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La comprensione del legame tra dieta e tiroide sta rapidamente espandendosi oltre l’ambito della nutrizione iodica, anche in conseguenza del cambiamento dello stile di vita e delle abitudini alimentari della popolazione generale. Scopo di questa rassegna è esaminare i fattori nutrizionali indispensabili per una corretta funzione tiroidea e esplorare le correlazioni tra assunzione di diversi alimenti, modelli alimentari e tireopatie, con uno speciale focussull’autoimmunità.

Background: The family of perfluoroalkyl and polyfluoroalkyl substances (PFAS) raised concern for their proven bioaccumulation and persistence in the environment and animals as well as for their hazardous health effects. As a result, new congeners of PFAS have rapidly replaced the so-called “old long-chain PFAS” (mainly PFOA and PFOS), currently out-of-law and banned by most countries. These compounds derive from the original structure of “old long-chain PFAS”, by cutting or making little conformational changes to their structure, thus obtaining new molecules with similar industrial applications. The new congeners were designed to obtain "safer" compounds. Indeed, old-long-chain PFAS were reported to exert thyroid disruptive effects in vitro, and in vivo in animals and humans. However, shreds of evidence accumulated so far indicate that the “restyling” of the old PFAS leads to the production of compounds, not only functionally similar to the previous ones but also potentially not free of adverse health effects and bioaccumulation. Studies aimed at characterizing the effects of new-PFAS congeners on thyroid function indicate that some of these new-PFAS congeners showed similar effects. Purpose: The present review is aimed at providing an overview of recent data regarding the effects of novel PFAS alternatives on thyroid function. Results and conclusions: An extensive review of current legislation and of the shreds of evidence obtained from in vitro and in vivo studies evaluating the effects of the exposure to novel PFOA and PFOS alternatives, as well as of PFAS mixture on thyroid function will be provided.

Objective: Studies have highlighted the inequities between the Indigenous and non-Indigenous populations with respect to the burden of cardiovascular disease and prevalence of predisposing risks resulting from historical and ongoing impacts of colonization. The objective of this study was to investigate factors associated with cardiovascular disease (CVD) within and specific to the Indigenous peoples living in Toronto, Ontario, and to evaluate the reliability and validity of the resulting model in a similar population. Methods: The Our Health Counts Toronto study measured the baseline health of Indigenous community members living in Toronto, Canada, using respondent-driven sampling. An iterative approach, valuing information from the literature, clinical insight and Indigenous lived experiences, as well as statistical measures was used to evaluate candidate predictors of CVD (self-reported experience of discrimination, ethnic identity, health conditions, income, education, age, gender and body size) prior to multivariable modelling. The resulting model was then validated using a distinct, geographically similar sample of Indigenous people living in Hamilton, Ontario, Canada. Results: The multivariable model of risk factors associated with prevalent CVD included age, diabetes, hypertension, body mass index and exposure to discrimination. The combined presence of diabetes and hypertension was associated with a greater risk of CVD relative to those with either condition and was the strongest predictor of CVD. Those who reported previous experiences of discrimination were also more likely to have CVD. Further study is needed to determine the effect of body size on risk of CVD in the urban Indigenous population. The final model had good discriminative ability and adequate calibration when applied to the Hamilton sample. Conclusion: Our modelling identified hypertension, diabetes and exposure to discrimination as factors associated with cardiovascular disease. Discrimination is a modifiable exposure that must be addressed to improve cardiovascular health among Indigenous populations.

Objectives: Indigenous peoples have a disproportionately high prevalence of incarceration in the Canadian justice system. However, there is limited Indigenous-driven research examining colonialism and the justice system, specifically associations between racism, externally imposed family disruptions, and history of ever being incarcerated. Therefore, this study examined the association between the proportion of previous incarceration and family disruption, experiences of racism, and victimization for Indigenous adults in London, Thunder Bay, and Toronto, Ontario, Canada. The three communities expressed that they did not want comparison between the communities; rather, they wanted analysis of their community to understand where more supports were needed. Methods: Indigenous community partners used respondent-driven sampling (RDS) to collect data from First Nations, Inuit, and Métis (FNIM) peoples in London, Thunder Bay, and Toronto. Prevalence estimates, 95% confidence intervals, and relative risk were reported using unweighted Poisson models and RDS-adjusted proportions. Results: Proportions of ever being incarcerated ranged from 43.0% in London to 54.0% in Toronto and 72.0% in Thunder Bay. In all three cities, history of child protection involvement and experiencing racism was associated with an approximate 25.0% increase in risk for previous incarceration. In Toronto and London, victimization was associated with increased risk for incarceration. Conclusion: This research highlights disproportionately high prevalence of ever being incarcerated among FNIM living in three Ontario cities. Experiencing racism, family disruption, and victimization are associated with incarceration. Decreasing the rates of family disruption, experiences of racism, and victimization should inform future policy and services to reduce the disproportionately high prevalence of incarceration for FNIM people living in urban settings.

Background: In Italy, nephrology residency is available in twenty-one nephrology schools, each with its own strengths and weaknesses. The present study is aimed at exploring the residents’ satisfaction with their training programs. Methods: Between April 20th and May 19th, 2021, a questionnaire on residency satisfaction consisting of 49 items was sent to 586 residents and 175 recently certified specialists (qualified to practice as nephrologists in 2019 and 2020), with a response rate of 81% and 51%, respectively. Results: Most residency fellowship programs received a good rating with regard to “satisfaction”, in particular for the following items: number of hospitalizations followed-up, chronic hemodialysis training, follow-up of transplanted patients, diagnosis and treatment of glomerulonephritis. The teachings that were identified as being of lower quality or insufficient intensity included vascular access management, ultrasound diagnostics and renal nutrition. The need for improvement in formal teaching programs was underlined. Young nephrologists were rather satisfied with their salary and with the quality of the work they were doing, but only few were interested in an academic career since it was generally held that it is “too difficult” to obtain a university position. Many young nephrologists who filled in the questionnaire felt that lack of experience in peritoneal dialysis and vascular access management was a barrier to finding an ideal job. Compared to other European training programs, the Italian program differs with regard to longer exposure to nephrology (as compared to internal medicine), and greater flexibility for internships in different settings, including abroad. Conclusions: This first nationwide survey on the satisfaction of residents in nephrology indicates that, despite rather good overall satisfaction, there is room for improvement to make nephrology a more appealing choice and to fulfill the needs of a growing number of renal disease patients. Graphical abstract:

