyroid tumour cells and is currently used as a preoperative diagnostic marker of thyroid malignancy. Gal-3 expression is downregulated by wt-p53 at the transcriptional level. In well-differentiated thyroid carcinomas (WDTCs) there is an unexplained paradoxical concomitant expression of Gal-3 and wt-p53. HIPK2 is a co-regulator of different transcription factors, and modulates basic cellular processes mainly through the activation of wt-p53. Since we demonstrated that HIPK2 is involved in p53-mediated Gal-3 downregulation, we asked whether HIPK2 deficiency might be responsible for such paradoxical Gal-3 overexpression in WDTC. Methodology/Principal Findings: We analyzed HIPK2 protein and mRNA levels, as well as loss of heterozygosity (LOH) at the HIPK2 locus (7q32-34), in thyroid tissue samples. HIPK2 protein levels were high in all follicular hyperplasias (FHs) analyzed. Conversely, HIPK2 was undetectable in 91.7% of papillary thyroid carcinomas (PTCs) and in 60.0% of follicular thyroid carcinomas (FTCs). HIPK2 mRNA levels were upregulated in FH compared to normal thyroid tissue (NTT), while PTC showed mean HIPK2 mRNA levels lower than FH and, in 61.5% of cases, also lower than NTT. We found LOH at HIPK-2 gene locus in 37.5% of PTCs, 14.3% of FTCs and 18.2% of follicular adenomas. To causally link these data with Gal-3 upregulation, we performed in vitro experiments, using the PTC-derived K1 cells, in which HIPK2 expression was manipulated by RNA interference (RNAi) or plasmid-mediated overexpression. HIPK2 RNAi was associated with Gal-3 upregulation, while HIPK2 overexpression with Gal-3 downregulation. Conclusions/Significance: Our results indicate that HIPK2 expression and function are impaired in WDTCs, in particular in PTCs, and that this event explains Gal-3 overexpression typically observed in these types of tumours. Therefore, HIPK2 can be considered as a new tumour suppressor gene for thyroid cancers

How future surgery will benefit from SARS-COV-2-related measures: a SPIGC survey conveying the perspective of Italian surgeons

COVID-19 negatively affected surgical activity, but the potential benefits resulting from adopted measures remain unclear. The aim of this study was to evaluate the change in surgical activity and potential benefit from COVID-19 measures in perspective of Italian surgeons on behalf of SPIGC. A nationwide online survey on surgical practice before, during, and after COVID-19 pandemic was conducted in March-April 2022 (NCT:05323851). Effects of COVID-19 hospital-related measures on surgical patients' management and personal professional development across surgical specialties were explored. Data on demographics, pre-operative/peri-operative/post-operative management, and professional development were collected. Outcomes were matched with the corresponding volume. Four hundred and seventy-three respondents were included in final analysis across 14 surgical specialties. Since SARS-CoV-2 pandemic, application of telematic consultations (4.1% vs. 21.6%; p &lt; 0.0001) and diagnostic evaluations (16.4% vs. 42.2%; p &lt; 0.0001) increased. Elective surgical activities significantly reduced and surgeons opted more frequently for conservative management with a possible indication for elective (26.3% vs. 35.7%; p &lt; 0.0001) or urgent (20.4% vs. 38.5%; p &lt; 0.0001) surgery. All new COVID-related measures are perceived to be maintained in the future. Surgeons' personal education online increased from 12.6% (pre-COVID) to 86.6% (post-COVID; p &lt; 0.0001). Online educational activities are considered a beneficial effect from COVID pandemic (56.4%). COVID-19 had a great impact on surgical specialties, with significant reduction of operation volume. However, some forced changes turned out to be benefits. Isolation measures pushed the use of telemedicine and telemetric devices for outpatient practice and favored communication for educational purposes and surgeon-patient/family communication. From the Italian surgeons' perspective, COVID-related measures will continue to influence future surgical clinical practice