A prospective evaluation of phrenic nerve injury after lung transplantation: Incidence, risk factors, and analysis of the surgical procedure.

BACKGROUND: Phrenic nerve injury (PNI) is a complication of lung transplantation related to the surgical procedure and associated with increased morbidity. However, the incidence and risk factors, specifically regarding surgical techniques, have not been adequately studied. METHODS: We conducted a prospective single-center study over 4-years, in recipients of lung transplantation with a normal pretransplant phrenic nerve conduction study (PNCS). Diaphragm ultrasound and PNCS were performed in the first 21 postoperative days and PNI was defined when both tests were abnormal. Patients were followed up until hospital discharge. The association between transplant characteristics and PNI was analyzed by using logistic regression models. RESULTS: Two hundred eleven lung grafts implanted in 127 patients were included in the study. After lung transplantation, PNI was diagnosed in 43.3% of the subjects and 29% of the operated hemithorax. Regression logistic model showed that the variables related to PNI were female gender (p = 0.02), bilateral lung transplantation (BLT) (p = 0.001), right lung graft (p = 0.003), clamshell incision (p = 0.01), mediastinal adhesions (p = 0.002), longer operative time (p = 0.003), intraoperative extracorporeal support (p = 0.02), and blood transfusion (p = 0.003). Conversely, age >61 years (p = 0.008) and higher thoracic diameter (p = 0.04) were protective factors. The use of electrocautery, cardiac mechanical retractors, and diaphragmatic traction was not associated with PNI. Morbidity was increased without any difference in mortality. CONCLUSIONS: PNI is a frequent complication after lung transplantation, associated with higher morbidity. Mainly risk factors were age, BLT, female gender, and variables related to surgical difficulties. Lung graft in the right hemithorax and mediastinal adhesiolysis were the most relevant technical variables.

New Sequence Type ST3449 in Multidrug-Resistant Pseudomonas aeruginosa Isolates from a Cystic Fibrosis Patient.

Pseudomonas aeruginosa is one of the most critical bacterial pathogens associated with chronic infections in cystic fibrosis patients. Here we show the phenotypic and genotypic characterization of five consecutive multidrug-resistant isolates of P. aeruginosa collected during a month from a CF patient with end-stage lung disease and fatal outcome. The isolates exhibited distinct colony morphologies and pigmentation and differences in their capacity to produce biofilm and virulence potential evaluated in larvae of Galleria mellonella. Whole genome-sequencing showed that isolates belonged to a novel sequence type ST3449 and serotype O6. Analysis of their resistome demonstrated the presence of genes blaOXA-396, blaPAO, aph(3')-IIb, catB, crpP and fosA and new mutations in chromosomal genes conferring resistance to different antipseudomonal antibiotics. Genes exoS, exoT, exoY, toxA, lasI, rhlI and tse1 were among the 220 virulence genes detected. The different phenotypic and genotypic features found reveal the adaptation of clone ST3449 to the CF lung environment by a number of mutations affecting genes related with biofilm formation, quorum sensing and antimicrobial resistance. Most of these mutations are commonly found in CF isolates, which may give us important clues for future development of new drug targets to combat P. aeruginosa chronic infections.

Predictive Value of Immune Cell Functional Assay for Non-Cytomegalovirus Infection in Lung Transplant Recipients: A Multicenter Prospective Observational Study.

INTRODUCTION: Immune cell functional assay (ImmuKnow®) is a non-invasive method that measures the state of cellular immunity in immunosuppressed patients. We studied the prognostic value of the assay for predicting non-cytomegalovirus (CMV) infections in lung transplant recipients. METHODS: A multicenter prospective observational study of 92 patients followed up from 6 to 12 months after transplantation was performed. Immune cell functional assay was carried out at 6, 8, 10, and 12 months. RESULTS: Twenty-three patients (25%) developed 29 non-CMV infections between 6 and 12 months post-transplant. At 6 months, the immune response was moderate (ATP 225-525ng/mL) in 14 (15.2%) patients and low (ATP<225ng/mL) in 78 (84.8%); no patients had a strong response (ATP≥525ng/mL). Only 1 of 14 (7.1%) patients with a moderate response developed non-CMV infection in the following 6 months compared with 22 of 78 (28.2%) patients with low response, indicating sensitivity of 95.7%, specificity of 18.8%, positive predictive value (PPV) of 28.2%, and negative predictive value (NPV) of 92.9% (AUC 0.64; p=0.043). Similar acute rejection rates were recorded in patients with mean ATP≥225 vs. <225ng/mL during the study period (7.1% vs. 9.1%, p=0.81). CONCLUSION: Although ImmuKnow® does not seem useful to predict non-CMV infection, it could identify patients with a very low risk and help us define a target for an optimal immunosuppression.

