ARTICLE | doi:10.20944/preprints202209.0346.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: gastrointestinal cramps; gastrointestinal pain; irritable bowel syndrome; hyoscine butyl bromide; peppermint oil; over-the-counter treatment; pharmacy-based patient survey
Online: 22 September 2022 (14:15:32 CEST)
Functional gastro-intestinal disorders (FGID) including irritable bowel syndrome (IBS) are frequently handled by self-management with over the counter (OTC) products such as hyoscine butylbromide (HBB), alone or in combination with paracetamol, and natural products such as peppermint oil. To obtain real-world information, we have performed an anonymous pharmacy-based patient survey among 1686 users of HBB, HBB + paracetamol and peppermint oil. Based on the distinct but overlapping indications for the three OTC products, multiple logistic regression was applied to compare them in users reporting gastrointestinal cramps and pain, bloating, flatulence, or IBS as cardinal symptom. All three treatments reduced symptoms and associated impairments of work/daily chores, leisure activities, and sleep by approximately 50%. Based on the four cardinal symptoms and the four dependent continuous variables of interest (change of intensity of symptoms and of the three impairment domains) a total of 16 logistic regression models were applied. HBB, HBB + paracetamol, and peppermint oil had similar reported overall effectiveness in those models. Gender, age, baseline symptom severity and impairment in one of three domains had small and inconsistent effects on perceived treatment success. We provide evidence that HBB, HBB + paracetamol, and peppermint oil have comparable effectiveness in their approved indications under real-world conditions in an OTC setting.
REVIEW | doi:10.20944/preprints202108.0332.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Gastrointestinal; systemic sclerosis; scleroderma
Online: 16 August 2021 (12:02:37 CEST)
Introduction: The gastrointestinal tract (GI) is the second most affected organ system in systemic sclerosis or systemic/localized scleroderma (SSc) and is an important topic for research. Approximately 90% of patients with scleroderma exhibit pathology of the GI tract. The systemic scleroderma has the potential to impact any part of the gastrointestinal tract, between the oral cavity and anorectum. The pathological complications of scleroderma adversely impact the health-related quality of life of the affected patients and increase the treatment burden of patients and medical professionals. Study Aim: We summarized the epidemiology, commonly reported clinical manifestations, complications, and available therapies for treating the GI pathology in systemic scleroderma patients. Methodology: We performed a literature review using the keywords "systemic sclerosis," "scleroderma," "GI manifestations in scleroderma," and "GI complications of scleroderma" across databases, including Google Scholar, Medline, Embase, and PubMed. We also analyzed a range of case reports concerning scleroderma manifestations and treatment modalities. Results: Our research revealed the annual incidence of SSc attributing to19.3 cases per million adults in the United States. We found the highest incidence of systemic scleroderma in patients within the age range of 44-55 years. Our results affirmed 5:1 incidence of systemic scleroderma that confirmed the higher impact of this disease condition in females than male populations. We found that the gastrointestinal manifestations of systemic scleroderma predominantly elevate the morbidity and mortality incidence among the affected patients. Esophageal and intestinal manifestations impact 90% and 40-70% of patients with systemic scleroderma. The small bowel hypomotility and small intestinal bacterial overgrowth (SIBO) in systemic scleroderma cases trigger the episodes of malabsorption and malnutrition that eventually add to 50% of the mortality rate. Systemic sclerosis is associated with the high incidence of fecal incontinence that triggers depression and its deleterious mental health manifestations in many clinical scenarios. Conclusion: The gastrointestinal complications in systemic sclerosis potentially deteriorate the daily living activities of the affected patients. The systematic management of the gastrointestinal complications of systemic scleroderma warrants multidisciplinary approaches. Prospective studies should focus on developing targeted therapies for improving the recovery patterns and prognostic outcomes in systemic scleroderma cases.
