Intracardiac Porcupine Quill Migration in a Dog: Multimodality Imaging Findings and Surgical Management.

The porcupine is a nocturnal quill-bearing rodent common throughout Italy. When threatened, it defends itself by erecting its quills, rattling its tail, and running sideways or backyard into predators. The quills are released upon contact with assailants and tend to migrate into several body tissues or cavities due to the unique inverted cuticles (crenate) directed downwards to the quill base (a sort of "harpoon effect"). Intracardiac migration of porcupine quills has been reported in a few dogs with severe clinical signs. This case report describes a single porcupine quill [Hystrix cristata, (HC)] migration through the heart in a dog and the use of multimodality imaging for the diagnosis and surgical approach. A 4-year-old 25 kg female mixed-breed dog was presented for evaluation of recurrent fever. Transthoracic echocardiographic examination showed a linear, hyperechoic foreign body traversing the interventricular septum from the heart base to the cardiac apex. Computed tomography and transesophageal echocardiography confirmed the presence of a single structure resembling a quill; a later esophageal endoscopy showed no anatomical alterations or mucosal injuries. Following median sternotomy and after accurate localization by intraoperative ultrasound, the quill was successfully removed. The dog had a good recovery without evidence of severe cardiac injury secondary to an intracardiac quill. To the best of the authors' knowledge, the identification of an intracardiac HC quill by ultrasonography and CT and its successful removal by ultrasound guide has not been previously reported.

Economic Impact of COVID-19 Lockdown on Italian NHS: Focus on Diabetes Mellitus.

BACKGROUND: In Italy, the adoption of a total lockdown has generated almost total suspension of outpatient visits except for emergencies. Even after lockdown, the pandemic fear created additional barriers to access the health services. The aim of our study is to evaluate the economic impact of the lockdown for COVID-19 on public health in Italy, focusing on its effects on diabetic population. MATERIALS AND METHODS: We analyzed the impact of the lockdown on excess mortality and morbidity in the Italian diabetic population during 2020. The analysis was divided into several steps: a quantification of specialist visit reduction, the calculation of excess mortality in the diabetic population, the economic evaluation of the slowdown in the use of innovative diabetic therapies. Furthermore, the impact of the lockdown on the reduction of procedures and follow-up visits in diabetic population was evaluated. The overall impact of the pandemic and lockdown effects on costs and quality of life was then calculated. RESULTS: During 2020, a drop of 28% in patient access has been observed. Diabetic patients recorded a twice higher mortality value compared to general population (20.4% vs 10.2%). The analysis of market data revealed a slowdown in consumption of new antidiabetic therapies (-14%, 27% vs 41%). We estimated an expense of €26.6 million for NHS and a loss of 257 utilities in diabetic population due to the missed benefits related to slowdown in innovative antidiabetic drugs use and non-optimal follow-up and control of diabetes complications. In simulation scenarios, we also estimated an overall expenditure ranging from €38.7 to 94.0 million and a loss of 294-836 utilities. CONCLUSION: Diabetic population paid a high tribute to pandemic and lockdown, both in terms of number of deaths and burden of diabetic complications, together with an overall deterioration of quality of life.

Effect of Polyvinyl Alcohol Ligands on Supported Gold Nano-Catalysts: Morphological and Kinetics Studies.

The effect of polyvinyl alcohol (PVA) stabilizers and gold nanoparticles supported on active carbon (AuNPs/AC) was investigated in this article. Polymers with different molecular weights and hydrolysis degrees have been synthesized and used, like the stabilizing agent of Au nano-catalysts obtained by the sol-immobilization method. The reduction of 4-nitrophenol with NaBH4 has been used as a model reaction to investigate the catalytic activity of synthesized Au/AC catalysts. In addition, we report several characterization techniques such as ultraviolet-visible spectroscopy (UV-Vis), dynamic light scattering (DLS), X-ray diffraction (XRD), transmission electron microscopy (TEM), and X-ray photoelectron spectroscopy (XPS) in order to correlate the properties of the polymer with the metal nanoparticle size and the catalytic activity. A volcano plot was observed linking the catalytic performance with hydrolysis degree and the maximum of the curve was identified at a value of 60%. The Au:PVA-60 weight ratio was changed in order to explain how the amount of the polymer can influence catalytic properties. The effect of nitroaromatic ring substituents on the catalytic mechanism was examined by the Hammett theory. Moreover, the reusability of the catalyst was investigated, with little to no decrease in activity observed over five catalytic cycles. Morphological and kinetic studies reported in this paper reveal the effect of the PVA polymeric stabilizer properties on the size and catalytic activity of supported gold nanoparticles.

