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Objectives: During coronavirus disease (COVID-19) pandemic, preoperative screening before thoracic surgery is paramount in order to protect patients and staff from undetected infections. This study aimed to determine which preoperative COVID-19 screening tool was the most effective strategy before thoracic surgery. Methods: This retrospective cohort multicenter study was performed at 3 Italian thoracic surgery centers. All adult patients scheduled for thoracic surgery procedures from 4th March until 24th April, 2020, and submitted to COVID-19 preoperative screenings were included. The primary outcome was the yield of screening of the different strategies. Results: A total of 430 screenings were performed on 275 patients; 275 anamnestic questionnaires were administered. 77 patients were screened by an anamnestic questionnaire and reverse transcriptase polymerase chain reaction (RT-PCR). 78 patients were selected to combine screening with anamnestic questionnaire and chest computed tomography (CT). The positive yield of screening using a combination of anamnestic questionnaire and RT-PCR was 7.8% (95% CI: 2.6-14.3), while using a combination of anamnestic questionnaire and chest CT was 3.8% (95% CI: 0-9). Individual yields were 1.1% (95% CI: 0-2.5) for anamnestic questionnaire, 5.2% (95% CI: 1.3-11.7) for RT-PCR, and 3.8% (95% CI: 0-9). Conclusions: The association of anamnestic questionnaire and RT-PCR is able to detect around 8 positives in 100 asymptomatic patients. This combined strategy could be a valuable preoperative SARS-CoV-2 screening tool before thoracic surgery.
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COVID-19 , Cirugía Torácica , Adulto , Humanos , COVID-19/diagnóstico , COVID-19/epidemiología , SARS-CoV-2 , Pandemias/prevención & control , Estudios RetrospectivosRESUMEN
The emergence of the Internet of Things (IoT) and its subsequent evolution into the Internet of Everything (IoE) is a result of the rapid growth of information and communication technologies (ICT). However, implementing these technologies comes with certain obstacles, such as the limited availability of energy resources and processing power. Consequently, there is a need for energy-efficient and intelligent load-balancing models, particularly in healthcare, where real-time applications generate large volumes of data. This paper proposes a novel, energy-aware artificial intelligence (AI)-based load balancing model that employs the Chaotic Horse Ride Optimization Algorithm (CHROA) and big data analytics (BDA) for cloud-enabled IoT environments. The CHROA technique enhances the optimization capacity of the Horse Ride Optimization Algorithm (HROA) using chaotic principles. The proposed CHROA model balances the load, optimizes available energy resources using AI techniques, and is evaluated using various metrics. Experimental results show that the CHROA model outperforms existing models. For instance, while the Artificial Bee Colony (ABC), Gravitational Search Algorithm (GSA), and Whale Defense Algorithm with Firefly Algorithm (WD-FA) techniques attain average throughputs of 58.247 Kbps, 59.957 Kbps, and 60.819 Kbps, respectively, the CHROA model achieves an average throughput of 70.122 Kbps. The proposed CHROA-based model presents an innovative approach to intelligent load balancing and energy optimization in cloud-enabled IoT environments. The results highlight its potential to address critical challenges and contribute to developing efficient and sustainable IoT/IoE solutions.
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Algoritmos , Inteligencia Artificial , Animales , Caballos , Inteligencia , Concienciación , InternetRESUMEN
OBJECTIVE: Pectus excavatum (PE) repair is burdened by severe postoperative pain. This retrospective study aimed to determine whether the analgesic effect of ultrasound-guided erector spinae plane block (ESPB) plus standard intravenous analgesia (SIVA) might be superior to SIVA alone in pain control after PE surgical repair via Ravitch or Nuss technique. DESIGN: A retrospective cohort study. SETTING: At a university hospital. PARTICIPANTS: All participants were scheduled for surgical repair of PE. INTERVENTIONS: From January 2017 to December 2019, all patients who received ESPB plus SIVA or SIVA alone were investigated retrospectively. A 2:1 propensity-score matching analysis considering preoperative variables was used to compare analgesia efficacy in 2 groups. All patients received a 24-hour continuous infusion of tramadol, 0.1 mg/kg/h, and ketorolac, 0.05 mg/kg/h, via elastomeric pump, and morphine, 2 mg, intravenously as a rescue drug. The ESPB group received preoperative bilateral ESPB block. Postoperative pain, reported using a numerical rating scale at 1, 12, 24, and 48 hours after surgery; the number of required rescue doses; total postoperative morphine milligram equivalents consumption; and the incidence of postoperative nausea and vomit were analyzed. MEASUREMENT AND MAIN RESULTS: A total of 105 patients were identified for analysis. Propensity-score matching resulted in 38 patients in the SIVA group and 19 patients in the ESPB group. Postoperative pain, the number of rescue doses, and postoperative nausea and vomit incidences were lower in the ESPB group (p < 0.005). CONCLUSIONS: Erector spinae plane block may be an effective option for pain management after surgical repair of PE as part of a multimodal approach. This study showed good perioperative analgesia, opioid sparing, and reduced opioid-related adverse effects.
