Evidence of On-Going Disparate Levels of Care for South Asian Patients with Inflammatory Bowel Disease in the United Kingdom during the Quinquennium 2015–2019

Over the last decade, there have been a number of studies which have documented disparate levels of care in the management of inflammatory bowel disease amongst various minority communities in the UK. Similar findings had previously been described in the USA, where access to biologics has been an issue. In this study, data on admissions to hospital of South Asian and White British patients with inflammatory bowel disease between 2015 and 2019 were collected from 12 National Health Service (NHS) trusts in England, three Health Boards in Wales and two Scottish health organizations using Freedom of Information requests. The analyses of data were based on the assumption that inflammatory bowel disease (IBD) has the same prevalence in the South Asian community and the White British community in the UK. Comparisons were made between the proportion of hospitalised patients who were South Asian and the proportion who were White British in the local community using a z statistic. In Leicester, Bradford, Croydon and Lothian, the proportion of patients from the South Asian community admitted to hospital was significantly greater than the proportion from the local White British community, which is consistent with the greater frequency and severity of the disease in the South Asian community in the UK. However, in Coventry, Wolverhampton, Walsall, Acute Pennine Trust in the north-west of England, Barking, Havering and Redbridge and Glasgow, South Asian patients were significantly under-represented, indicating significant issues with access to hospital-based healthcare for inflammatory bowel disease. This study provides evidence of on-going evidence of disparate levels of care for patients from a South Asian background, with inflammatory bowel disease being underserved by a number of NHS Trusts, Health Boards and comparable organisations. When there is on-going failure to achieve the objectives of the NHS of achieving equality in the delivery of care, it is critical to introduce effective policies which will alter the in-built inertia to change within such organisations.

Disaccharidase Deficiency in Pediatric Patients with Inflammatory Bowel Disease

Background: Disaccharidase (DS) deficiencies have been reported in pediatric patients with inflammatory bowel disease (IBD), but the relationship between duodenal inflammation and DS deficiency has not been evaluated outside of lactase deficiency. Methods: This study assessed DS levels and DS deficiencies in pediatric IBD patients who underwent endoscopy with assessment of DS activity. Records were reviewed for IBD subtype, pathology findings, and the results of DS analysis. Results: A total of 136 patients were identified. Overall, 89 (65.4%) patients had a diagnosis of Crohn’s disease (CD), 31 (22.8%) patients had a diagnosis of ulcerative colitis (UC), and 16 (11.8%) patients had a diagnosis of indeterminant colitis. Lactase deficiency was identified in 55.9% of patients, followed by maltase deficiency (19.9%), sucrase and palatinase deficiency (14%), and pan-deficiency (12.5%). When analyzing only patients with CD, patients with duodenitis were more likely to exhibit sucrase deficiency, palatinase deficiency, and pan-deficiency with a trend towards maltase deficiency. Conclusions: The most common DS deficiency was lactase deficiency; however, this was not related to duodenal inflammation. Pediatric patients with CD and duodenal inflammation exhibit DS deficiencies, namely, sucrase, palatinase, and pan-deficiency. Dietary adjustments may be warranted temporarily until duodenal inflammation is healed in patients with CD and duodenitis.

Wheat Breeding, Fertilizers, and Pesticides: Do They Contribute to the Increasing Immunogenic Properties of Modern Wheat?

Celiac disease (CD) is a small intestinal inflammatory condition where consumption of gluten induces a T-cell mediated immune response that damages the intestinal mucosa in susceptible individuals. CD affects at least 1% of the world’s population. The increasing prevalence of CD has been reported over the last few decades. However, the reason for this increase is not known so far. Certain factors such as increase in awareness and the development of advanced and highly sensitive diagnostic screening markers are considered significant factors for this increase. Wheat breeding strategies, fertilizers, and pesticides, particularly herbicides, are also thought to have a role in the increasing prevalence. However, less is known about this issue. In this review, we investigated the role of these agronomic practices in depth. Our literature-based results showed that wheat breeding, use of nitrogen-based fertilizers, and herbicides cannot be solely responsible for the increase in celiac prevalence. However, applying nitrogen fertilizers is associated with an increase in gluten in wheat, which increases the risk of developing celiac-specific symptoms in gluten-sensitive individuals. Additionally, clustered regularly interspaced short palindromic repeats (CRISPR) techniques can edit multiple gliadin genes, resulting in a low-immunogenic wheat variety that is safe for such individuals.