Background: Thyroid cancer is the most common endocrine malignancy. Current therapies are successful, however some patients progress to therapeutically refractive disease. The immunotherapeutic potential of the CXCL8-chemokine/CXCR2-chemokine-receptor system is currently being explored in numerous human cancers. This study aimed to evaluate if the targeting of CXCR2 by its selective antagonist, AZD5069, could modulate CXCL8-mediated pro-tumorigenic effects in thyroid-cancer (TC) cells in vitro. Methods: Normal human primary thyroid cells (NHT) and TC cell lines TPC-1 (RET/PTC), BCPAP, 8505C and 8305C (BRAFV600e) were treated with AZD5069 (100 pM-10 µM) over a time-course. Viability and proliferation were assessed by WST-1 and crystal violet assays. CXCL8 and CXCR2 mRNA were evaluated by RT-PCR. CXCL8-protein concentrations were measured in cell culture supernatants by ELISA. CXCR2 on cell surface was evaluated by flow-cytometry. Cell-migration was assessed by trans-well-migration chamber-system. Results: AZD5069 exerted negligible effects on cell proliferation or viability. AZD5069 significantly reduced CXCR2, (but not CXCL8) mRNAs in all cell types. CXCR2 was reduced on the membrane of some TC cell lines. A significant reduction of the CXCL8 secretion was found in TPC-1 cells (basal-secretion) and NHT (TNFα-induced secretion). AZD5069 significantly reduced basal and CXCL8-induced migration in NHT and different TC cells. Conclusions: Our findings confirm the involvement of the CXCL8/CXCR2-axis in promoting pro-tumorigenic effects in TC cells, further demonstrating its immunotherapeutic significance in human cancer.

Background: Autosomal dominant polycystic kidney disease (ADPKD) is a hereditary kidney disorder that may progress to kidney failure, accounting for 5–10% of all patients with end-stage kidney disease (ESKD). Clinical data, as well as molecular genetics and advanced imaging techniques have provided surrogate prognostic biomarkers to predict rapid decline in kidney function, nonetheless enhanced tools for assessing prognosis for ADPKD are still needed. The aim of this study was to analyze specific microRNAs involved in the pathogenesis of ADPKD and in the development of renal fibrosis, evaluating their potential role as predictors of renal function loss. Methods: We evaluated kidney function by estimated glomerular filtration rate (eGFR) in 32 ADPKD patients in different stages of kidney disease at T0 and after a 24-month follow up (T1). Patients were divided into two groups: Rapid disease progression ([RP], n 15) and Non-rapid disease progression ([NRP], n 17), according to the Mayo Clinic classification criteria. At T0, ADPKD patients underwent plasma sampling for quantitative analysis of h-miR-17-5p, h-miR-21-5p and h-miR-199a-5p microRNA expression, using the quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) method and a 3 T magnetic resonance imaging (MRI), using an advanced MRI imaging protocol, for the quantification of total kidney volume (TKV), total perfusion volume (TPV) and total fibrotic volume (TFV). Results: The expression of h-miR17-5p was higher (p< 0.05) in ADPKD patients with rapid disease progression. h-miR-17-5p, h-miR-21-5p and h-mir-199-5p showed a positive and significant correlation with the eGFR slope (mL/min/1.73 m2/year) (p< 0.05) but not with the eGFR at both T0 and T1. Both total fibrotic volume (cm3) and height-adjusted total fibrotic volume (cm3/m) were positively and significantly correlated to h-miR 21-5p and h-miR 199-5p (p< 0.05), but not to total kidney volume (cm3) and height-adjusted total kidney volume (cm3/m). Conclusions: The microRNAs we studied were associated with fibrosis and renal damage, suggesting their possible role as biomarkers able to identify ADPKD patients at high risk of disease progression regardless of the degree of kidney function, and therefore suitable for medical therapy, and may help uncovering new molecular mechanisms underlying cystogenesis. Graphical abstract:

Purpose: In the present short report, we encompass the radiobiological and dosimetric advantages of particle beam radiotherapy and we illustrate the oncological pathway for patients eligible for hadrontherapy being used at the National Center for Oncological Hadrontherapy (CNAO). Methods: With a narrative approach, we examined the clinical and practical aspects of hadrontherapy compared to traditional photon beam radiotherapy. We described the need to select patients considering the intrinsic characteristics both of the tumour and the patient. Moreover, we described the decisional oncological tree and the patient pathway by our facility. Results: Considering the dosimetric and radiobiological characteristics of particle beam radiotherapy, the selection of patients can not be done regardless of the intrinsic tumour and patient hallmarks. In particular, the tumour radioresistance, the patient radiosensitivity and the need to avoid post-actinic toxicities in long-term survivors should guide the clinical indication. The finite range of particles should be considered to avoid treatment uncertainties. Multidisciplinary national and international collaboration is crucial to better manage patients to treat with hadrontherapy and to create robust clinical evidence. Conclusion: Hadrontherapy, with its distinctive physical and biological advantages, heralds a promising era in the field of precision radiotherapy. Patients’ radiosensitivity, tumour radioresistance, and treatment uncertainties should be considered to enhance the efficacy and to ameliorate the selection of patients.

Thyroid nodules (TNs) are a common entity, with the majority being benign. Therefore, employing an accurate rule-out strategy in clinical practice is essential. In the thyroid field, the current era is significantly marked by the worldwide diffusion of ultrasound (US)-based malignancy risk stratification systems of TN, usually reported as Thyroid Imaging Reporting And Data System (TIRADS). With the advent of US (and later TIRADS), the role of thyroid scintigraphy (TS) in clinical practice has gradually diminished. The authors of the present paper believe that the role of TS should be reappraised, also considering its essential role in detecting autonomously functioning thyroid nodules and its limited contribution to detecting thyroid cancers. Thus, this document aims to furnish endocrinologists, radiologists, surgeons, and nuclear medicine physicians with practical information to appropriately use TS.

