Preliminary Study on Pulse Wave Changes in Patients with Inflammatory Arthropathies Treated with bDMARDs.

Background: Patients with inflammatory arthropathies exhibit an increased cardiovascular disease (CVD) risk as compared to the general population, which is not fully quantified by the conventional CVD risk scores. Biotechnological disease-modifying drugs (bDMARDs) have proved beneficial to reduce the overall CVD risk in these patients, although CVD remains a major cause of increased mortality. Since it has been shown that pulse wave parameters and in particular carotid-femoral pulse wave velocity (cfPWV) are predictors of CVD risk, the aim of this study was to evaluate their changes in patients with inflammatory arthropathies before and after bDMARD therapy. Methods: Pulse wave parameters were evaluated with applanation tonometry in patients with ankylosing spondylitis (AS), psoriatic arthritis (PsA), and rheumatoid arthritis (RA), before and after two years of bDMARD therapy. Results: At baseline, cfPWV was significantly associated with age (p < 0.001) and, among pulse wave parameters, the subendocardial viability ratio was negatively associated with C-reactive protein (CRP) (p = 0.04) and the HAQ-disability index (p = 0.03). At baseline, PsA patients showed a higher percentage of male subjects, higher CRP, and the highest cfPWV values (p = 0.048). After two years, pulse wave parameters improved in the AS and RA groups, but not in the PsA group. Conclusions: Our data confirm that pulse wave parameters are potentially reversible after bDMARD therapy, as they improved in AS and RA patients. In PsA patients, there were no changes, which may be due to the higher percentage of male subjects and higher baseline cfPWV values.

Nephrogenic diabetes insipidus in a geriatric patient affected by SARS-CoV-2: complexity of a diagnosis, complexity of a virus.

Background: Coronavirus disease 2019 (COVID-19) has an important impact on the kidney through direct and indirect damage mechanisms. Most previous studies have highlighted lesions caused by this virus in the early segments of the nephron. However, due to the antigenic characteristics of the virus, with almost ubiquitous receptors, and the molecular release it triggers, the distal segments of the nephron could also be affected. Methods: A 71 year-old-man with respiratory failure while suffering from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pneumonia presented with typical symptoms of diabetes insipidus after ~20 days of hospitalization. The water deprivation test led to the diagnosis of nephrogenic diabetes insipidus. The aetiological study was complex, in particular because of the patient's previous lithium therapy. Results: The sequence of pathognomonic events typical of diabetes insipidus associated with anamnestic, clinical and laboratory evidence strongly supported the diagnosis of nephrogenic diabetes insipidus due to SARS-CoV-2 rather than other aetiologies. Conclusions: The collecting duct could represent a target for SARS-CoV-2 infection, directly or indirectly, as a result of lesions of upstream portions of the nephron, which would cascade into the distal segment. Other molecules, besides angiotensin 2 converting enzyme, might be involved in facilitating the viral aggression. The complexity of the geriatric patient shows the importance of a comprehensive approach that integrates careful monitoring of clinical signs and symptoms and laboratory and instrumental tests. This is especially important in the context of SARS-CoV-2 infection and in the management of its unexpected complications.

A longitudinal study on the effect of obesity upon circulating renin-angiotensin system in normal pregnancy.

BACKGROUND AND AIMS: Obesity is the most common health issue in women of reproductive age, which profoundly affects maternal-fetal health. Despite progress in understanding key inflammatory and metabolic changes, the pathogenesis of the cardiovascular phenotype of obese pregnant women remains to be fully understood. This study aimed at: (i) evaluating the changes of the renin-angiotensin system (RAS) throughout pregnancy in obese vs normal weight (control) women, and (ii) evaluating the presence of any associations between maternal hemodynamic status and RAS changes. METHODS AND RESULTS: Thirty-eight normal weight and nineteen obese pregnant women were included. Clinical assessment, blood samples and maternal hemodynamic evaluation were performed at 12, 20, 30, and 36 weeks, while ultrasound assessment was scheduled at 20, 30, and 36 weeks of gestation. Measurements of sFlt-1, PlGF, Angiotensinogen, Renin, AngII, Ang1-7, ACE and ACE2 were performed by ELISA. Our data show that normotensive obese women had lower placental blood supply, as assessed by UV-Q and UV-Q/EFW, as compared to controls, and significantly higher levels of AngII and AngII/Ang1-7 ratio, which were inversely related to placental blood supply. CONCLUSIONS: Our study shows for the first time that normotensive obese women exhibited a significant progressive increase of AngII and AngII/Ang1-7 throughout pregnancy, which were inversely related to placental blood supply as assessed by UV-Q and UV-Q/EFW. Our data shed light on the early changes in pregnant obese women and suggest that RAS dysregulation is a prerequisite rather than a consequence of hypertensive disorders of pregnancy and other maternal neonatal complications.

