Simultaneous liver-kidney transplantation: future perspective.

BACKGROUND: The aims of this narrative review were (i) to describe the current indications of SLKT, (ii) to report evolution of SLKT activity, (iii) to report the outcomes of SLKT, (iv) to explain the immune-protective effect of liver transplant on kidney transplant, (v) to explain the interest of delay kidney transplantation, using hypothermic machine perfusion (HMP), (vi) to report kidney after liver transplantation (KALT) indications and (vii) to describe the value of the increase in the use of extended criteria donors (ECD) and particular controlled donation after circulatory death (cDCD) transplant, thanks to the development of new organ preservation strategies. METHOD: Electronic databases were screened using the keywords "Simultaneous", "Combined", "kidney transplantation" and "liver transplantation". The methodological and clinical heterogeneity of the included studies meant that meta-analysis was inappropriate. RESULTS:  A total of 1,917 publications were identified in the literature search. Two reviewers screened all study abstracts independently and 1,107 of these were excluded. Thus, a total of 79 full text articles were assessed for eligibility. Of these, 21 were excluded. In total, 58 studies were included in this systematic review. CONCLUSIONS:  Simultaneous liver-kidney transplantation has made a significant contribution for patients with dual-organ disease. The optimization of indication and selection of SLKT patients will reduce futile transplantation. Moreover, increasing the use of transplants from extended criteria donors, in particular cDCD, should be encouraged, thanks to the development of new modalities of organ preservation.

Associations Between Buprenorphine\Naloxone and Methadone Treatment and non-Opioid Substance Use in Prescription-Type Opioid Use Disorder: Secondary Analyses From the OPTIMA Study: Associations entre le traitement avec la buprénorphine/naloxone et avec la méthadone et l'utilisation de substances non opioïdes dans le trouble lié à l'usage d'opioïdes de type sur ordonnance : analyses secondaires de l'étude OPTIMA.

OBJECTIVES: There is limited evidence on how opioid agonist treatment (OAT) may affect psychoactive non-opioid substance use in prescription-type opioid use disorder (POUD) and whether this effect might explain OAT outcomes. We aimed to assess the effect of methadone on non-opioid substance use compared to buprenorphine/naloxone (BUP/NX), to explore whether non-opioid substance use is associated with opioid use and retention in treatment, and to test non-opioid use as a moderator of associations between methadone with retention in OAT and opioid use compared to BUP/NX. METHODS: This is a secondary analysis of data from the OPTIMA trial, an open-label, pragmatic, parallel, two-arm, pan-Canadian, multicentre, randomized-controlled trial to compare standard methadone model of care and flexible take-home dosing BUP/NX for POUD treatment. We studied the effect of methadone and BUP/NX on non-opioid substance use evaluated by urine drug screen (UDS) and by classes of non-opioid substances (i.e., tetrahydrocannabinol [THC], benzodiazepines, stimulants) (weeks 2-24) using adjusted generalized estimation equation (GEE). We studied the association between non-opioid substance-positive UDS and opioid-positive UDS and retention in treatment, using adjusted GEE and logistic regressions. RESULTS: Overall, methadone was not associated with non-opioid substance-positive UDS compared to BUP/NX (OR: 0.78; 95%CI, 0.41 to 1.48). When non-opioid substances were studied separately, methadone was associated with lower odds of benzodiazepine-positive UDS (OR: 0.63; 95% CI: 0.40 to 0.98) and THC-positive UDS (OR: 0.47; 95% CI: 0.28 to 0.77), but not with different odds of stimulant-positive UDS (OR: 1.29; 95% CI: 0.78 to 2.16) compared to BUP/NX. Substance-positive UDS, overall and separate classes, were not associated with opioid-positive UDS or retention in treatment. CONCLUSION: Methadone did not show a significant effect on overall non-opioid substance use in POUD compared to BUP/NX treatment but was associated with lower odds of benzodiazepine and THC use in particular. Non-opioid substance use did not predict OAT outcomes. Further research is needed to ascertain whether specific patterns of polysubstance use (quantity and frequency) may affect treatment outcomes.

