La osificación pulmonar difusa es una rara entidad que consiste en la formación de hueso maduro en el parénquima pulmonar, asociada a patología pulmonar difusa y crónica, cardíaca o ...extracardiopulmonar. Esta entidad constituye habitualmente un hallazgo anatomopatológico post mortem. En este caso se realiza el diagnóstico mediante biopsia pulmonar a cielo abierto
Presentamos el caso de un varón de 79 años, con disnea, tos seca y pérdida de peso. Había sido fumador. En la radiografía de tórax se apreciaba un infiltrado pulmonar bilateral reticulonodulillar. La tomografía computarizada evidenció afectación intersticial con predominio septal y múltiples cavidades con tendencia a la panalización; engrosamiento pleural, retracción del parénquima y fibrosis bilateral. Se estableció el diagnóstico clínico de fibrosis intersticial idiopática, y el paciente evolucionó desfavorablemente. Se realizó una biopsia a cielo abierto. La biopsia pulmonar evidenció zonas de colapso alveolar y otras enfisematosas, algunas con secreción y extravasación eritrocitaria. Había vasocongestión intersticial; los bronquiolos presentaban infiltrado inflamatorio mononuclear y algunos polimorfonucleares. Llamaba la atención la presencia de trabéculas óseas, algunas que incluían la médula ósea, de tipo adiposo, en focos multicéntricos, predominantemente intersticiales
La osificación pulmonar difusa constituye habitualmente un hallazgo incidental en autopsias de pacientes con antecedentes de enfermedad pulmonar crónica difusa, siendo inusual el diagnóstico en un paciente vivo. La osificación pulmonar difusa no posee significación pronóstica en la fibrosis pulmonar. Constituye un signo de cronicidad y gravedad de la enfermedad
Diffuse pulmonary ossification is a rare entity that presents with the formation of mature bone in the pulmonary parenchyma and is associated with diffuse and chronic lung disease, heart disease, or other system disorders. Diffuse pulmonary ossification is usually a postmortem finding by the pathologist. In the case we report, the diagnosis was established by open lung biopsy. The patient was a 79- year-old man with dyspnea, dry cough, and weight loss. He had been a smoker. A chest x-ray revealed reticulonodular bilateral pulmonary infiltrates. Computed tomography revealed interstitial disease predominantly in the septum with multiple cavitations that tended to form honeycomb patterns. Pleural thickening, retraction of the parenchyma, and bilateral fibrosis were also visible. A clinical diagnosis of interstitial fibrosis was established and the patient's course was unfavorable. An open lung biopsy was performed. The lung tissue specimens revealed zones with collapsed alveoli and others with emphysema, some of which produced secretion and erythrocytic extravasation. Interstitial vascular congestion was apparent; bronchioles presented mononuclear and some polymorphonuclear inflammatory infiltrates. Noteworthy was the presence of predominantly interstitial, multicentric foci of osseous trabeculae —some of which included adipose bone marrow. Diffuse pulmonary ossification is usually an incidental finding in autopsies of patients with a history of diffuse chronic pulmonary disease, but it is an unusual diagnosis in living patients. Diffuse pulmonary ossification is of no prognostic significance in pulmonary fibrosis. It is a marker of the chronicity and/or severity of the fibrosis
Diffuse pulmonary ossification is a rare entity that presents with the formation of mature bone in the pulmonary parenchyma and is associated with diffuse and chronic lung disease, heart disease, or ...other system disorders. Diffuse pulmonary ossification is usually a postmortem finding by the pathologist. In the case we report, the diagnosis was established by open lung biopsy. The patient was a 79-year-old man with dyspnea, dry cough, and weight loss. He had been a smoker. A chest x-ray revealed reticulonodular bilateral pulmonary infiltrates. Computed tomography revealed interstitial disease predominantly in the septum with multiple cavitations that tended to form honeycomb patterns. Pleural thickening, retraction of the parenchyma, and bilateral fibrosis were also visible. A clinical diagnosis of interstitial fibrosis was established and the patient s course was unfavorable. An open lung biopsy was performed. The lung tissue specimens revealed zones with collapsed alveoli and others with emphysema, some of which produced secretion and erythrocytic extravasation. Interstitial vascular congestion was apparent; bronchioles presented mononuclear and some polymorphonuclear inflammatory infiltrates. Noteworthy was the presence of predominantly interstitial, multicentric foci of osseous trabeculae --some of which included adipose bone marrow. Diffuse pulmonary ossification is usually an incidental finding in autopsies of patients with a history of diffuse chronic pulmonary disease, but it is an unusual diagnosis in living patients. Diffuse pulmonary ossification is of no prognostic significance in pulmonary fibrosis. It is a marker of the chronicity and/or severity of the fibrosis.
