The Impact of SARS-COV-2 on two Colorectal Cancer screening centres.

BowelScreen paused activity in March 2020 to prioritise the response to the COVID-19 pandemic. The aim of this study was to examine the impact of this delay. Cases affected by the pause and subsequently completed were compared to the same period in 2019. Endoscopy and histology data were obtained from the BowelScreen database and patient records. One-hundred and seven colonoscopies were performed during the study period. This compared with 224 colonoscopies during the same period in 2019. Median lead time to colonoscopy in 2020 was 74 days compared to 34 days in 2019. Adenoma detection rate was 59% for both periods. Advanced adenoma and cancer detection rates were similar in both periods. While there was a marked reduction in activity and significant delays for BowelScreen patients during the first wave of the COVID-19 pandemic, this does not appear to have impacted on clinical outcomes for patients who attended for screening colonoscopy.

Feasibility and Safety of a Combined Metabolic Strategy in Glioblastoma Multiforme: A Prospective Case Series.

Background: Glioblastoma multiforme (GBM) may be susceptible to metabolic strategies such as fasting and ketogenic diets, which lower blood glucose and elevate ketones. Combining these two strategies may be an ideal approach for sustaining a potentially therapeutic glucose ketone index (GKI). In this prospective case series, we observed whether a combined metabolic strategy was feasible, safe, and capable of sustaining a GKI <6 in patients with GBM. Methods: We provided recommendations and guidelines to 10 GBM patients at various stages of tumour progression and treatment that enabled them to complete a 5-7-day fast every 1-2 months combined with a modified ketogenic diet during the intervening weeks. Patients monitored their blood glucose and ketone levels and body weight. Adverse effects were assessed. Results: Patients completed a mean of 161 ± 74 days of the combined metabolic strategy, with 34 ± 18 (21%) days of prolonged fasting (mean fast duration: 6.0 ± 1.4 days) and 127 ± 59 (79%) days on the ketogenic diet. The mean GKI for all 10 patients was 3.22 (1.28 during the fasts, 5.10 during the ketogenic diet). Body weight decreased by 8.4 ± 6.9 kg (11.2% decrease in baseline weight). The most common adverse effects attributed to the fasts and ketogenic diet were fatigue, irritability, and feeling lightheaded. The metabolic strategy did not interfere with standard oncological treatments. Conclusion: This is the first study to observe the feasibility and safety of repeated, prolonged fasting combined with a modified ketogenic diet in patients with GBM. Using minimal support, patients maintained the combined metabolic strategy for 5-6 months while sustaining a potentially therapeutic mean GKI of 3.22. Weight loss was considerable. Adverse effects attributed to the metabolic strategy were mild, and it did not interfere with standard oncological treatments. Study Registration: This study is registered on the Australia New Zealand Clinical Trials Registry, number ACTRN12620001310954. The study was registered on 4 December 2020.

Autism and toe-walking: are they related? Trends and treatment patterns between 2005 and 2016.

PURPOSE: This study quantified toe-walking trends and treatment decisions in patients with autism spectrum disorder (ASD) in the United States between 2005 and 2016 using a large national private-payer database. METHODS: A retrospective database review was performed on paediatric patients with ASD, and for International Classification of Diseases-9/10 diagnosis codes for toe-walking. Patients were filtered based on treatment type by Current Procedural Terminology (CPT) code. Continued toe-walking rates were assessed for each patient population and treatment group. A Pearson's chi-squared test was used to evaluate differences in group characteristics. RESULTS: Of 2 221 009 paediatric patients in the database, 5739 patients had a diagnosis of ASD, and 8.4% of patients with ASD also had a diagnosis of toe-walking (n = 484). For typically developing children in the database, 0.47% of patients had a diagnosis of persistent toe-walking. In all, 59.3% of ASD patients underwent physical therapy, 7.4% serial casting and 3.3% surgical correction, compared with 38.1%, 3.6% and 1.2% of normally developing children, respectively (chi-square 6.4031; p < 0.040699). Without intervention, 63.6% of patients with ASD continued to toe-walk within ten years of their diagnosis, with 19.3% of patients without ASD (chi-square 82.9762; p < 0.0001). CONCLUSION: This study supports the association between a greater prevalence of toe-walking in children with ASD. We showed that patients with ASD and toe-walking receive surgical correction at nearly triple the rate of children without ASD who toe-walk. The continued rate of toe-walking is comparable between treatment groups as well as between ASD and typically developing children. Typically developing children have higher rates of toe-walking resolution without intervention than children with ASD. LEVEL OF EVIDENCE: Level II.

