Update on the Systemic Risks of Superpotent Topical Steroids.

INTRODUCTION: The potential for systemic effects due to percutaneous absorption of superpotent topical steroids has been a longstanding concern. The Food and Drug Administration currently recommends limiting the use of superpotent topical steroids to 50g per week for 2 or 4 consecutive weeks depending on the formulation, which is mostly based on the exact duration with which phase 3 clinical trials were allowed to be conducted per the FDA. This article reviews all published clinical incidence of adrenal adverse effects in the medical literature, specifically Cushing's syndrome (CS) and pathologic adrenal suppression (PAAS), to try to ascertain a more realistic limit for the safe use of superpotent topical steroids as it pertains to its potential systemic effects.

METHODS: Literature search was conducted using PubMed. Only cases of CS and PAAS secondary to the use of Class I superpotent topical steroids were included. Pediatric cases and full articles unavailable in English were excluded.

RESULTS: There were a total of 14 cases of CS and 5 cases of subsequent PAAS found in the current literature.

DISCUSSION: From our review of these cases, if the amount used per week is within FDA guidelines, it appears that patients needed to use superpotent topical steroids for far greater than 2 or 4 weeks to develop CS or PAAS. CS did not necessarily predict occurrence of PAAS, but in all cases CS appeared to be a prerequisite for developing PAAS. All cases of CS and all but one case of PAAS were reversible. If excessive amount of greater than 50g per week is avoided, it appears that superpotent topical steroids may be safe to use consecutively for months, perhaps even years, without causing systemic effects.

J Drugs Dermatol. 2017;16(7):643-648.

Multivendor implementation and comparison of volumetric whole-brain echo-planar MR spectroscopic imaging.

PURPOSE: To assess volumetric proton MR spectroscopic imaging (MRSI) of the human brain on multivendor MRI instruments. METHODS: Echo-planar spectroscopic imaging was developed on instruments from three manufacturers, with matched specifications and acquisition protocols that accounted for differences in sampling performance, radiofrequency (RF) power, and data formats. Intersite reproducibility was evaluated for signal-normalized maps of N-acetylaspartate (NAA), creatine (Cre), and choline using phantom and human subject measurements. Comparative analyses included metrics for spectral quality, spatial coverage, and mean values in atlas-registered brain regions. RESULTS: Intersite differences for phantom measurements were less than 1.7% for individual metabolites and less than 0.2% for ratio measurements. Spatial uniformity ranged from 79% to 91%. The human studies found differences of mean values in the temporal lobe, but good agreement in other white matter regions, with maximum differences relative to their mean of under 3.2%. For NAA/Cre, the maximum difference was 1.8%. In gray matter, a significant difference was observed for frontal lobe NAA. Primary causes of intersite differences were attributed to shim quality, B0 drift, and accuracy of RF excitation. Correlation coefficients for measurements at each site were over 0.60, indicating good reliability. CONCLUSION: A volumetric intensity-normalized MRSI acquisition can be implemented in a comparable manner across multivendor MR instruments.

Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin.

Follicular lymphoma (FL) and the GCB subtype of diffuse large B-cell lymphoma (DLBCL) derive from germinal center B cells. Targeted resequencing studies have revealed mutations in various genes encoding proteins in the NF-kappaB pathway that contribute to the activated B-cell (ABC) DLBCL subtype, but thus far few GCB-specific mutations have been identified. Here we report recurrent somatic mutations affecting the polycomb-group oncogene EZH2, which encodes a histone methyltransferase responsible for trimethylating Lys27 of histone H3 (H3K27). After the recent discovery of mutations in KDM6A (UTX), which encodes the histone H3K27me3 demethylase UTX, in several cancer types, EZH2 is the second histone methyltransferase gene found to be mutated in cancer. These mutations, which result in the replacement of a single tyrosine in the SET domain of the EZH2 protein (Tyr641), occur in 21.7% of GCB DLBCLs and 7.2% of FLs and are absent from ABC DLBCLs. Our data are consistent with the notion that EZH2 proteins with mutant Tyr641 have reduced enzymatic activity in vitro.

Predicting the degradability of waste activated sludge.

The objective of this study was to identify methods for estimating anaerobic digestibility of waste activated sludge (WAS). The WAS streams were generated in three sequencing batch reactors (SBRs) treating municipal wastewater. The wastewater and WAS properties were initially determined through simulation of SBR operation with BioWin (EnviroSim Associates Ltd., Flamborough, Ontario, Canada). Samples of WAS from the SBRs were subsequently characterized through respirometry and batch anaerobic digestion. Respirometry was an effective tool for characterizing the active fraction of WAS and could be a suitable technique for determining sludge composition for input to anaerobic models. Anaerobic digestion of the WAS revealed decreasing methane production and lower chemical oxygen demand removals as the SRT of the sludge increased. BioWin was capable of accurately describing the digestion of the WAS samples for typical digester SRTs. For extended digestion times (i.e., greater than 30 days), some degradation of the endogenous decay products was assumed to achieve accurate simulations for all sludge SRTs.

Heterotopic heart transplant combined with postoperative Sildenafil use for the treatment of restrictive cardiomyopathy.

We report successful management of a 22-month-old child with restrictive cardiomyopathy and severe pulmonary hypertension using the heterotopic heart transplant technique. Additional lessons learned from postoperative management, including the novel use of Sildenafil (Viagra, Pfizer, NY) for controlling pulmonary arterial pressure are described.