Donor Lung Preservation at 10°C: Clinical and Logistical Impact.

INTRODUCTION: Cold static donor lung preservation at 10°C appears to be a promising method to safely extend the cold ischemic time (CIT) and improve lung transplant (LTx) logistics. METHODS: LTx from November 2021 to February 2023 were included in this single institution, prospective, non-randomized study comparing prolonged preservation at 10°C versus standard preservation on ice. The inclusion criteria for 10°C preservation were suitable grafts for LTx without any donor retrieval concerns. PRIMARY ENDPOINT: primary graft dysfunction (PGD) grade-3 at 72-h. Secondary endpoints: clinical outcomes, cytokine profile and logistical impact. RESULTS: Thirty-three out of fifty-seven cases were preserved at 10°C. Donor and recipient characteristics were similar across the groups. Total preservation times (h:min) were longer (p<0.001) in the 10°C group [1st lung: median 12:09 (IQR 9:23-13:29); 2nd: 14:24 (12:00-16:20)] vs. standard group [1st lung: median 5:47 (IQR 5:18-6:40); 2nd: 7:15 (6:33-7:40)]. PGD grade-3 at 72-h was 9.4% in 10°C group vs. 12.5% in standard group (p=0.440). Length of mechanical ventilation (MV), ICU and hospital stays were similar in both groups. Thirty and ninety-day mortality rates were 0% in 10°C group (vs. 4.2% in standard group). IL-8 concentration was significantly higher 6-h post-LTx in the standard group (p=0.025) and IL-10 concentration was increased 72-h post-LTx in the 10°C group (p=0.045). CONCLUSIONS: Preservation at 10°C may represent a safe and feasible strategy to intentionally prolong the CIT. In our center, extending the CIT at 10°C may allow for semi-elective LTx and improve logistics with similar outcomes compared to the current standard preservation on ice.

Outcomes after lung transplantation from selected donors older than 70 years in a single centre: time to close the debate?

OBJECTIVES: The aim of this study was to compare the outcomes of lung transplantations using grafts from donors aged over 70 years against those performed using younger donors. METHODS: This retrospective single-centre analysis includes lung transplants conducted at our institution from January 2014 to June 2022. Lung recipients were classified into 2 groups based on donor age (group A <70 years; group B ≥70 years). Variables regarding demographics, peri and postoperative outcomes and survival were included. The statistical analysis approach included univariable analysis, propensity score matching to address imbalances in donor variables (smoking status), recipient characteristics (sex, age, diagnosis and lung allocation score) and calendar period and survival analysis. RESULTS: A total of 353 lung transplants were performed in this period, 47 (13.3%) using grafts from donors aged over 70 years. Donors in group B were more frequently women (70.2% vs 51.6%, P = 0.017), with less smoking history (22% vs 43%, P = 0.002) and longer mechanical ventilation time (3 vs 2 days, P = 0.025). Recipients in group B had a higher lung allocation score (37.5 vs 35, P = 0.035). Postoperative variables were comparable between both groups, except for pulmonary function tests. Group B demonstrated lower forced expiratory volume 1 s levels (2070 vs 2580 ml, P = 0.001). The propensity score matching showed a lower chance of chronic lung allograft dysfunction by 12% for group B. One-, three- and five-year survival was equal between the groups. CONCLUSIONS: The use of selected expanded-criteria donors aged over 70 years did not result in increased postoperative morbidity, early mortality or survival in this study.

[Questions and Answers in Lung Cancer]. / Preguntas y respuestas en cáncer de pulmón.

Over the past 2 decades, scientific evidence has strongly supported the use of low-radiation dose chest computed tomography (CT) as a screening technique for lung cancer. This approach has resulted in a significant reduction in mortality rates by enabling the detection of early-stage lung cancer amenable to potentially curative treatments. Regarding diagnosis, there are also novel methods under study, such as liquid biopsy, identification of the pulmonary microbiome, and the use of artificial intelligence techniques, which will play a key role in the near future. At present, there is a growing trend towards less invasive surgical procedures, such as segmentectomy, as an alternative to lobectomy. This procedure is based on 2 recent clinical trials conducted on peripheral tumors measuring less than 2 cm. Although these approaches have demonstrated comparable survival rates, there remains controversy due to uncertainties surrounding recurrence rates and functional capacity preservation. With regard to adjuvant therapy, immunotherapy, either as a monotherapy or in conjunction with chemotherapy, has shown encouraging results in resectable stages of locally advanced lung cancer, demonstrating complete pathologic responses and improved overall survival.After surgery treatment, despite the lack of solid evidence for long-term follow-up of these patients, clinical practice recommends periodic CT scans during the early years.In conclusion, there have been significant advances in lung cancer that have improved diagnostic techniques using new technologies and screening programs. Furthermore, the treatment of lung cancer is increasingly personalized, resulting in an improvement in the survival of patients.