Development of an atrophic acne scar risk assessment tool.

BACKGROUND: Acne is a chronic dermatological disease predominantly afflicting young adults and is often associated with the development of scars. Acne scarring is usually avoidable when acne is managed early and effectively. However, acne patients often fail to seek early treatment. New and innovative tools to raise awareness are needed. OBJECTIVE: This study presents the development and assessment of a tool aiming to assess the risk of atrophic acne scars. METHODS: A systematic literature review of clinical risk factors for acne scars, a Delphi-like survey of dermatological experts in acne and secondary data analysis, were conducted to produce an evidence-based risk assessment tool. The tool was assessed both with a sample of young adults with and without scars and was assessed via a database cross-validation. RESULTS: A self-administered tool for risk assessment of developing atrophic acne scars in young adults was developed. It is a readily comprehensible and practical tool for population education and for use in medical practices. It comprises of four risk factors: worst ever severity of acne, duration of acne, family history of atrophic acne scars and lesion manipulation behaviours. It provides a dichotomous outcome: lower vs. higher risk of developing scars, thereby categorizing nearly two-thirds of the population correctly, with sensitivity of 82% and specificity of 43%. CONCLUSION: The present tool was developed as a response to current challenges in acne scar prevention. A potential benefit is to encourage those at risk to self-identify and to seek active intervention of their acne. In clinical practice, we expect this tool may help clinicians identify patients at risk of atrophic acne scarring and underscore their requirement for rapid and effective acne treatment.

Placebo-controlled pilot trial testing dose titration and intravenous, intramuscular and subcutaneous routes for ketamine in depression.

OBJECTIVE: This pilot study assessed the feasibility, efficacy and safety of an individual dose-titration approach, and of the intravenous (IV), intramuscular (IM) and subcutaneous (SC) routes for treating depression with ketamine. METHOD: Fifteen treatment-refractory depressed participants received ketamine or midazolam (control treatment) in a multiple crossover, double-blind study. Ketamine was administered by IV (n = 4), IM (n = 5) or SC (n = 6) injection. Dose titration commenced at 0.1 mg/kg, increasing by 0.1 mg/kg up to 0.5 mg/kg, given in separate treatment sessions separated by ≥1 week, with one placebo control treatment randomly inserted. Mood, psychotomimetic and hemodynamic effects were assessed and plasma ketamine concentrations assayed. RESULTS: Twelve participants achieved response and remission criteria, achieved at doses as low as 0.1 mg/kg. All three routes of administration resulted in comparable antidepressant effects. Fewest adverse effects were noted with the SC route. Antidepressant response, adverse effects and ketamine concentrations were dose-related. CONCLUSION: Antidepressant response occurred at a range of doses and at <0.5 mg/kg. The dose-titration approach is a practical method for optimizing the efficacy - side-effects trade-off on an individual patient basis. This pilot study provides preliminary evidence for SC injection as a practical, feasible and efficacious treatment approach.

Understanding innate immunity and inflammation in acne: implications for management.

