Background: Treatment of advanced differentiated thyroid carcinoma (DTC) remains a challenge as 25-50% of patients with locally invasive or distant metastatic disease become refractory to radioiodine (RAI) therapy. Tyrosine kinase inhibitors (TKI) are increasingly used in this setting. The SELECT trial demonstrated that lenvatinib, a multikinase inhibitor, significantly improved progression free survival (PFS) compared to placebo. Our aim was to report the effectiveness and safety of lenvatinib in our series of patients with advanced DTC.
Methods: A total of 25 patients with advanced DTC followed at a single tertiary center from January of 2016 to January of 2022 were retrospectively reviewed.
Results: Patients were treated with a mean daily dose of lenvatinib of 16.9 mg for a mean of 9.1 months. Median estimated PFS was 31.3 months. One patient achieved complete response. The objective response rate (ORR) was 40% and the disease control rate was 84%. The mean change in summed longest diameter of target lesions from baseline to nadir was -36.9%. Lenvatinib prolonged the tumor volume doubling time in 86.7% patients. Interestingly, we found that patients treated with a lower dose of lenvatinib (<16.9 mg daily) had a significantly higher PFS and ORR than patients treated with higher dosages (>16.9 mg). Adverse events were frequently reported.
Conclusions: Our results confirm the effectiveness of lenvatinib in the management of patients with advanced DTC and support the need to adjust the dosage of lenvatinib to patient´s performance status and comorbidities.
The human male infertility has several causes interconnected to improper lifestyles such as smoking, sedentarism, environmental factors, toxins accumulation and energy imbalances. All these factors contribute to the obesity accompanied metabolic syndrome and hormonal alterations in the leptin-ghrelin axis. The leptin (Lep) has many pleiotropic effects in several biological systems, directly on the peripheral tissues or through the central nervous system. Many studies suggest that Lep is a key player in gonadal functions beside its documented role in reproductive regulation; however, further investigations are still necessary to elucidate all the molecular pathways involved in these mechanisms. Keeping into account that increased Lep levels in obese men are positively correlated with altered sperm parameters and testicular oxidative stress, evidence refers to Lep as a potential link between obesity and male infertility. This review represents an updated version on the concept of the Lep roles in mediating the male reproductive functions in obese patients.
Background: This single-center real-life study was conducted to evaluate the most effective combination of nutraceuticals and the most appropriate indications for the treatment of male infertile patients.
Methods: Infertile patients aged 20-55 years were treated with a combination of antioxidants (Androlen®; Enfarma, Misterbianco, Catania, Italy) (group A), with Androlen® (Enfarma) and a mixture of fibrinolytic molecules (Lenidase®, Enfarma) (group B), or Androlen® (Enfarma) and other molecules different from those used for the patients of the group B (group C). Patients were also subdivided according to the presence of varicocele, mild testicular hypotrophy, idiopathic infertility, and chronic male accessory gland infection.
Results: Forty-three patients were enrolled. In the overall analysis, only progressive motility significantly improved after therapy. Subgroup analysis showed a significant increase in progressive motility, total motile sperm count (TMSC), and in the percentage of alive spermatozoa after treatment in the group A. Progressive motility improved significantly in patients with varicocele, while the TMSC in patients with varicocele and those with idiopathic infertility. The percentage of alive spermatozoa increased in patients with testicular hypotrophy.
Conclusions: Treatment with antioxidants increased progressive sperm motility, especially in patients with varicocele or idiopathic infertility.
Background: Twenty-twenty-five percent of patients with differentiated thyroid cancer (DTC) can have elevated thyroglobulin antibodies (TgAb). The study aimed to find any prognostic significance of elevated TgAb during follow-up.
Methods: Ten-year retrospective study from a tertiary center including 79 patients with raised TgAb after total/staged thyroidectomy for DTC. We identified patients with stable (7.6%), increasing (15%) and decreasing levels of TgAb (77.2%); groups 1, 2 and 3 respectively. During follow-up we analyzed TgAb in subcategories by TgAb trend (>50% rise, <50% rise, >50% decline, <50% decline, positive to negative/normalization, negative to positive and stable levels), gender, age, surgery, autoimmune disease, histology, RAI uptake, distant metastases, and recurrence.
Results: The incidence of raised TgAb levels was 33.2%, with female predominance. No connection was identified regarding other parameters. 11.4% had distant metastases. The highest mean maximum levels of TgAb was in group 2 (1918.75 IU/mL) and the lowest in group 3 (412.70 IU/mL). The recurrence rate changed significantly between the 3 groups: 50% in group 1, 75% in group 2, and 25% in group 3 (P=0.002). Recurrence rates decreased to 15% in the subcategory where TgAb became negative/normal from positive (P=0.0001). In patients with a negative to positive TgAb level trend or >50% rise, recurrence rates were 100% (P=0.041) and 70% (P=0.012) respectively.
Conclusions: Patients with increasing TgAb levels during follow-up have a higher rate of recurrence, distinctly for those with negative to positive trend and >50% rise in TgAb. These patients need closer follow-up, and TgAb may be used as a dynamic follow-up marker.
