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1.
Front Public Health ; 12: 1355179, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38741913

RESUMO

Backgrounds: Improving quality of life (QOL) is one of the main aims of lung transplantation (LTx). There is a need to identify those who have poor quality of life early. However, research addressing inter individual quality of life variability among them is lacking. This study aims to identify group patterns in quality of life among lung transplant recipients and examine the predictors associated with quality of life subgroups. Methods: In total, 173 lung transplant recipients were recruited from one hospital in Guangdong Province between September 2022 and August 2023. They were assessed using the Lung Transplant Quality of Life scale (LT-QOL), Mindful Attention Awareness Scale (MAAS), Life Orientation Test-Revised scale (LOT-R), and Positive and Negative Affect Scale (PANAS). Latent profile analysis was used to identify QOL subtypes, and logistic regression analysis was used to examine the associations between latent profiles and sociodemographic and psychosocial characteristics. Results: Two distinct QOL profiles were identified: "low HRQOL" profile [N = 53 (30.94%)] and "high HRQOL" profile [N = 120 (69.06%)]. Single lung transplant recipients, and patients who reported post-transplant infection, high levels of negative emotion or low levels of mindfulness and optimism were significantly correlated with the low QOL subgroup. Conclusion: Using the domains of the LT-QOL scale, two profiles were identified among the lung transplant recipients. Our findings highlighted that targeted intervention should be developed based on the characteristics of each latent class, and timely attention must be paid to patients who have undergone single lung transplantation, have had a hospital readmission due to infection, exhibit low levels of optimism, low levels of mindfulness or high negative emotions.


Assuntos
Transplante de Pulmão , Qualidade de Vida , Transplantados , Humanos , Qualidade de Vida/psicologia , Transplante de Pulmão/psicologia , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Transplantados/psicologia , Transplantados/estatística & dados numéricos , Inquéritos e Questionários , China , Atenção Plena , Análise de Classes Latentes
3.
Transl Pediatr ; 12(4): 787-793, 2023 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-37181030

RESUMO

Background: Acute rejection after transplantation occurs as a result of complex immune responses following the detection of the major histocompatibility complex of the donors in recipients. As one of the risk factors of chronic rejection, acute rejection can directly lead to death. Therefore, early prevention and monitoring of transplant patients is critical. Pediatric acute rejection after lung transplantation is relatively rare compared to adults, and it remains a considerable challenge since information on rare primary disease complicated by acute rejection after lung transplantation in children is extremely limited, with only a single case series reported in the literature. Case Description: Here, we present a case of a 10-year-old female diagnosed with severe interstitial pneumonia, pulmonary heart disease and severe malnutrition. The patient underwent double-lung transplantation under general anesthesia. Through monitoring and management of immunosuppressants, prevention and control of infection, dynamic body fluid management, personalized nutritional support, psychological care and rehabilitation exercises, the patient achieved recovery and was safely discharged after 21 days. Conclusions: Characteristics of acute rejection after lung transplantation in children include rapid onset and progression of respiratory distress, significant difficulty in nursing and frustration in communication. Anti-infection, anti-rejection, and symptomatic measures in the acute phase are critical in controlling disease progression and improving prognosis.

