Change in eating habits after 2 years of pandemic restrictions among adolescents living in a city in northern Italy: results of the COALESCENT Observational Study (Change amOng ItAlian adoLESCENTs).

Background: Lockdown measures during the recent pandemic, due to the novel COVID-19, affected several other aspects of lifestyle, but little is known about their long-term impact, especially among adolescents. Our study aimed to assess the long-term consequences of changes in diet, exercise and screen activity levels, sleep quality, smoke, smartphone addiction and emotional distress among a sample of Italian adolescents, 2 years after the beginning of the pandemic. Methods: We submitted an online survey to high-school students in the province of Brescia, a city in Northern Italy, investigating changes in food consumption and in physical and screen activities, cooking skills, sleep duration and quality, emotional distress, smartphone addiction and nutrition knowledge. We assigned an Eating Habit Index (EHI) score from 0 to 54, reflecting a current worsening (lower score) or improvement (higher score) in overall diet quality, compared with the pre-pandemic period. The χ2 test or Fisher's exact probability test and Mann-Whitney test were used as appropriate; a binary logistic regression model was carried out, with EHI score≥33 as the dependent variable. Results: We collected 1686 questionnaires. Consumption of healthy foods increased, as it was for ultraprocessed foods (UPFs). EHI score>33 (75° percentile value) was associated with female gender (OR 1.81, p<0.0001), better nutrition knowledge (OR 1.54, p=0.001), better cooking skills (OR 1.43, p=0.01), lower consumption of UPFs before the pandemic (OR 2.19, p<0.0001), self-perception of healthier diet quality (OR: 4.05, p<0.0001) and no smartphone addiction (OR: 1.35, p=0.02). Conclusions: Considering the profound impact of lifestyle on both physical and mental health, our results could be relevant to understand how to promote healthy eating practices among young people.

Mediterranean-Oriented Dietary Intervention Is Effective to Reduce Liver Steatosis in Patients with Nonalcoholic Fatty Liver Disease: Results from an Italian Clinical Trial.

Results: One hundred and fifty five subjects aged 20-59 years underwent (i) liver ultrasound (US), (ii) clinical and anthropometric evaluations, (iii) blood tests, and (iv) assessment of dietary habits. According to US evaluation, 73 of them had severe, moderate, or mild liver steatosis (NAFLD patients) and 82 had no liver steatosis (healthy controls). Fifty-eight NAFLD patients and 73 controls completed the study. Among NAFLD patients, 26 (45%) downgraded steatosis severity, 12 of which achieved complete steatosis regression (21%). Three of the healthy controls developed NAFLD. The NAFLD patients improved their dietary habits and reduced BMI and waist circumference, during the study period, more than healthy controls. Liver steatosis remission/regression was independent of changes in BMI or liver enzymes and was more frequent among patients with mild steatosis at baseline. Conclusions: Mediterranean dietary advices, without a personalised meal planning, were efficient in reducing/remitting NAFLD, especially among patients with mild disease, which argues in favour of early identification and lifestyle intervention. This trial is registered with NCT03300661.

Cooking Skills, Eating Habits and Nutrition Knowledge among Italian Adolescents during COVID-19 Pandemic: Sub-Analysis from the Online Survey COALESCENT (Change amOng ItAlian adoLESCENTs).

BACKGROUND: Cooking skills (CS) have the potential to improve self-care behaviours and healthy development among adolescents. The COVID-19 pandemic has affected lifestyles worldwide, and the present study aims to investigate the level of CS after the pandemic, as well as its associations with nutrition knowledge and eating behaviours among a cohort of Italian adolescents. METHODS: We submitted an online survey about lifestyle changes to students aged 13-21 years during the pandemic. Based on overall culinary abilities, we divided respondents into high, medium and low CS. Worsening or improvement in diet quality was detected by assigning an eating habit index (EHI; 0-54). RESULTS: Out of the 1686 questionnaires collected, 21.5%, 63.6% and 14.9% reported high, medium and low CS, respectively. The EHI scores were statistically higher among students who were able to cook more than 20 recipes compared to those reporting no cooking abilities (30.2 ± 5.9 vs. 26.6 ± 5.7; p = 0.0001). High CS significantly correlated with better EHI (OR 1.44; p = 0.009), lower consumption of ultra-processed food (OR 1.80; p < 0.0001) and better nutrition knowledge (OR 1.42; p = 0.007). CONCLUSIONS: Adolescents with good CS showed better nutrition knowledge and healthier eating habits, including lower consumption of ultra-processed foods. Projects aimed to improve CS in adolescents can therefore promote healthier development.

