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Background: Very low-energy diets (VLEDs) prescribed prior to bariatric surgery have been associated with decreased operative time, technical difficulty, and postoperative morbidity. To date, limited data are available regarding the impact of VLEDs prior to colorectal surgery. We designed this study to determine whether preoperative VLEDs benefit patients with obesity undergoing colorectal surgery. Methods: This is a single-center retrospective cohort study. Individuals undergoing elective colorectal surgery with a body mass index (BMI) of greater than 30 kg/m2 from 2015 to 2022 were included. The exposure of interest was VLEDs for 2–4 weeks immediately prior to surgery. The control group consisted of patients prior to January 2018 who did not receive preoperative VLED. The primary outcome was 30 day postoperative morbidity. Multivariable logistic regression modeling was used to determine associations with 30 day postoperative morbidity. Results: Overall, 190 patients were included, 89 patients received VLEDs (median age: 66 years; median BMI: 35.9 kg/m2; 48.3% female) and 101 patients did not receive VLEDs (median age: 68 years; median BMI: 32.1 kg/m2; 44.6% female). One-hundred four (54.7%) patients experienced 30 day postoperative morbidity. Multivariable regression analysis identified three variables associated with postoperative morbidity: VLEDs [odds ratio (OR) 0.22, 95% confidence intervals (CI) 0.08–0.61, P < 0.01], Charlson comorbidity index (OR 1.25, 95% CI 1.03–1.52, P = 0.02), and rectal dissections (OR 2.71, 95% CI 1.30–5.65, P < 0.01). Conclusions: The use of a preoperative VLED was associated with a significant reduction in postoperative morbidity in patients with obesity prior to colorectal surgery. A high-quality randomized controlled trial is required to confirm these findings. [ABSTRACT FROM AUTHOR]

Hidradenitis suppurativa (HS) is a chronic inflammatory skin condition that can cause significant physical, mental, and socioeconomic burden. There remains a paucity of literature on HSin the pediatric population. This systematic review highlights recent advances in pediatric HS in epidemiology, presentation, comorbidities, and management. PubMed, Embase, Google Scholar, and Clinicaltrials.gov databases were used to identify trials and articles published on HS in pediatric patients between January 2015 and October 2019. A total of 39 articles were included. Current evidence suggests that pediatric onset HS may be associated with genetic factors along with endocrine and metabolic abnormalities. Delayed diagnosis in children with HS contributes to poor outcomes. Overall, children and adults with HS share similar lesion types and involved areas. Pediatric HS is associated with a number of comorbid conditions including acne, obesity, inflammatory joint disease, Down syndrome, inflammatory bowel disease, and diabetes. There are currently no pediatric treatment guidelines. Adalimumab is approved for the treatment of moderate-to-severe HS in children 12 and older. Other targeted immunomodulators and hormonal modulators are under investigation. Although the number of studies concerning HS are increasing, further investigation is warranted to better characterize HS, facilitate early diagnosis, and determine the best management for children. [ABSTRACT FROM AUTHOR]

Summary: Background: Atopic dermatitis is a systemic disorder characterized by abnormal barrier function across multiple organ sites. Causes of epidermal barrier breakdown are complex and driven by a combination of structural, genetic, environmental and immunological factors. In addition, alteration in microflora diversity can influence disease severity, duration, and response to treatment. Clinically, atopic dermatitis can progress from skin disease to food allergy, allergic rhinitis, and later asthma, a phenomenon commonly known as the atopic march. The mechanism by which atopic dermatitis progresses towards gastrointestinal or airway disease remains to be elucidated. Objectives: This review addresses how epithelial dysfunction linking microbiome alteration and immune dysregulation can predispose to the development of the atopic march. Methods: A literature search was conducted using the PubMed database for relevant articles with the keywords ‘atopic dermatitis’, ‘epithelial barrier’, ‘skin’, ‘gut’, ‘lung’, ‘microbiome’ and ‘immune dysregulation’. Results: Initial disruption in the skin epidermal barrier permits allergen sensitization and colonization by pathogens. This induces a T helper 2 inflammatory response and a thymic stromal lymphopoietin‐mediated pathway that further promotes barrier breakdown at distant sites, including the intestinal and respiratory tract. Conclusions: As there are no immediate cures for food allergy or asthma, early intervention aimed at protecting the skin barrier and effective control of local and systemic inflammation may improve long‐term outcomes and reduce allergen sensitization in the airway and gut. [ABSTRACT FROM AUTHOR]

Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Click here for the corresponding questions to this CME article. [ABSTRACT FROM AUTHOR]

Studies have shown that the US population continues to be exposed to polychlorinated biphenyls (PCBs), despite their ban more than three decades ago, but the reasons are not fully understood. The objectives of this paper are to characterize patterns of PCBs in blood by age, gender, and ethnicity, and identify major exposure factors. EPA's Stochastic Human Exposure and Dose Simulation (SHEDS)-dietary exposure model was applied, combining fish tissue PCB levels from a NYC Asian Market survey with National Health and Nutrition Examination Survey (NHANES) dietary consumption data, and then linked with blood biomarkers for the same NHANES study subjects. Results reveal that the mean concentration of total PCBs in blood was higher with increasing age; however, for the same age, gender, and ethnicity, the blood PCB concentrations measured in the later NHANES survey were significantly lower than those in the earlier one. The decrease within an age group between the two survey periods lessened with increasing age. Blood PCBs among different ethnicities ranked differently between the older and the younger age groups within each survey. Non-Hispanic Blacks had significantly higher blood PCBs for the >30 year age group. For the 12 to ≤30 year age group, the 'Asian, Pacific Islander, Native American or multiracial' group had the highest values, with patterns fairly consistent with fish consumption and modeled PCB exposure patterns. We conclude that for younger people, patterns correspond to reduced environmental contamination over time, and are strongly associated with fish consumption and dietary exposures. Higher PCB concentrations in blood of the older population may partially reflect past exposures to higher environmental PCB concentrations, particularly before the ban. [ABSTRACT FROM AUTHOR]

Introduction. Glioblastomas multiformes (GBM) remain incurable in most cases. Their invasion into normal brain makes current therapies ineffective. Post-mortem studies suggest about a 25% of GBMs invade less than 1 cm from the tumour bulk and 20% invade more than 3 cm. Aim of study. The study aims to use DTI to assess tumour extension and determine how previously reported patterns relate to the progression-free survival (PFS). Materials and methods. Twenty-five patients with GBM treated according to the EORTC/NCIC protocol were retrospectively analysed. Patients were imaged post-operatively at 1.5 T. The sequences were composed of standard anatomical and a standard DTI sequence. As described earlier p and q maps were constructed. For each of the p and q maps, regions of interest were drawn around the visible abnormality. Patients were assigned a diffuse, localised or minimally invasive pattern. Progression was defined according to the RANO criteria4 and PFS determined in days. Kaplan-Meier plots of survival for the three groups were plotted as were the proportion of patients who had not progressed at 24 months. Results. The median PFS for the diffuse group was 278 days, for the localised group 605 days and 820 days for the minimally invasive group. Three-fourth of the minimally invasive group were progression-free at 24 months (LOG RANK 9.25; p = 0.010). Conclusion. It is possible to identify three invasive phenotypes in GBMs using Diffusion tensor imaging , and these three phenotypes have different progression free survival. A minimal phenotype (20% of patients) predicts a greater delay to progression. [ABSTRACT FROM AUTHOR]

The article features the CHAD Explorer, a web application which can be used to explore time-activity stored in the Consolidated Human Activity Database (CHAD) developed by the U.S. Environmental Protection Agency (EPA).

Usually, small interfering RNAs and most antisense molecules need mechanical or chemical delivery methods to down-modulate the targeted mRNA. However, these delivery approaches complicate the interpretations of biological consequences. We show that locked nucleic acid (LNA)-based antisense oligonucleotides (LNA-ONs) readily down-modulate genes of interest in multiple cell lines without any delivery means. The down-modulation of genes was quick, robust, long-lasting and specific followed by potent down-modulation of protein. The efficiency of the effect varied among the 30 tumor cell lines investigated. The most robust effects were found in those cells where nuclear localization of the LNA-ON was clearly observed. Importantly, without using any delivery agent, we demonstrated that HER3 mRNA and protein could be efficiently down-modulated in cells and a tumor xenograft model. These data provide a simple and efficient approach to identify potential drug targets and animal models. Further elucidation of the mechanism of cellular uptake and trafficking of LNA-ONs may enhance not only the therapeutic values of this platform but also antisense molecules in general. [ABSTRACT FROM AUTHOR]

