Incidence, risk factors and clinical outcome of multidrug-resistant organisms after heart transplantation

BACKGROUND Transplant recipients commonly harbor multidrug-resistant organisms(MDROs),as a result of frequent hospital admissions and increased exposure to antimi-crobials and invasive procedures.AIM To investigate the impact of patient demographic and clinical characteristics on MDRO acquisition,as well as the impact of MDRO acquisition on intensive care unit(ICU)and hospital length of stay,and on ICU mortality and 1-year mortality post heart transplantation.METHODS This retrospective cohort study analyzed 98 consecutive heart transplant patients over a ten-year period(2013-2022)in a single transplantation center.Data was collected regarding MDROs commonly encountered in critical care.RESULTS Among the 98 transplanted patients(70%male),about a third(32%)acquired or already harbored MDROs upon transplantation(MDRO group),while two thirds did not(MDRO-free group).The prevalent MDROs were Acinetobacter baumannii(14%),Pseudomonas aeruginosa(12%)and Klebsiella pneumoniae(11%).Compared to MDRO-free patients,the MDRO group was characterized by higher body mass index(P=0.002),higher rates of renal failure(P=0.017),primary graft dysfunction(10%vs 4.5%,P=0.001),surgical re-exploration(34%vs 14%,P=0.017),mechanical circulatory support(47%vs 26%P=0.037)and renal replacement therapy(28%vs 9%,P=0.014),as well as longer extracorporeal circulation time(median 210 vs 161 min,P=0.003).The median length of stay was longer in the MDRO group,namely ICU stay was 16 vs 9 d in the MDRO-free group(P=0.001),and hospital stay was 38 vs 28 d(P=0.006),while 1-year mortality was higher(28%vs 7.6%,log-rank-χ2:7.34).CONCLUSION Following heart transplantation,a predominance of Gram-negative MDROs was noted.MDRO acquisition was associated with higher complication rates,prolonged ICU and total hospital stay,and higher post-transplantation mortality.

Is low postoperative cholesterol level really an independent risk factor of adverse outcomes after living donor liver transplantation?

To the Editor:We read with great interest the article by Yang et al.[1]evaluating the effects of postoperative serum total cholesterol(s TC)changes on early allograft dysfunction and survival after living donor liver transplantation(LDLT).By the multivariate regression analysis,they showed that patients with s TC<1.42 mmol/L on postoperative day 3 had 4.08-fold and 2.72-fold greater risks of

Recipient functional status impacts on short and long-term intestinal transplant outcomes in United States adults

BACKGROUND Recipient functional status prior to transplantation has been found to impact post-transplant outcomes in heart,liver and kidney transplants.However,information on how functional status,before and after transplant impacts post-transplant survival outcomes is lacking.AIM To investigate the impact of recipient functional status on short and long term intestinal transplant outcomes in United States adults.METHODS We conducted a retrospective cohort study on 1254 adults who underwent first-time intestinal transplantation from 2005 to 2022.The primary outcome was mortality.Using the Karnofsky Performance Status,functional impairment was categorized as severe,moderate and normal.Analyses were conducted using Kaplan-Meier curves and multivariable Cox regression.RESULTS The median age was 41 years,majority(53.4%)were women.Severe impairment was present in 28.3%of recipients.The median survival time was 906.6 days.The median survival time was 1331 and 560 days for patients with normal and severe functional impairment respectively.Recipients with severe impairment had a 56%higher risk of mortality at one year[Hazard ratio(HR)=1.56;95%CI:1.23–1.98;P<0.001]and 58%at five years(HR=1.58;95%CI:1.24–2.00;P<0.001)compared to patients with no functional impairment.Recipients with worse functional status after transplant also had poor survival outcomes.CONCLUSION Pre-and post-transplant recipient functional status is an important prognostic indicator for short-and long-term intestinal transplant outcomes.

