Anna Annunziata

miR-338-3p is over-expressed in blood, CFS, serum and spinal cord from sporadic amyotrophic lateral sclerosis patients

Amyotrophic lateral sclerosis (ALS) is a progressive and seriously disabling adult-onset neurological disease. Ninety percent of ALS patients are sporadic cases (sALS) with no clear genetic linkage. Accumulating evidence indicates that various microRNAs (miRNAs), expressed in a spatially and temporally controlled manner in the brain, play a key role in neuronal development. In addition, microRNA dysregulation contributes to some mental disorders and neurodegeneration diseases. In our research, the expression of one selected miRNA, miR-338-3p, which previously we have found over-expressed in blood leukocytes, was studied in several different tissues from sALS patients. For the first time, we detected a specific microRNA disease-related upregulation, miR-338-3p, in blood leukocytes as well in cerebrospinal fluid, serum, and spinal cord from sALS patients. Besides, staining of in situ hybridization showed that the signals of miR-338-3p were localized in the grey matter of spinal cord tissues from sALS autopsied patients. We propose that miRNA profiles found in tissue samples from sALS patients can be relevant to understand sALS pathogenesis and lead to set up effective biomarkers for sALS early diagnosis.

Acute and Chronic Effects of Noninvasive Ventilation on Left and Right Myocardial Function in Patients with Obstructive Sleep Apnea Syndrome: A Speckle Tracking Echocardiographic Study

In patients with obstructive sleep apnea syndrome (OSAS), repetitive hypoxia due to sleep‐induced apnea adversely affects the interaction between myocardial oxygen demand and supply, resulting in the development of subclinical cardiac dysfunction. The purpose of the study was to analyze the different involvement of left and right heart myocardial function in patients with OSAS treated with noninvasive ventilation (NIV).

Telomerase expression in amyotrophic lateral sclerosis (ALS) patients.

Telomerase and telomeric complex have been linked to a variety of disease states related to neurological dysfunction. In amyotrophic lateral sclerosis (ALS) patients, telomerase activity, as human telomerase reverse transcriptase (hTERT) expression, has not been characterized yet. Here, for the first time, we characterized telomerase and related pathway in blood sample and spinal cord from ALS patients compared with healthy controls. We found that hTERT expression level was significantly lower in ALS patients and was correlated either to p53 mRNA expression or p21 expression, pointing out the hypothesis that telomerase inhibition could be a pathogenetic contributor to neurodegeneration in ALS. As a consequence of the reduced telomerase activity, we identified shorter telomeres in leukocytes from sporadic ALS patients compared with healthy control group.

Primary paraganglioma of the lung: a case report.

IntroductionPrimary paraganglioma of the lung is a rare tumor of which few cases are reported in literature. Both solitary and diffuse primary pulmonary paragangliomas are described. The solitary form of this tumor is rare.Case presentationWe report the case of a 63-year-old Caucasian man with cough, intermittent palpitations and dyspnea. A contrast-enhanced computed tomography scan of his chest revealed a rounded, high-density lesion with irregular profiles measuring 24mm in diameter in the middle lobe. The lesion was suggestive of malignancy. Fine-needle aspiration cytology was performed. The results of the cytological tests were positive for malignant cells. Surgical resection was the choice of treatment. The results of the biochemical tests and postoperative histological examination allowed a definitive diagnosis: primary pulmonary paraganglioma.ConclusionsParagangliomas are identified and characterized with the use of computed tomography and other imaging methods, but for a definitive diagnosis, histopathological evaluation is necessary.We report a rare case of a primary pulmonary paraganglioma that was treated surgically. This case report adds valuable knowledge to the literature on pulmonary paragangliomas.

NIV in the Obese Patient After Surgery

Obese patients are at an increased risk of developing postoperative complications related to the respiratory and cardiovascular systems. The severity of these complications depends upon the preoperative respiratory status as well as intraoperative factors, such as the type and site of surgery performed and the anaesthesia that the patient is exposed to. During general anaesthesia and paralysis, functional residual capacity (FRC) markedly decreases and correlates with body weight leading to more atelectasis, severe alterations in respiratory mechanics and an increased risk of hypoxaemia. The mainstay of treatment of postoperative respiratory failure so far has been reintubation and mechanical ventilation, which are associated with complications like pneumonia, infections, increased costs, morbidity and mortality. Non-invasive ventilation (NIV) can reduce intubation rate, morbidity, mortality and the overall and intensive care unit (ICU) lengths of stay. Early initiation of a NIV therapy immediately after surgery may be beneficial, when residual drug effects are still present.

