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

Background: Primary graft dysfunction (PGD) is a risk factor for chronic lung allograft dysfunction (CLAD). However, the association between PGD and degree of allograft injury remains poorly defined. In this study, we leverage a novel biomarker for allograft injury, percentage donor-derived cell-free DNA (%ddcfDNA), to study the association between PGD, degree of allograft injury, and the development of CLAD., Methods: This prospective cohort study recruited 99 lung transplant recipients and collected plasma samples on days 1, 3, and 7 for %ddcfDNA measurements. Clinical data on day 3 was used to adjudicate for PGD. %ddcfDNA levels were compared between PGD grades. In PGD patients, %ddcfDNA was compared between those who developed CLAD and those who did not., Results: On posttransplant day 3, %ddcfDNA was higher in PGD than in non-PGD patients (median [IQR]: 12.2% [8.2, 22.0] vs 8.5% [5.6, 13.2] p = 0.01). %ddcfDNA correlated with the severity grade of PGD (r = 0.24, p = 0.02). Within the PGD group, higher levels of %ddcfDNA correlated with increased risk of developing CLAD (log OR(SE) 1.38 (0.53), p = 0.009). PGD patients who developed CLAD showed ∼2-times higher %ddcfDNA levels than patients who did not develop CLAD (median [IQR]: 22.4% [11.8, 27.6] vs 9.9% [6.7, 14.9], p = 0.007)., Conclusion: PGD patients demonstrated increased early posttransplant allograft injury, as measured by %ddcfDNA, in comparison to non-PGD patients, and these high %ddcfDNA levels were associated with subsequent development of CLAD. This study suggests that %ddcfDNA identifies PGD patients at greater risk of CLAD than PGD alone., (Published by Elsevier Inc.)

Background: The main cause of chronic renal allograft dysfunction (CRAD) still remains unclear. Insulin resistance (IR) may be a potential inducement, but there is insufficient evidence about this association. We aimed to establish a rat model of CRAD complicated with IR and to explore the function and pathologic changes of the renal allograft induced by IR., Methods: F344-to-Lewis rats of CRAD were fed a high-fat diet to induce IR. They were divided into 3 groups: IR (CRAD+IR), CRAD, and control (CTL). Serum levels of blood urea nitrogen (BUN) and serum creatinine (Scr) were measured to evaluate the renal function. The Homeostasis Model Assessment (HOMA)-IR index was detected by comparing the values of fasting serum insulin levels (FINS) with fasting blood glucose levels (FBG). The pathologic analysis was conducted by the degree of renal lesions including glomerular lesions, renal tubular lesions, hemorrhage, inflammatory cell infiltration, fibrillation, and hyperplasia of the renal interstitium., Results: In the second, third, and fourth month after surgery, serum levels of Scr and BUN in the IR group were reduced more than those in the CRAD group, while they were both higher compared to the CTL group, suggesting that renal function in the CRAD group was declined. The HOMA-IR in the IR group was greater than that in the CRAD and CTL groups, showing that simple high-fat diet feeding significantly and steadily increased FINS and FBG in CRAD complicated with IR rats. Pathologic changes indicated that the CRAD rat model was successfully constructed and was still in the early-middle stages of renal lesions 4 months after surgery, yet IR presented a significant effect on CRAD., Conclusion: These results indicate that the stable CRAD complicated with IR rat model can be established through a high-fat diet in CRAD rats in 4 months, and IR could be an influencing factor., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Background and Aim: Diarrhea in kidney transplant recipients influences outcome of transplantation. Data from India in this regard are sparse and do not address the differential outcome of infective and non-infective diarrhea. We studied the demographic data, laboratory findings, treatment response, disease duration, and outcome of diarrhea in kidney transplant recipients, and the differential outcome between infective and non-infective diarrhea, if any., Methods: All kidney transplant recipients who were referred to the Division of Gastroenterology with diarrhea between June 2015 and February 2017 were prospectively included. Demographic, clinical and laboratory data, graft function, treatment administered, and outcome were noted, and the patients were followed up for 3 months., Results: Forty-seven patients (median age 45 years, range 16-78; 34 men) with 64 episodes of diarrhea were studied. Thirty-three (51.5%) episodes were attributed to infections. Eleven (17%) were immunosuppressant-induced (mycophenolate 8, tacrolimus 2, cyclosporine 1). Twenty (31%) were due to other causes (antibiotics 6, laxatives 3, irritable bowel syndrome 3, sepsis 8). Fifty-three episodes (82%) had graft dysfunction during the diarrheal episodes. Mean increase in serum creatinine was 45% in the infectious diarrhea group and 95% in the non-infectious diarrhea group (p < 0.05). Median time to resolution of diarrhea was 3 days. With improvement in diarrhea, return to pre-diarrhea creatinine levels occurred in 87% of episodes at 3 months., Conclusion: One-half of episodes of diarrhea in kidney transplant recipients were non-infectious in origin. Seventeen percent were attributed to immunosuppressants, requiring dose modification. More than 80% were associated with worsening of graft function. Recovery of graft function to baseline was seen in a majority of cases with the resolution of diarrhea.

