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Background and aims To investigate diabetes treatment initiation and continuation in the next sixth months in newly diagnosed Italian subjects. Methods and results We analyzed administrative claims of 11,300,750 Italian residents. Subjects with incident diabetes were identified by glucose lowering drug prescriptions, disease-specific co-payment exemptions and hospital discharge codes occurring in 2018 but not in 2017. Incident cases were 65,932 of whom 91.4% received the prescription of a glucose lowering drug. Among the latter, those receiving a prescription of a noninsulin medication but no insulin were 84.8%, those receiving a prescription of insulin only were 9.4%, and those receiving prescriptions of both insulin and noninsulin drugs were 5.8%. Metformin was the most frequently drug initially prescribed in noninsulin treated subjects (~85%) and sulphonylurea receptor (SUR) agonists collectively ranked as second (~13%). Lispro (35%) and glargine (34%) were the most frequently prescribed molecules in subjects who were insulin treated. Differences in prescriptions were found in age categories, with increased use of SUR agonists across decades. In the first six months, as many as 50% of noninsulin treated patients continued with the initial drug, ~15% added a second agent, ~5% switched to another medication, and ~30% discontinued any glucose lowering treatment. Conclusions These data document that current guidelines are often neglected because prescriptions of SUR agonists as first agent are still quite common and insulin is prescribed more than expected. They point out the urgent need to improve the dissemination and implementations of guidelines in diabetes care.

Breast cancer (BC) is a heterogeneous disease and the most prevalent malignant tumor in women worldwide. The majority of BC cases are positive for estrogen receptor (ER) and progesterone receptor (PgR), both known to be involved in cancer pathogenesis, progression, and invasion. In line with this, hormonal deprivation therapy appears to be a useful tool and an effective treatment for these BC subtypes. Unfortunately, prognosis among patients with hormone-negative tumors or therapy-refractory and metastatic patients remains poor. Novel biomarkers are urgently needed in order to predict the course of the disease, make better therapy decisions and improve the overall survival of patients. In this respect, the androgen receptor (AR), a member of the hormonal nuclear receptor superfamily and ER and PgR, emerges as an interesting feature widely expressed in human BCs. Despite the advances, the precise tumorigenic mechanism of AR and the role of its endogenous ligands are yet not well-understood. In this review, we aim to elaborate on the prognostic impact of AR expression and current AR-targeting approaches based on previous studies investigating AR's role in different BC subtypes.

Background: Endoscopic surveillance in patients with Lynch syndrome (LS) is crucial due to a genetically based high risk of colorectal cancer (CRC). We aimed to compare the adenoma detection rate (ADR) between high-resolution white light endoscopy (WLE) alone and WLE plus dye chromoendoscopy (CE) in a cohort of LS patients. Methods: In a context of real-world data, we retrospectively enrolled 50 LS patients who had non-randomly undergone WLE versus CE surveillance examinations from 2007 to 2019. The 2 groups were compared at baseline (BL) in terms of the rate of patients with lesions and the number of lesions, and at follow-up (FU), to evaluate a possible enhanced detection rate. Longitudinal analysis of the effect of the endoscopy type on the main outcomes was performed by generalized linear mixed models. Results: Forty-two patients had undergone at least one diagnostic colonoscopy. At BL and at FU analysis, we found no significant differences in detection rates and clinical-pathological features between WLE and CE groups. At the longitudinal analysis, an increase in the endoscopy rank (i.e., the position of each colonoscopy for all the colonoscopies that a patient had undergone) was associated with an increase in polyp detection rate (p = 0.006) and ADR (p = 0.005), while a trend toward significance (p = 0.069) was found for endoscopy type (CE vs. WLE) in the detection of serrated lesions. Conclusions: CE is not superior to high-resolution WLE in increasing the ADR. Even under standard WLE, an active and careful endoscopic surveillance of LS patients can prevent CRC.

Funder: Fondazione Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/100007368, Funder: Tuscany Region, Italy; Id: http://dx.doi.org/10.13039/501100009888, Funder: Pisa University Hospital, Pisa, Italy, Funder: University of Pisa, Pisa, Italy; Id: http://dx.doi.org/10.13039/501100007514, The First World Consensus Conference on Pancreas Transplantation provided 49 jury deliberations regarding the impact of pancreas transplantation on the treatment of diabetic patients, and 110 experts' recommendations for the practice of pancreas transplantation. The main message from this consensus conference is that both simultaneous pancreas-kidney transplantation (SPK) and pancreas transplantation alone can improve long-term patient survival, and all types of pancreas transplantation dramatically improve the quality of life of recipients. Pancreas transplantation may also improve the course of chronic complications of diabetes, depending on their severity. Therefore, the advantages of pancreas transplantation appear to clearly surpass potential disadvantages. Pancreas after kidney transplantation increases the risk of mortality only in the early period after transplantation, but is associated with improved life expectancy thereafter. Additionally, preemptive SPK, when compared to SPK performed in patients undergoing dialysis, appears to be associated with improved outcomes. Time on dialysis has negative prognostic implications in SPK recipients. Increased long-term survival, improvement in the course of diabetic complications, and amelioration of quality of life justify preferential allocation of kidney grafts to SPK recipients. Audience discussions and live voting are available online at the following URL address: http://mediaeventi.unipi.it/category/1st-world-consensus-conference-of-pancreas-transplantation/246.

Background: The Covid-19 pandemic may have a deleterious impact on patients with autoimmune systemic diseases (ASD) due to their deep immune-system alterations. Objective: This study aims to investigate the prevalence of symptomatic Covid-19 and its correlations with both organ involvement and ongoing treatments in a large series of Italian ASD patients during the first wave of pandemic. Methods: Our multicenter telephone 6-week survey included 3,029 unselected ASD patients enrolled at 36 tertiary referral centers of northern, central, and southern Italian macro-areas with different diffusion of the pandemic. Symptomatic SARS-CoV-2 infection was classified as definite Covid-19 (presence of symptoms plus positive oral/nasopharyngeal swabs) or highly suspected Covid-19 (highly suggestive symptoms, in the absence of a swab testing). Results: A significantly higher prevalence of definite plus highly suspected Covid-19 compared to the Italian general population was detected in the whole ASD series (p=.000), as well as in patients from the three macro-areas (p=.000 in all). Statistically higher prevalence of Covid-19 was also found in connective tissue diseases compared to chronic arthritis subgroup (p=.000) and in ASD patients with pre-existing interstitial lung involvement (p=.000). Patients treated with either conventional disease-modifying anti-rheumatic drugs (DMARDs) and/or biological DMARDs showed a significantly lower prevalence of Covid-19 (p=.000 in both). Finally, scleroderma patients undergoing low-dose aspirin showed a significantly lower rate of Covid-19 compared to those without (p=0.003). Conclusion: The higher prevalence of Covid-19 in ASD patients, along with the significant correlations with important clinical features and therapeutic regimens, suggests the need to develop targeted prevention/management strategies during the current pandemic wave.

