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The severity of lung involvement is the main prognostic factor in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Carbohydrate antigen 15-3 (CA 15-3), a marker of lung damage and fibrosis, could help predict the prognosis of SARS-CoV-2 pneumonia. This was a retrospective and observational study. CA 15-3 was analyzed in the blood samples of patients consecutively admitted for SARS-CoV-2 pneumonia and whose blood samples were available in the biobank. Other prognostic markers were also measured (interleukin 6 [IL6], C-reactive protein [CRP], D-dimer, troponin T, and NT-ProBNP). The occurrence of in-hospital complications was registered, including death, the need for medical intensive care, and oxygen therapy at discharge. In this study, 539 patients were recruited (54.9% men, mean age: 59.6 ± 16.4 years). At admission, the mean concentrations of CA 15-3 was 20.5 ± 15.8 U/mL, and the concentration was correlated with male sex, older age, and other severity markers of coronavirus disease of 2019 (COVID-19) (IL6, CRP, D-dimer, troponine T, and NT-ProBNP). CA 15-3 levels were higher in patients who died (n = 56, 10.4%) (35.33 ± 30.45 vs. 18.8 ± 12.11, p p p = 0.011). Elevated CA 15-3 levels (above 34.5 U/mL) were a strong predictor of a complicated in-hospital course, in terms of a higher risk of death (adjusted odds ratio [OR] 3.74, 95% confidence interval [CI]: 1.22–11.9, p = 0.022) and need for intensive care (adjusted OR 4.56, 95% CI: 1.37–15.8) after adjusting for all other risk factors. The degree of lung damage and fibrosis evaluated in terms of CA 15-3 concentrations may allow early identification of the increased risk of complications in patients with SARS-CoV-2 pneumonia.

BackgroundThe relationship between asthma and vitamin D deficiency has been known for some time. However, interventional studies conducted in this regard have shown conflicting results.ObjectiveTo evaluate the efficacy of vitamin D supplementation in asthmatic patients in improving the degree of control of asthma.MethodsRandomised, triple-blind, placebo-controlled, parallel-group study in adult asthmatic patients with serum 25-hydroxyvitamin-D3 ResultsOne hundred and twelve patients were randomised (mean age 55 years, with 87 (78%) being women). Of the 112 patients, 106 (95%) completed the trial. Half the patients (56) were assigned to the intervention group and the other half to the control group. A statistically significant clinical improvement was observed in the intervention group (+3.09) compared with the control group (−0.57) (difference 3.66 (95% CI 0.89 to 5.43); pConclusionAmong adults with asthma and vitamin D deficiency, supplementation with weekly oral calcifediol compared with placebo improved asthma control over 6 months. Further research is needed to assess long-term efficacy and safety.Trial registration numberNCT02805907.

The safety of autologous bone marrow mononuclear cells (ABMNC) intraspinal infusion in amyotrophic lateral sclerosis (ALS) patients was evaluated considering breathing and sleep patterns. Patients between 20 and 65 years old were eligible if they had definite ALS, spinal onset, a disease duration between 6 and 36 months, FVC > 50%, and a below 90% oxygen saturation (T90)

BACKGROUND Haemophilus influenzae, a colonizer of the nasopharynx, in children causes mainly otitis and sinusitis. The primary objective of this study was to determine the prevalence of pharyngeal colonization by H. influenzae, and the secondary objectives were to identify risk factors associated with H. influenzae colonization and its antibiotic susceptibility. METHODS A prospective, multicenter study of nasopharyngeal carriers of H. influenzae was conducted in the pediatric consulting rooms of 10 primary healthcare centers in Murcia (Spain). The study consisted of 404 healthy children less than 5 years of age and was carried out during winter (January-March) and summer (July-September) of 2015. A nasopharyngeal sample was collected from each child, and an epidemiologic survey was completed by a pediatrician. RESULTS In total, 112 (27.7%) children had colonization by H. influenzae, with 73.2% of cases in winter and 26.8% of cases in summer (P < 0.001). The median (interquartile range) age in months of the colonized children (13 months, 12-47.5) was lower than that of the noncolonized children (46 months, 12-49) (P < 0.001). All H. influenzae found were nontypeable H. influenzae (NTHi). Among 112 isolates, 20% were ampicillin resistant, of which 10% produced β-lactamase, and 9% were ampicillin resistant and did not produce β-lactamase. A logistic regression analysis showed that young age (odds ratio: 0.98) and the winter period (odds ratio: 3.41; P < 0.001) were risk factors for colonization by NTHi. CONCLUSIONS Colonization by NTHi is high in this Mediterranean coast region with remarkable ampicillin resistant. Younger age and the winter period were facilitating factors.

