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  • Gao S
  • Huang X
  • Zhou X
  • Dai X
  • Han J
  • et al.
Ann Med. 2024 Dec;56(1):2314236 doi: 10.1080/07853890.2024.2314236.
BACKGROUND:

The burden of carbapenem-resistant gram-negative bacteria (CRGNB) among solid organ transplant (SOT) recipients has not been systematically explored. Here, we discern the risk factors associated with CRGNB infection and colonization in SOT recipients.

METHODS:

This study included observational studies conducted among CRGNB-infected SOT patients, which reported risk factors associated with mortality, infection or colonization. Relevant records will be searched in PubMed, Embase and Web of Science for the period from the time of database construction to 1 March 2023.

RESULTS:

A total of 23 studies with 13,511 participants were included, enabling the assessment of 27 potential risk factors. The pooled prevalence of 1-year mortality among SOT recipients with CRGNB was 44.5%. Prolonged mechanical ventilation, combined transplantation, reoperation and pre-transplantation CRGNB colonization are salient contributors to the occurrence of CRGNB infections in SOT recipients. Renal replacement therapy, post-LT CRGNB colonization, pre-LT liver disease and model for end-stage liver disease score increased the risk of infection. Re-transplantation, carbapenem use before transplantation and ureteral stent utilization increaesd risk of CRGNB colonization.

CONCLUSION:

Our study demonstrated that SOT recipients with CRGNB infections had a higher mortality risk. Invasive procedure may be the main factor contribute to CRGNB infection.

  • Jiang W
  • Xu Y
  • Yin Q
Ren Fail. 2024 Dec;46(1):2296000 doi: 10.1080/0886022X.2023.2296000.

To explore the effect of lupus nephritis (LN) on graft survival in renal transplant patients. Literature search was conducted in PubMed, EMBASE and Scopus database for randomized controlled trials (RCTs), cohort, and case-control studies. The target population of interest was adult patients (aged >18 years) with end-stage renal disease (ESRD) and no history of previous renal transplants. Primary outcomes of interest were graft survival and patient survival. Pooled effect estimates were calculated using random-effects models and reported as hazard ratio (HR) with 95% confidence intervals (CI). A total of 15 studies were included. Compared to patients with ESRD due to other causes, patients with LN undergoing kidney transplant had lower patient survival rate (HR 1.15, 95% CI: 1.01, 1.31; N = 15, I2=34.3%) and worse graft survival (HR 1.06, 95% CI: 1.01, 1.11; N = 16, I2=0.0%), especially when studies with deceased donor were pooled together. Studies with a larger sample size (>200) showed that LN was strongly associated with lower graft and patient survival rates. Elevated risk of mortality in LN patients was detected in case-control studies, but not RCTs. On the other hand, RCTs, but not case-control studies, showed an increased risk of poor graft survival in LN patients. The findings suggest that the presence of LN might have a negative impact on both the graft survival and the overall patient survival of post-transplant ESRD patients. Further studies that account for factors such as study methodology, donor characteristics, and sample size are needed to reach definitive conclusions. Renal transplant patients with LN should undergo regular follow-up examinations.

  • Albulushi A
  • Al-Riyami MB
  • Al-Rawahi N
  • Al-Mukhaini M
Curr Probl Cardiol. 2024 Jul;49(7):102579 doi: 10.1016/j.cpcardiol.2024.102579.
BACKGROUND:

Pulmonary hypertension (PH) poses a significant challenge in the selection of candidates for heart transplantation, impacting their eligibility and post-transplant outcomes. Mechanical circulatory support (MCS) devices, particularly left ventricular assist devices (LVADs), have emerged as a therapeutic option to manage PH in this patient population. This systematic review aims to evaluate the effectiveness of MCS devices in reversing fixed pulmonary hypertension in heart transplant candidates.

METHODS:

A comprehensive literature search was conducted across multiple databases, including PubMed, Scopus, and Web of Science, to identify studies that evaluated the effectiveness of MCS devices in reversing fixed pulmonary hypertension in heart transplant candidates. Data on pulmonary vascular resistance, PH reversal, heart transplant eligibility, and post-transplant outcomes were extracted and synthesized.

