Early onset of azithromycin to prevent CLAD in lung transplantation: Promising results of a retrospective single centre experience.

INTRODUCTION: Azithromycin (AZI) may be an effective immune modulator in lung transplant (LT) recipients, and can decrease chronic lung allograft dysfunction (CLAD) rates, the leading cause of mortality after the 1st year post-LT. The aim of the study is to assess the effect of AZI initiation and its timing on the incidence and severity of CLAD in LT recipients. METHODS: Single-center retrospective study, including LT recipients from 01/01/2011 to 30/06/2020. Four groups were established: those who started AZI at the 3rd week post-LT (group A), those who received AZI later than the 3rd week post-LT and had preserved FEV1 (B), those who did not receive AZI (C) and those who started AZI due to a decline in FEV1 (D). The dosage of AZI prescribed was 250 mg three times per week. CLAD was defined and graduated according to the 2019 ISHLT criteria. RESULTS: We included 358 LT recipients: 139 (38.83%) were in group A, 94 (26.25%) in group B, 91 (25.42%) in group C, and 34 (9.50%) in group D. Group A experienced the lowest CLAD incidence and severity at 1 (p = .01), 3 (p < .001), and 5 years post-LT, followed by Group B. Groups C and D experienced a higher incidence and severity of CLAD (p = .015). Initiation of AZI prior to FEV1 decline (Groups A and B) proved to be protective against CLAD after adjusting for differences between the treatment groups. CONCLUSIONS: Early initiation of AZI in LT recipients could have a role in decreasing the incidence and severity of CLAD. In addition, as long as FEV1 is preserved, initiating AZI at any time could also be useful to prevent the incidence of CLAD and reduce its severity.

Recomendaciones de la Sociedad Española de Cirugía Torácica para el manejo del derrame pleural maligno / Recommendations of the Spanish Society of Thoracic Surgery for the management of malignant pleural effusion

Este artículo resume la guía clínica de diagnóstico y tratamiento del derrame pleural maligno (DPM) auspiciada por la Sociedad Española de Cirugía Torácica (SECT). Se elaboraron 10 controversias clínicas bajo la metodología de preguntas PICO (Patient, Intervention, Comparison, Outcome) y la calidad de la evidencia y graduación de la fuerza de las recomendaciones se basó en el sistema Grading of Recommendations, Assessment, Development and Evaluations (GRADE). El análisis inmunocitoquímico y molecular del líquido pleural puede evitar procedimientos invasivos ulteriores con finalidad diagnóstica. Actualmente, el control definitivo del DPM se puede realizar indistintamente a través de una pleurodesis (talco poudrage o slurry) o de la inserción de un catéter pleural tunelizado (CPT). Es probable que la combinación de ambas técnicas (p.ej. toracoscopia con talco poudrage e inserción de un CPT, o instilación de talco slurry a través de un CPT) ocupe un lugar predominante en el manejo terapéutico futuro. (AU)

This article summarizes the clinical guidelines for the diagnosis and treatment of malignant pleural effusion (MPE) sponsored by the Spanish Society of Thoracic Surgery (SECT). Ten clinical controversies were elaborated under the methodology of PICO (Patient, Intervention, Comparison, Outcome) questions and the quality of the evidence and grading of the strength of the recommendations was based on the GRADE system. Immunocytochemical and molecular analyses of pleural fluid may avoid further invasive diagnostic procedures. Currently, the definitive control of MPE can be achieved either by pleurodesis (talc poudrage or slurry) or the insertion of a indwelling pleural catheter (IPC). It is likely that the combination of both techniques (i.e., thoracoscopy with talc poudrage and insertion of a IPC, or instillation of talc slurry through a IPC) will have a predominant role in the future therapeutic management. (AU)

Conformational Rearrangements Regulating the DNA Repair Protein APE1.

Apurinic apyrimidinic endonuclease 1 (APE1) is a key enzyme of the Base Excision Repair (BER) pathway, which primarily manages oxidative lesions of DNA. Once the damaged base is removed, APE1 recognises the resulting abasic site and cleaves the phosphodiester backbone to allow for the correction by subsequent enzymes of the BER machinery. In spite of a wealth of information on APE1 structure and activity, its regulation mechanism still remains to be understood. Human APE1 consists of a globular catalytic domain preceded by a flexible N-terminal extension, which might be involved in the interaction with DNA. Moreover, the binding of the nuclear chaperone nucleophosmin (NPM1) to this region has been reported to impact APE1 catalysis. To evaluate intra- and inter-molecular conformational rearrangements upon DNA binding, incision, and interaction with NPM1, we used Förster resonance energy transfer (FRET), a fluorescence spectroscopy technique sensitive to molecular distances. Our results suggest that the N-terminus approaches the DNA at the downstream side of the abasic site and enables the building of a predictive model of the full-length APE1/DNA complex. Furthermore, the spatial configuration of the N-terminal tail is sensitive to NPM1, which could be related to the regulation of APE1.

Novel genes and sex differences in COVID-19 severity.