4.
Front Immunol ; 14: 1084883, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37090693

RESUMO

Objective: An analysis of the clinical features of autoimmune encephalitis accompanied by anti-amphiphysin antibodies. Methods: The data of encephalitis patients with anti-amphiphysin antibodies were retrospectively evaluated, including demographics, neurological and laboratory findings, imaging, treatment, and prognostic predictions. Results: Ten patients aged between 29 and 78 years (median age 52 years) were included. The male: female ratio was 4:6. Limbic encephalitis was found in nine patients while epileptic seizures were present in seven patients. All patients showed anti-amphiphysin antibody positivity in sera while one ninth was positive for CSF antibody. The EEG findings were abnormal, including reductions in background activity, and the presence of diffuse slow waves, sharp waves, and spikes and waves. Five patients showed signs of increased T2 signals in the medial temporal lobe on MRI while PET showed either hyper- or hypo-metabolic changes in several brain regions, including the temporal lobe, hippocampus, basal ganglia, frontal and parietal cortices. Nine of ten patients were treated with immunotherapy, with improvements of varying degrees. There was a significant reduction in seizure frequency, and all patients were seizure-free at last follow-up. Conclusion: Autoimmune encephalitis with anti-amphiphysin antibodies has a variety of clinical manifestations. The most common symptom is limbic encephalitis. Although relief from seizures can be achieved relatively easily, many patients suffer psychiatric, cognitive, and sleep sequelae. The disease was found to be associated with a lower incidence of cancer than has been previously reported for paraneoplastic neurologic syndromes.


Assuntos
Doenças Autoimunes do Sistema Nervoso , Encefalite , Encefalite Límbica , Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Encefalite Límbica/terapia , Encefalite Límbica/tratamento farmacológico , Estudos Retrospectivos , Encefalite/diagnóstico , Encefalite/terapia , Convulsões/etiologia , Convulsões/tratamento farmacológico
5.
IDCases ; 32: e01758, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37092136

RESUMO

Objective: Nocardia are infrequent pathogens that disproportionately afflict organ transplant recipients. The present study aimed to summarize the clinical manifestations, diagnostic approaches, and treatment strategies of nocardiosis in lung transplant recipients. Methods: This retrospective study reviewed the clinical data of adult lung transplant recipients who were complicated with nocardiosis between January 2018 and December 2021 at the largest lung transplant center in South China. Results: The incidence of nocardiosis was 4.2% (13/316), including 9 cases of pulmonary nocardiosis and 4 disseminated nocardiosis (blood, pulmonary and intracranial). The accuracy in diagnosing nocardiosis was 77.8% by culture and 100% by metagenomic next-generation sequencing (mNGS). Nocardia farcinica was the most common causative pathogen. Trimethoprim-sulfamethoxazole-based combination therapy was administered initially, followed by a single antibiotic as the maintained therapy, lasting for 4-8 months. Conclusions: mNGS is more accurate than culture in diagnosing nocardiosis. Most patients responded well to the antibiotic therapy with combined antibiotics at the initial stage followed by a single antibiotic treatment.

6.
J Occup Med Toxicol ; 18(1): 2, 2023 Feb 13.
Artigo em Inglês | MEDLINE | ID: mdl-36782253

RESUMO

BACKGROUND: Patients with work-related lung disease (WRLD) are at increased risk of death caused by severe lung tissue damage and fibrosis. This study aimed to assess the clinical outcomes of lung transplantation (LTx) for WRLD and compare the results of LTx between WRLD and idiopathic pulmonary fibrosis (IPF). METHODS: This single-center retrospective cohort study reviewed the clinical data of patients who underwent LTx for WRLD or IPF at our hospital between January 2015 and December 2021. Cumulative survival rates after LTx were estimated using the Kaplan-Meier method. RESULTS: The final analysis included 33 cases of WRLD and 91 cases of IPF. The 33 WRLD patients consisted of 19 (57.6%) cases of silicosis, 8 (24.2%) cases of coal workers' pneumoconiosis, 3 (9.09%) cases of asbestosis, and 3 (9.09%) cases of other WRLD. Pneumothorax as an indication for LTx was significantly more common in the WRLD group than in the IPF group (51.5% vs. 2.2%, P < 0.001). There was no significant difference in the 5-year cumulative survival rate between the WRLD patients and the IPF patients (66.6% vs. 56.7%, P = 0.67). There was no significant difference in the best performance of exercise capacity and lung function between the two groups at 1 year post-transplant. CONCLUSIONS: LTx had similar survival outcomes and lung function for WRLD and IPF patients. Pneumothorax was the primary indication for lung transplantation in WRLD.

