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Rationale: The diagnostic concordance between transbronchial lung cryobiopsy (TBLC)-versus surgical lung biopsy (SLB) as the current gold standard-in interstitial lung disease (ILD) cases requiring histology remains controversial. Objectives: To assess diagnostic concordance between TBLC and SLB sequentially performed in the same patients, the diagnostic yield of both techniques, and subsequent changes in multidisciplinary assessment (MDA) decisions. Methods: A two-center prospective study included patients with ILD with a nondefinite usual interstitial pneumonia pattern (on high-resolution computed tomography scan) confirmed at a first MDA. Patients underwent TBLC immediately followed by video-assisted thoracoscopy for SLB at the same anatomical locations. After open reading of both sample types by local pathologists and final diagnosis at a second MDA (MDA2), anonymized TBLC and SLB slides were blindly assessed by an external expert pathologist (T.V.C.). Kappa-concordance coefficients and percentage agreement were computed for: TBLC versus SLB, MDA2 versus TBLC, MDA2 versus SLB, and blinded pathology versus routine pathology. Measurements and Main Results: Twenty-one patients were included. The median TBLC biopsy size (longest axis) was 7 mm (interquartile range, 5-8 mm). SLB biopsy sizes averaged 46.1 ± 13.8 mm. Concordance coefficients and percentage agreement were: TBLC versus SLB: κ = 0.22 (95% confidence interval [CI], 0.01-0.44), percentage agreement = 38% (95% CI, 18-62%); MDA2 versus TBLC: κ = 0.31 (95% CI, 0.06-0.56), percentage agreement = 48% (95% CI, 26-70)%; MDA2 versus SLB: κ = 0.51 (95% CI, 0.27-0.75), percentage agreement = 62% (95% CI, 38-82%); two pneumothoraces (9.5%) were recorded during TBLC. TBLC would have led to a different treatment if SLB was not performed in 11 of 21 (52%) of cases. Conclusions: Pathological results from TBLC and SLB were poorly concordant in the assessment of ILD. SLBs were more frequently concordant with the final diagnosis retained at MDA.
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Biópsia/métodos , Broncoscopia/métodos , Criocirurgia/métodos , Fibrose Pulmonar Idiopática/diagnóstico , Doenças Pulmonares Intersticiais/diagnóstico , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Tomografia Computadorizada por Raios XRESUMO
Club cell secretory protein (CCSP) knockout mice exhibit increased airway neutrophilia, as found in chronic obstructive pulmonary disease (COPD). We therefore investigated whether treating COPD airway epithelia with recombinant human CCSP (rhCCSP) could dampen exaggerated airway neutrophilia.Control, smoker and COPD air-liquid interface (ALI) cultures exposed to cigarette smoke extract (CSE) were treated with and without rhCCSP. The chemotactic properties of the supernatants were assessed using Dunn chambers. Neutrophil chemotaxis along recombinant human interleukin 8 (rhIL8) gradients (with and without rhCCSP) was also determined. rhCCSP-rhIL8 interactions were tested through co-immunoprecipitation, Biacore surface plasmon resonance (SPR) and in silico modelling. The relationship between CCSP/IL8 concentration ratios in the supernatant of induced sputum from COPD patients versus neutrophilic airway infiltration assessed in lung biopsies was assessed.Increased neutrophilic chemotactic activity of CSE-treated ALI cultures followed IL8 concentrations and returned to normal when supplemented with rhCCSP. rhIL8-induced chemotaxis of neutrophils was reduced by rhCCSP. rhCCSP and rhIL8 co-immunoprecipitated. SPR confirmed this in vitro interaction (equilibrium dissociation constant=8â µM). In silico modelling indicated that this interaction was highly likely. CCSP/IL8 ratios in induced sputum correlated well with the level of small airway neutrophilic infiltration (r2=0.746, p<0.001).CCSP is a biologically relevant counter-balancer of neutrophil chemotactic activity. These different approaches used in this study suggest that, among the possible mechanisms involved, CCSP may directly neutralise IL8.
