Validity and utility of urinary CXCL10/Cr immune monitoring in pediatric kidney transplant recipients

Individualized posttransplant immunosuppression is hampered by suboptimal monitoring strategies. To validate the utility of urinary CXCL10/Cr immune monitoring in children, we conducted a multicenter prospective observational study in children <21 years with serial and biopsy-associated urine samples (n = 97). Biopsies (n = 240) were categorized as normal (NOR), rejection (>i1t1; REJ), indeterminate (IND), BKV infection, and leukocyturia (LEU). An independent pediatric cohort of 180 urines was used for external validation. Ninety-seven patients aged 11.4 ± 5.5 years showed elevated urinary CXCL10/Cr in REJ (3.1, IQR 1.1, 16.4; P < .001) and BKV nephropathy (median = 5.6, IQR 1.3, 26.9; P < .001) vs. NOR (0.8, IQR 0.4, 1.5). The AUC for REJ vs. NOR was 0.76 (95% CI 0.66–0.86). Low (0.63) and high (4.08) CXCL10/Cr levels defined high sensitivity and specificity thresholds, respectively; validated against an independent sample set (AUC = 0.76, 95% CI 0.66–0.86). Serial urines anticipated REJ up to 4 weeks prior to biopsy and declined within 1 month following treatment. Elevated mean CXCL10/Cr was correlated with first-year eGFR decline (ρ = −0.37, P ≤ .001), particularly when persistently exceeding ≥4.08 (ratio = 0.81; P < .04). Useful thresholds for urinary CXCL10/Cr levels reproducibly define the risk of rejection, immune quiescence, and decline in allograft function for use in real-time clinical monitoring in children.     

Remote intervention engagement and outcomes in the Clinical Trials in Organ Transplantation in Children consortium multisite trial

Remote interventions are increasingly used in transplant medicine but have rarely been rigorously evaluated. We investigated a remote intervention targeting immunosuppressant management in pediatric lung transplant recipients. Patients were recruited from a larger multisite trial if they had a Medication Level Variability Index (MLVI) ≥2.0, indicating worrisome tacrolimus level fluctuation. The manualized intervention included three weekly phone calls and regular follow-up calls. A comparison group included patients who met enrollment criteria after the subprotocol ended. Outcomes were defined before the intent-to-treat analysis. Feasibility was defined as ≥50% of participants completing the weekly calls. MLVI was compared pre- and 180 days postenrollment and between intervention and comparison groups. Of 18 eligible patients, 15 enrolled. Seven additional patients served as the comparison. Seventy-five percent of participants completed ≥3 weekly calls; average time on protocol was 257.7 days. Average intervention group MLVI was significantly lower (indicating improved blood level stability) at 180 days postenrollment (2.9 ± 1.29) compared with pre-enrollment (4.6 ± 2.10), p = .02. At 180 days, MLVI decreased by 1.6 points in the intervention group but increased by 0.6 in the comparison group (p = .054). Participants successfully engaged in a long-term remote intervention, and their medication blood levels stabilized. NCT02266888.     

COVID-19 in pediatric kidney transplantation: The Improving Renal Outcomes Collaborative

There are limited data on the impact of COVID-19 in children with a kidney transplant (KT). We conducted a prospective cohort study through the Improving Renal Outcomes Collaborative (IROC) to collect clinical outcome data about COVID-19 in pediatric KT patients. Twenty-two IROC centers that care for 2732 patients submitted testing and outcomes data for 281 patients tested for SARS-CoV-2 by PCR. Testing indications included symptoms and/or potential exposures to COVID-19 (N = 134, 47.7%) and/or testing per hospital policy (N = 154, 54.8%). Overall, 24 (8.5%) patients tested positive, of which 15 (63%) were symptomatic. Of the COVID-19-positive patients, 16 were managed as outpatients, six received non-ICU inpatient care and two were admitted to the ICU. There were no episodes of respiratory failure, allograft loss, or death associated with COVID-19. To estimate incidence, subanalysis was performed for 13 centers that care for 1686 patients that submitted all negative and positive COVID-19 results. Of the 229 tested patients at these 13 centers, 10 (5 asymptomatic) patients tested positive, yielding an overall incidence of 0.6% and an incidence among tested patients of 4.4%. Pediatric KT patients in the United States had a low estimated incidence of COVID-19 disease and excellent short-term outcomes.     

4年间我院儿科临床大肠埃希菌耐药性变迁分析

目的：监测我院4年间儿科临床分离的大肠埃希菌的耐药情况，了解其耐药性发生和发展的规律，以指导儿科临床合理选用抗大肠埃希菌药物。方法：2001年1月-2004年12月从儿科临床标本分离的84株大肠埃希菌按照分离时间分为2001-2002年组（2001年1月-2002年12月）48株和2003-2004年组（2003年1月-2004年12月）36株，分别比较两组产超广谱B内酰胺酶（ESBLs）和对22种抗菌药物敏感性试验结果。结果：ESBLs检测结果：2001-2002年组产ESBLs株检测率为37．5％（15／40），2003-2004年组产酶株捡出率为46．9％（15／32），经x^2检验，P〉0．05，无显著性差异。药物敏感性实验结果：2003-2004年组比2001-2002年组耐药率明显升高，22种抗生素中除外亚胺培南未发现耐药菌外，其他抗生素耐药率均有不同程度增高，增幅为（16．7％-88．9％），经x^2检验，均有极显著性差异（P〈0．01），其中耐药率上升最快的5种抗生索分别为头孢曲松、头孢唑啉、头孢嚷肟、头孢拉定、头孢呋辛。耐药率上升较慢的5种抗生素分别为阿米卡星、头孢西丁、头孢哌酮／舒巴坦、头孢他定和四环素。结论：儿科临床大肠埃希菌耐药性发展迅速，以对头孢类抗生素耐药性上升最为显著，且呈多重耐药趋势。治疗上不宜选用头孢类抗生索和复方磺胺甲嗯唑，应选用头孢西丁、加酶抑制剂复合抗生素以及亚胺培南。     

儿科介入呼吸病学的历史 现状及展望

国内儿科呼吸内镜的开展要比成人晚10余年。1985年,我国儿科医院开始使用纤维支气管镜。20世纪90年代,首都医科大学附属北京儿童医院创建了国内首个儿科支气管镜室,国内开始建立对呼吸专业有重大意义的儿科气管镜方法。发展至今,支气管镜术在很多医院都成为了方法过关、安全可靠的有效诊疗手段,对支气管镜术在诊断中的需求性甚至和CT一样普及,特别是对呼吸系统重症和疑难病的诊断与治疗起到了巨大作用。未来,要将儿童介入呼吸病学发展为综合多学科的临床应用。     

Allogeneic hematopoietic cell transplantation in chemotherapy‐induced aplasia in children with high‐risk acute myeloid leukemia or myelodysplasia

Relapse remains the most common cause of treatment failure after hematopoietic cell transplantation for acute myeloid leukemia. Inability to achieve hematologic complete remission has been a barrier to transplant for patients with refractory disease. We describe six children with refractory myeloid disease undergoing transplant in chemotherapy‐induced aplasia, as a strategy to facilitate curative therapy in refractory patients. Clofarabine‐ or high‐dose cytarabine‐based chemotherapy regimens were used to achieve marrow aplasia, followed by reduced‐intensity conditioning and allogeneic transplant before hematologic recovery. Long‐term disease control was achieved in five, with one transplant‐related mortality, suggesting the feasibility of this approach.