Background: Non-invasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP) was firstly described in 2016. Since NIFTP is thought a non-malignant tumor, the Bethesda system for thyroid cytology proposes two estimations of risk of malignancy of the diagnostic categories, one considering NIFTP as cancer and another one considering it as a benign neoplasm. The present study aimed to review NIFTPs in a single center, re-assess them across categories of three Thyroid Imaging Reporting and Data Systems (TIRADSs), and define the indication for biopsy according to the category-specific size cut-offs. Methods: The study period was from 2017 to 2023. The institutional database was searched for histologically proven NIFTPs with preoperative ultrasound images. NIFTPs were re-assessed according to the American College of Radiology (ACR), European (EU), and Korean (K) TIRADSs. The indication for biopsy was defined according to TIRADS category-specific size threshold. Results: Twenty NIFTPs from 19 patients were included. The median size of the NIFTPs was 23 mm. According to ultrasound, 80–85% of NIFTPs were at low-intermediate risk and 5–15% at high risk without significant difference among the tree TIRADSs (p= 0.91). The indication for FNA, according to three TIRADSs, was found in 52–58% of cases with no significant difference among systems (p= 0.96). Conclusion: NIFTPs have heterogeneous presentation according to TIRADSs with very low indication rate for FNA.

Objective: Disparities in Indigenous reproductive health reflect Canada’s historic and ongoing colonial relationship with Indigenous peoples, which includes persistent inequities in health and social services. Reproductive justice scholars and activists advocate for intersectional approaches to enhancing Indigenous health equity that recognize land as a central determinant of wellness. The purpose of this study is to examine the association between relationships to land and wellness in a study of urban Indigenous women, two-spirit, trans, and gender diverse people of reproductive age in Canada’s largest city, Toronto. Methods: Data were obtained from the cross-sectional Our Health Counts (OHC) Toronto study, which employed respondent-driven sampling methods (n= 323) and a community-directed comprehensive health assessment survey. In an exploratory analysis, we took an Indigenous reproductive justice theoretical approach to multivariable logistic regression. Results: After adjusting for covariates, there was a statistically significant positive association between relationships to the land and wellness that was estimated with good precision (OR 3.7, 95% CI 2.5–5.3). Conclusion: Our findings indicate that among urban Indigenous women, two-spirit, trans, and gender diverse people of reproductive age there is a positive association between feeling strong in their relationships to land and feeling balanced in the four domains of health (physical, spiritual, mental, and emotional). The community-based, community-directed design of OHC Toronto was congruent with a reproductive justice approach to research. Reproductive justice theories are adaptable to quantitative research on Indigenous reproductive health and can yield novel insights for supporting Indigenous wellness.

Calciphylaxis is a rare disease characterized by ectopic calcification of skin arterioles resulting in ischemia, thrombosis and necrosis. Since end stage renal disease patients are those mainly affected, the term calcific uremic arteriolopathy (CUA) is also suggested. Early clinical manifestations are subtle, while overt necrotic ulcers may quickly spread and become infected so as to result in ominous outcome. Diagnosis might not be easy due to the number of other ischemic and non-ischemic skin lesions observed in uraemia. Skin biopsy, has been proposed as the diagnostic test and is often considered, but not systematically performed due to the hypothetical risk of further spreading of the lesions. Such ambiguity could be responsible for misdiagnosis or underdiagnosis. We review here five consecutive cases recorded in our Unit, all submitted to skin biopsy but with inconsistent results which generated some clinical frustration. Thus, we decided to carefully re-evaluate all of them together with pathologists and dermatologists. However, even after this ex-post discussion, we could not reach a complete agreement on the final diagnosis. In the meanwhile, papers were published in the literature that started to shed some light on the role of skin biopsy in the diagnosis of CUA.

Objectives: Methods for enumeration and population-based health assessment for First Nations, Inuit, and Metis (FNIM) living in Canadian cities are underdeveloped, with resultant gaps in essential demographic, health, and health service access information. Our Health Counts (OHC) was designed to engage FNIM peoples in urban centres in “by community, for community” population health assessment and response. Methods: The OHC methodology was designed to advance Indigenous self-determination and FNIM data sovereignty in urban contexts through deliberate application of Indigenous principles and linked implementation strategies. Three interwoven principles (good relationships are foundational; research as gift exchange; and research as a vehicle for Indigenous community resurgence) provide the framework for linked implementation strategies which include actively building and maintaining relationships; meaningful Indigenous community guidance, leadership, and participation in all aspects of the project; transparent and equitable sharing of project resources and benefits; and technical innovations, including respondent-driven sampling, customized comprehensive health assessment surveys, and linkage to ICES data holdings to generate measures of health service use. Results: OHC has succeeded across six urban areas in Ontario to advance Indigenous data sovereignty and health assessment capacity; recruit and engage large population-representative cohorts of FNIM living in urban and related homelands; customize comprehensive health surveys and data linkages; generate previously unavailable population-based FNIM demographic, health, and social information; and translate results into enhanced policy, programming, and practice. Conclusion: The OHC methodology has been demonstrated as effective, culturally relevant, and scalable across diverse Ontario cities.

Background The impact of radiotherapy (RT) in neuroendocrine neoplasms is still unknown, and outcomes could be improved by a better insight in RT response predictors. This retrospective analysis investigates the potential correlation between Ki-67 and RT response to evaluate its role as biological marker of radiosensitivity.Material and methods Data from patients treated at an Italian NET-referral center between 2015 and 2020 were retrieved. Inclusion criteria included: histologically-proven diagnosis of NEN, Ki-67 status, indication (symptomatic and/or ablative) and at least one post-RT radiological assessment.Results Forty-two patients and 63 different treatment lines were included. Primary tumors presented Ki-67 values < 3% in 21% of cases, between 3 and 20% in 45% and >20% in the remaining 33%. Almost all patients were metastatic at the time of RT, which was performed with symptomatic purpose in 43% of cases. At a median time of three months, a complete response on the target lesion was observed in nine cases (14%), a partial response in 17 (27%), stability in 23 (37%) and local progression in 14 (22%). With median FU of 22.8 months, OS does not show statistically significant differences among three Ki-67 groups. Considering all lines of therapy, the relationship between ORR and Ki-67, did not show statistically significant differences, even following adjustments for drug types and delivered RT doses.Conclusion No association between Ki67 and local tumor response to RT could be observed in the present cohort, regardless of whether the evaluation was performed on a categorical or continuous scale.