Clinical Outcomes of Thermal Ablation Re-Treatment of Benign Thyroid Nodules: A Multicenter Study from the Italian Minimally Invasive Treatments of the Thyroid Group.

Background: Thermal ablation (TA) is an established therapeutic option alternative to surgery in patients with solid benign thyroid nodules causing local symptoms. However, a variable part of thyroid nodules remain viable after these nonsurgical treatments, and as many as 15% of nodules treated with TA may require a second treatment over time. This study aimed to evaluate the outcomes of TA re-treatment on symptomatic benign thyroid nodules where the volume decreased by <50% after the first procedure ( = technique inefficacy). Methods: We performed a multicenter retrospective cohort study including patients who underwent re-treatment with TA for benign thyroid nodules, whose volume decreased by <50% after initial treatment. The primary aim was to evaluate volume and volume reduction ratio (VRR) over time and compare the 6- and 12-month VRR after first versus second treatment. The secondary aim was to identify protective or risk factors for technique inefficacy, regrowth, and further treatments, expressed as adjusted hazard ratios (HRs) and confidence interval [CI], after adjustment for sex, age, nodule volume, structure and function, nodule regrowth or symptom relapse, technique used and if the same technique was used for the first and second TA and time between them. Results: We included 135 patients. Re-treatment led to VRR of 50% and 52.2% after 6 and 12 months. VRR after re-treatment was greater than after first treatment in small and medium size nodules (<30 mL), while there were no differences for large nodules (>30 mL). After re-treatment technique inefficacy rate was 51.9%, regrowth rate was 12.6%, and further treatment rate was 15.6%. Radiofrequency ablation (RFA) was protective toward technique inefficacy (HR = 0.40 [CI 0.24-0.65]) and need of further treatments (HR = 0.30 [CI 0.12-0.76]). Large nodule volume (>30 mL) was associated with increased risk of re-treatment (HR = 4.52 [CI 1.38-14.82]). Conclusions: This is the first study evaluating the outcomes of re-treatment on symptomatic benign thyroid nodules with a VRR <50% after the initial TA treatment. Best results were seen in small and medium nodules (<30 mL) and after RFA. Prospective confirmatory studies are needed.

Real-World Retrospective Study into the Effects of Oral Semaglutide (As a Switchover or Add-On Therapy) in Type 2 Diabetes.

(1) Background: Oral semaglutide represents the first oral GLP-1 RA approved for the treatment of type 2 diabetes mellitus (T2DM). This real-world retrospective study aimed at evaluating its effectiveness and tolerability in the treatment of patients with T2DM when patients switched from a glucose-lowering agent to it and when it was added to the usual therapy. (2) Methods: Adult patients with T2DM taking oral semaglutide and followed in the ASUGI Diabetes Center were identified with the use of electronic medical records between October 2022 and May 2023. (3) Results: A total of 129 patients were recruited. The median follow-up was 6 months. Be it as a switchover or as an add-on therapy, oral semaglutide significantly reduced HbA1c and BMI. Switching from DPPIV inhibitors to oral semaglutide was associated with a significant reduction in HbA1c and BMI, switching from SGLT2 inhibitors was associated with a significant reduction in HbA1c, and switching from sulphonylureas was associated with a significant reduction in BMI. The median HbA1c change was associated with baseline HbA1c. SBP significantly decreased in the add-on group. Oral semaglutide was well tolerated. (4) Conclusions: This study shows that in the real-world setting, oral semaglutide is effective and safe as a switchover or as an add-on therapy for the treatment of T2DM.

