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.

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.

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.

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.

Relationship between different subpopulations of circulating CD4+ T lymphocytes and microvascular or systemic oxidative stress in humans.

BACKGROUND AND OBJECTIVE: Different components of the immune system, including innate and adaptive immunity (T effector lymphocytes and T regulatory lymphocytes - TREGs) may be involved in the development of hypertension, vascular injury and inflammation. However, no data are presently available in humans about possible relationships between T-lymphocyte subtypes and microvascular oxidative stress. Our objective was to investigate possible relationships between T-lymphocyte subtypes and systemic and microvascular oxidative stress in a population of normotensive subjects and hypertensive patients. PATIENTS AND METHODS: In the present study we enrolled 24 normotensive subjects and 12 hypertensive patients undergoing an elective surgical intervention. No sign of local or systemic inflammation was present. All patients underwent a biopsy of subcutaneous fat during surgery. A peripheral blood sample was obtained before surgery for assessment of T lymphocyte subpopulations by flow cytometry and circulating indices of oxidative stress. RESULTS: A significant direct correlation was observed between Th1 lymphocytes and reactive oxygen species (ROS) production (mainly in microvessels). Additionally, significant inverse correlations were observed between ROS and total TREGs, or TREGs subtypes. Significant correlations were detected between circulating indices of oxidative stress/inflammation and indices of microvascular morphology/Th1 and Th17 lymphocytes. In addition, a significant inverse correlation was detected between TREGs in subcutaneous small vessels and C reactive protein. CONCLUSIONS: Our data suggest that TREG lymphocytes may be protective against microvascular damage, probably because of their anti-oxidant properties, while Th1-Th17 lymphocytes seem to exert an opposite effect, confirming an involvement of adaptive immune system in microvascular damage.

Levothyroxine liquid solution versus tablet form for replacement treatment in pregnant women.

OBJECTIVE: To evaluate the need and the magnitude of levothyroxine (LT4) increase in hypothyroid pregnant women on liquid compared to tablet formulations. METHODS: Patients were recruited by searching our "thyroid patients" database. The selection criteria were as follows: a) pregnant women on treatment for hypothyroidism (both liquid and tablet LT4) who gave birth at our hospital between February 2012 and January 2014; b) thyroid stimulating hormone (TSH) and free thyroxine (FT4) levels obtained at least 3 months before missed menstrual cycle, with a TSH value less than 2.5 mIU/L and c) TSH and FT4 obtained within 12 weeks of pregnancy, and each month subsequently. RESULTS: During pregnancy, 8/31 (25.5%) of the women had to increase the dosage of LT4. Of these, 7/17 (41.2%) were on LT4 replacement therapy with tablets, and 1/14 (7.1%) with liquid formulation (p = 0.038). Daily LT4 was significantly increased in the liquid group only (52.9 ± 19.5 versus 67.5 ± 19.2 mcg/day (p = 0.013). A logistic regression analysis showed that the treatment with LT4 tablets was the only predictor of LT4 increase (OR: 0.44; 95% CI: 0.04-0.83; p = 0.031). CONCLUSION: Pregnant women on optimal replacement therapy before pregnancy require an increase of LT4 dosage more often when on a tablet than liquid formulation.

Yeast model for evaluating the pathogenic significance of SDHB, SDHC and SDHD mutations in PHEO-PGL syndrome.

SDH genes, encoding succinate dehydrogenase, act as tumour suppressor genes, linking mitochondrial dysfunction with tumourigenesis. Heterozygous germline mutations in SDHA, SDHB, SDHC, SDHD and in the assembly factor encoding gene SDHAF2 have all been shown to predispose to heritable endocrine neoplasias such as pheochromocytomas (PHEO) and paragangliomas (PGLs) called 'PHEO-PGL syndrome'. SDH genes mutations, in addition to deletions or truncations which are most likely pathogenic, often include missense substitutions which can be of uncertain significance. Unclassified missense substitutions may be difficult to interpret unless the cause-effect link between mutation and the disease is established by functional and in silico studies or by the familial segregation with the phenotype. Using the yeast model, here, we report functional investigations on several missense SDH mutations found in patients affected by pheochromocytomas or paragangliomas. The aim of this study was to evaluate whether and to which extent the yeast model may be useful for establishing the pathological significance of missense SDH mutations in humans. The results of our study demonstrate that the yeast is a good functional model to validate the pathogenic significance of SDHB missense mutations while, for missense mutations in SDHC and SDHD genes, the model can be informative only when the variation involves a conserved residue in a conserved domain.

