Bleeding Risk With Combination Intrapleural Fibrinolytic and Enzyme Therapy in Pleural Infection: An International, Multicenter, Retrospective Cohort Study.

BACKGROUND: Combination intrapleural fibrinolytic and enzyme therapy (IET) has been established as a therapeutic option in pleural infection. Despite demonstrated efficacy, studies specifically designed and adequately powered to address complications are sparse. The safety profile, the effects of concurrent therapeutic anticoagulation, and the nature and extent of nonbleeding complications remain poorly defined. RESEARCH QUESTION: What is the bleeding complication risk associated with IET use in pleural infection? STUDY DESIGN AND METHODS: This was a multicenter, retrospective observational study conducted in 24 centers across the United States and the United Kingdom. Protocolized data collection for 1,851 patients treated with at least one dose of combination IET for pleural infection between January 2012 and May 2019 was undertaken. The primary outcome was the overall incidence of pleural bleeding defined using pre hoc criteria. RESULTS: Overall, pleural bleeding occurred in 76 of 1,833 patients (4.1%; 95% CI, 3.0%-5.0%). Using a half-dose regimen (tissue plasminogen activator, 5 mg) did not change this risk significantly (6/172 [3.5%]; P = .68). Therapeutic anticoagulation alongside IET was associated with increased bleeding rates (19/197 [9.6%]) compared with temporarily withholding anticoagulation before administration of IET (3/118 [2.6%]; P = .017). As well as systemic anticoagulation, increasing RAPID score, elevated serum urea, and platelets of < 100 × 109/L were associated with a significant increase in bleeding risk. However, only RAPID score and use of systemic anticoagulation were independently predictive. Apart from pain, non-bleeding complications were rare. INTERPRETATION: IET use in pleural infection confers a low overall bleeding risk. Increased rates of pleural bleeding are associated with concurrent use of anticoagulation but can be mitigated by withholding anticoagulation before IET. Concomitant administration of IET and therapeutic anticoagulation should be avoided. Parameters related to higher IET-related bleeding have been identified that may lead to altered risk thresholds for treatment.

Transbronchial Lung Cryobiopsy in Patients with Interstitial Lung Disease: A Systematic Review.

Rationale: In 2018, a systematic review evaluating transbronchial lung cryobiopsy (TBLC) in patients with interstitial lung disease (ILD) was performed to inform American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax clinical practice guidelines on the diagnosis of idiopathic pulmonary fibrosis. Objectives: To perform a new systematic review to inform updated guidelines. Methods: Medline, Excerpta Medica Database, and the Cochrane Central Register of Controlled Trials (CCTR) were searched through June 2020. Studies that enrolled patients with ILD and reported the diagnostic yield or complication rates of TBLC were selected for inclusion. Data was extracted and then pooled across studies via meta-analysis. The quality of the evidence was appraised using the grading of recommendations, assessment, development, and evaluation approach. Results: Histopathologic diagnostic yield (number of procedures that yielded a histopathologic diagnosis divided by the total number of procedures performed) of TBLC was 80% (95% confidence interval [CI], 76-83%) in patients with ILD. TBLC was complicated by bleeding and pneumothorax in 30% (95% CI, 20-41%) and 8% (95% CI, 6-11%) of patients, respectively. Procedure-related mortality, severe bleeding, prolonged air leak, acute exacerbation, respiratory failure, and respiratory infection were rare. The quality of the evidence was very low owing to the uncontrolled study designs, lack of consecutive enrollment, and inconsistent results. Conclusions: Very low-quality evidence indicated that TBLC has a diagnostic yield of approximately 80% in patients with ILD, with manageable complications.

Use of a Genomic Classifier in Patients with Interstitial Lung Disease: A Systematic Review and Meta-Analysis.

