New Targets for Drug Treatment of Obesity.

Antiobesity medical management has shown unsatisfactory results to date in terms of efficacy, safety, and long-term maintenance of weight loss. This poor performance could be attributed to the complexity of appetite regulation mechanisms; the serious drug side effects; and, crucially, the lack of profile-matching treatment strategies and individualized, multidisciplinary follow-up. Nevertheless, antiobesity pharmacotherapy remains a challenging, exciting field of intensive scientific interest. According to the latest studies, the future of bariatric medicine lies in developing drugs acting at multiple levels of the brain-gut axis. Currently, research is focused on the generation of combination treatments based on gut hormones in a way that mimics changes underlying surgically induced weight loss, in addition to centrally acting agents; these aim to restore energy balance disruptions and enhance energy expenditure. Collectively, the pharmacological resolution of obesity could potentially be achieved with combination regimens targeting different molecules and levels of the energy homeostasis system, in parallel with matching patients' needs, resulting in a favorable metabolic profile.

The Long Journey towards Personalized Targeted Therapy in Poorly Differentiated Thyroid Carcinoma (PDTC): A Case Report and Systematic Review.

BACKGROUND: Poorly differentiated thyroid carcinoma (PDTC) has an intermediate prognosis between indolent well-differentiated thyroid carcinoma (TC) and anaplastic carcinoma. Herein, we present a case report with a PDTC component, along with a systematic review of the literature. CASE REPORT: We report a case of a 45-year-old man diagnosed with a PDTC component, along with hobnail and tall-cell variant features positive for BRAFV600E mutation, after a total thyroidectomy and neck dissection. Radioactive iodine (RAI)-131 therapy was applied, but an early recurrence led to complementary surgeries. The anti-Tg rise, the presence of new lymph nodes, and the negative whole-bodyradioiodine scan were suggestive of a radioiodine-resistant tumor. Lenvatinib, sorafenib, dabrafenib/trametinib, cabozantinib and radiotherapy were all administered, controlling the tumor for a period of time before the patient ultimately died post-COVID infection. Systematic Review: We searched PubMed, Scopus, and WebofScience to identify studies reporting clinicopathological characteristics, molecular marker expression, and management of non-anaplastic TC with any proportion of PDTC in adult patients. Of the 2007 records retrieved, 82were included in our review (PROSPERO-ID545847). CONCLUSIONS: Our case, together with the systematic review, imply that a combination of molecular-targetedtreatments may be safe and effective in patients with RAI-resistantBRAF-mutated advanced PDTC when surgery has failed to control tumor progression.

Surgical Treatment of Solitary Metachronous Adrenal Metastasis from Urothelial Carcinoma of the Urinary Bladder.

Urothelial cancer is a common neoplasm and metastatic disease correlates with a poor prognosis. Isolated adrenal gland metastases of urothelial carcinoma are quite rare, and management options can decide a patient's prognosis. Herein we report the case of a 76-year-old man with a metachronous solitary adrenal metastasis from a bladder carcinoma, who underwent adrenalectomy as part of his treatment. Furthermore, we discuss the cases of solitary adrenal metastases of urothelial carcinoma available in the literature, to identify key features to direct appropriate treatment of this rare metastatic site of urothelial cancer and improve prognosis and survival. Still, further prospective studies are needed to design effective therapeutic strategies.

Associations of Thyroid Hormones Profile During Normal Pregnancy and Postpartum With Anxiety, Depression, and Obsessive/Compulsive Disorder Scores in Euthyroid Women.