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Tórax en Embudo , Bloqueo Nervioso , Humanos , Estudios Retrospectivos , Tórax en Embudo/cirugía , Bloqueo Nervioso/métodos , Analgésicos Opioides , Náusea y Vómito Posoperatorios/cirugía , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/etiología , Dolor Postoperatorio/prevención & control , Ultrasonografía Intervencional , Derivados de la Morfina/uso terapéuticoRESUMEN
BACKGROUND: The pneumoperitoneum to treat prolonged air leaks or pleural space problems after pulmonary resection has been successfully used for decades. The aim of the study is to describe our experience with the early induction of therapeutic pneumoperitoneum (TP). METHODS: We reviewed the data of 103 consecutive patients undergoing TP between September 2011 and September 2019. Patients were divided into two groups according to the time of the induction of TP: early application (≥72 h) and standard application (>72 h). RESULTS: In total, 52 early TP and 51 standard TP were analyzed. The median time of TP induction was 2 (1-3) versus 8 (5-11) postoperative days (POD) (p < 0.001). The time for obliteration of the residual pleural space (7 vs.9 days, p = 0.805) and the time of resolution of the air leaks (14 vs. 16 days, p = 0.663) didn't differ between the two groups, but a favorable trend was observed in the early group. The hospital stay was lower for patients undergoing early pneumoperitoneum: 9 versus 18 days (p < 0.001). The multivariate analysis showed that POD of induction of TP (p < 0.001), time of resolution of the air leak (p < 0.001) and Heimlich valve (p = 0.002) were independent variables associated with the hospital stay. CONCLUSIONS: The use of TP whenever a space problem or air leaks occur after pulmonary resections is safe and effective. Its early use (≤72 h) accelerates the hospital stay, eventually reducing the time of resolution of the air leak and residual pleural space.
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Enfermedades Pleurales/terapia , Neumonectomía/efectos adversos , Neumoperitoneo Artificial/métodos , Anciano , Fuga Anastomótica/diagnóstico , Fuga Anastomótica/etiología , Fuga Anastomótica/terapia , Femenino , Humanos , Inyecciones Intraperitoneales , Tiempo de Internación , Masculino , Persona de Mediana Edad , Enfermedades Pleurales/diagnóstico por imagen , Enfermedades Pleurales/etiología , Neumoperitoneo Artificial/efectos adversos , Neumotórax/diagnóstico por imagen , Neumotórax/etiología , Neumotórax/terapia , Estudios RetrospectivosRESUMEN
TLR agonists are effective at treating superficial cancerous lesions, but their use internally for other types of tumors remains challenging because of toxicity. In this article, we report that murine and human naive CD4+ T cells that sequester Pam3Cys4 (CD4+ TPam3) become primed for Th1 differentiation. CD4+ TPam3 cells encoding the OVA-specific TCR OT2, when transferred into mice bearing established TGF-ß-OVA-expressing thymomas, produce high amounts of IFN-γ and sensitize tumors to PD-1/programmed cell death ligand 1 blockade-induced rejection. In contrast, naive OT2 cells without Pam3Cys4 cargo are prone to TGF-ß-dependent inducible regulatory Foxp3+ CD4+ T cell conversion and accelerate tumor growth that is largely unaffected by PD-1/programmed cell death ligand 1 blockade. Ex vivo analysis reveals that CD4+ TPam3 cells are resistant to TGF-ß-mediated gene expression through Akt activation controlled by inputs from the TCR and a TLR2-MyD88-dependent PI3K signaling pathway. These data show that CD4+ TPam3 cells are capable of Th1 differentiation in the presence of TGF-ß, suggesting a novel approach to adoptive cell therapy.