In spite of being at target for glucose (1) or traditional cardiovascular (CV) risk factors (2), individuals with type 1 diabetes (T1D) still have an excess of CV mortality and morbidity implying a role for other mechanisms including insulin resistance (IR). Impaired insulin action in T1D was established by clamp technique long ago (3). Estimated glucose disposal rate (eGDR) correlates well with the clamp technique (4) and is a risk marker for microangiopathy (5,6), diabetic kidney disease (DKD) (6), CV risk, and mortality (5,7). In this observational single-center study, we investigated to what extent eGDR is a predictor of CV events, coronary artery disease (CAD), and all-cause mortality irrespective of CV risk factors and DKD in 774 subjects with T1D over a 10-year follow-up, as previously described (8). eGDR (mg/kg/min) was calculated at baseline as follows (4): eGDR = 21.158 − (0.09 × WC) − (3.407 × HTN) − (0.551 × HbA1c), where WC is waist circumference (cm), HTN is hypertension (yes = 1, no = 0), and HbA1c is in %. Follow-up data were retrieved from the national and regional health care registers (ICD-9, Clinical Modification, codes) by searching for CV outcomes (primary outcome) up to 31 December 2017 and for all-cause death up to 31 October 2018. Incidence of CV outcomes was available for 736 participants (95.1%), and vital status was available for all individuals (8). We used univariate and multivariate Cox proportional hazards models to …

Pituitary tumors are a heterogeneous group of lesions (usually benign) and proper understanding of the anatomy, physiology, and pathology of the hypothalamic/pituitary region is essential to make an accurate diagnosis and define the essential treatment options (i.e., surgery, medical therapies, and radiotherapy, alone or in combination). Surgery is the primary treatment for acromegaly, Cushing disease, thyroid-stimulating hormone-secreting adenomas, resistant prolactinomas, and nonfunctioning pituitary adenomas causing mass effect. Medical and radiation therapy are reserved in cases in which surgery is not possible or does not provide a complete cure. In the last decades, tremendous innovations (i.e., targeted drugs and refined surgical tools and techniques) have expanded the treatment strategies for pituitary adenomas. We herein report the current indications for and depiction of the surgical techniques in pituitary surgery, review current medical treatments, and provide a glimpse of future possibilities.

Abstract. Background: Contrast–induced nephropathy (CIN) is a relevant cause of acute renal dysfunction and is associated with an increased morbidity and mortality. Purpose: Verify the effect of α-tocopherol pre-treatment on CIN prevention in subjects with chronic kidney disease. Methods: A Medline/Embase and clinicaltrials.gov were searched up to May 1st, 2017. Randomized controlled trials recruiting patients undergoing diagnostic or therapeutic radiocontrast infusion comparing the effect of either oral or i.v. multiple administration of pharmacological dose of α-tocopherol in preventing CIN versus placebo were included. A random-effects model, calculating Mantel-Haenszel odds ratio with 95% confidence interval, was applied to study the effect of α-tocopherol on CIN occurrence. Funnel plot analysis was used to assess publication bias, while agreement within studies was measured by the I2 index and tested with the Q-Cochran test. Results: Out of 242 studies, 4 trials were selected. CIN incidence resulted significantly lower in α-tocopherol compared to placebo group (5.8% vs. 15.4%, MH-OR [95% C.I.] 0.34 [0.19 – 0.59]). Alpha-tocopherol treatment was associated with both a tendential higher eGFR (mean difference 2.19 [95% C.I. -0.41; 4.79] mL/min) and lower creatinine level (mean difference −0.06 [95% C.I. −0.21; 0.09] mg/dl) compared to placebo. No relevant publication bias (p = 0.48) and heterogeneity (I2 = 0%; χ2 = 1.01, df = 3 [p = 0.80], I2 = 0%) were evident. Conclusions: Alpha-tocopherol pre-treatment is associated with reduction of incidence of CIN. Its administration deserves to be further explored as a simple and inexpensive tool for CIN prevention.

The aim of the present study was to retrospectively evaluate the longevity of teeth and implants during a long-term period in a cohort of periodontally compromised patients, treated and maintained in a private specialist periodontal practice, and to analyze the associated risk factors. Fifty-eight patients (30 men, 28 women) who had received active periodontal therapy (APT) and regular periodontal maintenance (PM) ≥ 10 years were included and evaluated. The following were evaluated: (1) statistically significant differences of clinical parameters assessed at six tooth or implant sites (plaque scores, bleeding score, periodontal probing depth, bleeding on probing, and gingival recession) and radiographic parameters (mesial and distal bone crest loss) between patients with and without tooth/implant loss during PM; and (2) associations between the number of teeth and implants lost and potential risk factors. During PM, the overall average tooth loss was 0.07 teeth/patient/year (0.04 teeth/patient/year for periodontal reasons), while the overall average implant loss was 0.4 implants/patient/year. The overall implant failure was 10.08%, and the rate of implant failure due to biologic reasons was 9.8%. Incidence of implant failures in patients with vs without recurrent periodontal disease was 83.3% vs 16.7% (P < .05). Results showed that in chronic periodontitis patients, ATP followed by long-term PM is successful in keeping the majority of periodontally compromised teeth. In the same patients, a higher tendency for implant loss than tooth loss was found.

Objectives A controlled, single-blind, randomized clinical trial was performed to evaluate usefulness of antibiotics in preventing pain and complications after tooth extractions and benefits of probiotics in reducing gastro-intestinal symptoms associated with antibiotic therapy. Materials and methods A total of 159 patients were enrolled in this trial. After tooth extractions, patients were allocated to one of the groups: group 1 received postoperatively amoxicillin + clavulanic acid; group 2 received the same antibiotic therapy with an adjunctive probiotic treatment; and group 3 received neither antibiotics nor probiotics. Follow-up visits were planned at 7, 14, and 21 days after tooth extractions (T1, T2, and T3), and parameters assessed were pain, presence of abscess, edema, fever, alveolitis, trismus, pain, difficulty in daily routine activities, and gastro-intestinal symptoms. Results The number of patients reporting pain at T1 was significantly higher in the control group when compared to group 2 (p = .016), while no difference for pain intensity was observed between groups. No surgical site infection was observed in any of the groups. Intestinal symptoms seemed to be tackled by probiotic administration. Conclusions Pain was the most important symptom in the control group. Antibiotics were not necessary after non-impacted tooth extractions, and probiotics can reduce gastro-intestinal symptoms associated with antibiotics.

The 2019 novel corona virus and the disease it causes (COVID-19) is a public health crisis that has profoundly modified the way medical and surgical care is delivered. Countries around the globe had a variable initial response to the COVID-19 pandemic from imposing massive lock downs and quarantine to surrendering to herd immunity. However, healthcare bodies worldwide recognized early on that a triumph against COVID-19 could only be achieved by maintaining the infrastructure of healthcare systems and their capacity to accommodate a potentially overwhelming increase in critical patient care needs. Therefore, they reacted by restricting medical care to emergency cases and postponing elective surgical procedures in all disciplines. The priority was made for treatment of COVID-19 patients and emergency cases. Nevertheless, the battle against the COVID-19 pandemic is still ongoing. In the absence of vaccines or effective drug treatments, its timeline remains uncertain and it cannot be forecast how long healthcare systems will need to cope with it in managing inpatient and outpatient services. Accordingly, extreme measures and restriction may become a recipe for a disaster in the context of the potential adverse health implications imposed by delaying timely medical and surgical care. Therefore, restrictive measures should be substituted with a comprehensive surgical and medical care strategy. One that provides a safe balance between the prevention of COVID-19 and the delivery of essential surgical care. This article provides an overview on how to safely deliver essential surgical care in the time of COIVD-19.

Androgen Receptor (AR) positivity is often displayed in breast cancer and especially in Male Breast Cancer (MBC), where it appears to be a heterogeneous feature, with its expression ranging between 38 and 81% of cases. Given the fact that circulating androgens represent the most important sex hormones in males and that breast carcinogenesis is characteristically subjected to hormonal mechanisms, our purpose was to investigate the clinicopathological significance of AR in MBC assessing if its expression could be associated with parameters of tumor aggressiveness. Clinical and pathological data were retrospectively reviewed for male patients with a diagnosis of invasive breast cancer. AR status was detected by immunohistochemistry on formalin-fixed, paraffin-embedded tumoral tissue sections. Correlations between AR expression and histopathological features were assessed using univariate and multiple comparisons where appropriate, assuming P values

