Enzyme-based chemical biosensors are based on biological recognition. In order to operate, the enzymes must be available to catalyze a specific biochemical reaction and be stable under the normal operating conditions of the biosensor. Design of biosensors is based on knowledge about the target analyte, as well as the complexity of the matrix in which the analyte has to be quantified. This article reviews the problems resulting from the interaction of enzyme-based amperometric biosensors with complex biological matrices containing the target analyte(s). One of the most challenging disadvantages of amperometric enzyme-based biosensor detection is signal reduction from fouling agents and interference from chemicals present in the sample matrix. This article, therefore, investigates the principles of functioning of enzymatic biosensors, their analytical performance over time and the strategies used to optimize their performance. Moreover, the composition of biological fluids as a function of their interaction with biosensing will be presented.

Planar 131 I scintigraphy is routinely used to detect radioiodineavid metastases of differentiated thyroid carcinoma (DTC). However, the modality has limitations, such as low sensitivity and lack of anatomic landmarks. We investigated whether SPECT with integrated low-dose CT may have additional value over planar imaging in detecting residue and metastases in DTC patients. Methods: We studied 117 consecutive thyroidectomized DTC patients. On 2 different hybrid dual-head g-cameras (55 patients on one camera and 62 on the other), 108 patients underwent 131 I diagnostic imaging and SPECT/ CT, and 9 underwent posttherapeutic 131 I planar imaging and SPECT/CT. We assigned an incremental value to SPECT/CT when it provided better identification and interpretation of the foci of radioiodine uptake, more correct anatomic localization and characterization, and precise differentiation between tumor lesions and physiologic uptake. Results: Planar imaging showed 116 foci of uptake in 52 of 117 patients, and SPECT/CT showed 158 foci in 59 of 117 patients, confirming all foci seen on planar imaging but identifying an additional 28 occult foci in 10 of 52 patients. Fourteen occult foci were shown on SPECT/CT in 7 further patients whose planar imaging findings were negative. SPECT/ CT correctly characterized 48 foci unclear on planar imaging, also defining location and extent. SPECT/CT was a determinant in classifying as neoplastic those foci for which planar imaging seemed to exclude malignancy, discriminating between residue and lymph node metastases in the neck, some of which were adjacent to salivary glands and had been missed on planar imaging. SPECT/CT also showed occult lesions in the mediastinum, abdomen, and pelvis and identified small bone metastases unsuspected on planar imaging. Globally, SPECT/CT had an incremental value over planar imaging in 67.8% of patients, modified therapeutic management in 35.6% of positive cases, and avoided unnecessary treatment in 20.3% of patients with only single benign lesions or physiologic uptake. Conclusion: 131 I SPECT/CT improved planar data interpretation, showing a higher number of DTC lesions, more precisely localizing and characterizing DTC foci, and more correctly differentiating between physiologic uptake and metastases, thus permitting the most appropriate therapeutic approach to be chosen. A wider use of this method is suggested complementary to planar imaging in selected DTC patients. Convent ional planar 131 I whole-body scintigraphy, in association with serum thyroglobulin measurement, is still considered the routine diagnostic procedure in patients with well-differentiated thyroid carcinoma (DTC). This modality is used in the detection of both thyroid tissue residue and local and distant metastases, after thyroidectomy for staging and after radioiodine ablation for restaging and long-term follow-up (1). A sensitivity of 45%275% and a specificity of 90%2100% have been reported in the literature for diagnostic planar 131 I whole-body imaging in detecting recurrences or me...

HAART, particularly stavudine, is associated with a high prevalence of subclinical hypothyroidism. Hypotheses are made regarding responsible mechanisms and risk factors. Thyroid function should be tested and sequentially rechecked in HAART patients.

Cholangiocarcinoma (CCA) is a highly-aggressive malignancy arising from the biliary tree, characterized by a steady increase in incidence globally and a high mortality rate. Most CCAs are diagnosed in the advanced and metastatic phases of the disease, due to the paucity of signs and symptoms in the early stages. This fact, along with the poor results of the local and systemic therapies currently employed, is responsible for the poor outcome of CCA patients and strongly supports the need for novel therapeutic agents and strategies. In recent years, the introduction of next-generation sequencing technologies has opened new horizons for a better understanding of the genetic pathophysiology of CCA and, consequently, for the identification and evaluation of new treatments tailored to the molecular features or alterations progressively elucidated. In this review article, we describe the potential targets under investigation and the current molecular therapies employed in biliary tract cancers. In addition, we summarize the main drugs against CCA under evaluation in ongoing trials and describe the preliminary data coming from these pioneering studies.