A comparative cross-sectional study on sleep quality in patients with a history of differentiated thyroid carcinoma and its correlation with quality of life.

PURPOSE: To evaluate sleep quality in differentiated thyroid carcinoma (DTC) patients and correlate sleep disturbances with quality of life (QoL). METHODS: 119 DTC patients were enrolled (DTC group). The Pittsburgh Sleep Quality Index (PSQI) and the Insomnia Severity Index (ISI) inventories were administered. The Thyroid-specific Patient-Reported Outcome (ThyPRO) questionnaire, the Billewicz scale (BS) and an ad-hoc visual analogic scale (VAS) were used to measure QoL and subjective therapy-related complaints. The same examinations were conducted in 53 subjects (control group) who had undergone surgery for benign thyroid pathology. RESULTS: L-T4 dosages and TSH levels differed between the groups. BS and VAS scores were comparable. PSQI documented a similar percentage of poor sleepers in the DTC (74%) and control (62%) groups. ISI showed no difference in subjects without clinically significant insomnia: DTC (43%) and controls (48%). ThyPRO showed significantly worse scores in DTC than control subjects. In DTC patients, PSQI (P = 0.002) and ISI (P = 0.04) correlated significantly with age. In control subjects, TSH displayed a significant positive association with PSQI (P = 0.02) and ISI (P < 0.05). The ThyPRO general score correlated significantly with PSQI in DTC patients. In both groups, ISI correlated significantly with several ThyPRO scales and the ThyPRO general score. "Anxiety" and "emotional susceptibility" were the scales most significantly related with PSQI and ISI. CONCLUSION: In disease-free DTC patients and subjects who undergo thyroid surgery for benign pathology, abnormal sleep components and insomnia are similar. The ThyPRO questionnaire closely reflects sleep disturbances in all subjects. Recognising and treating sleep disturbances might improve QoL.

Evaluation of Quality of Life in Patients with Differentiated Thyroid Cancer by Means of the Thyroid-Specific Patient-Reported Outcome Questionnaire: A 5-Year Longitudinal Study.

BACKGROUND: Patients with malignancy suffer impairment of their quality of life (QoL). QoL has been evaluated in thyroid cancer patients. Since 2010, a new inventory, the thyroid-specific patient-reported outcome (ThyPRO) measure for benign thyroid disorders, has been available. AIM: This study evaluated QoL longitudinally in patients with a history of differentiated thyroid cancer (DTC) by means of the ThyPRO questionnaire. Methods : From 2012 to 2016, QoL was evaluated yearly in 123 adult DTC patients by means of ThyPRO. The ThyPRO questionnaire consists of 13 scales on which higher scores represent greater impact on QoL in areas affected by thyroid pathology. Disease-specific morbidity due to possible inadequate L-T4 treatment was evaluated by means of the Billewicz scale (BS). The same examinations were conducted in 192 control subjects who had undergone surgery for benign thyroid pathology. RESULTS: DTC and control subjects had similar scores on all but one scale; scores on the hyperthyroid symptoms scale were significantly higher in DTC patients than in controls. Over the 5 years, scores did not change significantly in the DTC group. Overall, QoL and BS scores showed a slight, but not significant, improvement during the study period in DTC patients. BMI impacted on several ThyPRO scales. No significant differences between genders were noted in DTC. CONCLUSIONS: The ThyPRO questionnaire indicates that illness perception is similar after thyroidectomy for malign and benign pathology. Only a marginal improvement in QoL was noted in DTC subjects over the 5-year study period. In both groups, females showed a greater perception of illness than males.

Cross-sectional and prospective study on anti-Müllerian hormone changes in a cohort of pre-menopausal women with a history of differentiated thyroid cancer.

BACKGROUND: Anti-Müllerian hormone (AMH) decreases acutely after post-surgical radioactive iodine (RAI) ablation in females with differentiated thyroid cancer (DTC). AIM: We performed a cross-sectional and prospective study on AMH levels in pre-menopausal females with a history of DTC. METHODS: Fifty-nine females after surgery and RAI (group 1) and 30 females after surgery alone (group 2) were studied. The control group consisted of 141 healthy women (group 3). The prospective study was performed in 43 and 14 females from groups 1 and 2, respectively. RESULTS: On first evaluation, AMH levels were similar in groups 1 and 2, but lower than in group 3. In all groups, AMH was negatively related with chronological age and FSH levels. When subjects were stratified according to age, AMH levels were not different between groups. When AMH was evaluated up to 2 years after the baseline evaluation, no changes emerged in either group of women with DTC. In the prospective study, the incidence of abnormal menstrual cycles and the onset of menopause were observed in similar percentages of women with a history of RAI-treated DTC and of those treated with surgery alone. CONCLUSIONS: AMH can be considered a reliable index of ovarian reserve in women with DTC. Chronological age is the main factor influencing AMH levels in both DTC patients and controls. After age-related stratification, AMH levels are similar in women with DTC treated with RAI and those treated with surgery alone.

