The esophageal biopsy “pull” sign: a highly specific and treatment-responsive endoscopic finding in eosinophilic esophagitis (with video)

Esophageal biopsies in patients with eosinophilic esophagitis (EoE) can feel firm, with resistance appreciated when pulling the forceps to obtain the tissue sample. We aimed to assess the diagnostic utility of the esophageal biopsy pull sign, and determine its histologic associations and response to treatment

Accuracy of the Eosinophilic Esophagitis Endoscopic Reference Score in Diagnosis and Determining Response to Treatment

Little is known about the diagnostic utility of the eosinophilic esophagitis (EoE) endoscopic reference score (EREFS), and how scores change in response to treatment. We investigated the operating characteristics of the EREFS in diagnosis of EoE, how the score changes with treatment, and ways to optimize scoring system

How Bulk Sensitive is Hard X-ray Photoelectron Spectroscopy: Accounting for the Cathode-Electrolyte Interface when Addressing Oxygen Redox.

Sensitivity to the "bulk" oxygen core orbital makes hard X-ray photoelectron spectroscopy (HAXPES) an appealing technique for studying oxygen redox candidates. Various studies have reported an additional O 1s peak (530-531 eV) at high voltages, which has been considered a direct signature of the bulk oxygen redox process. Here, we find the emergence of a 530.4 eV O 1s HAXPES peak for three model cathodes-Li2MnO3, Li-rich NMC, and NMC 442-that shows no clear link to oxygen redox. Instead, the 530.4 eV peak for these three systems is attributed to transition metal reduction and electrolyte decomposition in the near-surface region. Claims of oxygen redox relying on photoelectron spectroscopy must explicitly account for the surface sensitivity of this technique and the extent of the cathode degradation layer

The utility of diagnostic selective nerve root blocks in the management of patients with lumbar radiculopathy: a systematic review.

OBJECTIVE: Lumbar radiculopathy (LR) often manifests as pain in the lower back radiating into one leg (sciatica). Unsuccessful back surgery is associated with significant healthcare costs and risks to patients. This review aims to examine the diagnostic accuracy of selective nerve root blocks (SNRBs) to identify patients most likely to benefit from lumbar decompression surgery. DESIGN: Systematic review of diagnostic test accuracy studies. ELIGIBILITY CRITERIA: Primary research articles using a patient population with low back pain and symptoms in the leg, SNRB administered under radiological guidance as index test, and any reported reference standard for the diagnosis of LR. INFORMATION SOURCES: MEDLINE (Ovid), MEDLINE In-Process & Other Non-Indexed Citations, EMBASE, Science Citation Index, Biosis, LILACS, Dissertation abstracts and National Technical Information Service from inception to 2018. METHODS: Risk of bias and applicability was assessed using the QUADAS-2 tool. We performed random-effects logistic regression to meta-analyse studies grouped by reference standard. RESULTS: 6 studies (341 patients) were included in this review. All studies were judged at high risk of bias. There was substantial heterogeneity across studies in sensitivity (range 57%-100%) and specificity (10%-86%) estimates. Four studies were diagnostic cohort studies that used either intraoperative findings during surgery (pooled sensitivity: 93.5% [95% CI 84.0 to 97.6]; specificity: 50.0% [16.8 to 83.2]) or 'outcome following surgery' as the reference standard (pooled sensitivity: 90.9% [83.1 to 95.3]; specificity 22.0% [7.4 to 49.9]). Two studies had a within-patient case-control study design, but results were not pooled because different types of control injections were used. CONCLUSIONS: We found limited evidence which was of low methodological quality indicating that the diagnostic accuracy of SNRB is uncertain and that specificity in particular may be low. SNRB is a safe test with a low risk of clinically significant complications, but it remains unclear whether the additional diagnostic information it provides justifies the cost of the test.National Institute for Health Research Health Technology Assessment programme grant (project number 09/111/01)

Hair Follicle Dermal Cells Support Expansion of Murine and Human Embryonic and Induced Pluripotent Stem Cells and Promote Haematopoiesis in Mouse Cultures

In the hair follicle, the dermal papilla (DP) and dermal sheath (DS) support and maintain proliferation and differentiation of the epithelial stem cells that produce the hair fibre. In view of their regulatory properties, in this study, we investigated the interaction between hair follicle dermal cells (DP and DS) and embryonic stem cells (ESCs); induced pluripotent stem cells (iPSCs); and haematopoietic stem cells. We found that coculture of follicular dermal cells with ESCs or iPSCs supported their prolonged maintenance in an apparently undifferentiated state as established by differentiation assays, immunocytochemistry, and RT-PCR for markers of undifferentiated ESCs. We further showed that cytokines that are involved in ESC support are also expressed by cultured follicle dermal cells, providing a possible explanation for maintenance of ES cell stemness in cocultures. The same cytokines were expressed within follicles in situ in a pattern more consistent with a role in follicle growth activities than stem cell maintenance. Finally, we show that cultured mouse follicle dermal cells provide good stromal support for haematopoiesis in an established coculture model. Human follicular dermal cells represent an accessible and readily propagated source of feeder cells for pluripotent and haematopoietic cells and have potential for use in clinical applications

Association Between Body Mass Index and Clinical and Endoscopic Features of Eosinophilic Esophagitis

Because eosinophilic esophagitis (EoE) causes dysphagia, esophageal narrowing, and strictures, it could result in low body mass index (BMI), but there are few data assessing this

Strengthening the reporting of observational studies in epidemiology using mendelian randomisation (STROBE-MR): explanation and elaboration.