7.
Clin Rheumatol ; 42(3): 941-947, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36441397

RESUMO

Lung transplantation is an ultimate lifesaving treatment for many patients with end-stage lung disease, whereas whether it is an optional intervention for the anti-melanoma differentiation-associated gene 5 (anti-MDA5)-positive dermatomyositis (DM)-associated rapid progressive interstitial lung disease (RP-ILD) remain controversial. We report two patients diagnosed with anti-MDA5-positive DM-associated RP-ILD, who were both bridging to lung transplant with extracorporeal membrane oxygenation (ECMO) after failing to respond to extensive immunosuppressants. The first patient received full rehabilitation, but the second patient died of DM flare at the early-stage post-lung transplantation. Most of the clinical information was parallel in these two patients except the anti-MDA5 antibody level, which gradually decreased and became negative in the first patient but always hovering in high titers in the second patient, although both of the two patients received standard immunosuppressive regimen for prevention of rejection after lung transplantation. A total of 11 patients with anti-MDA5-positive DM-associated RP-ILD who underwent lung transplantation from the literature were identified. Most patients (10/11, 90.1%) were successfully discharged and without DM flare during the follow-up period post-lung transplantation. Nine of them were followed up more than 1 year, and anti-MDA-5 antibody was reported to be negative in four patients, whereas the others were unavailable. Combined with the case series in the literature, our limited experience suggests that lung transplantation is a promising therapeutic option for end-stage patients with anti-MDA5-positive DM-associated RP-ILD, with ECMO as a bridge to lung transplantation, if necessary. However, clearance or a downtrend of anti-MDA5 antibody may be required pre-transplant to avoid DM flare and recurrent RP-ILD post-transplantation.


Assuntos
Dermatomiosite , Doenças Pulmonares Intersticiais , Transplante de Pulmão , Humanos , Autoanticorpos , Helicase IFIH1 Induzida por Interferon , Imunossupressores/uso terapêutico , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/cirurgia , Doenças Pulmonares Intersticiais/diagnóstico
8.
Basic Clin Pharmacol Toxicol ; 132(1): 71-82, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36180969

RESUMO

Intramuscular injections of progesterone (P4) are common during assisted reproduction, which can cause painful injection area reactions, and the current study was therefore initiated to determine whether P4 was involved in these adverse local effects. Female Sprague-Dawley rats were given daily intramuscular injection of vehicle oil or P4-in-oil with or without dermal administration of ketoprofen (Ket) gel at right biceps femoris muscle of hindlimb for 5 weeks. It was found that rats receiving repeated vehicle oil injections developed nociception-related behaviours together with induration formation and dorsal root ganglion (DRG) damage, indicating that the vehicle oil contributed to the side-effect reactions. Interestingly, P4 injections caused more nociception-related behaviours than those of vehicle oil as reflected by both nociception score and muscle withdrawal threshold evaluations, which were impressively relieved by Ket. In fact, P4 induced higher induration occurrence rate with larger volume that was alleviated by Ket. Further ELISA assays supported that P4 rather than vehicle oil profoundly elevated inflammatory factor levels. Moreover, an extensive upregulation of Nav 1.8 was observed at L2, L3, and L5 of DRG in response to P4, indicating a sole role of P4 in Nav 1.8 upregulation. Collectively, P4 may contribute to the painful injection area reactions via stimulating inflammation and DRG Nav 1.8 upregulation in rats.


Assuntos
Gânglios Espinais , Progesterona , Ratos , Feminino , Animais , Progesterona/farmacologia , Injeções Intramusculares , Ratos Sprague-Dawley , Dor/induzido quimicamente , Dor/tratamento farmacológico
9.
Front Cell Dev Biol ; 10: 1030390, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36478742

RESUMO

Neurodegenerative diseases (NDDs) are disorders in which neurons are lost owing to various factors, resulting in a series of dysfunctions. Their rising prevalence and irreversibility have brought physical pain to patients and economic pressure to both individuals and society. However, the pathogenesis of NDDs has not yet been fully elucidated, hampering the use of precise medication. Induced pluripotent stem cell (IPSC) modeling provides a new method for drug discovery, and exploring the early pathological mechanisms including mitochondrial dysfunction, which is not only an early but a prominent pathological feature of NDDs. In this review, we summarize the iPSC modeling approach of Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis, as well as outline typical mitochondrial dysfunction and recapitulate corresponding therapeutic strategies.

