RESUMO
Cardiothoracic surgeons work in high-intensity environments starting in surgical training and throughout their careers. They deal with critical patients. Their routine procedures are delicate, require extensive attention to detail, and can have detrimental effects on patients' lives. Cardiothoracic surgeons are required to perform at their best capacity incessantly. To do this, they must safeguard their mental and physical well-being. Preserving health through sleep, nutrition, exercise, and routine medical checkups ensures a cardiothoracic surgeon's well-being. Great personal effort and discipline is required to maintain health in a busy schedule. We offer our best recommendations from expert peers in the field.
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Estado Nutricional , Sono , Humanos , Sono/fisiologia , Procedimentos Cirúrgicos Cardíacos , Procedimentos Cirúrgicos Torácicos , Cirurgia Torácica/organização & administração , Exercício FísicoRESUMO
The implications of impaired esophagogastric junction relaxation (i.e. esophagogastric junction outflow obstruction and achalasia) in lung transplants recipients (LTRs) are unclear. Thus, we examined the prevalence and clinical outcomes of LTRs with an abnormally elevated integrated relaxation pressure (IRP) on high-resolution manometry before lung transplantation (LTx). After IRB approval, we reviewed data on LTRs who underwent LTx between January 2019 and August 2022 with a preoperative median IRP >15 mmHg. Differences in overall survival and chronic lung allograft dysfunction (CLAD)-free survival between LTRs with a normalized median IRP after LTx (N-IRP) and those with persistently high IRP (PH-IRP) were assessed using Kaplan-Meier curves and the log-rank test. During the study period, 352 LTx procedures were performed; 44 (12.5%) LTRs had an elevated IRP before LTx, and 37 (84.1%) completed a postoperative manometry assessment (24 [70.6%] males; mean age, 65.2 ± 9.1 years). The median IRP before and after LTx was 18.7 ± 3.8 mmHg and 12 ± 5.6 mmHg, respectively (P < 0.001); the median IRP normalized after LTx in 24 (64.9%) patients. Two-year overall survival trended lower in the N-IRP group than the PH-IRP group (77.2% vs. 92.3%, P = 0.086), but CLAD-free survival (P = 0.592) and rates of primary graft dysfunction (P = 0.502) and acute cellular rejection (P = 0.408) were similar. An abnormally elevated IRP was common in LTx candidates; however, it normalized in roughly two-thirds of patients after LTx. Two-year survival trended higher in the PH-IRP group, despite similar rates of primary graft dysfunction and acute cellular rejection as well as similar CLAD-free survival between the groups.
Assuntos
Junção Esofagogástrica , Transplante de Pulmão , Manometria , Humanos , Masculino , Feminino , Junção Esofagogástrica/fisiopatologia , Junção Esofagogástrica/cirurgia , Pessoa de Meia-Idade , Idoso , Estudos Retrospectivos , Resultado do Tratamento , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Acalasia Esofágica/cirurgia , Acalasia Esofágica/fisiopatologia , Transtornos da Motilidade Esofágica/fisiopatologiaRESUMO
The lungs and esophagus have a close anatomical and physiological relationship. Over the years, reflux-induced pulmonary injury has gained wider recognition, but the full effects of pulmonary disease on esophageal function are still unknown. Intrathoracic pressure dynamics potentially affect esophageal function, especially in patients with end-stage lung disease, both obstructive and restrictive. Lung transplantation is the only viable option for patients with end-stage pulmonary disease and has provided us with a unique opportunity to study these effects as transplantation restores the intrathoracic environment. Esophageal and foregut functional testing before and after transplantation provide insights into the pathophysiology of the foregut-pulmonary axis, such as how underlying pulmonary disease and intrathoracic pressure changes affect esophageal physiology. This review summarizes the available literature and shares the research experience of a lung transplant center, covering topics such as pre- and posttransplant foregut function, esophageal motility in lung transplant recipients, immune-mediated mechanisms of graft rejection associated with gastroesophageal reflux, and the role of antireflux surgery in this population.
