Association between itch and cancer in 16,925 patients with pruritus: Experience at a tertiary care center.

BACKGROUND: Pruritus has been associated with cancer. However, limited data are available on the types of underlying malignancies associated with pruritus. OBJECTIVE: We sought to characterize the association between pruritus and different cancer types, as well as variations by racial group. METHODS: Cross-sectional study of patients ≥18 years of age seen at the Johns Hopkins Health System during 2013-2017. Patients with pruritus were compared with patients without pruritus. Analyses were stratified by race. RESULTS: Patients with pruritus were more likely to have concomitant malignancy than those without pruritus (odds ratio 5.76, 95% confidence interval 5.53-6.00). Most strongly associated were cancers of the liver, gallbladder and biliary tract, hematopoietic system, and skin. Compared with white patients, black patients more frequently had soft tissue, dermatologic, and hematologic malignancies and less frequently had liver, respiratory, gastrointestinal, and gynecologic malignancies. LIMITATIONS: The cross-sectional design precludes analysis of the temporal association between pruritus and malignancy. The study is limited to a single tertiary care center. CONCLUSION: Pruritus is most strongly associated with cancers of the liver, skin, and hematopoietic system. Black patients with pruritus have a higher likelihood of skin, soft tissue, and hematologic malignancies than white patients, while whites have higher likelihoods of liver, respiratory, gastrointestinal, and gynecologic malignancies.

Novel mutation in the KCNJ10 gene in three siblings with seizures, ataxia and no electrolyte abnormalities.

We report a consanguineous family with three affected siblings with novel mutation in the KCNJ10 gene. All three presented with central nervous system symptoms in the form of infantile focal seizures, ataxia, slurred speech with early developmental delay and intellectual disability in two siblings. None had any associated electrolyte abnormalities and no symptomatic hearing deficits were observed.

Association between Itch and Cancer in 3836 Pediatric Pruritus Patients at a Tertiary Care Center.

Background: Pruritus is a well-recognized paraneoplastic phenomenon. Previous studies have examined the association of itch with a variety of malignancies in adults. However, no large study has examined this association in a pediatric population. Methods: A retrospective study was conducted of patients age 18 or less seen at Johns Hopkins Health System between 2012 and 2019. Results: A pediatric hospital population of 1,042,976 patients was reviewed. Pruritus was observed in 3836 pediatric patients of whom 130 also had cancer. Pediatric patients with pruritus were significantly more likely to have concomitant malignancy compared to pediatric patients without pruritus (OR 12.84; 95% CI 10.73-15.35, p < 0.001). Malignancies most strongly associated with pruritus included neoplasms of the blood (OR 14.38; 95% CI 11.30-18.29, p < 0.001), bone (OR 29.02, 95% CI 18.28-46.06, p < 0.001) and skin (OR 22.76, 95% CI 9.14-56.72, p < 0.001. Conclusions: Pruritus is significantly associated with malignancy in the pediatric hospital population. Clinicians should also be aware of the high burden of itch in pediatric malignancies and the variation in pruritus across malignancies.

Oligodendrocytes control potassium accumulation in white matter and seizure susceptibility.

The inwardly rectifying K+ channel Kir4.1 is broadly expressed by CNS glia and deficits in Kir4.1 lead to seizures and myelin vacuolization. However, the role of oligodendrocyte Kir4.1 channels in controlling myelination and K+ clearance in white matter has not been defined. Here, we show that selective deletion of Kir4.1 from oligodendrocyte progenitors (OPCs) or mature oligodendrocytes did not impair their development or disrupt the structure of myelin. However, mice lacking oligodendrocyte Kir4.1 channels exhibited profound functional impairments, including slower clearance of extracellular K+ and delayed recovery of axons from repetitive stimulation in white matter, as well as spontaneous seizures, a lower seizure threshold, and activity-dependent motor deficits. These results indicate that Kir4.1 channels in oligodendrocytes play an important role in extracellular K+ homeostasis in white matter, and that selective loss of this channel from oligodendrocytes is sufficient to impair K+ clearance and promote seizures.

Electrophysiological properties of NG2(+) cells: Matching physiological studies with gene expression profiles.

NG2(+) glial cells are a dynamic population of non-neuronal cells that give rise to myelinating oligodendrocytes in the central nervous system. These cells express numerous ion channels and neurotransmitter receptors, which endow them with a complex electrophysiological profile that is unique among glial cells. Despite extensive analysis of the electrophysiological properties of these cells, relatively little was known about the molecular identity of the channels and receptors that they express. The generation of new RNA-Seq datasets for NG2(+) cells has provided the means to explore how distinct genes contribute to the physiological properties of these progenitors. In this review, we systematically compare the results obtained through RNA-Seq transcriptional analysis of purified NG2(+) cells to previous physiological and molecular studies of these cells to define the complement of ion channels and neurotransmitter receptors expressed by NG2(+) cells in the mammalian brain and discuss the potential significance of the unique physiological properties of these cells. This article is part of a Special Issue entitled SI:NG2-glia(Invited only).