Introduction: Nesfatin-1 is a satiety peptide secreted by central, peripheral nervous system and some peripheral tissues. This meta-analysis was conducted to explore the associations with diagnostic accuracy of circulatory nesfatin-1 in polycystic ovary syndrome (PCOS).
Evidence acquisition: Relevant studies were retrieved by online database and manual searching. The standardized mean differences (SMDs) with 95% confidence intervals (CIs) were obtained by a random-effects meta-analysis. The subgroup analysis based on the Body Mass Index (BMI), fasting insulin (F-INS), and the homeostasis model assessment-estimated insulin resistance (HOMA-IR) was conducted. Meta-analysis of correlations and meta-regression were performed for the associations of nesfatin-1 with metabolic and hormonal covariates. The diagnostic test accuracy (DTA) meta-analysis was conducted for the utility of nesfatin-1 in PCOS. The publication bias was tested with Egger's and Begg's regression tests.
Evidence synthesis: The combined effect size including a total of 14 studies showed a significantly higher nesfatin-1 level in PCOS as compared to controls (SMD=0.93, Z=2.17, P=0.03). The nesfatin-1 was found to be significantly higher in a subgroup of studies with mean BMI>25 kg/m2 (SMD=1.35, Z=2.06, P=0.04), F-INS <13 mIU/mL (SMD=2.74, Z=3.59, P=0.0003), and HOMA-IR >2.7 (SMD=1.58, Z=2.65, P=0.008). The DTA meta-analysis produced a pooled diagnostic odds ratio of 19.58 and area under curve were of 0.888 for nesfatin-1 in PCOS.
Conclusions: The results indicate a multifactorial involvement such as endocrine and metabolic alterations in the form of BMI, insulin and HOMA-IR status with the higher nesfatin-1 levels in PCOS. The promising results of DTA meta-analysis warrants further research into the clinical and prognostic utility of nesfatin-1 in PCOS.
Background: The American Thyroid Association (ATA) recurrence risk prediction system considers vascular invasion (VI) as a relative indicator for adjuvant radioactive iodine (RAI) treatment, nevertheless VI final role in PTC management is yet to be defined. This study aims to assess the impact of histologic VI in papillary thyroid carcinoma (PTC).
Methods: A retrospective study with PTC patients admitted in our Thyroid Cancer Unit, between January 1960 and December 2016 was performed. We reviewed 905 patient records with 275 having full information about VI on their pathological reports. Demographic and clinical variables were obtained, and univariate/multivariate analysis was performed in order to obtain potential predictive prognostic factors.
Results: Fifty-one out 275 patients presented VI (18.5%; 95% CI 14.4-23.6%), these individuals had larger tumors (median 19 mm vs. 12 mm, P<0.001) with more frequent extraglandular invasion (54.0% vs. 17.1%, P<0.001), regional lymph nodes involvement (29.8% vs. 12.6%, P=0.003)and distant metastasis (10.9% vs. 1.9%, P=0.003) at diagnosis. VI was an independent predictor for regional lymph node and/or distant metastasis at diagnosis (OR 2.93 [IC 95% 1.16-7.41, P=0.008]). After a median follow-up time was 68.5 months patients with VI presented higher rates of local recurrence and lymph node metastasis recurrence.
Conclusions: In this study, the presence of VI in PTC is associated to higher rate of lymph node and distant metastasis at diagnosis. Its presence should be probably considered an adverse prognostic factor in PTC, perhaps justifying more aggressive therapeutic and follow-up approaches in such cases.
Background: The associations of cardiovascular autonomic neuropathy (CAN) with diabetic nephropathy and heart disease remain elusive. The aim of this study was to explore the correlations of CAN with urinary albumin excretion rate (UAER) and cardiac function in patients with type 2 diabetes mellitus (T2DM).
Methods: A total of 225 T2DM patients were assigned into CAN and non-CAN groups using cardiovascular reflex tests (CARTs). They were divided into macroalbuminuria, microalbuminuria and normoalbuminuria groups according to urinary albumin/creatinine ratio (UACR), or left ventricular diastolic dysfunction and normal groups based on left ventricular peak E/A velocity ratio (E/A). The correlations of CAN with albuminuria and left ventricular diastolic dysfunction, and the predictive values of UACR and E/A were analyzed.
Results: Compared with non-CAN group, CAN group had older age, longer T2DM duration, higher serum urine acid (SUA) level, UACR, systolic and diastolic pressure differences between supine and standing positions, and lower other CARTs parameters and E/A (P<0.001). Macroalbuminuria group had largest positional systolic and diastolic pressure differences, and lowest other CARTs parameters (P<0.001). Compared with normal group, left ventricular diastolic dysfunction group had larger positional systolic and diastolic pressure differences, and lower other CARTs parameters (P<0.001). CAN in T2DM patients was positively correlated with albuminuria and left ventricular diastolic dysfunction (P<0.001). Age, SUA, UACR and E/A were independent predictive factors (P=0.031, P=0.005, P<0.001, P<0.001). UACR and E/A had high predictive values.
Conclusions: In T2DM patients, CAN is positively correlated with declined UAER and cardiac function. UACR and E/A have high predictive values.