The pygmy white-toothed shrew Suncus etruscusis a widespread species whose distribution patterns are unclear. Paleontological data suggested an east to west pattern of dispersion in the Mediterranean basin during the Late Holocene but some doubts are still present especially considering the absence of fossil remains from key areas, such as mainland Italy. Here, we present a preliminary screening of the phylogeographic relationships among Italian pygmy white-toothed shrews and those from other Mediterranean areas. The Italian haplotypes were all very similar without an evident geographic structure; however, we found that the haplotype from Israel, the putative source area for the Mediterranean basin, is almost identical to the most common Italian haplotype. This excludes an ancient event of vicariance between the two areas and we can assume that these haplotypes arrived in the central Mediterranean through the westward wave of colonization, in agreement with the relatively recent arrival of the species in the area.

Purpose: Thyroid dysfunction in patients with Klinefelter syndrome (KS) remains an unresolved issue. Although low free thyroxine (FT4) levels within the normal range and normal thyroid stimulating hormone (TSH) levels have been reported, there is currently no data on nodular thyroid disease in this population. This study aims to evaluate the results of thyroid ultrasound (US) examinations in KS patients compared with healthy controls. Methods: A cohort of 122 KS and 85 age-matched healthy male controls underwent thyroid US screening and thyroid hormone analysis. According to US risk-stratification systems, nodules ≥1 cm were examined by fine needle aspiration (FNA). Results: Thyroid US detected nodular thyroid disease in 31% of KS compared to 13% of controls. No statistical differences in the maximum diameter of the largest nodules and in moderate and highly suspicious nodules were found between patients and the control group. Six KS patients and two controls with nodules underwent FNA and were confirmed as cytologically benign. In line with published data, FT4 levels were found significantly near the lower limit of the normal range compared to controls, with no differences in TSH values between the two groups. Hashimoto’s thyroiditis was diagnosed in 9% of patients with KS. Conclusions: We observed a significantly higher prevalence of nodular thyroid disease in KS compared to the control group. The increase in nodular thyroid disease is likely linked to low levels of FT4, inappropriate TSH secretion, and/or genetic instability.

Background: Severe secondary hyperparathyroidism (SHPT) is associated with mortality in end stage kidney disease (ESKD). Parathyroidectomy (PTX) becomes necessary when medical therapy fails, thus highlighting the interest to compare biochemical and clinical outcomes of patients receiving either medical treatment or surgery. Methods: We aimed to compare overall survival and biochemical control of hemodialysis patients with severe hyperparathyroidism, treated by surgery or medical therapy followed-up for 36 months. Inclusion criteria were age older than 18 years, renal failure requiring dialysis treatment (hemodialysis or peritoneal dialysis) and ability to sign the consent form. A control group of 418 patients treated in the same centers, who did not undergo parathyroidectomy was selected after matching for age, sex, and dialysis vintage. Results: From 82 Dialysis units in Italy, we prospectively collected data of 257 prevalent patients who underwent parathyroidectomy (age 58.2 ± 12.8 years; M/F: 44%/56%, dialysis vintage: 15.5 ± 8.4 years) and of 418 control patients who did not undergo parathyroidectomy (age 60.3 ± 14.4 years; M/F 44%/56%; dialysis vintage 11.2 ± 7.6 y). The survival rate was higher in the group that underwent parathyroidectomy (Kaplan–Meier log rank test = 0.002). Univariable analysis (HR 0.556, CI: 0.387–0.800, p= 0.002) and multivariable analysis (HR 0.671, CI:0.465–0.970, p= 0.034), identified parathyroidectomy as a protective factor of overall survival. The prevalence of patients at KDOQI targets for PTH was lower in patients who underwent parathyroidectomy compared to controls (PTX vs non-PTX: PTH &lt; 150 pg/ml: 59% vs 21%, p= 0.001; PTH at target: 18% vs 37% p= 0.001; PTH > 300 pg/ml 23% vs 42% p= 0.001). The control group received more intensive medical treatment with higher prevalence of vitamin D (65% vs 41%, p= 0.0001), calcimimetics (34% vs 14%, p= 0.0001) and phosphate binders (77% vs 66%, p= 0.002). Conclusions: Our data suggest that parathyroidectomy is associated with survival rate at 36 months, independently of biochemical control. Lower exposure to high PTH levels could represent an advantage in the long term. Graphical abstract:

Purpose: It is widely accepted that patients experience weight gain after total thyroidectomy, and preventive measures should be recommended. Methods: A prospective study was designed to assess the efficacy of a dietetic intervention to prevent post-thyroidectomy weight gain in patients undergoing surgery for both benign and malignant thyroid conditions. Patients undergoing total thyroidectomy were prospectively and randomly assigned to receive a personalized pre-surgery diet counseling (GROUP A) or no intervention (GROUP B), according to a 1:2 ratio. All patients underwent follow-up with body-weight measurement, thyroid function evaluation and lifestyle and eating habits assessment at baseline (T0), 45 days (T1) and 12 months (T2) post-surgery. Results: The final study group encompassed 30 patients in Group A and 58 patients in Group B. The two groups were similar in terms of age, sex, pre-surgery BMI, thyroid function and underlying thyroid condition. The evaluation of body weight variations showed that patients in Group A did not experience significant body weight changes at either T1 (p= 0.127) nor T2 (p= 0.890). At difference, patients in Group B underwent a significant body weight increase from T0 to both T1 (p= 0.009) and T2 (p= 0.009). TSH levels were similar in the two groups, both at T1 and T2. Lifestyle and eating habits questionnaires failed to register any significant difference between the two groups, apart from an increase in sweetened beverages consumption in Group B. Conclusions: A dietician counseling is effective in preventing the post-thyroidectomy weight gain. Further studies in larger series of patients with a longer follow-up appear worthwhile.