Background: Predicting the development of early allograft dysfunction (EAD) following liver transplantation (LT) remains challenging for transplant clinicians. The objectives of this study are to investigate the potential relationship between the protein profiles of pretransplant grafts and the onset of EAD, and then combine with clinical parameters to construct a mathematically predictive model., Methods: Clinical data of 121 LT procedures from donation after circulatory death at the authors' center were analyzed. The expression levels of 7 studied proteins were determined by immunohistochemistry. Another independent cohort of 37 subjects was designed for further validation of the predictive model., Results: With an incidence of 43.0% (52/121), EAD was linked to significantly increased risk of acute kidney injury and renal replacement therapy, as well as reduced 6-month patient and liver graft survival. Allograft weight and high intrahepatic vascular endothelial growth factor (VEGF) expression were identified as independent risk factors of EAD and survival outcomes. Liver grafts with high VEGF expression exhibited delayed functional recovery within the first postoperative week. The combination of VEGF overexpression and EAD yielded the highest frequency of renal dysfunction and the worst survival. Based on allograft weight and intrahepatic VEGF expression, an EAD risk assessment model was developed. The incidence of EAD differed significantly between grafts with risk scores ≥-1.72 and <-1.72. The model functioned well in the validation cohort., Conclusions: Pretransplant intrahepatic protein profiling contributes to the estimation of early graft performance and recipient outcomes following LT. The predictive model could allow for an accurate prediction of EAD.

Background: A unified definition of primary graft dysfunction (PGD) after heart transplantation was adopted in 2014, with moderate and severe PGD defined as a need for mechanical circulatory support. While risk factors for PGD are well identified, outcomes and resource utilization have not been well-studied. We examined the resource utilization and associated costs with PGD., Methods: All adult heart transplantations (2001-2016) from a statewide Society of Thoracic Surgery database were analyzed by dividing them into two groups-with PGD (requiring mechanical circulatory support) and without PGD., Results: Of the 718 heart transplants, 110 (15.3%) patients developed PGD. Prevalence of PGD for the study duration ranged from 3.7% to 22.7% with no significant trend. The most frequently used mechanical circulatory support device was intra-aortic balloon pump (88%), followed by extracorporeal membrane oxygenation (17%), and catheter-based circulatory support devices (3%). There were no significant differences in demographics or preoperative variables between the two groups. Resource utilization such as total intensive care unit hours, ventilation hours, reoperation for bleeding, blood product transfusions, and length of stay were significantly higher in the PGD group. Postoperative complications were also higher in PGD group including operative mortality (31.8% vs 3.8%, P < .0001). The median cost of heart transplantation was significantly higher in the PGD group $229 482 ($126 044-$388 889) vs $101 788 ($72 638-$181 180) P < .0001., Conclusion: Primary graft dysfunction following heart transplantation developed in 15% of patients. Patients with PGD had significantly higher complications, resource utilization, and mortality. Preventive measures to address the development of PGD would reduce resource utilization and improve outcomes., (© 2019 Wiley Periodicals, Inc.)

