BACKGROUND: Critical patients with the coronavirus disease 2019 (COVID-19), even those whose nucleic acid test results had turned negative and those receiving maximal medical support, have been noted to progress to irreversible fatal respiratory failure. Lung transplantation (LT) as the sole therapy for end-stage pulmonary fibrosis related to acute respiratory distress syndrome has been considered as the ultimate rescue therapy for these patients. METHODS: From February 10 to March 10, 2020, three male patients were urgently assessed and listed for transplantation. After conducting a full ethical review and after obtaining assent from the family of the patients, we performed three LT procedures for COVID-19 patients with illness durations of more than one month and extremely high sequential organ failure assessment scores. RESULTS: Two of the three recipients survived post-LT and started participating in a rehabilitation program. Pearls of the LT team collaboration and perioperative logistics were summarized and continually improved. The pathological results of the explanted lungs were concordant with the critical clinical manifestation, and provided insight towards better understanding of the disease. Government health affair systems, virology detection tools, and modern communication technology all play key roles towards the survival of the patients and their rehabilitation. CONCLUSIONS LT can be performed in end-stage patients with respiratory failure due to COVID-19-related pulmonary fibrosis. If confirmed positive-turned-negative virology status without organ dysfunction that could contraindicate LT, LT provided the final option for these patients to avoid certain death, with proper protection of transplant surgeons and medical staffs. By ensuring instant seamless care for both patients and medical teams, the goal of reducing the mortality rate and salvaging the lives of patients with COVID-19 can be attained.
Aged ; Betacoronavirus ; Coronavirus Infections ; complications ; mortality ; Extracorporeal Membrane Oxygenation ; Humans ; Lung Transplantation ; methods ; Male ; Middle Aged ; Pandemics ; Pneumonia, Viral ; complications ; mortality ; Pulmonary Fibrosis ; mortality ; surgery ; Respiratory Distress Syndrome, Adult ; mortality ; surgery

The 2019 novel coronavirus disease (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has occurred in China and around the world. SARS-CoV-2-infected patients with severe pneumonia rapidly develop acute respiratory distress syndrome (ARDS) and die of multiple organ failure. Despite advances in supportive care approaches, ARDS is still associated with high mortality and morbidity. Mesenchymal stem cell (MSC)-based therapy may be an potential alternative strategy for treating ARDS by targeting the various pathophysiological events of ARDS. By releasing a variety of paracrine factors and extracellular vesicles, MSC can exert anti-inflammatory, anti-apoptotic, anti-microbial, and pro-angiogenic effects, promote bacterial and alveolar fluid clearance, disrupt the pulmonary endothelial and epithelial cell damage, eventually avoiding the lung and distal organ injuries to rescue patients with ARDS. An increasing number of experimental animal studies and early clinical studies verify the safety and efficacy of MSC therapy in ARDS. Since low cell engraftment and survival in lung limit MSC therapeutic potentials, several strategies have been developed to enhance their engraftment in the lung and their intrinsic, therapeutic properties. Here, we provide a comprehensive review of the mechanisms and optimization of MSC therapy in ARDS and highlighted the potentials and possible barriers of MSC therapy for COVID-19 patients with ARDS.
Adoptive Transfer ; Alveolar Epithelial Cells ; pathology ; Animals ; Apoptosis ; Betacoronavirus ; Body Fluids ; metabolism ; CD4-Positive T-Lymphocytes ; immunology ; Clinical Trials as Topic ; Coinfection ; prevention & control ; therapy ; Coronavirus Infections ; complications ; immunology ; Disease Models, Animal ; Endothelial Cells ; pathology ; Extracorporeal Membrane Oxygenation ; Genetic Therapy ; methods ; Genetic Vectors ; administration & dosage ; therapeutic use ; Humans ; Immunity, Innate ; Inflammation Mediators ; metabolism ; Lung ; pathology ; physiopathology ; Mesenchymal Stem Cell Transplantation ; methods ; Mesenchymal Stem Cells ; physiology ; Multiple Organ Failure ; etiology ; prevention & control ; Pandemics ; Pneumonia, Viral ; complications ; immunology ; Respiratory Distress Syndrome, Adult ; immunology ; pathology ; therapy ; Translational Medical Research