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Bronquíolos/patologia , Quimiotaxia de Leucócito , Neutrófilos/citologia , Doença Pulmonar Obstrutiva Crônica/patologia , Uteroglobina/farmacologia , Humanos , Interleucina-8/metabolismo , Interleucina-8/farmacologia , Neutrófilos/efeitos dos fármacos , Doença Pulmonar Obstrutiva Crônica/metabolismo , Proteínas Recombinantes/farmacologia , Fumar , Escarro/citologiaRESUMO
BACKGROUND: Esophageal gastrointestinal stromal tumors (E-GISTs) represent less than 1% of all GISTs. The rarity of this lesion precludes the realization of randomized studies, and its treatment remains a matter of debate. We aimed to evaluate the feasibility of enucleation by video-assisted thoracic surgery (VATS) for low- to intermediate-risk E-GIST. METHODS: We performed a retrospective review of patients treated by enucleation through VATS between January 2004 and January 2014 and reviewed the literature. RESULTS: We included five patients (four men and one woman). Mean age was 53 years (range: 49-79). Three patients were diagnosed because of dysphagia and two others incidentally. The diagnosis was made by immunostaining demonstrating CD117 expression on tumor cells. The mitotic index of all E-GISTs was low (≤ 5 per 50 high-power field). Median postoperative follow-up was 5.5 years, and there was no recurrence. CONCLUSION: Thoracoscopic enucleation of E-GIST seems to represent a valuable option as the postoperative morbidity/mortality is low and the oncological outcome is good for low-to-intermediate grade of malignity tumors.This is a retrospective study focused on minimally invasive treatment of E-GIST. We evaluated the feasibility of VATS enucleation of low-to-medium grade of malignity E-GIST.
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Neoplasias Esofágicas/cirurgia , Esofagectomia/métodos , Tumores do Estroma Gastrointestinal/cirurgia , Cirurgia Torácica Vídeoassistida , Idoso , Bases de Dados Factuais , Neoplasias Esofágicas/patologia , Esofagectomia/efeitos adversos , Estudos de Viabilidade , Feminino , Tumores do Estroma Gastrointestinal/patologia , Humanos , Masculino , Pessoa de Meia-Idade , Gradação de Tumores , Estudos Retrospectivos , Cirurgia Torácica Vídeoassistida/efeitos adversos , Resultado do TratamentoRESUMO
BACKGROUND: The aim of this study was to evaluate outcomes of left subclavian artery (LSA) revascularization for hybrid aortic arch debranching. METHODS: Between 1998 and 2015, 68 patients (41 men; mean age, 67 ± 16 years) underwent thoracic endovascular aortic repair (TEVAR) with LSA coverage, 19.2% (n = 13) were never revascularized, and the remaining patients underwent LSA revascularization (n = 55; 80.8%). Revascularization was achieved by LSA-carotid transposition via a medial approach in 81.8% (n = 45) and a lateral approach in 18.2% (n = 10). The indication for TEVAR was aneurysmal disease in 30.9% (n = 17), dissection in 29% (n = 16; acute, n = 5), traumatic aortic injury in 21.8% (n = 12), pseudoaneurysm in 10.9% (n = 6), aortobronchial fistula in 5.5% (n = 3), and penetrating atherosclerotic ulcer in 1.9% (n = 1). Elective cases accounted for 52.7% (n = 29). Follow-up computed tomography scans were performed at 1 week, 3 and 6 months, and annually thereafter. RESULTS: LSA revascularization was achieved in all the cases. Thirty-day mortality rate was 12.7%. Thirty-day mortality related to LSA revascularization was 0%. No patient suffered a stroke. Vocal cord paralysis was detected in 7.2% of patients (n = 4). Hematoma requiring surgical drainage was observed in 3.6% of patients (n = 2). Lymph leak requiring revision surgery was observed in 1.8% of patients (n = 1). Phrenic nerve palsy was not observed. The local complication rate was significantly higher (P = 0.03) in patients with LSA transposition via a lateral approach (20%; n = 2) when compared to patients with LSA revascularization via a medial approach (11.1%; n = 5). After a mean follow-up of 31.5 months (range, 2-171 months), the patency of the LSA revascularization was maintained in all patients. CONCLUSIONS: During TEVAR, when LSA coverage is required, LSA revascularization is a durable procedure associated with a low morbidity rate. LSA transposition via a medial approach would appear to be associated with significantly fewer complications.
