Complement inhibition for prevention of antibody-mediated rejection in immunologically high-risk heart allograft recipients

Allosensitization represents a major barrier to heart transplantation (HTx). We assessed the efficacy and safety of complement inhibition at transplant in highly sensitized heart transplant recipients. We performed a single-center, single-arm, open-label trial (NCT02013037). Patients with panel reactive antibodies (PRA) ≥70% and pre–formed donor-specific antibodies (DSA) were eligible. In addition to standard of care, patients received nine infusions of eculizumab during the first 2 months posttransplant. The primary composite endpoint was antibody-mediated rejection (AMR) ≥pAMR2 and/or left ventricular dysfunction during the first year. Secondary endpoints included hemodynamic compromise, allograft rejection, and patient survival. Twenty patients were included. Median cPRA and mean fluorescence intensity of immunodominant DSA were 95% (90%–97%) and 6250 (5000–10 000), respectively. Retrospective B cell and T cell flow crossmatches were positive in 14 and 11 patients, respectively. The primary endpoint occurred in four patients (20%). Survival at 1 year was 90% with no deaths resulting from AMR. In a prespecified analysis comparing treated patients to matched control patients, we observed a dramatic reduction in the risk of biopsy-proven AMR in patients treated with eculizumab (HR = 0.36, 95% CI = 0.14–0.95, p = .032). Our findings support the prophylactic use of complement inhibition for heart transplantation at high immunological risk. ClinincalTrials.gov, NCT02013037.     

The natural killer cell activating receptor,NKG2D,is critical to antibody-dependent chronic rejection in heart transplantation

Chronic rejection is among the most pressing clinical challenges in solid organ transplantation. Interestingly, in a mouse model of heterotopic heart transplantation, antibody-dependent, natural killer (NK) cell-mediated chronic cardiac allograft vasculopathy occurs in some donor–recipient strain combinations, but not others. In this study, we sought to identify the mechanism underlying this unexplained phenomenon. Cardiac allografts from major histocompatibility complex (MHC) mismatched donors were transplanted into immune-deficient C57Bl/6.rag^−/− recipients, followed by administration of a monoclonal antibody against the donor MHC class I antigen. We found marked allograft vasculopathy in hearts from C3H donors, but near-complete protection of BALB/c allografts from injury. We found no difference in recipient NK cell phenotype or intrinsic responsiveness to activating signals between recipients of C3H versus BALB/c allografts. However, cardiac endothelial cells from C3H allografts showed an approximately twofold higher expression of Rae-1, an activating ligand of the NK cell receptor natural killer group 2D (NKG2D). Importantly, the administration of a neutralizing antibody against NKG2D abrogated the development of allograft vasculopathy in recipients of C3H allografts, even in the presence of donor-specific antibodies. Therefore, the activating NK cell receptor NKG2D is necessary in this model of chronic cardiac allograft vasculopathy, and strain-dependent expression of NK activating ligands correlates with the development of this disease.     

吲哚菁绿荧光引导腹腔镜解剖性肝段获取术在小儿活体肝移植中的应用价值

目的探讨吲哚菁绿荧光引导腹腔镜解剖性肝段获取术在小儿活体肝移植中的应用价值。方法采用回顾性描述性研究方法。收集2019年12月至2020年1月首都医科大学附属北京友谊医院收治的2例行活体肝移植患儿和2例供者的临床资料。病例1,女,年龄为1岁,体质量为8.7 kg。供者为患儿父亲,年龄为35岁,体质量为93.1 kg。病例2,男,年龄为1岁,体质量为7.5 kg。供者为患儿父亲,年龄为39岁,体质量为84.0 kg。2例供者均行吲哚菁绿荧光引导腹腔镜解剖性肝段获取术获取供肝。观察指标:(1)供者手术情况。(2)供者术后情况。(3)受者术后情况。(4)随访情况。采用电话、门诊、短信、微信方式进行随访。供者于术后第1、3、6个月随访1次,了解肝功能恢复情况。受者于术后每周随访1次,了解移植物功能情况,以及排斥反应、胆汁漏、胆道狭窄、血栓形成、血管狭窄等并发症发生情况。随访时间截至2020年7月。结果(1)供者手术情况。病例1供者总手术时间为234 min,供肝减体积处理时间为40 min,术中出血量为60 mL,未输血。经减体积处理后供肝实际质量为225.2 g。病例2供者总手术时间为220 min,供肝减体积处理时间为40 min,术中出血量为40 mL,未输血。经减体积处理后供肝实际质量为178.0 g。(2)供者术后情况。病例1供者丙氨酸氨基转移酶(ALT)、天冬氨酸氨基转移酶(AST)、总胆红素(TBil)于术后第2天达到峰值,分别为493 U/L、186.0 U/L、30.66μmol/L,于术后第3天下降为388 U/L、90.9 U/L、22.57μmol/L;术后首次下床活动时间为术后2 d、术后首次进食流质食物时间为术后1 d、术后拔除腹腔引流管时间为术后3 d、术后住院时间为4 d、围术期无≥Clavien-DindoⅡ级并发症发生。病例2供者ALT、AST、TBil于术后第1天达到峰值,分别为602 U/L、454.6 U/L、30.49μmol/L,于术后第4天下降为355 U/L、55.7 U/L、20.65μmol/L;术后首次下床活动时间为术后2 d、术后首次进食流质食物时间为术后1 d、术后拔除腹腔引流管时间为术后3 d、术后住院时间为5 d、围术期无≥Clavien-DindoⅡ级并发症发生。(3)受者术后情况。病例1 ALT、AST、TBil于术后第1天达到峰值,分别为670 U/L、288.7 U/L、22.13μmol/L,于术后第14天下降为54 U/L、33.0 U/L、5.75μmol/L;术后住院时间为20 d,围术期无≥Clavien-DindoⅡ级并发症发生。病例2 ALT、AST、TBil于术后第1天达到峰值,分别为520 U/L、93.9 U/L、31.42μmol/L,于术后第14天下降为87 U/L、60.8 U/L、11.51μmol/L;术后住院时间为25 d,围术期无≥Clavien-DindoⅡ级并发症发生。(4)随访情况。2例供者均获得术后1、3、6个月随访,术后1个月随访肝功能恢复至正常水平,术后3个月及6个月随访肝功能未见异常。2例受者均获得术后每周随访。随访期间,移植物功能均正常,均未发生排斥反应、胆汁漏、胆道狭窄、血栓形成、血管狭窄等并发症。结论吲哚菁绿荧光引导腹腔镜解剖性肝段获取术应用于小儿活体肝移植安全、可行,可由具有丰富腹腔镜供肝获取手术经验的团队施行。     