RESULTS:

The review included studies that demonstrated the potential of MCS devices, especially LVADs, to significantly reduce pulmonary vascular resistance and reverse fixed pulmonary hypertension in heart transplant candidates. These findings suggest that MCS devices can improve transplant eligibility and may positively impact post-transplant survival rates. However, the literature also indicates a need for further comparative studies to optimize MCS device selection and treatment protocols.

CONCLUSION:

MCS devices, particularly LVADs, play a crucial role in the management of fixed pulmonary hypertension in heart transplant candidates, improving their eligibility for transplantation and potentially enhancing post-transplant outcomes. Future research should focus on comparative effectiveness studies to guide clinical decision-making and optimize patient care in this challenging clinical scenario.

  • Torri F
  • Balzano E
  • Melandro F
  • Maremmani P
  • Bertini P
  • et al.
Transplantation. 2024 Jun 1;108(6):1394-1402 doi: 10.1097/TP.0000000000004963.
CET Conclusion
Reviewer: Mr Keno Mentor, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This study employed both normothermic regional perfusion (NRP) and ex-situ machine perfusion (MP) to liver grafts from DCD donors older than 70 years old. The authors hypothesised that the benefits of both reperfusion modalities could offset the higher risk due to advanced donor age. 11 livers were successfully transplanted and were functioning at a median follow up of 8 months. There was no control group, and the authors admit to being highly selective when recruiting donors to the study. This strong selection bias, combined with a short follow up period, means the results presented here do not demonstrate a clear benefit to the dual perfusion strategy.
Aims: This study aimed to report the safety and feasibility of using septuagenarian and octogenarian controlled donation after circulatory death (cDCD) donors in liver transplantation.
Interventions: Liver grafts were randomised to either ex situ dual hypothermic oxygenated machine perfusion (MP) or normothermic MP.
Participants: 11 cDCD (>70 years).
Outcomes: The main outcomes were primary nonfunction, ischemic cholangiopathy (IC), postreperfusion syndrome (PRS), early allograft dysfunction (EAD), acute kidney injury, alanine aminotransferase (ALT) peak, aspartate aminotransferase (AST) peak, bilirubin (Bil) and postoperative complications.
Follow Up: 7 months (median)
BACKGROUND:

In Italy, 20 min of continuous, flat-line electrocardiogram are required for death declaration. Despite prolonged warm ischemia time, Italian centers reported good outcomes in controlled donation after circulatory death (cDCD) liver transplantation by combining normothermic regional and end-ischemic machine perfusion (MP). The aim of this study was to evaluate the safety and feasibility of the use of septuagenarian and octogenarian cDCD donors with this approach.

METHODS:

All cDCD older than 70 y were evaluated during normothermic regional perfusion and then randomly assigned to dual hypothermic or normothermic MP.

RESULTS:

In the period from April 2021 to December 2022, 17 cDCD older than 70 y were considered. In 6 cases (35%), the graft was not considered suitable for liver transplantation, whereas 11 (65%) were evaluated and eventually transplanted. The median donor age was 82 y, being 8 (73%) older than 80. Median functional warm ischemia and no-flow time were 36 and 28 min, respectively. Grafts were randomly assigned to ex situ dual hypothermic oxygenated MP in 6 cases (55%) and normothermic MP in 5 (45%). None was discarded during MP. There were no cases of primary nonfunction, 1 case of postreperfusion syndrome (9%) and 2 cases (18%) of early allograft dysfunction. At a median follow-up of 8 mo, no vascular complications or ischemic cholangiopathy were reported. No major differences were found in terms of postoperative hospitalization or complications based on the type of MP.

CONCLUSIONS:

The implementation of sequential normothermic regional and end-ischemic MP allows the safe use of very old donation after circulatory death donors.