Impact of newly diagnosed prostate cancer at time of evaluation for renal transplantation.

Systematic screening for prostate cancer is widely recommended in candidates for renal transplant at the time of listing. There are concerns that overdiagnosis of low-risk prostate cancer may result in reducing access to transplant without demonstrated oncological benefits. The objective of the study was to assess the outcome of newly diagnosed prostate cancer in candidates for transplant at the time of listing, and its impact on transplant access and transplant outcomes according to treatment options. This retrospective study was conducted over 10 years in 12 French transplant centers. Patients included were candidates for renal transplant at the time of prostate cancer diagnosis. Demographical and clinical data regarding renal disease, prostate cancer, and transplant surgery were collected. The primary outcome of the study was the interval between prostate cancer diagnosis and active listing according to treatment options. Overall median time from prostate cancer diagnosis to active listing was 25.0 months [16.4-40.2], with statistically significant differences in median time between the radiotherapy and the active surveillance groups (p = .03). Prostate cancer treatment modalities had limited impact on access and outcome of renal transplantation. Active surveillance in low-risk patients does not seem to compromise access to renal transplantation, nor does it impact oncological outcomes.

Association Between Markers of Vulnerability for Cannabis-Related Harms and Source of Supply: Secondary Analysis of a Representative Population Survey.

OBJECTIVE: In 2018, the sale of non-medical cannabis was authorized in the province of Quebec in Canada, within a public monopoly under the Société Québécoise du Cannabis (SQDC). The objective of this study was to offer a description of the cannabis-using population regarding the sources of cannabis supply and to explore whether at-risk individuals are purchasing cannabis at SQDC. METHOD: We used data from a cross-sectional, representative population survey (age >18 years, n = 1799), the Enquête Québécoise sur le Cannabis, which was completed between February and June 2019. Analyses involved adjusted binary logistic regressions, incorporating population weights, to assess 7 potential indicators of harm. RESULTS: The vulnerability profiles of SQDC consumers (47.8%) and those acquiring their cannabis elsewhere (52.2%) were similar in terms of frequency of cannabis use (adjusted odds ratio [aOR] = 0.46; 95% confidence interval [CI] = 0.12-1.67), motivation to use (aOR = 0.62; 95% CI = 0.16-2.46), concomitant consumption of other substances (aOR = 0.80; 95% CI = 0.14-4.75), cannabis-impaired driving behaviours (aOR = 0.93; 95% CI = 0.26-3.36), psychological distress (aOR = 0.99; 95% CI = 0.26-3.79), and problematic cannabis use (aOR = 0.46; 95% CI = 0.13-1.64). However, SQDC consumers were more likely to be aware of the cannabinoid content of the product purchased compared to those who acquired their cannabis from other sources (aOR = 4.12; 95% CI = 1.10-15.40). CONCLUSIONS: No association was detected between the source of cannabis supply and potential vulnerability indicators of cannabis-related harms, but SQDC consumers were more aware of the cannabinoid content of the products purchased. These results suggest that the regulated government supply in Quebec is reaching a substantial portion of those with potential high vulnerability to harm. Whether this knowledge translates into a reduction in the negative consequences related to consumption is still to be determined.

Poor Antibody Response After Two Doses of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Vaccine in Transplant Recipients.

A low anti-spike antibody response of 28.6% was observed 28 days after BNT162b2 vaccine second dose among 133 solid organ transplant recipients without previous coronavirus disease 2019 (COVID-19). No serious adverse events were recorded. Four severe COVID-19 cases were reported between or after the 2 doses. Our data suggest to change the vaccine strategy.

Surgical complications risk in obese and overweight recipients for kidney transplantation: a predictive morphometric model based on sarcopenia and vessel-to-skin distance.