To the Editor: The emergence of new massive sequencing methods has proved revolutionary for the study of complex microbial populations such as the microbiota of the respiratory tract in patients with chronic obstructive pulmonary disease (COPD) [1]. Using this powerful methodology, our objective was to compare the microbiota in two groups of patients with COPD of different severity in order to detect potential microbiological markers that could help to provide a better understanding of the pathogenesis of this disease and the role played by the microbiota in its severity. The current study recruited nine patients with mild or moderate COPD and 10 patients with severe or very severe COPD in a stable condition (at least 3 months without exacerbation or use of antibiotics for any other reason). Diagnosis and classification of COPD was established according to Global Initiative for Chronic Obstructive Lung Disease (GOLD) recommendations [2]. After DNA extraction from good quality expectorated sputum, quantitative (q)PCR (7500 real time PCR system thermocycler; Life Technologies, Grand Island, NY, USA) was used to quantify the copy number of the 16S rRNA gene in each sample (total bacterial load), yielding a 468 bp amplicon located between nucleotides 340–808 in reference to the 16S rRNA gene of Escherichia coli strain MG1655 (National Center for Biotechnology Information (NCBI) reference sequence: NR_102804.1). In order to compare the results obtained, they were normalised to the number of human cells in the sample, quantified by qPCR, using the human albumin gene [3]. A region measuring 525 bp, between position 8 and 533 of the 16S rRNA gene was amplified and pyrosequenced (Roche GS FLX Titanium with Lib-L type microspheres; 454 Life Sciences, Branford, CT, USA). This region comprises the regions of gene hypervariability from V1 to V3 of the 16S rRNA gene …

It is necessary to ensure the quality of sleep studies conducted at home given that there can be potential variations. Automatic analysis is simple and could help in an audit. The objective is to find a predictive model of visual reading using an automatic analysis of saturation and respiratory signal in order to establish a reading standard with a polygraph used at home on patients who have sleep apnea-hypopnea clinical symptoms. The analysis was carried out using the following two definitions of hypopnea: an event with a duration ofor= 10 s with a decrease of30% of the respiratory signal; and an event associated either with a desaturation ofor= 3% or with a desaturation ofor= 4%. A total of 189 studies were selected from a representative sample of 218 patients. Two pneumologists carried out the readings together. The agreement between the visual respiratory disturbance index (RDI) [ie, apneas plus hypopneas] for both definitions and the automatic respiratory signal analysis (ie, automatic RDI [RDIa]) or the automatic desaturation index of 3% (DI3%a) and of 4% (DI4%a) showed limits from a Bland-Altman plot that were too large. However, a multiple linear regression analysis with RDIa and DI3%a or RDIa and DI4%a presented an acceptable level of agreement with RDI for both definitions (p0.001; r(2) = 96.2% and 97%, respectively). The 95% confidence interval for the differences between the RDI and the model was +/- 10.1 or +/- 8.8 events per hour, so a study should be revised outside of these limits. A predictive multiple regression model that uses the automatic analysis of the oximetry and respiratory signal could establish a standard for the visual reading of polygraphy at home.

Objective: Severe exacerbations in alpha-1-antitrypsin (AAT)-deficient patients with chronic obstructive pulmonary disease (COPD) and/or emphysema are a major cause of hospitalization. A multicentre, observational, retrospective study was undertaken to evaluate the effect of continuous AAT augmentation therapy in reducing the incidence of exacerbations in these patients. Methods: Patients treated with Trypsone® or Prolastin® for at least 18 months were recruited if their medical records for 18 months before starting augmentation therapy were available. The number of mild and severe exacerbations in the two periods was compared and hospitalization-related costs were analysed. Results: A total of 127 patients were recruited; 75 of them experienced at least one exacerbation in the period prior to augmentation. In the treatment period, the mean number of exacerbations per patient was reduced in both the total population and the population with exacerbations (mean ± SD: 1.2 ± 1.6 versus 1.0 ± 2.2 and 2.0 ± 1.6 versus 1.4 ± 2.7, respectively; p < 0.01). The percentage of patients experiencing exacerbations was reduced in the total population (59.1% versus 44.1%; p < 0.05). In the patient subgroup of the total population who experienced a change in their number of exacerbations between the two periods, 43.7% had a reduction and 21.4% had an increase ( p < 0.01). The number of severe exacerbations diminished in 42.9% of this subgroup and increased in 12.0% ( p < 0.001). Most adverse events were nonserious or not related to treatment. Hospitalization costs savings per patient associated with treatment ranged from approximately €400 to €900 ( p < 0.05). Conclusions: Augmentation therapy with AAT concentrates was associated with a reduction in the incidence and severity of exacerbations in AAT-deficient patients, which resulted in lower hospitalization expenditures.