MicroRNAs as Diagnostic Tools in Hepatocellular Carcinoma

Liver cancer is the fourth leading cause of cancer-related deaths worldwide, with hepatocellular carcinoma (HCC) accounting for approximately 80% of all liver cancers. The serum concentration of alpha-fetoprotein (AFP) is the only validated biomarker for HCC diagnosis. MicroRNAs (miRNAs) are small non-coding RNAs of 21–30 nucleotides playing a critical role in human carcinogenesis, with types of miRNAs with oncogenic (oncomiRs) or tumor suppressor features. The altered expression of miRNAs in HCC is associated with many pathological processes, such as cancer initiation, tumor growth, apoptosis escape, promotion of migration and invasion. Moreover, circulating miRNAs have been increasingly investigated as non-invasive biomarkers for HCC diagnosis. MiRNAs’ expression patterns are altered in HCC and several single miRNAs or miRNAs panels have been found significantly up or downregulated in HCC with respect to healthy controls or non-oncological patients (cirrhotic or with viral hepatitis). However, any of the investigated miRNAs or miRNAs panels has entered clinical practice so far. This has mostly to do with lack of protocols standardization, small sample size and discrepancies in the measurement techniques. This review summarizes the major findings regarding the diagnostic role of miRNAs in HCC and their possible use together with standard biomarkers in order to obtain an early diagnosis and easier differential diagnosis from non-cancerous liver disease.

Tribbles Gene Expression Profiles in Colorectal Cancer

Colorectal cancer (CRC) is the third most common cancer and the second leading cause of death due to cancer in the world. Therefore, the identification of novel druggable targets is urgently needed. Tribbles proteins belong to a pseudokinase family, previously recognized in CRC as oncogenes and potential therapeutic targets. Here, we analyzed the expression of TRIB1, TRIB2, and TRIB3 simultaneously in 33 data sets from CRC based on available GEO profiles. We show that all three Tribbles genes are overrepresented in CRC cell lines and primary tumors, though depending on specific features of the CRC samples. Higher expression of TRIB2 in the tumor microenvironment and TRIB3 overexpression in an early stage of CRC development, unveil a potential and unexplored role for these proteins in the context of CRC. Differential Tribbles expression was also explored in diverse cellular experimental conditions where either genetic or pharmacological approaches were used, providing novel hints for future research. This comprehensive bioinformatic analysis provides new insights into Tribbles gene expression and transcript regulation in CRC.

M1 Polarized Tumor-Associated Macrophages (TAMs) as Promising Prognostic Signature in Stage I–II Gastric Adenocarcinomas

Tumor-associated macrophages (TAMs) may be noticed in gastric carcinomas (GC), but their clinicopathological significance has not been yet explored. From a histological review of 400 cases of tubular/papillary adenocarcinomas, 24 cases of stage I–II gastric adenocarcinomas with intraglandular and stromal TAMs were identified. Their clinicopathological features were compared with 72 pT-matched as well as stage-matched control cases of adenocarcinomas without TAMs. TAMs present in GC cases were present either in glands or in neoplastic stroma, showing an immunoreactivity for CD68 and CD80; sometimes, they were organized in mature granulomas with occasional giant cells. Therefore, the stained TAMs were reminiscent of a specific polarized macrophage M1 phenotype; however, in any case of our cohort, no M2 phenotype macrophages were documented by CD 163 and CD 204 immunostainings. Statistically, no significant differences in age, gender, tumor location, size, and lymphovascular and perineural invasion between the case group with TAMs and pT- as well as stage-matched controls were reported; furthermore, the case group showed lower frequency of lymph node metastasis (p = 0.02). In addition, a significantly different clinical course and overall survival rate were also observed in gastric adenocarcinomas with M1 TAMs (p = 0.02) in comparison to controls. These results suggest that tumor-associated M1 macrophages are related to a quite indolent growth and a better prognosis of patients with this peculiar variant of gastric adenocarcinomas.

Colorectal Cancer Screening: Have We Addressed Concerns and Needs of the Target Population?