10.
BMC Infect Dis ; 22(1): 872, 2022 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-36418967

RESUMO

BACKGROUND: Cytomegalovirus (CMV) infection is a leading cause of morbidity and mortality after transplantation. This study aimed to investigate CMV seroprevalence, infection, and disease in Chinese thoracic organ transplant recipients. METHODS: The clinical data of the patients who underwent lung and/or heart transplantation between January 2015 and October 2020 were retrospectively collected from four transplantation centers in China. RESULTS: A total of 308 patients were analyzed. The CMV serostatus was donor positive (D+) recipient negative (R-) in 19 (6.17%) patients, D+/R+ in 233 (75.65%), D-/R+ in 36 (11.69%), and D-/R- in 20 (6.50%). CMV DNAemia was detected in 52.3% of the patients and tissue-invasive CMV disease was diagnosed in 16.2% of the patients. Only 31.8% of the patients adhered to the postdischarge valganciclovir therapy. The D+/R- serostatus (odds ratio [OR]: 18.32; 95% confidence interval [CI]:1.80-188.68), no valganciclovir prophylaxis (OR: 2.64; 95% CI: 1.05-6.64), and higher doses of rabbit anti-human thymocyte globulin (> 2 mg/kg) (OR: 4.25; 95% CI: 1.92-9.42) were risk factors of CMV disease. CONCLUSION: CMV seroprevalence was high in Chinese thoracic organ transplant donors and recipients. The low adherence rate to the postdischarge CMV prophylaxis therapy in Chinese patients is still an unresolved issue.


Assuntos
Infecções por Citomegalovirus , Transplante de Órgãos , Humanos , Citomegalovirus , Estudos Retrospectivos , Estudos Soroepidemiológicos , Assistência ao Convalescente , Antivirais/uso terapêutico , Alta do Paciente , Valganciclovir/uso terapêutico , Infecções por Citomegalovirus/tratamento farmacológico , Transplante de Órgãos/efeitos adversos
11.
Eur Radiol ; 32(4): 2235-2245, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34988656

RESUMO

BACKGROUND: Main challenges for COVID-19 include the lack of a rapid diagnostic test, a suitable tool to monitor and predict a patient's clinical course and an efficient way for data sharing among multicenters. We thus developed a novel artificial intelligence system based on deep learning (DL) and federated learning (FL) for the diagnosis, monitoring, and prediction of a patient's clinical course. METHODS: CT imaging derived from 6 different multicenter cohorts were used for stepwise diagnostic algorithm to diagnose COVID-19, with or without clinical data. Patients with more than 3 consecutive CT images were trained for the monitoring algorithm. FL has been applied for decentralized refinement of independently built DL models. RESULTS: A total of 1,552,988 CT slices from 4804 patients were used. The model can diagnose COVID-19 based on CT alone with the AUC being 0.98 (95% CI 0.97-0.99), and outperforms the radiologist's assessment. We have also successfully tested the incorporation of the DL diagnostic model with the FL framework. Its auto-segmentation analyses co-related well with those by radiologists and achieved a high Dice's coefficient of 0.77. It can produce a predictive curve of a patient's clinical course if serial CT assessments are available. INTERPRETATION: The system has high consistency in diagnosing COVID-19 based on CT, with or without clinical data. Alternatively, it can be implemented on a FL platform, which would potentially encourage the data sharing in the future. It also can produce an objective predictive curve of a patient's clinical course for visualization. KEY POINTS: • CoviDet could diagnose COVID-19 based on chest CT with high consistency; this outperformed the radiologist's assessment. Its auto-segmentation analyses co-related well with those by radiologists and could potentially monitor and predict a patient's clinical course if serial CT assessments are available. It can be integrated into the federated learning framework. • CoviDet can be used as an adjunct to aid clinicians with the CT diagnosis of COVID-19 and can potentially be used for disease monitoring; federated learning can potentially open opportunities for global collaboration.