Artificial intelligence and liver transplantation:Looking for the best donor-recipient pairing

Decision-making based on artificial intelligence(AI)methodology is increasingly present in all areas of modern medicine.In recent years,models based on deep-learning have begun to be used in organ transplantation.Taking into account the huge number of factors and variables involved in donor-recipient(DR)matching,AI models may be well suited to improve organ allocation.AI-based models should provide two solutions:complement decision-making with current metrics based on logistic regression and improve their predictability.Hundreds of classifiers could be used to address this problem.However,not all of them are really useful for D-R pairing.Basically,in the decision to assign a given donor to a candidate in waiting list,a multitude of variables are handled,including donor,recipient,logistic and perioperative variables.Of these last two,some of them can be inferred indirectly from the team’s previous experience.Two groups of AI models have been used in the D-R matching:artificial neural networks(ANN)and random forest(RF).The former mimics the functional architecture of neurons,with input layers and output layers.The algorithms can be uni-or multi-objective.In general,ANNs can be used with large databases,where their generalizability is improved.However,they are models that are very sensitive to the quality of the databases and,in essence,they are black-box models in which all variables are important.Unfortunately,these models do not allow to know safely the weight of each variable.On the other hand,RF builds decision trees and works well with small cohorts.In addition,they can select top variables as with logistic regression.However,they are not useful with large databases,due to the extreme number of decision trees that they would generate,making them impractical.Both ANN and RF allow a successful donor allocation in over 80%of D-R pairing,a number much higher than that obtained with the best statistical metrics such as model for end-stage liver disease,balance of risk score,and survival outcomes following liver transplantation scores.Many barriers need to be overcome before these deeplearning-based models can be included for D-R matching.The main one of them is the resistance of the clinicians to leave their own decision to autonomous computational models.

Small for size syndrome difficult dilemma: Lessons from 10 years single centre experience in living donor liver transplantation

AIM To analyze the incidence, risk factors, prevention, treatment and outcome of small for size syndrome(SFSS) after living donor liver transplantation(LDLT). METHODS Through-out more than 10 years: During the period from April 2003 to the end of 2013, 174 adult-to-adults LDLT(A-ALDLT) had been performed at National Liver Institute, Menoufiya University, Shibin Elkoom, Egypt. We collected the data of those patients to do this cohort study that is a single-institution retrospective analysis of a prospectively collected database analyzing the incidence, risk factors, prevention, treatment and outcome of SFSS in a period started from the end of 2013 to the end of 2015. The median period of follow-up reached 40.50 m, range(0-144 m). RESULTS SFSS was diagnosed in 20(11.5%) of our recipients. While extra-small graft [small for size graft(SFSG)], portal hypertension, steatosis and left lobe graft were significant predictors of SFSS in univariate analysis(P = 0.00, 0.04, 0.03, and 0.00 respectively); graft size was the only independent predictor of SFSS on multivariate analysis(P = 0.03). On the other hand, there was lower incidence of SFSS in patients with SFSG who underwent splenectomy [4/10(40%) SFSS vs 3/7(42.9%) no SFSS] but without statistical significance, However, there was none significant lower incidence of the syndrome in patients with right lobe(RL) graft when drainage of the right anterior and/or posterior liver sectors by middle hepatic vein, V5, V8, and/or right inferior vein was done [4/10(28.6%) SFSS vs 52/152(34.2%) no SFSS]. The 6-mo, 1-, 3-, 5-, 7-and 10-year survival in patients with SFSS were 30%, 30%, 25%, 25%, 25% and 25% respectively, while, the 6-mo, 1-, 3-, 5-, 7-and 10-year survival in patients without SFSS were 70.1%, 65.6%, 61.7%, 61%, 59.7%, and 59.7% respectively, with statistical significant difference(P = 0.00). CONCLUSION SFSG is the independent and main factor for occurrence of SFSS after A-ALDLT leading to poor outcome. However, the management of this catastrophe depends upon its prevention(i.e., selecting graft with proper size, splenectomy to decrease portal venous inflow, and improving hepatic vein outflow by reconstructing large draining veins of the graft).

