The role of EIF1AX in thyroid cancer tumourigenesis and progression.

PURPOSE: The EIF1AX gene was recently described as a new thyroid cancer-related gene. Its mutations were mainly reported in poorly differentiated (PDTC) and anaplastic thyroid cancers (ATC), but also in well-differentiated thyroid cancer (WDTC) and in benign thyroid lesions, although less frequently. Our aim was to address whether EIF1AX mutations are present in the different stages of thyroid tumourigenesis (from hyperplasia to well-differentiated and to poorly differentiated/undifferentiated lesions), and to clarify its role in this process. METHODS: We analysed the EIF1AX gene in a series of 16 PDTC and ATC cases with coexistent well-differentiated regions and/or benign lesions. In EIF1AX mutant cases we also assessed the presence of RAS genes mutations. RESULTS: We identified the mutation p.Ala113_splice in the EIF1AX gene in two PDTCs (neither present in the well-differentiated counterparts nor in the benign areas). One of these tumours also evidenced the mutation p.Glu61Arg in NRAS in both poorly and well-differentiated regions, further suggesting that the EIF1AX p.Ala113_splice mutation could be associated with tumoural progression. In another patient we did not find any EIF1AX alteration in the PDTC component, but we detected the EIF1AX p.Gly6_splice mutation in the PTC area (both regions were RAS wild-type). This mutation did not seem to be related with dedifferentiation. CONCLUSIONS: According to our results, distinct mutations on EIF1AX may be related to different phenotypes/behaviours. Despite being a small series, which reflects the difficulty in retrieving PDTC and ATC surgical samples with well-differentiated and/or benign areas, our study may provide new insights into thyroid cancer tumourigenesis and dedifferentiation.

[Study with thoracic and abdominal spiral CT in intensive care unit patients]. / Studio mediante TC spirale del torace e dell'addome nei pazienti ricoverati nei reparti di rianimazione.

INTRODUCTION: The severe clinical conditions of intensive care unit patients need frequent imaging studies to detect the pathologic changes in the patients' situation and to plan the correct therapeutic management. The yield of bedside plain radiography is often not diagnostic but moving the patients to the radiology department could affect their clinical conditions. Conventional CT is difficult to perform in these patients because they need continuous assistance and cannot cooperate during the diagnostic examination. MATERIAL AND METHODS: The authors examined with Spiral CT 46 unconscious patients in poor clinical conditions who presented a variety of pulmonary and abdominal diseases. Thirty coma patients were submitted to bedside chest radiography and then to Spiral CT because there was disagreement between the radiographic and the clinical findings. Sixteen patients with abdominal conditions underwent Spiral Ct, 11 of them after bedside US. The chest and abdomen were examined with Spiral CT in 2/16 patients and the abdomen only in 5 cases; twenty-two of 46 patients were under assisted ventilation. During all the Spiral CT studies, the patients had their arms along the body. Spiral CT results were compared with those of bedside chest radiography in 30 cases and with those of bedside abdominal US in 11 patients. DISCUSSION AND CONCLUSIONS: Spiral CT is a fast examination technique with no major artifacts which can be used safely also in unconscious patients. It confirmed a variety of pathologic conditions which may be misdiagnosed by conventional chest radiography, which improves the care of these patients. Bedside plain radiography is limited by several factors depending on the patient (no cooperation, variable respiration, still decubitus), the examination technique (X-ray projection, exposure, poor diagnostic yield), and the anatomical region of interest (mediastinal vessels). Even though our technical standard for conventional radiography was high, Spiral CT was better in detecting parenchymal consolidation and pleural effusion, a missed pneumothorax or thromboembolic disease. We always performed Spiral CT when the clinical findings did not match the results of bedside plain radiography. Moving the patients was very easy because the intensive care unit in our hospital is in the same building as the radiology department and there were dedicated devices supporting the coma patients.

[Acute iatrogenic myopathy during treatment of status asthmaticus. Our experience and review of the literature]. / Miopatia acuta iatrogena nel corso del trattamento dello stato di male asmatico. Nostra esperienza e revisione della letteratura.

CASE REPORT: A young man was admitted to the ICU for acute asthmatic respiratory failure. He was sedated with propofol, curarized with pancuronium and put on mechanical ventilation for 15 day because of the persistent asthmatics crisis. Drug therapy for asthma included high-dose corticosteroids. When sedation and paralysis were stopped, the patient, that was fully conscious, showed flaccid quadriplegia. A muscular biopsy showed elective loss of the myosin thick filaments. Electrophysiologic evaluation was compatible with both neurologic or muscular pathology. The evolution of the disease was good; a drop-out performed 5 months later showed a complete motor recovery. DISCUSSION: This case report confirms that in some patients, intensive treatment of status asthmaticus may cause myopathy. Only recently this myopathy has been correlated to an interaction between steroids and neuromuscular blockers. Many experimental and clinical observations suggest a negative interaction between steroids and non-depolarizing curare derivatives. In the case reported here, diagnosis was based on electrophysiologic examination and above all on muscular biopsy. CONCLUSION: The occurrence of an acute toxic myopathy should always be taken into account, considering the high number of patients admitted with respiratory failure requiring steroid treatment and curare administrative for mechanical ventilation. It therefore seems reasonable to reduce steroid therapy as soon as possible with a periodic suspension of curare administration. Curare usage should be critically evaluated. Some basic examination such as serum CPK monitoring should allow early detection of muscular damage.