Acne has long been understood to have a complex physiological basis involving several main factors: hormonally-stimulated sebum production, abnormal keratinization of the pilosebaceous duct, and an inflammatory immune response to Propionibacterium acnes. Recent studies at the molecular and cellular level have begun clarifying how all of these factors interact, and the role of the innate immune system is better appreciated. Inflammation has been demonstrated in all acne lesions - the preclinical microcomedo, comedones, inflammatory lesions, 'post-inflammatory' erythema or hyperpigmentation, and scarring. Inflammation localized to the pilosebaceous unit can be considered the defining feature of acne and should be addressed via multiple therapeutic pathways. Clinicians tend to think oral antibiotics should be used to 'calm' inflammatory acne, but there is good evidence showing that topical retinoids also have anti-inflammatory properties as a class effect. For best therapeutic outcomes, most patients with acne should be treated first line with a topical retinoid plus an antimicrobial agent, as has been demonstrated in thousands of patients involved in clinical trials and recommended by the Global Alliance to Improve Outcomes in Acne for more than a decade. Moving away from reliance on antibiotic therapy for acne is particularly important in an era of worsening antimicrobial resistance and worldwide calls to reduce antibiotic use. Improved understanding about the role of P. acnes and the innate immune system in acne should help clinicians in designing efficacious treatment strategies.

4-Hexyl-1,3-phenylenediol, a nuclear factor-κB inhibitor, improves photodamaged skin and clinical signs of ageing in a double-blinded, randomized controlled trial.

BACKGROUND: The nuclear factor-κB (NF-κB) pathway is a key mediator of inflammation; however, few studies have examined the direct effects of NF-κB inhibition on the skin. OBJECTIVES: To investigate NF-κB activity in cultured human fibroblasts and to investigate the effects of 4-hexyl-1,3-phenylenediol (an NF-κB inhibitor) on elastin and collagen gene expression in vitro and on the clinical appearance of photodamaged skin. METHODS: The amount and activity of NF-κB in human fibroblasts obtained from donors (17-78 years old) was measured after transfection with a NF-κB reporter and a luciferase promoter system. The expression of extracellular matrix (ECM) genes was determined using quantitative polymerase chain reaction. Women with moderate skin photodamage were randomized to daily treatment with a topical lotion containing 4-hexyl-1,3-phenylenediol (n = 30) or vehicle (n = 29) for 8 weeks, with clinical assessments at baseline and weeks 2, 4 and 8. RESULTS: Fibroblasts obtained from donors older than 50 years had higher NF-κB activity compared with cells from younger donors; inhibition of the NF-κB pathway with 4-hexyl-1,3-phenylenediol enhanced the expression of ECM genes. In women, treatment for 8 weeks with 4-hexyl-1,3-phenylenediol significantly improved crow's feet fine lines, cheek wrinkles, age spots, mottled pigmentation and radiance compared with both the vehicle and baseline. Furthermore, treatment with 4-hexyl-1,3-phenylenediol resulted in a twofold greater clinical improvement in overall photodamage compared with the vehicle group. CONCLUSIONS: Inhibition of the proinflammatory NF-κB pathway resulted in increased expression of ECM proteins in vitro and significant clinical improvement in photodamaged skin.

Cerebral amyloid angiopathy causing cortical microinfarction.

Cerebral amyloid angiopathy as a cause of recurrent small cortical strokes is under-recognised. These patients need haemosiderin-sensitive MRI to make a diagnosis and intensive antiplatelet treatment is dangerous.

Quality of colonoscopy performance among gastroenterology and surgical trainees: a need for common training standards for all trainees?