Purpose: The impact of mild subclinical hypothyroidism on pregnancy outcomes in TPOAb-negative women is poorly explored. The aim of the present study was the evaluation in a wide cohort of TPOAb-negative pregnant women the role of subclinical hypothyroidism (SCH) on several pregnancy outcomes. Methods: The study included women aged ≥ 18 years with a singleton pregnancy without known thyroid disease with serum TSH concentration between 0.4 and 10 mIU/L and TPOAb negative. Data about clinical and demographic features were collected. A blood sample was drown to test TSH, TPOAb, ANA and ENA concentration. The mean uterine artery pulsatility index was measured. Risk of adverse obstetric and fetal outcomes was collected. Results: The cohort included 2135 pregnant women. Pregnant women with TSH 4–10 mUI/L had a significantly higher frequency of family history of thyroid diseases, and personal history of celiac disease diseases, type 1 diabetes mellitus, rheumatic disease, antinuclear antibody (ANA) and anti-extractable nuclear antigen (ENA) positive tests. The risk for pre-eclampsia and small for gestational age (SGA) was significantly higher in pregnant women with first-trimester TSH 4–10 mIU/L. A first-trimester TSH serum level greater than 4 mIU/L was associated with a significant increase in the occurrence of abnormal uterine artery pulsatility index, with a more than threefold increase in the risk of developing pre-eclampsia and with the risk of SGA. Conclusions: In TPOAb-negative pregnant women, a first-trimester serum TSH level ranging from 4 to 10 mIU/L is significantly and independently linked to an increased uterine artery pulsatility index as well as to negative pregnancy outcomes such as pre-eclampsia, SGA and gestational diabetes.

Objective: The aim was to evaluate if bariatric surgery can affect the LT4 performance. The endpoints were the following: 1) difference between LT4 daily dose before and 1 year after surgery, 2) difference between LT4 dose per weight before and 1 year after surgery, 3) difference among LT4 preparations. Methods: The study period was between January 2018 and May 2022. Inclusion criteria were a) adults undergone bariatric surgery, b) with proven autoimmune hypothyroidism, c) on LT4 therapy before bariatric surgery, d) using any commercialized LT4 preparation. Excluded were patients a) proven to have or suspected for pre-surgical intestinal malabsorption, b) with other potential interfering factors on LT4 absorption; c) with heart, renal, and/or hepatic failure, d) with recent/current infection/inflammation, e) in pregnancy, f) with incomplete data about LT4 therapy. Results: According to the selection criteria, 40 patients were included. Both TSH and LT4 daily doses were not significantly different with respect to baseline values. On the contrary, the LT4 dose per weight was significantly increased, especially in RYGB patients. An increased LT4 dose per weight was observed with the reduction of weight. Conclusion: One year after bariatric surgery 1) the daily dose of LT4 remains unchanged, and 2) despite the significant weight reduction, LT4 dose per weight increases. Most data are referred to LT4 tablet and the performance of LT4 caps should be further investigated.

L’infiammazione correlata al tumore influenza il comportamento biologico delle cellule neoplastiche e, in definitiva, l’esito del paziente. Con specifico riguardo al cancro della tiroide, il tema dell’infiammazione associata al tumore è stato ampiamente studiato e recentemente rivisto. Tuttavia, il ruolo delle chemochine, che svolgono un ruolo cruciale nel determinare l’immunofenotipo dell’infiammazione correlata al tumore, non è stato affrontato in precedenti revisioni sull’argomento. L’evidenza sperimentale mostra che le cellule tumorali della tiroide secernono attivamente un ampio spettro di chemochine e, almeno per alcune di esse, solidi dati scientifici supportano un ruolo di queste molecole immunoattive nel comportamento aggressivo del tumore. La nostra proposta per un articolo di revisione sulle chemochine e sul cancro della tiroide nasce dall’idea che le chemochine, oltre ad avere la capacità di attrarre e mantenere le cellule immunitarie nel sito del tumore, producono anche diverse azioni pro-tumorigeniche, che includono pro-angiogenetica, citoproliferativa ed effetti pro-metastatici. Gli studi che tengono conto del ruolo di CCL15, ligando 12 del motivo C-X-C, CXCL16, CXCL1, CCL20 e CCL2 nel contesto del cancro della tiroide saranno esaminati su CXCL8. Il motivo per concentrarsi su CXCL8 è che questa chemochina è la più studiata nelle neoplasie umane, mostrando diversi effetti pro-tumorigenici. Questi includono l’aumento della crescita delle cellule tumorali, la metastatizzazione e l’angiogenesi in generale, contribuendo alla progressione di diversi tumori, incluso il cancro della tiroide. Miriamo a rivedere le attuali conoscenze sulla capacità delle cellule tiroidee normali e tumorali di secernere CXCL8; effetti pro-tumorigenici diretti/indiretti di CXCL8 dimostrati da studi in vitro e in vivo specificamente condotti su cellule di cancro alla tiroide; e strategie farmacologiche dimostrate efficaci per ridurre la secrezione di CXCL8 e/o i suoi effetti sulle cellule tumorali della tiroide.

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.

Purpose: Gestational diabetes mellitus (GDM) and thyroid dysfunction during gestation (GTD) are the two most prevalent endocrinopathies during pregnancy. The aim of the present review is to provide an overview of the peculiar aspects of GDM and GTD, to highlight the potential interactions and clinical consequences of these two frequent clinical conditions. Methods: A literature review regarding GDM and GTD was carried out with particular interest on meta-analyses and human studies dealing with the (i) shared risk factors between GDM and GTD, (ii) the epidemiological link between GTD and GDM, (iii) physiopathologic link between GTD and GDM, (iv) clinical consequences of GDM and GTD, and (v) post-partum implications of GDM and GTD. Results: The association between GDM and GTD is common and may be explained by the insulin-resistance state due to maternal GTD, to alterations in the placentation process or to the many shared risk factors. Discrepant results of epidemiologic studies can be explained, at least in part, by the changes in diagnostic criteria and screening strategies throughout the years for both conditions. GDM and GTD impact pregnancy outcome and have post-partum long-term consequences, but more studies are needed to prove an additional adverse effect. Conclusions: Based on the epidemiological and physio-pathological link between GDM and GTD, it could be suggested that a diagnosis of GTD could lead to screen GDM and the other way round.

