Lung allograft transbronchial cryobiopsy for critical ventilated patients: a randomised trial.

BACKGROUND: Transbronchial lung cryobiopsy is an emerging technique for diagnosing pulmonary rejection. However, no prospective studies of this procedure for critically ill lung transplant recipients who require mechanical ventilation in the intensive care unit (ICU) have been performed. METHODS: From March 2017 to January 2020, we performed a prospective, randomised, comparative study to assess the diagnostic yield, histological quality and safety of transbronchial lung biopsy using biopsy forceps, a 1.9-mm cryoprobe or a 2.4-mm cryoprobe. RESULTS: 89 out of 129 consecutive transbronchial biopsy procedures (forceps group, 28 procedures; 1.9-mm cryoprobe group, 31 procedures; 2.4-mm cryoprobe group, 30 procedures) were randomised. Compared with lung samples from the forceps and 1.9-mm cryoprobe groups, lung samples from the 2.4-mm cryoprobe group allowed the most definitive diagnoses (p<0.01 and p=0.02, respectively), the most diagnoses of acute lung rejection (p<0.01 and p=0.01, respectively) and the most diagnoses of rejection severity (p<0.01 and p<0.01, respectively). These samples were larger (p<0.01 and p=0.04, respectively), had the most adequate alveolar tissue (p<0.01 and p=0.02, respectively), had more vessels per procedure (p<0.01 and p=0.01, respectively) and had no significant crush artefacts. Moderate bleeding was observed in 23% of cases (p=0.01 and p=0.08, respectively). No severe bleeding was observed. CONCLUSIONS: Transbronchial lung biopsy using a 2.4-mm cryoprobe allows the safe collection of lung tissue samples from critically ill lung transplant recipients who require mechanical ventilation in the ICU and has good diagnostic performance.

Laparoscopic Extravesical Reimplantation in Children with Primary Obstructive Megaureter.

Introduction: Conservative management of primary obstructive megaureter (POM) appears as the best option in patients with adequate ureteral drainage. Nevertheless, surgical intervention is indicated in cases of recurrent urinary tract Infections (UTIs), deterioration of split renal function, and significant obstruction. The gold standard includes: Ureteral reimplantation with or without tapering by open approach. Our objective is to report our results in the treatment of POM by Laparoscopic-Assisted Extracorporeal Ureteral Tapering Repair (EUTR) and Laparoscopic Ureteral Extravesical Reimplantation (LUER) and to evaluate the efficacy and security of this procedure. Materials and Methods: From January 2011 to January 2018 a retrospective study was carried out by reviewing the clinical records of 26 patients diagnosed with POM. All patients underwent laparoscopic ureteral reimplantation following Lich Gregoir technique. In cases of ureteral tapering, an EUTR was performed with Hendren technique. Results: In all patients LUER and EUTR were performed without conversion. No ureteral tapering was necessary in six patients. There were no intraoperative complications. At 3 months in postoperative, 1 patient presented a febrile UTI, and subsequently, a vesicoureteral reflux (VUR) grade III was diagnosed by voiding cystourethrogram. In this case, a redo laparoscopic surgery was performed. After long-term follow-up, all patients were asymptomatic without recurrence of POM or VUR. Conclusion: Laparoscopic-assisted EUTR and LUER following Lich Gregoir technique for POM constitutes a safe and effective option, with a success rate similar to that of open procedure. Nevertheless, larger randomized prospective trials and long-term follow-up are required to validate this technique.

Curcumin encapsulated polylactic acid nanoparticles embedded in alginate/gelatin bioinks for in situ immunoregulation: Characterization and biological assessment.