Atypical Varicella-Zoster Virus Reactivation: A Case Report.

Varicella-zoster virus (VZV) commonly causes benign skin manifestations in children; it then establishes a latent infection and may reactivate, causing herpes zoster. The most common zoster complication is postherpetic neuralgia, but complications can also occur without a rash. VZV infection may cause neurological manifestations and even vasculopathy may occur, in both primary and reactivated VZV infection. Thrombotic complications are mainly described in children, while a few case reports have described cerebral venous sinus thrombosis (CVST), deep-vein thrombosis of the lower limbs and pulmonary embolism in adults. In this article we report the case of a young woman who developed systemic thromboembolic sequelae due to a hypercoagulable state following VZV reactivation. She had deep venous lower-limb thrombosis extended to the inferior vena cava (IVC), massive pulmonary embolism and CVST. Moreover, VZV reactivation caused an acute hepatitis and clinical manifestations suggesting viral encephalitis. LEARNING POINTS: Varicella-zoster virus (VZV) commonly causes self-limiting skin manifestation, but even neurological manifestations and thrombotic complications may occur.Only few isolated cases of VZV-related cerebral venous sinus thrombosis (CVST) and other types of deep-vein thrombosis have been reported in adults.Early diagnosis of VZV-related thrombosis and prompt anticoagulant and antiviral therapy can prevent a potentially fatal outcome and produce a good prognosis.

New pathogenic variants in ARMC5 gene in a series of Italian patients affected by primary bilateral macronodular adrenocortical hyperplasia (PBMAH).

BACKGROUND: To perform genetic screening for ARMC5 gene germline pathogenic variants in patients with primary bilateral macronodular adrenal hyperplasia (PBMAH). SUBJECTS AND METHODS: In a group of 10 PBMAH patients, we performed complete sequencing of the coding region of the ARMC5 gene and MLPA analysis for large deletion detection. In subjects with the ARMC5 variant, we searched ARMC5 gene somatic variants on tumor samples. RESULTS: Among 10 PBMAH patients, we identified four ARMC5 germline variants (40%). One variant, c:174dupC p.Glu59Argfs*44, was already known; one variant p.Gly323Asp, was already reported and classified as likely disease-causing VUS (class 3-4); two variants p.Leu596Arg and p.Arg811Pro, were never reported before. For p.Gly323Asp and p.Arg811Pro, we identified second deleterious variants at the somatic level, enforcing the possible pathogenic effect of germline variants. CONCLUSIONS: Our results underscore the importance of performing genetic testing also in sporadic PBMAH patients and broaden the spectrum of molecular variants involved in PBMAH syndrome.

Leveraging process mining for modeling progression trajectories in amyotrophic lateral sclerosis.

BACKGROUND: Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative disease whose spreading and progression mechanisms are still unclear. The ability to predict ALS prognosis would improve the patients' quality of life and support clinicians in planning treatments. In this paper, we investigate ALS evolution trajectories using Process Mining (PM) techniques enriched to both easily mine processes and automatically reveal how the pathways differentiate according to patients' characteristics. METHODS: We consider data collected in two distinct data sources, namely the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) dataset and a real-world clinical register (ALS-BS) including data of patients followed up in two tertiary clinical centers of Brescia (Italy). With a focus on the functional abilities progressively impaired as the disease progresses, we use two Process Discovery methods, namely the Directly-Follows Graph and the CareFlow Miner, to mine the population disease trajectories on the PRO-ACT dataset. We characterize the impairment trajectories in terms of patterns, timing, and probabilities, and investigate the effect of some patients' characteristics at onset on the followed paths. Finally, we perform a comparative study of the impairment trajectories mined in PRO-ACT versus ALS-BS. RESULTS: We delineate the progression pathways on PRO-ACT, identifying the predominant disabilities at different stages of the disease: for instance, 85% of patients enter the trials without disabilities, and 48% of them experience the impairment of Walking/Self-care abilities first. We then test how a spinal onset increases the risk of experiencing the loss of Walking/Self-care ability as first impairment (52% vs. 27% of patients develop it as the first impairment in the spinal vs. the bulbar cohorts, respectively), as well as how an older age at onset corresponds to a more rapid progression to death. When compared, the PRO-ACT and the ALS-BS patient populations present some similarities in terms of natural progression of the disease, as well as some differences in terms of observed trajectories plausibly due to the trial scheduling and recruitment criteria. CONCLUSIONS: We exploited PM to provide an overview of the evolution scenarios of an ALS trial population and to preliminary compare it to the progression observed in a clinical cohort. Future work will focus on further improving the understanding of the disease progression mechanisms, by including additional real-world subjects as well as by extending the set of events considered in the impairment trajectories.