Preliminary Study on the Effect of a Night Shift on Blood Pressure and Clock Gene Expression.

Night shift work has been found to be associated with a higher risk of cardiovascular and cerebrovascular disease. One of the underlying mechanisms seems to be that shift work promotes hypertension, but results have been variable. This cross-sectional study was carried out in a group of internists with the aim of performing a paired analysis of 24 h blood pressure in the same physicians working a day shift and then a night shift, and a paired analysis of clock gene expression after a night of rest and a night of work. Each participant wore an ambulatory blood pressure monitor (ABPM) twice. The first time was for a 24 h period that included a 12 h day shift (08.00-20.00) and a night of rest. The second time was for a 30 h period that included a day of rest, a night shift (20.00-08.00), and a subsequent period of rest (08.00-14.00). Subjects underwent fasting blood sampling twice: after the night of rest and after the night shift. Night shift work significantly increased night systolic blood pressure (SBP), night diastolic blood pressure (DBP), and heart rate (HR) and decreased their respective nocturnal decline. Clock gene expression increased after the night shift. There was a direct association between night blood pressure and clock gene expression. Night shifts lead to an increase in blood pressure, non-dipping status, and circadian rhythm misalignment. Blood pressure is associated with clock genes and circadian rhythm misalignement.

Immunocytochemistry Profile of Benign Thyroid Nodules Not Responding to Thermal Ablation: A Retrospective Study.

Purpose: Thermal ablations (TA) are gaining ground as alternative options to conventional therapies for symptomatic benign thyroid nodules. Little is known about the impact of nodule biology on the outcomes of TA. The aim of our study was to evaluate the baseline immunocytochemistry profile of thyroid nodules that were poorly responsive to TA in order to identify potential predictors of the treatment response. Methods: From a cohort of 406 patients with benign thyroid nodules treated with TA and followed for 5 years, we retrospectively selected two groups of patients: NONRESPONDERS (patients who did not respond to TA and were later surgically treated) and RESPONDERS (patients who responded to TA). The fine-needle aspiration cytology (FNAC) slides obtained before TA were stained for Galectin-3, HBME-1, CK-19, and Ki-67. Results: Benign nodules of NONRESPONDERS (n = 19) did not express CK-19 (p = 0.03), as compared to RESPONDERS (n = 26). We combined the absence of CK-19 and the presence of Ki-67 to obtain a composite biomarker of resistance to TA, which discriminated between likelihood of retreatment and no retreatment with an AUC of 0.68 (95%CI: 0.55-0.81) and a sensitivity, specificity, PPV, and NPV of 29%, 91%, 71%, and 64%, respectively. Conclusion: In benign thyroid nodules, the absence of CK-19 was associated with resistance to TA, while the presence of CK-19 was predictive of response to TA. If confirmed, this finding could provide rapid and inexpensive information about the potential outcome of TA on benign thyroid nodules. In addition, as CK-19 can be expressed in adenomatous hyperplasia, it could be speculated that these nodules, rather than follicular adenomas, might be better candidates for TA.

Children With Short Stature Display Reduced ACE2 Expression in Peripheral Blood Mononuclear Cells.

Background: The cause of short stature remains often unknown. The renin-angiotensin system contributes to growth regulation. Several groups reported that angiotensin-converting enzyme 2 (ACE2)-knockout mice weighed less than controls. Our case-control study aimed to investigate if children with short stature had reduced ACE2 expression as compared to controls, and its significance. Materials and Methods: children aged between 2 and 14 years were consecutively recruited in a University Hospital pediatric tertiary care center. Cases were children with short stature defined as height SD ≤ -2 diagnosed with growth hormone deficiency (GHD) or idiopathic short stature (ISS), before any treatment. Exclusion criteria were: acute diseases, kidney disease, endocrine or autoimmune disorders, precocious puberty, genetic syndromes, SGA history. ACE and ACE2 expression were measured in peripheral blood mononuclear cells, angiotensins were measured by ELISA. Results: Children with short stature displayed significantly lower ACE2 expression, being 0.40 fold induction (0.01-2.27) as compared to controls, and higher ACE/ACE2, with no differences between GHD and ISS. ACE2 expression was significantly and inversely associated with the risk of short stature, OR 0.26 (0.07-0.82), and it had a moderate accuracy to predict it, with an AUC of 0.73 (0.61-0.84). The cutoff of 0.45 fold induction of ACE2 expression was the value best predicting short stature, identifying correctly 70% of the children. Conclusions: Our study confirms the association between the reduction of ACE2 expression and growth retardation. Further studies are needed to determine its diagnostic implications.

