Functional Status and Quality of Life 6 Months After Extracorporeal Membrane Oxygenation Therapy for COVID-19-Related Pulmonary Failure.

Extracorporeal membrane oxygenation (ECMO) is increasingly used in COVID-19-related pulmonary failure and the number of patients recovering from COVID-19 is growing. Here, we assess survival and recovery 6 months after ECMO for COVID-19. From April 2020 to September 2021, n = 60 (60.5 [51.0-65.0] years, 23.3% female) were treated with venovenous/venoarterial ECMO for COVID-19. 41.7% were weaned off ECMO, survival-to-discharge was 40.0% (n = 24). Age (63.0 [60.0-66.8] vs. 55.0 [43.8-60.0] years, p < 0.001), vasoactive support (97.2% vs . 75.0%, p = 0.013), and pre-ECMO SOFA scores (13.0 [12.0-14.8] vs. 12.0 [10.0-13.8] p = 0.036) correlated with nonsurvival. All patients aged >65 years, with histories of neoplasia, immunocompromise, chronic renal failure, or frailty died. After 6 months, 20 were alive (6-month survival 33.3%, survival conditioned on survival-to-discharge 83.3%), with follow-up in 19. 57.9% showed no relevant, 26.3% moderate, 15.8% severe deficits. Cardiopulmonary status was satisfactory (mMRC level: 84.2% ≤2). 73.7% were independent in daily life. Cognitive impairments were frequent (52.6%). 26.3% showed moderate depression, 15.8% posttraumatic stress disorder. Social and work life were considerably affected. Extracorporeal membrane oxygenation thus can serve as salvage therapy in COVID-19, but advanced age, immunocompromise, histories of neoplasia, and frailty must be considered as relative contraindications. Age, vasoactive support, and SOFA scores assist discriminating in daily practice. Deficits after 6 months are substantial, and efforts need to focus on long-term recovery.

Misleading Germ Cell Phenotype in Pulmonary NUT Carcinoma Harboring the ZNF532-NUTM1 Fusion.

NUT carcinoma (aka NUT midline carcinoma) is a rare, still significantly underrecognized aggressive malignancy. Although historically considered a midline malignancy of children and young adults, NUT carcinoma can originate in almost any body site and in any age group. Beside the classic BRD4-NUTM1 fusion, less common fusion partners include BRD3, NSD3, ZNF532, and ZNF592. Other fusions, including CIC, MGA, MXD4, MXD1, and BCORL1 are associated with sarcomas or cancers of unknown histogenesis. Involvement of the Z4 zinc finger protein (ZNF) family members ZNF532 and ZNF592 is exceedingly rare with only 3 recently reported cases. We herein describe a ZNF532-NUTM1-rearranged NUT carcinoma presenting as a 7.5 cm mass in the left lower lung lobe of a 65-year-old woman. Histology revealed undifferentiated monotonous small round cells with focal epithelioid and rhabdoid elements within a variably myxoid stroma. Immunohistochemistry revealed paucity of keratins and variable p63 combined with extensive CD30 and PLAP expression, leading to initial diagnoses of combined small cell carcinoma, CD30-positive unclassified hematolymphoid malignancy and malignant germ cell neoplasm. Negativity for other more specific germ cell markers justified seeking a fourth opinion, which revealed diffuse expression of the NUT antibody. The diagnosis was then confirmed by fluorescence in situ hybridization. Targeted RNA sequencing revealed the ZNF532-NUTM1 fusion. Screening of 7 NUT carcinomas (5 with BRD4-NUTM1 and 2 with NSD3-NUTM1 fusions) for germ cell markers revealed focal SALL4 reactivity in 3 cases (combined with variable AFP expression in 2), but none expressed CD30 or PLAP. An aberrant germ cell immunophenotype should be considered in NUT carcinoma to avoid misinterpretation as genuine germ cell malignancy as both diseases predominantly affect the young population, frequently involve the mediastinum and can be associated with elevated serum AFP.

Low dose bivalirudin anticoagulation for lung transplantation with extracorporeal membrane oxygenation in a patient with acute heparin-induced thrombocytopenia.

A patient scheduled for lung transplantation needed veno-venous extracorporeal membrane oxygenation (ECMO) and developed acute heparin-induced thrombocytopenia (HIT). After 21 days on ECMO support, lung transplantation was successfully performed using veno-arterial ECMO with bivalirudin anticoagulation. The target activating clotting time values of 160-180 s resulted in low bivalirudin infusion rates of 0.1 mg/kg/h. Diffuse bleeding stopped quickly after ending the continuous bivalirudin infusion.