Despite the recognized benefits of colorectal cancer (CRC) screening, uptake is still suboptimal in many countries. In addressing this issue, one important element that has not received sufficient attention is population preference. Our review provides a comprehensive summary of the up-to-date evidence relative to this topic. Four OVID databases were searched: Ovid MEDLINE® ALL, Biological Abstracts, CAB Abstracts, and Global Health. Among the 742 articles generated, 154 full texts were selected for a more thorough evaluation based on predefined inclusion criteria. Finally, 83 studies were included in our review. The general population preferred either colonoscopy as the most accurate test, or fecal occult blood test (FOBT) as the least invasive for CRC screening. The emerging blood test (SEPT9) and capsule colonoscopy (nanopill), with the potential to overcome the pitfalls of the available techniques, were also favored. Gender, age, race, screening experience, education and beliefs, the perceived risk of CRC, insurance, and health status influence one’s test preference. To improve uptake, CRC screening programs should consider offering test alternatives and tailoring the content and delivery of screening information to the public’s preferences. Other logistical measures in terms of the types of bowel preparation, gender of endoscopist, stool collection device, and reward for participants can also be useful.

A Survey of Methodologies for Assessing Mast Cell Density and Activation in Patients with Functional Abdominal Pain Disorders

The aim was to assess methods utilized in assessing mast cell involvement in functional abdominal pain disorders (FAPDs), specifically to describe variability in methods utilized to assess both mast cell density and activation and determine if a consensus exists. After a literature search identified 70 manuscripts assessing mast cell density, data were extracted including FAPD diagnosis, site of biopsy, selection of microscopic fields analyzed, selection of mucosal region analyzed, method of mast cell identification, method to assess mast cell density, and if performed, method to assess mast cell activation. There appears to be some consensus favoring inmmunohistochemical stains over histochemical stains for identifying mast cells. Otherwise, considerable variability exists in methodology for assessing mast cell density and activation. Regardless of method, approximately 80% of studies found increased mast cell density and/or activation in comparison to controls with no method being superior. A wide variety of methods have been employed to assess mast cell density and activation with no well-established consensus and inadequate data to recommend specific approaches. The current methodology providing physiologic information needs to be translated to a standard methodology providing clinical information with the development of criteria establishing abnormal density and/or activation, and more importantly, predicting treatment response.

Microbiome–Gut Dissociation: Investigating the Origins of Obesity

The reduction of excessive weight remains a major public health challenge, with control currently limited to a calorie reduction strategy. Currently, attempts are being made at revisiting the fibre hypothesis based on the African studies of Denis Burkitt, that the lack of dietary fibre in the modern diet was responsible for the occurrence of obesity and many of the other non-communicable diseases of what he called “Western civilization”. However, the dilemma is that Burkitt himself stressed that other peoples of his day, such as the Maasai, remained healthy without consuming such high fibre diets. Equally, the present obesity epidemic is accompanied by diseases of a malfunctioning immune system and of poor mental health that do not seem to be adequately explained simply by a deficiency of dietary fibre. Though unknown in Burkitt’s day, an increasing degradation of a mutualistic intestinal microbiome would offer a better fit to the observed epidemiology, especially if the microbiome is not effectively passed on from mother to child at birth. Taking the broader view, in this article we posit a view of the microbiome as a cofactor of mammalian evolution, in which a maternal microbial inheritance complements the parental genetic inheritance of the animal, both engaging epigenetic processes. As this would require the microbiome to be fully integrated with the animal as it develops into an adult, so we have a meaningful evolutionary role for the microbiome–gut–brain axis. By a failure to correctly establish a microbiome–gut interface, the inhibition of maternal microbial inheritance sets the scene for the future development of non-communicable disease: compromised immune system function on the one hand and dysfunctional gut–brain communication on the other. The basic principle is that the fully functioning, diverse, microbiome achieves interkingdom communication by the generation of messenger chemicals, semiochemicals. It is envisaged that the in situ detection of these as yet ill-defined chemical entities by means of an ingestible sensor would indicate the severity of disease and provide a guide as to its amelioration.

Crohn’s Disease: The infectious Disease Incorporated’s Perspective

Infectious Diseases Incorporated (IDI) is an infectious disease think-tank, established in 1973. Crohn’s disease (CD) is a chronic, recurrent disease of the gastrointestinal tract that has reached epidemic proportions within industrialized nations. CD is said to be without cure. Since 2003, therapeutic interventions have focused on disruption of the pro-inflammatory Th1 response against an unknown antigen. In 2015, the Hruska Postulate was introduced and, in so doing, explained how, in the absence of acquired immunity, newborn infection by Mycobacterium avium subspecies paratuberculosis could cause fixation of the immune system’s Th1 response against the organism. The Hruska Postulate was utilized to answer all the documented epidemiological facts embedded in the natural history of Crohn’s disease and, in particular, why breastfeeding confers protection against the future development of Crohn’s disease. It is Infectious Diseases Incorporated’s (IDI) stated opinion that Crohn’s disease is both preventable and curable if treated appropriately in its early stages.