IntroductionPressure-support ventilation, is widely used in critically ill patients; however, the relative contribution of patient’s effort during assisted breathing is difficult to measure in clinical conditions. Aim of the present study was to evaluate the performance of ultrasonographic indices of diaphragm contractile activity (respiratory excursion and thickening) in comparison to traditional indices of inspiratory muscle effort during assisted mechanical ventilation.MethodConsecutive patients admitted to the ICU after major elective surgery who met criteria for a spontaneous breathing trial with pressure support ventilation were enrolled. Patients with airflow obstruction or after thoracic/gastric/esophageal surgery were excluded. Variable levels of inspiratory muscle effort were achieved by delivery of different levels of ventilatory assistance by random application of pressure support (0, 5 and 15 cmH2O). The right hemidiaphragm was evaluated by B- and M-mode ultrasonography to record respiratory excursion and thickening. Airway, gastric and oesophageal pressures, and airflow were recorded to calculate indices of respiratory effort (diaphragm and esophageal pressure–time product).Results25 patients were enrolled. With increasing levels of pressure support, parallel reductions were found between diaphragm thickening and both diaphragm and esophageal pressure–time product (respectively, R = 0.701, p < 0.001 and R = 0.801, p < 0.001) during tidal breathing. No correlation was found between either diaphragm or esophageal pressure–time product and diaphragm excursion (respectively, R = −0.081, p = 0.506 and R = 0.003, p = 0.981), nor was diaphragm excursion correlated to diaphragm thickening (R = 0.093, p = 0.450) during tidal breathing.ConclusionsIn patients undergoing in assisted mechanical ventilation, diaphragm thickening is a reliable indicator of respiratory effort, whereas diaphragm excursion should not be used to quantitatively assess diaphragm contractile activity.Electronic supplementary materialThe online version of this article (doi:10.1186/s13054-015-0894-9) contains supplementary material, which is available to authorized users.

PurposeHaving previously demonstrated that tissue miR-375 expression in medullary thyroid carcinoma (MTC) tissues is linked to prognosis, the aim of this study was to assess the diagnostic and prognostic value of circulating miR-375 levels in MTC patients.MethodsA series of 68 patients with MTC was retrospectively retrieved and assessed in terms of their clinicopathological characteristics. MiR-375 levels were measured in all patients’ presurgical blood samples. Both serum and tissue levels were tested prior to surgery in a subgroup of 57 patients. Serum miR-375 levels were also measured in serum from 49 patients with non-C-cell thyroid nodular diseases (non-CTN), 14 patients with pheochromocytoma, and 19 healthy controls.ResultsCirculating miR-375 levels were 101 times higher in the serum of patients with MTC than in all other patients and controls, with no overlap (P &lt; 0.01). No correlation emerged between serum and tissue miR-375 levels. Serum miR-375 levels were higher in MTC patients with N0 than in those with N1 disease (P = 0.01), and also in patients who were biochemically cured than in those who were not (P = 0.02). In the whole series of patients and controls, calcitonin (CT) and serum miR-375 levels were correlated at diagnosis (R2 = 0.40, P &lt; 0.01), but in a U-shaped manner: a positive correlation was found with low CT levels, then the correlation turns negative as CT rises (in MTC patients). A negative correlation was indeed found in MTC patients between serum miR-375 and CT (R2 = −0.10, P = 0.01). On ROC curve analysis, a cut-off of 2.1 for serum miR-375 proved capable of distinguishing between MTC patients and the other patients and controls with a 92.6% sensitivity and a 97.6% specificity (AUC: 0.978, P &lt; 0.01).ConclusionsSerum miR-375 levels can serve as a marker in the diagnosis of MTC, with a remarkable specificity. Serum miR-375 also proved a novel marker of prognosis in this disease. Further in vitro experiments to corroborate our results are currently underway.

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Insulin secretion is reduced in IR regardless the type of anesthesia. PCA increases insulin secretion, whereas epidural decreases it in patients with normal insulin sensitivity. These findings implicate that after surgery insulin administration is advisable in patients with preoperative insulin resistance while it should be given cautiously in those with normal preoperative insulin sensitivity.

IntroductionMedullary thyroid cancer (MTC) is a rare type of neuroendocrine tumor that produces a hormone called calcitonin (CT). Thyroidectomy is the preferred treatment for MTC, as chemotherapy has been shown to have limited effectiveness. Targeted therapy approaches are currently being used for patients with advanced, metastatic MTC. Several studies have identified microRNAs, including miR-21, as playing a role in the development of MTC. Programmed cell death 4 (PDCD4) is a tumor suppressor gene that is an important target of miR-21. Our previous research has shown that high levels of miR-21 are associated with low PDCD4 nuclear scores and high CT levels. The aim of this study was to investigate the potential of this pathway as a novel therapeutic target for MTC.MethodsWe used a specific process to silence miR-21 in two human MTC cell lines. We studied the effect of this anti-miRNA process alone and in combination with cabozantinib and vandetanib, two drugs used in targeted therapy for MTC. We analyzed the effect of miR-21 silencing on cell viability, PDCD4 and CT expression, phosphorylation pathways, cell migration, cell cycle, and apoptosis.ResultsSilencing miR-21 alone resulted in a reduction of cell viability and an increase in PDCD4 levels at both mRNA and protein levels. It also led to a reduction in CT expression at both mRNA and secretion levels. When combined with cabozantinib and vandetanib, miR-21 silencing did not affect cell cycle or migration but was able to enhance apoptosis.ConclusionSilencing miR-21, although not showing synergistic activity with TKIs (tyrosine kinase inhibitors), represents a potential alternative worth exploring as a therapeutic target for MTC.