Background: Usual interstitial pneumonia (UIP) is the histopathologic hallmark of idiopathic pulmonary fibrosis (IPF), the prototypical interstitial lung disease (ILD). Diagnosis of IPF requires that a typical UIP pattern be identified by using high-resolution chest computed tomography or lung sampling. A genomic classifier for UIP has been developed to predict histopathologic UIP by using lung samples obtained through bronchoscopy. Objective: To perform a systematic review to evaluate genomic classifier testing in the detection of histopathologic UIP to inform new American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Asociación Latinoamericana del Tórax guidelines. Data Sources: Medline, Embase, and the Cochrane Central Register of Controlled Trials were searched through June 2020. Data Extraction: Data were extracted from studies that enrolled patients with ILD and reported the use of genomic classifier testing. Synthesis: Data were aggregated across studies via meta-analysis. The quality of the evidence was appraised by using the Grading of Recommendations, Assessment, Development, and Evaluation approach. Results: Genomic classifier testing had a sensitivity of 68% (95% confidence interval [CI], 55-73%) and a specificity of 92% (95% CI, 81-95%) in predicting the UIP pattern in ILD. Confidence in an IPF diagnosis increased from 43% to 93% in one cohort and from 59% to 89% in another cohort. Agreement levels in categorical IPF and non-IPF diagnoses measured by using a concordance coefficient were 0.75 and 0.64 in the two cohorts. The quality of evidence was moderate for test characteristics and very low for both confidence and agreement. Conclusions: Genomic classifier testing predicts histopathologic UIP in patients with ILD with a specificity of 92% and improves diagnostic confidence; however, sensitivity is only 68%, and testing is not widely available.

Intrapleural Fibrinolytics and Deoxyribonuclease for Treatment of Indwelling Pleural Catheter-Related Pleural Infection: A Multi-Center Observational Study.

BACKGROUND: Indwelling pleural catheters (IPC) are increasingly used for management of recurrent (especially malignant) effusions. Pleural infection associated with IPC use remains a concern. Intrapleural therapy with tissue plasminogen activator (tPA) and deoxyribonuclease (DNase) significantly reduces surgical referrals in non-IPC pleural infection, but data on its use in IPC-related pleural infection are scarce. OBJECTIVE: To assess the safety and efficacy of intrapleural tPA and DNase in IPC-related pleural infection. METHODS: Patients with IPC-related pleural infection who received intrapleural tPA/DNase in five Australian and UK centers were identified from prospective databases. Outcomes on feasibility of intrapleural tPA/DNase delivery, its efficacy and safety were recorded. RESULTS: Thirty-nine IPC-related pleural infections (predominantly Staphylococcus aureus and gram-negative organisms) were treated in 38 patients; 87% had malignant effusions. In total, 195 doses (median 6 [IQR = 3-6]/patient) of tPA (2.5 mg-10 mg) and DNase (5 mg) were instilled. Most (94%) doses were delivered via IPCs using local protocols for non-IPC pleural infections. The mean volume of pleural fluid drained during the first 72 h of treatment was 3,073 (SD = 1,685) mL. Most (82%) patients were successfully treated and survived to hospital discharge without surgery; 7 required additional chest tubes or therapeutic aspiration. Three patients required thoracoscopic surgery. Pleurodesis developed post-infection in 23/32 of successfully treated patients. No major morbidity/mortality was associated with tPA/DNase. Four patients received blood transfusions; none had systemic or significant pleural bleeding. CONCLUSION: Treatment of IPC-related pleural infection with intrapleural tPA/DNase instillations via the IPC appears feasible and safe, usually without additional drainage procedures or surgery. Pleurodesis post-infection is common.

Cone-Beam Computed Tomography-Guided Electromagnetic Navigation for Peripheral Lung Nodules.