Is the Adrenal Incidentaloma Functionally Active? An Approach-To-The-Patient-Based Review.

Adrenal incidentalomas are a common occurrence. Most of them are adrenocortical adenomas that do not cause harm and do not require surgery, but a non-negligible proportion of incidentalomas is represented by functionally active masses, including cortisol-secreting adenomas (12%), pheochromocytomas (3-6%), aldosterone-secreting adenomas (2-3%), as well as malignant nodules, such as adrenocortical carcinomas (2-5%), which can be either functioning or non-functioning. All patients with an adrenal incidentaloma should undergo a few biochemical screening and confirmatory tests to exclude the presence of a functionally active mass. In this approach-to-the-patient-based review, we will summarize current recommendations on biochemical evaluation and management of functionally active adrenal incidentalomas. For this purpose, we will present four case vignettes, whereby we will describe how patients were managed, then we will review and discuss additional considerations tied to the diagnostic approach, and conclude with practical aspects of patient perioperative management. To improve the perioperative management of patients with functional adrenal incidentalomas, multidisciplinary meetings are advocated.

Arterial Stiffness in Thyroid and Parathyroid Disease: A Review of Clinical Studies.

Growing evidence shows that arterial stiffness measurement provides important prognostic information and improves clinical stratification of cardiovascular risk. Thyroid and parathyroid diseases are endocrine diseases with a relevant cardiovascular burden. The objective of this review was to consider the relationship between arterial stiffness and thyroid and parathyroid diseases in human clinical studies. We performed a systematic literature review of articles published in PubMed/MEDLINE from inception to December 2021, restricted to English languages and to human adults. We selected relevant articles about the relationship between arterial stiffness and thyroid and parathyroid diseases. For each selected article, data on arterial stiffness were extracted and factors that may have an impact on arterial stiffness were identified. We considered 24 papers concerning hypothyroidism, 9 hyperthyroidism and 16 primary hyperparathyroidism and hypoparathyroidism. Most studies evidenced an increase in arterial stiffness biomarkers in hypothyroidism, hyperthyroidism and primary hyperparathyroidism, even in subclinical and mild forms, although heterogeneity of measurement methods and of study designs prevented a definitive conclusion, suggesting that the assessment of arterial stiffness may be considered in the clinical evaluation of cardiovascular risk in these diseases.

Discriminatory Value of Adiponectin to Leptin Ratio for COVID-19 Pneumonia.

Purpose: Obesity is a risk factor for severe coronavirus disease 2019 (COVID-19). Circulating adipokines have been associated with inflammatory burden and amplified or dysregulated immune responses. This study aimed to evaluate the discriminatory ability of adipokines to identify COVID-19 pneumonia and to assess disease severity. Methods: We conducted an observational case-control study, with a prospective design, and recruited patients with diagnosis of COVID-19 pneumonia (n = 48) and healthy controls (n = 36), who were matched by age, sex, and BMI. Leptin, adiponectin, IL-6, and TNF-α were measured by ELISA. Results: Patients with COVID-19 pneumonia had higher levels of leptin, lower adiponectin/leptin (Adpn/Lep) ratio, and higher expression of IL-6. Leptin had an acceptable discriminatory accuracy for COVID-19 pneumonia in patients with BMI >30 (AUC 0.74 [0.58, 0.90]) with a cutoff of 7852 pg/mL and it was associated with maximum respiratory support. By contrast, Adpn/Lep had an excellent discriminatory accuracy for COVID-19 pneumonia in patients with BMI <25 (AUC 0.9 [0.74, 1.06]) with a cutoff of 2.23. Conclusion: Our data indicate that high Adpn/Lep (>2.23) in lean patients is consistent with a state of good health, which decreases in case of inflammatory states, ranging from adipose tissue dysfunction with low-grade inflammation to COVID-19 pneumonia.

