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Rationale: Diaphragm dysfunction is frequently observed in critically ill patients with difficult weaning from mechanical ventilation. Objectives: To evaluate the effects of temporary transvenous diaphragm neurostimulation on weaning outcome and maximal inspiratory pressure. Methods: Multicenter, open-label, randomized, controlled study. Patients aged ⩾18 years on invasive mechanical ventilation for ⩾4 days and having failed at least two weaning attempts received temporary transvenous diaphragm neurostimulation using a multielectrode stimulating central venous catheter (bilateral phrenic stimulation) and standard of care (treatment) (n = 57) or standard of care (control) (n = 55). In seven patients, the catheter could not be inserted, and in seven others, pacing therapy could not be delivered; consequently, data were available for 43 patients. The primary outcome was the proportion of patients successfully weaned. Other endpoints were mechanical ventilation duration, 30-day survival, maximal inspiratory pressure, diaphragm-thickening fraction, adverse events, and stimulation-related pain. Measurements and Main Results: The incidences of successful weaning were 82% (treatment) and 74% (control) (absolute difference [95% confidence interval (CI)], 7% [-10 to 25]), P = 0.59. Mechanical ventilation duration (mean ± SD) was 12.7 ± 9.9 days and 14.1 ± 10.8 days, respectively, P = 0.50; maximal inspiratory pressure increased by 16.6 cm H2O and 4.8 cm H2O, respectively (difference [95% CI], 11.8 [5 to 19]), P = 0.001; and right hemidiaphragm thickening fraction during unassisted spontaneous breathing was +17% and -14%, respectively, P = 0.006, without correlation with changes in maximal inspiratory pressure. Serious adverse event frequency was similar in both groups. Median stimulation-related pain in the treatment group was 0 (no pain). Conclusions: Temporary transvenous diaphragm neurostimulation did not increase the proportion of successful weaning from mechanical ventilation. It was associated with a significant increase in maximal inspiratory pressure, suggesting reversal of the course of diaphragm dysfunction. Clinical trial registered with www.clinicaltrials.gov (NCT03096639) and the European Database on Medical Devices (CIV-17-06-020004).
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Diafragma , Nervio Frénico , Anciano , Humanos , Presiones Respiratorias Máximas , Dolor , Respiración Artificial/efectos adversos , Desconexión del VentiladorRESUMEN
As new SARS-CoV-2 variants emerge, there is an urgent need to increase the efficiency and availability of viral genome sequencing, notably to detect the lineage in samples with a low viral load. SARS-CoV-2 genome next-generation sequencing (NGS) was performed retrospectively in a single center on 175 positive samples from individuals. An automated workflow used the Ion AmpliSeq SARS-CoV-2 Insight Research Assay on the Genexus Sequencer. All samples were collected in the metropolitan area of the city of Nice (France) over a period of 32 weeks (from 19 July 2021 to 11 February 2022). In total, 76% of cases were identified with a low viral load (Ct ≥ 32, and ≤200 copies/µL). The NGS analysis was successful in 91% of cases, among which 57% of cases harbored the Delta variant, and 34% the Omicron BA.1.1 variant. Only 9% of cases had unreadable sequences. There was no significant difference in the viral load in patients infected with the Omicron variant compared to the Delta variant (Ct values, p = 0.0507; copy number, p = 0.252). We show that the NGS analysis of the SARS-CoV-2 genome provides reliable detection of the Delta and Omicron SARS-CoV-2 variants in low viral load samples.
