Independent of disease severity or the need for hospitalisation, patients that experience coronavirus disease 2019 (COVID-19) are at high risk of having one or more sequelae or new symptoms within 3 months after the acute infection, a condition internationally recognised as “long COVID” (l-COVID) [1]. Depending on reports, the prevalence of patients that present with at least one residual symptom once recovered from the acute event varies from 43% to 62% [2], leading to a significant economic burden with estimated direct and indirect costs reaching $3.7 trillion in the USA [3]. According to a recent meta-analysis that included 194 studies conducted on patients with l-COVID, fatigue and breathlessness are two of the leading symptoms reported, independent of the severity of disease [2]. Despite reduced resting lung volumes and DLCO, patients with long COVID and dyspnoea have similar physiological response to exercise to healthy subjects. DLCO impairment can marginally explain heterogeneity of complex syndromes such as long COVID. https://bit.ly/40j4aX6

Background: Transfusion-dependent ß-thalassemia (TDT) is a disorder due to mutations in the gene encoding the ß-globin chain causing a reduced or absent production of haemoglobin A leading to severe anaemia and lifelong transfusion dependence. Gene therapy has now been accepted as a possible alternative cure to allogeneic bone marrow (BM) transplantation. Aims: We developed a gene therapy approach based on autologous mobilized hematopoietic stem cell transduced by lentiviral vector, expressing human ß-globin gene, administered by intrabone injection, following a myeloablative conditioning (NCT02453477). Methods and Results: Nine patients with severe TDT with different genotypes have been treated with a drug product with a median cell dose of 19.5x106 CD34+ cells/kg, a transduction efficiency from 38 to 77% and a median vector copy number/genome (VCN) in bulk CD34+ cells of 0.9 (range: 0.7–1.5). Overall, gene therapy was generally well-tolerated with no adverse events related to the investigational product. No severe infectious-related adverse events were reported, except for those related to neutropenia as expected after myeloablative conditioning. Polyclonal vector integrations profiles with no evidence of clonal dominance have been detected in all patients with the expected genomic distribution for lentiviral vectors. Clinical outcome showed a reduction of transfusion requirement both in frequency and volume in adult patients up to more than 50%. Among the pediatric patients, 4 out of 6 discontinued transfusions shortly after gene therapy and are transfusion-independent at the last follow-up (up to 75 months). A robust and persistent engraftment was observed in 7 out of 9 patients, with a marking of BM progenitors that, in engrafted patients, ranged between 25.3 and 79.8% and with a median VCN in CD34+ cells of 0.53 (range: 0.34–2.21). As a relevant target for transgene expression, BM erythroid cells were stably marked (VCN range 0.3 - 2.5). Summary and Conclusions: A longer follow-up will provide further results on long-term clinical efficacy and safety of this approach. References 1. Marktel et al, Nat Med 2019; 25(2):234

In an obstructive sleep apnea rabbit model, heliox never abolishes tidal inspiratory flow limitation (IFL), but increases inspiratory flow and tidal volume, substantially in some and nearly nil in other animals. Positive response to heliox cannot be predicted on the basis of breathing pattern characteristics or upper airway resistance that preceded IFL onset, but is related to the mechanical and geometrical features of upper airway collapsible segment, as indicated by model simulation.

Chronic obstructive pulmonary disease (COPD) patients often experience tidal expiratory flow-limitation (tEFL), a condition causing respiratory and cardiovascular detrimental effects. As the appearance of tEFL should increase expiratory (Rexp) relative to inspiratory (Rins) resistance, we hypothesized that Rexp/Rins can be used to detect tEFL. Rexp/Rins was measured with a commercial plethysmograph in 109 healthy subjects and, before and after bronchodilation (BD), in 64 COPD patients, 36 with and 28 without tEFL according to the NEP technique. Before BD, the median (interquartile range) of Rexp/Rins was significantly greater (P < 0.001) in COPD patients with tEFL (2.47(3.06;7.07)) than in COPD patients without tEFL (1.63(1.44;1.82)) and in healthy subjects (1.52(1.35;1.62)). In COPD patients Rexp/Rins above 1.98 predicted the presence of tEFL with 96 % specificity and 92 % sensitivity, Rexp2/Rins performing even better. After BD the predictive ability of Rexp/Rins slightly declined, but remained elevated. The non-invasive measurement of Rexp/Rins is an easy, inexpensive, routinely usable method to detect tEFL in spontaneously breathing COPD subjects.

Since its introduction in the clinical practice, body plethysmography has assisted pneumologists in the diagnosis of respiratory diseases and patients' follow-up, by providing easy assessment of absolute lung volumes and airway resistance. In the last decade, emerging evidence suggested that estimation of alveolar pressure by electronically-compensated plethysmographs may contain information concerning the mechanics of the respiratory system which goes beyond those provided by the simple value of airway resistance or conductance. Indeed, the systematic study of expiratory alveolar pressure-flow loops produced during spontaneous breathing at rest has shown that the marked expansion of expiratory loops in chronic obstructive pulmonary disease patients mainly reflects the presence of tidal expiratory flow-limitation. The presence of this phenomenon can be accurately predicted on the basis of loop-derived parameters. Finally, we present results suggesting that plethysmographic alveolar pressure may be used to estimate non-invasively intrinsic positive end-expiratory pressure (PEEPi) in spontaneously breathing patients, a task which previously could be only accomplished by introducing a balloon-tipped catheter in the esophagus.