Microbiota,renal disease and renal transplantation

Aim of this frontier review has been to highlight the role of microbiota in healthy subjects and in patients affected by renal diseases with particular reference to renal transplantation.The microbiota has a relevant role in conditioning the healthy status and the diseases.In particular gut microbiota is essential in the metabolism of food and has a relevant role for its relationship with the immune system.The indigenous microbiota in patients with chronic renal failure is completely different than that of the healthy subjects and pathobionts appear.This abnormality in microbiota composition is called dysbiosis and may cause a rapid deterioration of the renal function both for activating the immune system and producing large quantity of uremic toxins.Similarly,after renal transplantation the microbiota changes with the appearance of pathobionts,principally in the first period because of the assumption of immunosuppressive drugs and antibiotics.These changes may deeply interfere with the graft outcome causing acute rejection,renal infections,diarrhea,and renal interstitial fibrosis.In addition,change in the microbiota may modify the metabolism of immunosuppressive drugs causing in some patients the need of modifying the immunosuppressant dosing.The restoration of the indigenous microbiota after transplantation is important,either to avoiding the complications that impair the normal renal graft,and because recent studies have documented the role of an indigenous microbiota in inducing tolerance towards the graft.The use of prebiotics,probiotics,smart bacteria and diet modification may restore the indigenous microbiota,but these studies are just at their beginning and more data are needed to draw definitive conclusions.

Assessment of advanced age candidates for liver transplantation warrants more caution

For patients with fulminant liver failure and end-stage liver disease,liver transplantation remains the only effective treatment.Over the years,as a result of the ageing population,the average age of liver transplant donors and recipients has increased and currently about one quarter of patients receiving transplantation in the United States are above the age of 65.Recently,a study reported that patients aged 65 years or older had lower one-year survival compared to a younger cohort.Herein,we express our opinion about this interesting publication.

Long-term clinical outcomes and health-related quality of life in patients with isolated methylmalonic acidemia after liver transplantation:experience from the largest cohort study in China

Background Liver transplantation(LT)has been proposed as a viable treatment option for selected methylmalonic acidemia(MMA)patients.However,there are still controversies regarding the therapeutic value of LT for MMA.The systematic assessment of health-related quality of life(HRQoL)-targeted MMA children before and after LT is also undetermined.This study aimed to comprehensively assess the long-term impact of LT on MMA,including multiorgan sequelae and HRQoL in children and families.Methods We retrospectively evaluated 15 isolated MMA patients undergoing LT at our institution between June 2013 and March 2022.Pre-and post-transplant data were compared,including metabolic profiles,neurologic consequences,growth parameters,and HRQoL.To further assess the characteristics of the HRQoL outcomes in MMA,we compared the results with those of children with biliary atresia(BA).Results All patients had early onset MMA,and underwent LT at a mean age of 4.3 years.During 1.3–8.2 years of follow-up,the patient and graft survival rates were 100%.Metabolic stability was achieved in all patients with liberalized dietary protein intake.There was a significant overall improvement in height Z scores(P=0.0047),and some preexisting neurological complications remained stable or even improved after LT.On the Pediatric Quality of Life Inventory(PedsQL™)generic core scales,the mean total,physical health,and psychosocial health scores improved significantly posttransplant(P<0.05).In the family impact module,higher mean scores were noted for all subscales post-LT,especially family function and daily activities(P<0.01).However,the total scores on the generic core scales and transplant module were significantly lower(Cohen’s d=0.57–1.17)when compared with BA recipients.In particular,social and school functioning(Cohen’s d=0.86–1.76),treatment anxiety,and communication(Cohen’s d=0.99–1.81)were far behind,with a large effect size.Conclusions This large single-center study of the mainland of China showed an overall favorable impact of LT on isolated MMA in terms of long-term survival,metabolic control,and HRQoL in children and families.The potential for persistent neurocognitive impairment and inherent metabolic fragility requires long-term special care.

