ObjectivesCOVID-19 causes lung parenchymal and endothelial damage that lead to hypoxic acute respiratory failure (hARF). The influence of hARF severity on patients’ outcomes is still poorly understood.DesignObservational, prospective, multicentre study.SettingThree academic hospitals in Milan (Italy) involving three respiratory high dependency units and three general wards.ParticipantsConsecutive adult hospitalised patients with a virologically confirmed diagnosis of COVID-19. Patients aged <18 years or unable to provide informed consent were excluded.InterventionsAnthropometrical, clinical characteristics and blood biomarkers were assessed within the first 24 hours from admission. hARF was graded as follows: severe (partial pressure of oxygen to fraction of inspired oxygen ratio (PaO2/FiO2) <100 mm Hg); moderate (PaO2/FiO2 101–200 mm Hg); mild (PaO2/FiO2 201–300 mm Hg) and normal (PaO2/FiO2 >300 mm Hg).Primary and secondary outcome measuresThe primary outcome was the assessment of clinical characteristics and in-hospital mortality based on the severity of respiratory failure. Secondary outcomes were intubation rate and application of continuous positive airway pressure during hospital stay.Results412 patients were enrolled (280 males, 68%). Median (IQR) age was 66 (55–76) years with a PaO2/FiO2 at admission of 262 (140–343) mm Hg. 50.2% had a cardiovascular disease. Prevalence of mild, moderate and severe hARF was 24.4%, 21.9% and 15.5%, respectively. In-hospital mortality proportionally increased with increasing impairment of gas exchange (p<0.001). The only independent risk factors for mortality were age ≥65 years (HR 3.41; 95% CI 2.00 to 5.78, p<0.0001), PaO2/FiO2 ratio ≤200 mm Hg (HR 3.57; 95% CI 2.20 to 5.77, p<0.0001) and respiratory failure at admission (HR 3.58; 95% CI 1.05 to 12.18, p=0.04).ConclusionsA moderate-to-severe impairment in PaO2/FiO2 was independently associated with a threefold increase in risk of in-hospital mortality. Severity of respiratory failure is useful to identify patients at higher risk of mortality.Trial registration numberNCT04307459

According to the fact that Alzheimer's disease (AD) is more common in postmenopausal women, estrogen treatment has been proposed. Experimental studies, still mostly performed using animal models, demonstrated that estrogen exerts neuroprotective effects. We previously established neuroblast long-term cell cultures from human fetal olfactory epithelium. In the present study, we addressed the role of estrogen in these unique human cells, which express both the estrogen receptor (ER)-alpha and ERbeta. We found that 17beta-estradiol (17betaE(2)) and the selective estrogen receptor modulators (SERMs) raloxifene and tamoxifen exerted neuroprotective effects, which were independent of cell proliferation, by increasing resistance against beta-amyloid-induced toxicity, with the exception of the highest concentrations of raloxifene (10 and 100 nm). In addition, 17betaE(2) exposure protected from oxidative stress, reduced apoptosis, and increased the expression of the catalytic subunit of telomerase. Furthermore, we evaluated by quantitative real-time RT-PCR whether estrogen/SERMs modulate the expression of the recently discovered seladin-1 (selective AD indicator-1) gene, which exerts neuroprotective effects and is down-regulated in AD-vulnerable brain regions. 17betaE(2) (100 pm to 100 nm) and SERMs (1 nm) significantly increased the amount of seladin-1 mRNA. Conversely, 10 and 100 nm raloxifene reduced the expression of seladin-1. The effect of estrogen appears mainly mediated by ERalpha because the selective ERalpha agonist propylpyrazole-triol determined a much greater increase of seladin-1 expression than the ERbeta agonist diarylpropionitrile. Our results add new evidence, using human neuronal cells, for a beneficial effect of estrogen in preventing neurodegenerative diseases and suggest for the first time that seladin-1 may mediate this effect.

A comprehensive approach to lung function in bronchiectasis ABSTRACT Background: International guidelines recommend simple spirometry for bronchiectasis patients. However, pulmonary pathophysiology of bronchiectasis is very complex and still poorly understood. Our objective was to characterize lung function in bronchiectasis and identify specific functional sub-groups. Methods:This was a multicenter, prospective, observational study enrolling consecutive adults with bronchiectasis during stable sate. Patients underwent body-plethysmography before and after acute bronchodilation testing, diffusing lung capacity (DL CO ) with a 3-year follow up. Air trapping and hyperinflation were a residual volume (RV)>120%predicted and a total lung capacity>120%predicted. Acute reversibility was: ΔFEV 1 ≥12% and 200 ml from baseline (FEV 1rev ) and ΔRV ≥10% reduction from baseline (RV rev ). Sensitivity analyses included different reversibility cutoffs and excluded patients with concomitant asthma or chronic obstructive pulmonary disease.Results: 187 patients were enrolled (median age: 68 years; 29.4% males).Pathophysiological abnormalities often overlapped and were distributed as follows: air trapping (70.2%), impaired DL CO (55.7%), airflow obstruction (41.1%), hyperinflation (15.7%) and restriction (8.0%). 9.7% of patients had normal lung function. RV rev (17.6%) was more frequent than FEV 1rev (4.3%). Similar proportions were found after multiple sensitivity analyses. Compared with non-reversible patients, patients with RV rev had more severe obstruction (mean(SD) FEV 1 %pred: 83.0% (24.4) vs 68.9% (26.2); P=0.02) and air trapping (RV%pred, 151.9% (26.6) vs 166.2% (39.9); P=0.028). Conclusions:Spirometry alone does not encompass the variety of pathophysiological characteristics in bronchiectasis. Air trapping and diffusion impairment, not airflow obstruction, represent the most common functional abnormalities. RV rev is related to worse lung function and might be considered in bronchiectasis' workup and for patients' functional stratification. Demographics

