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1.
Transpl Int ; 35: 10433, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35620675

RESUMO

Background: Hyperammonemia after lung transplantation (HALT) is a rare but serious complication with high mortality. This systematic review delineates possible etiologies of HALT and highlights successful strategies used to manage this fatal complication. Methods: Seven biomedical databases and grey literature sources were searched using keywords relevant to hyperammonemia and lung transplantation for publications between 1995 and 2020. Additionally, we retrospectively analyzed HALT cases managed at our institution between January 2016 and August 2018. Results: The systematic review resulted in 18 studies with 40 individual cases. The mean peak ammonia level was 769 µmol/L at a mean of 14.1 days post-transplant. The mortality due to HALT was 57.5%. In our cohort of 120 lung transplants performed, four cases of HALT were identified. The mean peak ammonia level was 180.5 µmol/L at a mean of 11 days after transplantation. HALT in all four patients was successfully treated using a multimodal approach with an overall mortality of 25%. Conclusion: The incidence of HALT (3.3%) in our institution is comparable to prior reports. Nonetheless, ammonia levels in our cohort were not as high as previously reported and peaked earlier. We attributed these significant differences to early recognition and prompt institution of multimodal treatment approach.


Assuntos
Hiperamonemia , Transplante de Pulmão , Amônia , Estudos de Coortes , Humanos , Hiperamonemia/etiologia , Hiperamonemia/terapia , Transplante de Pulmão/efeitos adversos , Estudos Retrospectivos
2.
Am J Transplant ; 21(6): 2067-2078, 2021 06.
Artigo em Inglês | MEDLINE | ID: mdl-33210808

RESUMO

Complement is known to play a role in ischemia and reperfusion injury (IRI). A general paradigm is that complement is activated by self-reactive natural IgM antibodies (nAbs), after they engage postischemic neoepitopes. However, a role for nAbs in lung transplantation (LTx) has not been explored. Using mouse models of LTx, we investigated the role of two postischemic neoepitopes, modified annexin IV (B4) and a subset of phospholipids (C2), in LTx. Antibody deficient Rag1-/- recipient mice were protected from LTx IRI. Reconstitution with either B4 or C2nAb restored IRI, with C2 significantly more effective than B4 nAb. Based on these information, we developed/characterized a novel complement inhibitor composed of single-chain antibody (scFv) derived from the C2 nAb linked to Crry (C2scFv-Crry), a murine inhibitor of C3 activation. Using an allogeneic LTx, in which recipients contain a full nAb repertoire, C2scFv-Crry targeted to the LTx, inhibited IRI, and delayed acute rejection. Finally, we demonstrate the expression of the C2 neoepitope in human donor lungs, highlighting the translational potential of this approach.


Assuntos
Lesão Pulmonar , Transplante de Pulmão , Traumatismo por Reperfusão , Transplantes , Animais , Inativadores do Complemento , Humanos , Imunoglobulina M , Transplante de Pulmão/efeitos adversos , Camundongos , Traumatismo por Reperfusão/prevenção & controle
3.
Am J Transplant ; 20(12): 3658-3661, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32506577

RESUMO

End-stage lung disease and advanced cardiac conditions are frequently seen together and represent a clinical dilemma. Even though both issues may be amenable to surgical management, combining lung transplant with surgical valve repair is rarely done and theoretically associated with increased morbidity and mortality risks, especially in elderly patients. Here, we describe 2 patients presenting with end-stage lung disease and significant aortic stenosis who were successfully bridged to lung transplant via transcatheter aortic valve replacement. Patient 1 was a 66-year-old man who underwent a double lung transplant 56 days after transcatheter aortic valve replacement. Patient 2 was a 70-year-old man who underwent a single right lung transplant 103 days after transcatheter aortic valve replacement. Both patients had uneventful postoperative courses and are alive at the 1-year time point with excellent performance status. This report suggests that transcatheter aortic valve replacement may favorably impact lung transplant candidacy for patients with end-stage lung disease in the setting of severe aortic stenosis, likely representing a better alternative to concomitant aortic valve replacement and lung transplant in elderly patients.