  • Nasir BS
  • Weatherald J
  • Ramsay T
  • Cypel M
  • Donahoe L
  • et al.
J Heart Lung Transplant. 2024 Jun;43(6):1005-1009 doi: 10.1016/j.healun.2024.02.1454.
CET Conclusion
Reviewer: Mr John Fallon, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This is a small, randomised feasibility study conducted in a single Canadian lung transplant centre with the aim of designing a large multicentre RCT to definitively assess the use of routine versus on-demand ECMO during lung only transplantation. They perform a sensible power calculation based on the Blackwelder method and discussion across all Canadian lung centres with regards historic data and possible effect sizes, giving a needed trial size of 310 patients in each arm. They apply this to collected data on local and national transplant numbers to assess are reasonable study period and recruitment window. Based on their contribution to national transplant number they go on to generate an aim within their centre during a 6-month feasibility recruitment period. They determine their trial would likely be feasible and at low risk of failure if they randomised 19 participants with fewer than 5% loss-to-follow up and less than 10% protocol violations within the 6 months. During the feasibility study period they successfully randomise 28 patients. While the numbers are insufficient to comment on the two interventions, they demonstrate that over the proposed 3-year study period with all 4 Canadian lung transplant centres it is highly likely the trial could be achieved, and a definitive answer found. This is a commendable feasibility study, with complex interventions with potentially small effect sizes, it is crucial that should one embark on the cost, effort, and patient recruitment for such trials that the risk of failure is minimised as far as possible. Strategies such as a well-thought-out simple feasibility studies are key to larger trial successes.
Aims: Assess the feasibility of undertaking a multicentre RCT to compare two strategies of intraoperative mechanical circulatory support (routine ECMO versus on-demand ECMO) during lung transplantation.
Interventions: Standard of care being routine ECMO versus the intervention of on-demand ECMO utilised when required during transplantation.
Participants: 28 adult, lung only, primary transplant recipients where cardiopulmonary support was not mandatory were randomised.
Outcomes: The outcome measures were death, primary graft dysfunction (PGD), bleeding, cannulation site complications, and hypoperfusion-related complications (e.g., AKI, stroke, mesenteric ischemia).
Follow Up: 30 days

In most centers, extracorporeal membrane oxygenation (ECMO) is the preferred means to provide cardiopulmonary support during lung transplantation. However, there is controversy about whether intraoperative venoarterial (VA) ECMO should be used routinely or selectively. A randomized controlled trial is the best way to address this controversy. In this publication, we describe a feasibility study to assess the practicality of a protocol comparing routine versus selective VA-ECMO during lung transplantation. This prospective, single-center, randomized controlled trial screened all patients undergoing lung transplantation. Exclusion criteria include retransplantation, multiorgan transplantation, and cases where ECMO is mandatory. We determined that the trial would be feasible if we could recruit 19 participants over 6 months with less than 10% protocol violations. Based on the completed feasibility study, we conclude that the protocol is feasible and safe, giving us the impetus to pursue a multicenter trial with little risk of failure due to low recruitment.

  • Yl MK
  • Patil NS
  • Mohapatra N
  • Sindwani G
  • Dhingra U
  • et al.
Ann Surg. 2024 Jun 1;279(6):932-944 doi: 10.1097/SLA.0000000000006200.
CET Conclusion
Reviewer: Mr Keno Mentor, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: Temporary portocaval shunt (TPCS) formation is a frequently utilised in liver transplantation to reduce portal hypertension and blood loss during the hepatectomy phase. The benefit of this technique has been proven in acute liver failure, where physiological portosystemic shunts are not well developed, but the benefit in cases of chronic liver disease with cirrhosis is less clear. This unblinded randomised trial investigated the efficacy of TPCS in chronic liver patients undergoing live donor liver transplant. Intra-operative parameters including inotrope requirement, blood loss and renal function were significantly improved in the TPCS group. However, these superior haemodynamic parameters did not result in meaningful post-operative benefit, with no significant differences in key clinical parameters including morbidity, mortality and length of stay between the two groups. The technique should thus continue to be utilised on a case by case basis.
Aims: This study aimed to investigate the role of temporary portocaval shunt (TPCS) during recipient hepatectomy in live donor liver transplant recipients.
Interventions: Participants were randomised to TPCS versus no TPCS.
Participants: 60 live donor liver transplantation (LDLT) recipients.
Outcomes: The primary outcomes are intraoperative haemodynamic parameters (systolic blood pressure, diastolic blood pressure, mean arterial pressure), blood loss, transfusion requirement, renal function, and duration of surgery. The secondary outcomes include early graft dysfunction, morbidity, mortality, total ICU and hospital stay.
Follow Up: 90 days
OBJECTIVE:

To compare intraoperative hemodynamic parameters, blood loss, renal function, and duration of surgery with and without temporary portocaval shunt (TPCS) in live donor liver transplantation (LT) recipients. Secondary objectives were postoperative early graft dysfunction, morbidity, mortality, total intensive care unit, and hospital stay.

BACKGROUND:

Blood loss during recipient hepatectomy for LT remains a major concern. Routine use of TPCS during LT is not yet elucidated.

METHODS:

This study is a single-center, open-label, randomized control trial. The sample size was calculated based on intraoperative blood loss. After exclusion, a total of 60 patients, 30 in each arm (TPCS vs no TPCS) were recruited in the trial.

RESULTS:

The baseline recipient and donor characteristics were comparable between the groups. The median intraoperative blood loss ( P = 0.004) and blood product transfusions ( P < 0.05) were significantly less in the TPCS group. The TPCS group had significantly improved intraoperative hemodynamics in the anhepatic phase as compared with the no TPCS group ( P < 0.0001), requiring significantly less vasopressor support. This led to significantly better renal function as evidenced by higher intraoperative urine output in the TPCS group ( P = 0.002). Because of technical simplicity, the TPCS group had significantly fewer inferior vena cava injuries (3.3 vs 26.7%, P = 0.026) and substantially shorter hepatectomy time and total duration of surgery (529.4 ± 35.54 vs 606.83 ± 48.13 min, P < 0.0001). The time taken for normalization of lactate in the immediate postoperative period was significantly shorter in the TPCS group (median, 6 vs 13 h; P = 0.04). Although postoperative endotoxemia, major morbidity, 90-day mortality, total intensive care unit, and hospital stay were comparable between both groups, tolerance to enteral feed was earlier in the TPCS group.

CONCLUSIONS:

In live donor LT, TPCS is a simple and effective technique that provides superior intraoperative hemodynamics and reduces blood loss and duration of surgery.

  • Custódio G
  • Massutti AM
  • da Igreja MR
  • Lemos NE
  • Crispim D
  • et al.
Liver Transpl. 2024 Jun 1;30(6):607-617 doi: 10.1097/LVT.0000000000000298.
CET Conclusion
Reviewer: Mr John Fallon, Centre for Evidence in Transplantation, Nuffield Department of Surgical Sciences University of Oxford
Conclusion: This modest sized double-blinded, placebo-controlled RCT was robustly designed, with sound methodology, and demonstrated liraglutide treatment to the donor reduced circulating IL-6 and prevented increase in IL-10. While IL-6 is a pro-inflammatory cytokine which induces the expression of various transcription factors related to inflammation, in this study its reduction in the donor did not translate into any altered gene expression within the liver tissue. They also found no significant differences in their other inflammatory cytokines. In terms of correlation with outcome, the study was severely limited by the number transplanted in their own centre, resulting in a small cohort of recipients they were able to follow-up, they do not specifically report the rates of EAD, however on looking at the results, by Olthoff criteria the rates of EAD, were low and comparable. While the trial is not groundbreaking it is mechanistically interesting with the effects of the GLP-1 agonist measurable within the donors. It is also ethically interesting considering little research is done in donors currently, which could be a valuable window of opportunity to deliver therapies to improve organ outcomes.
Aims: To assess if delivery of liraglutide to brainstem death donors reduced donor inflammation prior to organ donations with correlation to liver transplant outcomes.
Interventions: The intervention group donors received 3mg of liraglutide subcutaneously (0.5mL) at the point of randomisation and then every 6 hours until donation. The placebo group received 0.5mL of normal saline.
Participants: 50 adult DBD donors, of which 12 livers went on to be transplanted in the study centre.
Outcomes: The primary outcome measure was IL-6 levels in the donor prior to first dose and immediately prior to retrieval. The secondary outcomes were donor plasma levels of IL-1β, IL-10, IFN-γ, TNF and BCL-2. Assessment of liver tissue for inflammation related gene expression and immunohistochemistry. The exploratory outcomes were the utilisation rate of the livers and early allograft dysfunction in the livers transplanted in the study centre.
Follow Up: The organ donation period