BACKGROUND: Electromagnetic navigation bronchoscopy (ENB) is a minimally invasive technology for the diagnosis of peripheral pulmonary nodules. However, ENB is limited by the lack of real-time confirmation of various biopsy devices. Cone-beam computed tomography (CBCT) could increase diagnostic yield by allowing real-time confirmation to overcome the inherent divergence of nodule location. OBJECTIVES: The aim of this study was to assess the diagnostic yield of ENB plus CBCT as compared with ENB alone for biopsy of peripheral lung nodules. METHOD: We conducted a retrospective study of patients undergoing ENB before and after the implementation of CBCT. Data from 62 consecutive patients with lung nodules located in the outer two-thirds of the lung who underwent ENB and combined ENB-CBCT were collected. Radial endobronchial ultrasound was used during all procedures as well. Diagnostic yield was defined as the presence of malignancy or benign histological findings that lead to a specific diagnosis. RESULTS: Thirty-one patients had ENB-CBCT, and 31 patients had only ENB for peripheral lung lesions. The median size of the lesion for the ENB-CBCT group was 16 (interquartile range (IQR) 12.6-25.5) mm as compared to 21.5 (IQR 16-27) mm in the ENB group (p = 0.2). In the univariate analysis, the diagnostic yield of ENB-CBCT was 74.2% and ENB 51.6% (p = 0.05). Following multivariate regression analysis adjusting for the size of the lesion, distance from the pleura, and presence of bronchus sign, the odds ratio for the diagnostic yield was 3.4 (95% CI 1.03-11.26, p = 0.04) in the ENB-CBCT group as compared with ENB alone. The median time for the procedure was shorter in patients in the ENB-CBCT group (74 min) than in those in the ENB group (90 min) (p = 0.02). The rate of adverse events was similar in both groups (6.5%, p = 0.7). CONCLUSIONS: The use of CBCT might increase the diagnostic yield in ENB-guided peripheral lung nodule biopsies. Future randomized clinical trials are needed to confirm such findings.

Tratamiento de lesiones osteocondrales de patela con trasplante autólogo: resultados funcionales e imagenológicos / Treatment of patellar osteochondral lesions with autologous grafts: functional and imaging results

Introducción El trasplante osteocondral autólogo es una técnica reproducible y con pocas complicaciones para el manejo de lesiones traumáticas grado III y IV de Outerbridge en patela. Con este estudio se busca evaluar los resultados funcionales e imagenológicos en pacientes manejados con esta técnica. Materiales y métodos Estudio descriptivo tipo serie de casos. Se incluyeron pacientes con lesiones traumáticas grado III y IV de Outerbridge (OB) en patela, menores de 25mm de diámetro, sin otras lesiones agregadas, operados con trasplante osteocondral autólogo entre marzo de 2013 y diciembre de 2016. Se evaluaron la escala visual análoga (EVA) y la escala funcional Kujala prequirúrgicas, y se compararon con los controles a los 3 y 6 meses. Se usó el score MOCART por resonancia magnética nuclear a los 6 meses postquirúrgicos para evaluar el porcentaje de osteointegración del injerto. Resultados El estudio incluyó 13 pacientes, 8 hombres (62%) con una edad promedio de 30 años. La lesión más frecuente fue la tipo IV de OB con un 86.6%. El EVA prequirúrgico promedio fue de 7.8 (±0.83), con controles a los 3 y 6 meses de 3.3 (±1.67) y 2.9 (±2.1) respectivamente, ambos con un valor de p <0.05. La escala funcional Kujala tuvo un promedio prequirúrgico de 33.3 (±10.1), con controles a los 3 y 6 meses de 56.1 (±21.1) y 74 (±17.6) respectivamente, ambos con un valor de p <0.05. El score MOCART promedio a los 6 meses fue de 70.5 (±12.1); 7 pacientes (53.8%) presentaron un valor mayor a 80. Discusión El Trasplante Osteocondral Autólogo en patela es una técnica con buenos resultados en pacientes con lesiones grado III y IV de OB, con mejoría significativa a los 3 y 6 meses del postoperatorio en la escala funcional de Kujala y reducción de la EVA. La tasa de integración del injerto medido por MOCART a los 6 meses fue 53%.

