Role of nutritional therapy on dietary habits and glycemic control in insulin-treated kidney transplant patients with diabetes.

AIMS: To evaluate the effect of nutritional therapy on glycemic compensation and key cardio-renal risk markers in patients with diabetes and kidney transplant, on insulin treatment by Multiple Daily Injection (MDI) or Continuous Subcutaneous Insulin Infusion (CSII). METHODS: 34 patients with diabetes on insulin treatment and kidney transplant recipients were enrolled;12 participated in the structured nutritional program (intervention group), 22 patients (control group) did not receive nutritional protocol. Both groups were then divided into subgroups according to the method of insulin administration (MDI and CSII). RESULTS: Statistically significant reduction in fasting blood glucose values, glycosylated hemoglobin (HbA1c) and glycosuria were observed in both groups at the end of the study. The intervention group, significantly reduced total cholesterolemia and the glycemic index, together with reduced dietary intake of lipids, cholesterol, soluble carbohydrates and increased consumption of carbohydrates and fiber. These improvements were even more pronounced in patients treated with CSII. CONCLUSIONS: A proper nutritional approach optimize glycometabolic outcomes and contribute significantly to the reduction of the major cardiovascular risk factors in renal transplant patients.

Unintentional recurrent laryngeal nerve injuries following thyroidectomy: Is it the surgeon who pays the bill?

BACKGROUND: Thyroidectomy is one of the most common intervention in general surgery and, after the turn of the century, its rate has sharply increased, along with a worldwide increased incidence of differentiated thyroid cancers. Therefore, injuries of the recurrent laryngeal nerve have become one of the most frequent cause of surgical malpractice claims, mostly following surgery for benign pathology. MAIN BODY: Even if the incidence of definitive paralysis is generally lower than 3%, during the last 20 years in Italy, the number of claims for damages has sharply raised. As a consequence, a lot of defensive medicine has been caused by this issue, and a witch-hunt has been accordingly triggered, so determining mostly a painful and lasting frustration for the surgeons, who sometimes are compelled to pay a lot of money for increasing insurance premiums and lawyers fees. Recurrent laryngeal nerve injury should be considered as a potentially catastrophic predictable but not preventable event, rather than the result of a surgical mistake. CONCLUSION: Purposes of the Authors are analyzing incidence, conditions of risk, and mechanisms of recurrent laryngeal nerve injuries, underlining notes of surgical technique and defining medical practice recommendations useful to reduce the risk of malpractice lawsuits and judgments against surgeons.

The evolving field of kinase inhibitors in thyroid cancer.

Most of the genetic events implicated in the pathogenesis of thyroid cancer (TC) involve genes with kinase activity. Thus, kinase inhibitors (KIs) are very relevant in this field. KIs are considered the most suitable treatment for patients with iodine-refractory differentiated TC; these patients comprise the subgroup with the poorer prognosis. To date, only sorafenib has been approved for this indication, but promising results have been reported with several other KIs. In particular, lenvatinib has demonstrated excellent efficacy, with both progression-free survival and objective tumour response being better than with sorafenib. Despite being considered to be well tolerated, both sorafenib and lenvatinib have shown a remarkable toxicity, which has led to dose reductions in the majority of patients and to treatment discontinuation in a significant proportion of cases. The role of KIs in differentiated TC may be revolutionised by the finding that selumetinib may restore a clinical response to radioactive iodine (RAI). Vandetanib and cabozantinib have been approved for the treatment of advanced, progressive medullary TC (MTC). Nevertheless, the toxicity of both compounds suggests their selective use in those patients with strong disease progression. Treatment with the mTOR-inhibitor everolimus, alone or in combination with somatostatin analogues, should be studied in metastatic MTC patients with slow progression of disease, these representing the vast majority of patients. KIs did not significantly impact on the clinical features of anaplastic TC (ATC).

Impact of long-acting octreotide in patients with early-stage MEN1-related duodeno-pancreatic neuroendocrine tumours.