Assuntos
Inteligência Artificial , COVID-19 , Algoritmos , Humanos , Radiologistas , Tomografia Computadorizada por Raios X/métodos
13.
Clin Exp Rheumatol ; 40(9): 1666-1673, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34796840

RESUMO

OBJECTIVES: The present study aimed to compare the post-lung transplant survival and complications of connective tissue disease (CTD)-related interstitial lung disease (ILD) and/or pulmonary arterial hypertension with idiopathic pulmonary fibrosis (IPF). METHODS: The clinical data of patients with CTD-ILD or IPF who received lung transplantation between 2015 and 2020 were retrospectively reviewed. Cumulative survival rates after transplantation were estimated using the Kaplan-Meier method. RESULTS: The study included 31 patients with confirmed CTD-ILD and 98 with IPF. Patients with CTD-ILD were significantly younger (53.2 ± 13.7 vs. 62.3 ± 7.2 years, p=0.001) and more likely female (61.3% vs. 7.1%, p<0.001) than patients with IPF. No significant difference was noticed in the 1-year and 5-year survival rates between CTD-ILD and IPF patients (1-year, 73.2% vs 71.4%, p=0.76; 5-year, 69.1% vs. 39.5%, p=0.21). The incidence of primary graft dysfunction was significantly higher in CTD-ILD patients (90.3% vs. 70.4%, p=0.03), while there was no significant difference in primary graft dysfunction-related mortality (6.5% vs. 6.1%, p=0.95) between the two groups. CONCLUSIONS: There was no significant difference in post-lung transplant survival and complications between CTD-ILD and IPF.


Assuntos
Doenças do Tecido Conjuntivo , Hipertensão Pulmonar , Fibrose Pulmonar Idiopática , Doenças Pulmonares Intersticiais , Transplante de Pulmão , Disfunção Primária do Enxerto , China/epidemiologia , Feminino , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/cirurgia , Fibrose Pulmonar Idiopática/complicações , Fibrose Pulmonar Idiopática/cirurgia , Doenças Pulmonares Intersticiais/complicações , Doenças Pulmonares Intersticiais/cirurgia , Transplante de Pulmão/efeitos adversos , Disfunção Primária do Enxerto/complicações , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos
14.
BMC Pulm Med ; 21(1): 348, 2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34742287

RESUMO

BACKGROUND: High-throughput next-generation sequencing (HT-NGS) has the potential to detect a large variety of pathogens; however, the application of HT-NGS in lung transplant (LTx) recipients remains limited. We aimed to evaluate the value of HT-NGS for pathogen detection and diagnosis of pulmonary infection during early-stage post-lung transplantation. METHODS: In this retrospective study, we enrolled 51 LTx recipients who underwent lung transplantation between January 2020 and December 2020. Bronchoalveolar lavage fluid (BALF) samples were collected for the detection of pathogens using both HT-NGS and conventional microbiological testing. The detection of pathogens and diagnostic performance of HT-NGS were compared with that of conventional methods. RESULTS: HT-NGS provided a higher positive rate of pathogen detection than conventional microbiological testing (88.24% vs. 76.47%). The most common bacteria detected via HT-NGS during early-stage post-lung transplantation were Enterococcus, Staphylococcus, Pseudomonas and Klebsiella, while all fungi were Candida and all viruses were Herpesvirus. Uncommon pathogens, including Strongyloides, Legionella, and Mycobacterium abscesses were identified by HT-NGS. The sensitivity of HT-NGS for diagnosing pulmonary infection was significantly higher than that of conventional microbiological testing (97.14% vs. 68.57%; P < 0.001). For three LTx recipients, treatment regimens were adjusted according to the results of HT-NGS, leading to a complete recovery. CONCLUSION: HT-NGS is a highly sensitive technique for pathogen detection, which may provide diagnostic advantages, especially in LTx recipients, contributing to the optimization of treatment regimens against pulmonary infection during early-stage post-lung transplantation.