Chronic allograft dysfunction (CAD), defined as the replacement of functional renal tissue by extracellular matrix proteins, remains the first cause of graft loss. The aim of our study was to explore the potential role of the cannabinoid receptor 1 (CB1) during CAD. We retrospectively quantified CB1 expression and correlated it with renal fibrosis in 26 kidney-transplanted patients who underwent serial routine kidney biopsies. Whereas CB1 expression was low in normal kidney grafts, it was highly expressed during CAD, especially in tubular cells. CB1 expression significantly increased early on after transplantation, from day 0 (D0) to month 3 post-transplant (M3) (22.5% ± 15.4% vs 33.4% ± 13.8%, P < .01), and it remained stable thereafter. CB1 expression correlated with renal fibrosis at M3 (P = .04). In an in vitro model of tacrolimus-mediated fibrogenesis by tubular cells, we found that tacrolimus treatment significantly induced mRNA and protein expression of CB1 concomitantly to col3a1 and col4a3 up regulation. Administration of rimonabant, a CB1 antagonist, blunted collagen synthesis by tubular cells (P < .05). Overall, our study strongly suggests an involvement of the cannabinoid system in the progression of fibrosis during CAD and indicates the therapeutic potential of CB1 antagonists in this pathology., (© 2019 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.)

We aimed to assess the main causes of intensive care unit (ICU) readmissions in lung transplant adults and to identify independent predictors of ICU mortality (primary end-point).This Spanish five-centre prospective cohort study enrolled all lung transplant adults with ICU readmissions after post-transplant ICU discharge between 2012 and 2016. Patients were followed until hospital discharge or death.153 lung transplant recipients presented 174 ICU readmissions at a median (interquartile range) of 6 (2-25) months post-transplant. Chronic lung allograft dysfunction was reported in 39 (25.5%) recipients, 13 of whom (all exitus) had restrictive allograft syndrome (RAS). Acute respiratory failure (ARF) (110 (71.9%)) was the main condition requiring ICU readmission. Graft rejection (six (5.4%) acute) caused only 12 (10.8%) readmissions whereas pneumonia (56 (36.6%)) was the main cause (50 admitted for ARF and six for shock), with Pseudomonas aeruginosa (50% multidrug resistant) being the predominant pathogen. 55 (35.9%) and 69 (45.1%) recipients died in the ICU and the hospital, respectively. Bronchiolitis obliterans syndrome (BOS) stage 2 (adjusted OR (aOR) 7.2 (95% CI 1.0-65.7)), BOS stage 3 (aOR 13.7 (95% CI 2.5-95.3)), RAS (aOR >50) and pneumonia at ICU readmission (aOR 2.5 (95% CI 1.0-7.1)) were identified in multivariate analyses as independent predictors of ICU mortality. Only eight (5.2%) patients had positive donor-specific antibodies prior to ICU readmission and this variable did not affect the model.ARF was the main condition requiring ICU readmission in lung transplant recipients and was associated with high mortality. Pneumonia was the main cause of death and was also an independent predictor. RAS should receive palliative care rather than ICU admission., Competing Interests: Conflict of interest: C. Mazo has nothing to disclose. Conflict of interest: T. Pont has nothing to disclose. Conflict of interest: M.A. Ballesteros has nothing to disclose. Conflict of interest: E. López has nothing to disclose. Conflict of interest: L. Rellán has nothing to disclose. Conflict of interest: J.C. Robles has nothing to disclose. Conflict of interest: J. Rello has nothing to disclose., (Copyright ©ERS 2019.)

Objectives: The use of 'marginal' hearts, such as from donors with diabetes mellitus (DM), could offer an opportunity to expand the donor pool in cardiac transplantation. Previous studies have shown that the phosphatidylinositol-3-kinase (PI3K)/Akt pathway is altered after ischaemia/reperfusion injury in the diabetic myocardium. We hypothesized that DM-induced cardiac dysfunction in donors is further impaired after heart transplantation and that PI3K/Akt-pathway alterations may be one of the underlying pathomechanisms., Methods: In the donor rats, DM was induced with a single dose of streptozotocin. Non-diabetic rats only received citrate buffer. After 8 weeks, the donor left ventricular (LV) cardiac function was measured. Then, the hearts were heterotopically transplanted into non-diabetic recipients. We evaluated LV graft function 1.5 h after transplantation via a Millar catheter system at different LV volumes. Histological analyses were performed, and the expression of 84 genes involved in PI3K/Akt signalling was profiled., Results: DM was associated with significantly decreased LV contractility and impaired relaxation. After transplantation, in the DM group, the grafts' systolic function (LV systolic pressure 112 ± 31 vs 155 ± 60 mmHg; dP/dtmax 2676 ± 896 vs 3584 ± 1779 mmHg/s, P < 0.05) and diastolic function (dP/dtmin 924 ± 205 vs 1748 ± 512 mmHg/s, P < 0.05) were significantly reduced at an intraventricular volume of 170 µl. The expression of 10 genes involved in PI3K/Akt signalling, as well as the phosphorylated Akt/total Akt protein expression ratio, were significantly down-regulated in the diabetic heart after transplantation., Conclusions: DM-induced cardiac dysfunction is further impaired after transplantation. Targeting the PI3K/Akt pathway may result in a functional amelioration of the a priori-diseased myocardia, which could increase the number of potential cardiac donors.