BACKGROUND: Somatostatin analogues (SSA) represent one of the main therapeutic option in patients affected with functioning well-differentiated neuroendocrine tumours (NETs). There are no studies specifically focusing on NETs associated with Multiple Endocrine Neoplasia type 1 (MEN1). AIM: To evaluate the efficacy of the long-acting SSA octreotide in MEN1 patients with early-stage duodeno-pancreatic NETs. PATIENTS AND METHODS: Forty patients with MEN1 were retrospectively evaluated. Twenty patients with evidence of one or more MEN1-related duodeno-pancreatic NETs < 20 mm in size (age range 26-61 years) were treated with octreotide long-acting octreotide (LAR) as first-line therapy. Treatment duration ranged 12-75 months. At the baseline radiological evaluation, multiple duodeno-pancreatic NETs (range 1-8, size 3-18 mm) were detected. RESULTS: An objective tumour response was observed in 10%, stable disease in 80% and progression of disease in 10% of cases. In six patients with abnormally increased CgA, gastrin and/or insulin serum concentrations, a significant clinical and hormonal response occurred in 100% of cases and was stable along the time. CONCLUSIONS: Therapy with SSA is highly safe and effective in patients with early-stage MEN1 duodeno-pancreatic NETs, resulting in long-time suppression of tumour and hormonal activity and 10% objective response. This suggests to early start therapy with SSA in patients with MEN1-related NETs.

Impact of cinacalcet hydrochloride in clinical management of primary hyperparathyroidism in multiple endocrine neoplasia type 1.

AIM: Primary hyperparathyroidism (PHPT) is one of main cause of morbidity in patients with multiple endocrine neoplasia type 1 (MEN1). Medical therapy with cinacalcet-hydrochloride may modify the therapeutic strategy of MEN1 related PHPT. We present an experience with cinacalcet-hydrochloride in two patients with MEN1 PHPT. METHODS: The study included two MEN1 patients belonging to the same family (a 50-year-old woman and her daughter aged 20 years) with PHPT secondary to multiple involvement of parathyroid glands and other MEN1 related tumors. As both patients refused to undergo parathyroid surgery, we decided to start medical treatment with cinacalcet at the dose of 30 mg/day, which was the first treatment for the youngest patient, while the oldest had already been treated with partial parathyroidectomy. Serum concentrations of PTH, calcium and phosphorus, 24-h urine calcium-to-creatinine ratio and renal-threshold-phosphate concentration were evaluated before and after therapy. RESULTS: Serum calcium and PTH levels were normalized after 1 and 6 months of therapy, respectively, and 60 and 54 months after the beginning of cinacalcet remained normal. Hypercalciuria, hypophosphoremia and renal-threshold-phosphate normalized during therapy with cinacalcet. At ultrasonography, parathyroid nodular lesion remained unchanged. Cinacalcet was well tolerated without occurrence of side effects. CONCLUSION: Cinacalcet seems to be highly effective in controlling PHPT in patients with MEN1 either in naïve patients or in those with postsurgical recurrence. If cinacalcet will be confirmed to ensure a long-time control of PHPT or even to prevent the development and progression of PHPT, this may led to modify the therapeutic strategy of MEN1 PHPT.

Assessment and clinical implications of RANK/RANKL/OPG pathway as markers of bone tumor progression in patients with NET harboring bone metastases.

INTRODUCTION: The impact on the survival of bone metastases (BM) in patients with neuroendocrine tumor (NET) is a matter of debate. BM have a key role in causing symptoms and in decreasing patients' quality of life. Although the mechanisms of the development of BM are not completely clear, it is now well understood that the Receptor Activator of Nuclear factor Kappa-B-/Ligand (RANK/RANKL)/osteoprotegerin (OPG) pathway plays a relevant role. AIM: To characterize the RANK/RANKL/OPG pathway in patients affected with NET. PATIENTS AND METHODS: Two cohorts of 15 patients each were enrolled in the study; one cohort was affected with NET without BM and the second cohort was affected with NET with BM. The serum RANK/RANKL/OPG pathway was assessed in both the groups. RESULTS: Serum OPG levels and RANKL/OPG ratio were lower and higher, respectively, in NET patients harboring BM than in those without BM. During the ROC analysis, a cut-off value of 1071 pg/ml for OPG and 0.62 for RANKL/OPG ratio were able to significantly distinguish between the two groups. CONCLUSIONS: This study indicates that RANK/RANKL/OPG pathway is imbalanced in patients with NET harboring BM. Specific alterations of this pathway could predict an early development of BM.

Interferon-γ inhibits integrin-mediated extracellular signal-regulated kinase activation stimulated by fibronectin binding in thyroid cells.