Assuntos
Estenose da Valva Aórtica , Transplante de Pulmão , Substituição da Valva Aórtica Transcateter , Idoso , Valva Aórtica/diagnóstico por imagem , Valva Aórtica/cirurgia , Estenose da Valva Aórtica/cirurgia , Humanos , Masculino , Índice de Gravidade de Doença , Resultado do Tratamento
4.
Transpl Int ; 32(12): 1268-1276, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31502728

RESUMO

Skin cancer is the most common malignancy affecting solid organ transplant recipients (SOTR), and SOTR experience increased skin cancer-associated morbidity and mortality. There are no formal multidisciplinary guidelines for skin cancer screening after transplant, and current practices are widely variable. We conducted three rounds of Delphi method surveys with a panel of 84 U.S. dermatologists and transplant physicians to establish skin cancer screening recommendations for SOTR. The transplant team should risk stratify SOTR for screening, and dermatologists should perform skin cancer screening by full-body skin examination. SOTR with a history of skin cancer should continue regular follow-up with dermatology for skin cancer surveillance. High-risk transplant patients include thoracic organ recipients, SOTR age 50 and above, and male SOTR. High-risk Caucasian patients should be screened within 2 years after transplant, all Caucasian, Asian, Hispanic, and high-risk African American patients should be screened within 5 years after transplant. No consensus was reached regarding screening for low-risk African American SOTR. We propose a standardized approach to skin cancer screening in SOTR based on multidisciplinary expert consensus. These guidelines prioritize and emphasize the need for screening for SOTR at greatest risk for skin cancer.


Assuntos
Técnica Delphi , Detecção Precoce de Câncer/métodos , Transplante de Órgãos/efeitos adversos , Neoplasias Cutâneas/diagnóstico , Consenso , Feminino , Guias como Assunto , Humanos , Masculino , Medição de Risco , Neoplasias Cutâneas/epidemiologia , Transplantados , Estados Unidos
5.
Cureus ; 16(6): e62638, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38903976

RESUMO

Persistent sinus tachycardia (pST) has been associated with adverse cardiovascular events in critically ill patients. Pharmacological control of heart rate with negative inotropic agents has proven to be safe but could be potentially dangerous in patients with concomitant right ventricular (RV) dysfunction. Ivabradine, a medication devoid of negative inotropy, could be a potentially safe solution for this patient population when adequate heart rate control is desired. A 17-year-old male with a history of vaping developed acute respiratory distress syndrome (ARDS) and RV dysfunction, requiring extra corporal life support (ECLS). He suffered from pST. Given his RV dysfunction, a beta-blocker was avoided, and ivabradine was used safely with improvement of his pST. This case demonstrates the efficacy of ivabradine to reduce heart rate and avoid the use of beta-blockers for patients with RV dysfunction, which could be detrimental. Ivabradine was shown to lower the heart rate without altering hemodynamic parameters.

6.
bioRxiv ; 2024 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-37886547

RESUMO

The significance of STING (encoded by the TMEM173 gene), in tissue inflammation and cancer immunotherapy has been increasingly recognized. Intriguingly, common human STING alleles R71H-G230A-R293Q (HAQ) and G230A-R293Q (AQ) are carried by ~60% of East Asians and ~40% of Africans, respectively. Here, we examine the modulatory effects of HAQ, AQ alleles on STING-associated vasculopathy with onset in infancy (SAVI), an autosomal dominant, fatal inflammatory disease caused by gain-of-function human STING mutations. CD4 T cellpenia is evident in SAVI patients and mouse models. Using STING knock-in mice expressing common human STING alleles HAQ, AQ, and Q293, we found that HAQ, AQ, and Q293 splenocytes resist STING-mediated cell death ex vivo, establishing a critical role of STING residue 293 in cell death. The HAQ/SAVI(N153S) and AQ/SAVI(N153S) mice did not have CD4 T cellpenia. The HAQ/SAVI(N153S), AQ/SAVI(N153S) mice have more (~10-fold, ~20-fold, respectively) T-regs than WT/SAVI(N153S) mice. Remarkably, while they have comparable TBK1, IRF3, and NFκB activation as the WT/SAVI, the AQ/SAVI mice have no tissue inflammation, regular body weight, and normal lifespan. We propose that STING activation promotes tissue inflammation by depleting T-regs cells in vivo. Billions of modern humans have the dominant HAQ, AQ alleles. STING research and STING-targeting immunotherapy should consider TMEM173 heterogeneity in humans.