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Aorta Torácica/cirurgia , Doenças da Aorta/cirurgia , Procedimentos Endovasculares/métodos , Artéria Subclávia/cirurgia , Procedimentos Cirúrgicos Vasculares/métodos , Idoso , Idoso de 80 Anos ou mais , Aorta Torácica/diagnóstico por imagem , Doenças da Aorta/diagnóstico por imagem , Doenças da Aorta/mortalidade , Aortografia/métodos , Angiografia por Tomografia Computadorizada , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Complicações Pós-Operatórias/etiologia , Estudos Retrospectivos , Fatores de Risco , Fatores de Tempo , Resultado do Tratamento , Procedimentos Cirúrgicos Vasculares/efeitos adversos , Procedimentos Cirúrgicos Vasculares/mortalidadeAssuntos
Aborto Espontâneo , Fístula Arteriovenosa , Artéria Pulmonar/anormalidades , Veias Pulmonares/anormalidades , Adulto , Feminino , Humanos , Osteoartropatia Hipertrófica Secundária/etiologia , Osteoartropatia Hipertrófica Secundária/patologia , Gravidez , Artéria Pulmonar/diagnóstico por imagemRESUMO
Introduction: Non-small cell lung cancer (NSCLC) is often associated with compromised lung function. Real-world data on the impact of surgical approach in NSCLC patients with compromised lung function are still lacking. The objective of this study is to assess the potential impact of minimally invasive surgery (MIS) on 90-day post-operative mortality after anatomic lung resection in high-risk operable NSCLC patients. Methods: We conducted a retrospective multicentre study including all patients who underwent anatomic lung resection between January 2010 and October 2021 and registered in the Epithor database. High-risk patients were defined as those with a forced expiratory volume in 1â s (FEV1) or diffusing capacity of the lung for carbon monoxide (DLCO) value below 50%. Co-primary end-points were the impact of risk status on 90-day mortality and the impact of MIS on 90-day mortality in high-risk patients. Results: Of the 46 909 patients who met the inclusion criteria, 42 214 patients (90%) with both preoperative FEV1 and DLCO above 50% were included in the low-risk group, and 4695 patients (10%) with preoperative FEV1 and/or preoperative DLCO below 50% were included in the high-risk group. The 90-day mortality rate was significantly higher in the high-risk group compared to the low-risk group (280 (5.96%) versus 1301 (3.18%); p<0.0001). In high-risk patients, MIS was associated with lower 90-day mortality compared to open surgery in univariate analysis (OR=0.04 (0.02-0.05), p<0.001) and in multivariable analysis after propensity score matching (OR=0.46 (0.30-0.69), p<0.001). High-risk patients operated through MIS had a similar 90-day mortality rate compared to low-risk patients in general (3.10% versus 3.18% respectively). Conclusion: By examining the impact of surgical approaches on 90-day mortality using a nationwide database, we found that either preoperative FEV1 or DLCO below 50% is associated with higher 90-day mortality, which can be reduced by using minimally invasive surgical approaches. High-risk patients operated through MIS have a similar 90-day mortality rate as low-risk patients.
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OBJECTIVE: To characterize pulmonary hemodynamic changes in relation to lung injury at 2 time points [48 h (H48) and 168 h (H168)] after pneumonectomy under intraoperative protective ventilation in order to improve postpneumonectomy pulmonary edema (PPE) prevention. METHOD: Fifteen pigs (25 ± 1.9 kg) were randomly allocated to nonsurgical (control, n = 5) and surgical (H48 and H168) groups. A left pneumonectomy under volume-controlled one-lung ventilation (OLV) (low tidal volume, positive end-expiratory pressure = 4 cm H2O, inspired oxygen fraction = 50%) was performed in surgical animals. Mean pulmonary artery pressure (MPAP) and pulmonary artery occlusion pressure were recorded. Pulmonary vascular resistance (PVR) was calculated. Pulmonary damage score (PDS) and bronchoalveolar albumin level were evaluated. Data were collected after induction (T0), after OLV (T1), after left pneumonectomy (T2), and at H48 or H168 (T3). RESULTS: Pneumonectomy caused precapillary pulmonary arterial hypertension (PAH) measured at T3 H48 (36.2 ± 3.67 mm Hg). PAH was delayed temporarily (both after OLV and after pneumonectomy) (p < 0.001), and linked with PVR (r = 0.93; p < 0.05). PDS and bronchoalveolar albumin level varied with MPAP (r = 0.76; p < 0.001 and r = 0.55; p < 0.05). CONCLUSION: Given that PAH is delayed and related to PVR increase, indicating secondary pulmonary vascular bed adaptation limits, pharmacological treatment should focus on a delayed failure in pulmonary capacitance in patients at risk of PPE.