Assuntos
Líquido da Lavagem Broncoalveolar/microbiologia , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Análise de Sequência de DNA/métodos , Idoso , Bactérias/isolamento & purificação , Feminino , Fungos/isolamento & purificação , Herpesviridae/isolamento & purificação , Humanos , Pneumopatias/microbiologia , Transplante de Pulmão/efeitos adversos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
15.
Gland Surg ; 10(4): 1387-1396, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33968690

RESUMO

BACKGROUND: It has been reported that tubeless video-assisted thoracoscopic surgery (tubeless-VATS) is feasible and safe for thoracic diseases. Herein, we compared the early outcomes of mediastinal lesion resection between the tubeless and traditional VATS. METHODS: Clinical data of all patients who underwent thoracoscopic mediastinal tumor resection were retrospectively collected. The study involved two groups: tubeless and traditional VATS group. Propensity score matching (PSM) was applied to eliminate the population bias. Intraoperative and postoperative variables were compared among matched cohorts. RESULTS: In total, 43 patients in the tubeless group and 231 patients in the traditional VATS group were included. After 1:1 PSM, baseline characteristics were comparable. Anesthesia time (177.63 vs. 202.53 min; P=0.004) was shorter in tubeless group, while operation time (90.95 vs. 101.47 min; P=0.109) was similar. Overall, the total postoperative morbidity rate was similar in the two groups (15% vs. 12.5%; P=0.556). Specially, 4/43 patients in tubeless VATS group need to be re-put chest tubes postoperatively. A significant lower similar level of visual analogue scale score was observed in tubeless VATS group (1.73±0.48 vs. 3.41±0.87, P<0.001) in postoperative day 1. Meanwhile, the number of patients using postoperative opioid analgesia was also lower in tubeless VATS group (22.88% vs. 48.38%, P=0.016). Furthermore, hospital duration after surgery (2.58 vs. 5.47 days; P=0.002) was shorter in tubeless group. CONCLUSIONS: Compared with traditional VATS, tubeless VATS for mediastinal tumor may shorten the anesthesia time, decrease postoperative pain and fasten postoperative recovery in carefully selected patients.

16.
Sci Transl Med ; 13(591)2021 04 28.
Artigo em Inglês | MEDLINE | ID: mdl-33910977

RESUMO

Acute lung injury (ALI) causes high mortality and lacks any pharmacological intervention. Here, we found that pazopanib ameliorated ALI manifestations and reduced mortality in mouse ALI models and reduced edema in human lung transplantation recipients. Pazopanib inhibits mitogen-activated protein kinase kinase kinase 2 (MAP3K2)- and MAP3K3-mediated phosphorylation of NADPH oxidase 2 subunit p47phox at Ser208 to increase reactive oxygen species (ROS) formation in myeloid cells. Genetic inactivation of MAP3K2 and MAP3K3 in myeloid cells or hematopoietic mutation of p47phox Ser208 to alanine attenuated ALI manifestations and abrogates anti-ALI effects of pazopanib. This myeloid MAP3K2/MAP3K3-p47phox pathway acted via paracrine H2O2 to enhance pulmonary vasculature integrity and promote lung epithelial cell survival and proliferation, leading to increased pulmonary barrier function and resistance to ALI. Thus, pazopanib has the potential to be effective for treating ALI.