When and why patients drop out from benign thyroid nodules follow-up: a single centre experience.

PURPOSE: Drop-out in clinical long-term follow-up is a general problem that is potentially harmful to patients. No data about patients that drop out from thyroid ultrasound follow-up is available literature. The aim of the present retrospective study was to evaluate the characteristics of patients that dropped out from ultrasound thyroid nodule follow-up. PATIENTS AND METHODS: We reviewed medical records of all consecutive patients who underwent a fine needle aspiration from January 2007 to March 2009 in our department. All the patients with benign nodule(s) were recommended annual ultrasounds; patients who had dropped out from follow-up were included and a telephone interview was obtained to evaluate the reasons for dropping out. RESULTS: 289/966 (30%) of patients with benign nodules dropped out during follow-up; 94% of them within the first 5 years. Phone interviews were obtained from 201/289 (70%) of the patients. In the 57% of cases, the main declared reason for dropping out was nodular dimension stability during the first 2-3 years; 8.7% of them had forgotten about the appointment; 6.4% of subjects claimed to check only serum TSH, and 3.2% stated that they would undergo an ultrasound only if the nodule(s) were symptomatic. Finally, 10.7% patients continued follow-up in other centres. CONCLUSION: we showed that a third of patients miss their thyroid ultrasound follow-ups, and that the major cause is the low perceived threat coming from the disease. As a certain amount of drop-out is inevitable, attempting to reinforce our patients' awareness regarding their own health state is mandatory. TRIAL REGISTRATION: Trial registration: no. 4084.

Incidence of De Quervain's thyroiditis during the COVID-19 pandemic in an area heavily affected by Sars-CoV-2 infection.

PURPOSE: To evaluate the possible association between Covid-19 infection and subacute thyroiditis. METHODS: We reviewed the medical and imaging records of patients referred to our Department's outpatient setting dedicated to 'thyroid emergency' (records with a 'bollino verde'-green sticker, classifed as urgent) from April 2020 to October 2020. This outpatient clinic is devoted to patients requiring evaluation for severe hypothyroidism, thyrotoxicosis and neck discomfort or pain. All patients with a newly-diagnosed subacute thyroiditis were selected. The data of all patients receiving a diagnosis of subacute thyroiditis was collected retrospectively, taking into account the same period of time (April-October) and starting from 2016. RESULTS: During the COVID-19 outbreak in our region (April 2020 to October 2020) 396 patients attended the outpatient emergency clinic. Among them, 10 (2.5%) patients received a diagnosis of subacute thyroiditis. In a single patient, a 44-year-old man, a COVID-19 pulmonary infection had been diagnosed 7 weeks before the diagnosis of subacute thyroiditis. All of the remaining patients were and remain COVID-19 free as confirmed by telephone interview. The percentage of patients who received a diagnosis of subacute thyroiditis in the same period starting from 2016 was very similar (2.9%, 2.9%, 2.6% and 3.0% in 2016, 2017, 2018 and 2019, respectively). CONCLUSIONS: Our data do not show an increase in the incidence of subacute thyroiditis in the Brescia area, a region with the highest prevalence of COVID-19 in Italy during the period of the pandemic outbreak.

The Vobarno Study.