Pathological N1/N2 in Clinical Stage I Bronchogenic Carcinoma. Analysis From a Prospective Multicentre Database

Objectives: To determine the incidence of occult N1/N2 nodal metastases and associated risk factors in patients with non-small cell lung cancer no larger than 3cm and deemed cN0 by CT and PET-CT in a prospective, multicentre national database. Methods: Patients with a NSCLC no larger than 3cm, deemed cN0 by PET-CT and CT scan, who had undergone at least a lobectomy, were selected from a national multicentre database of 3533 patients who had undergone anatomic lung resection between 2016 and 2018. Clinical and pathological variables of patients with pN0 and patients with pN1/N2 were compared to identify factors associated with the presence of lymph node metastases. Chi2 and the Mann–Whitney U test were used for categorical and numerical variables, respectively. All variables with p<0.2 in the univariate analysis were included in the multivariate logistic regression analysis. Results: The study included 1205 patients from the cohort. The incidence of occult pN1/N2 disease was 10.70% (95%CI, 9.01–12.58). The multivariable analysis revealed that the degree of differentiation, size, location (central or peripheral) and SUV of the tumour in PET, surgeon experience and number of lymph nodes resected were associated with occult N1/N2 metastases. Conclusions: The incidence of occult N1/N2 in patients with bronchogenic carcinoma with cN0 tumours no larger than 3cm is no negligible. Data about the degree of differentiation, tumour size in CT scan, maximal uptake of the tumour in PET-CT, location (central or peripheral), number of lymph nodes resected and surgeon seniority is relevant in order to detect patients at risk. (AU)

Donor lungs cold preservation at 10 ºC offers a potential logistic advantage in lung transplantation / La preservación fría a 10 ºC de los injertos ofrece ventajas logísticas en el trasplante pulmonar

Donor lung preservation at 10 °C appears to be an innovative and promising method that may improve transplant logistics by extending the cold ischemia time with excellent outcomes. We report the case of two lung transplants from two different donors involving the use of two different preservation methods, highlighting the benefits of using 10 °C lung storage. (AU)

La preservación pulmonar a 10 °C es una estrategia innovadora que podría mejorar la logística del trasplante pulmonar permitiendo prolongar el tiempo de isquemia fría de los injertos pulmonares con excelentes resultados. Presentamos el caso de dos trasplantes pulmonares de dos donantes diferentes empleando dos métodos de preservación distintos, recalcando los beneficios de utilizar este novedoso método de preservación a 10 °C. (AU)

Pathological N1/N2 in Clinical Stage I Bronchogenic Carcinoma. Analysis From a Prospective Multicentre Database.

OBJECTIVES: To determine the incidence of occult N1/N2 nodal metastases and associated risk factors in patients with non-small cell lung cancer no larger than 3cm and deemed cN0 by CT and PET-CT in a prospective, multicentre national database. METHODS: Patients with a NSCLC no larger than 3cm, deemed cN0 by PET-CT and CT scan, who had undergone at least a lobectomy, were selected from a national multicentre database of 3533 patients who had undergone anatomic lung resection between 2016 and 2018. Clinical and pathological variables of patients with pN0 and patients with pN1/N2 were compared to identify factors associated with the presence of lymph node metastases. Chi2 and the Mann-Whitney U test were used for categorical and numerical variables, respectively. All variables with p<0.2 in the univariate analysis were included in the multivariate logistic regression analysis. RESULTS: The study included 1205 patients from the cohort. The incidence of occult pN1/N2 disease was 10.70% (95%CI, 9.01-12.58). The multivariable analysis revealed that the degree of differentiation, size, location (central or peripheral) and SUV of the tumour in PET, surgeon experience and number of lymph nodes resected were associated with occult N1/N2 metastases. CONCLUSIONS: The incidence of occult N1/N2 in patients with bronchogenic carcinoma with cN0 tumours no larger than 3cm is no negligible. Data about the degree of differentiation, tumour size in CT scan, maximal uptake of the tumour in PET-CT, location (central or peripheral), number of lymph nodes resected and surgeon seniority is relevant in order to detect patients at risk.