Purpose: The prevalence of thyroid nodules (TN) in the general population has increased as screening procedures are implemented and an association with metabolic and cardiovascular disorders has been reported. The aim of this study was to investigate the reason leading to the diagnosis of TN and to compare the clinical characteristics of patients diagnosed incidentally with those of patients diagnosed for thyroid-related reasons. Methods: We designed a retrospective cross-sectional study including consecutive patients with TN from two high-volume hospital-based centers for thyroid diseases (Pavia and Messina) in Italy. Data regarding reason leading to TN diagnosis, age, sex, BMI, presence of cardio-metabolic comorbidities were collected. Results: Among the 623 enrolled subjects, the US diagnosis of TN was prompted by thyroid-related reasons in 421 (67.6%, TD group) and incidental in 202 (32.4%, ID group) with a similar distribution in the two centers (p= 0.960). The ID group patients were more frequently males (38.6% vs 22.1%, p&lt; 0.001) and significantly older (58.9 ± 13.7 vs 50.6 ± 15.5 years, p&lt; 0.001) than the TD group ones, and had a higher rate of cardiovascular comorbidities (73.8% vs 47.5%, p&lt; 0.001), despite having a similar BMI (27.9 ± 5.2 vs 27.8 ± 13.5, p= 0.893). Conclusions: Stratification of patients with TN according to the diagnostic procedure leading to diagnosis allows a better epidemiological characterization of this inhomogeneous and large population.

Objective: During the height of the COVID-19 pandemic, personal support workers (PSWs) were heralded as healthcare ‘heroes’ as many of them cared for high-risk, vulnerable older populations, and worked in long-term care, which experienced a high number of COVID-19 outbreaks and deaths. While essential to the healthcare workforce, there is little understanding of PSW working conditions during the pandemic. The aim of our study was to examine the working conditions (including job security, work policies, and personal experiences) for PSWs in the Greater Toronto Area during the COVID-19 pandemic from the perspectives of PSWs. Methods: This study used a mixed-methods design. From June to December 2020, we conducted a survey of 634 PSWs to understand their working conditions during the COVID-19 pandemic. Semi-structured interviews with 31 survey respondents were conducted from February to May 2021 to understand in greater depth how working conditions were impacting the well-being of PSWs. Results: We found PSWs faced a range of challenges related to COVID-19, including anxiety about contracting COVID-19, reduced work hours, taking leaves of absences, concerns about job security, and losing childcare. While the COVID-19 pandemic highlighted the PSW workforce and their importance to the healthcare system (especially in the long-term care system), pre-existing poor work conditions of insecure jobs with no paid sick days and benefits exacerbated COVID-19–related challenges. Despite these hardships, PSWs were able to rely on their mental resilience and passion for their profession to cope with challenges. Conclusion: Significant changes need to be made to improve PSW working conditions. Better compensation, increased job security, decreased workload burden, and mental health supports are needed.

Douglas, AS, Rotondi, MA, Baker, J, Jamnik, VK, and Macpherson, AK. A comparison of on-ice external load measures between subelite and elite female ice hockey players. J Strength Cond Res36(7): 1978–1983, 2022—This study quantified and examined differences in measures of on-ice external load for subelite and elite female ice hockey players. External load variables were collected from subelite (N= 21) and elite (N= 24) athletes using Catapult S5 monitors during the preseason. A total of 574 data files were analyzed from training and competition during the training camp. Significant differences between groups were found across all variables. Differences in training between the 2 groups ranged from trivial (forwards PlayerLoad, p= 0.03, effect-size [ES] = 0.18) to large (forwards Explosive Efforts [EEs], p< 0.001, ES = 1.64; defense EEs, p< 0.001, ES = 1.40). Match comparisons yielded similar results, with differences ranging from small (defense Low Skating Load [SL], p= 0.05, ES = 0.49; Medium SL, p= 0.04, ES = 0.52) to very large (forwards PlayerLoad, p< 0.001. ES = 2.25; PlayerLoad·min−1, p< 0.001, ES = 2.66; EEs, p< 0.001, ES = 2.03; Medium SL, p< 0.001, ES = 2.31; SL·min−1, p< 0.001, ES = 2.67), respectively. The differences in external load measures of intensity demonstrate the need to alter training programs of subelite ice athletes to ensure they can meet the demands of elite ice hockey. As athletes advance along the development pathway, considerable focus of their off-ice training should be to improve qualities that enhance their ability to perform high-intensity on-ice movements.

Background: Advanced Hybrid Closed-Loop system (AHCL) has profoundly changed type 1 diabetes therapy. This study primarily aimed to assess the impact on Glycemia Risk Index (GRI) and other continuous glucose monitoring (CGM) metrics when switching from one of four insulin strategies to AHCL in type 1 adult patients. Methods: A single-center, retrospective pre/post observational study; 198 patients (age 44.4 ± 12.7 years, 115 females/83 males, diabetes duration 24.7 ± 11.6 years, HbA1c 7.4 ± 1%), treated with different insulin therapies (MDI, CSII, SAP with PLGS, HCL) were assessed before and after switching to an AHCL (MiniMed 780G, Diabeloop Roche, Tandem Control-IQ) at 1, 3, 6, and 12 months. Mixed-effects multivariable regression models were used to estimate the mean pre/post variations at different time points, adjusted for potential confounders. Results: A month after the switch, there was an improvement in CGM metrics and HbA1c for all patients: GRI −10.7, GMI −0.27%, CV −2.1%, TAR>250−3.7%, TAR180-250−5.6%, TIR + 9.7%, HbA1c −0.54% (all p &lt; 0.001). This improvement was maintained throughout the observational period (at 3, 6, and 12 months, with all p-values &lt; 0.001). When improvements across the 780, Diabeloop, and Tandem CIQ devices were compared: Diabeloop demonstrated significantly better performance in terms of GRI, GMI, CV, TAR>250at T1 (for all p &lt; 0.01); 780 recorded highest average decrease in TAR180-250(p = 0.020), while Tandem achieved the most significant reduction in TBR54-69(p = 0.004). Conclusions: Adopting an AHCL leads to a rapid and sustained improvement in GRI and other parameters of metabolic control for up to a year, regardless of prior insulin therapies, baseline conditions or brands.