The Vobarno Study represents the first observational study aimed to assess in a general population sample the relationship between parameters of cardiac and vascular structure (and function) and blood pressure values, measured in the clinic and during the 24 hours. In the frame of The Vobarno Study blood samples for hematochemistry and DNA extraction, clinic and 24-hour blood pressure measurements, cardiac and carotid ultrasound, and aortic stiffness were measured in all subjects, living in a small town (Vobarno) between Brescia and the Garda Lake (Italy), and randomly selected from electoral roles. In this sample of a general population an extensive evaluation of organ damage, including left ventricular (LV) mass and hypertrophy, LV systolic function, left atrial dimensions and aortic root diameters, carotid intima media thickness (IMT) and carotid plaques, carotid and aortic stiffness were performed. In this study subjects were included in a long follow-up, lasting 25 years, and cardiovascular morbility and mortality were assessed up to 2019. This will allow to update the information related to cardiovascular morbidity and mortality in the study cohort. The present paper will report the results of some analyses performed, exploring epidemiological and clinical aspects of target organ damage.

Ultrasound of benign thyroid nodules: A 120 months follow-up study.

OBJECTIVE: Some evidence suggests that most benign nodules exhibit no significant size increase during 5 years of follow-up, although conflicting results have emerged. The aim of the present study is to evaluate the frequency and the magnitude of growth in benign nodules during 120 months of follow-up. DESIGN: We reviewed the medical and imaging records of patients who were submitted to ultrasound-guided FNA of thyroid nodules at our hospital from January 2007 to March 2009. We selected only patients with benign nodules who underwent annual ultrasound evaluation in our Department. RESULTS: Among 966 selected patients, 289 were lost during follow-up, meaning that the total number of patients analysed was 677 (474 women and 203 men), with a mean age of 45.6 (16-71) years. In 559/677 patients (82.7%), the size of the nodule remained stable during follow-up; 42 (6.2%) patients experienced spontaneous nodule shrinkage, and 75 (11.1%) patients showed nodule growth. Patients with or without nodule growth during follow-up were superimposable at baseline for age, gender, TSH values, number of patients on levothyroxine treatment and nodule characteristics. All baseline variables in predicting nodular growth were entered to an adjusted multivariate logistic regression model. None of the parameters taken into account was associated with nodular growth. CONCLUSIONS: In conclusion, the majority of benign nodules remained stable over the period of monitoring. On the basis of our experience, we recommend ultrasound examination at a distance of 2 and 5 years following cytological evaluation, then every 4-5 years from then on.

Guggulu and Triphala for the Treatment of Hypercholesterolaemia: A Placebo-Controlled, Double-Blind, Randomised Trial.

BACKGROUND: Several herbs are used for lowering high blood cholesterol levels in traditional medicines including Indian Medicine (Ayurveda). We aimed to assess the short-term effects of the combination of Guggulu (Commiphora mukul) and Triphala (Terminalia chebula, Terminalia belerica, and Phyllanthus emblica) on serum cholesterol in healthy subjects with hypercholesterolaemia. PATIENTS AND METHODS: This was a parallel randomised double-blind controlled trial that included 90 individuals at low-moderate cardiovascular risk. The main outcome measures were serum levels of total and low- and high-density lipoprotein cholesterol (LDL-C, HDL-C). Secondary outcome measures included BMI, waist circumference, and adverse events. Subjects were administered either Guggulu and Triphala or placebo three times daily for 3 months, with 3 months of follow-up after the end of treatment. RESULTS: At intention-to-treat analysis, from baseline to 3 months, total serum cholesterol decreased by 1.9% in the placebo (n = 44) and 3.3% (p = 0.01) in the intervention (n = 46) group. Serum LDL-C decreased by 4.9% (p = 0.03) and 4.8% (p = 0.02) in the placebo and intervention group, respectively, without differences between them. Two participants in the intervention group developed hypersensitivity rash (4.3%) as compared with none in the placebo group. CONCLUSIONS: Three months of treatment with Guggulu and Triphala did not show better effects than placebo on serum levels of total and LDL cholesterol, BMI, and waist circumference.

Liquid Levothyroxine Formulation Taken during Lunch in Italy: A Case Report and Review of the Literature.