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Hipertensão Pulmonar/etiologia , Pneumonectomia/efeitos adversos , Albuminas/análise , Animais , Hipertensão Pulmonar Primária Familiar , Feminino , Hemodinâmica , Pulmão/patologia , Ventilação Monopulmonar , Edema Pulmonar/etiologia , Suínos , Resistência VascularRESUMO
BACKGROUND: Early-stage lung cancer, primarily treated with surgery, often occur in poor surgical candidates (impaired respiratory function, prior thoracic surgery, severe comorbidities). Stereotactic ablative radiotherapy (SABR) is a non-invasive alternative that provides comparable local control. This technique is particularly relevant for surgically resectable metachronous lung cancer, in patients unable to undergo surgery.. The objective of this study is to evaluate the clinical outcome of patients treated with SABR for stage I metachronous lung cancer (MLC) versus stage I primary lung cancer (PLC). PATIENTS AND METHODS: 137 patients treated with SABR for stage I non-small cell lung cancer were retrospectively reviewed, of which 28 (20.4%) were MLC and 109 (79.6%) were PLC. Cohorts were evaluated for differences in overall survival (OS), progression-free survival (PFS), metastasis-free survival, local control (LC), and toxicity. RESULTS: After SABR, patients treated for MLC have comparable median age (76.6 vs 78.6, p = 0.2), 3-year LC (83.6% vs. 72.6%, p = 0.2), PFS (68.7% vs. 50.9%, p = 0.9), and OS (78.6% vs. 52.1%, p = 0.9) as PLC, along with similar rates of total (54.1% vs. 42.9%, p = 0.6) and grade 3 + toxicity (3.7% vs. 3.6%, p = 0.9). Previous treatment of MLC patients was either surgery (21/28, 75%) or SABR (7/28, 25%). The median follow-up was 53 months. CONCLUSION: SABR is a safe and effective approach for localized metachronous lung cancer.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Radiocirurgia , Humanos , Carcinoma Pulmonar de Células não Pequenas/radioterapia , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Neoplasias Pulmonares/radioterapia , Neoplasias Pulmonares/cirurgia , Estudos Retrospectivos , Resultado do Tratamento , Radiocirurgia/métodos , PulmãoRESUMO
INTRODUCTION: Both MET expression and the PD-L1 tumor proportion score (TPS) are companion diagnostics for treatment of advanced non-small cell lung carcinoma (aNSCLC) patients. We evaluated the rate of correlation between MET expression and the PD-L1 TPS in matched biopsies and surgically resected specimens from NSCLC patients. PATIENTS AND METHODS: This retrospective analysis assessed the prevalence and correlation between MET expression (SP44 clone) and the PD-L1 TPS (22C3 clone) by immunohistochemistry together with molecular alterations determined by targeted next-generation sequencing in matched lung biopsy and surgically lung resected specimens from 70 patients with NSCLC. RESULTS: The study found a significant correlation between the MET H-score in surgical samples and matched biopsies (P-value < 0.0001), as well as between the PD-L1 TPS in paired biopsies and surgical samples (P-value < 0.0001). However, there was no significant correlation between the MET H-score or expression subgroups and the PD-L1 TPS in both types of paired samples (P-value = 0.47, and P-value = 0.90). The MET H-score was significantly higher in adenocarcinoma compared to squamous cell carcinoma (P-value < 0.0001). A mutational analysis showed that the MET H-score was significantly higher in NSCLC cases with targetable molecular alterations (P-value = 0.0095), while no significant correlation was found for the PD-L1 TPS. CONCLUSIONS: Our study found no significant correlation between PD-L1 and MET expression in samples from NSCLC patients, highlighting the importance of personalized treatment strategies based on individual expression profiles. These findings provide valuable insight into the development of effective immunotherapy and targeted therapy for NSCLC patients.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Antígeno B7-H1/metabolismo , Biomarcadores Tumorais/metabolismo , Biópsia , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/patologia , Estudos RetrospectivosRESUMO