Assuntos
Lesão Pulmonar Aguda , Indazóis/farmacologia , MAP Quinase Quinase Quinase 2/antagonistas & inibidores , MAP Quinase Quinase Quinase 3/antagonistas & inibidores , Pirimidinas/farmacologia , Sulfonamidas/farmacologia , Lesão Pulmonar Aguda/tratamento farmacológico , Animais , Humanos , Peróxido de Hidrogênio , Camundongos , NADPH Oxidases/metabolismo , Fosforilação , Espécies Reativas de Oxigênio
17.
Ann Palliat Med ; 10(4): 4134-4142, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33832302

RESUMO

BACKGROUND: Early endotracheal extubation in operating room (E-OR) after lung transplantation is rarely reported worldwide. Herein, we aim to explore the feasibility and safety of E-OR after lung transplantation and demonstrate its potential benefits. METHODS: This study is a single-center retrospective database analysis of 18 patients. All lung transplantation patients with E-OR attempted between June 2018 and September 2019 were included retrospectively. Perioperative variables, including ischemia time, total blood loss, blood lactic acid, the partial pressure of oxygen, partial pressure of oxygen/fraction of inspiration oxygen ratio, time of semi-open pulmonary artery occlusion clamp, extubation rate, and complications after E-OR, were analyzed. Data were compared using non-parametric tests and expressed as the median or number (percentage). RESULTS: Clinical data of 18 patients with E-OR attempted were collected. Overall, 15/18 (83.33%) patients successfully underwent E-OR without reintubation. Reintubation occurred in 3/18 (16.67%) patients; one patient presented with decreased blood oxygen saturation and unconsciousness, while two patients developed hypoxemia and respiratory failure after E-OR. Extracorporeal membrane oxygenation (ECMO) was not used postoperatively. No grade 3 primary graft dysfunction was observed and all eighteen patients were alive 1 year after the transplant. No postoperative hemodialysis and tracheotomy occurred. The median length of stay in the intensive care unit (ICU) for E-OR patients was 120 hours, the median length of postoperative hospital stay was 19 days, and the median hospitalization cost was 35,577 USD. CONCLUSIONS: Early endotracheal extubation in operating room was feasible and did not delay postoperative recovery in these 18 lung transplantation recipients.


Assuntos
Extubação , Transplante de Pulmão , Humanos , Tempo de Internação , Salas Cirúrgicas , Estudos Retrospectivos
18.
J Biomol Struct Dyn ; 39(7): 2512-2525, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32228162

RESUMO

Myeloid cell leukemia-1 (Mcl-1) protein is a family of Bcl-2 (B cell lymphoma 2) rich proteases of the most common increase threshold for genetic aberrations observed in human cancer, including lung, breast, pancreatic, cervical, and ovarian cancers as well as leukemia and lymphoma. Mcl-1 is recognized as an attractive drug target in number of diseases, including cancer. In the present study we surveyed and collected queries compounds from PDB database of Mcl-1 protein and generated pharmacophore-based models adapted to screen the drug-like compounds from FDA approved database. The 206 best lead molecules from pharmacophore-screening were further evaluated by molecular docking, molecular dynamics simulation, MM-GBSA calculation, as well as experimental validation. Two hits, ZINC00601272 and ZINC00002166, showed the best docking scores, which showed a tendency to inhibit cell viability of HL60 and K562 leukemia cells with Mcl-1 expressions. Conclusively, the present study provides structural information of Mcl-1 inhibitors for next generations of cancer therapeutics through computational and experimental validation approach.Communicated by Ramaswamy H. Sarma.