Levothyroxine (L-T4) is among the most widely prescribed medications in the world, and it is considered by the World Health Organization an essential medicine for basic health care. Replacement therapy has always been considered straightforward although different factors may interfere with intestinal absorption of L-T4, including food, dietary fibre, coffee, drugs, and gastrointestinal diseases. For these reasons, current guidelines recommend that L-T4 should be taken in a fasting state because its absorption is maximised when it is taken on an empty stomach, reflecting the importance of gastric acidity in the absorption process. In addition to sodium L-T4 in tablet form, various formulations (soft-gel capsules and liquid solutions) have become available for clinical use in the last years promising improved absorption. We described a 31-year-old Italian man who took liquid levothyroxine formulation during lunch. He was under replacement therapy with liquid levothyroxine 75 mcg daily for hypothyroidism due to Hashimoto thyroiditis for three years. During confirmation of the L-T4 replacement therapy, the patient stated that he was going to continue to "take liquid levothyroxine during (his) lunch every day." We recommended taking the medication correctly in the morning at least thirty minutes before breakfast and repeating TSH, fT4, and fT3 after three months. The thyroid hormonal profiles taken after 3 and 6 months were comparable to those when the patient was taking the medication during lunch. In conclusion, liquid levothyroxine formulation should be preferred in case of malabsorption or potential malabsorption. Liquid formulation should be preferred due to the possibility of taking it during breakfast, which significantly improves the compliance of patients. Further studies are needed to evaluate the possibility of taking liquid L-T4 during lunch.

What Role Can Process Mining Play in Recurrent Clinical Guidelines Issues? A Position Paper.

In the age of Evidence-Based Medicine, Clinical Guidelines (CGs) are recognized to be an indispensable tool to support physicians in their daily clinical practice. Medical Informatics is expected to play a relevant role in facilitating diffusion and adoption of CGs. However, the past pioneering approaches, often fragmented in many disciplines, did not lead to solutions that are actually exploited in hospitals. Process Mining for Healthcare (PM4HC) is an emerging discipline gaining the interest of healthcare experts, and seems able to deal with many important issues in representing CGs. In this position paper, we briefly describe the story and the state-of-the-art of CGs, and the efforts and results of the past approaches of medical informatics. Then, we describe PM4HC, and we answer questions like how can PM4HC cope with this challenge? Which role does PM4HC play and which rules should be employed for the PM4HC scientific community?

The Effects of Cow-Milk Protein Supplementation in Elderly Population: Systematic Review and Narrative Synthesis.

BACKGROUND: To review currently available evidence on the effect of cow-milk proteins supplementation (CPS) on health in the elderly. METHODS: Five electronic databases (Pubmed, Web of Science, Embase, Cochrane Library, ClinicalTrials.gov) were searched for studies about CPS among older people. All types of publications were included, with the exception of systematic reviews, meta-analyses, opinion letters, editorials, case reports, conference abstracts and comments. An additional search in Google Scholar and a manual review of the reference lists were performed. RESULTS: Overall, 103 studies were included. Several studies explored the role of CPS in the preservation or improvement of muscle mass among healthy subjects (40 studies) and pre-frail, frail or sarcopenic patients (14), with evidence of beneficial effects. Other studies assessed the effect of CPS on bones (12), cardiovascular disease (8), inflamm-aging (7), chronic pulmonary disease (4), neurocognitive function (4), and vaccines (2), with weak evidence of positive effects. Seven studies in the field of protein metabolism investigated the role of CPS as an important contributor to nutritional needs. Other investigational areas are considered in the last five studies. CONCLUSIONS: The beneficial effects of CPS in achieving aged-related nutritional goals, in preserving muscle mass and in recovering after hospitalization may be particularly relevant in the elderly.

A new self-administered semi-quantitative food frequency questionnaire to estimate nutrient intake among Italian adults: development design and validation process.

Food Frequency Questionnaires (FFQs) are valuable research tools in nutritional epidemiology. This study aimed to develop and validate a new semi-quantitative FFQ, specifically designed for the Italian population and best fitted for self-administration. During the development process, we adapted to Italian needs the validated FFQ proposed by the Fred Hutchinson Cancer Research Center, revising food items, food frequency scale, portion sizes, and time frame. To assess the validity of the proposed FFQ, we compared the estimated daily intake using FFQ with the mean of 3-day food diaries and one 24-hour recall (considered as reference method). The validation process was conducted among a cohort of 51 healthy subjects enrolled in a clinical trial. Four statistical tests were applied on 23 estimated nutrient intakes. Spearman's coefficients ranged from 0.223 (sodium) to 0.748 (alcohol) and were good (≥0.50) and acceptable (0.20-0.49) for 7 and 16 nutrients, respectively. Cross classification showed a good agreement (≥50% in the same tertile or ≤10% in the opposite tertile) for 7 nutrients. The weighted Cohen's kappa values indicated an acceptable outcome (0.20-0.60) for 13 nutrients. Bland Altman plots did not show heteroscedasticity in the error terms, despite the presence of a bias. Our study provided a new Italian semi-quantitative FFQ for self-administration with an acceptable validation level. Its definitive release requires additional refinements and efforts.

