Warad, Deepti

We report a 9-year-old Chinese girl with congenital thrombotic thrombocytopenic purpura found to be a compound heterozygote for 2 pathogenic variants in the ADAMTS13 gene, including a novel variation. The girl suffered from recurrent, life-threatening episodes of thrombocytopenia and hemolysis, and laboratory testing showed ADAMST13 enzyme activity of <5%. Sequencing of the ADAMTS13 gene revealed a previously reported missense variant, c.1787C>T (p.Ala596Val), and a novel duplication defined as c.1007_1025dup19 (p.Asp343Leufs*53); the duplication is predicted to result in a premature stop codon and protein truncation. We propose that this novel variant is partly responsible for the patient’s early-onset and severe phenotype.

AbstractHCC is rare in the pediatric population, but is the second most common liver malignancy in children. Survival rates for primary unresectable HCC have been dismal. The objective of this study was to describe our experience with a multimodal approach for the management of unresectable HCC in two adolescent patients and to review the literature. Both patients are currently alive with no recurrence at 51 and 29 months post‐transplant. Multimodality treatment involving chemotherapy with doxorubicin, cisplatin, and sorafenib; TACE; timely liver transplantation; and post‐transplant therapy with sorafenib and mTOR inhibitors may help improve outcomes and prolong survival in pediatric patients with unresectable HCC.

IntroductionCentral venous access devices (CVADs) are frequently required as stable long‐lasting venous access in children with haemophilia, especially those requiring immune tolerance induction (ITI) for inhibitors. CVAD infection is one of the most frequently reported catheter‐related complications in this patient population.AimDetailed review of CVAD complications from the International ITI (I‐ITI) study and analysis of potential risk factors for such complications.MethodsRetrospective analysis of prospectively obtained data from the I‐ITI study primarily focused on CVAD‐related complications.ResultsA total of 115 children were recruited and 183 CVADs were placed in 99 subjects resulting in 121,206 CVAD‐days observed on‐study. A total of 124 CVAD infections were reported in 41 of 99 (41%) subjects with an overall infection rate of 0.94 per 1000 CVAD‐days (interquartile ranges 0–1.7). A similar number of infections were observed in the two treatment arms (median: 2 and 3 in high dose and low dose respectively). Infections occurred more frequently in the presence of external catheters than with fully implanted catheters (P = 0.026). Infected patients were significantly younger at the time of CVAD insertion (median age: 22 vs. 25 months, P = 0.020). Patients with Gram‐positive infections were also significantly younger than those with Gram‐negative infections (median age: 17 vs. 25 months, P < 0.0001).ConclusionCVAD infection was the most common complication observed in children with severe haemophilia and inhibitors in the frame of the I‐ITI study. Younger age at CVAD insertion and external CVAD were associated with higher risk for infection. ITI outcome was unaffected by CVAD infections.

Abstract Purpose: Immunotherapeutic strategies to treat patients with renal cell carcinoma (RCC) offer new opportunities for disease management. Further improvements to immunotherapy will require additional understanding of the host response to RCC development. Experimental Design: Using a novel approach to understanding the immune status of cancer patients, we previously showed that patients with a certain immune profile had decreased overall survival. Here, we examine in more detail the phenotypic changes in peripheral blood and the potential consequences of these changes in RCC patients. Results: We found that CD14+HLA-DRlo/neg monocytes were the most predominant phenotypic change in peripheral blood of RCC patients, elevated nearly 5-fold above the average levels measured in healthy volunteers. Intratumoral and peritumoral presence of CD14 cells was an independent prognostic factor for decreased survival in a cohort of 375 RCC patients. The amount of peripheral blood CD14+HLA-DRlo/neg monocytes was found to correlate with the intensity of CD14 staining in tumors, suggesting that the measurement of these cells in blood may be a suitable surrogate for monitoring patient prognosis. The interaction of monocytes and tumor cells triggers changes in both cell types with a loss of HLA-DR expression in monocytes, increases of monocyte survival factors such as GM-CSF in tumors, and increased production of angiogenic factors, including FGF2. Conclusions: Our results suggest a model of mutually beneficial interactions between tumor cells and monocytes that adversely affect patient outcome. Clin Cancer Res; 21(18); 4224–33. ©2015 AACR.

SummaryHaemorrhagic complications remain a challenge with surgical procedures in patients with bleeding disorders. In children and young adults, the most commonly performed surgeries are tonsillectomies and/or adenoidectomies. Adequate haemostasis in these patients with bleeding disorders is centred on comprehensive perioperative haemostatic support and dexterous surgical technique. The aim of this study was to assess postoperative bleeding complications with tonsillectomy and/or adenoidectomy in children and young adults with known bleeding disorders. Retrospective review of all patients aged <25 years with known bleeding disorders who underwent tonsillectomy and/or adenoidectomy at Mayo Clinic, Rochester MN between July 1992 and July 2012. In contrast to reported literature, we observed a higher rate of bleeding complications (10/19, 53%) despite aggressive haemostatic support and appropriate surgical techniques. Delayed bleeding (>24 h postoperatively) was more common than early bleeding; and recurrent bleeding was associated with older age. Children and young adults with haemorrhagic diatheses undergoing adenotonsillectomy are at a higher risk of delayed bleeding and require close monitoring with haemostatic support for a prolonged duration in the postoperative period. A uniform approach is needed to manage these patients perioperatively by establishing standard practice guidelines and ultimately reduce postsurgical bleeding complications.