Cytomegalovirus DNAemia and risk of mortality in allogeneic hematopoietic stem cell transplantation: Analysis from the Spanish Hematopoietic Transplantation and Cell Therapy Group

The net impact of cytomegalovirus (CMV) DNAemia on overall mortality (OM) and nonrelapse mortality (NRM) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) remains a matter of debate. This was a retrospective, multicenter, noninterventional study finally including 749 patients. CMV DNA monitoring was conducted by real-time polymerase chain reaction (PCR) assays. Clinical outcomes of interest were OM and NRM through day 365 after allo-HSCT. The cumulative incidence of CMV DNAemia in this cohort was 52.6%. A total of 306 out of 382 patients with CMV DNAemia received preemptive antiviral therapy (PET). PET use for CMV DNAemia, but not the occurrence of CMV DNAemia, taken as a qualitative variable, was associated with increased OM and NRM in univariate but not in adjusted models. A subcohort analysis including patients monitored by the COBAS Ampliprep/COBAS Taqman CMV Test showed that OM and NRM were comparable in patients in whom either low or high plasma CMV DNA threshold (<500 vs ≥500 IU/mL) was used for PET initiation. In conclusion, CMV DNAemia was not associated with increased OM and NRM in allo-HSCT recipients. The potential impact of PET use on mortality was not proven but merits further research.     

Association of antiviral prophylaxis and rituximab use with posttransplant lymphoproliferative disorders (PTLDs): A nationwide cohort study

Posttransplant lymphoproliferative disorder (PTLD) is a serious complication of solid organ transplantation (SOT). Most PTLD cases are associated with Epstein–Barr virus (EBV) infection. The role of antiviral prophylaxis or rituximab therapy for prevention of PTLD in SOT recipients is controversial. In a nationwide cohort, we assessed the incidence, presentation, and outcome of histologically proven PTLD. We included 4765 patients with a follow-up duration of 23 807 person-years (py). Fifty-seven PTLD cases were identified; 39 (68%) were EBV positive (EBV+ PTLD). Incidence rates for EBV+ PTLD at 1, 2, and 3 years posttransplant were 3.51, 2.24, and 1.75/1000 py and 0.44, 0.25, and 0.29/1000 py for EBV− PTLD. We did not find an effect of antiviral prophylaxis on early and late EBV+ PTLD occurrence (early EBV+ PTLD: SHR 0.535 [95% CI 0.199–1.436], p = .264; late EBV+ PTLD: SHR 2.213, [95% CI 0.751–6.521], p = .150). However, none of the patients (0/191) who received a rituximab-containing induction treatment experienced PTLD, but 57 of 4574 patients without rituximab induction developed PTLD. In an adjusted restricted mean survival time model, PTLD-free survival was significantly longer (0.104 years [95% CI 0.077–0.131]) in patients receiving rituximab as induction treatment. This study provides novel data on the association of rituximab induction and reduced risk for PTLD.     

Increased incidence and unusual presentations of CMV disease in kidney transplant recipients after conversion to belatacept

Belatacept may increase cytomegalovirus (CMV) disease risk after conversion from CNI-based therapy. We analyzed CMV disease characteristics after belatacept conversion. Propensity score matching was used to compare CMV disease incidence in belatacept- and CNI-treated kidney transplant recipients (KTRs). CMV disease characteristics and risk factors under belatacept were analyzed. In total, 223 KTRs (median age [IQR] 59.2 years [45.4–68.5]) were converted to belatacept (median of 11.5 months [2.5–37.0] post-transplantation); 40/223 (17.9%) developed CMV disease. Independent risk factors included increased age (p = .0164), D+/R− CMV serostatus (p = .0220), and low eGFR at conversion (p = .0355). Among 181 belatacept-treated patients matched to 181 controls, 32/181 (17.7%) experienced CMV disease (vs. 5/181 controls [2.8%]). CMV disease cumulative incidences were 6.33 and 0.91/100 person-years (p-y) in belatacept and control groups, respectively. CMV disease risk was particularly high in elderly patients (converted >70 years) and those with eGFR <30 ml/min; cumulative incidences were 18.4 and 5.2/100 p-y, respectively. CMV diseases under belatacept were atypical, with late-onset disease (24/40 patients [60%]), high CMV seropositivity (27/40, 67%), increased severe and tissue-invasive disease rates (gastrointestinal involvement in 32/40 [80%]) and life-threatening diseases (4/40 [10%]). These findings should stimulate further research to secure the use of belatacept as a valuable rescue therapy in KTRs.     