Brain death triggers an inflammatory cascade that damages organs before procurement, adversely affecting the quality of grafts. This randomized clinical trial aimed to compare the efficacy of liraglutide compared to placebo in attenuating brain death-induced inflammation, endoplasmic reticulum stress, and oxidative stress. We conducted a double-blinded, placebo-controlled, randomized clinical trial with brain-dead donors. Fifty brain-dead donors were randomized to receive subcutaneous liraglutide or placebo. The primary outcome was the reduction in IL-6 plasma levels. Secondary outcomes were changes in other plasma pro-inflammatory (IL-1β, interferon-γ, TNF) and anti-inflammatory cytokines (IL-10), expression of antiapoptotic ( BCL2 ), endoplasmic reticulum stress markers ( DDIT3/CHOP , HSPA5/BIP ), and antioxidant ( superoxide dismutase 2 , uncoupling protein 2 ) genes, and expression TNF, DDIT3, and superoxide dismutase 2 proteins in liver biopsies. The liraglutide group showed lower cytokine levels compared to the placebo group during follow-up: Δ IL-6 (-28 [-182, 135] vs. 32 [-10.6, 70.7] pg/mL; p = 0.041) and Δ IL-10 (-0.01 [-2.2, 1.5] vs. 1.9 [-0.2, 6.1] pg/mL; p = 0.042), respectively. The administration of liraglutide did not significantly alter the expression of inflammatory, antiapoptotic, endoplasmic reticulum stress, or antioxidant genes in the liver tissue. Similar to gene expression, expressions of proteins in the liver were not affected by the administration of liraglutide. Treatment with liraglutide did not increase the organ recovery rate [OR = 1.2 (95% CI: 0.2-8.6), p = 0.82]. Liraglutide administration reduced IL-6 and prevented the increase of IL-10 plasma levels in brain-dead donors without affecting the expression of genes and proteins related to inflammation, apoptosis, endoplasmic reticulum stress, or oxidative stress.

  • Verghese PS
  • Evans MD
  • Hanson A
  • Hathi J
  • Chinnakotla S
  • et al.
J Clin Virol. 2024 Jun;172:105678 doi: 10.1016/j.jcv.2024.105678.
BACKGROUND:

Valganciclovir (valG), a cytomegalovirus (CMV) prophylactic agent, has dose-limiting side effects. The tolerability and effectiveness of valacyclovir (valA) as CMV prophylaxis is unknown.

METHODS:

We conducted a randomized, open-label, single-center trial of valA versus valG for all posttransplant CMV prophylaxis in adult and pediatric kidney recipients. Participants were randomly assigned to receive valA or valG. Primary endpoints were the incidence of CMV viremia and side-effect related drug reduction with secondary assessment of incidence of EBV viremia.

RESULTS:

Of the 137 sequential kidney transplant recipients enrolled, 26 % were positive and negative for CMV antibody in donor and recipient respectively. The incidence of CMV viremia (4 of 71 [6 %]; 8 of 67 [12 %] P = 0.23), time to viremia (P = 0.16) and area under CMV viral load time curve (P = 0.19) were not significantly different. ValG participants were significantly more likely to require side-effect related dose reduction (15/71 [21 %] versus 1/66 [2 %] P = 0.0003). Leukopenia was the most common reason for valG dose reduction and granulocyte-colony stimulating factor was utilized for leukopenia recovery more frequently (25 % in valG vs 5 % in valA: P = 0.0007). Incidence of EBV viremia was not significantly different.