Donor lungs cold preservation at 10 °C offers a potential logistic advantage in lung transplantation.

Donor lung preservation at 10 °C appears to be an innovative and promising method that may improve transplant logistics by extending the cold ischemia time with excellent outcomes. We report the case of two lung transplants from two different donors involving the use of two different preservation methods, highlighting the benefits of using 10 °C lung storage.

Extension of Cold Static Donor Lung Preservation at 10°C.

BACKGROUND: Lung transplantation is performed on a 24/7 schedule to minimize organ ischemic time. Recent preclinical studies demonstrated superior graft preservation at 10°C compared with storage in an ice cooler (gold standard). METHODS: In this prospective, multicenter, nonrandomized clinical trial, we studied transplants from donors with overnight cross-clamp times (6:00 p.m. to 4:00 a.m.) that had an earliest allowed starting time of 6:00 a.m. Lungs meeting criteria for transplantation were retrieved, transported, and immediately transferred to a 10°C temperature-controlled incubator until implantation; 70 patients and 140 matched controls were included in this study. RESULTS: Total preservation times for lungs in the study group were 12 hours, 28 minutes (interquartile range, 10 hours, 14 minutes to 14 hours, 12 minutes) and 14 hours, 9 minutes (interquartile range, 12 hours, 3 minutes to 15 hours, 45 minutes) for the first and second lung implanted, respectively. Primary graft dysfunction grade 3 at 72 hours (primary outcome) was 5.7% in the study group versus 9.3% in matched controls (difference, −3.6; 95% confidence interval [CI], −10.5 to 5.3). No meaningful differences were observed in the need for postoperative extracorporeal membrane oxygenation (5.7 vs. 9.3%), median intensive care unit stay (5 vs. 5 days), or median hospital stay (25 vs. 30 days) between the two groups. One-year Kaplan­Meier survival was similar between the two groups (94 vs. 87%; hazard ratio, 0.65; 95% CI, 0.26 to 1.6). CONCLUSIONS: Extension of cold static preservation times at 10°C appears to be safe and has the potential to improve transplantation logistics and performance. (Funded by the UHN Foundation; Clinicaltrials.gov number, NCT04616365).

Interrupted versus continuous suture for bronchial anastomosis in lung transplantation: does it matter?

OBJECTIVES: Bronchial anastomotic complications remain a major concern in lung transplantation. We aim to compare 2 different techniques, continuous suture (CS) versus interrupted suture (IS) by analysing airway complications requiring intervention. METHODS: Lung transplantations between January 2015 and December 2020 were included. Airway complications requiring intervention were classified following the 2018 International Society for Heart and Lung Transplantation consensus and analysed comparing 3 groups of patients according to surgical technique: group A, both anastomosis performed with CS; group B, both with interrupted; and group C, IS for 1 side and CS for the contralateral side. RESULTS: A total of 461 anastomoses were performed in 245 patients. The incidence of airway complications requiring intervention was 5.7% [95% confidence interval (CI): 2.8-8.6] per patient (14/245) and 3.7% (95% CI: 2.0-5.4) per anastomosis (17/461). Complications that required intervention were present in 5 out of 164 (3.1%) anastomosis with interrupted technique, and in 12/240 (5%) with CS. No significant differences were found between techniques (P = 0.184). No statistical differences were found among group A, B or C in terms of incidence of anastomotic complications, demographics, transplant outcomes or overall survival (log-rank P = 0.513). In a multivariable analysis, right laterality was significantly associated to complications requiring intervention (OR 3.7 [95% CI: 1.1-12.3], P = 0.030). Endoscopic treatment was successful in 12 patients (85.7%). Retransplantation was necessary in 2 patients. CONCLUSIONS: In summary, although it seems that anastomotic complications requiring intervention occur more frequently with CS, there are no statistical differences compared to IS. Endoscopic treatment offers good outcomes in most of the airway complications after lung transplantation.