To assess the reliability of a simple, accessible, cost-effective rule-out tool, for use in triaging patients with Bethesda IV nodules to appropriate surgery. The diagnostic tool was assembled by combining the negativity for suspicious ultrasound features (irregular margins, microcalcification, and a taller-than-wide orientation), and mutational marker negativity (BRAF and NRAS). The tool, (US−/mutation−), was tested on 167 patients with solitary Bethesda IV nodules. The primary outcome was its negative predictive value (NPV) for lesions requiring total thyroidectomy (TT). The impact of mutational marker negativity, as part of the tool, was evaluated by comparing the NPV of (US−/mutation−) to that of (US−/mutation+). 10 out of 167 lesions were positive for a mutational marker. These underwent TT, and only 2/10 (20%) were benign, on final histology. In 6/8 malignant lesions, TT was concordant with current clinical guidelines. 157 patients comprised the negative study cohort, for both mutational markers and suspicious US features. These underwent thyroid lobectomy, and 17 cases resulted in malignancy, only 8 of which required completion thyroidectomy. Accordingly, the NPV of (US−/mutation−) for malignancy was 89% (140/157), and 95% (149/157) for malignancy requiring TT. However, the NPV of (US−/mutation+) was 20% for malignancy, and 40% for malignancy requiring TT. These differences were statistically significant (89% vs. 20%; p

Background Insights into the mechanism of resistance to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) could provide important information for further patient management, including the choice of second-line treatment. The EGFR T790M mutation is the most common mechanism of resistance to first- and second-generation EGFR TKIs. Owing to its biologic relevance in the response of non–small-cell lung cancer (NSCLC) to the selective pressure of treatment, the present study investigated whether the occurrence of T790M at progression differed among patients receiving gefitinib, erlotinib, or afatinib. Patients and Methods The present retrospective study included patients with NSCLC with an EGFR activating mutation, who had received gefitinib, erlotinib, or afatinib as first-line treatment. Plasma samples for the analysis of cell-free DNA were taken at disease progression and analyzed using a digital droplet polymerase chain reaction EGFR mutation assay. Results A total of 83 patients were enrolled; 42 had received gefitinib or erlotinib and 41afatinib. The patient characteristics were comparable across the 2 groups. The median time to progression (TTP) was 14.4 months for the gefitinib and erlotinib group and 10.2 months for the afatinib group (P = .09). Of the 83 patients, 47 (56.6%) were positive for the T790M in plasma. A greater incidence of T790M was observed in patients with progression during gefitinib or erlotinib therapy compared with patients treated with afatinib (33 [79%] vs. 14 [34%], respectively; odds ratio, 7.1; 95% confidence interval, 2.7-18.5; P = .0001). Conclusions Although gefitinib, erlotinib, and afatinib showed a comparable TTP in patients receiving first-line therapy, the incidence of T790M differed among them, as demonstrated by the present study, which could have implications for the choice of second-line treatment.

Backgrounds and aims To investigate relevant indicators of quality of care in a large population-based sample of people with diabetes representative of clinical practice in Italy in 2018. Methods and results We analyzed data from 11,300,750 subjects. All administrative healthcare claims collected in 2018 were scrutinized to identify subjects with diabetes and investigate several indicators of quality of care. Subjects with diabetes were identified by anti-hyperglycemic drug prescriptions, disease-specific co-payment exemption and hospital discharge codes. Indicators of quality of care pertained to monitoring (HbA1c, creatinine, lipid profile, microalbuminuria, eye examination, ECG, ultrasonography of carotid and lower limb arteries) and diabetes treatment (anti-hyperglycemic agents in subjects with cardiovascular disease, CVD). Subjects attending and nonattending Diabetes Clinics were compared. We identified 697,208 individuals with diabetes. HbA1c was assessed at least once in the year in 62.7%, creatinine in 62.3%, total cholesterol in 59.6%, microalbuminuria in 34.3%. Frequency of eye examination was 8.2%, ECG 23.5%, carotid ultrasonography 14.3%, lower limb ultrasonography 7.6%. Among anti-hyperglycemic drugs, SGLT-2 inhibitors were prescribed to ~5% and GLP-1 receptor agonists to ~5% although the proportion of subjects with CVD was ~45%. Subjects attending Diabetes Clinics had higher figures for all these monitoring and treatment indicators. Conclusions The implementation of national and international guidelines regarding disease monitoring and treatment is far from being satisfactory, especially among subjects nonattending Diabetes Clinics. Further efforts and investments are needed for better disseminating guidelines, more efficaciously engaging healthcare professionals and more strongly empowering the healthcare system to improve diabetes care.

IntroductionDiabetes is a highly prevalent disease worldwide and represents a challenge for patients and healthcare systems. This population-based study evaluated diabetes burden in Italy in 2018 by assessing all aspects of outpatient and hospital care.Research design and methodsWe investigated data of 11 300 750 residents in local health districts contributing to ARNO Diabetes Observatory (~20% of Italian inhabitants). All administrative healthcare claims were analyzed to gather information on access to medical resources. Subjects with diabetes, identified by antihyperglycemic drug prescriptions, disease-specific copayment exemption and hospital discharge codes, were compared with age, sex and residency-matched non-diabetic individuals.ResultsWe identified 697 208 subjects with ascertained diabetes, yielding a prevalence of 6.2% (6.5% in men vs 5.9% in women, p2-fold higher in subjects with diabetes, mainly driven by hospitalizations and outpatient care related to chronic complications rather than to glucose-lowering drugs, diabetes-specific devices, or metabolic monitoring.ConclusionsThe burden of diabetes in Italy is particularly heavy and, as a systemic disease, it includes all aspects of clinical medicine, with consequent high expenses in all areas of healthcare.

Germline PTEN pathogenic variants cause a spectrum of disorders collectively labeled PTEN Hamartoma Tumor Syndrome (PHTS) and featured by hamartomas, developmental anomalies and increased cancer risk. Studies on experimental models provided evidence that PTEN is a “haploinsufficient” tumor-suppressor gene, however, mechanisms involved in the pathogenesis of clinical manifestations in PHTS patients remain elusive. Beyond analyzing clinical and molecular features of a series of 20 Italian PHTS patients, we performed molecular investigations to explore the mechanisms involved in the pathogenesis of PTEN-associated manifestations, with special focus on mucocutaneous manifestations. Typical mucocutaneous features were present in all patients assessed, confirming that these are the most important clue to the diagnosis. The most frequent were papules located in the trunk or extremities (73.7%), oral mucosa papules (68.4%), acral/palmoplantar keratosis and facial papules (both 57.9%), according with literature data. Molecular analyses on one trichilemmoma suggested that the wild-type PTEN allele was retained and expressed, reinforcing the evidence that PTEN does not require a second somatic hit to initiate pathogenic processes. Unexpectedly, one patient also displayed a cutaneous phenotype consistent with atypical mole/melanoma syndrome; no variants were detected in known melanoma genes, but Whole Exome Sequencing showed the rare truncating variant c.495G>A in the CDH13 gene that might have cooperated with PTEN-haploinsufficiency to generate such phenotype. Our findings confirm the reproducibility of known PHTS manifestations in real-world practice, highlighting the role of mucocutaneous manifestations in facilitating prompt diagnosis of the syndrome, and provide some insights into the pathogenic process induced by PTEN alterations, which may contribute to its understanding.

Introduction Differentiated thyroid cancer (DTC; >90% of all TCs) derives from follicular cells. Surgery is the main therapeutic strategy, and radioiodine (RAI) is administered after thyroidectomy. When DTC progresses, it does not respond to RAI and thyroid-stimulating hormone (TSH)-suppressive thyroid hormone treatment, and other therapies (i.e. surgery, external beam radiation therapy and chemotherapy) do not lead to a better survival. Thanks to the understanding of the molecular pathways involved in TC progression, important advances have been done. Lenvatinib is a multitargeted tyrosine kinase inhibitor of VEGFR1-3, FGFR1-4, PDGFRα, RET, and KIT signaling networks implicated in tumor angiogenesis, approved in locally recurrent or metastatic, progressive, RAI-refractory DTC. Unmet needs regarding the patient clinical therapy responsiveness in aggressive RAI-refractory DTC still remain. Areas covered We provide an overview from the literature of in vitro, in vivo and real-life studies regarding lenvatinib as an investigational agent for the treatment of aggressive TC. Expert opinion According to the SELECT trial, the treatment should be initiated with a dosage of 24 mg/day, subsequently decreasing it in relation to the side effects. The decision making process in patients with aggressive RAI-refractory DTC should be personalized and the potential toxicity should be properly managed.