7.
Ann Card Anaesth ; 27(3): 260-262, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38963364

RESUMO

ABSTRACT: Venovenous (VV) ECMO is rarely used during decompensated circulatory states. Although VA ECMO is the routine option, VV ECMO may be an option in selected patients. We present a case of pulmonary edema due to acute heart failure in a patient 4- and 12-year post-lung transplantation who received VV ECMO. Using a thoughtful cannulation strategy, VV ECMO, and aggressive ultrafiltration, the patient was successfully decannulated, extubated, and discharged from the hospital. In cardiogenic pulmonary edema, VV ECMO represents an additional, and likely under-utilized tool, especially in patients who are at high risk for ventilator-associated lung injury. Cannula location and size should be given additional consideration to potentially transition to V-AV ECMO configuration if necessary.


Assuntos
Oxigenação por Membrana Extracorpórea , Insuficiência Cardíaca , Transplante de Pulmão , Humanos , Oxigenação por Membrana Extracorpórea/métodos , Insuficiência Cardíaca/cirurgia , Insuficiência Cardíaca/terapia , Insuficiência Cardíaca/complicações , Masculino , Edema Pulmonar/etiologia , Edema Pulmonar/terapia , Pessoa de Meia-Idade , Doença Aguda , Doença Crônica , Complicações Pós-Operatórias/terapia , Complicações Pós-Operatórias/etiologia
8.
Am J Med Sci ; 2024 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-39168408

RESUMO

A 53-year-old man with acute myeloid leukemia received an allogeneic hematopoietic cell transplant (HCT) from a matched unrelated donor. One month after his transplantation, he developed ARDS requiring initiation of VV-ECMO. He suffered from pancytopenia, managed with frequent transfusions, granulocyte-colony stimulating factor (G-CSF) and weekly thrombopoietin receptor agonist. On ECMO day 17, the patient developed severe hypotension after insertion of a chest tube for a large right-sided pneumothorax. CT angiography of the abdomen showed hemoperitoneum. Exploratory laparotomy revealed approximately 4 L of blood and a ruptured splenic hilum. A splenectomy was performed. Unfortunately, the patient continued to require multiple daily blood products and his condition continued to decline despite two reoperations. His family chose to discontinue ECMO and he passed away peacefully. Spontaneous splenic rupture after GM-CSF has never been reported in patients on VV-ECMO. This manuscript reviews the literature regarding the pathophysiology and clinical manifestation of this rare occurrence.