BACKGROUND AND STUDY AIM: Cecal intubation and polyp detection rates are objective measures of colonoscopy performance. Minimum cecal intubation rates greater than 90% have been endorsed by the American Society for Gastrointestinal Endoscopy (ASGE) and the Joint Advisory Group (JAG) UK. Performance data for medical and surgical trainee endoscopists are limited, and we used endoscopy quality parameters to compare these two groups. METHODS: Retrospective review of all single-endoscopist colonoscopies done by gastroenterology and surgical trainees ("registrars," equivalent to fellows, postgraduate year 5) with more than two years' endoscopy experience, in 2006 and 2007 at a single academic medical center. Completion rates and polyp detection rates for endoscopists performing more than 50 colonoscopies during the study period were audited. Colonoscopy withdrawal time was prospectively observed in a representative subset of 140 patients. RESULTS: Among 3079 audited single-endoscopist colonoscopies, seven gastroenterology trainees performed 1998 procedures and six surgery trainees performed 1081. The crude completion rate was 82%, 84% for gastroenterology trainees and 78% for surgery trainees (P < 0.0001). Adjusted for poor bowel preparation quality and obstructing lesions, the completion rate was 89%; 93% for gastroenterology trainees, and 84% for surgical trainees (P < 0.0001). The polyp detection rate was 19% overall, with 21% and 14% for gastroenterology and surgical trainees, respectively (P < 0.0001). The adenoma detection rate in patients over 50 was 12%; gastroenterology trainees 14% and surgical trainees 9% (P = 0.0065). In the prospectively audited procedures, median withdrawal time was greater in the gastroenterology trainee group and polyp detection rates correlated closely with withdrawal time (r = 0.99). CONCLUSION: The observed disparity in endoscopic performance between surgical and gastroenterology trainees suggests the need for a combined or unitary approach to endoscopy training for specialist medical and surgical trainees.

Natural options for the management of hyperpigmentation.

Facial hyperpigmented disorders are a common complaint in the adult population of all races. First-line topical treatments are usually hydroquinone or topical retinoids, which can cause irritant reactions. The need for better tolerated, yet effective, skin lightening agents that could be utilized by a wider population has led to the investigation of several potential botanical/natural compounds. There are currently many topical cosmetic formulations claiming skin depigmenting effects. A few of the ingredients (e.g. soy) are supported not only by in vitro results but also by a body of controlled clinical efficacy studies; other ingredients, instead, are backed mostly by in vitro data and a few small uncontrolled clinical studies. In this review, we describe the most common natural ingredients used for skin depigmentation and their major published studies: soy, licorice extracts, kojic acid, arbutin, niacinamide, N-acetylglucosamine, COFFEEBERRY(™) and green tea.

A pilot methodology study for the photographic assessment of post-inflammatory hyperpigmentation in patients treated with tretinoin.

BACKGROUND: Post-inflammatory hyperpigmentation (PIH) is a common occurrence in patients with acne vulgaris, particularly in those with skin of colour. AIMS: A previous study has demonstrated the benefit of tretinoin (retinoic acid) in the treatment of PIH; however, there is currently no standard protocol to evaluate change in PIH following treatment. Based on these findings, we performed a pilot, exploratory, blinded, intraindividual-controlled methodology study that consisted of a photographic assessment protocol with facial mapping. MATERIALS AND METHODS: The study was based on a secondary analysis of a phase 4, community-based trial of 544 acne patients who were treated with tretinoin gel microsphere 0.04% or 0.1%. Only patients with Fitzpatrick types III-V (skin of colour) were included in the study; subjects with Fitzpatrick skin type VI were excluded because the photographic assessment did not allow for proper evaluation. RESULTS: Despite the small number of subjects evaluated (n=25), the results revealed consistent assessment of improvement in PIH between two independent graders (weighted κ=0.84). CONCLUSION: Further study with a larger population is recommended to validate the accuracy of this method.

Endoscopic ultrasound and EUS-guided FNA in the diagnosis of rectal endometriosis.

Endometriosis is characterised by the presence of endometrial glands and stroma outside the uterus. The GI tract is the most common site for extra-pelvic endometriosis, in particular the rectum and sigmoid colon. Using endoscopic ultrasound (EUS), which combines endoscopy with real-time ultrasonography, the wall of the GI tract and adjacent structures can be examined. EUS-guided fine needle aspirates can be also obtained during the procedure. We report a case of rectosigmoid endometriosis which was diagnosed using EUS.

Analyses of volatile organic compounds from human skin.

