Citations

10571 Background: Pediatric medulloblastoma patients exposed to craniospinal radiation (CSI) are at high risk of developing endocrinopathies, including hypothyroidism. We sought to evaluate the role of genetic variation on hypothyroidism susceptibility among survivors of pediatric medullobastoma. Methods: Records from 61 medulloblastoma survivors treated at Texas Children’s Hospital between 1997 and 2013 were reviewed. All patients completed baseline and yearly follow-up thyroid assessments. Genome-wide genotyping was performed on Illumina HumanOmni1 and HumanOmni2.5 BeadChip single nucleotide polymorphism (SNP) arrays. Following standard quality control measures and exclusion of rare variants (minor allele frequency [MAF] < 5%), 572,562 autosomal SNPs were included in our analyses. The association between each SNP and hypothyroidism was tested using Fisher’s exact test and logistic regression, assuming additive allelic effects. Results: A total of 25 patients (41%) developed hypothyroidism with median follow-up of 8.3 years from diagnosis (range: 1.8-17.2 years). Primary hypothyroidism was identified in 9 (36%) cases, while the remaining 16 (64%) developed central hypothyroidism. Hypothyroidism was detected in 13 of 40 (33%) individuals exposed to < 30 Gy CSI and 12 of 21 (57%) individuals exposed to ≥30 Gy CSI (p = 0.06). Genome-wide association analysis identified several risk loci, including 3 variants associated with hypothyroidism (p-value < 1x10-5) at chromosome 2q11.2 ( NPAS2 gene). The top overall SNP (MAF = 27.5%, p-value = 6.5x10-7) remained strongly associated with hypothyroidism after accounting for possible confounders, including CSI dose, CSI type (proton/photon), age, sex, and genetic ancestry. Conclusions: Our findings suggest susceptibility to treatment-related hypothyroidism is strongly influenced by common genetic variation in NPAS2. The NPAS2 gene, a central component of the circadian rhythm network, is a transcriptional activator and regulator of DNA damage response and DNA repair genes.

Background: Periprosthetic joint infection (PJI) of the knee with concurrent disruption of the extensor mechanism is a devastating complication. Historically, knees with such complications have been salvaged with use of an arthrodesis or amputation. The purpose of this study was to assess the survival and functional outcomes of a 2-stage exchange arthroplasty combined with knitted monofilament polypropylene (Marlex; C.R. Bard) mesh reconstruction of the extensor mechanism. Methods: From 2000 to 2015, 16 patients underwent a 2-stage exchange arthroplasty and Marlex-mesh reconstruction for PJI with an extensor mechanism disruption. The study included 9 male patients and 7 female patients with a mean age at the time of reimplantation and mesh reconstruction of 64 years. The mean follow-up was 4 years. PJI was diagnosed on the basis of the Musculoskeletal Infection Society criteria. Clinical outcomes, including survivorship, Knee Society Score (KSS) results, and complications, were assessed. Results: Of 16 reconstructions, 13 were in place at the time of the latest follow-up. At 2 years, survivorship free of mesh failure was 86%, survivorship free of PJI was 87%, and survivorship free of PJI or mesh failure was 75%. The mean KSS improved from 48 prior to resection to 74 after mesh reconstruction and reimplantation. The mean extensor lag improved from 31° prior to resection to 3° after mesh reconstruction. Two patients required mesh revision, 1 patient required an above-the-knee amputation for complex wound complications related to reinfection, 1 patient developed a reinfection requiring irrigation and debridement, and 1 patient developed a superficial infection that required debridement. Conclusions: Two-stage exchange arthroplasty combined with Marlex-mesh reconstruction of the extensor mechanism is a viable alternative to knee arthrodesis or amputation. At 2 years, 75% of mesh reconstructions were in place and without evidence of PJI. Moreover, the functional outcomes were improved, with a negligible extensor lag. Level of Evidence: Therapeutic Level IV . See Instructions for Authors for a complete description of levels of evidence.

Objective: To determine the relative or combined effects of Crohn disease (CD) and ulcerative colitis (UC) and the operation performed on postoperative venous thromboembolism (VTE) to better guide recommendations on extended VTE prophylaxis. Summary Background Data: There is growing evidence to suggest patients with inflammatory bowel disease have an increased risk of postoperative VTE, but prior studies have not accounted for the operation performed nor acknowledged differences between CD and UC. Methods: The American College of Surgeons National Surgical Quality Improvement Project database from 2005 to 2016 was queried for patients with a diagnosis of CD, UC, malignancy, or benign disease (diverticular disease, Clostridium difficile) undergoing major abdominal surgery. Operations with a VTE rate >3% were designated high risk. Operation-specific univariate and multivariable logistic regression analyses were conducted. Results: A total of 231,718 operations were analyzed with 4426 patients experiencing a VTE (1.9%). The overall rate of VTE ranged widely based on the operation performed from 0.7% for enterostomy closure to 5.3% for open subtotal colectomy. Seven operations met our threshold of 3% to be considered high risk. For each operation, postoperative VTE rates were similar regardless of diagnostic indication when performed in the elective setting. However, when performed emergently, the same operations had significantly higher VTE rates. Compared with the malignancy and benign disease groups, neither CD nor UC was associated with increased odds of VTE after any operation. Conclusions: Postoperative VTE risk varies widely by the operation performed, and a diagnostic indication of CD or UC does not play a role. Extended duration VTE prophylaxis should be considered in all patients undergoing high-risk operations, regardless of their underlying diagnosis.