Objective: Recent studies have demonstrated the feasibility and favorable long-term results of tracheobronchial replacement using stented cryopreserved aortic allografts. We propose to investigate the outcomes of this emerging technique in the subgroup of patients with extensive tracheal cancer. Methods: This study was based on 13 patients with primary extensive tracheal cancer extracted from the prospective registry TRITON-01 (ClinicalTrials.gov Identifier: NCT04263129), which included 40 patients in total. We analyzed early and late outcomes in this subset of patients. Results: From March 2019 to September 2022, 13 patients were included in the study. There were 9 female and 4 male patients, with a mean age of 53.9 years [36-71 years]. They had tracheal replacement for extended adenoid cystic carcinoma (n = 11), squamous cell carcinoma (n = 1), and mucoepidermoid carcinoma (n = 1). A venovenous extracorporeal membrane oxygenation was used in the 6 last cases. The mean length of resection was 81 mm [50-120 mm]. There was no 30-day postoperative mortality. A complete resection (R0) was achieved in 11 patients. The main late complications consisted of tracheal granulomas related to the stent and requiring repeated bronchoscopies (n = 9), pneumonia (n = 3), airway infection (n = 1), bronchoesophageal fistula (n = 1), mechanical stent obstruction requiring change (n = 2), and mediastinitis treated by antibiotics, drainage, and omentoplasty (n = 1). With a maximal follow-up of 3 years and 7 months, cancer recurrence was observed in 2 patients. All patients were alive at last follow-up except 2 (84.6%). Conclusions: Airway replacement using stented CAA represents a feasible and promising solution for extensive tracheal cancer.
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Several therapies to improve the management of lymphoma are currently being investigated, necessitating the development of new biomarkers. However, this requires high-quality and clinically annotated biological material. Therefore, we established a lymphoma biobank including all available biological material (tissue specimens and matched biological resources) along with associated clinical data for lymphoma patients diagnosed, according to the WHO classification, between 2005 and 2022 in the Laboratory of Clinical and Experimental Pathology, Nice, France. We retrospectively included selected cases in a new collection at the Côte d'Azur Biobank, which contains 2150 samples from 363 cases (351 patients). The male/female ratio was 1.3, and the median age at diagnosis was 58 years. The most common lymphoma types were classical Hodgkin lymphoma, diffuse large B-cell lymphoma, and extra-nodal marginal zone lymphoma of MALT tissue. The main sites of lymphoma were the mediastinum, lymph node, Waldeyer's ring, and lung. The Côte d'Azur Biobank is ISO 9001 and ISO 20387 certified and aims to provide high quality and diverse biological material to support translational research projects into lymphoma. The clinico-pathological data generated by this collection should aid the development of new biomarkers to enhance the survival of patients with lymphoid malignancies.
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BACKGROUND: The aim of this study was to evaluate the short- and midterm results following endovascular repair of dissecting aortic arch aneurysm after surgical treatment of acute type A dissection. METHODS: Between 2003 and 2010, six consecutive patients previously operated for acute type A dissection underwent endovascular repair of dissecting aortic arch aneurysm (six men, mean age: 63 ± 9.8 years); one of the aneurysms was ruptured. Follow-up computed tomography scans were performed at 1 week, at 3 and 6 months, and annually thereafter. RESULTS: All endografts were successfully deployed (TAG [2], Valiant [4]). All the patients underwent hybrid technique with supra-aortic debranching (through a sternotomy approach in four cases and through a cervical approach in two cases) and simultaneous or staged endovascular stent-grafting. During the same operative time, one patient underwent, on full cardiopulmonary bypass, saphenous vein bypass from the ascending aorta to the anterior descending coronary artery. One permanent neurologic event was observed. After a mean follow-up of 22.3 ± 14.6 months, no aortic-related mortality was observed. No cases of stent-graft migration or secondary rupture were observed. The ruptured aortic arch aneurysm presented a type I endoleak at 6 months and was successfully treated with a second endograft. One patient died of an unrelated cause 7 months after surgical repair. CONCLUSIONS: Our experience demonstrates promising potential of endovascular repair of dissecting aortic arch aneurysm after surgical treatment of acute type A dissection. The potential to diminish the magnitude of the surgical procedure and the consequences of aortic arch exposure, and above all avoiding the need for circulatory arrest, is promising and mandates further investigation to determine the efficacy and durability of this technique.