Herein, we report a case of lung transplantation in a patient with profound preoperative hypercapnia, focusing on the cardiopulmonary bypass strategy used for brain perfusion during the operation. We applied the pH-stat method for acid-base regulation, and thereby achieved the desired outcome without any neurologic deficit.
Brain ; Cardiopulmonary Bypass ; Cerebrovascular Circulation ; Humans ; Hypercapnia ; Lung Transplantation ; Lung ; Methods ; Neurologic Manifestations ; Perfusion

BACKGROUND: Small cell lung cancer (SCLC) is characterized by poor differentiation, high malignancy and rapid growth fast, short double time, early and extensive metastatic malignancy. In clinical, chemotherapy is the main treatment method, while resistance to multiple chemotherapy drugs in six to nine months has been a major clinical challenge in SCLC treatment. Therefore, It has important clinical value to building SCLC aninimal model which is similar to patients with SCLC. Animal model of xenotransplantation (PDX) from the patients with small cell lung cancer can well retain the characteristics of primary tumor and is an ideal preclinical animal model. The study is aimed to establish SCLC PDX animal model and induce the chemoresistance model to help to study the mechanism of chemoresistance and individual treatment. METHODS: Fresh surgical excision or puncture specimens from SCLC patients were transplanted into B-NSGTM mice subcutaneous tissues with severe immunodeficiency in one hour after operation the B-NSGTM mice subcutaneous in 1 hour, and inject chemotherapy drugs intraperitoneally after its tumor growed to 400 mm³ with EP which is cisplatin 8 mg/kg eight days and etoposide 5 mg/kg every two days until 8 cycles. Measure the tumor volum and mice weights regularly, then re-engrafted the largest tumor and continue chemotherapy. RESULTS: Nine cases were conducted for B-NSG mice modeling. Three of nine cases could be engrafted to new B-NSG mice at least two generation. The SCLC PDX animal models have been established successfully. After adopting chemotherapy drugs, the chemoresistance PDX models have been established. High homogeneity was found between xenograft tumor and patient's tumor in histopathology, immunohistochemical phenotype (Syn, CD56, Ki67). CONCLUSIONS The SCLC PDX animal model and the chemoresistance PDX animal model have been successfully constructed, the success rate is 33%, which provides a platform for the clinical research, seeking for biological markers and choosing individual treatment methods of SCLC.
Animals ; Antineoplastic Combined Chemotherapy Protocols ; pharmacology ; Cisplatin ; administration & dosage ; Disease Models, Animal ; Drug Resistance, Neoplasm ; Etoposide ; administration & dosage ; Female ; Humans ; Interleukin Receptor Common gamma Subunit ; deficiency ; genetics ; Lung Neoplasms ; drug therapy ; metabolism ; pathology ; Mice, Inbred BALB C ; Mice, Inbred NOD ; Mice, Knockout ; Mice, SCID ; Small Cell Lung Carcinoma ; drug therapy ; metabolism ; pathology ; Transplantation, Heterologous ; methods ; Xenograft Model Antitumor Assays

Respiratory-gated ¹⁸F-fluorodeoxygluocse (¹⁸F-FDG) PET/CT has been successfully used to better localize malignancies in the lung or upper abdominal organs. However, clinical usefulness of respiratory-gated ¹⁸F-FDG PET/CT in detection of fever focus has not been reported yet. A 68-year-old male patient with a history of living donor liver transplantation and biliary stenting was referred for ¹⁸F-FDG PET/CT due to fever of unknown origin (FUO). To find the accurate fever focus, respiratory-gated and non-gated ¹⁸F-FDG PET/CT was performed. Respiratory-gated PET/CT readily revealed prominent hypermetabolic lesion in the distal common bile duct (CBD) area where previous surgical graft was in situ. Maximum standardized uptake value (SUVmax) and SUVratio (SUR) were greater in the gated PET/CT (SUVmax 5.4 and SUR 3.5) than in the non-gated PET/CT (SUVmax 4.6 and SUR 3.0). Fever dramatically subsided after removal of the graft in the CBD. This case report implies that respiratory-gated ¹⁸F-FDG PET/CT can visualize upper abdominal fever focus with better contrast than the conventional non-gated method.
Aged ; Common Bile Duct ; Fever of Unknown Origin ; Fever ; Humans ; Liver Transplantation ; Living Donors ; Lung ; Male ; Methods ; Positron-Emission Tomography ; Positron-Emission Tomography and Computed Tomography ; Respiratory-Gated Imaging Techniques ; Stents ; Transplants