PURPOSE: Sarcopenia or adipose tissue distribution within obese and overweight renal transplanted have been poorly evaluated. Our objective was to evaluate morphometric markers to predict surgical complications in kidney transplantation. METHODS: We retrospectively included patients with a BMI > 25 kg/m2 undergoing kidney transplantation from 2012 to 2017. Following measurements were performed on CT-scan sections: Sub-cutaneous Adipose Tissue surface (SAT), Visceral Adipose Tissue surface (VAT), Vessel-to-Skin distance (VSK), Abdominal Perimeter (AP), and Psoas surface. A multivariable logistic regression model with BMI was compared to a model containing morphometric variables to determine the best predictive model for surgical complications. RESULTS: 248 patients were included, 15 (6%) experienced transplant nephrectomy, 18 (7.3%) urinary leakage, and 29 (11.7%) subcapsular renal hematoma. Multivariable logistic regression evidenced that sarcopenia and VSK were risk factors of surgical complication within a year post-transplantation (respectively, OR = 0.9, 95%CI (0.8-0.9), p = 0.04 and OR = 1.2, 95%CI (1.1-1.3), p = 0.002). Area under the curve for a predictive model including VSK, age and psoas surface was 0.69, whereas BMI model was 0.65. CONCLUSION: Combined morphometric parameters of obesity were associated with surgical complications in kidney transplantation. Morphometric threshold may provide a more accurate and objective criteria than BMI to evaluate kidney transplantation outcomes. External validation is needed.

Retrieved but not transplanted kidneys: how to limit the losses? A retrospective national study.

Despite the organ shortage, a significant number of deceased donor kidneys are retrieved but not transplanted (RNTK). This study aims to describe and analyze the main causes of potential grafts discard and to propose adequate solutions. We collected data from the Cristal database of the French Biomedicine Agency about RNTK over one year. Expert opinion was taken from urologists with extensive expertise in renal transplantation. They retrospectively analyzed each record to assess the appropriateness of each graft refusal and subsequent kidney discard. Of 252 kidneys were retrieved but not transplanted in France over one year. The main reasons for discard were vascular abnormalities in 43.7% (n = 110), suspicion of malignant tumor in 18.7% (n = 47), and severe histological lesions on preimplantation biopsy in 12.3% (n = 31). The reason for kidney refusal was undetermined in 4.8% (n = 12). Iatrogenic lesions were responsible for 26.2% (n = 66). Overall, 46.0% (n = 16) and 25.0% (n = 63) of the grafts were, respectively, properly and improperly denied, and the analysis was not possible in 29.0% (n = 73). In total, 36.9% of RNTK could have been transplanted. Reduction of iatrogenic lesions, improvement of microsurgical repair skills, and proper histological examination are necessary to reduce the number of RNTK. A prospective study applying the proposed principles is undoubtedly essential to complete this work.

First-in-human use of a marine oxygen carrier (M101) for organ preservation: A safety and proof-of-principle study.

The medical device M101 is an extracellular hemoglobin featuring high oxygen-carrying capabilities. Preclinical studies demonstrated its safety as an additive to organ preservation solutions and its beneficial effect on ischemia/reperfusion injuries. OXYgen carrier for Organ Preservation (OXYOP) is a multicenter open-label study evaluating for the first time the safety of M101 added (1 g/L) to the preservation solution of one of two kidneys from the same donor. All adverse events (AEs) were analyzed by an independent data and safety monitoring board. Among the 58 donors, 38% were extended criteria donors. Grafts were preserved in cold storage (64%) or machine perfusion (36%) with a mean cold ischemia time (CIT) of 740 minutes. At 3 months, 490 AEs (41 serious) were reported, including two graft losses and two acute rejections (3.4%). No immunological, allergic, or prothrombotic effects were reported. Preimplantation and 3-month biopsies did not show thrombosis or altered microcirculation. Secondary efficacy end points showed less delayed graft function (DGF) and better renal function in the M101 group than in the contralateral kidneys. In the subgroup of grafts preserved in cold storage, Kaplan-Meier survival and Cox regression analysis showed beneficial effects on DGF independent of CIT (P = .048). This study confirms that M101 is safe and shows promising efficacy data.