Bronchial anastomotic breakdown was a major complication in the early days of lung transplantation. Their solution, achieved through an understanding of airway ischemia from the laboratory, was key to the initial clinical success. Subsequently, risk factors, such as prolonged ventilation in both donor and recipient, primary graft dysfunction, and recipient age, have emerged. Innovations, such as local tissue wrapping, telescoping the anastomosis, and bronchial artery revascularization, have not stood the test of time. The short donor bronchus, with a suture line at the level of the lobar bronchus carina, is a proven technique that should be adopted by surgeons., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: Early allograft dysfunction may be caused by several technical factors including vascular complications such as thrombosis, kinking, or extrinsic compression. Renal allograft compartment syndrome (RACS) is an unrecognized cause of early allograft dysfunction. This complication is characterized by increased pressure of the iliac fossa that reduces the blood supply to the graft with a potentially devastating consequence. The main objective when recognizing this condition is to create a tension-free muscle closure. Many approaches have been proposed involving mesh such as the mesh hood fascial closure technique. 1-4 PATIENT AND METHODS: We describe in the video an RACS during an operation. The recipient is a 23-year-old young man with a body mass index of 22, with renal failure secondary to chronic reflux. Past history of failure to peritoneal dialysis currently on hemodialysis. He received a living donor's kidney. After performing a standard anastomosis, his urine output was brisk. The fascia was then closed with no force, at which point he stopped making urine. A RACS was suspected; intraoperative examination and ultrasound showed no flow in the graft, with no signs of kinking. Immediately, reexploration was performed, showing the graft with abnormal color and turgor. After relieving the pressure, the graft returned to normal. The closure was redone with a large ellipsoid piece of polypropylene mesh draped loosely and without tension over the graft., Results: A Doppler ultrasound, after the skin closure was performed, showed good flow, and the postoperative course was unremarkable. There was minimal bulking in the right iliac area, making it cosmetically acceptable., Conclusion: RACS could be associated with a lack of compliance in the retroperitoneal cavity. 5 The RACS required a prompt intervention. The timely suspicion is a watershed in the prognosis of this rare pathology. We propose that mesh hood fascial closure is easy, effective, and a safe method to treat these complications., (Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.)

Objectives: Refractory hypoxaemia is the leading cause of mortality in the postoperative period after lung transplantation. The role of prone positioning as a rescue therapy in this setting has not been assessed. We evaluated its effects in lung transplant recipients presenting refractory hypoxaemia following the surgery., Methods: Prospectively collected data from 131 consecutive adult patients undergoing lung transplantation between January 2013 and December 2014 were evaluated. Twenty-two patients received prone position therapy. Indications, associated complications, time to initiation and duration of the manoeuvre were analysed and the effects of prone position on gas exchange were evaluated. Finally, outcomes in this cohort were compared against the rest of lung transplant recipients., Results: Prone positioning was more frequently implemented within the first 72 h (68.2%) and its main indication was primary graft dysfunction. The manoeuvre was maintained during a median of 21 h. After prone position, the pressure of arterial oxygen/fraction of inspired oxygen ratio significantly increased from 81.0 mmHg [interquartile range (IQR) 71.5-104.0] to 220.0 (IQR 160.0-288.0) (P < 0.001). No complications related with the technique were reported. Patients who underwent the manoeuvre had longer hospital stay [50.0 days (IQR 36.0-67.0) vs 30.0 (IQR 23.0-56.0), P = 0.006] than the rest of the population. No differences were found comparing either 1-year mortality (9.1% vs 15.6%; P = 0.740) or 1-year graft function [forced expiratory volume in 1 second of 70.0 (IQR 53.0-83.0) vs 68.0 (IQR 53.5-80.5), P = 0.469]., Conclusions: Prone positioning is safe and significantly improves gas exchange in patients with refractory hypoxaemia after lung transplantation. It should be considered as a possible treatment in these patients., (© The Author 2017. Published by Oxford University Press on behalf of the European Association for Cardio-Thoracic Surgery. All rights reserved.)

