Thyroid dysfunction in COVID-19 patients.

PURPOSE: "Non thyroidal illness syndrome" (NTIS) or "euthyroid sick syndrome" (ESS) is a possible biochemical finding in euthyroid patients with severe diseases. It is characterized by a reduction of serum T3 (fT3), sometimes followed by reduction of serum T4 (fT4). The relationship between thyroid hormones levels and mortality is well known and different studies showed a direct association between NTIS and mortality. The sudden spread of the 2019 novel coronavirus (SARS-CoV 2) infection (COVID-19) and its high mortality become a world healthcare problem. Our aim in this paper was to investigate if patients affected by COVID-19 presented NTIS and the relationship between thyroid function and severity of this infection. METHODS: We evaluated the thyroid function in two different groups of consecutive patients affected by COVID-19 with respect to a control group of euthyroid patients. Group A included patients hospitalized for COVID-19 pneumonia while patients requiring intensive care unit (ICU) for acute respiratory syndrome formed the group B. Group C identified the control group of euthyroid patients. RESULTS: Patients from group A and group B showed a statistically significant reduction in fT3 and TSH compared to group C. In group B, compared to group A, a further statistically significant reduction of fT3 and TSH was found. CONCLUSIONS: COVID-19 in-patients can present NTIS. FT3 and TSH serum levels are lower in patients with more severe symptoms.

Expected and paradoxical effects of obesity on cancer treatment response.

Obesity, whose prevalence is pandemic and continuing to increase, is a major preventable and modifiable risk factor for diabetes and cardiovascular diseases, as well as for cancer. Furthermore, epidemiological studies have shown that obesity is a negative independent prognostic factor for several oncological outcomes, including overall and cancer-specific survival, for several site-specific cancers as well as for all cancers combined. Yet, a recently growing body of evidence suggests that sometimes overweight and obesity may associate with better outcomes, and that immunotherapy may show improved response among obese patients compared with patients with a normal weight. The so-called 'obesity paradox' has been reported in several advanced cancer as well as in other diseases, albeit the mechanisms behind this unexpected relationship are still not clear. Aim of this review is to explore the expected as well as the paradoxical relationship between obesity and cancer prognosis, with a particular emphasis on the effects of cancer therapies in obese people.

Thyroid profile during the alternative Sunitinib dosing 2/1 schedule in metastatic renal cell carcinoma.

PURPOSE: Hypothyroidism is a common side effect of Sunitinib (SUN) treatment in metastatic renal cell carcinoma (mRCC) patients. We aimed to evaluate thyroid profile during the alternative 2/1 SUN treatment schedule and to assess the predictive value of hypothyroidism in terms of survival. METHODS: We performed a prospective observational study enrolling 42 consecutive mRCC patients starting first-line alternative SUN dosing 2/1 schedule. Thyroid function was assessed at baseline and during the first three SUN cycles (1 cycle = 6 weeks = 2 ON/1 OFF + 2 ON/1 OFF), and then after 6 and 12 months. Thyroid ultrasound was performed at baseline and after 3, 6, and 12 months. RESULTS: Subclinical hypothyroidism developed in 24% of patients during the first cycle; in other 24% in the second cycle and in 14% in the third cycle. The highest TSH values were reached during the second cycle, ON phase (6.58 ± 5.74 µI U/l). We observed a reduction in thyroid size, in echogenicity and in parenchymal perfusion in all patients. Progression-free survival (PFS) tended to be longer in patients with TSH ≥ 5 µI U/ml during the second cycle (p = 0.069). TSH level was an independent risk factor for PFS in men (p = 0.009) but not in women (p = 0.285). CONCLUSIONS: This is the first study investigating functional and morphological effects on thyroid during the alternative 2/1 SUN schedule in mRCC patients. We detected an early onset of subclinical hypothyroidism, observing the association between TSH ≥ 5 µI U/ml and: (i) longer PFS in men; (ii) progressive decrease of thyroid size in absence of significant changes in autoimmune thyroid profile.

Everolimus is a new anti-cancer molecule: Metabolic side effects as lipid disorders and hyperglycemia.

In the last few years, molecular targeted therapies have replaced traditional cytotoxic chemotherapy in the fight against many cancers to the extent that our understanding of tumor biology has become more sophisticated. This shift has markedly changed adverse event profiles, compared to cytotoxic chemotherapy, affecting a diverse range of organ systems. Everolimus was approved by the FDA in 2011 for the treatment of progressive pancreatic NE tumors. It is an inhibitor of mammalian target of rapamycin (mTOR) and exhibits antitumor activity via disruption of various signaling pathways and it's used in the treatment of advanced renal cell cancer, breast cancer and neuroendocrine tumors (NET); it's used also as anti-rejection agent for transplantation but with lower doses for anti-rejection (1.5-3.0 mg/day) than for anti-cancer (5-10 mg/day) treatment. Metabolic side effects are the most frequent reported and will be discussed in this review.

