Role of HLA molecular mismatch in clinical practice

To date, traditional pre-transplant risk factors have failed to provide accurate risk stratification in transplantation. As a result, the practice of precision medicine remains elusive, resulting in a one-size-fits-all therapeutic approach for most patients. However, recent advancements in the understanding of HLA molecules at the molecular level have revitalized interest in HLA mismatch assessment. This review discusses HLA molecular mismatch as a potential prognostic and predictive biomarker available at the time of transplantation and answers some of the common questions and critiques of this approach. We highlight the retrospective data that supports single molecule risk categorization and explore the next steps required to evaluate its potential in clinical practice.     

器官保存液培养阳性率、病原菌分布及临床意义研究

 目的 了解器官保存液（PS）微生物培养结果与受者移植后感染情况。方法 回顾性收集2016年6月—2020年12月上海某三甲医院485例器官移植患者器官PS微生物培养结果,根据器官PS培养结果将受者分为阳性组和阴性组,阳性组依据不同菌株进一步分组,分析不同组患者移植后3个月内的感染情况。结果 485例器官移植患者中,221例PS培养阳性,阳性率为45.57%,其中单一菌种142例（64.25%）,2种菌54例（24.43%）,≥3种菌25例（11.31%）。共分离病原菌327株,居前3位的是凝固酶阴性葡萄球菌（67株,20.49%）、肺炎克雷伯菌（37株,11.31%）和大肠埃希菌（27株,8.26%）。分离出常见多重耐药菌47株（14.37%）,其中耐碳青霉烯类肺炎克雷伯菌（CRKP）20株（42.55%）,耐碳青霉烯类鲍曼不动杆菌18株（38.29%）。阳性组患者移植后感染率（12.22%,27/221）数值高于阴性组（6.82%,18/264）,但差异无统计学意义（P=0.243）;≥3种菌组患者移植后感染率为32.00%（8/25）,高于单一菌组的9.15%（13/142）（P=0.004）;CRKP、白念珠菌阳性组患者移植后感染率分别为45.00%（9/20）、21.74%（5/23）,均高于其他病原菌组的8.20%（15/183）（P值分别为<0.001、0.034）。结论 常规监测器官PS培养结果对移植后感染防控具有指导意义,若PS培养CRKP、酵母菌或念珠菌阳性,建议立即进行相应抗感染的治疗。     

颈上交感神经节和单涎酸神经节苷脂联合移植抗帕金森病的实验研究

目的：观察颈上交感神经节（SCG）和单涎酸神经节苷酯（GM1）联合植入帕金森病（PD）大鼠脑内的抗PD效果及移植物的存活情况。方法：将用酶消化法制成的同种大鼠SCG细胞悬液和GM1立体定向植入PD大鼠损毁侧尾壳核内,比较单纯细胞移植组,联合移植组,上清液组和非移植组间及移植前,后诱发旋转行为的变化,移植6个月后移植区行组织学检查（HE,TH染色）。结果：两个实验组中的PD大鼠移植后的旋转行为较移植前和对照组明显改善,其中尤以联合移植组的旋转行为减少最为明显,而两个对照组的改善不明显,脑切片组织学观察可见实验组移植区内有存活良好的TH阳性细胞,联合移植组中的阳性细胞数目明显多于单纯细胞移植组。结论：1．GM1可提高SCG细胞在受体脑内的存活率,2．同种成年大鼠SCG细胞植入PD大鼠脑内可以存活,并可纠正PD大鼠的异常旋转行为。     

Low seroprevalence of SARS-CoV-2 antibodies in a liver transplant cohort

Solid organ transplant recipients might be at greater risk for acquisition and mortality because of SARS-CoV-2. There are no data regarding SARS-CoV-2 seroprevalence among liver transplant (LT) recipients, and whether it is different from that of the general population or other immunosuppressed groups. We evaluated the prevalence of IgG SARS-CoV-2 antibodies among LT recipients to estimate the frequency of asymptomatic SARS-CoV-2 infection using serological assays in our outpatient clinic. We conducted a cross-sectional analysis from 10 May to 26 October 2020 of all adult (>18 years) LT recipients that underwent a routine laboratory test for the outpatient clinic follow-up at the Hospital Universitari Vall d’Hebron (Barcelona) in which we included serological testing for SARS-CoV-2. Nine out of 294 LT recipients (3.1%) tested positive for anti-SARS-CoV-2 IgG antibodies. Five of them (55.5%) had suffered clinically symptomatic SARS-CoV-2 infection confirmed by RT-PCR, four (44.4%) had presented compatible symptoms but without microbiological confirmation and only one patient (1/9, 11.1%) tested positive without any previous symptom. SARS-CoV-2 seroprevalence among LT recipients in an area highly affected by the pandemic is lower than in the general population in the same area. These results render the possibility of asymptomatic infection in LT recipients very unlikely.     