REVIEW | doi:10.20944/preprints202012.0378.v1
Subject: Life Sciences, Biochemistry Keywords: gastrointestinal tract; dietary antigens; metabolites; microbiota; macronutrients; gastrointestinal immunity; mucosal immune regulation
Online: 15 December 2020 (12:20:48 CET)
The gastrointestinal tract contains multiple types of immune cells that maintain the balance between tolerance and activation at the first line of host defense facing non-self antigens, including dietary antigens, commensal bacteria, and sometimes unexpected pathogens. Maintaining homeostasis at the gastrointestinal tract requires stringent regulation of the immune responses against various environmental conditions. Diet can be converted into gut metabolites which have unique functional activities through host as well as microbial enzymatic activities. Accumulating evidences demonstrate that gastrointestinal metabolites have significant impacts on the regulation of intestinal immunity and further integrate immune response of distal mucosal tissue. Metabolites, especially derived from microbiota, regulate immune cell functions by various ways including recognition and activation of cell surface receptors, controlling of gene expression by epigenetic regulation and integration of cellular metabolism. These mucosal immune regulations are key to understand underlying mechanism for the development of gastrointestinal disorders. Here, we review the recent advancement of our understanding on the role of gut metabolites in the regulation of gastrointestinal immunity with highlighting the cellular and molecular regulatory mechanisms by macronutrients-derived metabolites.
CASE REPORT | doi:10.20944/preprints201812.0315.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Duodenum, gastrointestinal stromal tumor; treatment
Online: 26 December 2018 (12:25:28 CET)
Gastrointestinal stromal tumors are the mostly seen mesenchymal tumors of the gastrointestinal system. This rare tumor in duodenum is seen 5%. The diagnosis and treatment is hard because of its rarity and location. Case: A 63-year-old man with a solid mass at the third part of the duodenum, and local segmental resection of the tumor was performed. The histopathology was reported as gastrointestinal stromal tumor of the duodenum with negative surgical margins. Discussion: Gastrointestinal stromal tumors at the duodenum are seen rarely. They can be asymptomatic or may involve symptoms of upper GI bleeding and abdominal pain at presentation. Because of the misleading clinical presentation the differential diagnosis may be difficult. Tumors less than 2 cm can be followed by endoscopic ultrasound. Local segmental resection with 1cm clear margin is the treatment choice.
CASE REPORT | doi:10.20944/preprints201812.0316.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: Stomach, giant, gastrointestinal stromal tumor; treatment
Online: 26 December 2018 (12:29:23 CET)
Gastrointestinal stromal tumors are the mostly seen mesenchymal tumors of the gastrointestinal system and mostly seen at the stomach. We report a case of giant gastrointestinal stromal tumor of the stomach in a 71-year-old woman. The physical examination and radiological findings revealed that a giant mass occupied most of the abdominal cavity. The patient underwent an en-block resection of this giant mass with partial resection of the distal stomach and transverse colon and, reconstruction with gastro-jejunostomy and end-to end colo-colic anatomoses. The histopathologic diagnosis was revealed as gastrointestinal stromal tumor of the stomach. We suggest that complete surgical resection is the only effective radical treatment approach for giant gastrointestinal stromal tumors of the stomach.
ARTICLE | doi:10.20944/preprints201704.0062.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: survivin; high expression; gastrointestinal cancer; prognostic
Online: 11 April 2017 (10:51:06 CEST)
Previous studies on the prognostic impact of survivin expression in gastrointestinal (GI) cancer have yielded inconsistent results. This study was initiated to assess the relationship between survivin expression and overall survival (OS) or disease free survival (DFS) in GI cancer patients. We applied system literature searches on EMBASE, PubMed, Web of science, and the Cochrane library to conduct this up-to-date meta-analysis. Thirty studies with totally 3622 GI cancer patients were collected. The prevalence of high survivin expression in GI cancer was 0.57 (95% CI: 0.51-0.63). High survivin expression was significantly associated with shorter OS (HR 1.57, 95% CI: 1.42-1.74) and DFS (HR 1.38, 95% CI: 1.21-1.58). Subgroup analysis also showed significant association between high survivin expression and poorer OS or DFS in gastric cancer or colorectal cancer. In summary, our study indicated that high survivin expression was related to poor prognosis in GI cancer. Well-designed studies with large sample and more convincing data are needed to confirm our conclusion.