BACKGROUND: The incidence of cutaneous melanoma (cm) has increased in the last decades. germline mutations in the high-penetrance melanoma susceptibility gene CDKN2A (Cyclin-dependent kinase inhibitor 2a) are associated with a younger age at diagnosis and an increased risk to develop pancreatic cancer. METHODS: We retrospectively analyzed the data of patients with prior diagnosis of cm referring to our service from January 2005 to may 2017. the aim was to investigate the rate of multiple cms (mPm), assessing their clinical/pathological features. moreover, the genetic tests of patients who had undergone CDKN2A/CDKN2B, CDK4 and MITF screening were evaluated. RESULTS: One hundred fifteen patients (9.26%) were diagnosed with MPMs: 70 males (60.87%) and 45 women (39.13%). 75 patients (43 males and 32 females) underwent genetic screening for germline mutations. The screening revealed that 4/75 patients (5.33%) were carriers of the non-synonymous missense variation c.442g>a (p.ala148thr) in CDKN2A exon 2 in heterozygosis, 3 of whom had at least one in-situ melanoma. In 1 patient (1.33%) we detected the variation c.249C>A, p.His83Gln in CDKN2A exon 2 in heterozygosis and in 1 patient (1.33%) the mutation c.952g>a (p.glu318lys) in MITF gene was found. CONCLUSIONS: This study confirms the need for a full body skin examination and a prolonged surveillance in patients affected by cM, as MPMs were detected in up to 10% of total cases in our series and synchronous lesions in 1/5. Moreover, it reflects the great variability of cM high-susceptibility genes mutational status within the Italian territory. Patients carrying c.952g>a (p.glu318lys) MITF mutation have a higher risk to develop a nodular cm.

Adenomatous Polyposis Coli (APC) gene mutations are responsible for the onset of familial adenomatous polyposis (FAP) and sporadic colorectal cancer and have been associated with miRNAs dysregulation. The capacity of miR-155, a cancer-related miRNA, to target components of the WNT/β-CATENIN pathway suggests that APC gene mutations, controlling miRNAs expression, may critically regulate WNT/β-CATENIN signaling. To this end, APC gene target sequencing was performed on colonic adenomatous polyps and paired normal mucosa clinical specimens from FAP patients (n = 9) to elucidate the role of miR-155-5p in APC-mutant setting. The expression of selected miRNAs and WNT/β-CATENIN signaling components was characterized in FAP patients and non-FAP control subjects (n = 5). miR-155-5p expression and functional effects on WNT cascade, cell survival, growth, and apoptosis were investigated in different colorectal cancer cell lines. A somatic second hit in the APC gene was found in adenomatous polyps from 6 of 9 FAP patients. Heterozygous APC gene mutations in FAP patients were associated with altered expression of candidate miRNAs and increased levels of AXIN1 and AXIN2 mRNAs. miR-155-5p was downregulated in FAP patients and in the APC and β-CATENIN–mutant colorectal cancer cell lines, and critically regulates WNT/β-CATENIN cascade by targeting both AXIN1 and TCF4. Importantly, miR-155-5p may sustain long-term WNT/β-CATENIN activation in colorectal cancer cells upon WNT3A stimulation. Implications: This study supports a key role of miR-155-5p in modulating WNT/β-CATENIN signaling in colorectal cancer and unravels a new mechanism for AXIN1 regulation which represents a potential therapeutic target in specific tumor subtypes.

The role of opioids and opioid medications in ADHD symptoms is still largely understudied. We tested the hypothesis that, in Heroin Use Disorder (HUD), when patients are treated with Agonist Opioid medications (AOT), treatment outcome is associated with the presence of Adult Attention-Deficit/Hyperactive Disorder (A-ADHD) symptomatology. A retrospective cohort study of 130 HUD patients in Castelfranco Veneto, Italy, covering 30 years, was divided into two groups according to the Adult ADHD Self-Report Scale (ASRS) score and compared them using demographic, clinical and pharmacological factors. Survival in treatment was studied by utilizing the available data for leaving treatment and relapsing into addictive behavior and for mortality during treatment as poor primary outcomes. Thirty-five HUD subjects (26.9%) were unlikely to have A-ADHD symptomatology, and 95 (73.1%) were likely to have it. Only current age and co-substance use at treatment entry differed significantly between groups. Censored patients were 29 (82.9%) for HUD patients and 70 (73.9%) for A-ADHD/HUD patients (Mantel-Cox test = 0.66 p = 0.415). There were no significant linear trends indicative of a poorer outcome with the presence of A-ADHD after adjustment for demographic, clinical and pharmacological factors. Conclusions: ADHD symptomatology does not seem to exert any influence on the retention in AOT of HUD patients.

Background: Childhood obesity represents a public health crisis in the United States, affecting 13.9% of preschool-aged children. Most pathophysiologic mechanisms leading to obesity are introduced in early childhood, making this a critical period to consider. The Food and Fitness Initiative (FFI) is a community-based wellness program that focuses on healthy eating and physical activity, implemented in Northeast Iowa. A previous study showed that FFI lowered the rate of increase of body mass index (BMI) levels in school-aged children exposed to the initiative. Our aim is to describe the impact on BMI after implementing …

COVID-19 has profoundly modified the way healthcare is delivered. Jordan imposed lockdown and restrictive policies between March 17 and May 20, 2020. We aimed to assess the impact of such measures on thyroid cancer treatment plans. In the specified period, 12 patients were scheduled for surgery. Since papillary carcinoma was the preoperative diagnosis in all cases, radioactive iodine ablation (RIA) therapy was also planned 3–4 weeks following surgery after withdrawing thyroxine and achieving a thyroid stimulating hormone (TSH) level > 30 mU/L. Thyroxine withdrawal is the routine method applied for RIA in Jordan as it is less costly compared to the rapid method of exogenous stimulation using recombinant TSH. All surgical procedures were performed without delay since all patients were asymptomatic per flu-like illness and came from a region of low COVID-19 prevalence. These included total thyroidectomy (n = 11), bilateral therapeutic central compartment neck dissection (n = 7), lateral compartment neck dissection (n = 5). However, the RIA treatment plan was altered considerably according to the period in which they were operated. 6 out of the 7 patients operated in March changed to the stimulated method of RIA at a considerable additional extra cost. The seventh patient and the April patient opt to delay RIA until after lockdown. The remaining cases (operated in May) followed the usual withdrawal method as restrictions were due to an end. The restrictive measures applied during COVID-19 did not affect the safe and timely delivery of surgical care. However, it added a financial and psychological burden to the entire cancer management plan.

OBJECTIVE Event-related brain potential (ERP) studies have shown that bulimia nervosa (BN) is associated with facilitated processing of disorder-specific stimuli, visible in altered early components during presentation of food cues and bodies varying in size. Less is known about BN and late ERPs, typically less influenced by perceptual features and regarded as more reliable indices of motivational relevance. The purpose of this study was to use the late positive potential (LPP) to investigate the motivational significance of BN-relevant stimuli. METHODS Highly salient stimuli, such as pictures of personal binge foods and images that are pleasant, neutral, and unpleasant (e.g., human attacks) were presented to 24 women with bulimia and 24 healthy women (19.7 ± 2.1 and 20.5 ± 2.6 years, respectively). Pictures of erotic couples, previously shown to prompt the greatest appetitive reactions in healthy women, were used as pleasant cues. Based on BN aversion to body cues, we hypothesized that the motivational significance of erotic cues could be increased in bulimic women. RESULTS Consistent with the literature, the LPP was modulated by the salience of the pictures (F(2.8,130.7) = 24.6, p < .001). An additional interaction with diagnostic group (F(2.8,130.7) = 2.8, p = .047) indicated that bulimic women showed a larger LPP than healthy controls during pictures displaying binge foods (p = .037) and erotic couples (p = .031). CONCLUSIONS The findings provide objective evidence that BN is characterized by dysregulated emotional processing that is not limited to food cues. The implications are discussed within a transdiagnostic perspective on food-related disorders.