Animals ; Cell Culture Techniques ; Humans ; Lung ; cytology ; Regenerative Medicine ; methods ; Stem Cell Transplantation ; methods

BACKGROUND: Extracorporeal membrane oxygenation (ECMO) has been successfully used as a method for the interhospital transportation of critically ill patients. In South Korea, a well-established ECMO interhospital transport system is lacking due to limited resources. We developed a simplified ECMO transport system without mechanical ventilation for use by public emergency medical services. METHODS: Eighteen patients utilized our ECMO transport system from December 2011 to September 2015. We retrospectively analyzed the indications for ECMO, the patient status during transport, and the patient outcomes. RESULTS: All transport was conducted on the ground by ambulance. The distances covered ranged from 26 to 408 km (mean, 65.9±88.1 km) and the average transport time was 56.1±57.3 minutes (range, 30 to 280 minutes). All patients were transported without adverse events. After transport, 4 patients (22.2%) underwent lung transplantation because of interstitial lung disease. Eight patients who had severe acute respiratory distress syndrome showed recovery of heart and lung function after ECMO therapy. A total of 13 patients (70.6%) were successfully taken off ECMO, and 11 patients (61.1%) survived. CONCLUSION: Our ECMO transport system without mechanical ventilation can be considered a safe and useful method for interhospital transport and could be a good alternative option for ECMO transport in Korean hospitals with limited resources.
Ambulances ; Critical Illness* ; Emergency Medical Services ; Extracorporeal Membrane Oxygenation* ; Heart ; Humans ; Korea ; Lung ; Lung Diseases, Interstitial ; Lung Transplantation ; Methods ; Patient Transfer ; Respiration, Artificial ; Respiratory Distress Syndrome, Adult ; Retrospective Studies ; Transportation ; Ventilators, Mechanical*

PURPOSE: The purpose of this study was to compare the clinical and oncological outcomes between the primary and metastatic malignant tumor of humerus. MATERIALS AND METHODS: Between May 2005 and May 2014, 42 cases of malignant tumor in humerus that were followed-up for at least 1 year were entered into the study and analyzed retrospectively. Cases were divided into two groups, the primary (group 1, 15 cases) and metastatic (group 2, 27 cases), according to the origin of the tumor. The clinical and oncological outcomes between the primary and metastatic malignant tumor of humerus were analyzed and compared. RESULTS: In the group 1, nine cases were osteosarcoma and six cases were chondrosarcoma. The tumor lesions were distributed in the proximal area of the humerus. In the group 2, 12 cases originated from lung cancer, six cases from liver cancer, and two cases from bladder cancer. The lesions were usually distributed in the midshaft area. The patients underwent various surgical treatments, including wide excision with tumor prosthesis, curettage with bone grafting, intramedullary nailing, open reduction, and internal fixation with plate. Kaplan-Meier 5-year survival estimates were 87.5% for group 1, and 1-year survival estimates were 70.1% and 2-year survival estimates were 40.1% for group 2. The mean Musculoskeletal Tumor Society score was high in both groups. However group 1 showed a higher score on the functional index compared to group 2. CONCLUSION: Primary malignant bone tumors of the humerus usually involve the proximal site and tumor prosthesis is the main treatment. The metastatic malignant bone tumor usually involves the midshaft area and intramedullary nailing and radiation therapy is the main therapy. Although treatment of the primary malignant tumor increases the survival rate, treatment of metastatic malignant tumor does not affect the survival rate, though it helps in relieving pain.
Bone Transplantation ; Chondrosarcoma ; Curettage ; Fracture Fixation, Intramedullary ; Humans ; Humerus* ; Liver Neoplasms ; Lung Neoplasms ; Methods* ; Osteosarcoma ; Outcome Assessment (Health Care) ; Prostheses and Implants ; Retrospective Studies ; Survival Rate ; Urinary Bladder Neoplasms

