Pulmonary rehabilitation protocols in urgent lung transplantation patients

BACKGROUND:Prolonged invasive respiratory support and extracorporeal membrane oxygenation(ECMO)in patients requiring urgent lung transplantation(ULTx)present signifi cant challenges to clinical practice due to severe underlying diseases and complex conditions.The aim of the study was to report the clinical outcomes of patients who received ULTx and followed the perioperative rehabilitation protocol implemented in a lung transplant center.METHODS:A retrospective analysis was conducted in ULTx patients who required preoperative invasive mechanical ventilation(IMV)and ECMO between January 2018 and January 2023.Data were retrieved from electronic medical records at our lung transplant center.RESULTS:Fourteen patients(mean age 57.43±10.97 years;12 males,2 females)underwent ULTx with bridging ECMO and IMV.The mean body mass index was 23.94±3.33 kg/m²,and the mean Acute Physiology and Chronic Health Evaluation(APACHE)II score was 21.50±3.96.The Nutritional Risk Screening 2002(NRS 2002)scores were≥3.ULTx was performed after an 8.5-day waiting period(interquartile interval[IQR]5.0-26.5 d).Following the surgeries,the average lengths of ECMO and IMV were 1.0(IQR 1.0-2.0)d and 5.0(IQR 3.0-7.3)d,respectively.The total length of hospital stay was 60.1±30.8 d,with an average intensive care unit stay of 38.3±22.9 d and post-operative hospitalization stay of 45.8±26.1 d.Two patients died within 30 d after ULTx,with a 30-day survival rate of 85.71%.CONCLUSION:Patients receiving ULTx showed an acceptable short-term survival rate,validating the practicality and safety of the treatment protocols implemented in our center.

Intensive care unit-acquired weakness–preventive,and therapeutic aspects;future directions and special focus on lung transplantation

In this editorial,comments are made on an interesting article in the recent issue of the World Journal of Clinical Cases by Wang and Long.The authors describe the use of neural network model to identify risk factors for the development of intensive care unit(ICU)-acquired weakness.This condition has now become common with an increasing number of patients treated in ICUs and continues to be a source of morbidity and mortality.Despite identification of certain risk factors and corrective measures thereof,lacunae still exist in our understanding of this clinical entity.Numerous possible pathogenetic mechanisms at a molecular level have been described and these continue to be increasing.The amount of retrievable data for analysis from the ICU patients for study can be huge and enormous.Machine learning techniques to identify patterns in vast amounts of data are well known and may well provide pointers to bridge the knowledge gap in this condition.This editorial discusses the current knowledge of the condition including pathogenesis,diagnosis,risk factors,preventive measures,and therapy.Furthermore,it looks specifically at ICU acquired weakness in recipients of lung transplantation,because–unlike other solid organ transplants-muscular strength plays a vital role in the preservation and survival of the transplanted lung.Lungs differ from other solid organ transplants in that the proper function of the allograft is dependent on muscle function.Muscular weakness especially diaphragmatic weakness may lead to prolonged ventilation which has deleterious effects on the transplanted lung–ranging from ventilator associated pneumonia to bronchial anastomotic complications due to prolonged positive pressure on the anastomosis.

Hyperacute experimental model of rat lung transplantation using a coronary shunt cannula

