Here we sequence 633 genes, encoding the majority of known epigenetic regulatory proteins, in over 1000 pediatric tumors to define the landscape of somatic mutations in epigenetic regulators in ...pediatric cancer. Our results demonstrate a marked variation in the frequency of gene mutations across 21 different pediatric cancer subtypes, with the highest frequency of mutations detected in high-grade gliomas, T-lineage acute lymphoblastic leukemia, medulloblastoma, and a paucity of mutations in low-grade glioma, and retinoblastoma. The most frequently mutated genes are
H3F3A, PHF6, ATRX, KDM6A, SMARCA4, ASXL2, CREBBP, EZH2, MLL2, USP7, ASXL1, NSD2, SETD2, SMC1A,
and
ZMYM3
. Importantly, we identify novel loss-of-function mutations in the ubiquitin-specific-processing protease 7 (USP7) in pediatric leukemia, which result in a decrease in deubiquitination activity. Collectively, our results help to define the landscape of mutations in epigenetic regulatory genes in pediatric cancer and yield a valuable new database for investigating the role of epigenetic dysregulations in cancer.
To assess the efficacy of intraincisional clindamycin therapy as an alternative to nafcillin treatment in decreasing the risk of postoperative wound infections in dermatologic surgery.
Prospective, ...double-blinded, randomized, placebo-controlled trial conducted over a 7-month period.
Three private practice Mohs micrographic surgery referral centers.
A total of 1030 consecutive patients who underwent Mohs micrographic surgery with subsequent reconstruction.
Prior to reconstruction, patients were randomly assigned to receive either intraincisional buffered lidocaine with epinephrine containing clindamycin or buffered lidocaine with epinephrine without clindamycin. Nurses and physicians who scored the wound at follow-up were blinded to the treatment conditions.
Surgical wounds evaluated at the time of suture removal were scored according to a standardized assessment based on erythema, edema, and the presence of purulent discharge. Wounds scored 4 or higher were considered to be infected. Bacterial cultures obtained when indicated were also compared.
Of the 1172 surgical wounds included in the study, 29 had wound scores of 4 or higher, 6 in the study group and 23 in the control group (P =.001, Fisher exact test). Of these 29, 18 had culture-positive infections. Four of these occurred in the study group, and 14 occurred in the control group (P =.02, Fisher exact test).
The results of this study further support the efficacy of single-dose preoperative intraincisional antibiotic treatment for dermatologic surgery. With the relatively high prevalence of patient-reported penicillin allergies, buffered lidocaine containing clindamycin offers an inexpensive, safe, convenient, and effective alternative.
After an outbreak of Yersinia enterocolitica infections among black children in Atlanta, a seven-hospital study was conducted to determine the importance of this pathogen in other communities with ...large black populations. Of 4841 stool specimens from patients with gastroenteritis examined between November 1989and January 1990, Y. enterocolitica, Shigella, Campylobaeter, and Salmonella were identified in 38, 49, 60, and 98 specimens, respectively; 34 (92%) of 37 Y. enterocolitica isolates were serotype O:3. Of the 38 patients with yersiniosis, 37(97%) were children. Illnesses were clustered around the holidays, and 20 (62%) of 32 patients had been exposed to raw pork intestines in the 2 weeks before onset. Exposure was significantly associated with illness in a case-control study of eight patients identified at one hospital (P =.004). Infants ⩽ 6 months old with yersiniosis were more likely to have immature-to-total neutrophil ratios >0.50 than were infants of comparable age with salmonellosis (P = .02). Infrequently isolated in the past, Y. enterocolitica O:3 isemerging as an important enteric pathogen in this country, particularly among black children.
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