Curcumin is a known naturally occurring anti-inflammatory agent derived from turmeric, and it is commonly used as a herbal food supplement. Here, in order to overcome the inherent hydrophobicity of curcumin (Cur), polylactic acid (PLA) nanoparticles (NPs) were synthesised using a solvent evaporation, and an oil-in-water emulsion method used to encapsulate curcumin. Polymeric NPs also offer the ability to control rate of drug release. The newly synthesised NPs were analysed using a scanning electron microscope (SEM), where results show the NPs range from 50 to 250 nm. NPs containing graded amounts of curcumin (0 %, 0.5 %, and 2 %) were added to cultures of NIH3T3 fibroblast cells for cytotoxicity evaluation using the Alamar Blue assay. Then, the curcumin NPs were incorporated into an alginate/gelatin solution, prior to crosslinking using a calcium chloride solution (200 nM). These hydrogels were then characterised with respect to their chemical, mechanical and rheological properties. Following hydrogel optimization, hydrogels loaded with NP containing 2 % curcumin were selected as a candidate as a bioink for three-dimensional (3D) printing. The biological assessment for these bioinks/hydrogels were conducted using THP-1 cells, a human monocytic cell line. Cell viability and immunomodulation were evaluated using lactate dehydrogenase (LHD) and a tumour necrosis factor alpha (TNF-α) enzyme-linked immunosorbent (ELISA) assay, respectively. Results show that the hydrogels were cytocompatible and supressed the production of TNF-α. These bioactive hydrogels are printable, supress immune cell activation and inflammation showing immense potential for the fabrication of tissue engineering constructs.

Comorbidities and mortality risk factors for patients with bronchiectasis.

Introduction: Comorbidities in patients with bronchiectasis are common and have a significant impact on clinical outcomes, contributing to lower quality of life, lung function, and exacerbation frequency. At least 13 comorbidities have been associated with a higher risk of mortality in bronchiectasis patients. Nonetheless, the kind of relationship between bronchiectasis and comorbidities is heterogeneous and poorly understood.Areas covered: different biological mechanisms leading to bronchiectasis could have a role in the development of the associated comorbidities. Some comorbidities could have a causal relationship with bronchiectasis, possibly through a variable degree of systemic inflammation, such as in rheumatic disorders and bowel inflammatory diseases. Other comorbidities, such as COPD or asthma, could be associated through airway inflammation and there is an uncertain cause-effect relationship. Finally, shared risk factors could link different comorbidities to bronchiectasis such as in the case of cardiovascular diseases, where the known link between chronic systemic inflammation and pulmonary infection could play a significant role.Expert opinion: Although different tools have been developed to assess the role of comorbidities in bronchiectasis , we believe that the implementation of current strategies to manage them is absolutely necessary and could significantly improve long-term prognosis in patients with bronchiectasis.

New opacities in lung allograft after transbronchial cryobiopsy.

BACKGROUND: The occurrence of radiological opacities post-transbronchial cryobiopsy may pose serious difficulties in differential diagnosis and management of lung allografts. This prospective study evaluated the frequency, characteristics, and evolution of new lung opacities after performing transbronchial cryobiopsy. METHODS: From February 2018 to June 2018, 22 of 51 consecutive patients with an indication for transbronchial cryobiopsy underwent computed tomography (CT) of the thorax before and at 1, 4, and 8 weeks post-cryobiopsy. New CT images, required by the transplant team, were also evaluated during the next 6 months. Histological findings of transbronchial cryobiopsy and microbiological studies on bronchoalveolar lavage were evaluated as risk factors for opacities. RESULTS: After obtaining 112 cryobiopsy samples, 46 opacities >10 mm, including ground-glass, solid, cavitated, or a combination of these lesions were observed in 20 (91%) patients on post-cryobiopsy CT. All ground-glasses opacities on CT disappeared at 4 weeks. A single cavitated opacity persisted at 6 months. The remaining opacities disappeared or were decreased to <10 mm by 8 weeks. No correlations of the number, type, or evolution of opacities with the number or volume of cryobiopsy samples obtained, or with the histological diagnosis, type of transplant, or microbiologic culture results were observed. CONCLUSION: New pulmonary opacities >10 mm occur frequently after transbronchial cryobiopsy; a few may persist beyond 6 months. CT studies are recommended before implementing transbronchial cryobiopsy, whenever possible.