BACKGROUND Lung transplantation is a well-established treatment of end-stage lung disease.A rodent model is an inexpensive way to collect biological data from a living model after lung transplantation.However,mastering the surgical technique takes time owing to the small organ size.AIM To conduct rat lung transplantation using a shunt cannula(SC)or modified cannula(MC)and assess their efficacy.METHODS Rat lung transplantation was performed in 11 animals in the SC group and 12 in the MC group.We devised a method of rat lung transplantation using a coronary SC for coronary artery bypass surgery as an anastomosis of pulmonary arteri-ovenous vessels and bronchioles.The same surgeon performed all surgical proce-dures in the donor and recipient rats without using a magnifying glass.The success rate of lung transplantation,operating time,and PaO2 values were com-pared after 2-h reperfusion after transplantation.RESULTS Ten and 12 lungs were successfully transplanted in the SC and MC groups,respectively.In the SC group,one animal had cardiac arrest within 1 h after reperfusion owing to bleeding during pulmonary vein anastomosis.The opera-ting time for the removal of the heart-lung block from the donor and preparation of the left lung graft was 26.8±2.3 and 25.7±1.3 min in the SC and MC groups,respectively(P=0.21).The time required for left lung transplantation in the recipients was 37.5±2.8 min and 35.9±1.4 min in the SC and MC groups,respectively(P=0.12).PaO2 values at 2 h after reperfusion were 456.2±25.5 and INTRODUCTION Lung transplantation is a well-established treatment of end-stage lung disease.Many immune and non-immune mech-anisms in lung transplantation are highly complex,and post-transplant complications such as infections and primary and chronic lung allograft dysfunction must be reduced to improve survival.Therefore,there is a need for immunological and pathophysiological analyses using animal lung transplantation models.The rat lung transplantation model was first reported in 1971[1],followed by the Mizuta Cuff model[2]in 1989.Since then,various improvements in surgical techniques,cuffs,and instruments have been reported[3-7].The advantage of using a rodent model is that it permits inexpensive collection of biological data from a living model after lung transplantation.Although trained surgeons can perform the transplantation procedure,mastering the surgical technique takes time due to the small size of the organs.The risks associated with this technique include damage to the vulnerable pulmonary artery(PA)and pulmonary vein(PV)vessel walls during anastomosis,as well as stenosis of the anastomotic site.We developed an anastomotic technique using a coronary shunt cannula(SC)for cardiac coronary artery bypass surgery as an alternative to the previously reported cuff method[2-6].This method enables anastomosis by inserting and ligating a cannula into the lumen of the PA,PV,and bronchus(Br),which is simpler and more reliable than conventional methods.This study aimed to determine problems with rat lung transplantation using the SC,develop an improved cannula,and investigate its utility.RESULTS After creating 11 lung transplantation model animals in the SC group and 12 in the MC group,all animals underwent reperfusion.One animal in the SC group had cardiac arrest 1 h after reperfusion due to hemorrhage caused by vessel wall injury during PV anastomosis.Two hours after reperfusion,we visually confirmed the maintenance of recipient hemody-namics and blood flow in the graft pulmonary cannula in 10 animals in the SC group and 12 in the MC group.The operating time for the removal of the heart-lung block from the donor and graft lung creation was 26.8±2.3 min in the SC group and 25.7±1.3 min in the MC group(P=0.21,Table 1).The duration for left lung transplantation into the recipient was 37.5±2.8 min in the SC group and 35.9±1.4 min(P=0.12,Table 1)in the MC group.Although no significant difference was found between the SC and MC groups,animals in the MC group experienced a slightly shorter operating time,smoother surgical technique,and less stressful procedure for the surgeons compared with those in the SC group.The graft lung coloration(Grade 1/2/3)after reperfusion was 0/2/8(SC group)and 0/2/10(MC group),and all grafts were reported to be successful,except in one animal in the SC group that had cardiac arrest(Table 2).The PaO2 values after 2 h of reperfusion were 456.2±25.5 mmHg in the SC group and 461.2±21.5 mmHg in the MC group(P=0.63,Table 3),showing no significant difference between the groups.

Imaging features of intrathoracic complications of lung transplantation:What the radiologists need to know

Lung transplantation has been a method for treating end stage lung disease for decades. Despite improvements in the preoperative assessment of recipients and donors as well as improved surgical techniques, lung transplant recipients are still at a high risk of developing postoperative complications which tend to impact negatively the patients' outcome if not recognised early. The recognised complications post lung transplantation can be broadly categorised into acute and chronic complications. Recognising the radiological features of these complications has a significant positive impact on patients' survival post transplantation. This manuscript provides a comprehensive review of the radiological features of post lung transplantations complications over a time continuum.