Martínez, Salvador [et al.], The objective of this article is to assess the safety of intraspinal infusion of autologous bone marrow mononuclear cells (BMNCs) and, ultimately, to look for histopathological signs of cellular neurotrophism in amyotrophic lateral sclerosis (ALS) patients. We conducted an open single arm phase I trial. After 6 months observation, autologous BMNCs were infused into the posterior spinal cord funiculus. Safety was the primary endpoint and was defined as the absence of serious transplant-related adverse events. In addition, forced vital capacity (FVC), ALS-functional rating scale (ALS-FRS), Medical Research Council scale for assessment of muscle power (MRC), and Norris scales were assessed 6 and 3 months prior to the transplant and quarterly afterward for 1 year. Pathological studies were performed in case of death. Eleven patients were included. We did not observe any severe transplant-related adverse event, but there were 43 nonsevere events. Twenty-two (51%) resolved in ≤2 weeks and only four were still present at the end of follow-up. All were common terminology criteria for adverse events grade ≤2. No acceleration in the rate of decline of FVC, ALS-FRS, Norris, or MRC scales was observed. Four patients died on days 359, 378, 808, and 1,058 post-transplant for reasons unrelated to the procedure. Spinal cord pathological analysis showed a greater number of motoneurons in the treated segments compared with the untreated segments (4.2 ± 0.8 motoneurons per section [mns per sect] and 0.9 ± 0.3 mns per sect, respectively). In the treated segments, motoneurons were surrounded by CD90+ cells and did not show degenerative ubiquitin deposits. This clinical trial confirms not only the safety of intraspinal infusion of autologous BMNC in ALS patients but also provides evidence strongly suggesting their neurotrophic activity. © AlphaMed Press., This work was supported by the Carlos III Institute (FIS EC07/90762), Advanced Therapies and Transplant General Direction (Health Ministry, Spain) (TRA-137), ISCIII Spanish Cell Therapy Network (Tercel; RD06/0010/0023), DIGESIC-MEC BFU2008-00588, Ingenio 2010 MEC-CONSOLIDER CSD2007-00023, GVA Prometeo Grant 2009/028, Rotary Club Elche-Illice and by the Fundacion Diogenes.

Amyothrophic lateral sclerosis (ALS) is a disorder characterized by the progressive degeneration of motoneurons and subsequent weakness of the skeletal muscles. Respiratory insufficiency is the most common cause of death for these patients, and it occurs approximately within three years. Riluzole is the only drug that has shown a survival benefit, although it is limited to 6 months and offers no improvement in clinical symptoms (Miller et al., 2007). Bone marrow mononuclear cells have been proposed as a treatment for ALS (Deda et al., 2009). They can provide a neurotrophic effect and modulate the immune host environment. The benefits of bone marrow cells infusion into the spinal cord parenchyma of a SOD1-mutant mice, a model of motoneuron degeneration, has been tested by our group. After laminectomy, the cells were injected at the L5–S1 level, into the anterior horn of the spinal cord through the posterior funiculus. The mice experienced functional improvement as well as an increase in the number of motoneurons in the anterior horn of the spinal cord when compared with sham operated mice. However, no neural differentiation of the transplanted cells was observed (Pastor et al., 2012). These data generated in animal models support the evidence that the major mechanism of action of the bone marrow stem cells is based on trophic support by the production of molecules. These trophic factors are important in ALS and other diseases characterized by degeneration of spinal motoneurons (Suzuki and Sevendsen, 2008). In the case of the familial ALS mouse model SOD1 G93A, the main neurotrophic mediator is the glial derived neurotrophic factor (GDNF). It is able to prevent motoneuron degeneration although it does not promote muscle reinnervation or recovery of muscle function (Suzuki et al., 2007). Further analysis of the mice experimental spinal cords showed that the grafted cells formed cellular nests surrounding the motoneurons and that they expressed GDNF at the mRNA and protein level. This graft-derived GDNF acted as a neurotrophic signal in the microenvironment of spinal motoneurons, increasing neuronal survival, and improving the functional performance of the mice after the transplant (Pastor et al., 2012), in contrast to Suzuki et al. observations.

The foreign body aspiration is more frequent in children. The most usual etiology is the foreign bodies of vegetable nature, which can not be observed in the chest radiograph. The clinic signs are varied, including shortness of breath, cough and wheezing. Hemoptysis is a rare symptom, whose arising is generally connected with the existence of bronchiectasis. We present the case of a child who showed repeated hemoptysis and focal neumonitis due to Eikenelle corrodens three years after the aspiration of a spike. The diagnosis of the bronchial aspiration obtained after The most unusual in this case is the clinic manifestation of repeated hemoptysis, together with the long connected to the existence of foreign body inside the bronchus.

Foreign body aspiration requires emergency bronchoscopic examination when the product is chemically active. We describe the case of a female patient who aspirated a ferrous sulfate tablet that, in spite of being extracted immediately, caused lesions that persisted in the bronchial tree for 6 weeks. We then discuss the potential of ferrous sulfate substance to cause damage to the tracheobronchial tree.

Listeriosis is a infectious disease which can affect to immunosuppressed patients. We report a case of pneumonia by Listeria monocytogenes as unusual presentation, because the central nervous system infections are the most common clinical entities. Many cases reported had a underlying disease, most commonly Hodgkin's disease, and had received immunosuppressive therapy. In our case the patient was considered to be immunosuppressed by had received corticosteroids and had been diagnosed of stage IIIa squamous cell carcinoma 3 years ago. The illness began 48 hours before the admission to hospital, he had fever, mental confusion and the location of pneumonia was right lower lobe, 24 hours later the patient die.