PURPOSE: Anastomotic airway complications are a major cause of morbidity and mortality after lung transplantation (LTx). In this study, the authors identified types and clinical outcomes of airway complications after LTx. MATERIALS AND METHODS: All bronchial anastomotic complications were analyzed in a total of 94 LTx cases involving 90 recipients who underwent surgery between July 2006 and May 2014. Fifteen LTx cases (14 recipients) with incomplete medical records for fiberoptic bronchoscopy (FBS) and three cases underwent heart-lung transplantation (HLT) were excluded. Postoperative FBS at 24-48 hours, 1, 3, 6, and 12 months, and then yearly after the transplantation were performed. RESULTS: A total of 76 LTx cases (75 recipients) were analyzed. The mean age of the recipients was 49.55 years (range, 18-71 years), and 38 (49.4%) were male. Twenty-one out of 76 cases (27.6%) experienced early anastomotic complications, and 12 (15.8%) presented late anastomotic complications. The early anastomotic airway complications presented in various forms: stenosis, 1 case; narrowing, 1; necrosis & dehiscence, 3; fistula, 4; granulation, 10; and infection, 2. Late complications almost entirely presented in the form of bronchial stenosis; five recipients showed stenosis at the anastomosis site, and one of them showed improvement after ballooning. Five others were found to have stenosis at the bronchus intermedius, distal to the anastomosis site. Three of these patients showed improvement after ballooning or bronchoplasty. CONCLUSION: By serial surveillance via FBS after LTx, we detected anastomotic airway complications in 42.9% of cases, which were successfully managed with improved clinical outcomes.
Adolescent ; Adult ; Aged ; Analysis of Variance ; Anastomosis, Surgical/*adverse effects/methods ; Bronchi/blood supply/physiopathology/*surgery ; Bronchial Diseases/epidemiology/*etiology/physiopathology ; Bronchoscopy ; Female ; Humans ; Incidence ; *Lung Transplantation ; Male ; Middle Aged ; Postoperative Complications/epidemiology/*etiology/physiopathology ; Prevalence ; Republic of Korea/epidemiology ; Retrospective Studies ; Treatment Outcome

This study was purposed to investigate the effect of umbilical cord mesenchymal cells (UC-MSC) infusion on the pulmonary infection in haploidentical hematopoietic stem cell transplantation (hi-HSCT). The infection of 83 patients underwent hi-HSCT was detected and analysed, among them 42 patients received haploidentical hi-HSCT, 41 received hi-HSCT combined with UC-MSC infusion. The results showed that 31 cases (73.81% ± 6.78%) were infected by cytomegalovirus and 21 cases in patients received hi-HSCT experienced pulmonary infections, including infections of fungal, virus, bacteria, tubercle bacillus, PCP and so on, the incidence rate was (50 ± 7.72)%; the infection of cytomegalovirus (CMV) was found in 31 cases, the incidence rate was (78.05 ± 6.46)%. In patients received hi-HSCT combined with UC-MSC, only 15 patients experienced pulmonary infection, the incidence rate was (36.59 ± 7.52)%, and the infection of cytomegalovirus (CMV) was observed in 32 patients, the incidence rate was (78.05 ± 6.46)%. There was no obvious statistical difference between two groups(P > 0.05). It is concluded that the UC-MSC infusion not increases the infection rate in hi-HSCT.
Adolescent ; Adult ; Child ; Child, Preschool ; Cytomegalovirus Infections ; epidemiology ; Female ; Hematopoietic Stem Cell Transplantation ; methods ; Humans ; Lung Diseases ; epidemiology ; Male ; Mesenchymal Stromal Cells ; cytology ; Transplantation Conditioning ; Transplantation, Homologous ; Treatment Outcome ; Umbilical Cord ; cytology ; Young Adult