Diagnosis of Idiopathic Pulmonary Fibrosis: Differential Diagnosis.

Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive, and fibrotic interstitial lung disease of unknown origin with a characteristic imaging and histologic pattern called usual interstitial pneumonia (UIP). The diagnosis of IPF is a complex procedure that requires the support of various specialists, who must integrate clinical, radiological, and histological data. The multidisciplinary team (MDT) has become the new gold standard to diagnose and manage the disease, increasing the accuracy and agreement of the diagnosis between different centers. It is mandatory to exclude nonspecific interstitial pneumonia or other diseases that can cause the UIP pattern, particularly drugs or exposure diseases, including chronic hypersensitivity pneumonitis or systemic autoimmune disease. The role of the MDT is also to decide who could need a biopsy or to review patient diagnoses at regular intervals in those with additional information or unexpected evolution. This review provides updated information to achieve a proper IPF diagnosis.

Screening for Latent Tuberculosis Infection in Patients who are Candidate for Biological Therapies in Spain? A Multidisciplinary Survey. / ¿Cómo realizamos el cribado de infección tuberculosa latente en pacientes candidatos a terapias biológicas en España? Una encuesta multidisciplinar.

INTRODUCTION: Treatment with biological therapies increases the incidence of tuberculous disease. The introduction of systematic screening for latent tuberculosis infection in patients who are to receive these therapies has reduced this risk. In 2016, the consensus document on the prevention and treatment of tuberculosis in patients who are candidates for biological treatment was published in Spain. The main objective of this study was to evaluate adherence to these guidelines. METHODS: Multicenter, descriptive, observational study via an anonymous online survey sent to medical societies involved in biologics. RESULTS: We received 747 responses. Most respondents performed screening at the right time in the right patients (93.7%). Only 36.6% of respondents requested the appropriate diagnostic test, while 56.3% correctly recommended chemoprophylaxis. Up to 96% were familiar with the recommended chemoprophylaxis regimens, while only 63.9% initiated them at the right time. The specialist area that participated most and screened most patients for latent tuberculosis infection was rheumatology (54%). In most cases, pulmonologists were involved in an advisory capacity. CONCLUSIONS: This study shows poor overall adherence to recommendations, with only 56% of respondents reporting appropriate compliance. The incidence of tuberculous disease in patients who are to receive biological therapies could be reduced further by emphasizing the importance of the right diagnostic test and use of the diagnostic algorithm for latent tuberculosis infection.

Polymeric chemosensor for the detection and quantification of chloride in human sweat. Application to the diagnosis of cystic fibrosis.

We have developed a new extremely hydrophilic polymeric film suitable for the detection and quantification of chloride in human sweat directly on the skin. The film, or membrane, has chemically anchored 6-methoxyquinoline groups as chloride responsive fluorescent motifs. We have prepared the sensory material from a standard vinyl copolymer, by a convenient and easy solid-phase reaction. The sensory material has a water swelling percentage of 700%, facilitating an immediate detection of chloride, is reusable for at least 6 cycles and can be handled without care by unskilled persons. The initially high fluorescence of the material decreases in the presence of chloride, allowing the quantification of chloride concentration by using the colour definition of a digital picture or a fluorimeter. The suitability of the material to perform quantitative chloride analysis of human sweat by putting it in contact with the skin offers promise for its application in the sweat test used for the diagnosis of cystic fibrosis (CF).