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COVID-19 , SARS-CoV-2 , Humanos , Estudios Retrospectivos , Carga Viral , Secuenciación de Nucleótidos de Alto RendimientoRESUMEN
BACKGROUND: Mucosal antibodies can prevent virus entry and replication in mucosal epithelial cells and therefore virus shedding. Parenteral booster injection of a vaccine against a mucosal pathogen promotes stronger mucosal immune responses following prior mucosal infection compared with injections of a parenteral vaccine in a mucosally naive subject. We investigated whether this was also the case for the BNT162b2 coronavirus disease 2019 (COVID-19) messenger RNA vaccine. METHODS: Twenty recovered COVID-19 subjects (RCSs) and 23 severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-naive subjects were vaccinated with, respectively, 1 and 2 doses of the BNT162b2 COVID-19 vaccine. Nasal epithelial lining fluid (NELF) and plasma were collected before and after vaccination and assessed for immunoglobulin G (IgG) and IgA antibody levels to Spike and for their ability to neutralize binding of Spike to angiotensin-converting enzyme-2 receptor. Blood was analyzed 1 week after vaccination for the number of Spike-specific antibody-secreting cells (ASCs) with a mucosal tropism. RESULTS: All RCSs had both nasal and blood SARS-CoV-2-specific antibodies at least 90 days after initial diagnosis. In RCSs, a single dose of vaccine amplified preexisting Spike-specific IgG and IgA antibody responses in both NELF and blood against both vaccine homologous and variant strains, including Delta. These responses were associated with Spike-specific IgG and IgA ASCs with a mucosal tropism in blood. Nasal IgA and IgG antibody responses were lower in magnitude in SARS-CoV-2-naive subjects after 2 vaccine doses compared with RCSs after 1 dose. CONCLUSIONS: Mucosal immune response to the SARS-CoV-2 Spike protein is higher in RCSs after a single vaccine dose compared with SARS-CoV-2-naive subjects after 2 doses.
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COVID-19 , SARS-CoV-2 , Humanos , Vacuna BNT162 , Vacunas contra la COVID-19 , Vacunación , Inmunoglobulina G , Anticuerpos AntiviralesRESUMEN
BACKGROUND: 3-9% of low-grade preinvasive bronchial lesions progress to cancer. This study assessed the usefulness of an intensive bronchoscopy surveillance strategy in patients with bronchial lesions up to moderate squamous dysplasia. METHODS: SELEPREBB (ClinicalTrials.gov NCT00213603) was a randomised study conducted in 17 French centres. After baseline lung computed tomography (CT) and autofluorescence bronchoscopy (AFB) to exclude lung cancer and bronchial severe squamous dysplasia or carcinoma in situ (CIS), patients were assigned to standard surveillance (arm A) with CT and AFB at 36â months or to intensive surveillance (arm B) with AFB every 6â months. Further long-term data were obtained with a median follow-up of 4.7â years. RESULTS: 364 patients were randomised (A: 180, B: 184). 27 patients developed invasive lung cancer and two developed persistent CIS during the study, with no difference between arms (OR 0.63, 95% CI 0.20-1.96, p=0.42). Mild or moderate dysplasia at baseline bronchoscopy was a significant lung cancer risk factor both at 3â years (8 of 74 patients, OR 6.9, 95% CI 2.5-18.9, p<0.001) and at maximum follow-up (16 of 74 patients, OR 5.9, 95% CI 2.9-12.0, p<0.001). Smoking cessation was significantly associated with clearance of bronchial dysplasia on follow-up (OR 0.12, 95% CI 0.01-0.66, p=0.005) and with a reduced risk of lung cancer at 5â years (OR 0.15, 95% CI 0.003-0.99, p=0.04). CONCLUSION: Patients with mild or moderate dysplasia are at very high risk for lung cancer at 5â years, with smoking cessation significantly reducing the risk. Whereas intensive bronchoscopy surveillance does not improve patient outcomes, the identification of bronchial dysplasia using initial bronchoscopy maybe useful for risk stratification strategies in lung cancer screening programmes.
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Carcinoma de Células Escamosas , Neoplasias Pulmonares , Lesiones Precancerosas , Broncoscopía/métodos , Carcinoma de Células Escamosas/diagnóstico por imagen , Detección Precoz del Cáncer , Estudios de Seguimiento , Humanos , Hiperplasia , Neoplasias Pulmonares/diagnósticoRESUMEN
Despite new biological insights and recent therapeutic advances, many tumors remain at baseline during treatments. Therefore, there is an urgent need to find new therapeutic strategies to improve the care of patients with solid tumors. P2RX7 receptor (P2XR7), an ATP-gated ion channel characterized by its ability to form large pore within the cell membrane, is described by most of the investigators as a "chef d'orchestre" of the antitumor immune response. The purpose of this review is to detail the recent information concerning different cellular mechanisms linking P2RX7 to hallmarks of cancer and to discuss different progresses in elucidating how activation of the ATP/P2RX7/NLRP3/IL-18 pathway is a very promising approach to fight cancer progression by increasing antitumor immune responses.