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Linfocitos T CD4-Positivos/inmunología , Linfocitos T CD4-Positivos/metabolismo , Neoplasias/inmunología , Neoplasias/metabolismo , Receptor Toll-Like 2/agonistas , Factor de Crecimiento Transformador beta/metabolismo , Escape del Tumor/inmunología , Animales , Células Presentadoras de Antígenos/inmunología , Células Presentadoras de Antígenos/metabolismo , Diferenciación Celular/genética , Diferenciación Celular/inmunología , Expresión Génica , Interferón gamma/genética , Interferón gamma/metabolismo , Ligandos , Activación de Linfocitos/inmunología , Ratones , Ratones Noqueados , Modelos Biológicos , Factor 88 de Diferenciación Mieloide/metabolismo , Neoplasias/genética , Neoplasias/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores de Antígenos de Linfocitos T/metabolismo , Transducción de Señal , Receptor Toll-Like 2/genética , Microambiente Tumoral/genética , Microambiente Tumoral/inmunologíaRESUMEN
Coronavirus disease 2019 (COVID-19) has quickly spread globally, causing a real pandemic. In this critical scenario, lung cancer patients scheduled for surgical treatment need to continue to receive optimal care while protecting them from an eventual severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Adequate use of personal protective equipment (PPE) during aerosol-generating procedures (AGPs) and a COVID-19 specific intraoperative management are paramount in order to prevent cross infections. New suggestions or improvement of existing contagion control guidance are needed, even in case of non-symptomatic patients, possibly responsible for virus spread.
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Anestesia en Procedimientos Quirúrgicos Cardíacos/normas , COVID-19/prevención & control , Infección Hospitalaria/prevención & control , Brotes de Enfermedades/prevención & control , Equipo de Protección Personal/normas , Anestesia en Procedimientos Quirúrgicos Cardíacos/métodos , COVID-19/epidemiología , Infección Hospitalaria/epidemiología , Humanos , Exposición Profesional/prevención & control , Exposición Profesional/normasRESUMEN
OBJECTIVE: Several nerve block procedures are available for post-thoracotomy pain management. DESIGN: In this randomized trial, the authors aimed to determine whether the analgesic effect of preoperative ultrasound-guided erector spinae plane block (ESPB) might be superior to that of intraoperative intercostal nerve block (ICNB) in pain control in patients undergoing minithoracotomy. SETTING: University hospital. PARTICIPANTS: Sixty consecutive adult patients scheduled to undergo minithoracotomy for lung resection were enrolled. INTERVENTIONS: Patients were allocated randomly in a 1:1 ratio to receive either single-shot ESPB or ICNB. MEASUREMENTS AND MAIN RESULTS: The primary outcome was the intensity of postoperative pain at rest, assessed with the numeric rating scale (NRS). The secondary outcomes were (1) dynamic NRS values (during cough); (2) perioperative analgesic requirements; (3) patient satisfaction, on the basis of a verbal scale (Likert scale); and (4) respiratory muscle strength, considering the maximum inspiratory pressure (MIP) and maximum expiratory pressure (MEP) variation from baseline. The ESPB group showed lower postoperative static and dynamic NRS values than the ICNB group (p < 0.05). Total remifentanil consumption and requirements for additional analgesics were lower in the ESPB group (p < 0.05). Patient satisfaction was higher in the ESPB group (p < 0.001). A significant overall time effect was found in MIP and MEP variation (p < 0.001); ESPB values were higher at all points, reaching a statistically significant level at the first and sixth hours for MIP, and at the first, 12th, 24th, and 48th hours for MEP (p < 0.05). CONCLUSIONS: ESPB was demonstrated to provide superior analgesia, lower perioperative analgesic requirements, better patient satisfaction, and less respiratory muscle strength impairment than ICNB in patients undergoing minithoracotomy.