CASE REPORT | doi:10.20944/preprints202104.0122.v1
Subject: Medicine & Pharmacology, Veterinary Medicine Keywords: SARS-CoV-2; canine; gastrointestinal; infection; virus
Online: 5 April 2021 (12:23:45 CEST)
SARS-CoV-2 infects a range of host species. However, the susceptibility of companion animals to SARS-CoV-2 and their potential ability to transmit the virus to humans remains unclear. Here, we present a detailed clinical description of an immunosuppressed dog that was infected with SARS-CoV-2. The dog had severe gastrointestinal (GI) clinical signs, coagulopathy, elevated hepatic transaminases, and met canine systemic inflammatory response syndrome criteria, without respiratory clinical signs, mirroring a subset of humans with GI-restricted COVID-19. Viral sequencing demonstrated divergence from other reported sequences, based on phylogenetic analysis. The dog shed high levels of virus for a prolonged time period with positive virus isolation. The dog’s immunosuppressed state may have increased both susceptibility to infection and disease progression. Together, our findings suggest that certain individual companion animals may be at higher risk for severe SARS-CoV-2 infection, COVID-19-like disease, and high viral shedding, which may pose a transmission risk to humans.
ARTICLE | doi:10.20944/preprints202009.0356.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: SSI; MORBIDITY; MORTALITY; GASTROINTESTINAL; HPB; HOSPITAL STAY
Online: 16 September 2020 (08:38:38 CEST)
Aims: Primary AIM of the study was to evaluate effect of prolonged hospital stay on Surgical site infections We also evaluated effect of prolonged hospital stay on overall morbidity in Gastrointestinal and Hepatobiliary Surgery as secondary outcome. Methods: We retrospectively analysed all the patients who underwent gastrointestinal and hepatobiliary surgery between April 2017 to March 2020. On our analysis we found mean hospital stay in patient who did not develop SSI and/or morbidity was 4 days (Total hospital stay) vs 6 days who developed morbidity (hospital stay before diagnosis of SSI or diagnosis or morbid event). Based on this to avoid selection bias, we did 1:1 propensity score analysis between patients who had 4 or less than hospital stay vs patients who had 5 or more hospital stay before diagnosis of surgical site infection and/or morbid event. We took all the preoperative and intraoperative factors like Age, sex, malignant disease, ASA score, CDC grade of surgery, open or laparoscopic surgery, HPB surgeries, colorectal surgeries, Upper Gastrointestinal surgeries and small intestinal surgeries as covariates. We used nearest neighbor matching protocol with a calipher of 0.2. Cases were not reusable after matching. Statistical analysis was done using SPSS version 23. Results: We included 348 patients operated between April 2017 and March 2020 in our analysis. After 1:1 propensity score matching 58 patients included in study arm (prevent hospital stay more than 4 days) and 56 patients in control arm. Both groups were comparable with regard to Age, Sex, Surgery for malignant disease, ASA score, CDC grade of surgery, HPB surgeries, Small intestinal surgeries, Colorectal surgeries, upper gastrointestinal surgeries, intraoperative blood product requirement, intraoperative hypotension or any other event, operative time. Prolonged hospital stay (> 4 days) was significantly associated with surgical site infections (p<0.0001), morbidity (p=0.001). Open surgeries were associated with prolonged hospital stay. (p=0.032). Conclusion: Prolonged Hospital stay is associated with increase surgical site infection and morbidity in Gastrointestinal and Hepatobiliary Surgery.
REVIEW | doi:10.20944/preprints201810.0554.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: gut brain axis; microbiota; functional gastrointestinal disorders
Online: 24 October 2018 (07:41:58 CEST)
The central nervous system (CNS) and the human gastrointestinal (GI) tract communicate through the gut-brain axis (GBA). Such communication is bi-directional and involves neuronal, endocrine and immunological mechanisms. The scientific data are mounting that gut microbiota is a source of a number of neuroactive and immunocompetent substances, which shape the structure and function of brain regions involved in control of emotions, physical activity and cognition. Most of GI maladies are associated with altered transmission within the GBA and influenced both by genetic and environmental factors. Current treatment protocols widely advocated for the treatment of GI disorders may positively or adversely affect the composition of intestinal microbiota with diverse impact on therapeutic outcome. The alterations of gut microbiota have been associated with mood and depressive disorders. and mental health is frequently altered in the course of many GI and non-GI ailments. Deregulation of the GBA may constitute a grip point for the development of diagnostic tools and personalized microbiota-based therapy. For example next generation sequencing (NGS) offers detailed analysis of microbiome footprints in patients with mental and GI disorders. Psychobiotics are new class of beneficial bacteria, with documented efficacy in the treatment of gut-brain axis disorders.