Diffuse pulmonary ossification is a rare entity that presents with the formation of mature bone in the pulmonary parenchyma and is associated with diffuse and chronic lung disease, heart disease, or ...other system disorders. Diffuse pulmonary ossification is usually a postmortem finding by the pathologist. In the case we report, the diagnosis was established by open lung biopsy. The patient was a 79-year-old man with dyspnea, dry cough, and weight loss. He had been a smoker. A chest x-ray revealed reticulonodular bilateral pulmonary infiltrates. Computed tomography revealed interstitial disease predominantly in the septum with multiple cavitations that tended to form honeycomb patterns. Pleural thickening, retraction of the parenchyma, and bilateral fibrosis were also visible. A clinical diagnosis of interstitial fibrosis was established and the patient's course was unfavorable. An open lung biopsy was performed. The lung tissue specimens revealed zones with collapsed alveoli and others with emphysema, some of which produced secretion and erythrocytic extravasation. Interstitial vascular congestion was apparent; bronchioles presented mononuclear and some polymorphonuclear inflammatory infiltrates. Noteworthy was the presence of predominantly interstitial, multicentric foci of osseous trabeculae-some of which included adipose bone marrow. Diffuse pulmonary ossification is usually an incidental finding in autopsies of patients with a history of diffuse chronic pulmonary disease, but it is an unusual diagnosis in living patients. Diffuse pulmonary ossification is of no prognostic significance in pulmonary fibrosis. It is a marker of the chronicity and/or severity of the fibrosis.
La osificación pulmonar difusa es una rara entidad que consiste en la formación de hueso maduro en el parénquima pulmonar, asociada a patología pulmonar difusa y crónica, cardíaca o extracardiopulmonar. Esta entidad constituye habitualmente un hallazgo anatomopatológico
post mortem. En este caso se realiza el diagnóstico mediante biopsia pulmonar a cielo abierto.
Presentamos el caso de un varón de 79 años, con disnea, tos seca y pérdida de peso. Había sido fumador. En la radio-grafía de tórax se apreciaba un infiltrado pulmonar bilateral reticulonodulillar. La tomografía computarizada evidenció afectación intersticial con predominio septal y múltiples ca-vidades con tendencia a la panalización; engrosamiento pleural, retracción del parénquima y fibrosis bilateral. Se estableció el diagnóstico clínico de fibrosis intersticial idiopática, y el paciente evolucionó desfavorablemente. Se reali-zó una biopsia a cielo abierto. La biopsia pulmonar evidenció zonas de colapso alveolar y otras enfisematosas, algunas con secreción y extravasación eritrocitaria. Había vasocongestión intersticial; los bronquiolos presentaban infiltrado inflama-torio mononuclear y algunos polimorfonucleares. Llamaba la atención la presencia de trabéculas óseas, algunas que in-cluían la médula ósea, de tipo adiposo, en focos multicéntri-cos, predominantemente intersticiales.
La osificación pulmonar difusa constituye habitualmente un hallazgo incidental en autopsias de pacientes con antece-dentes de enfermedad pulmonar crónica difusa, siendo inu-sual el diagnóstico en un paciente vivo. La osificación pulmonar difusa no posee significación pronóstica en la fibrosis pulmonar. Constituye un signo de cronicidad y gravedad de la enfermedad.
Hypersomnia is one of the most consulted symptoms among patients evaluated at sleep disorder centers and it is frequently related to obstructive sleep apnea syndrome (OSAS). Our hypothesis is that ...Epworth sleepiness scale (ESS) is the parameter with the greatest predictive value in the OSAS diagnosis. We compared patients with OSAS diagnosis to a control group. In both groups we compared ESS with body mass index (BMI), neck circumference (NC), waist perimeter (WP). Anthropometric index (BMI, NC and WC), were similar in both groups (p < 0.10). When we analyzed ESS, a score greater than 10 was observed in the OSAS group, with a significant difference between groups (p < 0.001). Epworth sleepiness scale yielded 60% of sensibility, 82% of specificity and a positive predictive value of 85%. The negative predictive value was 52%. Confidence index was 70%. The relationship between OSAS and ESS scale was significant (Pearson Chi-Square value 7.5). Odds Ratio for apneas was 15 and its confidence interval was lower than 1.5 and upper than 141. We conclude that with ESS score exceeding 10 points OSAS should be suspected.
