PNEUMOTHORAX RELATED TO AIR TRAVEL IN PULMONARY LYMPHANGIOLEIOMYOMATOSIS

Introduction Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease affecting almost exclusively women and characterized by abnormal proliferation of smooth muscle cells (LAM cells) in the lungs, kidneys and axial lymphatics. In the lungs, LAM cell proliferation leads to the development of multiple thin-walled cysts resulting in the gradual onset of respiratory insufficiency and frequent pneumothorax (PT). Air travel (AT) could further increase the risk of PT in LAM through rupture of subpleural cysts induced by changes in atmospheric pressure in aircraft cabin. Methods To assess whether AT increases the risk of PT in LAM, we performed a retrospective surveyed of women members of European LAM patient associations. Data were collected through a questionnaire regarding the occurrence of PT episodes, including dates, affected side, and therapeutic modalities, as well as a list of AT after disease onset. A post-flight PT was defined as a PT diagnosed by a physician ≤ 30 days after AT. Flights performed after lung transplantation were withdrawn from the analysis. Results A total of 145 women responded to the survey. Their mean age was 48 ± 12 years. 207 episodes of PT were reported with a mean ± SD number of 2.5 ± 1.3 per patient. 128 patients with available dates allowed us to calculate the annual incidence of PT since the first symptoms attributable to LAM, and since LAM diagnosis which were respectively 7% and 5% (versus 0.006% in the general women population). 83 (57%) patients travelled by air. 75 patients with evaluable data performed a total of 191 AT. A PT occurred within 30 days after AT in 5/75 patients. One had bilateral PT. The probability of PT within 30 days after AT was 5/191 (2.6%) per patient, and 6/382 (1.6%) per lung. As compared to the 30 days before AT, the incidence of PT per lung was significantly higher during the 30 days after AT (RR 6, CI 1.02-113). In contrast, no difference in PT incidence was observed when comparing 2 other 30-days periods before and after AT. 2 Conclusions The incidence of PT in LAM is 1000 higher than in the general women population. The occurrence of PT increases significantly within 30 days after AT as compared to the 30 days before AT, suggesting that AT per se is a risk factor for PT occurrence in LAM

Four-day antithrombin therapy does not seem to attenuate hypercoagulability in patients suffering from sepsis

INTRODUCTION: Sepsis activates the coagulation system and frequently causes hypercoagulability, which is not detected by routine coagulation tests. A reliable method to evaluate hypercoagulability is thromboelastography (TEG), but this has not so far been used to investigate sepsis-induced hypercoagulability. Antithrombin (AT) in plasma of septic patients is decreased, and administration of AT may therefore reduce the acquired hypercoagulability. Not clear, however, is to what extent supraphysiologic plasma levels of AT decrease the acute hypercoagulability in septic patients. The present study investigates the coagulation profile of septic patients before and during four day high-dose AT therapy. METHODS: Patients with severe sepsis were randomly assigned to receive either 6,000 IU AT as a bolus infusion followed by a maintenance dose of 250 IU/hour over four days (n = 17) or placebo (n = 16). TEG, platelet count, plasma fibrinogen levels, prothrombin time and activated partial thromboplastin time were assessed at baseline and daily during AT therapy. RESULTS: TEG showed a hypercoagulability in both groups at baseline, which was neither reversed by bolus or by maintenance doses of AT. The hypercoagulability was mainly caused by increased plasma fibrinogen, and to a lesser extent by platelets. Plasmatic coagulation as assessed by the prothrombin time and activated partial thromboplastin time was similar in both groups, and did not change during the study period. CONCLUSION: The current study shows a distinct hypercoagulability in patients suffering from severe sepsis, which was not reversed by high-dose AT treatment over four days. This finding supports recent data showing that modulation of coagulatory activation in septic patients by AT does not occur before one week of therapy. Trial registration: Current Control Trials ISRCTN2293102

Endobronchial intubation detected by insertion depth of endotracheal tube, bilateral auscultation, or observation of chest movements: randomised trial

