Poly(ADP-ribose)polymerase (PARP)14-a member of the B aggressive lymphoma (BAL) family of macrodomain-containing PARPs-is an ADP ribosyltransferase that interacts with Stat6, enhances induction of certain genes by IL-4, and is expressed in B lymphocytes. We now show that IL-4 enhancement of glycolysis in B cells requires PARP14 and that this process is central to a role of PARP14 in IL-4-induced survival. Thus, enhancements of AMP-activated protein kinase activity restored both IL-4-induced glycolytic activity in Parp14 −/− B cells and prosurvival signaling by this cytokine. Suppression of apoptosis is central to B-lymphoid oncogenesis, and elevated macro-PARP expression has been correlated with lymphoma aggressiveness. Strikingly, PARP14 deficiency delayed B lymphomagenesis and reversed the block to B-cell maturation driven by the Myc oncogene. Collectively, these findings reveal links between a mammalian ADP ribosyltransferase, cytokine-regulated metabolic activity, and apoptosis; show that PARP14 influences Myc-induced oncogenesis; and suggest that the PARP14-dependent capacity to increase cellular metabolic rates may be an important determinant of lymphoma pathobiology.

Objectives A previous study proposed that serial full-thickness excisional biopsies of vocal fold leukoplakia therapeutically decreased dysplasia grade. The current investigation aimed to 1) analyze the pathological evolution and natural history of these lesions and 2) re-examine the role of serial excisions on dysplasia grade regression in long-term follow-up. Study Design Retrospective case series Methods Patients treated for vocal fold dysplasia (1994 – 2013) with serial full-thickness microflap-type excisions were identified and followed longitudinally. Excluded were those with one excision, invasive cancer at initial excision, or history of laryngeal cancer or radiation. Data from surgical procedures, associated pathology, and patient characteristics were recorded. Weighted repeated measures ordinal logistic regression measured associations with pathology findings. Results Of 55 patients [median age 65 (interquartile range 54 - 73), 89% male, 63% ever smokers, 27% alcohol users], 31 met inclusion criteria. During the study period, patients had two to 44 excisions with median time between excisions of 4.0 months. Each additional excision increased odds of higher-grade pathology by 4% (odds ratio 1.04, 95% confidence interval 1.01 – 1.06; p=0.007). A transition model demonstrated patients with moderate dysplasia, severe dysplasia, or carcinoma in situ on a prior biopsy had 2.64-, 5.64-, and 8.73-times increased odds of the same or higher pathology grade at the next excision. Conclusions Data does not support the hypothesis that serial full-thickness excisions decrease dysplasia grade. Progression of dysplasia appears to be non-linear, but higher-grade dysplasia is more likely to progress to malignancy.

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A 6-week-old male infant presented with 2 days of fever, emesis, and diarrhea, associated with episodic and chaotic rapid eye movements, determined to be opsoclonus. An electroencephalogram (EEG) obtained during the events was normal. He was treated empirically for meningitis, and an initial workup for neuroblastoma including urine homovanillic acid and vanillylmandelic acid levels, abdominal ultrasonography, and computed tomography (CT) of the chest, abdomen, and pelvis was negative. Stool and blood cultures were positive for Salmonella, and antibiotic regimen was adjusted appropriately. Over the next few days, his fever, emesis, and diarrhea subsided, and the opsoclonus resolved by hospital day 6. He was back to baseline by hospital day 9. Although there have been cases of parainfectious opsoclonus associated with Lyme disease, enterovirus, Streptococcus, and West Nile virus, this represents the first reported pediatric case of opsoclonus associated with salmonellosis. Only 2 such cases in adults have been reported in the literature.

Clinicians should be aware of an elevated prevalence of moyamoya syndrome in Down syndrome and sickle cell disease populations and should consider moyamoya syndrome in the differential diagnosis of postoperative stroke. Stroke risk is magnified in the perioperative setting related to perioperative dehydration and hypotension. Awareness and screening for cerebral vasculopathy in high-risk populations could prompt measures to decrease the occurrence of postoperative strokes after adenotonsillectomies.

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