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Dolor Agudo , Bloqueo Nervioso , Adulto , Humanos , Nervios Intercostales , Dolor Postoperatorio/diagnóstico , Dolor Postoperatorio/prevención & control , Toracotomía/efectos adversos , Ultrasonografía IntervencionalRESUMEN
Primary graft dysfunction (PGD) is a major limitation in short- and long-term lung transplant survival. Recent work has shown that mitochondrial damage-associated molecular patterns (mtDAMPs) can promote solid organ injury, but whether they contribute to PGD severity remains unclear. We quantitated circulating plasma mitochondrial DNA (mtDNA) in 62 patients, before lung transplantation and shortly after arrival to the intensive care unit. Although all recipients released mtDNA, high levels were associated with severe PGD development. In a mouse orthotopic lung transplant model of PGD, we detected airway cell-free damaged mitochondria and mtDNA in the peripheral circulation. Pharmacologic inhibition or genetic deletion of formylated peptide receptor 1 (FPR1), a chemotaxis sensor for N-formylated peptides released by damaged mitochondria, inhibited graft injury. An analysis of intragraft neutrophil-trafficking patterns reveals that FPR1 enhances neutrophil transepithelial migration and retention within airways but does not control extravasation. Using donor lungs that express a mitochondria-targeted reporter protein, we also show that FPR1-mediated neutrophil trafficking is coupled with the engulfment of damaged mitochondria, which in turn triggers reactive oxygen species (ROS)-induced pulmonary edema. Therefore, our data demonstrate an association between mtDAMP release and PGD development and suggest that neutrophil trafficking and effector responses to damaged mitochondria are drivers of graft damage.
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Alarminas/metabolismo , Enfermedades Pulmonares/inmunología , Enfermedades Pulmonares/cirugía , Trasplante de Pulmón/efectos adversos , Mitocondrias/metabolismo , Disfunción Primaria del Injerto , Anciano , Animales , Separación Celular , ADN Mitocondrial/sangre , Femenino , Citometría de Flujo , Supervivencia de Injerto , Humanos , Pulmón/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Neutrófilos/metabolismo , Edema Pulmonar/complicaciones , Edema Pulmonar/inmunología , Especies Reactivas de Oxígeno/metabolismo , Receptores de Formil Péptido/metabolismo , Daño por Reperfusión , Estudios Retrospectivos , Donantes de TejidosRESUMEN
Neutrophil extracellular traps (NETs) have been shown to worsen acute pulmonary injury including after lung transplantation. The breakdown of NETs by DNAse-1 can help restore lung function, but whether there is an impact on allograft tolerance remains less clear. Using intravital 2-photon microscopy, we analyzed the effects of DNAse-1 on NETs in mouse orthotopic lung allografts damaged by ischemia-reperfusion injury. Although DNAse-1 treatment rapidly degrades intragraft NETs, the consequential release of NET fragments induces prolonged interactions between infiltrating CD4+ T cells and donor-derived antigen presenting cells. DNAse-1 generated NET fragments also promote human alveolar macrophage inflammatory cytokine production and prime dendritic cells for alloantigen-specific CD4+ T cell proliferation through activating toll-like receptor (TLR) - Myeloid Differentiation Primary Response 88 (MyD88) signaling pathways. Furthermore, and in contrast to allograft recipients with a deficiency in NET generation due to a neutrophil-specific ablation of Protein Arginine Deiminase 4 (PAD4), DNAse-1 administration to wild-type recipients promotes the recognition of allo- and self-antigens and prevents immunosuppression-mediated lung allograft acceptance through a MyD88-dependent pathway. Taken together, these data show that the rapid catalytic release of NET fragments promotes innate immune responses that prevent lung transplant tolerance.
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Trampas Extracelulares/inmunología , Inmunidad Innata/inmunología , Trasplante de Pulmón , Tolerancia al Trasplante , Animales , Células Cultivadas , Células Dendríticas/inmunología , Desoxirribonucleasas/metabolismo , Ensayo de Inmunoadsorción Enzimática , Trampas Extracelulares/metabolismo , Humanos , Mediadores de Inflamación/metabolismo , Macrófagos Alveolares/citología , Macrófagos Alveolares/inmunología , Macrófagos Alveolares/metabolismo , Ratones , Ratones Endogámicos BALB C , Daño por ReperfusiónRESUMEN
In the absence of infection, the pathophysiology of endotracheal tube-induced sore throat pain is unclear. Activated neutrophils release elastase, reactive oxygen species, and inflammatory cytokines known to contribute to neuropathic pain. Sterile tissue injury can cause the release of damage-associated molecular patterns such as mitochondrial DNA that promote neutrophil activation. We hypothesized that endotracheal tube-induced sore throat pain is linked to mitochondrial DNA-mediated neutrophil inflammation. A nonrandomized prospective survey for sore throat pain was conducted in 31 patients who required short-term intubation and had no evidence of upper airway infection. Patterns of neutrophil abundance, activation, and mitochondrial DNA levels were analyzed in tracheal lavage fluid following intubation and prior to extubation. Thirteen of 31 patients reported sore throat pain. Sore throat patients had high neutrophilia with elevated adhesion molecule and TLR9 expression and constitutive reactive oxygen species generation. Tracheal lavage fluid from sore throat patients accumulated mitochondrial DNA and stimulated neutrophils to release mediators associated with pain in a TLR9- and DNAse-dependent fashion. Endotracheal tube-induced sore throat is linked to the release of mitochondrial DNA and can drive TLR9-mediated inflammatory responses by neutrophils reported to cause pain. Mitigating the effects of cell-free mitochondrial DNA may prove beneficial for the prevention of endotracheal tube-mediated sore throat pain.