Background: Prior studies have shown that patients with pulmonary fibrosis with mutations in the telomerase genes have a high rate of certain complications after lung transplantation. However, few studies have investigated clinical outcomes based on leukocyte telomere length., Methods: We conducted an observational cohort study of all patients with pulmonary fibrosis who underwent lung transplantation at a single center between January 1, 2007, and December 31, 2014. Leukocyte telomere length was measured from a blood sample collected before lung transplantation, and subjects were stratified into 2 groups (telomere length <10th percentile vs ≥10th percentile). Primary outcome was post-lung transplant survival. Secondary outcomes included incidence of allograft dysfunction, non-pulmonary organ dysfunction, and infection., Results: Approximately 32% of subjects had a telomere length <10th percentile. Telomere length <10th percentile was independently associated with worse survival (hazard ratio 10.9, 95% confidence interval 2.7-44.8, p = 0.001). Telomere length <10th percentile was also independently associated with a shorter time to onset of chronic lung allograft dysfunction (hazard ratio 6.3, 95% confidence interval 2.0-20.0, p = 0.002). Grade 3 primary graft dysfunction occurred more frequently in the <10th percentile group compared with the ≥10th percentile group (28% vs 7%; p = 0.034). There was no difference between the 2 groups in incidence of acute cellular rejection, cytopenias, infection, or renal dysfunction., Conclusions: Telomere length <10th percentile was associated with worse survival and shorter time to onset of chronic lung allograft dysfunction and thus represents a biomarker that may aid in risk stratification of patients with pulmonary fibrosis before lung transplantation., (Copyright © 2017 International Society for the Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)

The largest experience of pregnancy after solid organ transplantation is recorded in renal and liver recipients. Intestinal/multivisceral transplantation has shown steady improvements in graft and patient survival over the past 20 years and is rapidly becoming more established: the first pregnancy after this procedure was described 10 years ago, and so far eight cases of pregnancies with 100% successful live births have been reported worldwide. Specifically to this procedure, there are 2 factors to be considered in case of pregnancy: absorptive function of transplanted bowel and higher need of immune-suppressants. Close monitoring of renal function and of the graft by endoscopies and biopsies can be considered during the pregnancy to prevent episodes of rejection or enteritis, preserving the fetus by temporary malnutrition. As more intestinal transplant patients are surviving and regaining reproductive function, it is important to report this option to female recipients and to their health-care professionals.