A silent gigantic solitary fibrous tumor of the pleura: case report.

Solitary fibrous tumor of the pleura is a rare mesenchymal tumor, representing less than 5% of all neoplasms associated with the pleura. A 57-year-old man had general malaise without chest symptoms for 1 month. A chest roentgenogram and computed tomography showed a giant mass in the left thorax. Although the tumor compressed the descending aorta and other mediastinal structures strongly, thereby shifting them to the right side, the patient had no symptoms except malaise. The tumor was successfully resected via two separate thoracotomies. The tumor was measured (20 cm × 19 cm × 15 cm) and weighed (2150 g). The tumor was histologically and immunohistochemically diagnosed as benign. Although SFT is benign, a long follow-up period is essential as even patients with complete resection are at risk of recurrence many years after surgery.

Lung transplant recipients' views on the integration of their new organs.

AIM: Although donorship issues and the integration of the new organs are the most distinguishing aspects of lung transplantation (LTx) compared to other kinds of 'high-tech' medicine, there is a paucity of papers on that matter. Therefore, we aimed to evaluate these aspects in young adult LTx recipients with at least 1-year survival. METHODS: Semi-structured interviews; content analysis of specific parts of the interviews; frequency distributions of resulting categories. SAMPLE: Forty-five adults aged 18-42 years (mean: 32 +/- 5.5 years). Post-transplant survival ranged from 1 to 11 years. RESULTS: The majority of recipients (60%) fulfilled criteria of denial towards the foreign organ and/or the donor. However, they were rather sensitive towards the ethical and psychological impact of the upcoming option of living donorship in LTx. Also, the majority of recipients (79%) understood that there might as well be good reason not to opt for a LTx. CONCLUSIONS: LTx recipients appeared at first sight 'pragmatic' towards the gift of life, but they remained sensitive to its ethical and psychological challenges.

Evaluation of a 24-hour emergency bronchoscopy service in a tertiary care hospital.

BACKGROUND: Flexible bronchoscopy has become an important diagnostic and therapeutic tool for the management of patients with various diseases of the chest. Availability of a 24-hour bronchoscopy service equipped with experienced personnel is becoming increasingly important especially for intensive care patients. However, such services have been implemented only in a few medical centres. The aim of this study was to evaluate the usage of a 24-hour emergency service in a large university hospital with a 1 year prospective analysis of emergency bronchoscopy service in a tertiary care centre. METHODS: Frequencies, indications and efficiency of therapeutic interventions were evaluated after each bronchoscopy using a specially designed questionnaire. All bronchoscopies were performed as emergency procedures out of operational schedule. A total of 614 emergency bronchoscopies were performed, 88% of them in intensive care units. RESULTS: The vast majority (84.5%) of the procedures were necessary for therapeutic interventions; that is, atelectasis, airway secretion, aspiration or bronchopulmonary bleeding. According to prespecified criteria, 37.6% (n = 195) of therapeutic procedures were assessed as 'very helpful' and 3.9% (n = 20) as 'life saving'. Diagnostic bronchoscopies were performed mainly to collect airway material for microbiological evaluations in immunocompromised patients. In these cases, the diagnostic yield was approximately 50%. CONCLUSION: The availability of a 24-hour bronchoscopy service has been found to improve patient care and was occasionally considered life saving. Thus, comparable services should be made more widely available.

Effects of exogenous surfactant instillation in clinical lung transplantation: a prospective, randomized trial.