Background Autologous osteochondral grafting is a reproducible technique with few complications for the management of grade III and IV Outerbridge patellar injuries. This study aims to evaluate the functional and imaging results in patients managed with this technique. Methods A Case Series study was performed. The study included patients with grade III and IV Outerbridge (OB) traumatic patellar injuries of less than 25mm in diameter, with no other aggregate lesions, and operated on using autologous osteochondral grafts between March 2013 and December 2016. A pre-surgical assessment was made using a visual analogue scale (VAS) and the Kujala functional scale, and was compared with controls at 3 and 6 months. The MOCART score was used by nuclear magnetic resonance at 6 months post-operatively to evaluate the percentage of osteointegration of the graft. Results The study included 13 patients, 8 men (62%) with a mean age of 30 years. The most frequent lesion was type IV OB, with 86.6%. The mean pre-surgical VAS was 7.8 (± 0.83), with controls at 3 and 6 months of 3.3 (± 1.67) and 2.9 (± 2.1), respectively, both with a value of P<.05. The Kujala functional scale had a pre-surgical mean of 33.3 (± 10.1), with controls at 3 and 6 months of 56.1 (± 21.1) and 74 (± 17.6), respectively, both with a value of P<.05. The mean (magnetic resonance observation of cartilage repair tissue) MOCART score at 6 months was 70.5 (± 12.1), and 7 patients (53.8%) had a value greater than 80. Discussion Autologous osteochondral graft in the patella is a technique that obtained good results in patients with grade III and IV OB lesions. There is a significant improvement 3 and 6 months after surgery in the Kujala functional scale and a reduction of the VAS. The graft integration rate measured by MOCART at 6 months was 53%.

Hiperintensidad de tracto corticoespinal en resonancia magnética nuclear como signo de lesión de neurona motora superior en esclerosis lateral amiotrófica, reporte de caso y revisión de literatura / High-intensity signal in the corticospinal tract in MRI as a sign of upper motor neuron lesion in amyotrophic lateral sclerosis: Case report and literature review

RESUMEN La esclerosis lateral amiotrófica (ELA) es una enfermedad neurodegenerativa que compromete principalmente el sistema motor. Puede ser adquirida de manera esporádica o hereditaria y presenta una incidencia que varía entre 1.5 a 2.7 casos por 100.000 personas/año, con una mediana de supervivencia de 2 a 4 años. Esta enfermedad está caracterizada por compromiso de ambas motoneuronas, superior e inferior y sus manifestaciones clínicas pueden variar desde leve debilidad muscular en etapas tempranas, hasta falla respiratoria asociada en etapas tardías. El diagnóstico es esencialmente clínico y se hace de acuerdo a los criterios revisados de El Escorial para el diagnóstico de Esclerosis Lateral Amiotrófica (ELA). A pesar de esto, el diagnóstico de ELA en etapas tempranas sigue siendo un reto, lo que retrasa su identificación. Por esta razón surge el interés por identificar nuevos biomarcadores que ayuden al diagnóstico más temprano de la entidad. A continuación se presentará el caso de una mujer de 53 años, a la cual se le realiza un diagnóstico de ELA y en la que se encuentra como hallazgo de resonancia magnética cerebral (RM) cerebral, hiperintensidad bilateral del tracto corticoespinal. Discutiremos en este caso la importancia de los hallazgos en neuroimagen como biomarcador de daño en la enfermedad.

SUMMARY Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder that mainly involves the motor system. It may be sporadic or hereditary, and has an incidence ranging from 1.5 to 2.7 cases per 100,000 persons / year, with a median survival of 2 to 4 years. This disease is characterized by damage of both upper and lower motor neurons, and its clinical manifestations can vary from mild muscle weakness in early stages, to respiratory failure associated in later stages. The diagnosis is based on clinical findings and is made according to the revised El Escorial criteria. Although, the diagnosis of ALS remains a challenge in the early stages and delays it's identification. For this reason, interest to identify new biomarkers that help earlier identification and monitoring of the progression of the disease are being studied. Authors present a case of a woman of 53 years old with a clinical diagnosis of ALS and evidence of corticospinal tract high intensity signal on brain MRI. We will discuss the relevance of brain imaging findings as a biomarker of upper motoneuron damage in ALS.