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Aneurisma da Aorta Torácica/cirurgia , Dissecção Aórtica/cirurgia , Ruptura Aórtica/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Doença Aguda , Idoso , Dissecção Aórtica/diagnóstico por imagem , Aneurisma da Aorta Torácica/diagnóstico por imagem , Ruptura Aórtica/diagnóstico por imagem , Aortografia/métodos , Prótese Vascular , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/instrumentação , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/instrumentação , Feminino , França , Humanos , Masculino , Pessoa de Meia-Idade , Reoperação , Stents , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
RATIONALE: Diaphragmatic function is a major determinant of the ability to successfully wean patients from mechanical ventilation (MV). Paradoxically, MV itself results in a rapid loss of diaphragmatic strength in animals. However, very little is known about the time course or mechanistic basis for such a phenomenon in humans. OBJECTIVES: To determine in a prospective fashion the time course for development of diaphragmatic weakness during MV; and the relationship between MV duration and diaphragmatic injury or atrophy, and the status of candidate cellular pathways implicated in these phenomena. METHODS: Airway occlusion pressure (TwPtr) generated by the diaphragm during phrenic nerve stimulation was measured in short-term (0.5 h; n = 6) and long-term (>5 d; n = 6) MV groups. Diaphragmatic biopsies obtained during thoracic surgery (MV for 2-3 h; n = 10) and from brain-dead organ donors (MV for 24-249 h; n = 15) were analyzed for ultrastructural injury, atrophy, and expression of proteolysis-related proteins (ubiquitin, nuclear factor-κB, and calpains). MEASUREMENTS AND MAIN RESULTS: TwPtr decreased progressively during MV, with a mean reduction of 32 ± 6% after 6 days. Longer periods of MV were associated with significantly greater ultrastructural fiber injury (26.2 ± 4.8 vs. 4.7 ± 0.6% area), decreased cross-sectional area of muscle fibers (1,904 ± 220 vs. 3,100 ± 329 µm²), an increase of ubiquitinated proteins (+19%), higher expression of p65 nuclear factor-κB (+77%), and greater levels of the calcium-activated proteases calpain-1, -2, and -3 (+104%, +432%, and +266%, respectively) in the diaphragm. CONCLUSIONS: Diaphragmatic weakness, injury, and atrophy occur rapidly in critically ill patients during MV, and are significantly correlated with the duration of ventilator support.
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Diafragma/lesões , Debilidade Muscular/etiologia , Respiração Artificial/efeitos adversos , Adulto , Calpaína/análise , Diafragma/química , Diafragma/patologia , Diafragma/fisiopatologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Debilidade Muscular/patologia , Debilidade Muscular/fisiopatologia , Atrofia Muscular/etiologia , Atrofia Muscular/patologia , Atrofia Muscular/fisiopatologia , Fatores de Tempo , Fator de Transcrição RelA/análise , Proteínas Ubiquitinadas/análise , Adulto JovemRESUMO
OBJECTIVES: The evaluation of an increasing number of diagnostic and predictive markers is playing a central role in precision thoracic oncology. Multiplex immunohistochemistry (mIHC), alongside next-generation sequencing, is ideally situated for this purpose and maximizes tumor tissue preservation for molecular analyses that use increasingly large panels. However, the standardization and validation of mIHC that supports routine clinical laboratory processes are mandatory. After a previous proof-of-concept study, we now (i) optimized two automated four-plex assays on a commercially available IHC autostainer for use in daily practices worldwide and (ii) evaluated the repeatability and concordance of the assessment of the cell density. PATIENTS AND METHODS: Two four-plex mIHC assays [i) TTF1, p40, PD-L1, CD8; and, ii) ALK, ROS1, BRAFV600E, NTRK] were optimized on the BenchMark ULTRA autostainer (Ventana Medical Systems, Inc.), as determined in comparison to conventional IHC chromogenic assays. Intra-site repeatability was evaluated on serial tumor sections from non-small cell lung carcinomas (NSCLC). The concordance was assessed by linear fit to plots of the percentage staining evaluated on tumor sections from 89 NSCLC patients. RESULTS: Following optimization, an average concordance for a staining rate of 95.4% was achieved between conventional IHC and mIHC across all selected markers. Assessment of intra-site repeatability showed strong concordance for all these markers (average, R2 = 0.96; P-value < 0.001). CONCLUSIONS: Our optimized mIHC assay gave a sensitive and repeatable assessment of two panels of eight diagnostic and predictive biomarkers for NSCLC. The availability of standardized protocols to determine these biomarkers on a widely available IHC platform will expand the number of pathology laboratories able to determine the eligibility of patients with NSCLC for targeted treatment or immunotherapy in a reliable and concordant manner, thus providing a unique sample-sparing tool to characterize limited tissue samples in thoracic oncology.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Anticorpos Monoclonais/uso terapêutico , Antígeno B7-H1/análise , Biomarcadores Tumorais/análise , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Humanos , Imuno-Histoquímica , Neoplasias Pulmonares/patologia , Proteínas Tirosina Quinases , Proteínas Proto-Oncogênicas/uso terapêuticoRESUMO
