Giuseppe Fiorentino

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.

Obesity Duration Is Associated to Pulmonary Function Impairment in Obese Subjects

Obesity is associated with pulmonary function disturbances. We hypothesized that lung function decreases with increasing duration of obesity. We evaluated pulmonary function tests (PFTs) in 188 nonsmoking subjects with primary obesity (aged 8–76 years; 36% with systemic hypertension). Duration of obesity was assessed by questionnaire in adults, and by height and weight growth patterns in children. Asthma and/or other allergic diseases were investigated by standardized questionnaires. BMI and BMI‐standard deviation scores (SDS) were 38.7 and 2.4 kg/m2, respectively. Forty‐six percent of patients were atopic. Among subjects with ever asthma (33%), 20 had current asthma (11% of the total). Forced vital capacity (FVC), forced expiratory volume in 1 s, total lung capacity (TLC), and functional residual capacity (FRC) were 103, 104, 95, and 76% predicted, respectively. Mean duration of obesity was 8.3 years. Compared with subjects who had been obese for ≤5 years, patients who had been obese for >15 years had significantly lower values on PFTs (P < 0.05). In subjects with systemic hypertension, PFTs were lower than in patients without hypertension (P < 0.01). Duration of obesity was significantly related to all PFTs (P ≤ 0.001). In a multiple regression analysis where duration and severity of obesity, hypertension, atopy, asthma, and family history of atopic diseases were independent variables, duration of obesity was a predictor of lower PFTs (P < 0.01). Of the remaining variables, only hypertension contributed to lower lung volumes. In obese individuals, lung function was significantly lower in subjects with greater years of obesity. Fat loss programs should be encouraged to prevent late pulmonary function impairment.

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.

Management of acute respiratory failure in interstitial lung diseases: overview and clinical insights

BackgroundInterstitial lung diseases (ILDs) are a heterogeneous group of diseases characterized by widespread fibrotic and inflammatory abnormalities of the lung. Respiratory failure is a common complication in advanced stages or following acute worsening of the underlying disease. Aim of this review is to evaluate the current evidence in determining the best management of acute respiratory failure (ARF) in ILDs.MethodsA literature search was performed in the Medline/PubMed and EMBASE databases to identify studies that investigated the management of ARF in ILDs (the last search was conducted on November 2017).ResultsIn managing ARF, it is important to establish an adequate diagnostic and therapeutic management depending on whether the patient has an underlying known chronic ILD or ARF is presenting in an unknown or de novo ILD. In the first case both primary causes, such as acute exacerbations of the disease, and secondary causes, including concomitant pulmonary infections, fluid overload and pulmonary embolism need to be investigated. In the second case, a diagnostic work-up that includes investigations in regards to ILD etiology, such as autoimmune screening and bronchoalveolar lavage, should be performed, and possible concomitant causes of ARF have to be ruled out.Oxygen supplementation and ventilatory support need to be titrated according to the severity of ARF and patients’ therapeutic options. High-Flow Nasal oxygen might potentially be an alternative to conventional oxygen therapy in patients requiring both high flows and high oxygen concentrations to correct hypoxemia and control dyspnea, however the evidence is still scarce. Neither Non-Invasive Ventilation (NIV) nor Invasive Mechanical Ventilation (IMV) seem to change the poor outcomes associated to advanced stages of ILDs. However, in selected patients, such as those with less severe ARF, a NIV trial might help in the early recognition of NIV-responder patients, who may present a better short-term prognosis. More invasive techniques, including IMV and Extracorporeal Membrane Oxygenation, should be limited to patients listed for lung transplant or with reversible causes of ARF.ConclusionsDespite the overall poor prognosis of ARF in ILDs, a personalized approach may positively influence patients’ management, possibly leading to improved outcomes. However, further studies are warranted.

Continuous Mouthpiece Daytime Amyotrophic Lateral Sclerosis in Noninvasive Ventilation: Definitive Solid Therapy?

To the Editor: Treatment options for amyotrophic lateral sclerosis (ALS) are very limited.[1][1] In some cases, noninvasive ventilation (NIV) by mouthpiece ventilation is a technique that is useful in the treatment of chronic ventilatory failure, particularly in neuromuscular patients.[2][2] The

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].

Critical evaluation of the treatment for Duchenne muscular dystrophy during the transition from adolescence to adulthood.

CRITICAL EVALUATION OF THE TREATMENT FOR DUCHENNE MUSCULAR DYSTROPHY DURING THE TRANSITION FROM ADOLESCENCE TO ADULTHOOD In their article, Pandya et al. assessed the health profiles of 208 adults with Duchenne muscular dystrophy (DMD) in 5 states in the USA. Many of the interventions with this condition are needed in the second decade, a critical period as individuals transition from adolescence to adulthood and switch from having pediatric to adult providers. These changes create additional stresses on the affected individuals and their families. Their data are similar to those in the literature, but they do not reflect some aspects of the issues we consider to be important. First, there are no data regarding physical therapy. For adults, maintaining upper extremity function, especially finger flexion, helps to preserve functional abilities that enable independence; in conjunction with the prevention of painful contractures and stiffness, this can improve quality of life. Stretching of the lower extremities should also continue after the period of ambulation and into adulthood because this can provide relief from symptoms of stiffness and can improve pain. In addition to stretching, patients can benefit from therapy in a pool with assistance and support for the head and the neck, where the buoyancy provides a degree of freedom of movement. Second, the authors addressed therapy for heart failure but not cardiac arrhythmias. If ejection fraction is <35%, or if symptomatic ventricular arrhythmias occur, the risks and benefits of implantable cardioverter-defibrillator use should be considered and discussed with the patient and family. This is a difficult topic for adolescents and young adults. Third, decreased mobility and weakened cough place DMD patients at increased risk of pulmonary infections. There are some patients (32.7%) who use a cough-assist device, but we believe this treatment is essential for reducing morbidity and mortality. One of the more difficult aspects associated with invasive mechanical ventilation is that it requires a caregiver to be present 24 hours/day. Nursing support is not well covered by most insurance plans in the USA and this places both financial and emotional strain on families. Fourth, a variety of social issues are becoming more evident as the adult DMD population grows. These issues are as important as the physical ones just described, and include the need for quality care, personal independence, educational and employment opportunities, meaningful relationships, and sexual activity. A social worker is also an integral part of the multidisciplinary team. Development of outcome measures to monitor progression in adult DMD is fundamental. To ensure good quality of life, the transition of care from childhood and adolescence to adulthood needs timely planning, to permit a smooth transition. Ideally, care should coordinated by a multidisciplinary team, to monitor and address needs and maximize health. It is necessary to have a structured transition phase from pediatric to adult care in DMD. This highlights the importance of outpatient multidisciplinary follow-up. Further clinical trials are needed to confirm these observations.