Assuntos
Refluxo Gastroesofágico , Pneumopatias , Transplante de Pulmão , Humanos , Estudos Retrospectivos , Pulmão , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/epidemiologia , Transplante de Pulmão/efeitos adversos , Pneumopatias/cirurgiaRESUMO
OBJECTIVES: We aimed to evaluate how the current working climate of cardiothoracic surgery and burnout experienced by cardiothoracic surgeons influences their spouses and significant others (SOs). METHODS: A 33-question well-being survey was developed by the American Association for Thoracic Surgery Wellness Committee and distributed by e-mail to the SOs of cardiothoracic surgeons and to all surgeon registrants of the 2020 and 2021 American Association for Thoracic Surgery Annual Meetings with a request to share it with their SO. The 5-item Likert-scale survey questions were dichotomized, and associations were determined by χ2 or independent samples t tests, as appropriate. RESULTS: Responses from 238 SOs were analyzed. Sixty-six percent reported that the stress on their cardiothoracic surgeon partner had a moderate to severe influence on their family, and 63% reported that their partner's work demands didn't leave enough time for family. Fifty-one percent reported that their partner rarely had time for intimacy, 27% reported poor work-life balance, and 23% reported that interactions at home were usually or always not good-natured. SOs were most affected when their partner was <5 years out from training, worked in private vs academic practice, and worked longer hours. Having children, particularly younger than age 19 years, and a lack of workplace support resources further diminished well-being. CONCLUSIONS: The current work culture of cardiothoracic surgeons adversely affects their SOs, and the risk for families is concerning. These data present a major area for exploration as we strive to understand and mitigate the factors that lead to burnout among cardiothoracic surgeons.
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Esgotamento Profissional , Cirurgiões , Cirurgia Torácica , Procedimentos Cirúrgicos Torácicos , Criança , Humanos , Estados Unidos , Adulto Jovem , Adulto , Procedimentos Cirúrgicos Torácicos/educação , Cirurgiões/educação , Inquéritos e Questionários , EmpregoRESUMO
Humoral and cellular immune responses to SARS-CoV-2 and other coronaviruses in lung transplant recipients are unknown. We measured antibodies and T cell responses against the SARS-CoV-2 spike S2 and nucleocapsid antigens and spike antigens from common respiratory coronaviruses (229E, NL63, OC43, and HKU1) after vaccination or infection of LTxRs. 148 LTxRs from single center were included in this study: 98 after vaccination and 50 following SARS-CoV-2 infection. Antibodies were quantified by enzyme-linked immunosorbent assay. The frequency of T cells secreting IL2, IL4, IL10, IL17, TNFα, and IFNγ were enumerated by enzyme-linked immunospot assay. Our results have shown the development of antibodies to SARS-CoV-2 spike protein in infected LTxRs (39/50) and vaccinated LTxRs (52/98). Vaccinated LTxRs had higher number of T cells producing TNFα but less cells producing IFNγ than infected LTxRs in response to the nucleocapsid antigen and other coronavirus spike antigens. We didn't find correlation between the development of antibodies and cellular immune responses against the SARS-CoV-2 spike protein after vaccination. Instead, LTxRs have pre-existing cellular immunity to common respiratory coronaviruses, leading to cross-reactive immunity against SARS-CoV-2 which likely will provide protection against SARS-Cov-2 infection.
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COVID-19 , SARS-CoV-2 , Humanos , Transplantados , Fator de Necrose Tumoral alfa , Anticorpos , Imunidade Celular , ELISPOT , Anticorpos AntiviraisRESUMO
PURPOSE: Esophageal anastomotic leaks (ALs) after esophagectomy are a common and serious complication. The incidence, diagnostic approach, and management have changed over time. We described the diagnosis and management of patients who developed an esophageal AL after an Ivor Lewis esophagectomy at our center. METHODS: After IRB approval, we queried our prospectively maintained database for patients who developed an esophageal AL after esophagectomy from August 2016 through July 2022. Data pertaining to demographics, comorbidities, surgical and oncological characteristics, and clinical course were extracted and analyzed. RESULTS: During the study period, 145 patients underwent an Ivor Lewis esophagectomy; 10 (6.9%) developed an AL, diagnosed a median of 7.5 days after surgery, and detected by enteric contents in wound drains (n = 3), endoscopy (n = 3), CT (n = 2), and contrast esophagogram (n = 2). Nine patients (90%) had an increasing white blood cell count and additional signs of sepsis. One asymptomatic patient was identified by contrast esophagography. All patients received enteral nutritional support, intravenous antibiotics, and antifungals. Primary treatment of ALs included endoscopic placement of a self-expanding metal stent (SEMS; n = 6), surgery (n = 2), and SEMS with endoluminal vacuum therapy (n = 2). One patient required surgery after SEMS placement. The median length of ICU and total hospital stays were 11.5 and 22.5 days, respectively. There was no 30-day mortality. CONCLUSION: The incidence of esophageal ALs at our center is similar to that of other high-volume centers. Most ALs can be managed without surgery; however, ALs remain a significant source of postoperative morbidity despite clinical advancements that have improved mortality.