Assuntos
Leucemia , Simulação de Dinâmica Molecular , Humanos , Leucemia/tratamento farmacológico , Leucemia/genética , Simulação de Acoplamento Molecular , Células Mieloides , Relação Quantitativa Estrutura-Atividade
19.
Oncoimmunology ; 9(1): 1848068, 2020 11 29.
Artigo em Inglês | MEDLINE | ID: mdl-33299661

RESUMO

Understanding the cancer risks in different transplant recipients helps early detection, evaluation, and treatment of post-transplant malignancies. Therefore, we performed a meta-analysis to determine the cancer risks at multiple sites for solid organ transplant recipients and their associations with tumor mutation burden (TMB), which reflects the immunogenicity. A comprehensive search of PubMed, Web of Science, EMBASE, Medline, and Cochrane Library was conducted. Random effects models were used to calculate the standardized incidence ratios (SIRs) versus the general population and determine the risks of different cancers. Linear regression (LR) was used to analyze the association between the SIRs and TMBs. Finally, seventy-two articles met our criteria, involving 2,105,122 solid organ transplant recipients. Compared with the general population, solid organ transplant recipients displayed a 2.68-fold cancer risk (SIR 2.68; 2.48-2.89; P <.001), renal transplant recipients displayed a 2.56-fold cancer risk (SIR 2.56; 2.31-2.84; P <.001), liver transplant recipients displayed a 2.45-fold cancer risk (SIR 2.45; 2.22-2.70; P <.001), heart and/or lung transplant recipients displayed a 3.72-fold cancer risk (SIR 3.72; 3.04-4.54; P <.001). The correlation coefficients between SIRs and TMBs were 0.68, 0.64, 0.59, 0.79 in solid organ recipients, renal recipients, liver recipients, heart and/or lung recipients, respectively. In conclusion, our study demonstrated that solid organ transplant recipients displayed a higher risk of some site-specific cancers, providing individualized guidance for clinicians to early detect, evaluate, and treat cancer among solid organ transplantation recipients. In addition, the increased cancer risk of solid organ transplant recipients is associated with TMB, suggesting that iatrogenic immunosuppression may contribute to the increased cancer risk in transplant recipients. (PROSPERO ID CRD42020160409).


Assuntos
Leucemia Mieloide Aguda , Transplante de Órgãos , Estudos de Coortes , Humanos , Incidência , Transplante de Órgãos/efeitos adversos , Transplantados
20.
Cancer Med ; 9(24): 9595-9610, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33047902

RESUMO

We performed a meta-analysis to determine cancer risks at multiple sites and their associations with tumor mutation burden (TMB), an index for immunogenicity, in heart or lung transplant recipients. A comprehensive search of PubMed, Web of Science, EMBASE, and Medline was conducted. Random effects models were used to calculate standardized incidence ratios (SIRs) versus the general population and to determine the risks of different cancers. Weighted linear regression (WLR) was used to analyze the associations between the SIRs and TMBs. (PROSPERO CRD42020159599). Data from 21 studies including 116,438 transplant recipients (51,173 heart transplant recipients and 65,265 lung transplant recipients) with a total follow-up of 601,330.7 person-years were analyzed. Compared with the general population, heart transplant recipients displayed a 3.13-fold higher cancer risk [SIR: 3.13; 95% confidence interval (CI): 2.38-4.13; p < 0.001]; lung transplant recipients displayed a 4.28-fold higher cancer risk [SIR: 4.28; 95% CI: 3.18-5.77; p < 0.001]. The correlation coefficients were 0.54 (p = 0.049) and 0.79 (p < 0.001) in heart and lung transplant recipients, respectively, indicating that 29% and 63% of the differences in the SIRs for cancer types might be explained by the TMBs. Our study demonstrated that both heart and lung transplant recipients displayed a higher risk of certain site-specific cancers. These findings can provide individualized guidance for clinicians for detection of cancer among heart or lung transplantation recipients. In addition, we provided evidence that increased risks of post-transplant cancers can be attributed to immunosuppression.


Assuntos
Transplante de Coração/efeitos adversos , Terapia de Imunossupressão/efeitos adversos , Transplante de Pulmão/efeitos adversos , Neoplasias/diagnóstico , Humanos , Terapia de Imunossupressão/métodos , Neoplasias/etiologia , Estudos Prospectivos , Sistema de Registros , Fatores de Risco , Transplantados
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