Tocilizumab for the treatment of severe COVID-19 pneumonia with hyperinflammatory syndrome and acute respiratory failure: A single center study of 100 patients in Brescia, Italy.

A hyperinflammatory syndrome (HIS) may cause a life-threatening acute respiratory distress syndrome (ARDS) in patients with COVID-19 pneumonia. A prospective series of 100 consecutive patients admitted to the Spedali Civili University Hospital in Brescia (Italy) between March 9th and March 20th with confirmed COVID-19 pneumonia and ARDS requiring ventilatory support was analyzed to determine whether intravenous administration of tocilizumab (TCZ), a monoclonal antibody that targets the interleukin 6 (IL-6) receptor, was associated with improved outcome. Tocilizumab was administered at a dosage of 8 mg/kg by two consecutive intravenous infusions 12 h apart. A third infusion was optional based on clinical response. The outcome measure was an improvement in acute respiratory failure assessed by means of the Brescia COVID Respiratory Severity Score (BCRSS 0 to 8, with higher scores indicating higher severity) at 24-72 h and 10 days after tocilizumab administration. Out of 100 treated patients (88 M, 12 F; median age: 62 years), 43 received TCZ in the intensive care unit (ICU), while 57 in the general ward as no ICU beds were available. Of these 57 patients, 37 (65%) improved and suspended noninvasive ventilation (NIV) (median BCRSS: 1 [IQR 0-2]), 7 (12%) patients remained stable in NIV, and 13 (23%) patients worsened (10 died, 3 were admitted to ICU). Of the 43 patients treated in the ICU, 32 (74%) improved (17 of them were taken off the ventilator and were discharged to the ward), 1 (2%) remained stable (BCRSS: 5) and 10 (24%) died (all of them had BCRSS≥7 before TCZ). Overall at 10 days, the respiratory condition was improved or stabilized in 77 (77%) patients, of whom 61 showed a significant clearing of diffuse bilateral opacities on chest x-ray and 15 were discharged from the hospital. Respiratory condition worsened in 23 (23%) patients, of whom 20 (20%) died. All the patients presented with lymphopenia and high levels of C-reactive protein (CRP), fibrinogen, ferritin and IL-6 indicating a HIS. During the 10-day follow-up, three cases of severe adverse events were recorded: two patients developed septic shock and died, one had gastrointestinal perforation requiring urgent surgery and was alive at day 10. In conclusion, our series showed that COVID-19 pneumonia with ARDS was characterized by HIS. The response to TCZ was rapid, sustained, and associated with significant clinical improvement.

Could Serum TSH Levels Predict Malignancy in Euthyroid Patients Affected by Thyroid Nodules with Indeterminate Cytology?

BACKGROUND: Serum TSH levels in the upper-normal range were reported to be associated with increased risk of thyroid malignancy. However, measurement of TSH levels is currently not recommended for assessing the risk of malignancy in patients with newly diagnosed thyroid nodules. OBJECTIVE: To evaluate a possible relationship between the serum levels of TSH and the histological outcome of patients undergoing thyroidectomy for thyroid nodules with indeterminate cytology. MATERIALS AND METHODS: We collected the clinical data of all patients who had performed ultrasound-guided FNA of thyroid nodules with cytological diagnosis of indeterminate lesions (TIR3A and TIR3B) and serum TSH levels within the normal range. All patients had been submitted to thyroid surgery (hemi or thyroidectomy, as appropriate), and histological diagnosis had been performed. RESULTS: A histological diagnosis of thyroid malignancy was rendered in 74/378 (19.6%) nodules. Patients with histologically proven thyroid malignancy were characterized by higher serum levels of TSH as compared to patients with histologically proven benign nodules (3.03 ± 1.16 vs. 2.37 ± 1.19 mIU/L, p < 0.001). To further analyze the role of serum TSH in predicting thyroid cancer, patients were stratified in 4 groups according to quartiles of TSH concentrations. The prevalence of malignancy was 12.2% for the first quartile and 50.0% for the last quartile. ROC curve analysis identified that a serum TSH level of ≥2.7 mIU/L predicted thyroid malignancy with a sensitivity of 61% and a specificity of 65%. CONCLUSIONS: TSH levels in the upper-normal range are associated with an increased risk of thyroid malignancy in patients affected by thyroid nodules with indeterminate cytology at FNA. The measurement of serum TSH levels represents an easily performed additional tool for decision-making in patients with indeterminate cytological findings.