Purpose: To show the use of the short acting opioid remifentanil for labour analgesia when epidural analgesia is considered to be contraindicated.Clinical features: After Ethics Committee approval and informed consent, six patients (36-40 wk gestation), in whom epidural analgesia was considered contraindicated (women refusing regional analgesia, presenting with coagulation or platelet abnormalities or sepsis) benefited from patient-controlled intravenous analgesia (PCIA) with remifentanil. The Abbott Lifecare patient-controlled analgesia (PCA) pump with remifentanil 50 µg·ml -1 was set to deliver remifentanil continuous background infusion of 0.05 µg·kg -1 ·min -1 and 25 µg boluses with a five minutes lockout period. The PCIA was started when the parturients experienced regular painful contractions (cervical dilatation of at least 4 cm) and stopped just before delivery (cervix fully dilated). Maternal monitoring included non-invasive blood pressure measurements, heart rate, percutaneous arterial oxyhemoglobin saturation and respiratory rate. Percutaneous fetal heart rate was continuously monitored. All patients remained alert or sleepy but easily arousable and were satisfied with their analgesia. No particular side effects have been noticed. Apgar scores were between 6 and 10.Conclusion: Remifentanil PCIA combining low continuous background infusion and small bolus doses is an alternative when epidural analgesia in labour is contraindicated. Under careful anesthesia monitoring, the technique seems to be safe for both mother and baby, at least when delivery occurs at or near the normal term of pregnancy.Objectif : Décrire l'utilisation de l'opioïde de courte durée, rémifentanil, pour l'analgésie pendant le travail obstétrical lorsque l'analgésie épidurale est contre-indiquée.Éléments cliniques : Six patientes (de 36 à 40 sem de grossesse), chez qui l'analgésie épidurale était contreindiquée (des femmes qui refusaient l'analgésie régionale, présentaient des anomalies de coagulation ou de plaquettes ou de la septicémie), ont consenti à participer à l'étude, approuvée par le Comité d'éthique, et ont bénéficié de l'analgésie intraveineuse autocontrôlée (AIAC) avec du rémifentanil. Une pompe Abbott Lifecare pour l'analgésie autocontrôlée (AAC) a été installée avec 50 µg·ml-1 de rémifentanil administrés en perfusion de fond continue de 0,05 µg·kg-1·min-1 et en bolus de 25 µg entrecoupés de périodes réfractaires de cinq minutes. Le début de l'AIAC correspondait à des contractions douloureuses régulières (dilatation cervicale d'au moins 4 cm) et la fin, avec la naissance du bébé (col complètement dilaté). Le monitorage des mères comprenait la mesure non effractive de la tension artérielle, de la fréquence cardiaque, de la saturation percutanée du sang artériel en oxyhé-moglobine et de la fréquence respiratoire. La fréquence cardiaque foetale a été placée aussi sous monitorage continu. Toutes les patientes sont demeurées éveillées ou somnolentes, mais faciles à réveiller et ont été satisfaites de l'analgésie. Aucun effet ...

Both hypo- and hyperthyroidism markedly impair female sexual function. A rapid improvement is observed with the restoration of euthyroidism, although a longer period of time may be needed for full normalization. Preliminary data suggest that thyroid autoimmunity may selectively impair sexual desire, independently from thyroid function.

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Different steps and conditions for DNA extraction for microbiota analysis in sputum have been reported in the literature. We aimed at testing both dithiothreitol (DTT) and enzymatic treatments of sputum samples and identifying the most suitable DNA extraction technique for the microbiota analysis of sputum. Sputum treatments with and without DTT were compared in terms of their median levels and the coefficient of variation between replicates of both DNA extraction yield and real-time PCR for the 16S rRNA gene. Treatments with and without lysozyme and lysostaphin were compared in terms of their median levels of real-time PCR for S. aureus. Two enzyme-based and three beads-based techniques for DNA extraction were compared in terms of their DNA extraction yield, real-time PCR for the 16S rRNA gene and microbiota analysis. DTT treatment decreased the coefficient of variation between replicates of both DNA extraction yield and real-time PCR. Lysostaphin (either 0.18 or 0.36 mg/mL) and lysozyme treatments increased S. aureus detection. One enzyme-based kit offered the highest DNA yield and 16S rRNA gene real-time PCR with no significant differences in terms of alpha-diversity indexes. A condition using both DTT and lysostaphin/lysozyme treatments along with an enzymatic kit seems to be preferred for the microbiota analysis of sputum samples.

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