MiRNA-122 Promotes Ischemia-Reperfusion Injury after Lung Transplantation via the Toll-like Receptor Signaling Pathway

Objective:MiRNAs have been recently implicated in the pathogenesis of ischemia-reperfusion(IR)injury.This study aimed to investigate the miRNA expression profiles,in the early stages after lung transplantation(LT)and to study the involvement of the Toll-like receptor(TLR)signaling pathway in lung IR injury following LT.Methods:We established the left LT model in mice and selected the miRNA-122 as a research target.The mice were injected with a miRNA-122-specific inhibitor,following which pathological changes in the lung tissue were studied using different lung injury indicators.In addition,we performed deep sequencing of transplanted lung tissues to identify differentially expressed(DE)miRNAs and their target genes.These target genes were used to further perform gene ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)analysis.Results:A total of 12 DE miRNAs were selected,and 2476 target genes were identified.The GO enrichment analysis predicted 6063 terms,and the KEGG analysis predicted 1554 biological pathways.Compared with the control group,inhibiting the expression of miRNA-122 significantly reduced the lung injury and lung wet/dry ratio(P<0.05).In addition,the activity of myeloperoxidase and the expression levels of tumor necrosis factor-alpha and TLR2/4 were decreased(P<0.05);whereas the expression of interleukin-10 was increased(P<0.05).Furthermore,the inhibition of miRNA-122 suppressed the IR injury-induced activation of the TLR signaling pathway.Conclusion:Our findings showed the differential expression of several miRNAs in the early inflammatory response following LT.Of these,miRNA-122 promoted IR injury following LT,whereas its inhibition prevented IR injury in a TLR-dependent manner.

Extracorporeal membrane oxygenation in lung transplantation:Indications,techniques and results

The use of extracorporeal membrane oxygenation(ECMO)in the field of lung transplantation has rapidly expanded over the past 30 years.It has become an important tool in an increasing number of specialized centers as a bridge to transplantation and in the intra-operative and/or post-operative setting.ECMO is an extremely versatile tool in the field of lung transplantation as it can be used and adapted in different configurations with several potential cannulation sites according to the specific need of the recipient.For example,patients who need to be bridged to lung transplantation often have hypercapnic respiratory failure that may preferably benefit from veno-venous(VV)ECMO or peripheral veno-arterial(VA)ECMO in the case of hemodynamic instability.Moreover,in an intraoperative setting,VV ECMO can be maintained or switched to a VA ECMO.The routine use of intra-operative ECMO and its eventual prolongation in the postoperative period has been widely investigated in recent years by several important lung transplantation centers in order to assess the graft function and its potential protective role on primary graft dysfunction and on ischemia-reperfusion injury.This review will assess the current evidence on the role of ECMO in the different phases of lung transplantation,while analyzing different studies on pre,intra-and post-operative utilization of this extracorporeal support.

Primary graft dysfunction following lung transplantation:From pathogenesis to future frontiers

Lung transplantation is the treatment of choice for patients with end-stage lung disease.Currently,just under 5000 lung transplants are performed worldwide annually.However,a major scourge leading to 90-d and 1-year mortality remains primary graft dysfunction.It is a spectrum of lung injury ranging from mild to severe depending on the level of hypoxaemia and lung injury post-transplant.This review aims to provide an in-depth analysis of the epidemiology,pathophysiology,risk factors,outcomes,and future frontiers involved in mitigating primary graft dysfunction.The current diagnostic criteria are examined alongside changes from the previous definition.We also highlight the issues surrounding chronic lung allograft dysfunction and identify the novel therapies available for ex-vivo lung perfusion.Although primary graft dysfunction remains a significant contributor to 90-d and 1-year mortality,ongoing research and development abreast with current technological advancements have shed some light on the issue in pursuit of future diagnostic and therapeutic tools.

Chronic lung allograft dysfunction post-lung transplantation:The era of bronchiolitis obliterans syndrome and restrictive allograft syndrome

Chronic lung allograft dysfunction(CLAD)following lung transplantation limits long-term survival considerably.The main reason for this is a lack of knowledge regarding the pathological condition and the establishment of treatment.The consensus statement from the International Society for Heart and Lung Transplantation on CLAD in 2019 classified CLAD into two main phenotypes:Bronchiolitis obliterans syndrome and restrictive allograft syndrome.Along with this clear classification,further exploration of the mechanisms and the development of appropriate prevention and treatment strategies for each phenotype are desired.In this review,we summarize the new definition of CLAD and update and summarize the existing knowledge on the underlying mechanisms of bronchiolitis obliterans syndrome and restrictive allograft syndrome,which have been elucidated from clinicopathological observations and animal experiments worldwide.