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.

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.

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.

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.

Association of vascular risk factors with cervical artery dissection and ischemic stroke in young adults.

BACKGROUND: Little is known about the risk factors for cervical artery dissection (CEAD), a major cause of ischemic stroke (IS) in young adults. Hypertension, diabetes mellitus, smoking, hypercholesterolemia, and obesity are important risk factors for IS. However, their specific role in CEAD is poorly investigated. Our aim was to compare the prevalence of vascular risk factors in CEAD patients versus referents and patients who suffered an IS of a cause other than CEAD (non-CEAD IS) in the multicenter Cervical Artery Dissection and Ischemic Stroke Patients (CADISP) study. METHODS AND RESULTS: The study sample comprised 690 CEAD patients (mean age, 44.2 ± 9.9 years; 43.9% women), 556 patients with a non-CEAD IS (44.7 ± 10.5 years; 39.9% women), and 1170 referents (45.9 ± 8.1 years; 44.1% women). We compared the prevalence of hypertension, diabetes mellitus, hypercholesterolemia, smoking, and obesity (body mass index ≥ 30 kg/m²) or overweightness (body mass index ≥ 25 kg/m² and <30 kg/m²) between the 3 groups using a multinomial logistic regression adjusted for country of inclusion, age, and gender. Compared with referents, CEAD patients had a lower prevalence of hypercholesterolemia (odds ratio 0.55; 95% confidence interval, 0.42 to 0.71; P<0.0001), obesity (odds ratio 0.37; 95% confidence interval, 0.26 to 0.52; P<0.0001), and overweightness (odds ratio 0.70; 95% confidence interval, 0.57 to 0.88; P=0.002) but were more frequently hypertensive (odds ratio 1.67; 95% confidence interval, 1.32 to 2.1; P<0.0001). All vascular risk factors were less frequent in CEAD patients compared with young patients with a non-CEAD IS. The latter were more frequently hypertensive, diabetic, and current smokers compared with referents. CONCLUSION: These results, from the largest series to date, suggest that hypertension, although less prevalent than in patients with a non-CEAD IS, could be a risk factor of CEAD, whereas hypercholesterolemia, obesity, and overweightness are inversely associated with CEAD.

Real-time elastography: a useful tool for predicting malignancy in thyroid nodules with nondiagnostic cytologic findings.

OBJECTIVES: The aim of this study was to evaluate the predictive value of sonography and sonographic elastography in thyroid nodules with nondiagnostic cytologic findings. METHODS: The study included 101 patients (74 female, mean age ± SD, 55 ± 11 years [range, 27-70 years]; and 27 male, mean age, 62 ± 9 years [range, 42-72 years]) who had at least 1 nodule with nondiagnostic cytologic findings at two different fine-needle aspiration cytologic evaluations and with an indication for hemi or total thyroidectomy for clinical suspicion of malignancy, nodule size, or the occurrence of a coexisting nodule with cytologic findings suspicious for malignancy. All of the patients underwent sonography and elastography 2 months after the second fine-needle aspiration and before surgery. The elastogram was matched with an elasticity color scale and classified as follows: score 1, nodules with high elasticity (soft); score 2, nodules with indeterminate elasticity; and score 3, nodules with low elasticity (hard). RESULTS: A total of 135 nodules (93.7%) were hyperplastic; 15 (9.4%) were papillary carcinomas; and 9 (6.3%) were follicular adenomas. The association of scores 2 and 3 identified 12 of 15 thyroid cancers (sensitivity, 80.0%; specificity, 93.7%; positive predictive value, 57.1%; negative predictive value, 97.8%; and accuracy, 92.4%), whereas the association of conventional sonographic features plus scores 2 and 3 identified all of the cancers (specificity, 70.8%; positive predictive value, 26.3%; negative predictive value, 100%; and accuracy, 73.6%). CONCLUSIONS: Our data suggest that elastography could be a promising tool in the management of nodules that are nondiagnostic at cytologic evaluation, reducing unnecessary surgery.