Despite novel therapies for melanoma, drug resistance remains a significant hurdle to achieving optimal responses. NRAS‐mutant melanoma is an archetype of therapeutic challenges in the field, which ...we used to test drug combinations to avert drug resistance. We show that BET proteins are overexpressed in NRAS‐mutant melanoma and that high levels of the BET family member BRD4 are associated with poor patient survival. Combining BET and MEK inhibitors synergistically curbed the growth of NRAS‐mutant melanoma and prolonged the survival of mice bearing tumors refractory to MAPK inhibitors and immunotherapy. Transcriptomic and proteomic analysis revealed that combining BET and MEK inhibitors mitigates a MAPK and checkpoint inhibitor resistance transcriptional signature, downregulates the transcription factor TCF19, and induces apoptosis. Our studies demonstrate that co‐targeting MEK and BET can offset therapy resistance, offering a salvage strategy for melanomas with no other therapeutic options, and possibly other treatment‐resistant tumor types.
Synopsis
Oncogenic NRAS has been deemed undrugabble; an alternative approach is to target NRAS effectors and non‐oncogene addictions. Co‐targeting MEK and BET synergistically downregulated TCF19 and restrained the growth of NRASMut melanoma tumors including tumors resistant to targeted and immunotherapies.
High BRD4 levels are associated with poor outcome in NRASMut melanoma patients, suggesting that BRD4 plays a key role and hence, constitutes a vulnerability that can be therapeutically exploited.
Combining BET and MEK inhibitors restrained the growth of NRASMut melanoma and prolonged the survival of mice bearing tumors refractory to MAPK and checkpoint inhibitors with no overt toxicity.
Co‐targeting BET and MEK mitigates a MAPK‐ and checkpoint‐inhibitor resistance transcriptional signature (IPRES) and downregulates the transcription factor TCF19.
TCF19 blockade triggers apoptosis of NRASMut melanoma cells.
Downregulation of TCF19 is associated with response to targeted or immunotherapies.
Oncogenic NRAS has been deemed undrugabble; an alternative approach is to target NRAS effectors and non‐oncogene addictions. Co‐targeting MEK and BET synergistically downregulated TCF19 and restrained the growth of NRASMut melanoma tumors including tumors resistant to targeted and immunotherapies.
In spite of the numerous studies on chronic obstructive pulmonary disease (COPD), the cellular and molecular basis of the disease's development remain unclear. Neutrophils and eosinophils are known ...to be key players in COPD. Recently, neutrophil extracellular trap cell death (NETosis), a mechanism due to decondensation and extrusion of chromatin to form extracellular traps, has been demonstrated in COPD. However, there is limited knowledge about eosinophil extracellular trap cell death (EETosis) and its role in the pathogenesis of COPD. The aim of this study was to evaluate EETosis in stable COPD. Induced sputum obtained from healthy smokers and low exacerbation risk COPD A or B group patients or high exacerbation risk COPD C or D group patients were included. Samples were examined using electron microscopy and immunofluorescence. Healthy smokers (n=10) and COPD A (n=19) group exhibited neutrophilic or paucigranulocytic phenotypes, with NETosis being absent in these patients. In contrast, COPD B (n=29), with eosinophilic or mixed phenotypes, showed EETosis and incipient NETosis. COPD C (n=18) and COPD D groups (n=13) were differentiated from low exacerbation rate-COPD group by the abundant cellular debris, with COPD C group having an eosinophilic pattern and numerous cells undergoing EETosis. A hallmark of this group was the abundant released membranes that often appeared phagocytosed by neutrophils, which coincidentally exhibited early NETosis changes. The COPD D group included patients with a neutrophilic or mixed pattern, with abundant neutrophil extracellular trap-derived material. This study is the first to demonstrate EETosis at different stages of stable COPD. The results suggest a role for eosinophils in COPD pathophysiology, especially at the beginning and during the persistence of the disease, regardless of whether the patient quit smoking, with EETosis debris probably triggering uncontrolled NETosis. The main target of these findings should be young smokers with the potential to develop COPD.
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