Optimization of Transbronchial Cryobiopsy in Lung Transplant Recipients.

BACKGROUND: Previous studies suggest that transbronchial lung biopsy using a cryoprobe is superior to transbronchial lung biopsy using forceps for evaluating lung grafts, although the technique can be associated an increase in complications. Because cryoprobe experience is limited, assessment of a greater number of cases is warranted. This prospective study evaluates the diagnostic yield, complications, and risk factors associated with the cryoprobe technique. METHODS: From April 2013 to April 2016, 321 consecutive cryoprobe transbronchial biopsies were indicated in single or bilateral lung transplant patients with acute or chronic clinical lung injury or in asymptomatic patients before hospital discharge after lung transplantation. RESULTS: With a mean of 4.32 lung parenchyma specimens per procedure, adequate alveolar lung parenchyma was obtained in 96.6% (84.27 ± 44.14 mm2) of cases. Obtaining at least 4 samples increased the histological diagnostic certainty (P < .001). Moderate to severe bleeding was observed in 7.48% of patients and was significantly more frequent in patients with unilateral transplantation (odds ratio, 0.10; 95% confidence interval, 0.02-0.30; P < .001) and in those with high blood pressure during scanning (odds ratio, 0.31; 95% confidence interval, 0.12-0.86; P = .019). Pneumothorax was observed in 7.7% of the patients, but only 3.7% of these patients required pleural drainage. CONCLUSIONS: Obtaining 4 or more cryobiopsy samples is valuable and safe for lung allograft monitoring. Being a recipient of a unilateral lung transplant or having arterial hypertension during bronchoscopy seem to be risk factors associated with increased bleeding.

Utility of Bronchoalveolar Lavage for the Diagnosis of Asbestos-Related Diseases. / Utilidad del lavado broncoalveolar en el diagnóstico de enfermedades relacionadas con el amianto.

INTRODUCTION: Bronchoalveolar lavage (BAL) analysis has been proposed as an objective technique for confirming asbestos exposure. However, the reliability and diagnostic yield of this procedure has not been studied in Spain. The aim of this study was to assess the usefulness of the analysis of asbestos bodies (AB) in bronchoalveolar lavage (BAL) for the diagnosis of asbestos-related diseases (ARD). METHODS: BAL samples from 72 patients (66 male, mean age 66 years) undergoing bronchoscopy were analyzed. Lung tissue from 23 of these patients was also analyzed. Asbestos exposure was assessed by anamnesis and a review of the patient's medical records. BAL and lung samples were processed and AB count was determined by light microscopy. The accepted threshold value to diagnose asbestos-related diseases was 1 AB/ml BAL or 1000 AB/gr dry tissue. RESULTS: Thirty-nine patients reported exposure to asbestos. Of these, 13 (33%) presented AB values above 1 AB/ml BAL. In the 33 non-exposed patients, 5 (15%) presented AB values above 1 AB/ml BAL. There was a significant difference between the AB levels of exposed and non-exposed patients (P=.006). The ROC curve showed that a value of 0.5 AB/ml BAL achieved the most satisfactory sensitivity, 46%, and a specificity of 83%. The correlation between AB levels in BAL and lung was 0.633 (P=.002). CONCLUSIONS: BAL study provides objective evidence of exposure to asbestos. The good correlation between the AB counts in BAL and lung tissue indicates that both techniques are valid for the analysis of asbestos content.

BALF cytokines in different phenotypes of chronic lung allograft dysfunction in lung transplant patients.