ARTICLE | doi:10.20944/preprints202203.0187.v2
Subject: Life Sciences, Virology Keywords: human parechovirus; HPeV; PeV-A; Panama; gastrointestinal infection; respiratory infection
Online: 27 April 2022 (08:07:52 CEST)
Human Parechoviruses, officially known as Parechovirus A (PeV-A), is associated with mild gastrointestinal and respiratory illness in young children, however, they may also give rise to Central Nervous System (CNS) infections and neonatal sepsis. While studies have delved into the detection of PeV-A in different populations, the detection of PeV-A in Hispanic populations in Latin American countries is not well-known. The aim of this study was to determine the presence of PeV-A in respiratory, gastrointestinal, and neurological clinical samples of pediatric patients in Panama. Two hundred samples of pediatric patients with a negative diagnosis for the main respiratory viruses, rotavirus and neurological viruses such as herpesvirus, enterovirus and cytomegalovirus, collected between 2014 and 2015, were analyzed by real-time RT-PCR. Eight positive PeV-A infections were detected, 2 in respiratory samples, 5 in stool samples and one detected in cerebrospinal fluid. This is the fisrt report of PeV-A in Panamá.
ARTICLE | doi:10.20944/preprints202005.0216.v1
Subject: Keywords: children; infectious disease; lower respiratory tract infections; gastrointestinal
Online: 12 May 2020 (12:59:25 CEST)
The objective of this study was to describe the overall pattern of morbidity and mortality of children seen at the Thai Binh Pediatric Hospital in Vietnam, with a focus on infectious diseases. A retrospective review of hospitalisation records was conducted from 1 January 2015 to 31 December 2019. Data were obtained from a total of 113,999 records. The median age of patients was 18 months, with 83.98% of patients aged <5 years. Infectious diseases accounted for 61.0% of all cases. The most prevalent diseases were lower respiratory tract infections (32.8%), followed by gastrointestinal infections (13.3%) and confirmed influenza (5.4%). Most infections were not microbiologically documented. A total of 81.4% patients received at least one antibiotic. Most patients (97.0%) were hospitalised for less than 15 days. Regarding outcomes, 87.8% patients were discharged home with a favourable outcome. 12.0% were transferred to the Vietnam National Children’s Hospital because their condition had worsened and 0.1% died. In total, infectious diseases accounted for 40.4% of deaths, followed by neonatal disorders (34.6%). Our data serves a basis for the identification of needs for diagnostic tools and for future evaluation of the effect of the targeted implementation of such facilities. Point-of-care tests, including real-time PCR assays to identify common pathogens should be implemented for more accurate diagnosis and more appropriate antibiotic use.
ARTICLE | doi:10.20944/preprints201906.0033.v1
Subject: Medicine & Pharmacology, Oncology & Oncogenics Keywords: gastrointestinal stromal tumors, GIST, Sunitinib, Imatinib, predictive factors
Online: 5 June 2019 (08:53:25 CEST)
Imatinib 400 mg is the standard of care for medical treatment of advanced GISTs. In the majority of cases, however, GISTs eventually develop resistance to imatinib. The optimal second line treatment has not been established yet and imatinib dose escalation (800 mg) or sunitinib represent two feasible options. The objective of this retrospective, multi-institutional, study is to analyze the validity of several parameters as possible predictive factors of response to sunitinib after imatinib failure. We reviewed 128 metastatic GISTs treated with sunitinib between January 2007 to June 2017. Primary tumour site, metastatic site, c-KIT/PDGFR-α mutational status, PET-FDG status and type of disease progression to sunitinib were assessed as possible predictive factors of response. This study identifies the gastric site of primary tumor as a predictive factor to sunitinib efficacy in second line setting. The mutational status (GIST WT), the site of metastasis (peritoneum) and the FDG-PET status (negative), although not statistically significant, seem to be elements of increased activity for sunitinib treatment. These results provide the rationale to drive physician for sunitinib choice in second line setting for metastatic GISTs, to improve patients selection and to maximize the benefit from the treatment, on the basis of possible predictive factors of response.
REVIEW | doi:10.20944/preprints202112.0433.v1
Subject: Life Sciences, Microbiology Keywords: Lactobacillus spp, Bacillus spp., Anti-cancer, Probiotics, Gastrointestinal, Dysbiosis.