The histological distinction of lung neuroendocrine carcinoma, including small cell lung carcinoma (SCLC), large cell neuroendocrine carcinoma (LCNEC) and atypical carcinoid (AC), can be challenging in some cases, while bearing prognostic and therapeutic significance. To assist pathologists with the differentiation of histologic subtyping, we applied a deep learning classifier equipped with a convolutional neural network (CNN) to recognize lung neuroendocrine neoplasms. Slides of primary lung SCLC, LCNEC and AC were obtained from the Laboratory of Clinical and Experimental Pathology (University Hospital Nice, France). Three thoracic pathologists blindly established gold standard diagnoses. The HALO-AI module (Indica Labs, UK) trained with 18,752 image tiles extracted from 60 slides (SCLC = 20, LCNEC = 20, AC = 20 cases) was then tested on 90 slides (SCLC = 26, LCNEC = 22, AC = 13 and combined SCLC with LCNEC = 4 cases; NSCLC = 25 cases) by F1-score and accuracy. A HALO-AI correct area distribution (AD) cutoff of 50% or more was required to credit the CNN with the correct diagnosis. The tumor maps were false colored and displayed side by side to original hematoxylin and eosin slides with superimposed pathologist annotations. The trained HALO-AI yielded a mean F1-score of 0.99 (95% CI, 0.939-0.999) on the testing set. Our CNN model, providing further larger validation, has the potential to work side by side with the pathologist to accurately differentiate between the different lung neuroendocrine carcinoma in challenging cases.
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Hybrid repair of ruptured aortic arch repair has been proposed as a valuable approach. However, the presence of an anterior mediastinal hematoma must be carefully detected because of the inherent risk of rupture at sternotomy. We report the case of a patient presenting a ruptured aortic arch aneurysm with anterior rupture who underwent hybrid repair using a temporary extra-anatomic brain perfusion followed by total rerouting of the supra-aortic trunks. We propose this adjunctive technique as a means of allowing a safe endovascular exclusion of aortic arch lesions and avoiding the risk of acute and total aortic rupture in case of anterior rupture of aortic arch aneurysms.
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Aneurisma da Aorta Torácica/cirurgia , Ruptura Aórtica/cirurgia , Implante de Prótese Vascular , Procedimentos Endovasculares , Perfusão/métodos , Idoso , Aneurisma da Aorta Torácica/complicações , Aneurisma da Aorta Torácica/diagnóstico por imagem , Aneurisma da Aorta Torácica/fisiopatologia , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/etiologia , Ruptura Aórtica/fisiopatologia , Aortografia/métodos , Circulação Cerebrovascular , Hematoma/diagnóstico por imagem , Hematoma/etiologia , Hemodinâmica , Humanos , Masculino , Tomografia Computadorizada por Raios X , Resultado do TratamentoRESUMO
PURPOSE: To analyze the impact of stent-graft design on the outcome of endovascular repair of acute traumatic thoracic aortic transection. METHODS: Forty-eight patients (38 men; mean age 37 ± 11 years) underwent endovascular repair for an acute traumatic aortic rupture between April 2001 and March 2011. Up to October 2007, 32 patients (mean age 41 ± 16 years; group 1) were treated with the first generation of commercially available thoracic stent-grafts (10 Talent, 20 Excluder/TAG, 2 Zenith). From November 2007, 16 patients (mean age 42 ± 19 years; group 2) were treated with second-generation thoracic stent-grafts (13 Valiant and 3 C-TAG). The 2 groups were statistically comparable. Follow-up computed tomography was performed at 1 week; at 3 and 6 months; and annually thereafter. RESULTS: In the 2 groups, the mortality rate related to aortic repair was nil. All the patients have completed each of their scheduled follow-up evaluations and CT scans. The morbidity rate was significantly reduced (p = 0.0003) from 18.7% (first generation) to 6.2% (second generation). Type I endoleak (n = 1), inadvertent coverage of the supra-aortic trunks (n = 3), and stent-graft collapse (n = 2) occurred only with the first-generation stent-grafts. One iliac artery rupture occurred with a second-generation stent-graft. CONCLUSION: Enhanced stent-graft conformability and more accurate delivery systems have significantly decreased the morbidity of endovascular repair of acute traumatic transection of the thoracic aorta. The increasing clinical experience may also have contributed to improved results.