Objective To determine which bedside method of detecting inadvertent endobronchial intubation in adults has the highest sensitivity and specificity

Benefits in cardiac function by CD38 suppression: Improvement in NAD+ levels, exercise capacity, heart rate variability and protection against catecholamine-induced ventricular arrhythmias

CD38 enzymatic activity regulates NAD+ and cADPR levels in mammalian tissues, and therefore has a prominent role in cellular metabolism and calcium homeostasis. Consequently, it is reasonable to hypothesize about its involvement in cardiovascular physiology as well as in heart related pathological conditions. Aim: To investigate the role of CD38 in cardiovascular performance, and its involvement in cardiac electrophysiology and calcium-handling. Methods and results: When submitted to a treadmill exhaustion test, a way of evaluating cardiovascular performance, adult male CD38KO mice showed better exercise capacity. This benefit was also obtained in genetically modified mice with catalytically inactive (CI) CD38 and in WT mice treated with antibody 68 (Ab68) which blocks CD38 activity. Hearts from these 3 groups (CD38KO, CD38CI and Ab68) showed increased NAD+ levels. When CD38KO mice were treated with FK866 which inhibits NAD+ biosynthesis, exercise capacity as well as NAD+ in heart tissue decreased to WT levels. Electrocardiograms of conscious unrestrained CD38KO and CD38CI mice showed lower basal heart rates and higher heart rate variability than WT mice. Although inactivation of CD38 in mice resulted in increased SERCA2a expression in the heart, the frequency of spontaneous calcium release from the sarcoplasmic reticulum under stressful conditions (high extracellular calcium concentration) was lower in CD38KO ventricular myocytes. When mice were challenged with caffeine-epinephrine, CD38KO mice had a lower incidence of bidirectional ventricular tachycardia when compared to WT ones. Conclusion: CD38 inhibition improves exercise performance by regulating NAD+ homeostasis. CD38 is involved in cardiovascular function since its genetic ablation decreases basal heart rate, increases heart rate variability and alters calcium handling in a way that protects mice from developing catecholamine induced ventricular arrhythmias.Fil: Agorrody, Guillermo. Universidad de la Republica. Facultad de Medicina; UruguayFil: Peclat, Thais R.. Mayo Clinic College Of Medicine; Estados UnidosFil: Peluso, Gonzalo. Universidad de la Republica. Facultad de Medicina; UruguayFil: Gonano, Luis Alberto. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani". Universidad Nacional de La Plata. Facultad de Ciencias Médicas. Centro de Investigaciones Cardiovasculares "Dr. Horacio Eugenio Cingolani"; ArgentinaFil: Santos, Leonardo. Instituto Pasteur de Montevideo; UruguayFil: van Schooten, Wim. Teneobio; Estados UnidosFil: Chini, Claudia C. S.. Mayo Clinic College Of Medicine; Estados UnidosFil: Escande, Carlos. Instituto Pasteur de Montevideo; UruguayFil: Chini, Eduardo N.. Mayo Clinic College Of Medicine; Estados UnidosFil: Contreras, Paola. Universidad de la Republica. Facultad de Medicina; Urugua

Air travel and incidence of pneumothorax in lymphangioleiomyomatosis.

Pulmonary lymphangioleiomyomatosis (LAM) is a rare disease of women characterized by multiple lung cysts leading to respiratory insufficiency and frequent pneumothorax (PT). Air travel (AT) could increase the risk of PT in LAM through rupture of subpleural cysts induced by atmospheric pressure changes in aircraft cabin. To determine whether AT increases the risk of PT in LAM, we performed a retrospective survey of members of European LAM patient associations. A flight-related PT was defined as occurring ≤30 days after AT. 145 women reported 207 PT. In 128 patients with available data, the annual incidence of PT was 8% since the first symptoms of LAM and 5% since LAM diagnosis, compared to 0.006% in the general female population. Following surgical or chemical pleurodesis, the probability of remaining free of PT recurrence was respectively 82, 68, and 59% after 1, 5 and 10 years, as compared to only 55, 46 and 39% without pleurodesis (p = 0.026). 70 patients with available data performed 178 AT. 6 flight-related PT occurred in 5 patients. PT incidence since first symptoms of LAM was significantly higher ≤30 days after AT as compared to non-flight periods (22 versus 6%, risk ratio 3.58, confidence interval 1.40-7.45). The incidence of PT in LAM is about 1000 times higher than in the general female population, and is further increased threefold after AT. Chemical or surgical pleurodesis partly reduces the risk of PT recurrence in LAM