Online: 27 December 2021 (14:50:58 CET)
Malignant neoplasm is one of the most incurable diseases among inflammatory diseases. Researchers have been studying for decades to win over this lethal disease and provide the light of hope to humankind. The gastrointestinal bacteria of human hold a complex ecosystem and maintain homeostasis. One hundred trillion microbes are residing in the gastrointestinal tract of human. Disturbances in the microbiota of human’s gastrointestinal tract can create immune response against inflammation and also can develop diseases , including cancer. The bacteria of the gastrointestinal tract of human, can secrete a variety of metabolites and bioproducts which aid in the preservation of homeostasis in the host and gut. During pathogenic dysbiosis, on the other hand, numerous microbiota subpopulations may increase and create excessive levels of toxins, which can cause inflammation and cancer. Furthermore, the immune system of host and the epithelium cell can be influenced by gut microbiota. Probiotics, which are bacteria that live in the gut, have been protected against tumor formation. Probiotics are now studied to see if they can help fight dysbiosis in cancer patients undergoing chemotherapy or radiotherapy because of their capacity to maintain gut homeostasis. Countless numbers of gut bacteria have demonstrated anti-cancer efficiency in cancer treatment, prevention, and boosting the efficiency of immunotherapy. The review article has briefly explained the anti-cancer immunity of gut microbes and their application in treating a variety of cancer. This review paper also highlights the pre-clinical studies of probiotics against cancer and the completed and ongoing clinical trials on cancers with the two most common and highly effective probiotics Lactobacillus and Bacillus spp.
REVIEW | doi:10.20944/preprints202102.0592.v1
Subject: Chemistry, Analytical Chemistry Keywords: gastrointestinal diseases; nutraceutical; natural anti-inflammatory; natural antioxidant; watercress
Online: 25 February 2021 (17:03:03 CET)
The incidence of gastrointestinal diseases (cancer in particular) has increased progressively with considerable morbidity, mortality, and a high economic impact on the healthcare system. Dietary intake of natural bioactive phytochemicals showed to have cancer-preventing and therapeutic effects. This includes the cruciferous vegetable derivative phenethyl isothiocyanate (PEITC), a bioactive compound from watercress. PEITC antioxidant, anti-inflammatory and anti-cancer properties are of particular importance. This review summarizes the current knowledge on the role of PEITC as a potential natural nutraceutical or an adjuvant against oxidative/inflammatory-related disorders in the gastrointestinal tract. We also discuss the safe and recommended dose of PEITC. Besides, we establish a framework to guide the research and development of sustainable methodologies for obtaining and stabilizing this natural nutraceutical for industrial use. This is a topic that still needs more scientific development, but with the potential to lead to a viable strategy in the prevention of cancer and other associated diseases of the gastrointestinal tract.
ARTICLE | doi:10.20944/preprints201807.0088.v1
Subject: Chemistry, Analytical Chemistry Keywords: nutrient profiling; simulated gastrointestinal digestion; antioxidant activity; fish soup
Online: 5 July 2018 (08:51:14 CEST)
Different kinds of freshwater fish soups show a diverse range of health functions, due to their different nutritional substances and corresponding bioactivities. Crucian carp soup and snakehead soup have different dietotherapy functions, crucian carp soup is suitable for lactating women and snakehead soup is suitable for postoperative patients. In the current study, the changes of nutrient profiles in the different fish soups, such as chemical composition, free amino acids, mineral and fatty acid contents, were investigated. The antioxidant activities of the fish soups were evaluated by using the DPPH radical scavenging activity, the ferrous ion chelating activity, the hydroxyl radical-scavenging activity and the reducing power effect. In order to learn the theoretical basis of the potential role fish soup plays in diet therapy functions after being digested by the human body, the nutrient profiling and bioactivities of the fish soup samples after simulated gastrointestinal digestion were also explored. The intensive profiles of nutritional composition and antioxidant activities of these two kinds of fish soups were expected to partly provide the theoretical basis of therapeutic effects.