Somatostatin analogs therapy in gastroenteropancreatic neuroendocrine tumors: current aspects and new perspectives.

Gastroenteropancreatic neuroendocrine tumors (GEP-NETs) are rare tumors that present many clinical features secreting peptides and neuroamines that cause distinct clinical syndromes such as carcinoid syndrome. However most of them are clinically silent until late presentation with mass effects. Surgical resection is the first line treatment for a patient with a GEP-NET while in metastatic disease multiple therapeutic approaches are possible. GEP-NETs are able to express somatostatin receptors (SSTRs) bounded by somatostatin (SST) or its synthetic analogs, although the subtypes and number of SSTRs expressed are very variable. In particular, SST analogs are used frequently to control hormone-related symptoms while their anti-neoplastic activity seems to result prevalently in tumor stabilization. Patients who fail to respond or cease to respond to standard SST analogs treatment seem to have a response to higher doses of these drugs. For this reason, the use of higher doses of SST analogs will probably improve the clinical management of these patients.

Caco-2 cell line as a model to evaluate mucoprotective proprieties.

Physical protection of mucosa surface and reduction of inflammatory processes are currently considered the main strategies in the treatment and prevention of mucosal diseases. However, the majority of models used to verify the activity of new mucoprotective agents are based on limiting instrumental assessment or the sacrifice of experimental animals. In this study, for the first time, some in vitro experimental methods using Caco-2 cell line are proposed as predicting in vivo behaviour and action of mucoprotective agents. To this purpose, hyaluronic acid and natural polysaccharides for their bioadhesive activity, hydrocortisone and natural polyphenols as anti-inflammatory agents have been chosen. The obtained results demonstrated that the techniques (Con A/o-pd assay and Franz cell system) of mucoadhesive evaluation on Caco-2 cells are useful to compare the activity of each experimental sample and to assess the adhesion time to the mucosal cell surface. Moreover, the reduction of intercellular adhesion molecule-1 (ICAM-1) expression in Caco-2 cells can be considered directly correlated to the mucosal anti-inflammatory effect induced by the hydrocortisone and natural polyphenols. In conclusion, the study supported the use of Caco-2 cell as a model to compare and investigate the effect of different active substances on the mucosa and its diseases.

Involvement of inducible nitric oxide synthase and cyclooxygenase-2 in the anti-inflammatory effects of a red orange extract in human chondrocytes.

In the present study, a complex of compounds (red orange complex, ROC), obtained from three red orange varieties (Citrus sinensis varieties: Moro, Tarocco and Sanguinello), containing cyanidin glycosides, hydroxycinnamic acids, flavanone glycosides and ascorbic acid, was screened to discover new lead compounds in the suppression of the production of key molecules released during inflammatory events in interleukin-1beta (IL-beta) stimulated human primary chondrocytes. The expression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX)-2 and intercellular adhesion molecule-1 (ICAM-1), and the release of nitric oxide, prostaglandin (PG)E(2) and interleukin-8 (IL-8) were determined. Indomethacin was used as an anti-inflammatory drug reference. ROC acts as a potent inhibitor of iNOS and COX-2 gene expression while also suppressing the production of PGE(2) and nitrite in human chondrocytes. In addition, ROC induces a significant decrease in ICAM expression and IL-8 release. These findings suggest that ROC exerts anti-inflammatory effects probably through the suppression of COX-2 and iNOS expression.

Improved adhesion to mucosal cells of water-soluble chitosan tetraalkylammonium salts.

Chitosan is a natural polymer whose bioadhesive properties make it a useful material for filming over and protecting damaged or sensitive mucosae. Much effort has been expended to develop this employ, and new applications are in the offing. The aim of the present study was to optimize the synthesis under sonochemical conditions of water-soluble chitosan tetraalkylammonium salts and to assess the mucoadhesive properties of the resulting water-soluble cationic polyelectrolytes. Aqueous solutions of several tetralkylammonium chitosan derivatives, viz. N-trimethyl- (1), N-diethylmethyl- (2), N-carboxymethyl- (3) and N-[N,N-diethylaminomethyl(diethyldimethylene ammonium)(n)]methylchitosan (4) were tested along with the parent biopolymer and its citric acid salt (5), both at neutral and acidic pH. We used a published technique for evaluating in vitro bioadhesion to isolated buccal cells, a mucosal model that can predict bioadhesive behavior in vivo. Derivatives 1 and 4 gave the best results.