9.
bioRxiv ; 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38328174

RESUMO

Rationale: Patients with end stage lung diseases require lung transplantation (LTx) that can be impeded by ischemia-reperfusion injury (IRI) leading to subsequent chronic lung allograft dysfunction (CLAD) and inadequate outcomes. Objectives: We examined the undefined role of MerTK (receptor Mer tyrosine kinase) on monocytic myeloid-derived suppressor cells (M-MDSCs) in efferocytosis (phagocytosis of apoptotic cells) to facilitate resolution of lung IRI. Methods: Single-cell RNA sequencing of lung tissue and BAL from post-LTx patients was analyzed. Murine lung hilar ligation and allogeneic orthotopic LTx models of IRI were used with Balb/c (WT), cebpb -/- (MDSC-deficient), Mertk -/- or MerTK-CR (cleavage resistant) mice. Lung function, IRI (inflammatory cytokine and myeloperoxidase expression, immunohistology for neutrophil infiltration), and flow cytometry of lung tissue for efferocytosis of apoptotic neutrophils were assessed in mice. Measurements and Main Results: A significant downregulation in MerTK-related efferocytosis genes in M-MDSC populations of CLAD patients compared to healthy subjects was observed. In the murine IRI model, significant increase in M-MDSCs, MerTK expression and efferocytosis was observed in WT mice during resolution phase that was absent in cebpb -/- Land Mertk -/- mice. Adoptive transfer of M-MDSCs in cebpb -/- mice significantly attenuated lung dysfunction, and inflammation leading to resolution of IRI. Additionally, in a preclinical murine orthotopic LTx model, increases in M-MDSCs were associated with resolution of lung IRI in the transplant recipients. In vitro studies demonstrated the ability of M-MDSCs to efferocytose apoptotic neutrophils in a MerTK-dependent manner. Conclusions: Our results suggest that MerTK-dependent efferocytosis by M-MDSCs can significantly contribute to the resolution of post-LTx IRI.

10.
JCI Insight ; 2024 Aug 22.
Artigo em Inglês | MEDLINE | ID: mdl-39172530

RESUMO

Lung transplantation (LTx) outcomes are impeded by ischemia-reperfusion injury (IRI) and subsequent chronic lung allograft dysfunction (CLAD). We examined the undefined role of MerTK (receptor Mer tyrosine kinase) on monocytic myeloid-derived suppressor cells (M-MDSCs) in efferocytosis to facilitate resolution of lung IRI. Single-cell RNA sequencing of lung tissue and bronchoalveolar lavage (BAL) from post-LTx patients were analyzed. Murine lung hilar ligation and allogeneic orthotopic LTx models of IRI were used with Balb/c (WT), Cebpb-/- (MDSC-deficient), Mertk-/- or MerTK-CR (cleavage resistant) mice. A significant downregulation in MerTK-related efferocytosis genes in M-MDSC populations of CLAD patients was observed compared to healthy subjects. In the murine IRI model, significant increase in M-MDSCs, MerTK expression, efferocytosis and attenuation of lung dysfunction was observed in WT mice during injury resolution that was absent in Cebpb-/- and Mertk-/- mice. Adoptive transfer of M-MDSCs in Cebpb-/- mice significantly attenuated lung dysfunction and inflammation. Additionally, in a murine orthotopic LTx model, increases in M-MDSCs were associated with resolution of lung IRI in the transplant recipients. In vitro studies demonstrated the ability of M-MDSCs to efferocytose apoptotic neutrophils in a MerTK-dependent manner. Our results suggest that MerTK-dependent efferocytosis by M-MDSCs can substantially contribute to the resolution of post-LTx IRI.

11.
Am J Respir Cell Mol Biol ; 48(2): 145-9, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23087052

RESUMO

Lung transplantation is considered the definitive treatment for many end-stage lung diseases. However, the lung is rejected more commonly than other solid organ allografts. Obliterative bronchiolitis (OB) is the leading cause of chronic allograft dysfunction, and the key reason why the 5-year survival of lung transplant recipients is only 50%. The pathophysiology of OB is incompletely understood. Although a clear role for the immune response to donor antigens has been observed (also known as anti-human leukocyte antigens), evidence is emerging about the role of autoimmunity to self-antigens. This review highlights the current understanding of humoral immunity in the development of OB after lung transplantation.