Meta-analysis on the Association Between Thyroid Hormone Disorders and Arterial Stiffness.

Context: Aortic stiffness is an emerging predictor of cardiovascular morbidity and mortality. Current data about the effect of subclinical and overt thyroid hormone disorders on aortic stiffness are often conflicting. Objective: Primary outcome was to investigate if subclinical and overt thyroid hormone disorders were associated with aortic stiffness. Secondary outcome was to identify disease effect modifiers. Methods: Data sources were PubMed, Google Scholar, SCOPUS, Web of Sciences, and the Cochrane Library. Eligible studies included reports of pulse wave velocity (PWV), which is the gold standard method for measuring aortic stiffness, in patients with subclinical and overt thyroid disorders. Two investigators independently identified eligible studies and extracted data. Pooled mean difference was the summary effect measure. Data were presented in forest plots with outlier and influential case diagnostics. Univariate meta-regression analysis was used to identify effect modifiers. Results: Eleven observational studies were selected, including 1239 patients with subclinical hypothyroidism, 81 patients with overt hypothyroidism, 338 patients with thyrotoxicosis, and 12 715 controls. PWV was significantly higher in subclinical (P < .001) and overt hypothyroidism (P < .001), as well as in patients with thyrotoxicosis (P = .027) compared with controls. Age was an effect modifier in hypothyroid patients. Conclusion: This study shows that both overt and subclinical hypothyroidism as well as thyrotoxicosis were associated with an increase of aortic stiffness. The impact of treatment of these conditions on aortic stiffness should be assessed in clinical trials.

Minimally-invasive treatments for benign thyroid nodules: recommendations for information to patients and referring physicians by the Italian Minimally-Invasive Treatments of the Thyroid group.

PURPOSE: In this paper, the members of the Italian Working Group on Minimally-Invasive Treatments of the Thyroid (MITT group) aim to summarize the most relevant information that could be of help to referring physicians and that should be provided to patients when considering the use of MITT for the treatment of benign thyroid nodules. METHODS: An interdisciplinary board of physicians with specific expertise in the management of thyroid nodules was appointed by the Italian MITT Group. A systematic literature search was performed, and an evidence-based approach was used, including also the knowledge and the practical experience of the panelists to develop the paper. RESULTS: The paper provides a list of questions that are frequently asked by patients to operators performing MITT, each with a brief and detailed answer and more relevant literature references to be consulted. CONCLUSIONS: This paper summarizes the most relevant information to be provided to patients and general practitioners/referring physicians about the use of MITT for the treatment of benign thyroid nodules.

Type 1 diabetes is associated with significant changes of ACE and ACE2 expression in peripheral blood mononuclear cells.

BACKGROUND AND AIMS: The renin-angiotensin system (RAS), which is a key mediator of cardiovascular homeostasis, has two main axes. The classic one, including angiotensin-converting enzyme (ACE) and Angiotensin (Ang) II, promoting vasoconstriction, and the "alternative" one, including ACE2 and Ang1-7, with opposed actions to AngII. ACE2 has been identified as the main receptor of SARS-CoV2, whereby it enters the cells, leading to the downregulation of surface ACE2 and RAS tissue unbalance. Given that diabetes is associated with an increase in COVID-19 severity and death, we aimed at evaluating RAS expression in patients with type 1 diabetes (T1D). METHODS AND RESULTS: This is a case-control study comparing 39 T1D patients to 33 controls, with a median age of 29 and 32 years, and no comorbidities. ACE and ACE2 gene expression was assessed in peripheral blood mononuclear cells. T1D patients had higher ACE expression and circulating AngII, which were related to glucose levels. T1D patients had lower ACE2 expression. However, ACE2 expression was also related to the sex of participants, being higher in the female group. T1D women did not show the same increase of ACE2 expression that was seen in control women. CONCLUSION: T1D promotes the increase of ACE, AngII, and ACE/ACE2, which might contribute to the higher cardiovascular risk, as well as to severe tissue injury induced by SARS-CoV2 in these patients. The ratio ACE/ACE2 does not differ between men and women with T1D, which might explain why CVD or COVID-19 do not show substantial gender differences in these patients.