Urinary Iodine Concentration in a Cohort of Adult Outpatients with Thyroid Diseases in Liguria 14 Years after the Law on Salt Iodization.

Italy is considered a mildly iodine-deficient country. The aim of this study was to evaluate the iodine status of a cohort of adults living in Liguria after the 2005 salt iodization program. We searched all medical records of patients examined in two endocrine outpatient clinics in Genoa and Savona for data on urinary iodine. Subjects were under evaluation for thyroid diseases. Information on the type of salt used was found in few clinical records. Iodized salt use was reported in 29%, 20%, and 13% of records of people living in Genoa districts, the Savona district and nearby districts, respectively. The average urinary iodine concentration was 112.9 ± 62.3 µg/L (n = 415, median 101.0 µg/L). Non-significant differences (P > 0.05) were found between subjects with (median 103.5 µg/L) and without (median 97.5 µg/L) a thyroid gland, between the periods 2009-2013 (median 105.0 µg/L) and 2014-2018 (median 97.5 µg/L), and between Genoa (median 94.0 µg/L), Savona (median 105.0 µg/L) and the other districts (median 114.5 µg/L). No correlation with age, body mass index, creatinine, free thyroxine, thyroglobulin, levo-thyroxine dosage, or thyroid volume was observed. These data suggest a borderline status of iodine sufficiency in this cohort.

Case report: lenvatinib in neoadjuvant setting in a patient affected by invasive poorly differentiated thyroid carcinoma.

We report a case of an elderly woman presenting with a huge cervical mass invading the tracheal lumen. Diagnosed as invasive poorly differentiated thyroid cancer, after an endotracheal biopsy, stenting and radiotherapy, it was judged eligible for total thyroidectomy, but surgery was delayed due to pulmonary thromboembolism. The patient was therefore treated with lenvatinib with a neoadjuvant intent until hemodynamic stability was obtained. Thyroidectomy and radioiodine therapy were then performed and the postdose scan revealed an area of modest uptake in the anterior part of the neck. The patient is now in a good clinical status and she continues her follow-up program without any adjuvant therapy.

An H-TERT Mutated Skin Metastasis as First Occurrence in a Case of Follicular Thyroid Carcinoma.

Differentiated thyroid cancer arising from thyroid follicular epithelial cells is the most frequent endocrine malignancy, and skin metastases are very rare. We describe a case of a 70-year-old women with a history of an indeterminate thyroid nodule on cytology. A painless, erythematous skin nodule of about 7 mm diameter was removed from the scalp and diagnosed as a metastasis from thyroid cancer. After total thyroidectomy, a histological diagnosis of follicular thyroid cancer was made. Two cycles of radioactive iodine were performed. Both the follicular thyroid carcinoma (FTC) and the metastasis were investigated for the presence of BRAF/RAS and TERT promoter mutations. The results showed that the cutaneous metastasis was BRAF wild-type and TERT promoter-mutated (position g.1,295,228 C>T); in contrast, the primary thyroid lesion was negative for both molecular markers.

Retrospective cytological evaluation of indeterminate thyroid nodules according to the British Thyroid Association 2014 classification and comparison of clinical evaluation and outcomes.

The cytology of 130 indeterminate nodules (Thy 3) was retrospectively reviewed according to the British Thyroid Association 2014 classification. Nodules were divided into Thy 3a (atypical features) and Thy 3f (follicular lesion) categories. Histology was available as a reference for 97 nodules. Pre-surgical evaluations comprised biochemical tests, color-Doppler ultrasonography (US), semi-quantitative elastography-US (USE), contrast-enhanced US (CEUS), and mutation analysis from cytological slides. Thyroid malignancy was the final diagnosis for 19% of surgically-treated nodules. No statistically significant difference in the risk of malignancy was found between Thy 3a (26%) and Thy 3f (14%) nodules. Histology of the Thy 3a and Thy 3f nodules showed a higher incidence of Hurtle cell adenomas in Thy 3f (29%) than in Thy 3a (3%) nodules (P=0.01). The only pre-surgical difference concerned the BRAF V600E mutation, which was positive in some Thy 3a but not in any Thy 3f nodules (P=0.04). Receiver-operating characteristic (ROC) analysis was used to obtain cut-off values from US (score), USE (ELX 2/1 strain index), and CEUS (time-to-peak index and peak index) data. The cut-off values were similar for Thy 3a and Thy 3f nodules. Data showed that malignancy can be suspected if the US score is >2, ELX 1/2 strain index >1, time-to-peak index >1, and peak index <1. In a sub-group of 24 revised nodules (12 Thy 3a and 12 Thy 3f) with histology as a reference, the diagnostic power of cumulative pre-surgical analysis by means of US, USE, and CEUS showed high positive and negative predictive values (83% and 100%, respectively) for the presence of malignancy in Thy 3a and Thy 3f nodules. In conclusion, in our series of revised Thy 3 nodules, malignancy was low and displayed no significant differences between Thy 3a and Thy 3f categories. The use of cut-offs based on histology as a reference could reduce surgery. Our data support the conviction that, in mutation-negative Thy 3a and Thy 3f nodules, observation should be the first choice when not all instrumental results are suspect.