Background: Chronic allograft dysfunction (CAD) is a main cause of graft failure in kidney transplantation., Methods: We retrospectively analyzed 279 kidney transplant recipients who survived with a functioning graft for at least 2 years. CAD was defined as chronic graft deterioration, excluding other specific causes. We defined the pattern of decline in estimated glomerular filtration rate (eGFR), as follows: (1) "plateau" was defined as decline in eGFR ≤2 mL/min/1.73 m 2 /year; "long plateaus" were those lasting more than 5 years; (2) "rapid decline" was a decrease in eGFR ≥20 mL/min/1.73 m 2 /year. Patients diagnosed with CAD were categorized according to the occurrence of rapid decline and/or long plateau as follows: group 1, neither rapid decline nor long plateau; group 2, rapid decline only; group 3, long plateau only; and group 4, both rapid decline and long plateau., Results: From a total of 81 graft losses, 51 (63%) failed because of CAD, with a median of 9.4 years. Sixteen patients belonged to group 1, 14 to group 2, 12 to group 3, and nine to group 4. Mean graft survival times in the four groups were 7.7 ± 1.1, 6.1 ± 3.1, 16.2 ± 2.5, and 10.8 ± 3.6 years, respectively (P < .001). There were significant differences among groups in donor age, year of transplantation, mean eGFR at baseline, and acute rejection rate after transplantation., Conclusions: The results indicate that this cohort of kidney transplant recipients who had CAD comprised subgroups with different clinical courses., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Lung transplantation (LTx) is a well-established treatment for end-stage pulmonary disease. However, data regarding microbiology and outcome of patients with non-cystic fibrosis bronchiectasis (NCFB) after lung transplantation are limited., Methods: A retrospective analysis between August 1992 and September 2014 of all patients undergoing lung transplantation at our program of all recipients with a primary diagnosis of bronchiectasis was performed. Microbiology of sputum and bronchoalveolar lavage specimens, lung function and clinical parameters pre- and post-LTx were assessed retrospectively. Overall survival was compared to the total cohort of lung transplant recipients at institution. The survival and development of chronic lung allograft dysfunction (CLAD) was compared in patients with and without chronic Pseudomonas aeruginosa (PSA) infection after LTx., Results: 34 patients were transplanted. Median age at transplantation was 40 (IQR 33-52) years. The most common etiologies of bronchiectasis were idiopathic (41%), chronic obstructive pulmonary disease (COPD) (21%) and post-infectious (15%). The most common organism of pre- and posttransplant chronic airway infection was PSA. One-year Kaplan-Meier survival for patients with bronchiectasis was 85% and 5-year survival was 73% and similar to the entire cohort. All three patients with an associated diagnosis of immunodeficiency died due to infection and sepsis within the first year. Patients with persistent colonization with Pseudomonas aeruginosa after transplantation had worse long-term survival by trend and developed chronic lung allograft dysfunction more frequently., Conclusions: Overall survival of patients with bronchiectasis after LTx is comparable to other underlying diseases. A reduced survival was observed in patients with the underlying diagnosis of immunodeficiency., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Heart transplantation is currently the definitive gold standard surgical approach in the treatment of refractory heart failure. However, the shortage of donors limits the achievement of a greater number of heart transplants, in which the use of mechanical circulatory support devices is increasing. With well-established indications and contraindications, as well as diagnosis and treatment of rejection through defined protocols of immunosuppression, the outcomes of heart transplantation are very favorable. Among early complications that can impact survival are primary graft failure, right ventricular dysfunction, rejection, and infections, whereas late complications include cardiac allograft vasculopathy and neoplasms. Despite the difficulties for heart transplantation, in particular, the shortage of donors and high mortality while on the waiting list, in Brazil, there is a great potential for both increasing effective donors and using circulatory assist devices, which can positively impact the number and outcomes of heart transplants.

Objective: To investigate the roles and underlying mechanism of an inflammatory mediator-lipocalin-2 (Lcn2) in small-for-size fatty graft liver injury., Background: Understanding of the distinct mechanism regulating small-for-size fatty liver graft injury will be crucial to prevent marginal graft failure during living donor liver transplantation (LDLT)., Methods: The roles of Lcn2 in small fatty graft injury were investigated in orthotopic liver transplantation model rats, human LDLT samples, an in vitro simulated ischemia-reperfusion (IR) model, and a hepatic ischemic reperfusion plus major hepatectomy (IR + H) model in mice., Results: Our result showed that Lcn2 was significantly upregulated together with elevation of chemokine (C-X-C motif) ligand 10 (CXCL10) and activation/infiltration of intragraft macrophages after liver transplantation using small-for-size fatty liver graft compared with that of using small-for-size normal liver graft. Intragraft and plasma levels of Lcn2 were intensified in patients who underwent transplantation with small-for-size fatty graft after LDLT. Lcn2 and CXCL10 were expressed higher in fatty hepatocytes after the simulated IR injury compared with normal hepatocytes. Overexpression of Lcn2 significantly deteriorated IR + H-induced hepatic injury in correlation with upregulation of CXCL10 and augmentation of infiltrated macrophages. On the contrary, hepatic injury of small fatty liver remnant after IR + H operation was attenuated in the Lcn-2 mice because of suppression of CXCL10 expression and diminishment of macrophage infiltration., Conclusions: Lcn2 is an important regulator in small-for-size fatty liver graft injury and targeting Lcn2 may be feasible for preventing marginal graft failure in LDLT.

Primary graft dysfunction is a leading cause of morbimortality in the immediate postoperative period of patients undergoing lung transplantation. Among the treatment options are: lung protective ventilatory strategies, nitric oxide, lung surfactant therapy, and supportive treatment with extracorporeal membrane oxygenation (ECMO) as a bridge to recovery of lung function or re-transplant. We report the case of a 9-year-old girl affected by cystic fibrosis who underwent double-lung transplantation complicated with a severe primary graft dysfunction in the immediate postoperative period and refractory to standard therapies. Due to development of multiple organ failure, it was decided to insert arteriovenous ECMO catheters (pulmonary artery-right atrium). The postoperative course was satisfactory, allowing withdrawal of ECMO on the 5th post-surgical day. Currently the patient survives free of rejection and with an excellent quality of life after 600 days of follow up., (Copyright © 2012 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Published by Elsevier España. All rights reserved.)