This work was supported by the MECD [grant numbers FPU16/01200], 'Doctoral College "Imaging the Mind" (FWF; W1233-B)', a grant from Junta de Andalucia, Spain [Grant Code P12.SEJ.391], and a grant from the Spanish Ministry of Economy and Competitiveness/MINECO (Grant Code: PSI2013-43777-P)., Background: Studies on food cue reactivity have documented that altered responses to high-calorie food are associated with bulimic symptomatology, however, alterations in sexual motivations and behaviors are also associated clinical features in this population, which justify their inclusion as a research target. Here, we study responses to erotic cues—alongside food, neutral and aversive cues—to gain an understanding of specificity to food versus a generalized sensitivity to primary reinforcers. Methods: We recorded peripheral psychophysiological indices –the startle reflex, zygomaticus, and corrugator responses—and self-reported emotional responses (valence, arousal, and dominance) in 75 women completing the Bulimia Test-Revised (BULIT-R). Multiple regression analysis tested whether BULIT-R symptoms were predicted by selfreported and psychophysiological responses to food versus neutral and erotic versus neutral images. Results: The results showed that individuals with higher bulimic symptoms were characterized by potentiated eye blink startle response during binge food (vs. neutral images) and more positive valence ratings during erotic (vs. neutral) cues. Conclusions: The results highlight the negative emotional reactivity of individuals with elevated bulimic symptoms toward food cues, which could be related to the risk of progression to full bulimia nervosa and thereby addressed in prevention efforts. Results also point to the potential role of reactivity to erotic content, at least on a subjective level. Theoretical models of eating disorders should widen their conceptual scope to consider reactivity to a broader spectrum of primary reinforcers, which would have implications for cue exposure-based treatments. Plain English summary: We examined appetitive and aversive cue responses in college women to investigate how bulimic symptoms relate to primary reinforcers such as food and erotic images. We recorded peripheral psychophysiological indices (the startle reflex, zygomaticus, and corrugator responses) and self-reported emotional responses (valence, arousal, and dominance) in 75 college women that were presented with the Spanish version of the Bulimia Test-Revised. The results showed that bulimic symptoms increase both psychophysiological defensiveness toward food cues and subjective pleasure toward erotic cues. The findings suggest a generalized sensitivity to primary reinforcers in the presence of bulimic symptoms, and emphasize the relevance of adopting a wider framework in research and treatment on bulimia nervosa., MECD FPU16/01200, Doctoral College "Imaging the Mind" (FWF) W1233-B, Junta de Andalucia European Commission P12.SEJ.391, Spanish Ministry of Economy and Competitiveness/MINECO PSI2013-43777-P

Over the past decade, the incidence of thyroid cancer has rapidly increased worldwide, and thyroid surgery has become one of the most common performed surgical procedure. Even though conventional open thyroidectomy remains the gold standard, this approach leaves a neck scar which could be worrying mainly for young women. The recent progress in surgical technology, as well as patient cosmetic requests, have led to the development of alternative access to the thyroid lodge. Thus, alternative techniques have been established in order to potentially provide a more appealing cosmetic result, both with a minimally-invasive cervical or remote-access approach. However, the introduction of these new techniques was initially approached with caution due to technical challenges, the introduction of new complications and, above all, skepticism about the oncologic effectiveness. Among several alternative approaches proposed, the minimally invasive video-assisted thyroidectomy and the robot-assisted transaxillary thyroidectomy became popular and obtained the favor of the scientific community. Moreover, the recent introduction of the trans-oral endoscopic thyroidectomy with vestibular approach, although the safety and the efficacy are still under discussion, deserves particular attention since it represents the only technique truly scarless and provides the best cometic result. The purpose of this article is to provide an overview of the current main alternative approaches for the treatment of thyroid cancer with particular focus on the oncological effectiveness of the procedures.

Insomnia, vasomotor symptoms (VMS) and depression often co-occur after the menopause, with consequent health problems and reductions in quality of life. The aim of this position statement is to provide evidence-based advice on the management of postmenopausal sleep disorders derived from a systematic review of the literature. The latter yielded results on VMS, insomnia, circadian rhythm disorders, obstructive sleep apnea (OSA) and restless leg syndrome (RLS). Overall, the studies show that menopausal hormone therapy (MHT) improves VMS, insomnia, and mood. Several antidepressants can improve insomnia, either on their own or in association with MHT; these include selective serotonin reuptake inhibitors (SSRIs), serotonin and norepinephrine reuptake inhibitors (SNRIs), and mirtazapine. Long-term benefits for postmenopausal insomnia may also be achieved with non-drug strategies such as cognitive behavioral therapy (CBT) and aerobic exercise. Continuous positive airway pressure (CPAP) and mandibular advancement devices (MADs) both reduce blood pressure and cortisol levels in postmenopausal women suffering from OSA. However, the data regarding MHT on postmenopausal restless legs syndrome are conflicting.

Purpose: To compare the inverted flap and the subretinal aspiration technique for full-thickness macular hole (FTMH) surgery. Methods: Forty consecutive eyes with a stage IV FTMH were randomly assigned into 2 treatment groups. After core vitrectomy and perimacular internal limiting membrane (ILM) peeling, in group A, the subretinal remnant macular fluid was aspirated with a 41-G cannula after the air-fluid exchange procedure, while in group B, the technique of an inverted ILM flap was completed. Differences in postoperative best-corrected visual acuity (BCVA) and occurrence of intraoperative or postoperative complications between the 2 groups were evaluated. Results: All FTMHs were closed after the first surgery with no intraoperative or postoperative complications. In group A, 16 patients (80%) showed improvement of BCVA and 4 (20%) showed stabilization. In group B, 12 patients (60%) had improved BCVA, while 6 (30%) remained stable and 2 (10%) worsened. Postoperative BCVA for group A was significantly better than for group B (p = 0.022). Conclusions: The surgical techniques had similar rates of closure of FTMH, although BCVA outcomes were significantly better in the subretinal aspiration group.

Background: Refractory glaucoma still represents a challenge for ophthalmologists to manage intraocular pressure. The present study aimed to evaluate long term efficacy and safety of a second Ahmed valve implantation after the failure of a first implant in patients with refractory glaucoma and elevated intraocular pressure (IOP). Methods: Retrospective, multicenter non-comparative case series. Twenty-eight patients were retrospectively recruited between January 2011 and December 2017. Demographic data, glaucoma type, visual acuity, intraocular pressure, medical therapy, and complications were registered. Three criteria of success were established: Type 1 surgical success: IOP &le, 15 mmHg and a reduction of IOP &ge, 40% from baseline, Type 2 surgical success: IOP &le, 18 mmHg and a reduction of IOP &ge, 30% from baseline, and Type 3 surgical success: IOP &le, 21 mmHg and a reduction of IOP &ge, 20% from baseline. Surgical failure has been established as IOP less than 5 mmHg or over 21 mmHg and less than a 20% reduction of IOP from baseline despite medications in two consecutive visits, light perception loss referable to glaucoma, and the necessity for further glaucoma surgery. Failure was observed in six (21%) patients. (3) Results: Mean IOP and mean glaucoma medication number significantly reduced from baseline after the second implantation, and the surgical success rate at 72 months ranged from 10% to 78% based on the different criteria of success. Failure was observed in six (21%) patients. Conclusions: This study confirmed the safety and efficacy of a second Ahmed valve implantation in patients with refractory glaucoma and elevated IOP at baseline.