Hashimoto's thyroiditis (HT) is an autoimmune disorder characterized by the presence of specific antibodies and by a lymphocytic infiltration of the thyroid secreting inflammatory cytokines. Macrophages, lymphocytes, and cytokines play a pivotal role in both development and progression of Th1-mediated autoimmune diseases, and a direct role in the destruction of thyroid follicles and follicular cell function in autoimmune thyroiditis. Integrins are integral membrane receptors involved in cell-extra-cellular matrix (ECM) interaction with both structural and signaling functions. The integrin- ECM interaction is necessary for the correct function and survival of thyroid follicular cells. The purpose of this study was to determine the effect of cytokine stimulation on integrin expression and signaling in the thyroid cell. Primary cultures from normal thyroids were treated with interferon-γ (IFN-γ), INF-α, tumor necrosis factor-α, interleukin 1a or these cytokines all together. Integrin expression, cell adhesion to fibronectin (FN) and FN-stimulated extracellular signal-regulated kinase (ERK) phosphorylation were determined after cytokine treatment. IFN-γ and IFN-α were the most effective, reducing the expression of the integrin αvß3 and slightly increasing the α3ß1. Cell treatment with IFN-γ strongly impaired cell adhesion to FN. At the same time, the treatment with IFN-γ dramatically inhibited the stimulation of ERK phosphorylation induced by cell adhesion to FN. In conclusion, IFN-γ inhibits the expression of the integrin αvß3, reducing the cell adhesion to FN and the following intracellular signaling in thyroid cells in culture. These results suggest that integrins may be a target of the infiltrating lymphocytes and have a role in the pathogenesis of autoimmune thyroiditis.

Fibrous Variant of Hashimoto's Thyroiditis as a Diagnostic Pitfall in Thyroid Pathology.

Fibrous variant of Hashimoto's thyroiditis is a rare condition occurring in about 10% cases, mainly middle age people. It is characterized by an extensive fibrous proliferation without extension into the surrounding structures. A 55-year-old female was referred to our department for an unexplained onset of cervical discomfort. She presented a voluminous goiter of hard consistence, dyspnea and dysphagia. Given the compressive symptoms and the non-diagnostic result of the biopsy, a total thyroidectomy was performed. Microscopically the thyroid parenchyma was characterized by broad bands of fibrosis with severe atrophy of thyroid follicles and lymphocytic inflammatory infiltrate distributed within and around the lobules. In view of the morphological and immunohistochemical findings, a diagnosis of HTFV was made. The fibrosclerotic process is the key feature of several thyroid diseases so that the clinician and the pathologist have to consider that many diagnostic pitfalls can occur in this field. The differential diagnosis between HTFV and RD is sometimes arduous due to the partial clinical and morphological overlapping and to the poor efficacy of conventional cytology as well as pre-surgical biopsy. Considering these features, histological examination is mostly mandatory.

Thyroid nodules treated with percutaneous radiofrequency thermal ablation: a comparative study.

PURPOSE: Percutaneous radiofrequency thermal ablation (RTA) was reported as an effective tool for the management of thyroid nodules (TNs). The aim of this study was to investigate the effects of RTA and to establish whether they were treatment-related by comparison with a matched, untreated control group. PATIENTS AND METHODS: The study population included 40 patients with compressive TNs: 22 had nontoxic TNs, and 18 had toxic TNs and were treated with methimazole. In all patients, a fine-needle aspiration cytology was performed to exclude a thyroid malignancy. STUDY DESIGN: Twenty patients were treated with RTA (group A), and 20 others did not receive any treatment (group B). At baseline, age, gender, and TN features did not differ significantly between groups. All patients were clinically, biochemically, and morphologically evaluated at baseline and after 1, 3, 6, and 12 months. RESULTS: TN volume significantly decreased in group A (1.8 ± 0.3 ml at 12 months vs. 13.3 ± 1.8 ml at baseline; P < 0.0001) and remained stable in group B [11.7 ± 1.5 ml at 12 months vs. 11.2 ± 1.5 ml at baseline; P = not significant (NS)]. At 3-, 6-, and 12-month evaluations, TN volume was significantly lower in group A than in group B (P < 0.005). At the end of the follow-up, pressure symptoms were improved in all patients in group A but persisted unchanged in group B. In group A, hyperthyroidism completely recovered in 40% and improved in 40% of patients with toxic TNs, whereas it persisted in all patients with toxic TNs in group B. RTA was safe and well tolerated in all patients. CONCLUSIONS: RTA induced a marked TN volume shrinkage resulting in parallel improvement of pressure symptoms. In most patients with toxic TNs, hyperthyroidism significantly improved as well. RTA may represent a valid therapeutic approach in patients with TNs not receiving conventional treatments.

Thyroid diseases in elderly.