Ineffective esophageal motility is associated with acute rejection after lung transplantation independent of gastroesophageal reflux

BACKGROUND Gastroesophageal reflux is associated with poorer outcomes after lung transplant,likely through recurrent aspiration and allograft injury.Although prior studies have demonstrated a relationship between impedance-pH results and transplant outcomes,the role of esophageal manometry in the assessment of lung transplant patients remains debated,and the impact of esophageal dysmotility on transplant outcomes is unclear.Of particular interest is ineffective esophageal motility(IEM)and its associated impact on esophageal clearance.AIM To assess the relationship between pre-transplant IEM diagnosis and acute rejection after lung transplantation.METHODS This was a retrospective cohort study of lung transplant recipients at a tertiary care center between 2007 and 2018.Patients with pre-transplant anti-reflux surgery were excluded.Manometric and reflux diagnoses were recorded from pre-transplant esophageal function testing.Time-to-event analysis using Cox proportional hazards model was applied to evaluate outcome of first episode of acute cellular rejection,defined histologically per International Society of Heart and Lung Transplantation guidelines.Subjects not meeting this endpoint were censored at time of post-transplant anti-reflux surgery,last clinic visit,or death.Fisher’s exact test for binary variables and student’s t-test for continuous variables were performed to assess for differences between groups.RESULTS Of 184 subjects(54%men,mean age:58,follow-up:443 person-years)met criteria for inclusion.Interstitial pulmonary fibrosis represented the predominant pulmonary diagnosis(41%).During the follow-up period,60 subjects(33.5%)developed acute rejection.The all-cause mortality was 16.3%.Time-to-event univariate analyses demonstrated significant association between IEM and acute rejection[hazard ratio(HR):1.984,95%CI:1.03-3.30,P=0.04],confirmed on Kaplan-Meier curve.On multivariable analysis,IEM remained independently associated with acute rejection,even after controlling for potential confounders such as the presence of acid and nonacid reflux(HR:2.20,95%CI:1.18-4.11,P=0.01).Nonacid reflux was also independently associated with acute rejection on both univariate(HR:2.16,95%CI:1.26-3.72,P=0.005)and multivariable analyses(HR:2.10,95%CI:1.21-3.64,P=0.009),adjusting for the presence of IEM.CONCLUSION Pre-transplant IEM was associated with acute rejection after transplantation,even after controlling for acid and nonacid reflux.Esophageal motility testing may be considered in lung transplant to predict outcomes.

Intraoperative care of elderly patients with COVID-19 undergoing double lung transplantation:Two case reports

BACKGROUND Lung transplantation is considered an effective method for treating patients with end-stage coronavirus disease 2019(COVID-19).The nurses play a pivotal role in lung transplantation for COVID-19 patients.CASE SUMMARY Two elderly patients were admitted to the emergency department due to cough,and the nucleic acid test was positive.The patients were preliminarily diagnosed with COVID-19.The chest computed tomography scan revealed massive lung consolidation,and the patients did not improve after treatment with antiviral drugs,glucocorticoids,antibiotics,and other drugs.Under the support of pure oxygen in extracorporeal membrane oxygenation,the patients’oxygen levels were still poor,indicating that they were in the terminal stage of viral pneumonia.The patients underwent double-lung transplantation and received intraoperative care.The extracorporeal membrane oxygenation device was removed within a week of the surgical procedure,and the respiratory circulation of the patients were stabilized.CONCLUSION High-quality care for COVID-19 patients undergoing lung transplantation ensures patient safety during operation while protecting the safety of the medical staff.

Acute postoperatory visual loss following bilateral lung transplantation surgery:a case series

Dear Editor,I am Rosa Gutiérrez Bonet,former ophthalmology resident at Puerta de Hierro University Hospital,Madrid,Spain.I write to present four cases of cortical blindness（CB）after bilateral lung transplant（LT）.