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Adenosina Trifosfato/metabolismo , Inmunoterapia , Neoplasias/terapia , Receptores Purinérgicos P2X7/metabolismo , Transducción de Señal/fisiología , Animales , Proliferación Celular/fisiología , Humanos , Neoplasias/metabolismoRESUMEN
BACKGROUND: NGS from plasma samples in non-squamous cell lung carcinoma (NSCC) can aid in the detection of actionable genomic alterations. However, the absolute clinical value of NGS in liquid biopsy (LB) made at baseline is currently uncertain. We assessed the impact of plasma-based NGS using an in-house test and an outsourced test in comparison to a routine molecular pathology workflow. METHODS: Twenty-four advanced/metastatic treatment-naïve NSCC patients were prospectively included. NGS analyses were conducted both in-house using the Oncomine cfTNA Panel and in an external testing center using the Foundation Liquid assay. NGS analysis and/or specific molecular based assays were conducted in parallel on tissue or cytological samples. RESULTS: Both LB tests were well correlated. Tissue NGS results were obtained in 67% of patients and demonstrated good correlation with LB assays. Activating EGFR mutations were detected using LB tests in three patients. PD-L1 expression assessed in tissue sections enabled the initiation of pembrolizumab treatment in five patients. CONCLUSION: NGS from LB is feasible in routine clinical practice using an in-house or an outsourced test at baseline. However, the impact on therapy selection was limited in this small series of patients and LB was not able to replace tissue-based testing in our hands.
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Carcinoma , Neoplasias Pulmonares , Secuenciación de Nucleótidos de Alto Rendimiento , Humanos , Biopsia Líquida , Pulmón , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Estudios ProspectivosRESUMEN
BACKGROUND: Exogenous lipoid pneumonia is a rare disease resulting from intra-alveolar accumulation of lipids of mineral, vegetal, or animal origin, that induce a foreign body type of inflammatory reaction in the lungs. Gastroesophageal reflux disease and other esophageal abnormalities have often been associated with this disease. CASE PRESENTATION: We herein report the case of an 83-year-old patient in whom a follow-up chest computed tomography scan, for a lingular consolidation, showed multifocal ground glass and consolidative opacities with areas of low attenuation, suggestive of exogenous lipid pneumonia. The patient had been on piascledine capsules (avocado/soybean unsaponifiables) for 20 years and had a hiatal hernia with documented gastroesophageal reflux disease. After thorough history taking, no other predisposing factors were found. The diagnosis was confirmed using oil red staining of bronchoalveolar lavage showing lipid-laden macrophages and extracellular lipid droplets. CONCLUSIONS: To our knowledge, this is the first case of ELP secondary to avocado/soybean unsaponifiables in the literature.
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Glycine max , Persea , Extractos Vegetales/efectos adversos , Neumonía Lipoidea/inducido químicamente , Anciano de 80 o más Años , Femenino , HumanosRESUMEN
Histopathology is the fundamental tool of pathology used for more than a century to establish the final diagnosis of lung cancer. In addition, the phenotypic data contained in the histological images reflects the overall effect of molecular alterations on the behavior of cancer cells and provides a practical visual reading of the aggressiveness of the disease. However, the human evaluation of the histological images is sometimes subjective and may lack reproducibility. Therefore, computational analysis of histological imaging using so-called "artificial intelligence" (AI) approaches has recently received considerable attention to improve this diagnostic accuracy. Thus, computational analysis of lung cancer images has recently been evaluated for the optimization of histological or cytological classification, prognostic prediction or genomic profile of patients with lung cancer. This rapidly growing field constantly demonstrates great power in the field of computing medical imaging by producing highly accurate detection, segmentation or recognition tasks. However, there are still several challenges or issues to be addressed in order to successfully succeed the actual transfer into clinical routine. The objective of this review is to emphasize recent applications of AI in pulmonary cancer pathology, but also to clarify the advantages and limitations of this approach, as well as the perspectives to be implemented for a potential transfer into clinical routine.