OBJECTIVEPrehabilitation, intended as a multidisciplinary approach where physical training is combined with educational and counselling training, in cardiology could optimizing care, and has been shown to be able to reduce morbidity and mortality in several diseases. The present study aims to assess the effectiveness of a prehabilitation program in elderly patients (over 65) with chronic heart failure and to evaluate functional and quality indices of life.PATIENTS AND METHODSThis is randomized, single blind controlled trial. Fourteen older adult patients diagnosed with chronic heart failure were enrolled. Patients were randomly assigned into the study or the control group. Patients in the study group underwent physical training organized into 10 twice-weekly meetings, nutritional and lifestyle counseling.RESULTSIn the Study Group, the quality of life improved significantly (EQoL-5D), and between the two groups there is a statistically significant difference in the motor dimension of SF-36.CONCLUSIONSBecause of our preliminary results, prehabilitation program should be included among the management strategies of in elderly patients with chronic heart failure to better manage their disease and to improve their Quality of Life.

Sixty-three, open-chest normal rats were subjected to mechanical ventilation (MV) with tidal volumes (V-T) ranging from 7.5-39.5ml kg(-1) and PEEP 2.3 cmH(2)O. Arterial blood gasses and pressure, and lung mechanics were measured during baseline ventilation (V-T = 7.5m1 kg(-1)) before and after test ventilation, when cytokine, von Willebrand factor (vWF), and albumin concentration in serum and broncho-alveolar lavage fluid (BALF), wet-to-dry weight ratio (W/D), and histologic injury scores were assessed. Elevation of W/D and serum vWF and cytokine concentration occurred with V-T > 25ml kg(-1). With V-T > 30ml kg(-1) cytokine and albumin concentration increased also in BALF, arterial oxygen tension decreased, lung mechanics and histology deteriorated, while W/D and vWF and cytokine concentration increased further. Hence, the initial manifestation of injurious MV consists of damage of extra-alveolar vessels leading to interstitial edema, as shown by elevated vWF and cytokine levels in serum but not in BALF. Failure of the endothelial-epithelial barrier occurs at higher stress-strain levels, with alveolar edema, small airway injury, and mechanical alterations.

In stable chronic obstructive pulmonary disease (COPD) patients spontaneously breathing at rest, tidal expiratory flow limitation is the major determinant of the occurrence of expiratory looping in the plethysmographic flow-alveolar pressure diagram. In these patients the magnitude and the characteristics of the loop can be used as predictors of the presence of tidal expiratory flow limitation.

The World Health Organization (WHO) has declared COVID-19 disease a public health emergency of international concern. Even though no age-group is safe from the SARS-CoV-2 infection, the burden is extremely higher and most severe among persons aged 70 years and over, with a well-known mortality rates of more than 20% among octogenarians. The presence of multiple pre-existing comorbidities is associated with more severe SARS-CoV-2 infection manifestation, reflecting the presence of pre-existent physical and/or cognitive frailty. One of the main problems in patients with cognitive disorders is the management of drug therapy. In fact, there are a number of interactions and contraindications in the simultaneous administration of the antiviral drugs and the drugs that are commonly taken by older people. The aim of this review is to provide a clear and simple indication on how to improve the pharmacological and non-pharmacological management of patients with dementia and at the same time suffering from COVID-19 disease.

Background & aims. Behavioral factors, including protein intake, influence the quantity and quality of skeletal muscle. The aim of this study was to provide a better insight into the comprehension of aging-related changes of daily meat consumption throughout an individual's life span (from 18 to 98 years). Methods. For the present study, the database Longevity Check-up 7 + (Look-up 7 +) is used. A brief questionnaire exploring lifestyle habits, dietary preferences and the consumption of selected foods was administered. A frequency questionnaire was administered to collect information on how often in a week participants consumed a standardized portion size of meat (beef, pork, chicken or turkey). Results. The mean age of the 8,144 participants was 55.4 +/- 15.1 years (range: 18-98 years), with 4624 (56.8%) women. As compared with participants in the first tertile of daily meat intake, those in the third tertile were younger and showed slightly higher BMI. Systolic and diastolic blood pressure, as well as blood cholesterol level, was similar across different tertiles. Daily meat protein intake (as measured by the daily portion of meat) declined significantly during the young and adult age, both in men and women. Overall, among old subjects the meat-derived protein intake was less than 3.5 grams per day. Conclusions. The results of the Look-up 7 + survey suggest a significant decline in daily meat-derived protein intake with advancing age. Our findings also indicate that the higher meat consumption does not correlate with higher prevalence of cardiovascular risk factors, such as blood pressure and cholesterol and glucose levels.