OBJECTIVE: Despite the introduction of low potassium-based preservation strategies for clinical lung transplantation, relevant early graft dysfunction occurs in up to 20% of cases after lung transplantation. This was found to be frequently associated with postreperfusion surfactant dysfunction. We performed a randomized, prospective study investigating the effect of exogenous surfactant instillation into human donor lungs on posttransplant surfactant function and on clinical outcome. METHODS: Exogenous surfactant was instilled into 15 donor lungs before retrieval via bronchoscopy. Bronchoalveolar lavage fluids were taken before instillation as well as 24 hours after transplantation. Surfactant function, phospholipids, and protein content in bronchoalveolar lavage fluids were assessed and clinical data prospectively recorded. Pulmonary function testing was performed 4 weeks after lung transplantation. Additionally, the best forced expiratory volume in 1 second was determined within the first year after lung transplantation. The control group consisted of 14 patients receiving donor lungs without surfactant instillation in randomized order. Pulmonary function test results were further compared with those of 154 consecutive recipients of bilateral lung transplants, which were not involved in the study (historical control). RESULTS: No deaths occurred during the first year after lung transplantation. Surfactant function in donor lungs was within normal ranges before harvest. In the control group, surfactant function was markedly impaired after reperfusion. This was significantly improved by surfactant substitution. Protein content of the bronchoalveolar lavage fluid in the surfactant group was significantly lower, indicating less leakage through the alveolocapillary membrane. Forced expiratory volume in 1 second after 4 weeks was significantly higher in the surfactant group than in either control group (P = .034 and .01, respectively). Interestingly, the best forced expiratory volume in 1 second during the first year after lung transplantation was significantly higher in both control groups compared with forced expiratory volume measured in examinations 4 weeks after lung transplantation (P = .01). The best forced expiratory volumes in 1 second of control patients were comparable with those in surfactant lungs 4 weeks after transplant. CONCLUSIONS: This study indicates a protective effect of exogenous surfactant instillation to donor lungs before retrieval on post-lung transplantation surfactant function and on early clinical outcome. This approach may help to improve the outcome after lung transplantation in the future.

Polyoma virus nephropathy in native kidneys after lung transplantation.

Polyoma virus nephropathy is recognized as an emerging clinical problem in renal transplantation; however, polyoma in native kidneys is unusual. We report a patient who developed polyoma nephropathy in his native kidneys 15 months after successful lung transplantation. His immunosuppression consisted of tacrolimus, mycophenolate mofetil, and large doses of steroids because of three rejection episodes. When the condition was recognized, cidofovir was an effective treatment (3 doses of 2-3mg/kg); however, his renal function deteriorated nonetheless. Tubulitis and interstitial cell infiltration in his native kidneys were evidence that the changes were in response to viral injury. Polyoma nephropathy of native kidneys is unusual. An earlier course of cisplatin treatment because of metastatic seminoma prior to lung transplantation may have been contributory to pre-existing renal injury. After cidofovir was begun, the polyoma viral load in serum and urine decreased substantially; however, after high-dose steroid treatment of two rejection episodes, each time a significant increase in viral load was seen. We stained biopsies of native kidneys from 30 recipients of other organs. The biopsies were done for various reasons but not because polymoma virus was suspected. We found no additional cases.

Tacrolimus versus cyclosporine induction therapy in pulmonary transplantation in miniature swine.

OBJECTIVE: Tacrolimus has been shown to provide superior immunosuppression in various solid organ transplant settings. The purpose of our study was to compare the survival of porcine lung allografts after induction with either cyclosporine A (CsA) or tacrolimus. METHODS: Single lung transplantation from MHC mismatched donors was performed in 10 minipigs. Immunosuppression included 1.5 mg/kg per day methylprednisolone and 1.0 mg/kg per day azathioprine. CsA (n=5) was adjusted to trough levels of 300-500 ng/ml, tacrolimus (n=5) was adjusted to 16-26 ng/ml. All immunosuppressive drugs were discontinued on postoperative day (POD) 28. Allograft survival was monitored by sequential chest radiographs, bronchoscopy and transbronchial biopsy histology. Peripheral blood leukocytes were scanned for donor chimerism and CD3, CD4, CD8 and CD25 expression. RESULTS: The animals survived a 4-week course of immunosuppression without radiological or histological signs of rejection on POD 28. Median allograft survival in CsA-treated animals was 55+/-15 days and all animals rejected their grafts within 42 days after withdrawal of immunosuppression. In tacrolimus-treated animals, median survival was 152+/-65 days with the longest survivor being electively sacrificed on POD 390 (P=0.0064). The degree of donor leukocyte chimerism and the frequency of CD4+CD25+ T-cells were higher in the tacrolimus group, however, these differences were not statistically significant. CONCLUSION: The results of our study show that primary immunosuppression with tacrolimus is superior to cyclosporine after pulmonary allotransplantation in a large animal model.

Consulting the "experts": a pilot study on perceptions of professional support among lung transplant recipients and accompanying relatives.