Assuntos
Fístula Anastomótica , Neoplasias Esofágicas , Humanos , Fístula Anastomótica/diagnóstico , Fístula Anastomótica/etiologia , Fístula Anastomótica/terapia , Esofagectomia/efeitos adversos , Neoplasias Esofágicas/cirurgia , Endoscopia Gastrointestinal/efeitos adversos , Estudos Retrospectivos , Complicações Pós-Operatórias/diagnóstico , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Anastomose Cirúrgica/efeitos adversos , Resultado do TratamentoRESUMO
Next generation sequencing of human cancer mutations has identified novel therapeutic targets. Activating Ras oncogene mutations play a central role in oncogenesis, and Ras-driven tumorigenesis upregulates an array of genes and signaling cascades that can transform normal cells into tumor cells. In this study, we investigated the role of altered localization of epithelial cell adhesion molecule (EpCAM) in Ras-expressing cells. Analysis of microarray data demonstrated that Ras expression induced EpCAM expression in normal breast epithelial cells. Fluorescent and confocal microscopy showed that H-Ras mediated transformation also promoted epithelial-to-mesenchymal transition (EMT) together with EpCAM. To consistently localize EpCAM in the cytosol, we generated a cancer-associated EpCAM mutant (EpCAM-L240A) that is retained in the cytosol compartment. Normal MCF-10A cells were transduced with H-Ras together with EpCAM wild-type (WT) or EpCAM-L240A. WT-EpCAM marginally effected invasion, proliferation, and soft agar growth. EpCAM-L240A, however, markedly altered cells and transformed to mesenchymal phenotype. Ras-EpCAM-L240A expression also promoted expression of EMT factors FRA1, ZEB1 with inflammatory cytokines IL-6, IL-8, and IL1. This altered morphology was reversed using MEK-specific inhibitors and to some extent JNK inhibition. Furthermore, these transformed cells were sensitized to apoptosis using paclitaxel and quercetin, but not other therapies. For the first time, we have demonstrated that EpCAM mutations can cooperate with H-Ras and promote EMT. Collectively, our results highlight future therapeutic opportunities in EpCAM and Ras mutated cancers.
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Transição Epitelial-Mesenquimal , Transdução de Sinais , Humanos , Linhagem Celular Tumoral , Citosol/metabolismo , Molécula de Adesão da Célula Epitelial/genética , Molécula de Adesão da Célula Epitelial/metabolismo , Transição Epitelial-Mesenquimal/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/genética , Homeobox 1 de Ligação a E-box em Dedo de Zinco/metabolismoRESUMO
Accumulation of senescent cells contributes to age-related diseases including idiopathic pulmonary fibrosis (IPF). Insulin-like growth factor binding proteins (IGFBPs) regulate many biological processes; however, the functional contributions of IGFBP2 in lung fibrosis remain largely unclear. Here, we report that intranasal delivery of recombinant IGFBP2 protects aged mice from weight loss and demonstrated antifibrotic effects after bleomycin lung injury. Notably, aged human-Igfbp2 transgenic mice reveal reduced senescence and senescent-associated secretory phenotype factors in alveolar epithelial type 2 (AEC2) cells and they ameliorated bleomycin-induced lung fibrosis. Finally, we demonstrate that IGFBP2 expression is significantly suppressed in AEC2 cells isolated from fibrotic lung regions of patients with IPF and/or pulmonary hypertension compared with patients with hypersensitivity pneumonitis and/or chronic obstructive pulmonary disease. Altogether, our study provides insights into how IGFBP2 regulates AEC2-cell-specific senescence and that restoring IGFBP2 levels in fibrotic lungs can prove effective for patients with IPF.