Assuntos
Formação de Anticorpos , Bronquiolite Obliterante/imunologia , Transplante de Pulmão/efeitos adversos , Bronquiolite Obliterante/etiologia , Humanos , Interleucina-17/fisiologia , Transplante de Pulmão/imunologia , Taxa de Sobrevida , Linfócitos T Reguladores/imunologia , Células Th17/imunologia
12.
J Heart Lung Transplant ; 42(5): 562-574, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36628837

RESUMO

BACKGROUND: Dysregulation of inflammation-resolution pathways leads to postlung transplant (LTx) ischemia-reperfusion (IR) injury and allograft dysfunction. Our hypothesis is that combined treatment with specialized pro-resolving lipid mediators, that is, Resolvin D1 (RvD1) and Maresin-1 (MaR1), enhances inflammation-resolution of lung IR injury. METHODS: Expression of RvD1 and MaR1 was analyzed in bronchoalveolar lavage (BAL) fluid of patients on days 0, 1, and 7 post-LTx. Lung IR injury was evaluated in C57BL/6 (WT), FPR2-/-, and LGR6 siRNA treated mice using a hilar-ligation model with or without administration with RvD1 and/or MaR1. A donation after circulatory death and murine orthotopic lung transplantation model was used to evaluate the protection by RvD1 and MaR1 against lung IR injury. In vitro studies analyzed alveolar macrophages and type II epithelial cell activation after treatment with RvD1 or MaR1. RESULTS: RvD1 and MaR1 expressions in BAL from post-LTx patients was significantly increased on day 7 compared to days 0 and 1. Concomitant RvD1 and MaR1 treatment significantly mitigated early pulmonary inflammation and lung IR injury in WT mice, which was regulated via FPR2 and LGR6 receptors. In the murine orthotopic donation after cardiac death LTx model, RvD1 and MaR1 treatments significantly attenuated lung IR injury and increased PaO2 levels compared to saline-treated controls. Mechanistically, RvD1/FPR2 signaling on alveolar macrophages attenuated HMGB1 and TNF-α secretion and upregulated uptake of macrophage-dependent apoptotic neutrophils (efferocytosis), whereas MaR1/LGR6 signaling mitigated CXCL1 secretion by epithelial cells. CONCLUSIONS: Bioactive proresolving lipid mediator-dependent signaling that is, RvD1/FPR2 and MaR1/LGR6- offers a novel therapeutic strategy in post-LTx injury.


Assuntos
Ácidos Docosa-Hexaenoicos , Pneumopatias , Transplante de Pulmão , Traumatismo por Reperfusão , Animais , Camundongos , Células Epiteliais Alveolares/efeitos dos fármacos , Líquido da Lavagem Broncoalveolar/química , Ácidos Docosa-Hexaenoicos/análise , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/etiologia , Inflamação/genética , Inflamação/metabolismo , Pneumopatias/tratamento farmacológico , Pneumopatias/etiologia , Pneumopatias/metabolismo , Pneumopatias/cirurgia , Transplante de Pulmão/efeitos adversos , Macrófagos Alveolares/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Receptores Acoplados a Proteínas G , Traumatismo por Reperfusão/tratamento farmacológico , Traumatismo por Reperfusão/etiologia , Traumatismo por Reperfusão/genética , Traumatismo por Reperfusão/metabolismo , RNA Interferente Pequeno
13.
ERJ Open Res ; 9(2)2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37009016

RESUMO

Rationale: Nontuberculous mycobacterial (NTM) diseases are difficult-to-treat infections, especially in lung transplant (LTx) candidates. Currently, there is a paucity of recommendations on the management of NTM infections in LTx, focusing on Mycobacterium avium complex (MAC), M. abscessus and M. kansasii. Methods: Pulmonologists, infectious disease specialists, LTx surgeons and Delphi experts with expertise in NTM were recruited. A patient representative was also invited. Three questionnaires comprising questions with multiple response statements were distributed to panellists. Delphi methodology with a Likert scale of 11 points (5 to -5) was applied to define the agreement between experts. Responses from the first two questionnaires were collated to develop a final questionnaire. The consensus was described as a median rating >4 or <-4 indicating for or against the given statement. After the last round of questionnaires, a cumulative report was generated. Results: Panellists recommend performing sputum cultures and a chest computed tomography scan for NTM screening in LTx candidates. Panellists recommend against absolute contraindication to LTx even with multiple positive sputum cultures for MAC, M. abscessus or M. kansasii. Panellists recommend MAC patients on antimicrobial treatment and culture negative can be listed for LTx without further delay. Panellists recommend 6 months of culture-negative for M. kansasii, but 12 months of further treatment from the time of culture-negative for M. abscessus before listing for LTx. Conclusion: This NTM LTx study consensus statement provides essential recommendations for NTM management in LTx and can be utilised as an expert opinion while awaiting evidence-based contributions.