REVIEW | doi:10.20944/preprints202103.0598.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Camellia sinensis; tea polyphenols; gut microbiota; gastrointestinal bacteria; systematic review
Online: 24 March 2021 (16:18:03 CET)
A diet high in polyphenols is associated with a diversified gut microbiome. Tea is the second most consumed beverage in the world, after water. The health benefits of tea might be attributed to the presence of polyphenol compounds such as catechins, theaflavins, tannins, and flavonoids. Although many studies are on tea, little is known of its effects on trillions of gut microbiota. Hence, this review is aimed at systematically studying the effect of tea polyphenols on the stimulation or suppression of gut microbiota in humans and animals. It was conducted according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. Articles were retrieved from PubMed and Scopus databases, and data were extracted from 6 human trials and 15 animal studies. Overall, huge variations were observed in terms of microbiota composition between humans and animals. A more consistent pattern of diversified microbiota was observed in animal studies. Tea alleviated the gut microbiota imbalance caused by high-fat diet-induced obesity, diabetes, and ultraviolet-induced damage. Overall changes in microbiota composition measured by beta diversity analysis showed that tea had shifted the microbiota from the pattern seen in animals that received tea-free intervention. In humans, the prebiotic-like effect was observed towards gut microbiota, but these results appear in lower-quality studies. Beta diversity in human microbiota remains intact despite tea intervention; supplementation with different teas affected different types of bacterial taxa in the gut. These studies suggest that tea polyphenols may have a prebiotic effect in disease-induced animals and in a limited number of human interventions. Further intervention is needed to identify the mechanisms of action underlying the effects of tea on gut microbiota.
REVIEW | doi:10.20944/preprints202012.0706.v1
Subject: Behavioral Sciences, Other Keywords: fecal incontinence; unconscious elderly; irritable bowel syndrome; gastrointestinal symptoms; constipation; diarrhea
Online: 28 December 2020 (13:24:54 CET)
The irritable bowel syndrome (IBS) is functional gastrointestinal tract disease, include abnormal defecation and abdominal pain. The Rome IV criteria define fecal incontinence as "recurrent and uncontrolled stool leakage that lasts more than 3 months." Fecal incontinence is common in patients with IBS and can have a significant negative impact on daily life and reduce the patient's quality of life. Diet and lifestyle guidance are needed to prevent fecal incontinence. Fecal incontinence can be reduced by ingesting dietary fiber, which can improve stool properties, and avoiding foods with stool-softening properties. Additionally, defecation habit guidance is important for preventing fecal incontinence. If rectal sensation is normal, it is recommended to go to the bathroom as soon as there is a desire to defecate. In elderly people, if there is stool in the rectum due to decreased rectal sensation and it continues to accumulate in the rectum without triggering the urge to defecate, overflowing leaky fecal incontinence may occur. For such patients, defecation habit training teaching them to defecate even if they do not have the desire to defecate may be effective. Education and advice on defecation reduces fecal incontinence and is beneficial to caregivers.
ARTICLE | doi:10.20944/preprints202005.0239.v1
Subject: Medicine & Pharmacology, Allergology Keywords: Acute Kidney Injury; Gastrointestinal surgery; HPB surgery; perioperative care; critical care
Online: 14 May 2020 (12:03:15 CEST)
AIM: Aim of our study was to evaluate incidence and causative factors for acute kidney injury in gastrointestinal and hepatobiliary surgeries. Material and methods: All the gastrointestinal surgeries performed between April 2018 to March 2020, in our institution have been analysed for acute kidney injury. Acute kidney injury defined according to acute kidney injury network classification. Categorical variables were evaluated by chi square test and continuous variables by Mann Whitney U test. Statistical analysis was done using SPSS version 23. P< 0.05 was considered significant Results: We performed 331 gastrointestinal and hepatobiliary surgery from April 2018 to March 2020. After exclusion 317 patients were included in study population.14 patients (4.4%) were defined as having acute kidney injury according to acute kidney injury network classifications. On univariate analysis acute kidney injury was associated with open surgery (p= 0.002, Intra operative hypotension (p=0.006), CDC grade of surgery (p<0.001), increased used to blood products (p=0.004), higher ASA grade (p<0.0001), increased operative time(p<0.0001). On multivariate logistic regression analysis higher ASA grade (p=0.001) and increased operative time (0.015) independently predicted acute kidney injury. Acute kidney injury was also significantly associated with 90 days mortality. ( p= <0.0001) Conclusion:Post-operative acute kidney injury was associated with significant mortality in gastrointestinal and hepatobiliary surgery. Open surgery, higher CDC grade surgery, more blood products, higher ASA grades, increase operative time predicted acute kidney injury in post operative periods. Higher ASA grades and increased operative time predicted acute kidney injury.