Mendelian randomisation (MR) studies allow a better understanding of the causal effects of modifiable exposures on health outcomes, but the published evidence is often hampered by inadequate reporting. Reporting guidelines help authors effectively communicate all critical information about what was done and what was found. STROBE-MR (strengthening the reporting of observational studies in epidemiology using mendelian randomisation) assists authors in reporting their MR research clearly and transparently. Adopting STROBE-MR should help readers, reviewers, and journal editors evaluate the quality of published MR studies. This article explains the 20 items of the STROBE-MR checklist, along with their meaning and rationale, using terms defined in a glossary. Examples of transparent reporting are used for each item to illustrate best practices

Variation in the SLC23A1 gene does not influence cardiometabolic outcomes to the extent expected given its association with L-ascorbic acid

Background: Observational studies showed that circulating l-ascorbic acid (vitamin C) is inversely associated with cardiometabolic traits. However, these studies were susceptible to confounding and reverse causation. Objectives:We assessed the relation between l-ascorbic acid and 10 cardiometabolic traits by using a single nucleotide polymorphism in the solute carrier family 23 member 1 (SLC23A1) gene (rs33972313) associated with circulating l-ascorbic acid concentrations. The observed association between rs33972313 and cardiometabolic outcomes was compared with that expected given the rs33972313-l-ascorbic acid and l-ascorbic acid–outcome associations. Design: A meta-analysis was performed in the following 5 independent studies: the British Women's Heart and Health Study (n = 1833), the MIDSPAN study (n = 1138), the Ten Towns study (n = 1324), the British Regional Heart Study (n = 2521), and the European Prospective Investigation into Cancer (n = 3737). Results: With the use of a meta-analysis of observational estimates, inverse associations were shown between l-ascorbic acid and systolic blood pressure, triglycerides, and the waist-hip ratio [the strongest of which was the waist-hip ratio (−0.13-SD change; 95% CI: −0.20-, −0.07-SD change; P = 0.0001) per SD increase in l-ascorbic acid], and a positive association was shown with high-density lipoprotein (HDL) cholesterol. The variation at rs33972313 was associated with a 0.18-SD (95% CI: 0.10-, 0.25-SD; P = 3.34 × 10−6) increase in l-ascorbic acid per effect allele. There was no evidence of a relation between the variation at rs33972313 and any cardiometabolic outcome. Although observed estimates were not statistically different from expected associations between rs33972313 and cardiometabolic outcomes, estimates for low-density lipoprotein cholesterol, HDL cholesterol, triglycerides, glucose, and body mass index were in the opposite direction to those expected. Conclusions: The nature of the genetic association exploited in this study led to limited statistical application, but despite this, when all cardiometabolic traits were assessed, there was no evidence of any trend supporting a protective role of l-ascorbic acid. In the context of existing work, these results add to the suggestion that observational relations between l-ascorbic acid and cardiometabolic health may be attributable to confounding and reverse causation

Cytoplasmic p53 couples oncogene-driven glucose metabolism to apoptosis and is a therapeutic target in glioblastoma.

Cross-talk among oncogenic signaling and metabolic pathways may create opportunities for new therapeutic strategies in cancer. Here we show that although acute inhibition of EGFR-driven glucose metabolism induces only minimal cell death, it lowers the apoptotic threshold in a subset of patient-derived glioblastoma (GBM) cells. Mechanistic studies revealed that after attenuated glucose consumption, Bcl-xL blocks cytoplasmic p53 from triggering intrinsic apoptosis. Consequently, targeting of EGFR-driven glucose metabolism in combination with pharmacological stabilization of p53 with the brain-penetrant small molecule idasanutlin resulted in synthetic lethality in orthotopic glioblastoma xenograft models. Notably, neither the degree of EGFR-signaling inhibition nor genetic analysis of EGFR was sufficient to predict sensitivity to this therapeutic combination. However, detection of rapid inhibitory effects on [18F]fluorodeoxyglucose uptake, assessed through noninvasive positron emission tomography, was an effective predictive biomarker of response in vivo. Together, these studies identify a crucial link among oncogene signaling, glucose metabolism, and cytoplasmic p53, which may potentially be exploited for combination therapy in GBM and possibly other malignancies