No abstract

Papillary thyroid microcarcinoma (PTMC) usually has a favorable prognosis but can also be aggressive, with neck and distant metastases. We evaluated the diagnostic role of I SPECT/CT in detecting metastases in PTMC patients during long-term follow-up and whether the procedure should be included in the current diagnostic protocol. We retrospectively studied 351 consecutive PTMC patients who had undergone thyroidectomy and radioiodine therapy; 21 were at high risk, 94 at low risk, and 236 at very low risk. During follow-up, the patients underwent diagnostic I whole-body scanning (WBS) followed by SPECT/CT. WBS found 248 radioiodine-avid foci in 126 patients, and SPECT/CT found 298 in 139 patients, confirming all foci found on WBS. SPECT/CT also correctly classified 76 of the avid foci as unclear or wrongly classified on WBS. Globally, SPECT/CT detected and correctly classified 64 neoplastic lesions in 27 of 30 patients with metastases, and WBS evidenced 39 of 64 lesions, 28 of which were unclear or wrongly classified, in 16 of the 30 patients. Nineteen of 27 patients, including 13 at very low risk, had only neck metastases, 9 of 19 being T1aN0M0 with an undetectable thyroglobulin level. Three of 27 patients, including 1 at very low risk, had only distant metastases with an undetectable or very low thyroglobulin level. Five of 27 patients had neck and distant metastases with a thyroglobulin level <2.5 ng/mL in 1 case, between 2.5 and 10 in 3 cases, and >10 in the remaining case. SPECT/CT also reduced WBS false-positive results in 15 of 139 patients (10.8%). SPECT/CT had an incremental value over WBS in 38.1% of patients with positive findings and changed the classification and therapeutic management in 21.6%. Metastases occurred in 8.5% of patients during long-term follow-up. SPECT/CT performed better than WBS, particularly in patients at very low risk with inconclusive WBS results, a TNM stage of T1aN0M0, and an undetectable or very low level of thyroglobulin. Prolonged surveillance is justified in PTMC patients, and wider use ofI SPECT/CT in the diagnostic protocol is suggested.

Purpose To combine peripheral blood indices and clinical factors in a prognostic score for metastatic castration-resistant prostate cancer (mCRPC) patients treated with radium-223 dichloride ([223Ra]RaCl2). Patients and methods Baseline neutrophil-to-lymphocyte ratio (NLR), derived NLR (donor), lymphocyte-to-monocyte ratio (LMR), platelet-to-lymphocyte ratio (PLR), systemic inflammation index (SII), Eastern Cooperative Oncology Group performance status (ECOG PS), Gleason score (GS) group, number of bone metastases, prostate-specific antigen (PSA), alkaline phosphatase (ALP), line of therapy, previous chemotherapy, and the presence of lymphadenopathies were collected from seven Italian centers between 2013 and 2020. Lab and clinical data were assessed in correlation with the overall survival (OS). Inflammatory indices were then included separately in the multivariable analyses with the prognostic clinical factors. The model with the highest discriminative ability (c-index) was chosen to develop the BIO-Ra score. Results Five hundred and nineteen mCRPC patients (median OS: 19.9 months) were enrolled. Higher NLR, dNLR, PLR, and SII and lower LMR predicted worse OS (all with a p < 0.001). The multivariable model including NLR, ECOG PS, number of bone metastases, ALP, and PSA (c-index: 0.724) was chosen to develop the BIO-Ra score. Using the Schneeweiss scoring system, the BIO-Ra score identified three prognostic groups (36%, 27.3%, and 36.6% patients, respectively) with distinct median OS (31, 26.6, and 9.6 months, respectively; hazard ratio: 1.62, p = 0.008 for group 2 vs. 1 and 5.77, p < 0.001 for group 3 vs. 1). Conclusions The BIO-Ra score represents an easy and widely applicable tool for the prognostic stratification of mCRPC patients treated with [223Ra]RaCl2 with no additional costs.

In this paper, we investigate the role of shape and texture features from 18F-FDG PET/CT to discriminate between benign and malignant solitary pulmonary nodules. To this end, we retrospectively evaluated cross-sectional data from 111 patients (64 males, 47 females, age = 67.5 ± 11.0) all with histologically confirmed benign (n=39) or malignant (n=72) solitary pulmonary nodules. Eighteen three-dimensional imaging features, including conventional, texture, and shape features from PET and CT were tested for significant differences (Wilcoxon-Mann-Withney) between the benign and malignant groups. Prediction models based on different feature sets and three classification strategies (Classification Tree, k-Nearest Neighbours, and Naïve Bayes) were also evaluated to assess the potential benefit of shape and texture features compared with conventional imaging features alone. Eight features from CT and 15 from PET were significantly different between the benign and malignant groups. Adding shape and texture features increased the performance of both the CT-based and PET-based prediction models with overall accuracy gain being 3.4–11.2 pp and 2.2–10.2 pp, respectively. In conclusion, we found that shape and texture features from 18F-FDG PET/CT can lead to a better discrimination between benign and malignant lung nodules by increasing the accuracy of the prediction models by an appreciable margin.