BACKGROUND: Human skin emits a variety of volatile metabolites, many of them odorous. Much previous work has focused upon chemical structure and biogenesis of metabolites produced in the axillae (underarms), which are a primary source of human body odour. Nonaxillary skin also harbours volatile metabolites, possibly with different biological origins than axillary odorants. OBJECTIVES: To take inventory of the volatile organic compounds (VOCs) from the upper back and forearm skin, and assess their relative quantitative variation across 25 healthy subjects. METHODS: Two complementary sampling techniques were used to obtain comprehensive VOC profiles, viz., solid-phase microextraction and solvent extraction. Analyses were performed using both gas chromatography/mass spectrometry and gas chromatography with flame photometric detection. RESULTS: Nearly 100 compounds were identified, some of which varied with age. The VOC profiles of the upper back and forearm within a subject were, for the most part, similar, although there were notable differences. CONCLUSIONS: The natural variation in nonaxillary skin odorants described in this study provides a baseline of compounds we have identified from both endogenous and exogenous sources. Although complex, the profiles of volatile constituents suggest that the two body locations share a considerable number of compounds, but both quantitative and qualitative differences are present. In addition, quantitative changes due to ageing are also present. These data may provide future investigators of skin VOCs with a baseline against which any abnormalities can be viewed in searching for biomarkers of skin diseases.

Endoscopic pneumatic dilation versus botulinum toxin injection in the management of primary achalasia.

BACKGROUND: Achalasia is an oesophageal motility disorder, of unknown cause, which results in increased lower oesophageal sphincter (LOS) tone and symptoms of difficulty swallowing. Treatments are aimed at reducing the LOS tone. Current endoscopic therapeutic options include pneumatic dilation (PD) or botulinum toxin injection (BTX). OBJECTIVES: The objective of this review was to compare the efficacy and safety of two endoscopic treatments, pneumatic dilatation and intrasphincteric botulinum toxin injection, in the treatment of oesophageal achalasia. SEARCH STRATEGY: We searched the Cochrane Upper Gastrointestinal and Pancreatic Diseases Group trials register, the Cochrane Central Register of Controlled Trials, MEDLINE (1966 to Oct 2005), EMBASE (1980 to Oct 2005), BIOSIS (1969 to Oct 2005) and Web of Science (1955 to October 2005). We also searched abstracts from significant Gastroenterology meetings (DDW, UEGW) and reference lists of articles. SELECTION CRITERIA: Randomised controlled trials comparing PD to BTX injection in patients with primary achalasia. DATA COLLECTION AND ANALYSIS: Two review authors independently performed quality assessment and data extraction. MAIN RESULTS: Six studies involving 178 participants were included. Two studies were excluded from the meta-analysis of remission rates on the basis of clinical heterogeneity of the initial endoscopic protocols. There was no significant difference in remission between PD or BTX treatment within four weeks of the initial intervention, with a relative risk of remission of 1.15 (95% CI 0.95 to 1.38, P = 0.39) for PD compared to BTX. There was also no significant difference in the mean oesophageal pressures between the treatment groups; weighted mean difference for PD of -0.77 (95% CI -2.44 to 0.91, P = 0.37). Data on remission rates following the initial endoscopic treatment was available for two studies at six months and three studies at 12 months. At six months 22 of 29 PD participants were in remission compared to 7 of 27 in the BTX group, giving a relative risk of 2.90 (95% CI 1.48 to 5.67, P = 0.002); whilst at 12 months 33 of 47 PD participants were in remission compared to 11 of 43 BTX participants, relative risk of 2.67 (95% CI 1.58 to 4.52, P = 0.0002). No serious adverse outcomes occurred in participants receiving BTX, whilst PD was complicated by perforation in three cases. AUTHORS' CONCLUSIONS: The results of this meta-analysis would suggest that PD is the more effective endoscopic treatment in the long term (greater than six months) for patients with achalasia.

The celtic coincidence--the frequency and clinical characterisation of hereditary haemochromatosis in patients with coeliac disease.