Background: Routine systems for monitoring vascular access (VA) performance are lacking. We developed a vascular access triage system to evaluate the monthly performance of the access, developed a specific score and assessed the association between score improvement and clinical outcomes. Methods: Vascular access was triaged (Green, Yellow or Red) according to a score generated by dialytic and clinical parameters in all patients who, from 1/1/2014 to 31/03/2014, had been receiving haemodialysis treatment for at least 3 consecutive months in our Unit and who were then followed up for 4 years. Results: We enrolled 130 patients, 78 with arteriovenous fistula (AVF) and 52 with tunnelled central venous catheter (CVC). During a median of 29 ± 11 months of follow up (range 3–46 months), 28 deaths and 303 hospitalizations (lasting 16 ± 30 days) were recorded. Vascular access triage scores improved over time (2014 vs 2015 vs 2016 vs 2017) in the population with an AVF (Green from 25% to 58% to 77% to 79%, Yellow from 65% to 39% to 18% to 20% and Red from 10% to 3% to 5% to 1%, respectively; χ2p &lt; 0.01) but not in the CVC group (Green 58% to 57% to 80% to 92%; Yellow 37% to 36% to 20% to 8%; Red 5% to 7% to 0%; χ2= n.s). Blood pressure and dialysis efficiency improved in the population as a whole and in the two subgroups (AVF and CVC) separately. AVF and CVC populations, stratified separately according to median VA score, had different event-free follow-up, which was higher (p = 0.0085) in patients with lower scores in the AVF population only. Conclusion: The vascular access monitoring system improved the vascular access score as well as some clinical and dialytic parameters. Green triage in AVF patients identify those with better outcomes, in agreement with the commonly recognized clinical value of a well-functioning vascular access.

Background:First Nations, Inuit and Métis Peoples across geographies are at higher risk of SARS-CoV-2 infection and COVID-19 because of high rates of chronic disease, inadequate housing and barriers to accessing health services. Most Indigenous Peoples in Canada live in cities, where SARS-CoV-2 infection is concentrated. To address gaps in SARS-CoV-2 information for these urban populations, we partnered with Indigenous agencies and sought to generate rates of SARS-CoV-2 testing and vaccination, and incidence of infection for First Nations, Inuit and Métis living in 2 Ontario cities.Methods:We drew on existing cohorts of First Nations, Inuit and Métis adults in Toronto (n= 723) and London (n= 364), Ontario, who were recruited using respondent-driven sampling. We linked to ICES SARS-CoV-2 databases and prospectively monitored rates of SARS-CoV-2 testing, diagnosis and vaccination for First Nations, Inuit and Métis, and comparator city and Ontario populations.Results:We found that SARS-CoV-2 testing rates among First Nations, Inuit and Métis were higher in Toronto (54.7%, 95% confidence interval [CI] 48.1% to 61.3%) and similar in London (44.5%, 95% CI 36.0% to 53.1%) compared with local and provincial rates. We determined that cumulative incidence of SARS-CoV-2 infection was not significantly different among First Nations, Inuit and Métis in Toronto (7364/100 000, 95% CI 2882 to 11 847) or London (7707/100 000, 95% CI 2215 to 13 200) compared with city rates. We found that rates of vaccination among First Nations, Inuit and Métis in Toronto (58.2%, 95% CI 51.4% to 64.9%) and London (61.5%, 95% CI 52.9% to 70.0%) were lower than the rates for the 2 cities and Ontario.Interpretation:Although Ontario government policies prioritized Indigenous populations for SARS-CoV-2 vaccination, vaccine uptake was lower than in the general population for First Nations, Inuit and Métis Peoples in Toronto and London. Ongoing access to culturally safe testing and vaccinations is urgently required to avoid disproportionate hospital admisson and mortality related to COVID-19 in these communities.

Background: A more severe course of COVID-19 was associated with low levels of Vitamin D (VitD). Moreover in vitro data showed that VitD up-regulates the mRNA of the Angiotensin Converting Enzyme 2 (ACE-2), the SARS-COV-2 receptor in different type of cells. ACE-2 is expressed in several type of tissues including thyroid cells, on which its mRNA was shown to be up-regulated by interferon-gamma (IFN-γ). The aim of the present study was to investigate if treatment with VitD alone or in combination with IFN-γ would increase ACE-2 both at mRNA and protein levels in primary cultures of human thyrocytes. Materials and methods: Primary thyroid cell cultures were treated with VitD and IFN-γ alone or in combination for 24 h. ACE-2 mRNA levels were measured by Real-time Polymerase Chain Reaction (RT-PCR). The presence of ACE-2 on thyroid cell membrane was assessed by immunocytochemistry basally and after the previous mentioned treatments. Results: ACE-2 mRNA levels increased after treatment with VitD and IFN-γ alone. The combination treatment (VitD + IFN-γ) showed an additive increase of ACE-2-mRNA. Immunocytochemistry experiments showed ACE-2 protein on thyroid cells membrane. ACE-2 expression increased after treatment with VitD and IFN-γ alone and further increased by the combination treatment with VitD + IFN-γ. Conclusions: VitD would defend the body by SARS-COV2 both by regulating the host immune defense and by up-regulating of the expression of the ACE-2 receptor. The existence of a co-operation between VitD and IFN-γ demonstrated in other systems is supported also for ACE-2 up-regulation. These observations lead to an increased interest for the potential therapeutic benefits of VitD supplementation in COVID-19.