Purpose: The aim of this study is to highlight the role of the endoscopic endonasal approach (EEA) in pediatric craniopharyngiomas by reviewing our experience and the key lessons learned from the application of this approach in children. Methods: Between 1998 and 2017, 12 pediatric craniopharyngiomas were treated via EEA at our institution. Demographic data, preoperative assessment, tumor features, surgical results, complications, and recurrences were analyzed. Results: Visual defects were the most frequent presenting sign. Seven craniopharyngiomas were infradiaphragmatic, and five were supradiaphragmatic. The EEA was successfully performed in all cases with no complication related to children’s sinonasal anatomy. Gross total resection (GTR) rate was of 75%. Endocrinological disturbances improved in one case (20%) and worsened in three (60%). New onset of diabetes insipidus was observed in four (36%) children. Visual defect improved in 91% of cases, with no new postoperative deficit. Postoperative cerebrospinal fluid (CSF) leak occurred in one patient (8%). Three patients (27%) experienced tumor regrowth, and one craniopharyngioma recurred (mean follow-up, 78 months). Conclusions: The EEA offers a straight route to the sellar-suprasellar, making it the ideal approach for pediatric infradiaphragmatic craniopharyngiomas. In supradiaphragmatic craniopharyngiomas, the extended EEA provides a clearer and close-up visualization of the tumor-hypothalamus interface, which can grant better results in terms of quality of life. The pediatric skull base anatomy should not represent a contraindication for the endoscopic technique. Larger series encompassing a wider spectrum of pediatric craniopharyngiomas are needed to further support the benefits of this surgical approach.

Rationale: Genotype–phenotype relationships are emerging in primary ciliary dyskinesia (PCD), but little is known about lung volume changes over time. Objectives: To investigate the evolution of st...

Body awareness disorders and reactivity are mentioned across a range of clinical problems. Constitutional differences in the control of the bodily state are thought to generate a vulnerability to psychological symptoms. Autonomic nervous system dysfunctions have been associated with anxiety, depression, and post-traumatic stress. Though interoception may be a transdiagnostic mechanism promoting the improvement of clinical symptomatology, few psychometrically sound, symptom-independent, self-report measures, informed by brain–body circuits, are available for research and clinical use. We validated the Italian version of the body perception questionnaire (BPQ)—short form and found that response categories could be collapsed from five to three and that the questionnaire retained a three-factor structure with items reduced from 46 to 22 (BPQ-22). The first factor was loaded by body awareness items, the second factor comprised some items from the body awareness scale and some from the subdiaphragmatic reactivity scale (but all related to bloating and digestive issues), and the third factor by supradiaphragmatic reactivity items. The BPQ-22 had sound psychometric properties, good convergent and discriminant validity and test–retest reliability and could be used in clinical and research settings in which the body perception assessment is of interest. Psychometric findings in light of the polyvagal theory are discussed.

Edentulism is one of the most significant problems given the increase in the elderly population. The aim of the present investigation is to evaluate a case report with angled screwdriver solutions and new kinds of low-profile attachments in full arch rehabilitation with divergent implants. In this clinical case we will analyze how low-profile abutments with angled screwdriver channel in the OT Bridge system (Rhein83, Bologna, Italy) can be a predictable solution over time to create a fixed prosthesis on disparallel implants with a digital structure (New Ancorvis, Bologna, Italy) for the satisfaction of the patient and of the work team.

Graves’ disease (GD) is an organ-specific autoimmune disorder of the thyroid, which is characterized by circulating TSH-receptor (TSH-R) stimulating antibodies (TSAb), leading to hyperthyroidism. Graves’ ophthalmopathy (GO) is one of GD extra-thyroidal manifestations associated with the presence of TSAb, and insulin-like growth factor-1 receptor (IGF-1R) autoantibodies, that interact with orbital fibroblasts. Cytokines are elevated in autoimmune (i.e., IL-18, IL-6) and non-autoimmune hyperthyroidism (i.e., TNF-α, IL-8, IL-6), and this could be associated with the chronic effects of thyroid hormone increase. A prevalent Th1-immune response (not related to the hyperthyroidism per se, but to the autoimmune process) is reported in the immune-pathogenesis of GD and GO; Th1-chemokines (CXCL9, CXCL10, CXCL11) and the (C-X-C)R3 receptor are crucial in this process. In patients with active GO, corticosteroids, or intravenous immunoglobulins, decrease inflammation and orbital congestion, and are considered first-line therapies. The more deepened understanding of GO pathophysiology has led to different immune-modulant treatments. Cytokines, TSH-R, and IGF-1R (on the surface of B and T lymphocytes, and fibroblasts), and chemokines implicated in the autoimmune process, are possible targets of novel therapies. Drugs that target cytokines (etanercept, tocilizumab, infliximab, adalimumab) have been tested in GO, with encouraging results. The chimeric monoclonal antibody directed against CD20, RTX, reduces B lymphocytes, cytokines and the released autoantibodies. A multicenter, randomized, placebo-controlled, double-masked trial has investigated the human monoclonal blocking antibody directed against IGF-1R, teprotumumab, reporting its effectiveness in GO. In conclusion, large, controlled and randomized studies are needed to evaluate new possible targeted therapies for GO.

Background: Papillary thyroid carcinoma (PTC) accounts for the majority of thyroid cancer and affects a large number of individuals. The pathogenesis of PTC has not been completely elucidated thus far. Metabolic reprogramming is a common feature in tumours. Our previous research revealed the reprogramming of lipid metabolism in PTC. Further studies on lipid metabolism reprogramming may help elucidate the pathogenesis of PTC. Methods: Clinical samples of PTC and para-tumour tissue were analysed using lipidomic, proteomic, and metabolomic approaches. A multi-omics integrative strategy was adopted to identify the important pathways in PTC. The findings were further confirmed using western blotting, tissue microarray, and bioinformatics. Findings: The differentially expressed substances included 146 lipids, 2975 proteins, and 217 metabolites in PTC samples. Multi-omics data and the results of integrated analysis revealed that the three steps of fatty acid metabolism (hydrolysis, transportation, and oxidation) were significantly enhanced in PTC. The key enzymes in the three steps, namely LPL, FATP2, and CPT1A, respectively, were overexpressed. Moreover, their expression was strongly associated with the TNM stage, lymph node metastasis, and PTC prognosis. In addition, the levels of several types of phospholipids and sphingolipids increased significantly in PTC. Interpretation: Our data suggested that enhanced fatty acid metabolism supplied additional energy and substrates for tumour growth, invasion, and metastasis in PTC. This may help elucidate the mechanism underlying PTC pathogenesis and identify the potential therapeutic targets for PTC. Funding Information: Work in the authors' laboratory is supported by grants from National Natural Science Foundation of China (No. 81702647, NO. 81972819), Taishan Scholar Foundation of Shandong Province (No. tspd20181201), Collaborative Innovation Center of Technology and Equipment for Biological Diagnosis and Therapy in Universities of Shandong, Natural Science Foundation of Shandong Province (No. ZR201702190483, No. ZR2020YQ57), Key Technology Research and Development Program of Shandong (No. 2016GSF201161). Declaration of Interests: The authors declare no competing interests. Ethics Approval Statement: This prospective study was approved by the institutional ethical committee of Qilu Hospital of Shandong University, Shandong Province, China. All the specimens were collected in the Qilu Hospital of Shandong University. The participants provided written informed consent for the use of thyroid tissue specimens for research.