The long-term success of lung transplantation (LT) is limited by chronic lung allograft dysfunction (CLAD). Different phenotypes of CLAD have been described, such as bronchiolitis obliterans syndrome (BOS) and restrictive allograft syndrome (RAS). The purpose of this study was to investigate the levels of cytokines and chemokines in bronchoalveolar lavage fluid (BALF) as markers of these CLAD phenotypes. BALF was collected from 51 recipients who underwent (bilateral and unilateral) LT. The study population was divided into three groups: stable (ST), BOS, and RAS. Levels of interleukin (IL)-4, IL-5, IL-6, IL-10, IL-13, tumor necrosis factor alpha (TNF-α), interferon-gamma (IFN-γ), and granulocyte-macrophage colony-stimulating factor (GM-CSF) were measured using the multiplex technology. BALF neutrophilia medians were higher in BOS (38%) and RAS (30%) than in ST (8%) (P=.008; P=.012). Regarding BALF cytokines, BOS and RAS patients showed higher levels of INF-γ than ST (P=.02; P=.008). Only IL-5 presented significant differences between BOS and RAS (P=.001). BALF neutrophilia is as a marker for both CLAD phenotypes, BOS and RAS, and IL-5 seems to be a potential biomarker for the RAS phenotype.

Controlling the thermoelectric properties of polymers: application to PEDOT and polypyrrole.

Poly(3,4-ethylenedioxythiophene) (PEDOT) and polypyrrole (PPy) films have been prepared by an electrochemical method in a three electrode cell. The films have been obtained at different oxidation levels regarded as bipolaron, polaron and neutral states by varying the voltage, as is usually done in conjugated heterocyclic polymers. The voltage (-0.2 < V < 1.0 V) has been applied versus a Ag/AgCl reference electrode, producing a variation of one order of magnitude in the electrical conductivity and the Seebeck coefficient of the films. In the voltage range explored, the electrical conductivity increases from 80 to 766 S cm(-1) in PEDOT and from 15 to 160 S cm(-1) in PPy, while the Seebeck coefficient decreases from 37.0 to 9.6 µV K(-1) for PEDOT and from 51.0 to 6.7 µV K(-1) for PPy. The thermal conductivity remains unchanged with the oxidation state of the film, κ ≈ 0.35 ± 0.02 W m(-1) K(-1) for PEDOT and 0.17 ± 0.02 W m(-1) K(-1) for PPy. A maximum thermoelectric efficiency of 1.4 × 10(-2) for PEDOT and 6.8 × 10(-3) for PPy has been achieved. These changes are related to the doping level of the polymer films and they can be accurately controlled by the applied voltage. In this work, we provide a very simple method to control and optimize the power factor or the figure of merit of conducting polymers.

Assessment of exposure to drugs of abuse during pregnancy by hair analysis in a Mediterranean island.

AIMS: This study aims to estimate the prevalence of drug use by pregnant women living in Ibiza, using structured interviews and biomarkers in maternal hair. In addition, the potentially detrimental effects of maternal drug abuse on their newborns were investigated. Ibiza has a large international night-life resort associated with clubs, music and use of recreational drugs. DESIGN, SETTING AND PARTICIPANTS: Hair samples were collected prospectively from January to March 2010 from a cohort of consecutive mothers after giving birth in the Hospital Can Misses in Ibiza. MEASUREMENTS: Opiates, cocaine, cannabis, methadone, amphetamines, 3,4-methylenedioxymethamphetamine (MDMA) and their metabolites were detected in a 3-cm-long proximal segment of maternal hair corresponding to the last trimester of pregnancy by gas chromatography coupled to mass spectrometry (n = 107). Data on socio-demographic characteristics and on tobacco, alcohol, drugs of prescription and drugs of abuse consumption during pregnancy were collected using a structured questionnaire. FINDINGS: Hair analysis showed an overall 16% positivity for drugs of abuse in the third trimester of pregnancy, with a specific prevalence of cannabis, cocaine, MDMA and opiates use of 10.3, 6.4, 0.9 and 0%, respectively. In the questionnaires, only 1.9% of mothers declared using drugs of abuse during pregnancy. Gestational drug of abuse consumption was associated with active tobacco smoking, a higher number of smoked cigarettes and the mother being Spanish. CONCLUSIONS: Illicit drug use is substantially under-reported among pregnant women living in Ibiza, particularly among Spanish nationals. Voluntary, routine objective biological toxicology screening should be considered as part of routine examinations in antenatal clinics on this Mediterranean island.