Ten-year estimated risk of bone fracture in women with differentiated thyroid cancer under TSH-suppressive levothyroxine therapy.

INTRODUCTION: After thyroidectomy and radioiodine therapy, patients with differentiated thyroid cancer (DTC) are indefinitely treated with levothyroxine (L-T4). Osteoporosis is a debated consequence of hypothyroxinaemia. The aim of this study was to evaluate bone mineral density (BMD) and fracture risk assessed by FRAX in a cohort of DTC women. MATERIAL AND METHODS: Seventy-four women with DTC (aged 56.5 ± 9.9 years) treated at the mean age of 51.9 ± 12.0 years were studied. Baseline BMD and FRAX were evaluated after 3.0 years (median). BMD and FRAX were further evaluated 5.5 years (median) after the baseline evaluation. A cohort of 120 euthyroid women, matched for age, BMI, and menopausal status, were evaluated as controls. RESULTS: L-T4 dosages were 813.6 ± 208.8 µg/week and 782.1 ± 184.4 µg/week at the baseline and second evaluation, respectively. The risks of major osteoporotic fracture (MOF) and hip fracture (HF) were similar in DTC patients and in controls. In DTC women, significant changes in FRAX were found, with a higher increase in the probability of HF than of MOF. A similar change was found in controls. A significant inverse correlation (P < 0.001) between L-T4 dosage and HF/MOF probability on both first and second evaluations was found. A significant inverse correlation (P = 0.05) was found between fT4, TSH and duration of therapy and HF/MOF probability only on the second evaluation. CONCLUSIONS: FRAX increase is a multi-factorial, age-related phenomenon. The absence of correlations between L-T4 dosage, length of therapy or fT4 levels and FRAX does not enable us to attribute an increased fracture risk to DTC women with well-controlled disease on therapy. (Endokrynol Pol 2016; 67 (4): 350-358).

The Ribonucleic Complex HuR-MALAT1 Represses CD133 Expression and Suppresses Epithelial-Mesenchymal Transition in Breast Cancer.

Epithelial-to-mesenchymal transition (EMT) is a core process underlying cell movement during embryonic development and morphogenesis. Cancer cells hijack this developmental program to execute a multi-step cascade, leading to tumorigenesis and metastasis. CD133 (PROM1), a marker of cancer stem cells, has been shown to facilitate EMT in various cancers, but the regulatory networks controlling CD133 gene expression and function in cancer remain incompletely delineated. In this study, we show that a ribonucleoprotein complex including the long noncoding RNA MALAT1 and the RNA-binding protein HuR (ELAVL1) binds the CD133 promoter region to regulate its expression. In luminal nonmetastatic MCF-7 breast cancer cells, HuR silencing was sufficient to upregulate N-cadherin (CDH2) and CD133 along with a migratory and mesenchymal-like phenotype. Furthermore, we found that in the basal-like metastatic cell line MDA-MB-231 and primary triple-negative breast cancer tumor cells, the repressor complex was absent from the CD133-regulatory region, but was present in the MCF-7 and primary ER+ tumor cells. The absence of the complex from basal-like cells was attributed to diminished expression of MALAT1, which, when overexpressed, dampened CD133 levels. In conclusion, our findings suggest that the failure of a repressive complex to form or stabilize in breast cancer promotes CD133 upregulation and an EMT-like program, providing new mechanistic insights underlying the control of prometastatic processes. Cancer Res; 76(9); 2626-36. ©2016 AACR.

BRAF Mutations in an Italian Regional Population: Implications for the Therapy of Thyroid Cancer.