BACKGROUND: Lung transplantation is extremely stressful for patients and accompanying support persons. PURPOSE: To improve delivery of care, we designed a cross-sectional study about unmet needs and perceived helpfulness of staff. METHODS: The sample consisted of 30 adult lung transplant recipients with cystic fibrosis (and 22 relatives) and 20 age-matched recipients with other reasons for transplantation (and 17 relatives). Mean survival since transplantation was 5 years. Data were collected via questionnaires (numerical rating scales and fill-in-the-blank items). RESULTS: Most patients in both groups were satisfied with staff support (nurse, doctor) especially during the acute stage of illness. Relatives were less satisfied at all stages. Patients' satisfaction with doctors' support was higher after than before transplantation, but the opposite was true for relatives. Insufficient continuity of care was the most frequent critical comment from patients and support persons. Recommendations to improve delivery of care included providing access to psychosocial professionals and broadening the information provided before transplantation. CONCLUSIONS: Regular screening of customer satisfaction should become routine. Particular attention should be paid to support persons.

Lung transplantation with lungs from donors fifty years of age and older.

BACKGROUND: A shortage of donors has led to the progressive expansion of criteria for donor selection in lung transplantation. The outcome of recipients of lungs from donors aged 50 years or older is analyzed systematically. METHODS: From March 1998 to June 2003, 49 recipients received lungs from donors aged 50 years or older (range 50-64 years, mean 54 +/- 3 years). This group of recipients was compared with 244 patients receiving lungs from donors aged less than 50 years (range 7-49 years, mean 32 +/- 11 years). This study was undertaken on all 293 patients at our institution who received Perfadex-preserved lungs (Vitrolife, Goteborg, Sweden). RESULTS: Recipient age, sex, and indications for transplant did not differ significantly between groups. Also, the percentage of the different types of transplants (bilateral or single lung transplantation) performed was equal in both cohorts. Donor Pa(O2) /F(IO2) ratios before lung retrieval (415 +/- 91 vs 439 +/- 113, respectively) and length of ischemic time (347 +/- 67 minutes vs 351 +/- 84 minutes, respectively) did not differ significantly between the older and younger donor groups. The following posttransplant parameters were also not statistically different: first Pa(O2)/F(IO2) at intensive care unit arrival (274 +/- 125 in the older donor group vs 253 +/- 119 in the younger donor group, respectively), mechanical ventilation time (328 +/- 427 hours vs 269 +/- 425 hours, respectively), and length of stay in the intensive care unit (16 +/- 18 days vs 14 +/- 18 days, respectively). Recipient survival in the older and younger donor groups at 30 days, 3, 6, 12, 24, and 60 months was 77% +/- 6%, 75% +/- 6%, 73% +/- 7%, 73% +/- 7%, 68% +/- 5%, and 68% +/- 4% versus 86% +/- 2%, 83% +/- 3%, 80% +/- 3%, 78% +/- 3%, 71% +/- 4%, and 66% +/- 4%, respectively. CONCLUSIONS: Lung grafts from elderly donors have been considered as marginal organs for transplantation. However, this study indicates that transplantation of lungs from carefully selected donors aged 50 years or more may lead to similar short- and long-term outcomes compared with lungs from younger donors. The use of lungs from elderly donors may help to increase the number of donor organs in lung transplantation.

Pulmonary preservation with LPD and celsior solution in porcine lung transplantation after 24 h of cold ischemia.

OBJECTIVE: Pulmonary preservation for transplantation is associated with ischemia reperfusion injury resulting in endothelial cell and surfactant dysfunction. The purpose of the study was to compare two extracellular type solutions, low potassium dextrane (LPD) and Celsior in their ability of ameliorating lung ischemia reperfusion injury. METHODS: In 12 donor pigs, the left lung was perfused with either LPD (n = 6) or Celsior (n = 6) solution. After 24 h cold storage, the lungs were transplanted into 12 recipient animals. After reperfusion of the left lung, the right pulmonary artery and bronchus were clamped. Bronchoalveolar lavage fluid (BALF) was obtained before the surgical procedure and 2 h after reperfusion. Surfactant activity was measured from BALF using a pulsating bubble surfactometer. Hemodynamic and respiratory parameters were assessed in 30-min intervals for 7 post-operative hours. RESULTS: In both study groups two of six animals died from severe ischemia reperfusion injury, thus survival did not differ between groups. Rise of pulmonary vascular resistance index (P = 0.01) and sequestration of neutrophiles (P = 0.08) was less pronounced in Celsior group when compared to LPD animals. A difference in surfactant activity between both groups was not evident after 2 h of reperfusion. CONCLUSIONS: Both solutions might provide safe pulmonary preservation for 24 h of cold ischemia. While surfactant activity was affected to the same extent in both groups, Celsior solution provided slightly superior endothelial preservation.