Thyroid diseases are the commonest endocrine disorders in the general population. In most of the cases, they are consistent with benign conditions which may be asymptomatic or affect people at a variable extent. Since they often represent chronic conditions their prevalence increases by age and reaches in elderly the highest rates. Thyroid nodules are a common clinical finding. Most subjects with thyroid nodules have few or no symptoms. Thyroid nodules are more commonly non-functioning. However, in elderly, toxic multinodular goiter is the most frequent cause of spontaneous hyperthyroidism and often, it emerges insidiously from nontoxic multinodular goiter. Although autoimmune thyroiditis is the most common cause of hypothyroidism in elderly subjects, other causes, such as drugs, neck radiotherapy, thyroidectomy or radioiodine therapy, are frequently observed among these subjects. A small subset of medications including dopamine agonists, glucocorticoids and somatostatin analogs affect thyroid function through suppression of TSH. Other medications that may affect TSH levels are metformin, antiepileptic medications, lithium carbonate and iodine-containing medications. Other drugs can alter T4 absorption, T4 and T3 transport in serum and metabolism of T4 and T3, such as proton-pump inhibitors and antacids, estrogens, mitotane and fluorouracil, phenobarbital and rifampin. Amiodarone administration is associated with thyrotoxicosis or hypothyroidism. Thyroid cancer has similar characteristics in elderly as in general population, however the rate of aggressive forms such as the anaplastic histotype, is higher in older than younger subjects. Diagnosis of thyroid diseases includes a comprehensive medical history and physical examination and appropriate laboratory tests. A correct diagnosis of thyroid diseases in the elderly is crucial for proper treatment, which consists in the removal of medications that may alter thyroid function, in the use of levo-thyroxine in case of hypothyroidism, anti-thyroid drugs in case of hyperthyroidism and use of surgery, radioiodine therapy and percutaneous ablative procedures in selected cases. In conclusion, thyroid diseases in patients older than 60 years deserve attention from different points of view: the prevalence is different from the young adult; symptoms are more nuanced and makes difficult the diagnosis; age and comorbidity often force therapeutic choices and may limit safety and efficacy of therapy. Finally, in elderly patients for whom specific therapy is necessary, more gradual and careful therapeutic approach and close follow-up are recommended in order to minimize the alterations of thyroid function which are induced by many drugs commonly used in clinical practice.

Real-time subtyping via PFGE reveals potential epidemiological relatedness among human salmonellosis cases in Northern Italy.

AIM: This study aimed to assess the applicability of a combined approach of traditional and molecular epidemiology in order to detect salmonellosis outbreaks in the Piedmont region (Italy), characterized by high Salmonella prevalence. METHODS AND RESULTS: Pulsed field gel electrophoresis (PFGE) was used in real-time and in combination with clinical surveillance to assess the relatedness of salmonellosis human cases; subsequently, PFGE profiles of clinical isolates were compared with those of isolates from food items collected during the same study period to identify putative food sources of Salmonella. The real-time subtyping approach allowed the identification of an outbreak (21 isolates), which was undetected by epidemiological surveillance. CONCLUSIONS: Traditional epidemiological investigation did not allow the formulation of hypotheses on food items possibly associated with the outbreak owing mainly to patients' difficulties in remembering foods they ate, and the tendency of health-care professionals to direct patient's suspicion towards specific food items. SIGNIFICANCE AND IMPACT OF THE STUDY: This finding highlighted the value of real-time molecular subtyping in salmonellosis outbreak identification. In order to improve national epidemiological investigations implementing public health agency network and planning, information campaigns for health-care professionals are required.

A new strategy for treatment of a congenital arteriovenous fistula of the neck. Case report.

Congenital arteriovenous fistulas (AVF) without associated vascular malformations are uncommon. Only a very few cases of AVF have been reported in the neck. We describe our findings in a patient with AVF treated by a combined vascular and endovascular approach.

Human flash-VEP and quantitative EEG are independently affected by acute scopolamine.

Scopolamine in acute intramuscular doses of 0.25-0.75 mg reduced the P2-N3 flash-VEP amplitude and, in the quantitative EEG, the 8.5-12.0 Hz power and total power in 8 healthy young male volunteers. The effects on flash-VEP and EEG total power were dose dependent and were evident 30 min and 90 min respectively after drug administration, regardless of dose. The reduction in 8.5-12.0 Hz power was limited to the 0.50 and 0.75 mg doses. No systematic effects on the pattern-VEP were observed. Possible interferences with flash- or pattern-VEP amplitude of the scopolamine-induced EEG changes were identified and removed by regression analysis and computation of VEP residuals from the regression function. The P2-N3 flash-VEP residuals proved EEG independent and showed relationships with dose and time after drug administration that were superimposable on those of the original data, with comparable significance levels at the drug/placebo and pre/postdrug statistical comparisons. The results indicate that VEP estimates of drug effects which are independent from EEG changes can be identified in human studies and allow some inference on the cholinergic specificity of the systems affecting late flash-VEP components. The statistical approach used in this study is suitable for application in VEP studies when effects of interacting factors are to be expected.