BACKGROUND The evaluation of aortic valve calcium burden is important when planning for transcatheter aortic valve implantation (TAVI). Although a robust golden standard methodology is available for calcium evaluation on noncontrast-enhanced (NCE) computed tomographic (CT) series, a standard reference for calcium assessment on contrast-enhanced CT series is currently lacking. METHODS Two hundred and forty-four preprocedural CT scans from patients who had received TAVI were analysed. We correlated the aortic calcium volumes obtained on CE series at three thresholds [450, 850, and 'probe + 100' Hounsfield Units (HU)] with the Agatston score obtained on NCE scans. A subgroup analysis was performed taking into account the contrast enhancement of the left ventricular outflow tract (LVOT), with a prespecified cut-off of 300 HU. RESULTS The overall population analysis showed higher correlation with the Agatston score using the 850 HU threshold (r = 0.45, P

Purpose. Recent clinical practice guidelines consider thyroid lobectomy a viable alternative for low-risk papillary thyroid carcinoma PTC measuring 1–4 cm in size. We aimed to assess the likelihood of finding postoperatively determined high-risk histopathologic features that would lead to the recommendation of completion thyroidectomy. Methods. A retrospective review of patients who underwent total thyroidectomy for PTC measuring 1–4 cm in size between Jan 2012-Jan 2018 was conducted. Patients with pre-operative high-risk characteristics were excluded; history of radiation exposure, positive family history, clinically suspicious cervical lymphadenopathy, and gross extrathyroidal extension (ETE). A hypothetical group of 245 patients remained eligible for lobectomy. The pathology specimens from the cancer-containing lobes were evaluated for high-risk features: aggressive histology, capsular and/or vascular invasion, microscopic ETE, and multifocality. A subgroup analysis was performed with 2 cm being the cut-off size. Results. The average age was 39 years with 73% being females. Mean cancer size was 16 mm. Evaluation of the cancer-containing lobe for high-risk features revealed: aggressive histology (33%), ETE (12%), capsular invasion (33%), vascular invasion (17%), and ipsilateral multifocality (30%). The cumulative risk of having ≥ 1 high-risk feature mandating completion thyroidectomy was 59%. The risk was considerably higher for lesions ≤ 2 cm compared to larger lesions (64% vs.48%; p = 0.049; RR = 1.3). Conclusion. A considerable proportion of patients initially eligible for lobectomy have high-risk features that only become evident at pathology. Therefore, a comprehensive approach is advocated to determine the extent of surgery for PTC incorporating patient preferences regarding risks and benefits.

Breast cancer (BC) is the most frequent non-cutaneous malignancy in women. Histological grade, expression of estrogen and progesterone receptors (ER and PgR), overexpression/amplification of the human epidermal growth factor receptor 2 (HER2) oncogene, and proliferative activity measured with ki-67 provide important information on the biological features of BC and guide treatment choices. However, a biomarker that allows a more accurate prognostic stratification is still lacking. Thymidine kinase-1 (TK1), a ubiquitous enzyme involved in the pyrimidine nucleotide recovery pathway, is a cell-proliferation marker with potential prognostic and predictive impacts in BC. Eighty (80) cases of invasive BC with a long-term follow-up were retrospectively selected, and clinicopathological data were collected for each patient. TK1 tissue expression was evaluated immunohistochemically. Data suggested that TK1 expression levels are positively correlated with ER and PgR expression, and negatively correlated with HER2 status and the impact on patients’ distant recurrence-free survival (DRFS): in detail, among patients undergoing adjuvant chemotherapy, lower TK1 levels are correlated with better DRFS. Therefore, these results contribute to furthering the knowledge of TK1, suggesting a possible and important role of this enzyme as a biomarker in the stratification of BC patients.

Tyrosine kinase inhibitors (TKIs) are emerging as potentially effective options in the treatment of cancer, acting on the pathways involved in growth, avoidance of apoptosis, invasiveness, angiogenesis, and local and distant spread. TKIs induce significant adverse effects, that can negatively affect patients’ quality of life. The most common adverse events (AEs) include fatigue, hand–foot skin reaction, decreased appetite, nausea, diarrhea, hypertension, vomiting, weight loss, endocrinopaties and metabolic disorders. Patients in therapy with TKIs can develop endocrine-metabolic disorders, including dyslipidemia (~50%), diabetes (~15–40%), and dysthyroidism (~20%). In some cases, patients show an improved glycemia or hypoglycemia. The effects of TKIs on adrenal or gonadal function are still not completely known. It was shown a higher prevalence of subclinical hypocortisolism in patients treated with imatinib, while an increase of cortisol was reported in patients receiving vandetanib. Long-term treatment with imatinib could impact significantly the ovarian reserve and embryo developmental capacity. It is important to evaluate patients, measure glucose levels, and manage hyperglycemia. Mild treatment-related hyperglycemia can be controlled modifying the diet and with exercise, while grade 3 and 4 hyperglycemia can lead to dose reductions and/or oral antihyperglycemic therapy. Regarding thyroid dysfunctions, it is recommendable to measure the thyroid-stimulating hormone (TSH)/free thyroxine (FT4) levels before starting the therapy, and every 3–4 weeks during the first 6 months as changes in FT4 levels precede the changes in TSH by 3–6 weeks. Additional studies are necessary to definitely clarify the mechanism of TKIs-induced endocrine-metabolic effects.

ContextAtypical parathyroid adenomas (APAs) are neoplasms with uncertain malignant potential but lack unequivocal histological signs of malignancy.ObjectiveThis work aims to retrospectively evaluate the clinical and biochemical profiles of patients with APA, the outcome after parathyroidectomy (PTX), and the presence of CDC73 germline and somatic mutations.MethodsThis monocentric study was conducted on consecutive patients undergoing PTX for primary hyperparathyroidism (PHPT) between June 2000 and December 2020. Fifty-eight patients with a confirmed histopathological diagnosis of APA, and age- and sex-matched controls with parathyroid adenoma (PA) were also included.ResultsFifty-four patients had sporadic PHPT and 4 had familial isolated hyperparathyroidism (FIHP). Thirty-four patients (59%) had symptomatic disease. Serum calcium and parathyroid hormone (PTH) levels were significantly higher in symptomatic compared to asymptomatic patients (P = .048 and .008, respectively). FIHP patients were younger than their sporadic counterparts (30 ± 17 years vs 55 ± 13 years). APA patients had significantly higher serum calcium and PTH levels and lower 25-hydroxyvitamin D concentration, bone mineral density, and T score at one-third distal radius compared to those with PA. Four of 56 APA patients displayed a CDC73 germline mutation. No somatic CDC73 mutation was identified in 24 tumor specimens. The mean follow-up after surgery was 60 ± 56.4 months. All but 6 patients (90%), 5 with apparently sporadic PHPT and 1 with FIHP, were cured after surgery.ConclusionThe large majority of patients with APA, despite a moderate/severe phenotype, have a good prognosis. Germline CDC73 mutation–positive patients had a higher rate of persistent/recurrent disease. CDC73 gene alterations do not seem to have a relevant role in the tumorigenesis of sporadic APA.

Background Childhood obesity represents a public health crisis in the United States. Thus, focusing on early childhood is crucial to modify the consequences associated with obesity. The Food and Fitness Initiative (FFI) is a community-based wellness program implemented in Northeast Iowa since 2009. FFI focuses on healthy eating and physical activity. Our aim is to describe the impact on body mass index (BMI) after implementing FFI in a Northeast Iowa Community Action Head Start (HS) population. Methods Retrospective BMI data was collected from all children attending 14 HS sites from 2012 to 2018. Children with BMI measurements during July to December of the first year in HS were included in the study. Follow-up data the second year in HS was obtained. Overweight and obesity prevalence, as well as, BMI changes between year 1 and 2 in HS were analyzed. Results Data from 1013 children were collected, 850 (84%) had qualifying BMI measurements during their first year in HS and 352 of those children (41%) had follow-up data in their second year. There was a decrease in BMI between years 1 and 2 in HS that approached statistical significance ( t = 1.83, P = .07, d = .10). There were no statistically significant changes in the percent of overweight (Wald χ2 = .50, P = .48) or obese (Wald χ2 = 1.71, P = .19) children between the first and second year. Conclusion The FFI wellness program can be feasibly integrated into the HS curriculum and shows promising short-term results in improving BMI, but not to a statistically significant level when evaluated over 1 year.