Ultrasound Microvascular Blood Flow Evaluation: A New Tool for the Management of Thyroid Nodule?

BACKGROUND: Toshiba Medical System has developed a new Doppler technique [Superb Microvascular Imaging (SMI)] that has improved microvascular flow imaging. SMI depicts perinodular and intranodular thyroid microvascular flow in higher detail compared to standard colour Doppler (CD) and power Doppler (PD) imaging. OBJECTIVE: Assess the nodular microvascular architecture by SMI compared to CD and PD features in a series of thyroid nodules submitted to fine needle aspiration cytology, in order to evaluate the potential of SMI in detecting thyroid cancer. MATERIALS AND METHODS: From April 2016 to July 2017, 254 patients with thyroid nodules, evaluated as at high risk for malignancy in agreement with AACE/ACE/AME guidelines, were submitted to cytology. All nodules were previously submitted to ultrasound grayscale, CD, PD, and SMI evaluation. Benign and malignant nodules were stratified in accordance to the number of vessels visualised by SMI: score 1 with a maximum of two blood vessels and score 2 with three or more vessels. RESULTS: Score 1 was found in 59.6% of benign nodules and in 17.9% of malignant nodules, whereas score 2 was found in 40.4% and in 82.1%, respectively (sensitivity 81.7%; specificity 60.5%, p < 0.001). Variables significantly associated with malignancy in the univariate analysis were gender (OR, 0.18; 95% CI, 0.08-0.37; p < 0.001), vascularity (OR, 1.91; 95% CI, 1.65-3.89; p < 0.001), and SMI (OR, 6.72; 95% CI, 3.89-11.59; p < 0.001); multivariate logistic model confirmed SMI score 2 as an independent risk factor for malignancy (OR, 6.99; 95% CI, 3.46-12.09; p < 0.001). CONCLUSIONS: This prospective pilot study showed that SMI can depict intranodular flow in higher detail compared to CDI and PDI, thus improving thyroid cancer detection.

p.Ser891Ala RET gene mutations in medullary thyroid cancer: Phenotypical and genealogical characterization of 28 apparently unrelated kindreds and founder effect uncovering in Northern Italy.

Applying genetic screening in medullary thyroid cancer (MTC) patients we identified an unexpectedly high frequency of c.2671T>G, p.Ser891Ala RET mutation carriers. Our aim was to: (a) deeply characterize the clinical expression of this mutation, (b) identify the presence of a founder effect in our region. Genetic analysis was performed in 251 relatives from 28 Ser891Ala kindreds, among 108 p.Ser891Ala asymptomatic carriers, 64 were submitted to thyroidectomy: mean age for 10 subjects presenting C-cells hyperplasia was 30.2 ± 13.7 years, raising to 37.9 ± 10.3 in 14 subjects with micro-MTC and to 55.0 ± 14.7 years in 39 subjects with MTC. Age-related progression across histopathological groups CCH/microMTC and MTC were statistically significant: genetic screening in Ser891Ala families could be safely postponed at the age of 14. To investigate the hypothesis of a common ancestor for Ser891Ala mutation we genotyped for 18 polymorphic microsatellite markers encompassing RET locus all subjects belonging to Ser891Ala families and we identified a founder effect, estimating the age of a common ancestor, dating back to 1493 AD. Ethnographic data collected in historical archives support laboratory results; the high prevalence of this mutation in our region could suggest the hypothesis of a population study to realize a preventive intervention in a rare neoplastic disease.