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Ruptura Aórtica/cirurgia , Implante de Prótese Vascular/instrumentação , Prótese Vascular , Procedimentos Endovasculares/instrumentação , Stents , Artérias Torácicas/cirurgia , Lesões do Sistema Vascular/cirurgia , Doença Aguda , Adulto , Ruptura Aórtica/diagnóstico por imagem , Ruptura Aórtica/mortalidade , Aortografia/métodos , Implante de Prótese Vascular/efeitos adversos , Implante de Prótese Vascular/mortalidade , Distribuição de Qui-Quadrado , Procedimentos Endovasculares/efeitos adversos , Procedimentos Endovasculares/mortalidade , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Desenho de Prótese , Medição de Risco , Fatores de Risco , Artérias Torácicas/diagnóstico por imagem , Artérias Torácicas/lesões , Fatores de Tempo , Tomografia Computadorizada por Raios X , Resultado do Tratamento , Lesões do Sistema Vascular/diagnóstico por imagem , Lesões do Sistema Vascular/mortalidade , Adulto JovemRESUMO
Complex chest and lung infections with bronchial fistula are life-threatening situations with a mortality rate of up to 20%. If medical treatment fails, these patients require aggressive procedures to heal. Transposition of the omentum is a valuable, nonstandard option in these complex cases with aggressive infection involving the pleural space, with or without a bronchial fistula, when medical treatment is unsuccessful. We present a 29-year-old female patient diagnosed with primary immunodeficiency and invasive fungal infection with involvement of the left upper lobe and mediastinal and vertebral bodies treated with a lobectomy and intrathoracic transposition of the omentum.
Assuntos
Pneumopatias Fúngicas/cirurgia , Omento/transplante , Adulto , Ascomicetos , Feminino , Humanos , PneumonectomiaRESUMO
Background: Distal airway metaplasia may precede honeycombing in progressive fibrosing interstitial lung disease (ILD). The SCGB1A1+ bronchiolar-specific club cell may play a role in this aberrant regenerative process. Objective: To assess the presence of club cells in the small airways of patients suffering from ILD. Methods: Small airways (internal diameter <2 mm) in lung samples [surgical lung biopsy (SLB) and/or transbronchial lung cryobiopsy (TBLC)] from 14 patients suffering from ILD and 10 controls were morphologically assessed and stained for SCGB1A1. SCGB1A1 was weighted by epithelial height as a marker of airway generation (SCGB1A1/EH). Correlations between clinical, functional, and high-resolution CT (HRCT) prognostic factors and histomorphometry were assessed. Results: Small airways from samples with ILD patterns were significantly less dense in terms of SCGB1A1+ cells [0.064 (0.020-0.172)] as compared to controls' sample's small airways [0.393 (0.082-0.698), p < 0.0001]. Usual interstitial pneumonia (UIP) patterns most frequently contained small airways with limited or absent SCGB1A1 expression (SCGB1A1/EH <0.025): UIP (18/33; 55%) as compared with non-UIP patterns (4/31; 13%) or controls (0/29; 0%): p < 0.0001. In addition, correlations with HRCT indicated a significant negative relationship between SCGB1A1 and bronchiectasis as a feature of bronchiolization (Rho -0.63, p < 0.001) and a positive relationship with both forced vital capacity (FVC) and Hounsfield unit (HU)-distribution pattern in kurtosis (Rho 0.38 and 0.50, respectively, both p < 0.001) as markers of fibrotic changes. Conclusion: Compared with controls, the small airways of patients with ILD more often lack SCGB1A1, especially so in UIP. Low densities of SCGB1A1-marked cells correlate with bronchiectasis and fibrotic changes. Further research investigating SCGB1A1 staining as a pathological feature of the bronchiolization process is merited.