An Efficient Allocation for Lung Transplantation Using Ant Colony Optimization

A relationship between lung transplant success and many features of recipients’/donors has long been studied.However,modeling a robust model of a potential impact on organ transplant success has proved challenging.In this study,a hybrid feature selection model was developed based on ant colony opti-mization(ACO)and k-nearest neighbor(kNN)classifier to investigate the rela-tionship between the most defining features of recipients/donors and lung transplant success using data from the United Network of Organ Sharing(UNOS).The proposed ACO-kNN approach explores the features space to identify the representative attributes and classify patients’functional status(i.e.,quality of life)after lung transplantation.The efficacy of the proposed model was verified using 3,684 records and 118 input features from the UNOS.The developed approach examined the reliability and validity of the lung allocation process.The results are promising regarding accuracy prediction to be 91.3%and low computational time,along with better decision capabilities,emphasizing the potential for automatic classification of the lung and other organs allocation pro-cesses.In addition,the proposed model recommends a new perspective on how medical experts and clinicians respond to uncertain and challenging lung alloca-tion strategies.Having such ACO-kNN model,a medical professional can sum-marize information through the proposed method and make decisions for the upcoming transplants to allocate the donor organ.

Risk Factors of Post-Operative Extracorporeal Membrane Oxygenation Support after Lung Transplantation: A Retrospective Analysis

Background: Extracorporeal membrane oxygenation (ECMO) is an effective adjuvant therapy for cardiopulmonary support during the period of lung transplantation (LTx). However, factors associated with the application of ECMO after LTx remain controversial. The purpose of this study is to clarify the risk factors of post-operative ECMO support and to evaluate the outcomes. Methods: It was a hospital, single-center, retrospective study. 266 patients underwent LTx supported by ECMO were included. According to whether or not the patients received continourly ECMO support after the surgery, the enrolled patients were further divided into intra-operative ECMO group (group I, 105 cases) and post-operative ECMO group (group P, 161 cases). The peri-operative data of the donors and recipients were collected. The independent risk factors associated with post-operative ECMO support during LTx were identified. The relationship between primary graft dysfunction (PGD)/post-operative survival and duration of ECMO support was also analyzed. Results: Prolonged donor ventilation ≥ 5 days, pre-operative recipient mechanical ventilation, bilateral lung transplantation (BLT), veno-venous (V-V) ECMO and PGD in recipient were independent risk factors for post-operative ECMO support. The risk of PGD and post-operative death increased along with the increase of ECMO bypass time, and the mortality risk in group P was 2.33 (95% confidence interval: 1.16 - 4.67) times as that in group I. Conclusions: Mechanical ventilation for donor ≥ 5 days, pre-operative mechanical ventilation, BLT, V-V-ECMO and PGD in recipient were independent risk factors for post-operative ECMO support after LTx, and post-operative ECMO could not reduce recipients’ hospital mortality.

Diaphragmatic Plication for Patients with Acute Phase Phrenic Nerve Paralysis Following Lung Transplantation: A Case Report

Phrenic nerve injury can occur as a complication of lung transplantation. A 54-year-old man underwent single-lung transplantation due to interstitial pneumonia. The patient required circulatory support with venoarterial extracorporeal membrane oxygenation and was unable to be weaned from ventilatory support with nitric oxide. Although enhanced CT scanning showed stenotic anastomosis of the right pulmonary artery (PA), pulmonary angiograph findings revealed that PA flow was normal under sedation and considerably decreased with spontaneous breathing. Fluoroscopy showed that the right diaphragm moved inversely to the position of the left diaphragm, indicating that the right phrenic nerve was paralytic. We performed diaphragmatic plication 7 days after lung transplantation and weaning from ventilator support was accomplished soon thereafter. Phrenic nerve dysfunction is an important clinical problem following lung transplantation. In the present case, diaphragmatic plication was effective for treatment of circulatory failure due to phrenic nerve paralysis even in acute phase after lung transplantation.