14.
Med Mycol ; 50(4): 396-8, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-21939346

RESUMO

It is well known that cross reactions with other fungal pathogens including Histoplasma capsulatum can occur with the use of the Platelia™ Aspergillus galactomannan assay. We report two patients with confirmed blastomycosis whose bronchoalveolar lavage (BAL) fluid tested positive for Aspergillus galactomannan despite no evidence of aspergillosis.


Assuntos
Blastomicose/diagnóstico , Técnicas de Laboratório Clínico/métodos , Reações Cruzadas , Técnicas Imunoenzimáticas/métodos , Micologia/métodos , Idoso , Aspergilose/diagnóstico , Aspergillus/química , Galactose/análogos & derivados , Humanos , Masculino , Mananas/análise
16.
Front Immunol ; 12: 711102, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34456920

RESUMO

Lung transplant patients have the lowest long-term survival rates compared to other solid organ transplants. The complications after lung transplantation such as primary graft dysfunction (PGD) and ultimately chronic lung allograft dysfunction (CLAD) are the main reasons for this limited survival. In recent years, lung-specific autoantibodies that recognize non-HLA antigens have been hypothesized to contribute to graft injury and have been correlated with PGD, CLAD, and survival. Mounting evidence suggests that autoantibodies can develop during pulmonary disease progression before lung transplant, termed pre-existing autoantibodies, and may participate in allograft injury after transplantation. In this review, we summarize what is known about pulmonary disease autoantibodies, the relationship between pre-existing autoantibodies and lung transplantation, and potential mechanisms through which pre-existing autoantibodies contribute to graft injury and rejection.


Assuntos
Autoanticorpos/imunologia , Transplante de Pulmão/efeitos adversos , Complicações Pós-Operatórias/etiologia , Bronquiolite Obliterante/imunologia , Glicosilação , Humanos , Pneumopatias/etiologia , Pneumopatias/imunologia , Doenças Pulmonares Intersticiais/imunologia , Complicações Pós-Operatórias/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Receptor Tipo 1 de Angiotensina/imunologia , Receptor de Endotelina A/imunologia , Transplante Homólogo
17.
Respir Med Case Rep ; 33: 101409, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34401257

RESUMO

BACKGROUND: Macrophage activating syndrome (MAS) is a form of hemophagocytic lymphohistiocytosis (HLH), a rare complication of autoimmune disease that is characterized by cytokine storm and multiorgan failure. CASE SUMMARY: A 32-year-old male presented with acutely decompensated pulmonary arterial hypertension and right heart failure secondary to MAS. The patient was immediately started on inhaled and intravenous epoprostenol, vasopressors and dexamethasone and anakinra were administered. Despite the therapies given, the patient's condition continued to decline, and he was placed on veno-arterial extracorporeal membrane oxygenation (VA-ECMO) support. Over a few days, his clinical condition improved, and he was decannulated from VA-ECMO and later transitioned oral treprositinil and was discharged home. Due to its non-specific clinical manifestations, the diagnosis of MAS depends on high clinical suspicion and initial laboratory work up such as thrombocytopenia, transaminitis, hyperferritinemia, hypertriglyceridemia, hypofibrinogenemia, etc. In our patient, MAS led to decompensated Pulmonary Arterial Hypertension (PAH) leading to right heart failure that was refractory to inhaled and intravenous epoprostenol and vasopressors and required VA-ECMO as a bridge to recovery while his MAS was managed by anakinra and dexamethasone. CONCLUSION: MAS can result in acute decompensation of PAH and right heart failure. Besides RV failure management, immunosuppressants such as anakinra, etoposide, etc. should be utilized early in the management of MAS. In refractory right heart failure, VA-ECMO can be considered as a bridge to recovery. There is a paucity of literature supporting the utilization of VA-ECMO in the management of refractory right heart failure caused by MAS in adults and much of the data stems from pediatric studies. This case serves as a fine example of successful use of VA-ECMO in adult population.