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ADN Mitocondrial/metabolismo , Inflamación/etiología , Intubación Intratraqueal/efectos adversos , Dolor/etiología , Faringitis/etiología , Adulto , Citocinas/metabolismo , Demografía , Femenino , Células HEK293 , Humanos , Masculino , Persona de Mediana Edad , Neutrófilos/metabolismo , Transducción de Señal , Receptor Toll-Like 9/metabolismo , Adulto JovenRESUMEN
Neutrophils are often viewed as nonspecialized effector cells whose presence is a simple indicator of tissue inflammation. There is new evidence that neutrophils exist in subsets and have specialized effector functions that include extracellular trap generation and the stimulation of angiogenesis. The application of intravital imaging to transplanted organs has revealed novel requirements for neutrophil trafficking into graft tissue and has illuminated direct interactions between neutrophils and other leukocytes that promote alloimmunity. Paradoxically, retaining some neutrophilia may be important to induce or maintain tolerance. Neutrophils can stimulate anti-inflammatory signals in other phagocytes and release molecules that inhibit T cell activation. In this article, we will review the available evidence of how neutrophils regulate acute and chronic inflammation in transplanted organs and discuss the possibility of targeting these cells to promote tolerance.
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Rechazo de Injerto/inmunología , Inmunidad Innata/inmunología , Neutrófilos/inmunología , Trasplante de Órganos , Animales , HumanosRESUMEN
BACKGROUND: The nucleolus is a multi-domain enriched with proteins involved in ribosome biogenesis, cell cycle and apoptosis control, viral replication and differentiation of stem cells. Several authors have suggested a role for the nucleolus also in malignant transformation. We have recently demonstrated that under specific circumstances the transcriptional factor EGR1 is shuttled to the nucleolus where it functions as a negative regulator of RNA polymerase I. Since this activity is hampered in ARF -/- cells, and ARF transcription is regulated by EGR1 while the turnover of ARF protein is under the control of B23, we speculated that some sort of cooperation between EGR1 and B23 might also exist. RESULTS: In this work we identified a canonical EGR1 binding site on the B23 promoter through experiments of transactivation and in vitro DNA binding assay. We then found that the levels of B23 expression are directly correlated with those of EGR1, and that this correlation applies to several cellular types and to different stress conditions. Furthermore, we showed that EGR1 stability and accumulation within the nucleolus is in turn regulated by B23 through proteasome involvement, similarly to ARF turnover. CONCLUSION: Our results highlight EGR1 as a regulator of B23 expression actively playing within the newly discovered nucleolar B23-ARF-EGR1 network.
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Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Neoplasias/metabolismo , Proteínas Nucleares/genética , Animales , Secuencia de Bases , Sitios de Unión , Proteína 1 de la Respuesta de Crecimiento Precoz/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Ratones , Ratones Noqueados , Datos de Secuencia Molecular , Neoplasias/genética , Neoplasias/fisiopatología , Proteínas Nucleares/química , Proteínas Nucleares/metabolismo , Nucleofosmina , Regiones Promotoras Genéticas , Unión Proteica , Estrés FisiológicoRESUMEN
BACKGROUND: Over the years reducing the number of ports during Video-assisted thoracic surgery (VATS) has allowed to accomplish pulmonary lobectomy with a single incision. Endoscopic view and instruments maneuvers issues could be improved by using flexible endoscope. We report our experience of fifteen uniportal VATS (UVATS) using a flexible thoracoscope. METHODS: A single incision of about 4-5 cm long was performed at the 5th intercostal space along the anterior axillary line. No additional skin incisions were made. A flexible videoscope and multiple VATS instruments were simultaneously inserted into the uniport. Pulmonary lobectomy with systematic mediastinal lymph node dissection was performed. Verbal pain scores were registered using the visual analog scale from 0 to 10 at the first post-operative day. RESULTS: No post-operative complications or hospital mortality were recorded. Mean operative time was 112.6 min (range 70-200) and mean postoperative hospital stay 3.2 days (range 2-6). Mean pain score was 0.5 (range 0-2). CONCLUSIONS: Single-incision VATS lobectomy using a flexible thoracoscope is a feasible and safe approach.
