Management of respiratory complications and rehabilitation in individuals with muscular dystrophies: 1st Consensus Conference report from UILDM - Italian Muscular Dystrophy Association (Milan,January 25-26, 2019)

Respiratory complications are common in the patient with muscular dystrophy. The periodic clinical and instrumental respiratory evaluation is extremely important. Despite the presence in the literature of updated guidelines, patient associations often report lack of knowledge of these pathologies, particularly in peripheral hospitals. The purpose of this work, inspired by the Italian Muscular Dystrophy Association (UILDM) is to improve management of respiratory problems necessary for the management of these patients complex. To this end, the main items that the specialist can meet in the follow-up of these pathologies have been analyzed and discussed, among which the respiratory basal evaluation, the criteria of adaptation to non-invasive ventilation, management of bronchial secretions, situations of respiratory emergency, indications for tracheostomy and the subject of advance directives of treatment (DAT).Key words: respiratory failure, muscular dystrophy, cough efficacy, spirometry, polygraphy, non-invasive ventilation, arterial blood gases, cough machine, invasive ventilation, tracheostomy, mechanical ventilation     

A decomposition approach for the combined master surgical schedule and surgical case assignment problems

This research aims at supporting hospital management in making prompt Operating Room (OR) planning decisions, when either unpredicted events occur or alternative scenarios or configurations need to be rapidly evaluated. We design and test a planning tool enabling managers to efficiently analyse several alternatives to the current OR planning and scheduling. To this aim, we propose a decomposition approach. More specifically, we first focus on determining the Master Surgical Schedule (MSS) on a weekly basis, by assigning the different surgical disciplines to the available sessions. Next, we allocate surgeries to each session, focusing on elective patients only. Patients are selected from the waiting lists according to several parameters, including surgery duration, waiting time and priority class of the operations. We performed computational experiments to compare the performance of our decomposition approach with an (exact) integrated approach. The case study selected for our simulations is based on the characteristics of the operating theatre (OT) of a medium-size public Italian hospital. Scalability of the method is tested for different OT sizes. A pilot example is also proposed to highlight the usefulness of our approach for decision support. The proposed decomposition approach finds satisfactory solutions with significant savings in computation time.     

Aortic Stiffness Assessed by Global Pulse Wave Velocity in Postmenopausal Women: An Ultrasonographic Study

Objective: The first goal of our study was to investigate major determinants of aortic stiffness in postmenopausal women using an echocardiographic method to calculate global pulse wave velocity (PWVg) rather than the less accurate carotid–femoral pulse wave velocity (PWVc). The second goal was to relate PWVg to the absolute risk of major cardiovascular (CV) events estimated by CV risk factors. Patients and methods: Two hundred forty‐four consecutive women who presented to our heart station were screened. One hundred twenty‐two were postmenopausal, either natural or surgical, whereas 122 were premenopausal. The mean age of the patients was 54 ± 13 years. Individuals were categorized as current smokers, former smokers, or nonsmokers and hypertensive or not. Hypercholesterolemia and diabetes mellitus were defined. Aortic stiffness was assessed by PWVg measured with pulsed Doppler, the interval between the beginning of QRS complex and the foot of the systolic upstroke in the Doppler spectral envelope was calculated at the aortic valve site and at the right common femoral artery. PWVg was calculated between the aortic valve and right common femoral artery by dividing the straight line distance between the two by the transit time. Results: There was a highly significant statistical difference (P < 0.0012) in PWVg between menstruating women and postmenopausal women. Similarly, this difference in PWVg was also noted among the menstruating population (P < 0.0014) when comparing normotensive women and hypertensive women. In postmenopausal women, PWVg was 6.8 m/sec in normotensive women and 7.56 m/sec in hypertensive women (P < 0.007). Conclusion: PWVg was increased in postmenopausal women compared with menstruating women. Systemic hypertension has an independent, but additive effect on aortic stiffness assessed by PWVg. Our study supports the usefulness of the assessment of aortic stiffness as a marker of CV disease and to identify subjects at risk at an early age.     

Increased expression of glutamine transporter SNAT2/SLC38A2 promotes glutamine dependence and oxidative stress resistance,and is associated with worse prognosis in triple-negative breast cancer

Background Glutamine (Gln) is an abundant nutrient used by cancer cells. Breast cancers cells and particularly triple-receptor negative breast cancer (TNBC) are reported to be dependent on Gln to produce the energy required for survival and proliferation. Despite intense research on the role of the intracellular Gln pathway, few reports have focussed on Gln transporters in breast cancer and TNBC.Methods The role and localisation of the Gln transporter SLC38A2/SNAT2 in response to Gln deprivation or pharmacological stresses was examined in a panel of breast cancer cell lines. Subsequently, the effect of SLC38A2 knockdown in Gln-sensitive cell lines was analysed. The prognostic value of SLC38A2 in a cohort of breast cancer was determined by immunohistochemistry.Results SLC38A2 was identified as a strongly expressed amino acid transporter in six breast cancer cell lines. We confirmed an autophagic route of degradation for SLC38A2. SLC38A2 knockdown decreased Gln consumption, inhibited cell growth, induced autophagy and led to ROS production in a subgroup of Gln-sensitive cell lines. High expression of SLC38A2 protein was associated with poor breast cancer specific survival in a large cohort of patients (p = 0.004), particularly in TNBC (p = 0.02).Conclusions These results position SLC38A2 as a selective target for inhibiting growth of Gln-dependent breast cancer cell lines.Subject terms: Breast cancer, Cancer metabolism     

Temperature monitoring and lesion volume estimation during double-applicator laser-induced thermotherapy in ex vivo swine pancreas: a preliminary study

Tissue temperature distribution plays a crucial role in the outcome of laser-induced thermotherapy (LITT), a technique employed for neoplasias removal. Since recent studies proposed LITT for pancreatic tumors treatment, assessment of temperature and of its effects around the laser applicator could be useful to define optimal laser settings. The aims of this work are temperature monitoring and measurement of ablated tissue volume in an ex vivo porcine pancreas undergoing double-applicator LITT. A three-dimensional numerical model is implemented to predict temperature rise and volumes of ablated tissue in treated pancreas. Experiments are performed to validate the model, with two modalities: (1) 12-fiber Bragg grating sensors are adopted to monitor the heating and cooling during LITT at several distances from the applicators tip, and (2) 1.5-T MR imaging is used to estimate the ablated volume. Experimental data agree with theoretical ones: at 2 mm from both applicators tips, the maximum temperature increase is approximately 60 °C downward from the tips, while it increases of about 40 °C and 30 °C, respectively, at the level and upward from the tips. This behavior occurs also at other distances, proving that the tissue downward from the tip is mostly heated. Furthermore, the estimated volume with MRI agrees with theoretical one (i.d., 0.91?±?0.09 vs. 0.95 cm³). The encouraging results indicate that the model could be a suitable tool to choose the optimal laser settings, in order to control the volume of ablated tissue.