Background: Dietary exposure from food to toxic inorganic arsenic (iAs) in the general U.S. population has not been well studied. Objectives: The goal of this research was to quantify dietary As exposure and analyze the major contributors to total As (tAs) and iAs. Another objective was to compare model predictions with observed data. Method s: Probabilistic exposure modeling for dietary As was conducted with the Stochastic Human Exposure and Dose Simulation-Dietary (SHEDS-Dietary) model, based on data from the National Health and Nutrition Examination Survey. The dose modeling was conducted by combining the SHEDS-Dietary model with the MENTOR-3P (Modeling ENvironment for TOtal Risk with Physiologically Based Pharmacokinetic Modeling for Populations) system. Model evaluation was conducted via comparing exposure and dose-modeling predictions against duplicate diet data and biomarker measurements, respectively, for the same individuals. Results: The mean modeled tAs exposure from food is 0.38 μg/kg/day, which is approximately 14 times higher than the mean As exposures from the drinking water. The mean iAs exposure from food is 0.05 μg/kg/day (1.96 μg/day), which is approximately two times higher than the mean iAs exposures from the drinking water. The modeled exposure and dose estimates matched well with the duplicate diet data and measured As biomarkers. The major food contributors to iAs exposure were the following: vegetables (24%); fruit juices and fruits (18%); rice (17%); beer and wine (12%); and flour, corn, and wheat (11%). Approximately 10% of tAs exposure from foods is the toxic iAs form. Conclusions: The general U.S. population may be exposed to tAs and iAs more from eating some foods than from drinking water. In addition, this model evaluation effort provides more confidence in the exposure assessment tools used. [ABSTRACT FROM AUTHOR]

Background: Occurrence of tumors at multiple sites is a hallmark of malignant cancers and contributes to the high mortality of cancers. The formation of multi-site cancers (MSCs) has conventionally been regarded as a result of hematogenous metastasis. However, some MSCs may appear as unusual in the sense of vascular dissemination pattern and therefore be explained by alternative metastasis models or even by non-metastatic independent formation mechanisms. Results: Through literature review and incorporation of recent advance in understanding aging and development, we identified two alternative mechanisms for the independent formation of MSCs: 1) formation of separate tumors from cancer-initiating cells (CICs) mutated at an early stage of development and then diverging as to their physical locations upon further development, 2) formation of separate tumors from different CICs that contain mutations in some convergent ways. Either of these processes does not require long-distance migration and/or vascular dissemination of cancer cells from a primary site to a secondary site. Thus, we classify the formation of these MSCs from indigenous CICs (iCICs) into a new mechanistic category of tumor formation -- multigenesis. Conclusion: A multigenesis view on multi-site cancer (MSCs) may offer explanations for some "unusual metastasis" and has important implications for designing expanded strategies for the diagnosis and treatment of cancers. [ABSTRACT FROM AUTHOR]

Linked Article: Howells et al. Br J Dermatol 2021; 185:921–934. [ABSTRACT FROM AUTHOR]

The role of dietary factors is an important and controversial topic in the pathogenesis of atopic dermatitis (AD). Despite the preponderance of consumer products utilizing oral micronutrients supplementation for relief AD symptoms, less attention has been paid on the utility of topical micronutrients, specifically for individuals with AD. We review evidence on topical formulations of vitamins (A, B, C, D, and E) and trace minerals (magnesium, manganese, zinc, and iodine) for treatment of AD. While topical B, C, and E formulations appear to provide some benefit to AD individuals, topical vitamin A has no utility, and topical vitamin D may exacerbate symptoms. Magnesium, zinc, and iodine all appear to improve AD through anti‐inflammatory and anti‐microbial effects, though future studies must evaluate their use as monotherapy. The exposition of the effects that topical micronutrients have on AD offers an adjuvant treatment modality for this common inflammatory dermatosis. [ABSTRACT FROM AUTHOR]

A letter to the editor is presented in response to the article "Probabilistic Modeling of Dietary Arsenic Exposure and Evaluation with 2003-2004 NHANES Data," by Jianping Xue and colleagues.

A letter to the editor is presented regarding the open peer review of articles published.