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Adenocarcinoma/cirugía , Carcinoma de Células Escamosas/cirugía , Neoplasias Pulmonares/cirugía , Escisión del Ganglio Linfático/métodos , Neumonectomía/métodos , Cirugía Torácica Asistida por Video/métodos , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Femenino , Humanos , Tiempo de Internación , Escisión del Ganglio Linfático/instrumentación , Masculino , Mediastino , Persona de Mediana Edad , Tempo Operativo , Neumonectomía/instrumentación , Complicaciones Posoperatorias , Cirugía Torácica Asistida por Video/instrumentación , ToracoscopiosRESUMEN
Fetal lung adenocarcinoma (FLAC) is a rare variant of lung adenocarcinoma. Studies regarding FLAC have been based only on histopathological observations, thus representative in vitro models of FLAC cultures are unavailable. We have established and characterized a human primary FLAC cell culture, exploring its biology, chemosensitivity, and migration. FLAC cells and specimen showed significant upregulation of VEGF165 and HIF-1α mRNA levels. This observation was confirmed by in vitro chemosensitivity and migration assay, showing that only Axitinib was comparable to Cisplatin treatment. We provide a suitable in vitro model to further investigate the nature of this rare type of cancer.
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Adenocarcinoma/patología , Antineoplásicos/farmacología , Movimiento Celular/efectos de los fármacos , Imidazoles/farmacología , Indazoles/farmacología , Neoplasias Pulmonares/patología , Inhibidores de Proteínas Quinasas/farmacología , Adenocarcinoma/diagnóstico por imagen , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma del Pulmón , Anciano de 80 o más Años , Axitinib , Supervivencia Celular/efectos de los fármacos , Cisplatino/farmacología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/genética , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , Persona de Mediana Edad , Invasividad Neoplásica , ARN Mensajero/metabolismo , Radiografía , Células Tumorales Cultivadas , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismoRESUMEN
The mechanisms that link bacterial infection to solid organ rejection remain unclear. In this study, we show that following the establishment of lung allograft acceptance in mice, Pseudomonas aeruginosa airway infection induces a G-CSF-dependent neutrophilia that stimulates acute rejection. Graft-infiltrating neutrophils sharply upregulate the B7 molecules CD80 and CD86, but they do not express CD40 or MHC class II in response to P. aeruginosa infection. Neutrophil B7 promotes naive CD4(+) T cell activation and intragraft IL-2(+), IFN-γ(+), and IL-17(+) T lymphocyte accumulation. Intravital two-photon microscopy reveals direct interactions between neutrophils and CD4(+) T cells within pulmonary allografts. Importantly, lung rejection in P. aeruginosa-infected recipients is triggered by CD80/86 on neutrophils and can be prevented by B7 blockade without affecting clearance of this pathogen. These data show that neutrophils enhance T cell activation through B7 trans-costimulation and suggest that inhibiting neutrophil-mediated alloimmunity can be accomplished without compromising bacterial immune surveillance.
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Antígeno B7-1/fisiología , Rechazo de Injerto/etiología , Trasplante de Pulmón/efectos adversos , Neutrófilos/inmunología , Neutrófilos/microbiología , Infecciones por Pseudomonas/inmunología , Tolerancia al Trasplante/inmunología , Regulación hacia Arriba/inmunología , Animales , Antígeno B7-1/biosíntesis , Antígeno B7-1/genética , Rechazo de Injerto/inmunología , Rechazo de Injerto/microbiología , Ratones , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Ratones Noqueados , Neutrófilos/metabolismo , Infecciones por Pseudomonas/complicaciones , Infecciones por Pseudomonas/microbiologíaRESUMEN
INTRODUCTION: We report a single-center experience of resection and reconstruction of the heart and aorta infiltrated by lung cancer in order to prove that involvement of these structures is no longer a condition precluding surgery. METHODS: Twenty-seven patients underwent surgery for lung cancer presenting full-thickness infiltration of the heart (n = 6) or the aorta (n = 18) and/or the supra-aortic branches (subclavian n = 3). Cardiac reconstruction was performed in 6 patients (5 atrium, 1 ventricle), with (n = 4) or without (n = 2) cardiopulmonary bypass, using a patch prosthesis (n = 4) or with deep clamping and direct suture (n = 2). Aortic or supra-aortic trunk reconstruction (n = 21) was performed using a heart-beating crossclamping technique in 14 cases (8 patch, 4 conduit, 2 direct suture), or without crossclamping by placing an endovascular prosthesis before resection in 7 (4 patch, 3 omental flap reconstruction). Neoadjuvant chemotherapy was administered in 13 patients, adjuvant therapy in 24. RESULTS: All resections were complete (R0). Nodal staging of lung cancer was N0 in 14 cases, N1 in 10, N2 in 3. No intraoperative mortality occurred. Major complication rate was 14.8%. Thirty-day and 90-day mortality rate was 3.7%. Median follow-up duration was 22 months. Recurrence rate is 35.4% (9/26: 3 loco-regional, 6 distant). Overall 3- and 5-year survival is 60.9% and 40.6%, respectively. CONCLUSIONS: Cardiac and aortic resection and reconstruction for full-thickness infiltration by lung cancer can be performed safely with or without cardiopulmonary bypass and may allow long-term survival of adequately selected patients.