Platelet transfusion refractoriness after T-cell-replete haploidentical transplantation is associated with inferior clinical outcomes

Haploidentical stem cell transplantation (haplo-SCT) has been an alternative source of bone marrow for patients without human leukocyte antigen (HLA)-matched donors. The aim of this study was to investigate the relationships between platelet transfusion refractoriness (PTR) and clinical outcomes in the setting of haplo-SCT. Between May 2012 and March 2014, 345 patients who underwent unmanipulated haplo-SCT were retrospectively enrolled. PTR occurred in 20.6% of all patients. Patients in the PTR group experienced higher transplant-related mortality (TRM, 43.7% vs. 13.5%, P<0.001), lower overall survival (OS, 47.9%vs. 76.3%, P<0.001) and lower leukemia-free survival (LFS, 47.9% vs. 72.3%, P<0.001) compared to patients in the non-PTR group. The multivariate analysis showed that PTR was associated with TRM (P=0.002), LFS (P<0.001), and OS (P<0.001).The cumulative incidences of PTR in patients receiving >12 platelet (PLT) transfusions (third quartile of PLT transfusions) were higher than in patients receiving either >6 (second quartile) or >3 (first quartile) PLT transfusions (56.1% vs. 41.6% vs. 28.2%,respectively; P<0.001). The multivariate analysis also showed that PTR was associated with the number of PLT transfusions(P<0.001). PTR could predict poor transplant outcomes in patients who underwent haploidentical SCT.

Does ischemia-free machine perfusion lead to early allograft dysfunction (EAD) free liver transplantation?

Normothermic machine perfusion(NMP)is an innovative technique used in solid organ transplantation that involves perfusing the organ with specialized solution or leukocyte depleted red blood cells at near-normal body temperature aiming at mimicking physiological conditions,and providing optimal conditions for organ preservation which leads to reduced risk of ischemia reperfusion injury(IRI)when compared to the standard static cold storage(SCS)(1).One of the key advantages of NMP is its ability to assess the quality of the organ in real-time and assessment of the organ performance prior to transplantation.By continuously monitoring parameters such as blood flow,oxygen consumption,and lactate production,clinicians can evaluate the viability of the organ and make more informed decisions about its suitability for transplantation.This real-time assessment can help reduce the risk of transplanting organs that may not function optimally or have a higher likelihood of complications post-transplant.Additionally,NMP may expand the pool of donor organs by allowing for the use of organs that may have been deemed marginal or unsuitable for transplantation using traditional methods(1,2).

The impact of HLA haplotype and alleles mismatches of donor-recipient pairs on outcome of haplo-identical hematopoietic stem cell transplantation with a third part cord blood unit

Objective To analyze allele mismatches of HLA-A,-B,-C,-DRB1,-DQB1 and haplotype mismatch of donor-recipient pairs on the outcome of haploidentical transplantation combined with a third part cord blood unit.Methods 230 pairs of donor-recipient were performed HLA-A,B,C,DRB1,DQB1 typing using

Current role in facial allograft transplantation:what have we learned?

Face transplant(FT)has evolved enormously in the last 10 years since the successful completion of the first facial transplant.This procedure has become a new reconstructive option for complex facial deformities to restore the anatomy of patients with severely disfigured faces.The authors review the literature and discuss the main surgical,immunological,and ethical aspects as well as the results described in patients undergoing FT.To date there have been more than thirty FT worldwide.The main indication was post-traumatic deformity.In all cases a standard immunosuppression was performed with three drugs,although acute rejection episodes were observed,that could be controlled with conventional immunosuppressive regimen.Overall,functional and aesthetic results have been excellent at short-term and high satisfaction rate exceeded initial expectations,although long-term data are still scarce.Major complications were opportunistic infections.Five deaths that occurred have reopened the ethical debate about the potential complications and concerns of providing informed consent to recipients.Continuous progresses in microsurgical techniques and preoperative planning have promoted the evolution from partial to full FT.All these are on the basis of accurate and careful selection of well-motivated candidates.The next challenge will be getting new immunosuppressive treatment strategies.Although clinical experience has demonstrated the FT viability,it is still considered an experimental procedure in which we have much to learn to define its true role in the current reconstructive surgery and resolve major technical,medical and ethical problems involved.