Association of genetic variation of the six gene prognostic model for castration-resistant prostate cancer with survival.

BACKGROUND: We previously identified a blood RNA transcript-based model consisting of six immune or inflammatory response genes (ABL2, SEMA4D, ITGAL, C1QA, TIMP1, and CDKN1A) that was prognostic for survival in cohorts of men with castration-resistant prostate cancer (CRPC). We investigated whether inherited variation in these six genes was associated with overall survival (OS) in men with CRPC. METHODS: The test cohort comprised 600 patients diagnosed with CRPC between 1996 and 2011 at Dana-Farber Cancer Institute. Genotyping of 66 tagging single nucleotide polymorphisms (SNPs) spanning the six genes was performed on blood derived DNAs. For the top four SNPs (P < 0.05), validation was conducted in an independent cohort of 223 men diagnosed with CRPC between 2000 and 2014. Multivariable Cox regression adjusting for known prognostic factors estimated hazard ratios (HR) and 95% confidence intervals (CI) of the association of genetic variants with OS. RESULTS: Two thirds of patients in both cohorts had metastases at CRPC diagnosis. Median OS from CRPC diagnosis was 3.6 (95%CI 3.3-4.0) years in the test cohort and 4.6 (95%CI 3.8-5.2) years in the validation cohort. Fifty-nine SNPs in Hardy-Weinberg equilibrium were analyzed. The major alleles of rs1318056 and rs1490311 in ABL2, and the minor alleles of rs2073917 and rs3764322 in ITGAL were associated with increased risk of death in the test cohort (adjusted-HRs 1.27-1.39; adjusted-p <0.05; false discovery rate <0.35). In the validation cohort, a similar association with OS was observed for rs1318056 in ABL2 (adjusted-HR 1.44; 95%CI 0.89-2.34) and rs2073917 in ITGAL (adjusted-HR 1.41; 95%CI 0.82-2.42). The associations did not reach statistical significance most likely due to the small sample size of the validation cohort (adjusted-p = 0.142 and 0.209, respectively). Additional eQTL analysis indicated that minor alleles of rs1318056 and rs1490311 in ABL2 are associated with a lower ABL2 expression in blood. CONCLUSIONS: These findings corroborate our initial work on the RNA expression of genes involved in immunity and inflammation from blood and clinical outcome and suggest that germline polymorphisms in ABL2 and ITGAL may be associated with the risk of death in men with CRPC. Further studies are needed to validate these findings and to explore their functional mechanisms.

Evaluation of outcomes in renal transplantation with hypothermic machine perfusion for the preservation of kidneys from expanded criteria donors.

In 2012, an expert working group from the French Transplant Health Authority recommended the use of hypothermic machine perfusion (HMP) to improve kidney preservation and transplant outcomes from expanded criteria donors, deceased after brain death. This study compares HMP and cold storage (CS) effects on delayed graft function (DGF) and transplant outcomes. We identified 4,316 kidney transplants from expanded criteria donors (2011-2014) in France through the French Transplant Registry. DGF occurrence was analyzed with a logistic regression, excluding preemptive transplants. One-year graft failure was analyzed with a Cox regression. A subpopulation of 66 paired kidneys was identified: one preserved by HMP and the other by CS from the same donor. Kidneys preserved by HMP (801) vs CS (3515) were associated with more frequent recipient comorbidities and older donors and recipients. HMP had a protective effect against DGF (24% in HMP group and 38% in CS group, OR = 0.49 [0.40-0.60]). Results were similar in the paired kidneys (OR = 0.23 [0.04-0.57]). HMP use decreased risk for 1-year graft failure (HR = 0.77 [0.60-0.99]). Initial hospital stays were shorter in the HMP group (P < 0.001). Our results confirm the reduction in DGF occurrence among expanded criteria donors kidneys preserved by HMP.