Cardiac Diseases in Hematology Cancer and Acute Respiratory Failure: Ventilatory Approach

In the last two decades, the survival of patients with hematological malignancies has improved because of new chemotherapeutic regimens, bone marrow transplantation, peripheral stem cell rescue, and better supportive measures [1]. Hematological neoplasms require aggressive treatments, implying a high risk of adverse events, including severe drug toxicity or the consequences of aplasia. The cardiotoxicity of anticancer agents depends on many factors such as the molecular site of action, the immediate and cumulative dose, the method of administration, and the presence of any underlying cardiac condition. Whereas anthracyclines remain the most common cause of chemotherapy-induced cardiomyopathy (CCMP), recently developed targeted therapies can also cause cardiac dysfunction [2]. From 15 to 20% of the hematological patients require supportive therapy in the ICU and acute respiratory failure (ARF) remains the first reason for admission to ICU in patient with hematological disease [3]. When there is no condition requiring immediate intubation noninvasive mechanical ventilation (NIV) has been advocated as the preferable first-line form of ventilatory support. Over the last decade, the use of NIV in patients with hematological malignancy has increased in everyday practice [4].

Wide-Ranging Analysis of MicroRNA Profiles in Sporadic Amyotrophic Lateral Sclerosis Using Next-Generation Sequencing

MicroRNA (miRNA) has emerged as an important regulator of gene expression in neurodegenerative disease as amyotrophic lateral sclerosis (ALS). In the nervous system, dysregulation in miRNA-related pathways is subordinated to neuronal damage and cell death, which contributes to the expansion of neurodegenerative disorders, such as ALS. In the present research, we aimed to profile dysregulation of miRNAs in ALS blood and neuromuscular junction as well as healthy blood control by next-generation sequencing (NGS). The expression of three upregulated miRNAs, as miR-338-3p, miR-223-3p, and miR-326, in the ALS samples compared to healthy controls, has been validated by qRT-PCR in a cohort of 45 samples collected previously. Bioinformatics tools were used to perform ALS miRNAs target analysis and to predict novel miRNAs secondary structure. The analysis of the NGS data identified 696 and 49 novel miRNAs which were differentially expressed in ALS tissues. In particular, in neuromuscular junction the differential expression of miR-338-3p, which we previously found upregulated in different types of ASL tissues, miR-223-3p, and miR-326 was elevated compared to normal control. ALS miRNAs gene target were significantly involved in neuronal related pathway as BDFN1 and HIF-1genes. This study presents the direct experimental evidence that, overall, miR-338-3p is highly expressed in ALS tissues including neuromuscular junction characterizing ALS from normal tissues. Beside, our analysis identified, for the first time, novel miRNAs highly expressed in ALS tissues. In conclusion, the results indicate that miRNAs has an important role in the diagnosis and treatment of ALS.

Continuous noninvasive ventilation for respiratory failure in patients with amyotrophic lateral sclerosis: current perspectives

Respiratory failure is a recognized late complication of amyotrophic lateral sclerosis. It is related to the neurological progression of the diseases with the impairment of the respiratory musculature. Survival and quality of life of amyotrophic lateral sclerosis patients is improved by using noninvasive mechanical ventilation. The rate of long-term mechanical ventilation is different within and between countries. Cultural factors, socioeconomic conditions, and physician attitude often influence the decision to start noninvasive ventilation. Technical elements, like the choice of the correct interface, solid caregivers support, and the communication between the patient and the physician are essential for achieving therapeutic goals, especially in the case of continuous treatment.

Mouthpiece ventilation in neuromuscular disease

Introduction: Ventilation with mouthpiece is used since 1990 and there are evidence in literature documenting effectiveness of treatment and increase compliance by the patient. Despite this, there is little knowledge and praticality of the use of non invasive mechanical ventilation (NIV) via a simple mouthpiece. Objective: To evaluate feasibility of mouthpiece ventilation (MPV) in patients with different neuromuscular disease who require NIV and were non compliant. Methods: we treated 3 patient with amyotrophic lateral sclerosis, 1 with Steiner syndrome, 3 with Duchenne dystrophy, 2 with quadriplegia due to spinal cord lesions. All patients were non compliant to NIV and previously refused NIV for claustrophobia, skin breakdowun, conjunctivitis and gastric distension. Each patient was reassessed and was proposed a new trial in NIV with the mouthpiece. Results: All patients tolerated treatment with MPV. The preferred mode was pressure control, inspiratory pressure was set beetween 10- 16, wich ensured an optimal tidal volume (8-10 mL/kg); no back up rate is needed for daytime use so no air blows into the patient9s face. Two patients presented sleep apoea syndrome with secondary respiratory failure, during night time were treated with spontaneous timed mode. Discussion: The mouthpiece should alvays be considered for patient with neuromuscular disease that has to start NIV; it is useful to promote a positive approach and a rapid acceptance of the new condition; it should be considered for patients poorly tolerant to NIV or use NIV many hours a day sometimes alternatin with the nasal or fullface mask. In our experience MPV alone or combined with other interfaces improves the quality of patient9s life and promotes greater adherence to NIV.

Noninvasive Mechanical Ventilation in Duchenne Muscular Dystrophy: What Have We Learned?

Duchenne muscular dystrophy (DMD) is caused by a mutation of the dystrophin gene. The progressive reduction in forced vital capacity predicts the development of respiratory failure, which evolves from nocturnal to daytime hypercapnia until the occurrence of respiratory symptoms. Treatment of pulmonary complications with noninvasive ventilatory support may improve quality of life and reduce the high morbidity, as well as early mortality, associated with DMD.