An injectable, degradable hydrogel plug for tracheal occlusion in congenital diaphragmatic hernia (CDH)

Congenital Diaphragmatic Hernia (CDH) is a birth defect characterized by failed closure of diaphragm, herniation of viscera in the thoracic cavity and impaired lung development. In most severe cases, fetoscopic endoluminal tracheal occlusion (FETO) is performed through a catheter-mounted balloon to contain pulmonary hypoplasia. To support the success rate of FETO and overcome some of the associated drawbacks, this work aimed at finding an injectable, degradable substitute for the balloon not requiring prenatal removal. Two different types of gels were evaluated as tracheal plugs: calcium-alginate and hyaluronan/methylcellulose blends (HA-MC). The effect of composition on hydrogel properties was evaluated, to identify formulations meeting design requirements. Anatomical tracheal casts were fabricated and filled with a simulated lung fluid to assess injectability, cohesiveness, sealing pressure and persistence of plugs. In vitro cytotoxicity and adhesion of mouse fibroblasts on hydrogels were also investigated. For both hydrogels, adjusting formulation enabled to obtain gelation time within the design range. Furthermore, when injected in the tracheal model, good cohesion and capability to adapt to the anatomical shape were also observed. Effective sealing up to 80 cm H 2 0 was reached for selected compositions and was maintained for over 4 weeks in the in vitro model. Swelling and weight loss were also strongly influenced by composition and varied from few days to several weeks. Despite the absence of in vitro cytotoxicity, a favourably low cell-adhesion was observed for both hydrogels. However, due to their shear-thinning behaviour, HA-MC blends appeared as a particularly suitable candidate for single-surgery tracheal occlusion

Effect of bronchodilation on expiratory flow limitation and resting lung mechanics in COPD.

ABSTRACT: Bronchodilator drugs produce variable improvements in forced expiratory volume in 1 s (FEV1), but larger changes in end-expiratory lung volume (EELV) in chronic obstructive pulmonary disease (COPD), which were suggested to be related to the presence of expiratory flow limitation (EFL) at rest. We tested this concept in 42 COPD patients (FEV1 42.3¡13.8% predicted) during spontaneous breathing before and after 5 mg nebulised salbutamol. EFL was detected by within-breath changes in respiratory system reactance measured by a multifrequency forced oscillation method, while changes in EELV were assessed by inspiratory capacity (IC). Bronchodilation (BD) increased IC (from 1.8¡0.5 to 2.1¡0.6 L, p,0.001) and reduced inspiration resistance (R – insp) at 5 Hz (from 5.1¡1.6 to 4.2¡1.5 cmH2O?s?L-1, p,0.001). R – insp identified BD responders with a discriminative power of 80.1%. In total, 20 patients were flow-limited before BD. They showed worse spirometry and higher residual volume, but significant improvements in IC were seen in all patients irrespective of flow limitation. Changes inR – insp were confined to flow-limited patients, as were reactance changes. BD reduced the degree of heterogeneity in the respiratory system, a change best seen with inspiratory values. BD has complex effects on lung mechanics in COPD, and EFL affects both this and the response of some respiratory variables to treatment. However, changes in EELV are consistently seen, irrespective of the presence of flow limitation at rest

Optimization of an Optical Magnetic Twisting Cytometry system for the study of cell mechanics.

none6noneM Pastena;M Baroffio;C Folli;A Pedotti;V Brusasco;R L DellacaPastena, M.; Baroffio, Michele; Folli, C.; Pedotti, A.; Brusasco, Vito; Dellaca, R. L

Comparison of a visual analogue scale and Lake Louise symptom scores for acute mountain sickness.

Assessment of the presence and severity of acute mountain sickness (AMS) is based on subjective reporting of the sensation of symptoms. The Lake Louise symptom scoring system (LLS) uses categorical variables to rate the intensity of AMS-related symptoms (headache, gastrointestinal distress, dizziness, fatigue, sleep quality) on 4-point ordinal scales; the sum of the answers is the LLS self-score (range 0–15). Recent publications indicate a potential for a visual analogue scale (VAS) to quantify AMS. We tested the hypothesis that overall and single-item VAS and LLS scores scale linearly. We asked 14 unacclimatized male subjects [age 41 (14), mean (SD) yr; height 176 (3) cm;weight 75 (9) kg] who spent 2 days at 3647mand 4 days at 4560mto fill out LLS questionnaires, with a VAS for each item (i) and a VAS for the overall (o) sensation of AMS, twice a day (n¼172). Even though correlated (r¼0.84), the relationship between LLS(o) and VAS(o) was distorted, showing a threshold effect for LLS(o) scores below 5, with most VAS(o) scores on one side of the identity line. Similar threshold effects were seen for the LLS(i) and VAS(i) scores. These findings indicate nonlinear scaling characteristics that render difficult a direct comparison of studies done with either VAS or LLS alone