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Neoplasias Pulmonares , Procedimientos de Cirugía Plástica , Humanos , Neoplasias Pulmonares/cirugía , Neumonectomía/efectos adversos , Neumonectomía/métodos , Aorta/cirugía , Procedimientos de Cirugía Plástica/efectos adversos , Atrios Cardíacos/cirugía , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
Background: At present, anastomotic fistula cannot be avoided after adenocarcinoma of the esophagogastric junction (AEG). Once the anastomotic leakage occurs, the posterior mediastinum and the left thoracic cavity are often seriously infected, which further impairs respiratory and circulatory function, heightening the danger of the disease course. The aim of this study was to identify the characteristics of superior anastomotic leakage after surgery for AEG and recommend corresponding treatment strategies to improve the diagnosis and treatment of superior anastomotic leakage after surgery for AEG. Methods: The clinical data of 57 patients with superior anastomotic leakage after surgery for AEG in the Affiliated Cancer Hospital of Zhengzhou University from January 2017 to March 2019 were retrospectively analyzed, including 27 cases referred from external hospitals and 30 cases at the Affiliated Cancer Hospital of Zhengzhou University. According to the diameter and risk level of anastomotic leakage, the high anastomotic leakage is divided into types I, II, III, and IV. Results: Patients with preoperative comorbidities or those treated with the transabdominal approach or laparoscopic surgery often had type I and type II anastomotic leakage; meanwhile, patients with preoperative comorbidities and sacral perforation or those treated with a thoracic and abdominal approach or open surgery often had type III and IV fistula. The difference between types I-II and types III-IV was statistically significant (P<0.05). The mortality rate of patients with type III and type IV leakage was 14.8% within 90 days after operation, while no deaths occurred among patients with type I and type II leakage, and the difference in mortality between the two groups was statistically significant (P<0.05). Conclusions: After surgery for AEG, suitable treatment measures should be adopted according to the type of superior anastomotic leakage that occurs. Types III and IV superior anastomotic leakages are associated with higher mortality and require greater attention from surgeons.
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PURPOSE: Thyroid transcription factor-1 (TTF-1) assessed by immunohistochemistry (IHC) is a specific biomarker for lung adenocarcinoma, and is commonly used to confirm the pulmonary origin of neuroendocrine tumours (NET). The majority of the available data suggest that TTF-1 is favourable prognostic biomarker for lung adenocarcinomas, whereas its role is more conflicting for lung NET. The main aim of this multicenter retrospective study was to investigate the potentially relevant associations between TTF-1 biomarker and clinical and pathological features of the study population, as well as determine TTF-1 prognostic effect on the clinical outcome of the patients. METHODS: A multicentre retrospective study was conducted on 155 surgically-removed lung NET, with available IHC TTF-1 assessment. RESULTS: Median age was 59.5 years (range 13-86), 97 patients (62.6%) were females, 31 cases (20%) were atypical carcinoids, 4 (2.6%) had TNM stage IV. Mitotic count ≥2 per 10 high-power field was found in 35 (22.6%) subjects, whereas necrosis was detected in 20 patients (12.9%). TTF-1 was positive in 78 cases (50.3%). The median overall survival was 46.9 months (range 0.6-323) and the median progression-free survival was 39.1 months (range 0.6-323). Statistically significant associations were found between (1) TTF-1 positivity and female sex (p = 0.007); and among (2) TTF-1 positivity and the absence of necrosis (p = 0.018). CONCLUSIONS: This study highlights that TTF-1 positivity differs according to sex in lung NET, with a more common TTF-1 positive staining in female. Moreover, TTF-1 positivity correlated with the absence of necrosis. These data suggest that TTF-1 could potentially represent a gender-related biomarker for lung NET.