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Células Epiteliais Alveolares , Fibrose Pulmonar Idiopática , Idoso , Animais , Humanos , Camundongos , Células Epiteliais Alveolares/metabolismo , Bleomicina/efeitos adversos , Bleomicina/metabolismo , Senescência Celular/genética , Fibrose Pulmonar Idiopática/induzido quimicamente , Fibrose Pulmonar Idiopática/genética , Fibrose Pulmonar Idiopática/metabolismo , Camundongos TransgênicosRESUMO
BACKGROUND: We recently demonstrated decreased tumor suppressor gene liver kinase B1 (LKB1) level in lung transplant recipients diagnosed with bronchiolitis obliterans syndrome. STE20-related adaptor alpha (STRADα) functions as a pseudokinase that binds and regulates LKB1 activity. METHODS: A murine model of chronic lung allograft rejection in which a single lung from a B6D2F1 mouse was orthotopically transplanted into a DBA/2J mouse was employed. We examined the effect of LKB1 knockdown using CRISPR-CAS9 in vitro culture system. RESULTS: Significant downregulation of LKB1 and STRADα expression was found in donor lung compared to recipient lung. STRADα knockdown significantly inhibited LKB1, pAMPK expression but induced phosphorylated mammalian target of rapamycin (mTOR), fibronectin, and Collagen-I, expression in BEAS-2B cells. LKB1 overexpression decreased fibronectin, Collagen-I, and phosphorylated mTOR expression in A549 cells. CONCLUSIONS: We demonstrated that downregulation of LKB1-STRADα pathway accompanied with increased fibrosis, results in development of chronic rejection following murine lung transplantation.
Assuntos
Fibronectinas , Transplante de Pulmão , Animais , Camundongos , Fibronectinas/genética , Fibronectinas/metabolismo , Regulação para Baixo , Camundongos Endogâmicos DBA , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Pulmão/metabolismo , Biomarcadores , Genes Supressores de Tumor , Aloenxertos , Colágeno/genética , Colágeno/metabolismo , Mamíferos/genética , Mamíferos/metabolismoRESUMO
OBJECTIVES: Gastro-oesophageal reflux disease after lung transplantation may be associated with chronic lung allograft dysfunction. Aspiration may continue on medical management of reflux, but antireflux surgery potentially reduces all reflux. We compared outcomes between medical and surgical management of reflux in lung recipients. METHODS: Lung recipients with an elevated DeMeester score (≥14.72) on post-transplant reflux testing between 2015 and 2020 were included. Patients were divided into 2 groups: group A (underwent surgery) and group B (medically managed). Endpoints were pulmonary function, allograft dysfunction-free survival and overall survival. Further analysis included subgroups: A1 (early surgery, <6 months) and A2 (late surgery, >6 months), and B1 (DeMeester <29.9) and B2 (DeMeester ≥30). RESULTS: A total of 186 included subjects were divided into groups A [n = 46 (A1, n = 36; A2, n = 10)] and B [n = 140 (B1, n = 78; B2, n = 62)]. Compared to medically managed patients, patients who underwent surgery had a higher prevalence of hiatal hernia (P < 0.001) and a lower prevalence of oesophageal motility disorders (P = 0.036). Recipients who underwent surgery had superior pulmonary function at 5 years compared to group B (P < 0.05) and longer allograft dysfunction-free survival than subgroup B2 (P = 0.028). Furthermore, early surgery was associated with longer survival than late surgery (P = 0.021). CONCLUSIONS: Antireflux surgery in recipients with reflux improved long-term allograft function, and early surgery showed a survival benefit. Allograft dysfunction-free survival of lung recipients who underwent surgery was significantly better than that of medically managed patients with DeMeester ≥30. We present an algorithm for appropriate selection of candidates for antireflux surgery after lung transplantation.