Evaluation of Uncontrolled Donation After Circulatory Death Lungs by Conventional In Situ Effluent Gas Analysis and Ex Vivo Lung Perfusion

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External validation of the European Society of Thoracic Surgeons morbidity and mortality risk models.

OBJECTIVES: There is a wide variety of predictive models of postoperative risk, although some of them are specific to thoracic surgery, none of them is widely used. The European Society for Thoracic Surgery has recently updated its models of cardiopulmonary morbidity (Eurolung 1) and 30-day mortality (Eurolung 2) after anatomic lung resection. The aim of our work is to carry out the external validation of both models in a multicentre national database. METHODS: External validation of Eurolung 1 and Eurolung 2 was evaluated through calibration (calibration plot, Brier score and Hosmer-Lemeshow test) and discrimination [area under receiver operating characteristic curves (AUC ROC)], on a national multicentre database of 2858 patients undergoing anatomic lung resection between 2016 and 2018. RESULTS: For Eurolung 1, calibration plot showed suboptimal overlapping (slope = 0.921) and a Hosmer-Lemeshow test and Brier score of P = 0.353 and 0.104, respectively. In terms of discrimination, AUC ROC for Eurolung 1 was 0.653 (95% confidence interval, 0.623-0.684). In contrast, Eurolung 2 showed a good calibration (slope = 1.038) and a Hosmer-Lemeshow test and Brier score of P = 0.234 and 0.020, respectively. AUC ROC for Eurolung 2 was 0.760 (95% confidence interval, 0.701-0.819). CONCLUSIONS: Thirty-day mortality score (Eurolung 2) seems to be transportable to other anatomic lung-resected patients. On the other hand, postoperative cardiopulmonary morbidity score (Eurolung 1) seems not to have sufficient generalizability for new patients.

Lung transplantation from uncontrolled and controlled donation after circulatory death: similar outcomes to brain death donors.

Controlled donation after circulatory death donors (cDCD) are becoming a frequent source of lungs grafts worldwide. Conversely, lung transplantations (LTx) from uncontrolled donors (uDCD) are sporadically reported. We aimed to review our institutional experience using both uDCD and cDCD and compare to LTx from brain death donors (DBD). This is a retrospective analysis of all LTx performed between January 2013 and December 2019 in our institution. Donor and recipient characteristics were collected and univariate, multivariate and survival analyses were carried out comparing the three cohorts of donors. A total of 239 (84.7%) LTx were performed from DBD, 29 (10.3%) from cDCD and 14 (5%) from uDCD. There were no statistically significant differences in primary graft dysfunction grade 3 at 72 h, 30- and 90-day mortality, need for extracorporeal membrane oxygenation after procedure, ICU and hospital length of stay, airway complications, CLAD incidence or survival at 1 and 3 years after transplant (DBD: 87.1% and 78.1%; cDCD: 89.7% and 89.7%; uDCD: 85.7% and 85.7% respectively; P = 0.42). Short- and mid-term outcomes are comparable between the three types of donors. These findings may encourage and reinforce all types of donation after circulatory death programmes as a valid and growing source of suitable organs for transplantation.

Post-transplant outcomes of standard and extended criteria donation after circulatory death donor lungs categorized by donation after brain death lung criteria.

OBJECTIVES: Most transplant centres use donation after brain death (DBD) criteria to assess the quality of controlled donation after circulatory death (cDCD) lungs. However, research on the relationship between DBD extended criteria and cDCD lung transplantation outcomes is limited. We investigated the outcomes of using DBD extended criteria donor organs in cDCD lung transplantation, compared to the standard criteria cDCD lung transplantation. METHODS: A retrospective chart review of consecutive cDCD lung referrals to Hospital Universitario Puerta de Hierro-Majadahonda from June 2013 to December 2019 was undertaken. Donors were divided into standard and extended criteria groups. Early outcomes after lung transplant were compared between these groups using the Kaplan-Meier method and log-rank test. RESULTS: Thirty out of 91 cDCD donor lung offers were accepted for transplantation, of which 11 were from standard criteria donors and 19 were extended criteria donors. The baseline characteristics of the 2 recipient groups were similar. There were no differences in the rates of grade 3 primary graft dysfunction at 72 h after lung transplantation (21% vs 18%), duration of mechanical ventilation (48 h vs 36 h), total intensive care unit stay (10 days vs 7 days) and 1-year survival (89% vs 90%). CONCLUSIONS: Carefully selecting cDCD lungs from outside the standard acceptability criteria may expand the existing donor pool with no detrimental effects on lung transplantation outcomes.