Safety and immunogenicity of adjuvanted recombinant subunit herpes zoster vaccine in lung transplant recipients

Lung transplant recipients are at high risk for herpes zoster and preventive measures are a significant unmet need. We investigated the safety and immunogenicity of two doses of a recombinant zoster vaccine (RZV) in lung transplant recipients (≥50 years). We enrolled 50 patients of which 49 received at least one vaccine dose. Anti-glycoprotein E (gE) antibody levels (n = 43) increased significantly compared to baseline (median optical density [OD] 1.96; interquartile range [IQR]: 1.17–2.89) after the first (median OD 3.41, IQR 2.54–3.81, p < .0001) and second vaccine dose (median OD 3.63, IQR 3.39–3.86, p < .0001). gE-specific polyfunctional CD4+ T cell frequencies (n = 38) also increased from baseline (median 85 per 10⁶ CD4+ T cells; IQR: 46–180) to the first (median 128 per 10⁶ CD4+ T cells; IQR: 82–353; p = .023) and after the second dose (median 361 per 10⁶ CD4+ T cells; IQR: 146–848; p < .0001). Tenderness (83.0%; 95%CI: 69.2–92.4%) and redness (31.9%; 95%CI: 19.1–47.1%) at injection site were common. One rejection episode within 3 weeks of vaccination was observed. This is the first study demonstrating that RZV was safe and elicited significant humoral and cell-mediated immunity in lung transplant recipients. RZV is a new option for the prevention of shingles in this population.     

Primary hyperoxaluria diagnosed after kidney transplant: A review of the literature and case report of aggressive renal replacement therapy and lumasiran to prevent allograft loss

Primary hyperoxaluria type 1 is a rare inherited disorder caused by abnormal liver glyoxalate metabolism leading to overproduction of oxalate, progressive kidney disease, and systemic oxalosis. While the disorder typically presents with nephrocalcinosis, recurrent nephrolithiasis, and/or early chronic kidney disease, the diagnosis is occasionally missed until it recurs after kidney transplant. Allograft outcomes in these cases are typically very poor, often with early graft loss. Here we present the case of a child diagnosed with primary hyperoxaluria type 1 after kidney transplant who was able to maintain kidney function, thanks to aggressive renal replacement therapy as well as initiation of a new targeted therapy for this disease. This case highlights the importance of having a high index of suspicion for primary hyperoxaluria in patients with chronic kidney disease and nephrocalcinosis/nephrolithiasis or with end stage kidney disease of uncertain etiology, as initiating therapies early on may prevent poor outcomes.     

Tension band plates have greater risks of complications in temporary epiphysiodesis

PurposeThis study aimed to compare the efficacy of decreasing leg-length discrepancy (LLD) and postoperative complications between tension band plates (TBP) and percutaneous transphyseal screws (PETS).MethodsThis retrospective study reviewed LLD patients who underwent temporary epiphysiodesis at the distal femur and/or proximal tibia from 2010 to 2017 (minimum two years follow-up). Efficacy of decreasing LLD was assessed one and two years postoperatively. Complications were classified with the modified Clavien-Dindo-Sink complication classification system. Knee deformities were assessed by percentile and zone of mechanical axis across the tibial plateau.ResultsIn total, 53 patients (25 boys, 28 girls) underwent temporary epiphysiodesis (mean age, 11.4 years). The efficacy of decreasing LLD at two years between the TBP (n = 38) and PETS (n = 15) groups was comparable. Seven grade III complications were recorded in six TBP patients and in one PETS patient who underwent revision surgeries for knee deformities and physis impingement. Four grade I and two grade II complications occurred in the TBP group. The mechanical axis of the leg shifted laterally in the PETS group and medially in the TBP groups (+7.1 percentile versus -4.2 percentile; p < 0.05). Shifting of the mechanical axis by two zones was noted medially in four TBP patients and laterally in two PETS patients.ConclusionMore implant-related complications and revision surgeries for angular deformities were associated with TBP. A tendency of varus and valgus deformity after epiphysiodesis using TBP and PETS was observed, respectively. Patients and families should be informed of the risks and regular postoperative follow-up is recommended.Level of evidenceLevel III     

省直医院运营效率及其提升策略分析——以河南省为例

目的 分析省直医院运营效率及其影响因素,为提高省直医院运营效率提供参考依据。方法 采用随机抽样的方法,选取河南省10家省直医院,综合使用Malmquist指数和Tobit模型,对“十三五”期间省直医院运营效率的变化趋势和主要影响因素进行回顾性分析,并提出“十四五”期间的提升策略。结果 样本医院床医比由2015年的1[DK]∶0.86降低至2019年的1[DK]∶1.13;样本医院总诊疗人次数与年出院人次数的比值由2015年的13.0下降至2019年的10.92;2015—2018年样本医院运营效率呈良好态势,2018—2019年运营效率下滑（M=0.993）;技术效率降低是样本医院运营效率下滑的主要因素;2018—2019年专科医院运营效率下降（M=0.937）;卫生技术人员占比对样本医院运营效率的影响最为显著（β=3.80,P＜0.05）。结论 省直医院应从重点提高卫生技术人员占比方面提升运营效率,尤其是专科医院应加快引进高学历、高水平医疗人才,改善技术效率,从而实现运营效率的提升。