Background. Molecular diagnostics has offered new techniques for searching for mutations in thyroid indeterminate lesions. The study's aim was to evaluate the BRAF mutations' incidence in an Italian regional population. Subjects and Methods. 70 Caucasian patients born in Liguria with indeterminate or suspicious cytological diagnoses. Results. A BRAF gene mutation was successfully analyzed in 56/70 patients. The mutation was BRAF V600E in 12/56 cases (21%) and BRAF K601E in 2/56 (4%). Of the BRAF mutated samples on cytological diagnosis (14/56 cases), 2/14 cases (14%) were benign on final histology and 12/14 (86%) were malignant. All BRAF-mutated cases on cytology that were found to be benign on histological examination carried the K601E mutation. Of the nonmutated BRAF cases (42/56, 75%) which were later found to be malignant on definitive histology, 5 cases were follicular carcinomas (36%), 3 cases were incidentally found to be papillary microcarcinomas (22%), 2 were cases papillary carcinomas (14%), 1 was case follicular variant of papillary carcinoma (7%), 1 was case medullary carcinoma (7%), 1 case was Hurtle cell tumor (7%), and 1 case was combined cell carcinoma and papillary oncocytic carcinoma (7%). Conclusions. The presence of the BRAF V600E mutation may suggest a more aggressive surgical approach. BRAF K601E mutation did not correlate with malignancy indexes.

Papillary thyroid cancer in a struma ovarii: a report of a rare case.

After removal of an ovarian mass in a 43-year-old woman, a struma ovarii was diagnosed. Within this teratoma, a papillary thyroid cancer was found. The tumor was negative for BRAF, NRAS, KRAS, PIK3CA and c-KIT mutations on molecular analysis. Thyroid function and morphology were normal. Thyroidectomy, L-T4 TSH-suppressive therapy and rhTSH-induced radioiodine ablation were performed. So far, the follow-up has been favorable. This is the first case of thyroid cancer in a struma ovarii in which mutations of PIK3CA exons 9 and 20, and c-KIT exons 9, 11 and 13 have been evaluated and the third in which ablation has been performed under rhTSH. The prognosis of patients with thyroid cancer in a struma ovarii is generally poor. In our patient, as in those who undergo ablative radioactive iodine therapy, this was not the case.

The use of semi-quantitative ultrasound elastosonography in combination with conventional ultrasonography and contrast-enhanced ultrasonography in the assessment of malignancy risk of thyroid nodules with indeterminate cytology.

BACKGROUND: The pre-surgical selection of thyroid nodules with indeterminate cytology (Thy 3 according to British Thyroid Association) after fine-needle aspiration biopsy (FNAB) is currently required in order to reduce unnecessary total thyroidectomy. The objective of our study was to use a surgical series of Thy 3 nodules to evaluate the predictive role of ultrasound elastosonography (USE) and contrast-enhanced ultrasonography (CEUS) in pre-surgical diagnoses of malignancy. SUBJECTS AND METHODS: We enrolled 63 patients with Thy 3 nodules in which cytological-histological correlation was available. The ELX 2/1 strain index was obtained by means of semi-quantitative USE, which was performed before surgery in addition to conventional ultrasonography (US) and contrast-enhanced US (CEUS) on the Thy 3 nodules. The ELX 2/1 strain index, a five-item US score and both peak (P) index and time to peak (TTP) index from CEUS were correlated with the histological results. After surgical diagnosis, the data were analysed by using a receiver-operating characteristic (ROC) curve. RESULTS: Histology was benign in 50 and malignant in 13 Thy 3 nodules. No difference in maximal diameter was noted between benign (22.8 ± 1.6 mm) and malignant (18.9 ± 2.9 mm) nodules. Significant correlations were found between histology and cumulative US findings (p=0.005), ELX 2/1 index (p=0.002), P index (p=0.01) and TTP index (p=0.02). On analysing data from US, USE and CEUS, significant ROC areas under the curve were observed (p<0.0001). A cut-off value was set for US (>2), ELX 2/1 (>0.95), P index (<0.99) and TTP index (>0.98) scores. The diagnostic power of the cumulative pre-surgical analysis of Thy 3 nodules with US, USE and CEUS, considering the experimental cut-off points obtained from the ROC curves was: sensitivity 64%, specificity 92%, PPV 75% and accuracy 84%. CONCLUSION: The ELX 2/1 index in conjunction with the US score can be useful in orienting surgical strategies in Thy 3 nodules. The information added by CEUS is less sensitive than that provided by US and USE. The use of a cut-off based on histology can reduce thyroidectomy. Observation should be the first choice when not all instrumental results are suspect.