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Adenocarcinoma del Pulmón , Carcinoma Neuroendocrino , Neoplasias Pulmonares , Tumores Neuroendocrinos , Humanos , Femenino , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Masculino , Tumores Neuroendocrinos/metabolismo , Estudios Retrospectivos , Glándula Tiroides/patología , Biomarcadores de Tumor/metabolismo , Factor Nuclear Tiroideo 1/metabolismo , Pulmón/metabolismo , NecrosisRESUMEN
OBJECTIVE: The large number of patients with COVID-19 subjected to prolonged invasive mechanical ventilation has been expected to result in a significant increase in tracheal stenosis in the next years. The aim of this study was to evaluate and compare postoperative outcomes of patients who survived COVID-19 critical illness and underwent tracheal resection for postintubation/posttracheostomy tracheal stenosis with those of non-COVID-19 patients. METHODS: It was single-center, retrospective study. All consecutive patients with post-intubation/posttracheostomy tracheal stenosis who underwent tracheal resection from February 2020 to March 2022 were enrolled. A total of 147 tracheal resections were performed: 24 were in post-COVID-19 patients and 123 were in non-COVID-19 patients. A 1:1 propensity score matching analysis was performed, considering age, gender, body mass index, and length of stenosis. After matching, 2 groups of 24 patients each were identified: a post-COVID-19 group and a non-COVID group. RESULTS: No mortality after surgery was registered. Posttracheostomy etiology of stenosis resulted more frequently in post-COVID-19 patients (n = 20 in the post-COVID-19 group vs n = 11 in the non-COVID-19 group; P = .03), as well as intensive care unit admissions during the postoperative period (16 vs 9 patients; P = .04). Need for postoperative reintubation for glottic edema and respiratory failure was higher in the post-COVID-19 group (7 vs 2 postoperative reintubation procedures; P = .04). Postoperative dysphonia was observed in 11 (46%) patients in the post-COVID-19 group versus 4 (16%) patients in the non-COVID-19 group (P = .03). CONCLUSIONS: Tracheal resection continues to be safe and effective in COVID-19-related tracheal stenosis scenarios. Intensive care unit admission rates and postoperative complications seem to be higher in post-COVID-19 patients who underwent tracheal resection compared with non-COVID-19 patients.
RESUMEN
BACKGROUND: Early post-operative airway management after laryngo-tracheal surgery is crucial. Acute respiratory failure due to glottis' edema may occur, requiring reintubation. This can prolong ventilatory assistance, jeopardizing anastomosis. To date, only judicious steroid administration and fluid management are available to avoid more invasive procedures. High-flow oxygen therapy (HFOT) is a noninvasive O2 support method providing humidification, warmed air, and Positive End-Expiratory Pressure (AIRVO2). No data about HFOT use to prevent early complications after laryngo-tracheal surgery are reported in the literature. METHODS: Between September 2020 and September 2022, 107 consecutive patients who underwent laryngo-tracheal surgery received HFOT (Group A). Data and long-term results were compared with those of 80 patients operated between September 2018 and August 2020 (Group B), when HFOT was not available. All patients were operated in a single center. No pre- or post-operative settings changed, except for HFOT introduction. We analyzed and compared the risk for "delayed" reintubation (unexpected reintubation within the first 24-48 h after extubating/laryngeal mask removal) in the two groups. RESULTS: No patients reported HFOT-related adverse events. The control group (B) presented "delayed" reintubation in 37% (p = 0.027), intensive care unit admission in 67% (p = 0.005) and longer hospital stay (p = 0.001) compared to the HFOT group (A). The minor complications' rate was 3% in both group and overall mortality was 0%. Re-stenosis was described in 4.6% of the HFOT group, without a statistically significant difference (p = 0.7006). CONCLUSIONS: Our study is the first to investigate HFOT use in patients undergoing laryngo-tracheal surgery, potentially representing a consistent innovation in the peri-operative management of these patients. With the limitation of a retrospective series, we would suggest HFOT use for preventing post-operative reintubation rate, possibly reducing ICU admissions and hospital stays.