Assuntos
Refluxo Gastroesofágico , Hérnia Hiatal , Laparoscopia , Transplante de Pulmão , Humanos , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/cirurgia , Fundoplicatura , Hérnia Hiatal/cirurgia , Pulmão , Estudos RetrospectivosRESUMO
Gastroesophageal reflux (GER) and pretransplant antibodies against lung self-antigens (SAbs) collagen-V and/or k-alpha 1 tubulin are both independently associated with allograft dysfunction after lung transplantation (LTx). The role of GER in inducing lung injury and SAbs is unknown. We aimed to study the association between pre-LTx GER and SAbs. After IRB approval, we retrieved SAb assays conducted between 2015 and 2019 and collected 24 hour GER data for these patients. Patients were divided into 2 groups: no reflux (GER-) and pathologic reflux (GER+) to compare the prevalence of SAbs. Multivariate analysis was used to study the association between GER and SAbs in the whole cohort and in restrictive lung disease (RLD) and obstructive lung disease (OLD) subsets. Proximal esophageal reflux (PER) events ≥5 was considered abnormal. Patients (n = 134; 73 men) were divided into groups: GER- (54.5%, n = 73) and GER+ (45.5%, n = 61). The prevalence of GER was higher in the RLD than in the OLD subset (p < 0.001). The overall prevalence of SAbs was 53.7% (n = 72), higher in the GER+ than the GER- group (65.6% vs 43.8%, p = 0.012), but comparable between RLD and OLD subsets. Overall, SAbs were associated with GER (p = 0.012) and abnormal PER (p = 0.017). GER and abnormal PER increased the odds of SAbs in the RLD subset (OR [95% CI]: 2.825 [1.033-7.725], p = 0.040 and OR [95% CI]: 3.551 [1.271-9.925], p = 0.014, respectively) but not in the OLD subset. LTx candidates have a high prevalence of SAbs, which are significantly associated with GER and abnormal PER in patients with RLD.
Assuntos
Refluxo Gastroesofágico , Pneumopatias , Transplante de Pulmão , Masculino , Humanos , Resultado do Tratamento , Refluxo Gastroesofágico/complicações , Refluxo Gastroesofágico/epidemiologia , PulmãoRESUMO
OBJECTIVE: Aspiration of duodenogastric refluxate may damage the respiratory epithelium of lung allografts in transplant recipients. We sought to define a mechanism by which aspiration of duodenogastric fluid augments the risk of bronchiolitis obliterans syndrome after lung transplant in a murine model. METHODS: We analyzed the immunological effects of acute aspiration of duodenogastric fluid (0.5 mL/kg) on transplant naive (strain DBA/2J) and transplanted mice (strain B6D2F1/J to strain DBA/2J). Serum antibodies to the lung self-antigens (SAgs) K-alpha1 tubulin and collagen-V were determined by enzyme-linked immunosorbent assay. Exosomes were isolated from serum, and immunoblot membranes were probed for antibodies to lung SAgs. Lung sections were assessed for fibrotic burden and obliterative bronchiolitis lesions by histologic and immunohistochemical analyses, including trichrome staining. RESULTS: Transplanted mice that received duodenogastric fluid developed higher levels of antibodies to the lung SAgs K-alpha1 tubulin and collagen-V and exosomes with lung SAgs on posttransplant days 14 and 28 than transplanted mice with sham aspiration or transplant naive mice (with and without aspiration). All lung allografts demonstrated severe grade A4 rejection on posttransplant day 14, with the highest mean fibrotic burden and mean number of obliterative bronchiolitis-like lesions per microscopic field on day 28 in recipients with aspiration. CONCLUSIONS: This study links aspiration of duodenogastric fluid after lung transplant to higher autoimmune responses to lung SAgs and the release of circulating exosomes with lung SAgs, which together promote sustained immune responses leading to extensive lung parenchymal damage and, ultimately, severe obliterative bronchiolitis-the histologic hallmark of bronchiolitis obliterans syndrome.