Mesangial expansion at 5 years predicts death and death‐censored graft loss after renal transplantation

Death with a functioning graft and death‐censored renal allograft failure remain major problems for which effective preventative protocols are lacking. The retrospective cohort study aimed to determine whether histologic changes on a 5‐year surveillance kidney biopsy predict adverse outcomes after transplantation in recipients who had: both Type 2 diabetes (T2DM) and obesity (BMI ≥ 30 kg/m²) at the time of transplantation (T2DM/Obesity, n = 75); neither (No T2DM/No obesity, n = 78); No T2DM/Obesity (n = 41), and T2DM/No obesity (n = 47). On 5‐year biopsies, moderate‐to‐severe mesangial expansion was more common in the T2DM/Obesity group (Banff mm score ≥2 = 49.3%; Tervaert classification MS ≥ 2b = 26.7%) compared to the other groups (p < .001 for both scores). Risk factors included older age, higher BMI, HbA1C, and triglycerides at 1‐year post‐transplant. Moderate‐to‐severe mesangial expansion correlated with death with function (HR 1.74 (1.01, 2.98), p = .045 Banff and 1.89 (1.01, 3.51) p = .045 Tervaert) and with death‐censored graft loss (HR 3.2 (1.2, 8.8), p = .02 Banff and HR 3.8 (1.3, 11.5), p = .01 Tervaert) over a mean of 11.6 years of recipient follow‐up post‐transplant. These data suggest that mesangial expansion in recipients with T2DM and obesity may reflect systemic vascular injury and might be a novel biomarker to predict adverse outcomes post renal transplant.     

Health-related quality of life,uncertainty and coping strategies in solid organ transplant recipients during shielding for the COVID-19 pandemic

Strict isolation of vulnerable individuals has been a strategy implemented by authorities to protect people from COVID-19. Our objective was to investigate health-related quality of life (HRQoL), uncertainty and coping behaviours in solid organ transplant (SOT) recipients during the COVID-19 pandemic. A cross-sectional survey of adult SOT recipients undergoing follow-up at our institution was performed. Perceived health status, uncertainty and coping strategies were assessed using the EQ-5D-5L, Short-form Mishel Uncertainty in Illness Scale (SF-MUIS) and Brief Cope, respectively. Interactions with COVID-19 risk perception, access to health care, demographic and clinical variables were assessed. The survey was completed by 826 of 3839 (21.5%) invited participants. Overall, low levels of uncertainty in illness were reported, and acceptance was the major coping strategy (92%). Coping by acceptance, feeling protected, self-perceived susceptibility to COVID-19 were associated with lower levels of uncertainty. Health status index scores were significantly lower for those with mental health illness, compromised access to health care, a perceived high risk of severe COVID-19 infection and higher levels of uncertainty. A history of mental health illness, risk perceptions, restricted healthcare access, uncertainty and coping strategies was associated with poorer HRQoL in SOT recipients during strict isolation. These findings may allow identification of strategies to improve HRQoL in SOT recipients during the pandemic.     

Clinical manifestations and outcomes of coronavirus disease-19 in heart transplant recipients: a multicentre case series with a systematic review and meta-analysis

Available data on clinical presentation and mortality of coronavirus disease-2019 (COVID-19) in heart transplant (HT) recipients remain limited. We report a case series of laboratory-confirmed COVID-19 in 39 HT recipients from 3 French heart transplant centres (mean age 54.4 ± 14.8 years; 66.7% males). Hospital admission was required for 35 (89.7%) cases including 14/39 (35.9%) cases being admitted in intensive care unit. Immunosuppressive medications were reduced or discontinued in 74.4% of the patients. After a median follow-up of 54 (19–80) days, death and death or need for mechanical ventilation occurred in 25.6% and 33.3% of patients, respectively. Elevated C-reactive protein and lung involvement ≥50% on chest computed tomography (CT) at admission were associated with an increased risk of death or need for mechanical ventilation. Mortality rate from March to June in the entire 3-centre HT recipient cohort was 56% higher in 2020 compared to the time-matched 2019 cohort (2% vs. 1.28%, P = 0.15). In a meta-analysis including 4 studies, pre-existing diabetes mellitus (OR 3.60, 95% CI 1.43–9.06, I² = 0%, P = 0.006) and chronic kidney disease stage III or higher (OR 3.79, 95% CI 1.39–10.31, I² = 0%, P = 0.009) were associated with increased mortality. These findings highlight the aggressive clinical course of COVID-19 in HT recipients.     

African American polycystic kidney patients receive higher risk kidneys,but do not face increased risk for graft failure or post-transplant mortality

African Americans (AA) are disproportionately affected by end-stage renal disease (ESRD) and have worse outcomes following renal transplantation. Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic condition leading to ESRD necessitating transplant. We explored this population with respect to race by conducting a retrospective analysis of the UNOS database between 2005 and 2019. Our study included 10,842 (AA n = 1661; non-AA n = 9181) transplant recipients whose primary diagnosis was ADPKD. We further stratified the AA ADPKD population with respect to blood groups (AA blood type B n = 295 vs AA non-B blood type n = 1366), and also compared this cohort to AAs with a diagnosis of DM (n = 16,706) to identify unique trends in the ADPKD population. We analyzed recipient and donor characteristics, generated survival curves, and conducted multivariate analyses. African American ADPKD patients waited longer for transplants (924 days vs 747 days P < .001), and were more likely to be on dialysis (76% vs 62%; p < .001). This same group was also more likely to have AA donors (21% vs 9%; p < .001) and marginally higher KDPI kidneys (0.48 vs 0.45; p < .001). AA race was a risk factor for delayed graft function (DGF), increasing the chance of DGF by 45% (OR 1.45 95% CI 1.26–1.67; p < .001). AA race was not associated with graft failure (HR 1.10 95% CI 0.95–1.28; p = .21) or patient mortality (HR 0.84 95% CI 0.69–1.03; p = .09). Racial disparities exist in the ADPKD population. They should be continually studied and addressed to improve transplant equity.