Objectives To retrospectively evaluate the conditions of the peri-implant tissues in treated patients with chronic periodontitis (CP) and in patients without chronic periodontitis (noCP). Materials and methods A chart review was used to evaluate 267 implants, 134 placed in 42 CP treated patients and 133 placed in 46 noCP patients. The primary outcome was to evaluate the condition of the peri-implant tissues (health, peri-mucositis, and peri-implantitis). The secondary outcome was to evaluate the possible association of some variables, such as, Plaque Index (PI), Bleeding Index (BI), probing pocket depth (PD), bleeding on probing (BoP), bone level (BL), loading time, type of implant placement and loading protocol, type of prosthesis, type of bone, implant manufacturer, and implant diameter and length, with the implant health condition. Results The analysis of patient files revealed that after 10-15 years of loading (mean loading time 13.4 ± 2.07 years), six noCP patients (13%) experienced implant loss with a total of nine implants (6.7%) lost. The remaining 124 implants were classified: 54 (43.5%) as healthy, 45 (36.3%) with peri-implant mucositis, and 25 (20.2%) with peri-implantitis. Twelve CP subjects (28.5%) experienced implant loss with a total of 19 implants (14.1%) lost. The remaining 115 implants were classified: 34 (29.5%) as healthy, 40 (34.7%) with peri-implant mucositis and 41 (35.6%) with peri-implantitis. Compared with noCP subjects, only treated CP subjects with recurrent periodontal disease (RPD) showed differences statistically significant (p Conclusions After 10-15 years of loading, in CP patients treated in a private practice setting, most implants (70.1%) were classified with some type of peri-implant inflammation. In patients with RPD, a higher tendency for implant loss and peri-implant biologic complications was found.

The purpose of this study is to describe the Minimally Invasive Intraoral Approach (MIIA) performed on selected cases of abscesses and neck phlegmons of odontogenic origin when the infection has not spread beyond the inferior mandibular margin. This technique allows us to avoid cervicotomy by a direct approach to the abscess, draining it through the oral cavity. If the limits have already been crossed, then cervicotomy is necessary. The aim of the study is to show the surgical outcomes that we have achieved during a time span of two years, and to show the effectiveness of the MIIA and its results. We selected 66 patients with abscesses and neck phlegmons, from January 2018 to June 2020. Among these cases, five patients were excluded as it was not possible to recover medical records from database. The MIIA technique has been performed on 16 patients (26.2%) when a successful dental extraction and drainage of the submandibular lodge were accomplished. The patients who underwent the MIIA surgery have all perfectly healed and did not suffer from relapses during the follow-up. The results show the achievement of excellent healing, underlining the lower impact required by MIIA when compared to a more traditional approach through cervicotomy.

Lung Ultrasound (LUS) is regarded to be potentially useful to diagnose lung injury in older adults living in nursing homes with suspected COVID-19 pneumonia. We aimed at evaluating presence lung injury among senior nursing home residents by LUS performed with portable wireless scanner echography. The study population consisted of 150 residents with a mean age of 88 years (85% female) residing in 12 nursing homes in Northern Italy. Subjects had to have a history of recent onset of symptoms compatible with COVID-19 pneumonia or have been exposed to the contagion of patients carrying the disease. COVID-19 testing was performed with SARS-CoV-2 nasal-pharyngeal (NP) swabs. Positive subjects to LUS scanning were considered those with non-coascelent B-lines in >3 zones, coalescent B-lines in >3 zones and with iperdensed patchy non-consolidated lungs. Sixty-three percent had positive NP testing and 65% had LUS signs of pulmonary injury. LUS had a sensitivity of 79% in predicting positive NP testing. Sixteen percent of residents tested negative for SARSCoV-2 carried the signs of COVID-19 lung injury at LUS. There were 92 patients (61%) with current or recent symptoms.Positivity to LUS scanning was reported in 73% of residents with symptoms, while it was 53% in those without (P=0.016). A positive NP testing was observed in 66% of residents with symptoms and in 57% of those without (P=0.27). We conclude that assessment of LUS by portable wireless scanner echography can be profitability utilized to diagnose lung injury among senior nursing home residents with or without symptoms compatible with COVID-19 pneumonia.

Non-albuminuric diabetic kidney disease (Alb-DKD) has been associated with a raised risk of CV outcomes and all-cause mortality in T1D. We report about the association between DKD phenotypes and CV outcomes in a single-centre, prospective, 10.4±2.9 years observation of 774 T1D. Rates of outcomes and vital status were censored on December 2017. Out of 774 T1D, 692 (89.4%) had no-DKD, 53 DKD 1-2 (6.8%), 17 (2.2%) Alb-DKD and 12 (1.6%) Alb+DKD. Incidences of CV outcomes, coronary events and ESRD were available for 736 subjects (95.1%). A CV event occurred in 49 T1D (6.7%; 6.42 events x 1000 PYs), rising from no-DKD (4.2%) to DKD 1-2 (28.6%) and Alb-DKD (35.3%). In Alb+DKD, due to competition with all-cause death, only 1 event occurred. Compared to no-DKD, the adjusted HRs were 4.43 (95%CI 2.27-8.61, p Disclosure M. Garofolo: None. E. Gualdani: None. F. Campi: None. M. Aragona: None. D. Lucchesi: None. C. Bianchi: None. R. Miccoli: None. P. Francesconi: None. G. Penno: None. S. Del Prato: Advisory Panel; Self; Applied Therapeutics, AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Takeda Pharmaceutical Company Limited.

Microvascular complications (MC) affect CV risk and mortality in T2D. We explored the association of cumulative burden of retinopathy, nephropathy and peripheral neuropathy with mortality, CV events and ESRD in a single-centre, observational study involving 986 T2D over a 12.9±2.7 yrs follow-up. Vital status and rates of outcomes were censored on December 2017. The cohort included 491 (49.8%), 318 (32.3%), 135 (13.7%) and 42 (4.3%) people with no, 1, 2 or 3 MC. All-cause mortality (23.3%) increased from no-MC (15.3%) to 1 MC (23.3%, HR 1.60; 95%CI 1.16-2.20), 2 MC (41.5%, 3.19; 2.25-4.51) and 3 MC (59.5%, 5.32; 3.38-8.36; p Disclosure M. Garofolo: None. E. Gualdani: None. R. Giannarelli: None. D. Lucchesi: None. R. Miccoli: None. P. Francesconi: None. S. Del Prato: Advisory Panel; Self; Applied Therapeutics, AstraZeneca, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novartis Pharmaceuticals Corporation, Novo Nordisk A/S. Research Support; Self; AstraZeneca, Boehringer Ingelheim International GmbH. Speaker’s Bureau; Self; AstraZeneca, Boehringer Ingelheim International GmbH, Eli Lilly and Company, Merck Sharp & Dohme Corp., Novo Nordisk A/S, Sanofi, Takeda Pharmaceutical Company Limited. G. Penno: None.

Background:One of the most serious and potentially life-threatening adverse events associated with anterior cervical spine surgery is postoperative hematoma with acute airway obstruction. The causes of unpredicted delayed bleeding are, however, not fully elucidated. Here, we report a case of delayed arterial bleeding and sudden airway obstruction following a two-level ACDF.Case Description:A 52-year-old male presented with the right paracentral disc herniations at the C4–C5 and C5–C6 levels. A two-level ACDF was performed. Notably, on the 5thpostoperative day, the patient developed an acute respiratory distress due to a large right lateral retrotracheal hematoma requiring emergency evacuation at the bedside. This was followed by formal ligation of a branch of the right superior thyroid artery in the operating room. In addition, an emergency tracheotomy was performed. By postoperative day 15, the tracheotomy was removed, and the patient was neurologically intact.Conclusion:A superior thyroid artery hemorrhage should be suspected if a patient develops delayed neck swelling with or without respiratory decompensation several days to weeks following an ACDF. Notably, these hematomas should be immediately recognized and treated (i.e., decompression starting at the bedside and completed in the operating room) to prevent catastrophic morbidity or mortality.

COVID‐19 has been declared a pandemic by the World Health Organization. As of April 1, 2020, Italy was the country with the second highest number of cases in the world. The spread of COVID‐19 has required a rapid reorganization of health service delivery in face of the pandemic. Breast cancer units have reprioritized their workload to guarantee the health of oncologic patients at the highest risk and regular screening activities. However, at the end of the pandemic emergency, many benign and reconstructive cases will return to our attention and their surgical treatment will be necessary as soon as possible.