Assuntos
Síndrome de Bronquiolite Obliterante , Colágeno Tipo V , Transplante de Pulmão , Aspiração Respiratória de Conteúdos Gástricos , Tubulina (Proteína) , Animais , Camundongos , Autoantígenos/imunologia , Síndrome de Bronquiolite Obliterante/etiologia , Síndrome de Bronquiolite Obliterante/imunologia , Síndrome de Bronquiolite Obliterante/patologia , Colágeno Tipo V/imunologia , Suco Gástrico/imunologia , Rejeição de Enxerto , Secreções Intestinais/imunologia , Pulmão/imunologia , Pulmão/patologia , Transplante de Pulmão/efeitos adversos , Camundongos Endogâmicos DBA , Tubulina (Proteína)/imunologia , Aspiração Respiratória de Conteúdos Gástricos/complicações , Aspiração Respiratória de Conteúdos Gástricos/imunologiaRESUMO
BACKGROUND: Safety data on perioperative outcomes of laparoscopic antireflux surgery (LARS) after lung transplantation (LT) are lacking. We compared the 30-day readmission rate and short-term morbidity after LARS between LT recipients and matched nontransplant (NT) controls. METHODS: Adult patients who underwent LARS between January 1, 2015, and October 31, 2021, were included. The participants were divided into two groups: LT recipients and NT controls. First, we compared 30-day readmission rates after LARS between the LT and NT cohorts. Next, we compared 30-day morbidity after LARS between the LT cohort and a 1-to-2 propensity score-matched NT cohort. RESULTS: A total of 1328 patients (55 LT recipients and 1273 NT controls) were included. The post-LARS 30-day readmission rate was higher in LT recipients than in the overall NT controls (14.5% vs. 2.8%, p < 0.001). Compared to matched NT controls, LT recipients had a lower prevalence of paraesophageal hernia, a smaller median hernia size, and higher peristaltic vigor. Also compared to the matched NT controls, the LT recipients had a lower median operative time but a longer median length of hospital stay. The proportion of patients with a post-LARS event within 30 postoperative days was comparable between the LT and matched NT cohorts (21.8% vs 14.5%, p = 0.24). CONCLUSIONS: Despite a higher perceived risk of comorbidity burden, LT recipients and matched NT controls had similar rates of post-LARS 30-day morbidity at our large-volume center with expertise in transplant and foregut surgery. LARS after LT is safe.
Assuntos
Refluxo Gastroesofágico , Laparoscopia , Transplante de Pulmão , Adulto , Humanos , Refluxo Gastroesofágico/cirurgia , Complicações Pós-Operatórias/epidemiologia , Morbidade , Fundoplicatura , Resultado do TratamentoRESUMO
BACKGROUND: Hospitalized lung transplant (LT) recipients (LTRs) have higher post-LT morbidity and mortality than those who are well enough to wait for transplant at home. Outcomes after LT for COVID-19-associated acute respiratory distress syndrome (CARDS) may be even worse; thus, we compared post-LT outcomes between hospitalized LTRs transplanted for CARDS and those transplanted for restrictive lung disease (RLD). METHODS: Between 2014 and 2021, hospitalized LTRs ≥18 years old with CARDS or RLD were included. Primary and secondary outcomes were 1-year post-LT survival and postoperative morbidity. For each patient in the CARDS group, an analysis of 1-to-1 matched patients from the RLD group was performed using logistic regression modeling. RESULTS: Of 764 LTRs, 163 (21.3%) were hospitalized at the time of LT; 132 met the inclusion criteria: 11 (8.3%) were transplanted for CARDS and 121 (91.7%) for RLD. LTRs with CARDS were younger with longer pre-LT hospitalization stays and higher rates of pretransplant mechanical ventilation, dialysis, and ECMO as a bridge to transplant. A propensity-matched analysis demonstrated comparable rates of intrathoracic adhesions, posttransplant duration of mechanical ventilation, PGD3 at 72 hours, and delayed chest closure. Compared to LTRs with RLD, those with CARDS had significantly longer posttransplant hospital stays and a higher prevalence of ACR ≥A2 and DSA >2000 MFI, but comparable 1-year survival rates. CONCLUSION: Even with careful selection, LT for patients with CARDS was associated with significant morbidity; however, 1-year survival of recipients with CARDS was comparable to that of matched hospitalized recipients with RLD.
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COVID-19 , Pneumopatias , Lesão Pulmonar , Transplante de Pulmão , Humanos , Adolescente , COVID-19/epidemiologia , Prevalência , Estudos Retrospectivos , TransplantadosRESUMO
The prevalence of burnout among physicians has been increasing over the last decade, but data on burnout in the specialty of cardiothoracic surgery are lacking. We aimed to study this topic through a well-being survey. A 54-question well-being survey was developed by the Wellness Committee of the American Association for Thoracic Surgery (AATS) and sent by email from January through March of 2021 to AATS members and participants of the 2021 annual meeting. The 5-item Likert-scale survey questions were dichotomized, and associations were determined by Chi-square tests or independent samples t-tests, as appropriate. The results from 871 respondents (17% women) were analyzed. Many respondents reported at least moderately experiencing: 1) a sense of dread coming to work (50%), 2) physical exhaustion at work (58%), 3) a lack of enthusiasm at work (46%), and 4) emotional exhaustion at work (50%). Most respondents (70%) felt that burnout affected their personal relationships at least "some of the time," and many (43%) experienced a great deal of work-related stress. Importantly, most respondents (62%) reported little to no access to workplace resources for emotional support, but those who reported access reported less burnout. Most respondents (57%) felt that the COVID-19 pandemic has negatively affected their well-being. On a positive note, 80% felt their career was fulfilling and enjoyed their day-to-day job at least "most of the time." Cardiothoracic surgeons experience high levels of burnout, similar to that of other medical professionals. Interventions aimed at mitigating burnout in this profession are discussed.