Quality of life 1 year after lung transplantation.

Lung transplantation is a viable therapeutic option for patients with end-stage lung disease. The focus of interest has shifted from advances in surgical techniques to improved quality of life for the transplant recipient. A prospective longitudinal repeated measures design was used to determine the impact of lung transplantation on quality of life and life satisfaction. Using 4 measurement points (before transplantation, after 8 weeks, and after 6 and 12 months), 61 patients were followed from before to 1 year after successful lung transplantation. Quality of life was measured using 2 generic (SF-36, Quality of Life Profile for Chronic Diseases) and 1 lung-specific (Saint George's Respiratory Questionnaire) questionnaires. All dimensions of the health-related scores improved significantly after transplantation, except bodily pain. Patients reported the most significant improvements until 6 months after transplantation. Lung transplantation had no influence on social functioning or role emotional. The Saint George's Respiratory Questionnaire ratings showed similar significantly better scores for transplant recipients at 6 months, and stagnations for most dimensions afterward.

Pulmonary preservation with Bretscheider's HTK and Celsior solution in minipigs.

BACKGROUND: Pulmonary preservation with high potassium/low oncotic pressure Euro-Collins (EC) solution is associated with endothelial dysfunction and reduced surfactant function. We compared two low potassium solutions, histidine-tryptophane-ketoglutarate (HTK) and Celsior, to EC in lung ischemia-reperfusion injury. METHODS: In 19 minipigs, the left lung was perfused in situ with cold preservation solution (EC, n=6; HTK, n=6; Celsior, n=7). Reperfusion was started after 90 min of warm ischemia. The right pulmonary artery and main bronchus were clamped. Bronchoalveolar lavage (BAL) was obtained before ischemia and after 2 h of reperfusion. Surfactant activity was determined from the BAL in a pulsating bubble surfactometer. RESULTS: Animals in the EC group survived 3.7+/-1.4 h. Six Celsior and five HTK treated animals survived the observation period of 7 h (P<0.001). Compliance of the reperfused lung deteriorated less in both Celsior and HTK groups (P<0.001). In EC and HTK animals, the pO(2)/FiO(2) ratio was lower (P=0.002), and pulmonary vascular resistance was higher (P=0.02) than in Celsior animals. Surfactant function was impaired after reperfusion in all groups. CONCLUSIONS: Compared to EC, HTK solution showed moderate and Celsior distinct improvement of post-ischemic pulmonary function. However, surfactant function was not well preserved in any group.

Surfactant function in lung transplantation after 24 hours of ischemia: advantage of retrograde flush perfusion for preservation.

OBJECTIVE: Surfactant function was shown to be impaired in clinical and experimental lung transplantation. This study was designed to define the impact of retrograde flush perfusion on graft and surfactant function after an extended period of ischemia. METHODS: Left lung transplantation was performed after 24 hours of graft ischemia in 12 pigs. In half of the grafts antegrade cold flush perfusion (Perfadex) was used for preservation. In the second group grafts were flushed in a retrograde fashion via the left atrium. Graft function was monitored for 7 hours after transplantation. Before transplantation (basal) and after 2 hours of reperfusion, bronchoalveolar lavage fluid was obtained. Minimal surface tension of bronchoalveolar lavage fluid was determined and the ratio of small and large surfactant aggregates was calculated. Lung water content was analyzed online in the reperfusion period. RESULTS: Right-sided heart failure developed in 2 animals of group 1 (antegrade perfusion) within 2 and 4.5 hours of reperfusion, respectively. All other pigs survived the observation period. PO(2)/FIO(2) (P =.001) and dynamic lung compliance (P =.001) were superior in retrogradely flushed grafts. A comparable increase of minimal surface tension was found after reperfusion in both groups. Small/large surfactant aggregate ratio after reperfusion (P =.03), as well as extravascular lung water content, was higher in the antegrade perfusion group. CONCLUSION: Retrograde flush perfusion for 24-hour lung preservation with low-potassium dextran (Perfadex) solution led to better initial graft function than the standard antegrade perfusion technique. A moderate impairment of surfactant function was found in both groups, which was more pronounced in the antegrade perfusion group.