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Inteligencia Artificial , Neoplasias Pulmonares/patología , Humanos , Patología Clínica/métodosRESUMEN
We assessed the relationships between changes in lung compliance, lung volumes and dynamic hyperinflation in patients with emphysema who underwent bronchoscopic treatment with nitinol coils (coil treatment) (n=11) or received usual care (UC) (n=11). Compared with UC, coil treatment resulted in decreased dynamic lung compliance (CLdyn) (p=0.03) and increased endurance time (p=0.010). The change in CLdyn was associated with significant improvement in FEV1 and FVC, with reduction in residual volume and intrinsic positive end-expiratory pressure, and with increased inspiratory capacity at rest/and at exercise. The increase in end-expiratory lung volume (EELV) during exercise (EELVdyn-ch=EELVisotime EELVrest) demonstrated significant attenuation after coil treatment (p=0.02).
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Resistencia Física/fisiología , Neumonectomía/métodos , Enfisema Pulmonar/fisiopatología , Enfisema Pulmonar/cirugía , Mecánica Respiratoria/fisiología , Adulto , Anciano , Aleaciones , Broncoscopía , Femenino , Humanos , Rendimiento Pulmonar , Mediciones del Volumen Pulmonar , Persona de Mediana Edad , Estudios ProspectivosAsunto(s)
Adenocarcinoma del Pulmón/terapia , Fístula Bronquial/diagnóstico por imagen , Neoplasias Pulmonares/terapia , Stents , Síndrome de la Vena Cava Superior/cirugía , Fístula Vascular/diagnóstico por imagen , Adenocarcinoma del Pulmón/complicaciones , Adenocarcinoma del Pulmón/diagnóstico por imagen , Anciano , Anticuerpos Monoclonales Humanizados/administración & dosificación , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Fístula Bronquial/etiología , Broncoscopía , Carboplatino/administración & dosificación , Quimioradioterapia , Humanos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/diagnóstico por imagen , Pemetrexed/administración & dosificación , Criterios de Evaluación de Respuesta en Tumores Sólidos , Síndrome de la Vena Cava Superior/diagnóstico por imagen , Síndrome de la Vena Cava Superior/etiología , Fístula Vascular/etiologíaAsunto(s)
Infecciones por Actinomycetales/patología , Enfermedades Pulmonares/microbiología , Enfermedades Pulmonares/patología , Rhodococcus equi , Infecciones por Actinomycetales/complicaciones , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Enfermedades Pulmonares/complicaciones , Neoplasias Pulmonares/patología , Malacoplasia/etiologíaRESUMEN
BACKGROUND: Video-assisted thoracoscopic segmentectomies have become the gold standard for the treatment of early-stage non-small cell lung cancer less than two centimeters. The main difficulty is the identification of intersegmental boundary lines which dictate postoperative morbidities. METHODS: We conducted a retrospective study to compare the perioperative outcomes of patients who underwent minimally invasive segmentectomy using the traditional deflation-inflation method or the novel indocyanine green (ICG) technique. Using a prospectively maintained database, we performed a retrospective analysis of 197 consecutive anatomical segmentectomies, from 2020 to 2023. Clinical effectiveness, postoperative complications, and histological data were compared. RESULTS: A total of 73 (37%) patients had the inflation-deflation method and 124 (63%) had the intravenous ICG method. There were no significant differences in chest tube duration, prolonged air leak, postoperative complications, and postoperative hospital stays. Surgical margin width was also similar between the two groups. The multivariable analysis confirmed these results. Lastly, intravenous ICG brought no additional value in complex segmentectomies. CONCLUSION: This monocentric and retrospective analysis found no added value of the intravenous ICG on the perioperative results of minimally invasive segmentectomies. The place of this novel technique in the surgical armamentarium remains to be defined. Specific indications such as complex segmentectomy or patients with chronic pulmonary disease require further study.