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Introduction: Incidentally detected malignancies in lung explants portend risk of early cancer recurrence and metastases with posttransplant immunosuppression. We present a series of lung transplant recipients with previously unverified malignancies in native lung explants. Design: We reviewed the histopathology, radiographic imaging, and management of lung explant malignancies at our institution over 10 years (2011-2020). Endpoints were survival and allograft rejection. Results: An explant malignancy was found in 1.3% (11/855) of lung transplant recipients (6 [55%] men; median age 68 years; 6 [55%] ex-smokers [median pack-years, 25]). Nine (82%) were adenocarcinoma, 1 (9%) was squamous cell carcinoma (SCC), and 1 (9%) was follicular lymphoma. Three patients (27%) had multifocal involvement (≥3 lobes), 4 (36%) had nodal involvement, and the median (range) tumor size was 2.7 (0.4-19) cm. The median interval between last imaging and transplant was 58 (29-144) days. Mycophenolate mofetil was discontinued or reduced in all; everolimus was used in 2 patients, and cisplatin-pemetrexed chemotherapy was used in 2 patients. The prevalence of acute cellular rejection and chronic rejection was 27% and 9%, respectively. Lung recipients with cancer had significantly lower survival than those without (36.4% vs 67.3%, p = 0.002); median survival was 27 (17, 65) months in 4 recipients who were alive and cancer-free at the end of the study period. Conclusions: Unidentified malignancies, commonly adenocarcinoma, can be detected in explanted native lungs. Pneumonectomy may be curative in SCC, lymphoproliferative disorders, and stage I adenocarcinoma. Modulating immunosuppression to prevent allograft rejection and tumor proliferation is warranted.
Assuntos
Adenocarcinoma , Neoplasias Pulmonares , Transplante de Pulmão , Masculino , Humanos , Idoso , Feminino , Transplante de Pulmão/efeitos adversos , Recidiva Local de Neoplasia , Pulmão , Pneumonectomia , Neoplasias Pulmonares/cirurgia , Rejeição de Enxerto/prevenção & controle , Adenocarcinoma/cirurgia , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/etiologia , Imunossupressores/uso terapêutico , Estudos RetrospectivosRESUMO
Lung transplantation is a life-saving intervention and the most effective therapy for select patients with irreversible lung disease. Despite the effectiveness of lung transplantation, it is a major operation with several opportunities for complications. For example, recipient and donor factors, technical issues, early postoperative events, and immunology can all contribute to potential complications. This article highlights some of the key surgery-related complications that can undermine a successful lung transplantation. The authors offer their expert opinion and experience to help practitioners avoid such complications and recognize and treat them early should they occur.
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Pneumopatias , Transplante de Pulmão , Humanos , Pneumopatias/etiologia , Pneumopatias/cirurgia , Transplante de Pulmão/efeitos adversos , Complicações Pós-Operatórias/etiologia , Doadores de TecidosRESUMO
To determine the effects and immunological mechanisms of low-dose interleukin-2 (IL-2) in a murine model of chronic cardiac allograft rejection (BALB/c to C57BL/6) after costimulatory blockade consisting of MR1 (250 µg/ip day 0) and CTLA4-Ig (200 µg/ip day 2), we administered low-dose IL-2 (2000 IU/day) starting on posttransplant day 14 for 3 weeks. T regulatory (Treg) cell infiltration of the grafts was determined by immunohistochemistry; circulating exosomes by western blot and aldehyde bead flow cytometry; antibodies to donor MHC by immunofluorescent staining of donor cells; and antibodies to cardiac self-antigens (myosin, vimentin) by ELISA. We demonstrated that costimulation blockade after allogeneic heart transplantation induced circulating exosomes containing cardiac self-antigens and antibodies to both donor MHC and self-antigens, leading to chronic rejection by day 45. Treatment with low-dose IL-2 prolonged allograft survival (>100 days), prevented chronic rejection, and induced splenic and graft-infiltrating CD4+ CD25+ Foxp3 Treg cells by day 45 and circulating exosomes (Foxp3+) with PD-L1 and CD73. MicroRNA 142, associated with the TGFß pathway, was significantly downregulated in exosomes from IL-2-treated mice. In conclusion, low-dose IL-2 delays rejection in a murine model of chronic cardiac allograft rejection and also induces graft-infiltrating Tregs and circulating exosomes with immunoregulatory molecules.