OBJECTIVE: Thyroid dysfunction (overt and subclinical) has been consistently linked to pregnancy adversity and abnormal fetal growth and development. Mood disorders such as anxiety, depression, and obsessive-compulsive disorder (OCD) are frequently diagnosed during pregnancy and at postpartum, and emerging evidence suggests association with impaired offspring neurodevelopment and growth. This study aimed to examine potential associations between thyroid function and mood symptoms during pregnancy and postpartum. DESIGN: This is a prospective study measuring thyroid hormones and assessing mood symptoms by employing specific questionnaires in the same cohort of 93 healthy pregnant women at the 24th (2nd trimester) and 36th (3rd trimester) gestational weeks and at the 1st postpartum week. METHODS: Serum thyroid hormones, TSH, anti-TPO, and anti-Tg antibodies were measured at the 24th (2nd trimester) and 36th (3rd trimester) gestational weeks and at the 1st postpartum week. Specific validated questionnaires were employed at the same time-points to assess separately symptoms of anxiety [Generalized Anxiety Disorder Inventory (GADI), Penn State Worry Questionnaire (PSWQ), STAI-State Anxiety inventory (STAI-S), STAI-Trait Anxiety Inventory (STAI-T)], depression [Edinburgh Postnatal Depression Scale (EPDS), Stein's Blues Scale (BLUES), Beck Depression Inventory (BDI)], and obsessive compulsive disorder (OCD) [Yale-Brown Obsessive Compulsive scale (Y-BOCS)]. RESULTS: At the 2nd trimester, GADI score correlated negatively with FT3 (p < 0.010, r = -0.545) and positively with TSH (p < 0.050, r = 0.837) concentrations; GADI, PSWQ, EPDS and Y-BOCS scores correlated negatively with FT4 concentrations (p < 0.010, r = -0.768; p < 0.010, r = -0.384; p < 0.050, r = -0.364; p < 0.010, r = -0.544, respectively). At the 3rd trimester, BLUES score correlated positively with rT3 concentrations (p = 0.00, r = 0.89); GADI, EPDS, and Y-BOCS scores correlated negatively with FT4 concentrations (p = 0.001, r = - 0.468; p = 0.036, r = -0.39; p = 0.001, r = -0.625, respectively); GADI, STAI-S, and Y-BOCS scores correlated positively with TSH concentrations (p = 0.015, r = 0.435; p = 0.024, r = 0.409 p = 0.041, r = 0.389, respectively). At postpartum, PSWQ, STAI-T, EPDS, and BDI scores correlated positively with rT3 concentrations (p = 0.024, r = 0.478; p = 0.014, r = 0.527; p = 0.046, r = 0.44; p = 0.021, r = 0.556, respectively, Y-BOCS score correlated positively with TSH (p = 0.045, r = 0.43), and BLUES score correlated positively with anti-TPO antibody concentrations (p = 0.070, r = 0.586). CONCLUSION: The reported findings demonstrate positive associations between low-normal thyroid function at the 2nd and 3rd trimesters of pregnancy and postpartum with anxiety, depression, and OCD scores.

The effect of smoking on the risk of gestational diabetes mellitus and the OGTT profile during pregnancy.

OBJECTIVE: To analyze the relationship between smoking and the risk of GDM, as well as with the OGTT profile during pregnancy. PATIENTS AND METHODS: A total of 7437 pregnant women were studied. OGTT was performed at the 3rd trimester. Women were categorized as non-smokers (A), as those who ceased smoking at pregnancy (B), and as smokers (C). RESULTS: 5434 (73.1%) women were group A, 1191 (16%) group B and 812 (10.9%) group C. The rates of GDM among the groups were: A 33.7%, B 34.2%, C 34.2% (ns). However, the number of individuals requiring insulin treatment was significantly different: A 39.2%, B 47.5%, C 50.6% (p < 0.001). Regarding OGTT, fasting glucose levels were significantly higher in group C (89 ±â€¯13 vs 86 ±â€¯12 mg/dl) compared to A, whereas 3-h glucose values were significantly lower (104 ±â€¯33 vs 112 ±â€¯32 mg/dl) (p < 0.001). Group B demonstrated intermediate glucose concentrations. Similar findings were observed in women without GDM. In women with GDM, higher 1-h glucose levels were measured in group C (210 ±â€¯31 vs 205 ±â€¯28 mg/dl) compared with A (p = 0.024). Further, group C sub-analysis found that those who smoked more than 10 cigarettes showed significantly lower 3-h glucose levels (111 ±â€¯31 vs 128 ±â€¯40 mg/dl) compared to those who smoked less than 10 (p = 0.006). HbA1c in women with GDM was higher in group C (4.6 ±â€¯0.6 vs 4.5 ±â€¯0.6%) compared with A (p = 0.027). CONCLUSIONS: The present study did not show any correlation between smoking and GDM risk. However, OGTT profile and HbA1c differed according to smoking status in women with and without GDM.