Here, we describe the results of a genome-wide study conducted in 11 939 coronavirus disease 2019 (COVID-19) positive cases with an extensive clinical information that were recruited from 34 hospitals across Spain (SCOURGE consortium). In sex-disaggregated genome-wide association studies for COVID-19 hospitalization, genome-wide significance (P < 5 × 10-8) was crossed for variants in 3p21.31 and 21q22.11 loci only among males (P = 1.3 × 10-22 and P = 8.1 × 10-12, respectively), and for variants in 9q21.32 near TLE1 only among females (P = 4.4 × 10-8). In a second phase, results were combined with an independent Spanish cohort (1598 COVID-19 cases and 1068 population controls), revealing in the overall analysis two novel risk loci in 9p13.3 and 19q13.12, with fine-mapping prioritized variants functionally associated with AQP3 (P = 2.7 × 10-8) and ARHGAP33 (P = 1.3 × 10-8), respectively. The meta-analysis of both phases with four European studies stratified by sex from the Host Genetics Initiative (HGI) confirmed the association of the 3p21.31 and 21q22.11 loci predominantly in males and replicated a recently reported variant in 11p13 (ELF5, P = 4.1 × 10-8). Six of the COVID-19 HGI discovered loci were replicated and an HGI-based genetic risk score predicted the severity strata in SCOURGE. We also found more SNP-heritability and larger heritability differences by age (<60 or ≥60 years) among males than among females. Parallel genome-wide screening of inbreeding depression in SCOURGE also showed an effect of homozygosity in COVID-19 hospitalization and severity and this effect was stronger among older males. In summary, new candidate genes for COVID-19 severity and evidence supporting genetic disparities among sexes are provided.

Recommendations of the Spanish Society of Thoracic Surgery for the management of malignant pleural effusion.

This article summarizes the clinical guidelines for the diagnosis and treatment of malignant pleural effusion (MPE) sponsored by the Spanish Society of Thoracic Surgery (SECT). Ten clinical controversies were elaborated under the methodology of PICO (Patient, Intervention, Comparison, Outcome) questions and the quality of the evidence and grading of the strength of the recommendations was based on the GRADE system. Immunocytochemical and molecular analyses of pleural fluid may avoid further invasive diagnostic procedures. Currently, the definitive control of MPE can be achieved either by pleurodesis (talc poudrage or slurry) or the insertion of a indwelling pleural catheter (IPC). It is likely that the combination of both techniques (i.e., thoracoscopy with talc poudrage and insertion of a IPC, or instillation of talc slurry through a IPC) will have a predominant role in the future therapeutic management.

Recomendaciones de la sociedad Española de cirugía torácica para el manejo del derrame pleural maligno [Pré-print] / Recommendations of the Spanish Society of Thoracic Surgery for the management of malignant pleural effusion

This article summarizes the clinical guidelines for the diagnosis and treatment of malignant pleural effusion (MPE) sponsored by the Spanish Society of Thoracic Surgery (SECT). Ten clinical controversies were elaborated under the methodology of PICO (Patient, Intervention, Comparison, Outcome) questions and the quality of the evidence and grading of the strength of the recommendations was based on the GRADE system. Immunocytochemical and molecular analyses of pleural fluid may avoid further invasive diagnostic procedures. Currently, the definitive control of MPE can be achieved either by pleurodesis (talc poudrage or slurry) or the insertion of a tunneled pleural catheter (TPC). It is likely that the combination of both techniques (i.e., thoracoscopy with talc poudrage and insertion of a TPC, or instillation of talc slurry through a TPC) will have a predominant role in the future therapeutic management.

Este artículo resume la guía clínica de diagnóstico y tratamiento del derrame pleural maligno (DPM) auspiciada por la Sociedad Española de Cirugía Torácica (SECT). Se elaboraron 10 controversias clínicas bajo la metodología de preguntas PICO (Patient, Intervention, Comparison, Outcome) y la calidad de la evidencia y graduación de la fuerza de las recomendaciones se basó en el sistema Grading of Recommendations, Assessment, Development and Evaluations (GRADE). El análisis inmunocitoquímico y molecular del líquido pleural puede evitar procedimientos invasivos ulteriores con finalidad diagnóstica. Actualmente, el control definitivo del DPM se puede realizar indistintamente a través de una pleurodesis (talco poudrage o slurry) o de la inserción de un catéter pleural tunelizado (CPT). Es probable que la combinación de ambas técnicas (p.ej. toracoscopia con talco poudrage e inserción de un CPT, o instilación de talco slurry a través de un CPT) ocupe un lugar predominante en el manejo terapéutico futuro.

Herida traqueal por arma blanca con orificio de entrada y salida / Tracheal stab wound with entrance and exit orífices

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Using FloSeal® to control digestive bleeding in the distal large bowel.

We present an alternative treatment to resolve lower gastrointestinal bleeding by the application of FloSeal, a haemostatic matrix. Fundamentally, the treatment consists of inserting the tube containing the Sengstaken-Blakemore probe impregnated with FloSeal into the rectum-sigma. This procedure is simple, easy to reproduce and can be very useful to control bleeding in the last section of the gastrointestinal tract.

Transverse Cervicothoracic Stabbing: Multidisciplinary Management of a Surgical Emergency.