Assuntos
Exossomos , Transplante de Coração , MicroRNAs , Aloenxertos , Animais , Autoantígenos/metabolismo , Antígeno B7-H1/metabolismo , Modelos Animais de Doenças , Fatores de Transcrição Forkhead/metabolismo , Rejeição de Enxerto/etiologia , Rejeição de Enxerto/prevenção & controle , Sobrevivência de Enxerto , Transplante de Coração/efeitos adversos , Interleucina-2/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Endogâmicos C57BL , Linfócitos T ReguladoresRESUMO
Background: Persistent orthostatic hypotension (OH) is a lesser-known complication of lung transplantation (LTx). In this retrospective case series, we describe the clinical manifestations, complications, and treatment of persistent OH in 13 LTx recipients. Methods: We identified LTx recipients who underwent transplantation between March 1, 2018, and March 31, 2020, with persistent symptomatic OH and retrospectively queried the records for clinical information. Results: Thirteen patients were included in the analysis, 9 (69%) had underlying pulmonary fibrosis, and 12 (92%) were male. The median age, height, and body mass index at LTx were 68 years, 70 inches, and 27 kg/m2, respectively. Six (46%) patients were deceased at the time of chart abstraction with a median (IQR) posttransplant survival of 12.6 months (6, 21); the 7 remaining living patients were a median of 19.6 months (18, 32) posttransplant. Signs and symptoms of OH developed a median of 60 (7, 75) days after transplant. Patients were treated with pharmacological agents and underwent extensive physical therapy. Most patients required inpatient rehabilitation (n = 10, 77%), and patients commonly developed comorbid conditions including weight loss, renal insufficiency with eGFR <50 (n = 13, 100%), gastroparesis (n = 7, 54%), and tachycardia-bradycardia syndrome (n = 2, 15%). Falls were common (n = 10, 77%). The incidence of OH in LTx recipients at our center during the study period was 5.6% (13/234). Conclusions: Persistent OH is a lesser-known complication of LTx that impacts posttransplant rehabilitation and may lead to comorbidities and shortened survival. In addition, most LTx recipients with OH at our center were tall, thin men with underlying pulmonary fibrosis, which may offer an opportunity to instate pretransplant OH screening of at-risk patients.
RESUMO
Pre-lung transplant (LTx) gastroesophageal reflux (GER) and circulating antibodies against the lung self-antigens (SAbs) collagen V and K-alpha-1 tubulin may predispose recipients to chronic lung allograft dysfunction (CLAD). We aimed to study the association of pre-LTx GER or pre-LTx SAbs with CLAD. METHODS: In this retrospective analysis of patients who underwent LTx between 2015 and 2019, pre-LTx GER and SAbs were dichotomously defined as present or absent. The study group comprised recipients with either GER' SAbs, or both, and the control group comprised recipients without GER or SAbs. Endpoints included CLAD and survival. RESULTS: Ninety-five LTx recipients were divided into a study group (n = 71; 75%) and a control group (n = 24; 25%). Pretransplant GER was associated with pre-LTx SAbs (odds ratio [95% confidence intervals], 5.022 [1.419-17.770]; P = 0.012). In addition, the study group (either GER' SAbs, or both) had a higher risk of CLAD (hazard ratio [95% confidence intervals], 8.787 [1.694-45.567]; P = 0.010) and lower CLAD-free survival after LTx than the control group (P = 0.007); however, overall survival was similar between the 2 groups (P = 0.618). CONCLUSIONS: GER was associated with elevated SAbs in LTx candidates, and either GER, SAbs, or both were associated with CLAD in LTx recipients. This association suggests that GER may cause an immune response to normally sequestered lung-associated self-antigens that drives ongoing lung injury.