CONCLUSIONS:

ValA has significantly less dose-limiting side effects than valG. In our study population, a significant increase in CMV viremia was not observed, in adults and children after kidney transplant, compared to valG.

TRIAL REGISTRATION NUMBER:

NCT01329185.

  • Maiwall R
  • Singh SP
  • Angeli P
  • Moreau R
  • Krag A
  • et al.
Hepatol Int. 2024 Jun;18(3):833-869 doi: 10.1007/s12072-024-10650-0.

Acute-on-chronic liver failure (ACLF) is a syndrome that is characterized by the rapid development of organ failures predisposing these patients to a high risk of short-term early death. The main causes of organ failure in these patients are bacterial infections and systemic inflammation, both of which can be severe. For the majority of these patients, a prompt liver transplant is still the only effective course of treatment. Kidneys are one of the most frequent extrahepatic organs that are affected in patients with ACLF, since acute kidney injury (AKI) is reported in 22.8-34% of patients with ACLF. Approach and management of kidney injury could improve overall outcomes in these patients. Importantly, patients with ACLF more frequently have stage 3 AKI with a low rate of response to the current treatment modalities. The objective of the present position paper is to critically review and analyze the published data on AKI in ACLF, evolve a consensus, and provide recommendations for early diagnosis, pathophysiology, prevention, and management of AKI in patients with ACLF. In the absence of direct evidence, we propose expert opinions for guidance in managing AKI in this very challenging group of patients and focus on areas of future research. This consensus will be of major importance to all hepatologists, liver transplant surgeons, and intensivists across the globe.

  • Cerrato C
  • Jahrreiss V
  • Nedbal C
  • Ripa F
  • Marco V
  • et al.
J Endourol. 2024 Jun;38(6):536-544 doi: 10.1089/end.2023.0398.

Introduction and Objective: Renal transplantation is the treatment for end-stage renal disease that offers better quality of life and survival. Among the possible complications that might affect allografts, urolithiasis might have severe consequences, causing acute kidney injury (AKI) or septic events in immunocompromised patients. Allograft stones might be treated with percutaneous nephrolithotomy (PCNL). The aim of this Cochrane style review was to assess the safety and efficacy of PCNL in patients with renal transplant. Methods: A comprehensive search in the literature was performed including articles between July 1982 and June 2023, with only English original articles selected for this review. Results: The final review encompassed nine articles (108 patients). The mean age was 46.4 ± 8.7 years, with a male:female ratio of 54:44. The average time from transplantation to urolithiasis onset was 47.54 ± 23.9 months. Predominant symptoms upon presentation were AKI (32.3%), followed by urinary tract infection and fever (24.2%), and oliguria (12.9%). The mean stone size was 20.1 ± 7.3 mm, with stones located in the calices or pelvis (41%), ureteropelvic junction (23.1%), or proximal ureter (28.2%). PCNL (22F-30F) was more frequently performed than mini-PCNLs (16F-20F) (52.4% vs 47.6%). Puncture was guided by ultrasound (42.9%), fluoroscopy (14.3%), or both (42.9%). The stone-free rate (SFR) and complication rates were 92.95% (range: 77%-100%) and 5.5%, respectively, with only one major complication reported. Postoperatively, a ureteral stent and nephrostomy were commonly placed in 47%, with four patients needing a second look PCNL. During an average follow-up of 32.5 months, the recurrence rate was 3.7% (4/108), and the mean creatinine level was 1.37 ± 0.28 mg/dL. Conclusions: PCNL remains a safe and effective option in de novo allograft urolithiasis, allowing to treat large stones in one-step surgery. A good SFR is achieved with a low risk of minor complications. These patients should be treated in an endourology center in conjunction with the renal or transplant team.