BACKGROUND: Hereditary Haemochromatosis (HH) and Coeliac disease (CD) are common disorders in Northern European populations, particularly the Irish population. AIMS: To investigate whether there was increased frequency of the two common HFE gene mutations, C282Y and H63D, associated with HH amongst a cohort of CD patients, and to determine the penetrance of the HH associated genotypes in this cohort. METHODS: HFE genotypes of a cohort of CD patients were determined using standard PCR techniques. HFE allele frequencies were compared to those of a previously reported, ethnically similar, cohort of 800 neonates, using Fishers exact test. Patients with HH-associated genotypes were subsequently evaluated. RESULTS: The C282Y and H63D allele frequencies, 24/222 (11%) and 28/222 (13%) respectively, in the CD patients were similar to those of the neonatal group, 171/1600 (11%) and 242/1600 (15%). Eight patients had HH-associated genotypes, of which two demonstrated biochemical evidence of iron overload. CONCLUSION: The HFE mutations associated with Hereditary Haemochromatosis are not more common in Irish CD patients.

Net1 and Myeov: computationally identified mediators of gastric cancer.

Gastric adenocarcinoma (GA) is a significant cause of mortality worldwide. The molecular mechanisms of GA remain poorly characterised. Our aim was to characterise the functional activity of the computationally identified genes, NET 1 and MYEOV in GA. Digital Differential Display was used to identify genes altered expression in GA-derived EST libraries. mRNA levels of a subset of genes were quantitated by qPCR in a panel of cell lines and tumour tissue. The effect of pro- and anti-inflammatory stimuli on gene expression was investigated. Cell proliferation and invasion were measured using in an in-vitro GA model following inhibition of expression using siRNA. In all, 23 genes not previously reported in association with GA were identified. Two genes, Net1 and Myeov, were selected for further analysis and increased expression was detected in GA tissue compared to paired normal tissue using quantitative PCR. siRNA-mediated downregulation of Net1 and Myeov resulted in decreased proliferation and invasion of gastric cancer cells in vitro. These functional studies highlight a putative role for NET1 and Myeov in the development and progression of gastric cancer. These genes may provide important targets for intervention in GA, evidenced by their role in promoting invasion and proliferation, key phenotypic hallmarks of cancer cells.

Efficacy of oral isotretinoin in the control of skin and nasal colonization by antibiotic-resistant propionibacteria in patients with acne.

BACKGROUND: Skin colonization by antibiotic-resistant propionibacteria is commonplace among acne patients globally. Increasing attention is now being paid to how resistance rates might be reduced to preserve the future efficacy of antibiotics, especially erythromycin and clindamycin in acne therapy. OBJECTIVE: To assess the efficacy of oral isotretinoin in the control of antibiotic-resistant propionibacteria. METHODS: Acne patients (72 in the U.K., 62 in the U.S.A.) colonized with high numbers of antibiotic-resistant propionibacteria were sampled before, during and 12 weeks after oral isotretinoin therapy. Propionibacterial samples were collected from five acne-prone skin surface sites using a detergent scrub method and from the anterior nares using moistened swabs. Total and antibiotic-resistant propionibacteria were enumerated by viable counting on media with and without selective antibiotics. RESULTS: After 16 weeks of oral isotretinoin therapy, mean population densities of viable propionibacteria and variants resistant to erythromycin, clindamycin or tetracycline had fallen by more than 90% at all skin sites and in the nares. The sole exception was a smaller reduction in tetracycline-resistant strains on the lower back. In general, greater reductions were observed on skin than in the nares. By the end of the treatment period only three patients (all in Philadelphia) yielded no antibiotic-resistant strains from any site. Post-treatment, propionibacterial counts remained well below pretreatment levels but had begun to recover on the face and in the nares. The recovering propionibacterial population included both susceptible and resistant strains. Changes during and post-treatment at the two centres were similar but not identical. CONCLUSIONS: Oral isotretinoin effectively reduced skin and nasal colonization by antibiotic-resistant propionibacteria. However, viable populations of resistant isolates persisted post-treatment at multiple sites. Novel methods are required to eradicate antibiotic-resistant propionibacteria completely, especially from the nasal reservoir.