Effect on the donor lungs of using abdominal normothermic regional perfusion in controlled donation after circulatory death.

OBJECTIVES: Controlled donation after circulatory death (cDCD) donors are becoming a common source of organs for transplantation globally. However, the graft survival rate of cDCD abdominal organs is inferior to that of organs from brain-dead donors. The rapid retrieval (RR) technique is used by most donor organ procurement teams. The abdominal normothermic regional perfusion (A-NRP) technique has been implemented to minimize warm ischaemic damage to the abdominal organs. However, there is limited information on the effect of A-NRP on the quality of the donor lungs. This study aimed to compare lung transplantation outcomes using lungs procured from cDCD donors using the A-NRP and abdominal RR techniques. METHODS: A single-centre retrospective analysis of consecutive transplant recipients of cDCD lungs from June 2013 to December 2019 was performed. The recipients were divided into 2 cohorts according to the abdominal procurement technique used. The recipient and donor characteristics (age, sex, cause of brain injury, warm ischaemic time, diagnosis, lung allocation score and other factors), incidence of primary graft dysfunction and early survival were monitored. RESULTS: Twenty-eight consecutive lung transplantation recipients were identified (median age 59 years; 61% male); 14 recipients received lungs using the A-NRP and 14 using abdominal RR for abdominal organ retrieval. There were no significant differences in the baseline characteristics, primary graft dysfunction (P = 0.70), hospital mortality (P = 1.0) and 1-year survival rate (P = 1.0) between the 2 groups. CONCLUSIONS: No difference was observed in lung transplantation outcomes irrespective of the abdominal organ procurement technique used (A-NRP or abdominal RR).

Thoracic surgery during the coronavirus disease 2019 (COVID-19) pandemic in Madrid, Spain: single-centre report.

OBJECTIVES: We reviewed the incidence of coronavirus disease 2019 cases and the postoperative outcomes of patients who had thoracic surgery during the beginning and at the highest point of transmission in our community. METHODS: We retrospectively reviewed patients who had undergone elective thoracic surgery from 12 February 2020 to 30 April 2020 and were symptomatic or tested positive for severe acute respiratory syndrome coronavirus 2 infection within 14 days after surgery, with a focus on their complications and potential deaths. RESULTS: Out of 101 surgical procedures, including 57 primary oncological resections, 6 lung transplants and 18 emergency procedures, only 5 cases of coronavirus disease 2019 were identified, 3 in the immediate postoperative period and 2 as outpatients. All 5 patients had cancer; the median age was 64 years. The main virus-related symptom was fever (80%), and the median onset of coronavirus disease 2019 was 3 days. Although 80% of the patients who had positive test results for severe acute respiratory syndrome coronavirus 2 required in-hospital care, none of them were considered severe or critical and none died. CONCLUSIONS: These results indicate that, in properly selected cases, with short preoperative in-hospital stays, strict isolation and infection control protocols, managed by a dedicated multidisciplinary team, a surgical procedure could be performed with a relatively low risk for the patient.

Manipulation of extinction features in frequency combs through the usage of graphene.

Lately, the integration of two-dimensional materials into semiconductor devices has allowed the modification of their effective index by simply applying a modest voltage (between 0 and 3 volts). In this work, we present a device composed of two evanescently coupled silicon microring resonators where both rings have a graphene layer on top. This design is aimed to produce frequency combs with transmission characteristics controlled upon voltage application to the graphene layer. We numerically analyze the device response as a function of the incident wavelength and applied voltage. The results showed a low input intensity (0.6 GW/cm2) needed and a rapid response time (0.1 µs), in comparison to devices controlled by heat injection.