Long-term efficacy and safety of percutaneous ethanol injection (PEI) in cystic thyroid nodules: A systematic review and meta-analysis.

BACKGROUND: Percutaneous ethanol injection (PEI) is used for the treatment of benign cystic thyroid nodules. This systematic review and meta-analysis aimed to obtain strong evidence of its long-term efficacy and safety. METHODS: PubMed, CENTRAL, Scopus and Web of Science databases were searched until November 2020 for studies reporting data on volume reduction rate (VRR), compressive symptoms and cosmetic concerns. Associated complications were assessed. A random-effects model was designed to pool the data. RESULTS: Out of 385 papers, nine studies evaluating 1667 nodules were finally included. Overall, VRR at 6, 12, 24, 36, 60 and 120 months was 77%, 81%, 72%, 68%, 74% and 69%, respectively. Significant reductions in the compressive symptoms and cosmetic concerns were observed. No permanent complications were observed. CONCLUSIONS: The present meta-analysis showed that PEI could significantly reduce the volume of benign cystic thyroid nodules. This reduction was already effective at 6 months post-treatment, and the effect was stable over time.

Image-guided thermal ablation in autonomously functioning thyroid nodules. A retrospective multicenter three-year follow-up study from the Italian Minimally Invasive Treatment of the Thyroid (MITT) Group.

OBJECTIVES: To report the results of a multicenter retrospective evaluation of the clinical outcomes of thermal ablation (TA) in a large series of autonomously functioning thyroid nodules (AFTN) with a follow-up protracted up to 3 years. METHODS: Patients treated with single TA for an AFTN in Italy were included. Changes in nodule volume, TSH values, and ongoing anti-thyroid therapy were assessed at the 2-, 6-, 12-, 24-, and 36-month follow-up controls. Complications and need of any additional therapy after TA were also registered. RESULTS: A total of 361 patients (244 females, 117 males, median age 58 years, IQR 46-70 years) were included. Nodule volume was significantly reduced at all time points (p < 0.001) (median volume reduction 58% at 6-month and 60% at 12-month). Serum TSH values increased significantly at all time points. After TA, anti-thyroid therapy was withdrawn in 32.5% of patients at 2 months, in 38.9% at 6 months, and in 41.3% at 12 months. A significant difference in the rate of patients who withdrawn medical therapy at 12 months was registered between small (< 10 mL) (74%), medium (49%), or large (> 30 mL) nodules (19%). A single major complication occurred (0.25%). Additional treatments were needed in 34/361 (9.4%) of cases including 4 (1.1%) surgical treatment. CONCLUSIONS: Image-guided thermal ablation offers a further safe and effective therapeutic option in patients with AFTN. Clinical outcomes are significantly more favorable in small than in large size AFTN. KEY POINTS: • Thermal ablations (TA) can be safely and effectively used in patients with autonomously functioning thyroid nodules (AFTN). • TA results in a clinically significant nodule volume reduction that is paralleled by TSH level normalization and anti-thyroid drug therapy discontinuation (after TA anti-thyroid therapy was withdrawn in 41.3% at 12 months). • Clinical outcomes after TA are more favorable in small nodules, and when a large amount of thyroid nodule tissue is ablated.

TRAIL/DR5 pathway promotes AKT phosphorylation, skeletal muscle differentiation, and glucose uptake.