Expression of bradykinin as a substrate of CD26 /DPP IV in rats ischemia/reperfusion injury following lung transplantation

Objective To investigate the expression of bradykinin as a substrate of CD26 /DPP IV in rats with ischemia/reperfusion injury following lung transplantation ( LTx) . Methods Thirty - six syngeneic male SD rats were randomly allocated into control group and experimental group ( n = 18 each) ,and 36 rats served as do-

Evaluate of transesophageal echocardiography during lung transplantation

Objective To investigate the clinical value of transesophageal echocardiography during the lung transplantation. Methods From August 2005 to August 2009, 19 patients with advanced lung diseases received lung transplantation. The average age was (48. 35 ± 13. 04) years. The echocardiographic probe was placed in patient’ s esophagus before surgery. The left and right

Clinical analysis of 100 cases of lung transplantation for end-stage palmonary disease

Objective To estimate the indications,operative technique,perioperative treatment,postoperative complications and the outcome of lung transplantation ( LTx) for end - stage pulmonary diseases. Methods The clinical data of 100 patients with end - stage lung diseases receiving LTx in our hospital were retrospectively ana-

Successful Tacrolimus Therapy Extended by Everolimus in Retroperitoneal Angiomyolipoma after Lung Transplantation:A Case Report

Lymphangioleiomyomatosis (LAM) is a rare disease that affects women, especially in child-bearing age. Clinical manifestations include angiomyolipoma, pneumothorax, chylothorax, cystic changes of lungs and progressive pulmonary failure. In this article, we report a case of lung transplantation (LuTX) for end stage pulmonary LAM and the treatment of angiomyolipoma showing growth after LuTX resulting in complete remission with combination therapy of everolimus and tacrolimus.

Success of intravenous immunoglobulin and steroids in managing severe COVID-19 following lung transplantation:A case report

BACKGROUND Coronavirus disease 2019(COVID-19)pneumonia with severe septic shock and acute respiratory distress syndrome(ARDS)are critical illnesses for patients following transplant.Intravenous immunoglobulin(IVIG)plays a role in both immune support and inflammation control,especially in immunocompromised patients.This case report describes the first successful experience using IVIG and pulse steroids to manage this critical condition following lung transplantation.CASE SUMMARY A 65-year-old male patient reported a history of chronic obstructive pulmonary disease and poor lung function and received bilateral sequential lung transplantations.Postoperatively,he developed COVID-19 pneumonia,severe septic shock,and ARDS.He recovered from this critical condition after empirical antibiotics administration and veno-venous extracorporeal membrane oxygenation,in addition to IVIG and pulse steroids.CONCLUSION IVIG is a valuable adjunct in managing severe sepsis in lung transplant recipients after COVID-19 infection.We aim,for the first time,to report the success of such a management approach for COVID-19 ARDS and sepsis in the post-lung transplant setting.With further investigations,this is a starting point for wider analysis of such an approach in this setting and consequently helps guide clinical practice for such a challenging patient population moving forward.

Lung transplantation in China between 2015 and 2018

Background:Lung transplantation(LT)has been demonstrated as the only effective therapy for patients with end-stage lung diseases.Increasing listed lung transplant candidates and expanding volumes of lung transplant centers across China require wellorganized programs and registry data collection based on the large population.This study aimed to summarize and analyze the data of LT development in China.Methods:We retrospectively collected and analyzed data from the China Lung Transplantation Registry(CLuTR).Key data were reported from the registry with transplant types,indications,donor and recipient characteristics,outcomes and survival.The survival<30 days,1-year and 3-year survival rates were estimated with risk factors identified.Results:CLuTR contained data from 1053 lung transplants performed through January 1st,2015 to December 31st,2018 reported by 18 registered transplant centers.The largest category of diagnosis before transplantation was idiopathic interstitial pneumonitis.The total<30 days,1-year and 3-year survival rates in CLuTR were 81.45%,70.11%,and 61.16%with discrepancy by indications.Large proportion of recipients who were more than 60 years old required higher standard of care.Infection-related complications resulted in more death events in the early post-surgery periods.New York Heart Association grading at listing,extra-corporeal membrane oxygenation usage peri-transplantation,allograft dysfunction(primary graft dysfunction>Grade 0),renal insufficiency(estimated glomerular filtration rate<60 mL min_11.73 m^2),were independently associated with a higher risk for 3-year mortality in the entire cohort.Conclusions:Facing more end-stage of lung diseases and comorbidities,this study analyzed the outcomes and survival of LT recipients in China.Further prospectively stratified analyses with longer follow-up will be needed.