Thrombotic microangiopathy (TMA) is a life-threatening complication after transplantation including liver transplantation, and its typical clinical picture is characterized by hemolytic anemia, thrombocytopenia, renal dysfunction, neurological abnormalities, and fever. We report the case of a 56-year-old female with end-stage liver disease who underwent living donor liver transplantation (LDLT), and whose postoperative course was characterized by renal failure and progressive hyperbilirubinemia. Two weeks after LDLT, she started to show progressive thrombocytopenia, anemia, oliguria, and encephalopathy. From these clinical manifestations, she was diagnosed as having TMA and underwent plasma exchanges with continuous hemodialysis under temporary holding calcineurin inhibitors. The patient promptly responded to the treatment, with improved hematological, hepatic, and renal conditions, and was discharged from hospital a month later in a stable condition. We describe this case of TMA after LDLT with poor graft function and extensively review the disease in liver transplant recipients.

Native renal infarction is uncommon in patients with atrial fibrillation (AF)-related thromboembolism. Graft infarction is also rare, with such cases mostly occurring in the main graft artery postoperatively. To date, there have been no studies of AF-related graft kidney infarction. We herein describe the first case of AF-related graft kidney infarction. The clinical manifestations of this condition mimic and follow those of acute pyelonephritis; therefore, these diseases should be differentially diagnosed as early as possible using lactic dehydrogenase testing and computed tomography. Aggressive treatment with intravascular thrombolysis should be administered, even when the diagnosis is delayed, in order to restore a viable renal function.

Purpose of Review: Lung transplantation (LTx) has become established as a standard intervention for patients suffering from end-stage lung disease. Transplant recipients are, however, predisposed to numerous unique complications arising from the surgery, transplant immunology and the lifelong medication. Clinicians working in intensive care are increasingly likely to be exposed to these patients and it is therefore important to have a working knowledge of the common complications., Recent Findings: Common complications encountered following LTx include primary graft dysfunction (PGD), airway complications, acute rejection, chronic lung allograft dysfunction (CLAD), thrombotic microangiopathy (TMA) and infection, all of which impact significantly on long-term survival. PGD arises in the first weeks following transplantation. Acute rejection, airway complications and TMA represent the main complications in the first posttransplantation year. CLAD usually occurs later, but continues to represent the main obstacle to long-term survival. Infection poses significant risk at all stages following transplantation and a full spectrum of bacterial, fungal and viral pathogens has been implicated., Summary: This review highlights the most important complications after LTx and gives an update on diagnostic algorithms and treatment challenges for patients following LTx.

Chronic allograft dysfunction is one of the most important reasons for late graft loss after renal transplantation. Its etiology is multifactorial and combines immunological as well as non-immunological mechanisms. It is known from large registry data that MHC mismatches are inversely correlated to long term allograft survival. Although this is a well known aspect, the mechanisms of MHC-driven graft damage and the impact of other immunological factors leading to chronic rejection are poorly understood. In patients it is impossible to study MHC mismatches without considering non-MHC differences. Further more common animal models for chronic rejection are all characterized by non-MHC as well as MHC disparities. To exclusively study MHC mediated immunoresponses we established a rat model of renal transplantation using congenic rat strains differing in their entire MHC class I and class II, but sharing the genetic background of the LEW rat. After an initial short term of immunosuppression all animals developed renal impairment with severe albuminuria. Half of the animals died of renal failure in week 7 to 14 and showed pathological characteristics of chronic allograft damage including IF/TA and severe glomerulopathy. The majority of these recipients developed circulating donor-specific MHC alloantibodies. Allografts were significantly infiltrated with T-cells, macrophages and NK-cells. We established a MHC congenic rat model to investigate immunological mechanisms of chronic renal allograft rejection exclusively induced by a complete MHC mismatch. We demonstrated humoral as well as cellular immunoresponses leading to chronic allograft loss in 50% of animals., (Copyright 2009 Elsevier B.V. All rights reserved.)