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Verde de Indocianina , Neoplasias Pulmonares , Neumonectomía , Cirugía Torácica Asistida por Video , Humanos , Masculino , Femenino , Estudios Retrospectivos , Anciano , Persona de Mediana Edad , Neoplasias Pulmonares/cirugía , Neoplasias Pulmonares/patología , Neumonectomía/métodos , Cirugía Torácica Asistida por Video/métodos , Complicaciones Posoperatorias , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Pulmón de Células no Pequeñas/patologíaRESUMEN
The aim of this study was to assess the potential value of circulating active and inactive IL-18 levels in distinguishing pseudo and true tumor progression among NSCLC patients receiving immune checkpoint inhibitor treatments (ICIs). METHODS: This ancillary study includes 195 patients with metastatic non-small-cell lung cancer (NSCLC) treated with ICI in monotherapy, either pembrolizumab or nivolumab. Plasmatic levels of IL-18-related compounds, comprising the inhibitor IL-18 binding protein (IL-18BP), the inactive IL-18 (corresponding to IL-18/IL-18BP complex), and the active free IL-18, were assayed by ELISA. Objective tumoral response was analyzed by 18FDG PET-CT at baseline, 7 weeks, and 3 months post treatment induction, using PERCIST criteria. RESULTS: Plasmatic IL-18BP and total IL-18 levels are increased at baseline in NSCLC patients compared with healthy controls, whereas IL-18/IL-18BP complexes are decreased, and free IL-18 levels remain unchanged. Neither of the IL-18-related compounds allowed to discriminate ICI responding to nonresponding patients. However, inactive IL-18 levels allowed to discriminate patients with a first tumor progression, assessed after 7 weeks of treatment, with worse overall survival. In addition, we showed that neutrophil concentration is also a predictive indicator of patients' outcomes with OS (HR = 2.6, p = 0.0001) and PFS (HR = 2.2, p = 0.001). CONCLUSIONS: Plasmatic levels of inactive IL-18, combined with circulating neutrophil concentrations, can effectively distinguish ICI nonresponding patients with better overall survival (OS), potentially guiding rapid decisions for therapeutic intensification.
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INTRODUCTION: Lung cancer (LC) is the most common cause of cancer-related deaths worldwide. Its early detection can be achieved with a CT scan. Two large randomised trials proved the efficacy of low-dose CT (LDCT)-based lung cancer screening (LCS) in high-risk populations. The decrease in specific mortality is 20%-25%.Nonetheless, implementing LCS on a large scale faces obstacles due to the low number of thoracic radiologists and CT scans available for the eligible population and the high frequency of false-positive screening results and the long period of indeterminacy of nodules that can reach up to 24 months, which is a source of prolonged anxiety and multiple costly examinations with possible side effects.Deep learning, an artificial intelligence solution has shown promising results in retrospective trials detecting lung nodules and characterising them. However, until now no prospective studies have demonstrated their importance in a real-life setting. METHODS AND ANALYSIS: This open-label randomised controlled study focuses on LCS for patients aged 50-80 years, who smoked more than 20 pack-years, whether active or quit smoking less than 15 years ago. Its objective is to determine whether assisting a multidisciplinary team (MDT) with a 3D convolutional network-based analysis of screening chest CT scans accelerates the definitive classification of nodules into malignant or benign. 2722 patients will be included with the aim to demonstrate a 3-month reduction in the delay between lung nodule detection and its definitive classification into benign or malignant. ETHICS AND DISSEMINATION: The sponsor of this study is the University Hospital of Nice. The study was approved for France by the ethical committee CPP (Comités de Protection des Personnes) Sud-Ouest et outre-mer III (No. 2022-A01543-40) and the Agence Nationale du Medicament et des produits de Santé (Ministry of Health) in December 2023. The findings of the trial will be disseminated through peer-reviewed journals and national and international conference presentations. TRIAL REGISTRATION NUMBER: NCT05704920.