Thyroidal effect of metformin treatment in patients with polycystic ovary syndrome.

OBJECTIVE: Metformin is widely used for the treatment of type 2 diabetes. Growing evidence supports the beneficial effects of metformin also in patients with polycystic ovary syndrome (PCOS). It was recently reported that metformin has a TSH-lowering effect in hypothyroid patients with diabetes being treated with metformin. DESIGN: Aim of this study was to evaluate the effect of metformin treatment on the thyroid hormone profile in patients with PCOS. PATIENTS AND MEASUREMENTS: Thirty-three patients with PCOS were specifically selected for being either treated with levothyroxine for a previous diagnosis of hypothyroidism (n = 7), untreated subclinically hypothyroid (n = 2) or euthyroid without levothyroxine treatment (n = 24) before the starting of metformin. The serum levels of TSH and FT(4) were measured before and after a 4-month period of metformin therapy. RESULTS: Thyroid function parameters did not change after starting metformin therapy in euthyroid patients with PCOS. In the 9 hypothyroid patients with PCOS, the basal median serum levels of TSH (3·2 mIU/l, range = 0·4-7·1 mIU/l) significantly (P < 0·05) decreased after a 4-month course of metformin treatment (1·7 mIU/l, range = 0·5-5·2 mIU/l). No significant change in the serum levels of FT4 was observed in these patients. The TSH-lowering effect of metformin was not related to the administered dose of the drug, which was similar in euthyroid as compared with hypothyroid patients with PCOS (1406 ± 589 vs 1322 ± 402 mg/day, respectively; NS). CONCLUSIONS: These results indicate that metformin treatment has a TSH-lowering effect in hypothyroid patients with PCOS, both treated with l-thyroxine and untreated.

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.

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.

Spectrum and prevalence of FP/TMEM127 gene mutations in pheochromocytomas and paragangliomas.

CONTEXT: Pheochromocytomas and paragangliomas are genetically heterogeneous neural crest-derived neoplasms. We recently identified germline mutations of the novel transmembrane-encoding gene FP/TMEM127 in familial and sporadic pheochromocytomas consistent with a tumor suppressor effect. OBJECTIVES: To examine the prevalence and spectrum of FP/TMEM127 mutations in pheochromocytomas and paragangliomas and to test the effect of mutations in vitro. DESIGN, SETTING, AND PARTICIPANTS: We sequenced the FP/TMEM127 gene in 990 individuals with pheochromocytomas and/or paragangliomas, including 898 previously unreported cases without mutations in other susceptibility genes from 8 independent worldwide referral centers between January 2009 and June 2010. A multiplex polymerase chain reaction-based method was developed to screen for large gene deletions in 545 of these samples. Confocal microscopy of 5 transfected mutant proteins was used to determine their subcellular localization. MAIN OUTCOME MEASURES: The frequency and type of FP/TMEM127 mutation or deletion was assessed and correlated with clinical variables; the subcellular localization of 5 overexpressed mutants was compared with wild-type FP/TMEM127 protein. RESULTS: We identified 19 potentially pathogenic FP/TMEM127 germline mutations in 20 independent families, but no large deletions were detected. All mutation carriers had adrenal tumors, including 7 bilateral (P = 2.7 × 10(-4)) and/or with familial disease (5 of 20 samples; P = .005). The median age at disease onset in the FP/TMEM127 mutation group was similar to that of patients without a mutation (41.5 vs 45 years, respectively; P = .54). The most common presentation was that of a single benign adrenal tumor in patients older than 40 years. Malignancy was seen in 1 mutation carrier (5%). Expression of 5 novel FP/TMEM127 mutations in cell lines revealed diffuse localization of the mutant proteins in contrast with the discrete multiorganelle distribution of wild-type TMEM127. CONCLUSIONS: Germline mutations of FP/TMEM127 were associated with pheochromocytoma but not paraganglioma and occurred in an age group frequently excluded from genetic screening algorithms. Disease-associated mutations disrupt intracellular distribution of the FP/TMEM127 protein.

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.