Selected Topics in the Pathology of the Thyroid and Parathyroid Glands in Children and Adolescents

The goals of this chapter in keeping with the overall general themes of this special edition will be (1) to highlight aspects of development of the thyroid and parathyroid glands with particular focus on the role and contribution of the neural crest (or not) and how this may impact on the pathology that is seen, (2) to emphasize those lesions particularly more commonly arising in the pediatric population that actually generate specimens that the surgical pathologist would encounter, and (3) highlight more in depth specific lesions associated with heritable syndromes or specific gene mutations since the heritable syndromes tends to manifest in the pediatric age group. In this light, the other interesting areas of pediatric thyroid disease including medical thyroid diseases, congenital hypothyroidism, anatomic variants and aberrations of development that lead to structural anomalies will not be emphasized here.     

小儿鼻颅底针形内窥镜的检查与手术

目的：探讨应用针形内窥镜对小儿鼻颅底疾病进行探查与手术的方法及疗效。方法：在外径１．９ｍｍ的进口针形内窥镜及电视同图像系统监视下,对８例小儿（７ｄ￣１２岁）鼻颅底有关疾病进行探杳与手术。结果：先天性后鼻孔闭锁３例中,１例好转,３例痊愈。外伤性脑脊液鼻漏１例,经修补痊愈先天性脑膜脑膨出２例,确诊后１例暂缓治疗。另１例行内窥镜手术痊愈。颅底神经母细胞瘤２例取材作病理检查确诊。结论：在电视图像监视下应用     

Antimicrobial susceptibility and serotype replacement of Streptococcus pneumoniae in children before and after PCV13 introduction in Taiwan

BackgroundSince 2015, 13-valent pneumococcal conjugate vaccine (PCV13) was included in the national immunization program in Taiwan. Subsequently, the serotypes of the main circulating Streptococcus pneumoniae strains have changed. PCV administration is also associated with changes in the antimicrobial susceptibility of S. pneumoniae strains. Therefore, in this study, we analyzed the serotype distribution and antimicrobial susceptibility of S. pneumoniae in pediatric infections.MethodsChildren with S. pneumoniae infections, including invasive pneumococcal disease (IPD) and non-IPD, were enrolled from January 2010 to December 2020. The samples were collected from Mackay Memorial Hospital, MacKay Children's Hospital, and Hsinchu Mackay Hospital in Taiwan. We analyzed the epidemiology of sample collection site, infection diagnosis, and the serotype and antimicrobial susceptibility of S. pneumoniae strains. The study period was divided into time points before and after PCV13 administration.ResultsIn total, 322 isolates were collected during the study period. The incidence of IPD declined annually, from 29.7% before 2015 to 7.3% after 2015 (p < 0.001). The prevalence of serotype 19 A had increased gradually since 2010 but declined rapidly after 2013. Serotypes 15 A and 23 A were the most common serotypes after 2015. The non-susceptibility of the S. pneumoniae isolates to penicillin, cefotaxime, and ceftriaxone decreased. Based on meningitis breakpoints, the non-susceptibility to cefotaxime and ceftriaxone gradually decreased, but increased in 2020.ConclusionPCV13 was considerably effective in reducing the incidence of IPD in children; however, the prevalence of serotypes 15 A and 23 A increased. The increase in antimicrobial non-susceptibility caused by non-vaccine serotypes must be continuously monitored.     

A better incision for pectus excavatum repair: avoiding the keloid triangle

The most common approach to the pepair of pectus excavatum and pectus carinatum deformities is via a central transverse submammary incision. The subsequent suprasternal scar is conspicuous and prone to hypertrophic and keloid scarring. To avoid the keloid triangle and to produce a less noticeable scar, we have utilized bilateral inframammary incisions for repairs of five female and two male patients with pectus defects. This approach provides excellent access for cartilage resection, sternotomy, and sternal tupport without increasing opearative time or compromising operative exposure. On follow-up for up to 25 months, all patients have had excellent cosmetic and functional results. Chest wall configuration and stability, wound healing, and scar formation have all been without complication. No keloid or hypertrophic scars have developed. To date, there has been no recurrence of pectus defects. We believe bilateral inframammary incisions are a superior approach for pectus repairs by enchancing cosmesis with less noticeable scars and fewer hypertropic and keloid scars, all without compromising operative exposure or increasing operative time.