Changes in body composition in early breast cancer patients treated with aromatase inhibitors

Purpose The aim of the study was to analyze the modification of total and regional body composition in early breast cancer patients treated with aromatase inhibitors (AIs).Methods This is a prospective, single-center, observational, longitudinal study. Four-hundred and twenty-eight patients treated with adjuvant aromatase inhibitors were enrolled at the Medical Oncology and Breast Unit of Spedali Civili Hospital in Brescia from September 2014 to June 2022. Several body composition parameters including total and regional fat and lean body mass were investigated with dual-energy X-ray absorptiometry (DXA) scan at baseline and after 18 months of treatment with aromatase inhibitors.Results A significant increase in fat body mass (mean + 7.2%, 95% confidence interval [CI]: 5.5;8.9%) and a reduction in lean body mass (mean -3.1%, 95% CI -3.9; -2.4) were documented in this population. The changes in fat and lean body mass varied considerably according to different body districts ranging between + 3.2% to + 10.9% and from-1.3% to -3.9%, respectively.Conclusion Aromatase inhibitor adjuvant therapy in early breast cancer is associated with changes in body composition, with a wide variability among different body districts, leading to a risk of sarcopenic obesity. Supervised physical exercise that focuses on single body parts that may display detrimental variations may be beneficial for AIs treated patients

Activation of RyR2 by class I kinase inhibitors

Kinase inhibitors are a common treatment for cancer. Class I kinase inhibitors that target the ATP-binding pocket are particularly prevalent. Many of these compounds are cardiotoxic and can cause arrhythmias. Spontaneous release of Ca2+ via cardiac ryanodine receptors (RyR2), through a process termed store overload-induced Ca2+ release (SOICR), is a common mechanism underlying arrhythmia. We explored whether class I kinase inhibitors could modify the activity of RyR2 and trigger SOICR to determine if this contributes to the cardiotoxic nature of these compounds.Centro de Investigaciones Cardiovasculare

The LOFAR Two-Metre Sky Survey (LoTSS): VI. Optical identifications for the second data release

The second data release of the LOFAR Two-Metre Sky Survey (LoTSS) covers 27% of the northern sky, with a total area of $\sim 5,700$ deg$^2$. The high angular resolution of LOFAR with Dutch baselines (6 arcsec) allows us to carry out optical identifications of a large fraction of the detected radio sources without further radio followup; however, the process is made more challenging by the many extended radio sources found in LOFAR images as a result of its excellent sensitivity to extended structure. In this paper we present source associations and identifications for sources in the second data release based on optical and near-infrared data, using a combination of a likelihood-ratio cross-match method developed for our first data release, our citizen science project Radio Galaxy Zoo: LOFAR, and new approaches to algorithmic optical identification, together with extensive visual inspection by astronomers. We also present spectroscopic or photometric redshifts for a large fraction of the optical identifications. In total 4,116,934 radio sources lie in the area with good optical data, of which 85% have an optical or infrared identification and 58% have a good redshift estimate. We demonstrate the quality of the dataset by comparing it with earlier optically identified radio surveys. This is by far the largest ever optically identified radio catalogue, and will permit robust statistical studies of star-forming and radio-loud active galaxies.Comment: 29 pages. Accepted by A&A; data products available at https://lofar-surveys.org/dr2_release.htm