Purpose: An increase in serum TSH concentrations in the absence of thyroid disease, named isolated hyperthyrotropinemia, is frequently observed in subjects with obesity. It is directly associated with body mass index, and it is reversible following weight loss. Autoimmune hypothyroidism is frequently associated with obesity, it is usually progressive and needs replacement treatment with L-thyroxine. The aim of this study was to investigate the role of thyroglobulin antibodies (TgAb) to define the thyroidal status in subjects with overweight or obesity. Methods: This is a retrospective study including 749 consecutive adult patients with overweight or obesity. Of those, 76 were excluded from the analysis due to hyperthyroidism, previous thyroidectomy or radioiodine therapy for hyperthyroidism, hemiagenesis or drug-induced hypothyroidism. Serum thyrotropin (TSH), free thyroxine (FT4), free 3,5,3’-triiodothyronine (FT3), TgAb and thyroperoxidase antibodies (TPOAb) were measured in all patients. Results: Out of 673 patients, 408 did not have thyroid disease. Among patients with thyroid disease (n= 265), 130 had nodular disease with no humoral signs of thyroid autoimmunity and 135 (20%) had autoimmune thyroiditis, defined by the presence of TPOAb and/or TgAb. The prevalence of hyperthyrotropinemia, either directly measured or presumed based on L-thyroxine treatment at the time of data collection, was 63.9% in patients with both TgAb and TPOAb, 47.1% in those with isolated positivity of TPOAb, 42.8% in patients with isolated positivity of TgAb, and 14.5% in those with no detectable TgAb or TPOAb. Conclusions: Our results confirm a high prevalence of autoimmune thyroiditis (20%) in patients with obesity. TgAb may be associated with hypothyroidism in the absence of TPOAb. TgAb measurement may turn helpful to unravel a proportion of subjects that may have or may develop primary hypothyroidism requiring specific substitutive treatment.

Background: Thyroid disorders, both overt and subclinical, are highly prevalent conditions in the general population. Although a clear relationship between overt thyroid dysfunctions and cardiovascular complications has long been established, data regarding subclinical thyroid dysfunction are by far more controversial. Purpose: The present review will be aimed at providing a summary of most recent evidence coming from meta-analyses regarding the complex relationship between thyroid dysfunction and cardiovascular disease. Conclusions: The review will summarize, in the first part, the physiopathological link between thyroid hormone imbalances and the cardiovascular system. In the second part the review will outline the evidence coming from meta-analyses regarding the cardiovascular risk related with both overt and subclinical thyroid dysfunctions. Particular attention will be put towards studies showing data stratified for patient’s age, TSH levels and pre-existing cardiovascular disease. Finally, an overview regarding the effects of specific therapy for subclinical thyroid diseases in terms of amelioration of cardiovascular outcomes will be included.

Purpose: Per- and poly-fluoroalkyl-substances (PFASs) are synthetic compounds that raised concern due to their potential adverse effects on human health. Long-chain PFAS were banned by government rules in many states, and thus, new emerging PFAS were recently introduced as substitutes. Among these, Perfluoro{acetic acid, 2-[(5-methoxy-1,3-dioxolan-4-yl)oxy]}, ammonium salt (C6O4) was recently introduced to produce a range of food contact articles and literature data about this compound are scanty. The aim of this study was to evaluate the in vitro effects of exposure to C6O4, compared with PFOA and PFOS on thyroid cells. Methods: FRTL5 rat-thyroid cell lines and normal human thyroid cells (NHT) were incubated with increasing concentrations of C6O4 for 24, 48, 72, and 144 h to assess cell viability by WST-1. Cell viability was confirmed by AnnexinV/PI staining. Long-chain PFAS (PFOA and PFOS) were used at same concentrations as positive controls. The proliferation of cells exposed to C6O4, PFOA, and PFOS was measured by staining with crystal violet and evaluation of optical density after incubation with SDS. Changes in ROS production by FRTL5 and NHT after exposure to C6O4 at short (10, 20, and 30 min) and long-time points (24 h) were evaluated by cytofluorimetry. Results: C6O4 exposure did not modify FRTL5 and NHT cell viability at any concentration and/or time points with no induction of necrosis/apoptosis. At difference, PFOS exposure reduced cell viability of FRTL5 while and NHT, while PFOA only in FRTL5. FRTL5 and NHT cell proliferation was reduced by incubation with by PFOA and PFOS, but not with C6O4. ROS production by NHT and FRTL5 cells was not modified after C6O4 exposure, at any time/concentration tested. Conclusions: The present in vitro study constitutes the first evaluation of the potential adverse effects of the new emerging PFAS C6O4 in cultured rat and human thyroid cells, suggesting its safety for thyroid cells in vitro.

Purpose: The relationship between thyroid function and obesity is a widely investigated one. The impact of thyroid hormones in determining the outcome of dietary/lifestyle interventions remains to be fully elucidated. The aim of this study was to compare basal and post dietary-intervention circulating thyroid-function parameters, lipid profile and fasting-glucose in euthyroid obese patients according to a success or failure of a dietary intervention program. Methods: In a retrospective longitudinal case–control study we enrolled 50 euthyroid obese patients who experienced a success in dietary intervention, as defined by a BMI reduction of at least 5% from baseline (Success Group) and 50 sex and age-matched euthyroid obese patients who experienced failure in dietary intervention as defined by either stable or increased body weight throughout the follow-up (Failure Group). Serum thyroid function parameters and metabolic profile at baseline and at the end of follow-up were collected. Results: At baseline, the two groups showed similar BMI, total-cholesterol, HDL-cholesterol and fasting-blood-glucose, but patients in Success Group had a significantly higher TSH as compared with Failure Group (2.20 ± 0.97 vs 1.66 ± 0.73, respectively, p&lt; 0.001). Throughout a mean follow-up of 21.4 months TSH significantly decreased in Success Group (2.20 ± 0.97 vs 2.06 ± 0.98; p= 0.029) and increased in Failure Group (1.63 ± 0.72 vs 2.01 ± 0.99; p&lt; 0.001). Multiple regression analysis showed that the outcome of the dietary intervention was significantly and independently related to baseline BMI (0.925; 0.861–0.993), age (0.957; 0.922–0.993), TSH (0.531; 0.290–0.973) and TSH-changes (1.011; 1.000–1.022) during follow-up. Conclusions: Baseline serum TSH level is related to the final outcome of a dietary intervention program in obese patients. Level of evidence III: Evidence obtained from a retrospective cohort or case–control analytic studies.