TNF-related apoptosis-inducing ligand (TRAIL) is a protein that induces apoptosis in cancer cells but not in normal ones, where its effects remain to be fully understood. Previous studies have shown that in high-fat diet (HFD)-fed mice, TRAIL treatment reduced body weight gain, insulin resistance, and inflammation. TRAIL was also able to increase skeletal muscle free fatty acid oxidation. The aim of the present work was to evaluate TRAIL actions on skeletal muscle. Our in vitro data on C2C12 cells showed that TRAIL treatment significantly increased myogenin and MyHC and other hallmarks of myogenic differentiation, which were reduced by Dr5 (TRAIL receptor) silencing. In addition, TRAIL treatment significantly increased AKT phosphorylation, which was reduced by Dr5 silencing, as well as glucose uptake (alone and in combination with insulin). Our in vivo data showed that TRAIL increased myofiber size in HFD-fed mice as well as in db/db mice. This was associated with increased myogenin and PCG1α expression. In conclusion, TRAIL/DR5 pathway promotes AKT phosphorylation, skeletal muscle differentiation, and glucose uptake. These data shed light onto a pathway that might hold therapeutic potential not only for the metabolic disturbances but also for the muscle mass loss that are associated with diabetes.

Current Status and Challenges of US-Guided Radiofrequency Ablation of Thyroid Nodules in the Long Term: A Systematic Review.

BACKGROUND: US-guided minimally-invasive techniques, such as radiofrequency ablation (RFA) have emerged as an alternative treatment for benign and malignant thyroid nodules. This systematic review aims to provide an overview on the long-term outcomes of US-guided RFA in patients with benign and malignant thyroid nodules. METHODS: We systematically searched PubMed/MEDLINE, EMBASE, and Scopus to identify articles reporting the outcomes of thyroid RFA after a follow-up of at least 3 years. RESULTS: A total of 20 studies met the inclusion criteria and were included in the review. In patients with benign thyroid nodules, RFA significantly reduced nodule volume and this was generally maintained for the following 5 years. However, a small but not negligible proportion of nodules regrew and some of them required further treatments over time. In patients with malignant nodules, RFA has been used not only to treat differentiated thyroid cancer (DTC) neck recurrences, but also to treat papillary thyroid microcarcinoma (PTMC). In most patients with PTMC, RFA led to complete disappearance of the tumor. When it was compared to surgery, RFA was not inferior in terms of oncologic efficacy but it had a lower complication rate. However, RFA did not allow for final pathology, disease staging and accurate risk stratification. CONCLUSIONS: US-guided RFA significantly reduces benign thyroid nodules and destroys most PTMC, and this is generally maintained for at least 5 years after the initial treatment. Further studies addressing the risk of regrowths in patients with benign thyroid nodules, as well as the risk of recurrence in patients with PTMC are needed.

Meta-analysis on the Effect of Mild Primary Hyperparathyroidism and Parathyroidectomy Upon Arterial Stiffness.

CONTEXT: Current data about the cardiovascular manifestations of mild primary hyperparathyroidism (pHPT) are often conflicting. Pulse wave velocity (PWV) is the gold standard for assessing aortic stiffness, and it predicts cardiovascular morbidity and mortality. OBJECTIVE: Primary outcomes were to investigate if mild pHPT was associated with higher PWV and if parathyroidectomy (PTX) reduced PWV in mild pHPT. Secondary outcome was to investigate blood pressure changes after PTX. METHODS: Sources were PubMed, Google Scholar, SCOPUS, Web of Science, and the Cochrane Library. Eligible studies included reports of PWV in patients with mild pHPT and controls, or in patients with mild pHPT before and after PTX. Two investigators independently identified eligible studies and extracted data. Pooled mean difference (MD) was the summary effect measure. Data were presented in forest plots with outlier and influential case diagnostics. Nine observational studies and one randomized clinical trial were selected, including 433 patients with mild pHPT, 171 of whom underwent PTX, and 407 controls. PWV was significantly higher in mild pHPT than in controls (MD = 1.18, 0.67 to 1.68, P < .0001). Seven studies evaluated the effect of PTX on PWV. PTX significantly reduced PWV (MD = -0.48, -0.88 to -0.07, P = .022). CONCLUSION: Aortic stiffness is increased in patients with mild pHPT, supporting the notion that mild pHPT is also associated with adverse cardiovascular manifestations. PTX significantly reduced arterial stiffness in mild pHPT, indicating that the benefit of PTX over cardiovascular manifestations should not be dismissed but it deserves further studies.