18.
Ann Thorac Surg ; 111(3): e201-e203, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32652070

RESUMO

Surgically treatable valvular heart disease is common in patients with end-stage lung disease. Nevertheless, advanced lung disease is often seen as a contraindication to cardiac surgery, and severe valvular disease is seen as a contraindication to lung transplantation. This report describes the case of a patient presenting with very severe chronic obstructive pulmonary disease and severe mitral regurgitation who was managed with transcatheter mitral valve repair and who subsequently underwent successful lung transplantation. Critical valvular heart disease in patients with chronic respiratory failure may be amenable to transcatheter therapy, which may favorably affect lung transplantation candidacy.


Assuntos
Cateterismo Cardíaco/métodos , Implante de Prótese de Valva Cardíaca/métodos , Próteses Valvulares Cardíacas , Transplante de Pulmão/métodos , Insuficiência da Valva Mitral/cirurgia , Valva Mitral/cirurgia , Insuficiência Respiratória/cirurgia , Ecocardiografia , Feminino , Humanos , Pessoa de Meia-Idade , Valva Mitral/diagnóstico por imagem , Insuficiência da Valva Mitral/complicações , Insuficiência da Valva Mitral/diagnóstico , Período Pré-Operatório , Desenho de Prótese , Radiografia Torácica , Insuficiência Respiratória/complicações
19.
Sci Immunol ; 6(61)2021 07 09.
Artigo em Inglês | MEDLINE | ID: mdl-34244314

RESUMO

Asthma is a common inflammatory lung disease with no known cure. Previously, we uncovered a lung TNFR2+ conventional DC2 subset (cDC2s) that induces regulatory T cells (Tregs) maintaining lung tolerance at steady state but promotes TH2 response during house dust mite (HDM)-induced asthma. Lung IFNß is essential for TNFR2+ cDC2s-mediated lung tolerance. Here, we showed that exogenous IFNß reprogrammed TH2-promoting pathogenic TNFR2+ cDC2s back to tolerogenic DCs, alleviating eosinophilic asthma and preventing asthma exacerbation. Mechanistically, inhaled IFNß, not IFNα, activated ERK2 signaling in pathogenic lung TNFR2+ cDC2s, leading to enhanced fatty acid oxidation (FAO) and lung Treg induction. Last, human IFNß reprogrammed pathogenic human lung TNFR2+ cDC2s from patients with emphysema ex vivo. Thus, we identified an IFNß-specific ERK2-FAO pathway that might be harnessed for DC therapy.


Assuntos
Asma/imunologia , Células Dendríticas/transplante , Interferon beta/uso terapêutico , Receptores Tipo II do Fator de Necrose Tumoral/genética , Células Th2/imunologia , Transferência Adotiva , Animais , Asma/patologia , Células Cultivadas , Células Dendríticas/imunologia , Dermatophagoides pteronyssinus/imunologia , Modelos Animais de Doenças , Ácidos Graxos/metabolismo , Humanos , Tolerância Imunológica/imunologia , Fatores Imunológicos/uso terapêutico , Interferon-alfa/farmacologia , Pulmão/citologia , Pulmão/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína Quinase 1 Ativada por Mitógeno/metabolismo , Oxirredução , Receptor de Interferon alfa e beta/genética , Transdução de Sinais/imunologia , Linfócitos T Reguladores/imunologia
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