Tracheobronchial injuries are closely related to orotracheal intubations and chest traumas. Stabbing injuries are very rare and often life threatening because of the damage to vital structures such as the respiratory tract and large arterial or venous vessels. Early diagnosis and treatment of penetrating neck injuries increase survival rates. We report a case of the tracheobronchial section with a penetrating stabbing wound on the left laterocervical area associated with contralateral pneumothorax, requiring urgent surgical pulmonary repair, tracheal suture, and tracheotomy. Prompt action with a multidisciplinary approach resulted in a favorable outcome.

C-reactive protein and serum amyloid a overexpression in lung tissues of chronic obstructive pulmonary disease patients: a case-control study.

BACKGROUND: Although researchers have consistently demonstrated systemic inflammation in chronic obstructive pulmonary disease (COPD), its origin is yet unknown. We aimed to compare the lung bronchial and parenchymal tissues as potential sources of major acute-phase reactants in COPD patients and resistant smokers. METHODS: Consecutive patients undergoing elective surgery for suspected primary lung cancer were considered for the study. Patients were categorized as COPD or resistant smokers according to their spirometric results. Lung parenchyma and bronchus sections distant from the primary lesion were obtained. C-reactive protein (CRP) and serum amyloid A (SAA1, SAA2 and SAA4) gene expressions were evaluated by RT-PCR. Protein levels were evaluated in paraffin embedded lung tissues by immunohistochemistry and in serum samples by nephelometry. RESULTS: Our study included 85 patients with COPD and 87 resistant smokers. In bronchial and parenchymal tissues, both CRP and SAA were overexpressed in COPD patients. In the bronchus, CRP, SAA1, SAA2, and SA4 gene expressions in COPD patients were 1.89-fold, 4.36-fold, 3.65-fold, and 3.9-fold the control values, respectively. In the parenchyma, CRP, SAA1, and SAA2 gene expressions were 2.41-, 1.97-, and 1.76-fold the control values, respectively. Immunohistochemistry showed an over-stained pattern of these markers on endovascular cells of COPD patients. There was no correlation with serum protein concentration. CONCLUSIONS: These results indicate an overexpression of CRP and SAA in both bronchial and parenchymal tissue in COPD, which differs between both locations, indicating tissue/cell type specificity. The endothelial cells might play a role in the production of theses markers.

Comparative study of talc poudrage versus pleural abrasion for the treatment of primary spontaneous pneumothorax.

Primary spontaneous pneumothorax is a pathology mainly affecting healthy young patients. Clinical guidelines do not specify the type of pleurodesis that should be conducted, due to the lack of comparative studies on the different techniques. The aim of this study was to compare talc poudrage and pleural abrasion in the treatment of spontaneous pneumothorax. A retrospective comparative study was performed, including 787 patients with primary spontaneous pneumothorax. The 787 patients were classified into two groups: Group A (pleural abrasion) n = 399 and Group B (talc pleurodesis) n = 388. The variables studied were recurrence, surgical time, morbidity and in-hospital length of stay. Statistical analysis was done by an unpaired t-test and Fisher's exact test (SSPS 18.0). Statistically significant differences were observed in the variables: surgical time (A: 46 ± 12.3; B: 37 ± 11.8 min; P < 0.001); length of stay (A: 4.7 ± 2.5; B: 4.3 ± 1.8 days; P = 0.01); apical air camera (A: 25; B: 4; P < 0.001); pleural effusion (A: 6; B: 0; P = 0.05). Talc poudrage shows shorter surgical times and length of stay, and lower re-intervention rates. Morbidity is lower in patients with talc poudrage. Statistically significant differences were not observed in recurrence, persistent air leaks, atelectasis and haemothorax.

Breast cancer in males.

BACKGROUND: Male breast cancer has a very low incidence (<1%). It has traditionally been considered to have a poorer prognosis than breast cancer in females due to delayed diagnosis as a cause of decreased survival. Our goal is to analyze our series and to identify factors influencing survival. METHODS: We conducted a retrospective study from 1997-2008 (n = 32). Inclusion criteria were male gender and histological confirmation of breast cancer. We analyzed epidemiological data (age and personal and family history), tumors (size, grade of differentiation, histological type, location, TNM stage, receptors), therapeutic regimen (surgical technique, adjuvant therapy) and survival (relapse, followup, death). RESULTS: Male breast cancer represents 0.9% of all breast cancers treated in our center. The average age of our patients was 66.84 years. Only 9.3% demonstrated gynecomastia as a presenting complaint. Histologically, 90% were infiltrating ductal type; 59.25% were diagnosed in early stages (I-II) compared to 40.74% in stages III-IV. Aggressive surgical techniques are still performed, compared to conservative techniques (74.19% vs. 19.36%). With a median follow-up of 52.82 months, the mortality rate was 16%. Existence of distant metastasis has been the only statistically significant factor in survival. CONCLUSIONS: The percentage of cases of male breast cancer is very low compared to breast cancer in females. Limited studies in the literature make gender-specific findings difficult. A low percentage of conservative surgical procedures are performed, even though this has increased considerably in recent years. The existence of distant metastasis was the main determinant of survival.