DATA DESCRIPTOR | doi:10.20944/preprints202202.0305.v1
Subject: Life Sciences, Biochemistry Keywords: Physicochemical properties; Gastrointestinal absorption; Lipinski's rules; Veber's rules; Ghose's rules; Muegge's rules
Online: 24 February 2022 (08:35:30 CET)
The discovery of more bioactive compounds for non-invasive administration has been the goal of research groups focused on pharmacotherapy. Phytonutrients have always been attractive for researchers because they are a significant source of bioactive phytochemicals, but it is challenging to determine which components show high biomedical activity. However, based on the chemical structure of these active compounds, their physicochemical properties can be calculated to predict the probability of gastrointestinal (GI) absorption after oral administration. Indeed, different researchers have proposed several rules (e.g., Lipinski's, Veber's, Ghose's, and Muegge's rules) to attain these predictions for synthetic compounds. Most phytochemicals do not fully comply with these rules even though they show high bioactivity and high GI absorption experimentally. Here, we provide a detailed methodology using web-based platforms to determine the physicochemical properties of five phytochemicals in the phytonutrients ginger, echinacea, and tobacco. Furthermore, we analyzed the calculated data and established a protocol based on the combination and integration of these rules, plus other extended parameter ranges, to reliably predict the GI absorption of natural compounds. The presented data and methodology can be beneficial for evaluating bioactive natural compounds as potential drug candidates and predicting their oral bioavailability in patients.
ARTICLE | doi:10.20944/preprints202010.0032.v1
Subject: Materials Science, Biomaterials Keywords: Nanomedicine; human ferritin; gastrointestinal tumors; non-camptothecin topoisomerase I inhibitors; drug-delivery; CD71
Online: 2 October 2020 (09:21:53 CEST)
Gastrointestinal tumors including pancreatic and colorectal cancers represent one of the greatest public health issues worldwide, leading to million global deaths. Recent research demonstrated that the human heavy chain ferritin (HFt) can encapsulate different type of drugs in its cavity and can bind to its receptor, CD71, in several solid and hematological tumors, thus highlighting the potential use of ferritin for tumor-targeting therapies. Here, we describe the development and characterization of a novel nanomedicine based on the HFt that is named The-0504. In particular, this novel system is a nano-assembly comprising an engineered version of HFt that entraps about 80 molecules of a potent, wide-spectrum, non-camptothecin topoisomerase I inhibitor (Genz-644282). The-0504 can be produced by a standardized pre-industrial process as a pure and homogeneously formulated product with favourable lyophilization properties. The preliminary anticancer activity was evaluated in cultured cancer cells and in a mouse model of pancreatic cancer. Overall results reported here make The-0504 a candidate for further preclinical development against CD-71 expressing deadly tumors
REVIEW | doi:10.20944/preprints202006.0135.v1
Subject: Medicine & Pharmacology, Gastroenterology Keywords: enteric nervous system; ENS; gastrointestinal tract; GI; glucagon-like peptide 2; GLP-2
Online: 11 June 2020 (11:58:03 CEST)
The gastrointestinal (GI) tract is innervated by the enteric nervous system (ENS), an extensive neuronal network that traverses along its walls. Due to local reflex circuits, the ENS is capable of functioning with and without input from the central nervous system. The functions of the ENS range from the propulsion of food to nutrient handling, blood flow regulation and immunological defense. Records of it first being studied emerged in the early 19th century when the submucosal and myenteric plexuses were discovered. This was followed by extensive research and further delineation of its development, anatomy, and function during the next two centuries. The morbidity and mortality associated with the underdevelopment, infection or inflammation of the ENS highlights its importance and the need for us to completely understand its normal function. This review will provide a general overview of the ENS to date and connect specific GI disorders such as short bowel syndrome with neuronal pathophysiology. Exciting opportunities in which the ENS could be used as a therapeutic target for common GI diseases will also be highlighted, as the further unlocking of such mechanisms could open the door to more therapy-related advances, and ultimately change our approach to GI disorders.
REVIEW | doi:10.20944/preprints201903.0231.v1
Subject: Earth Sciences, Environmental Sciences Keywords: cyanotoxin; cyanobacterial bloom; cylindrospermopsin; microcystin; inflammation; diarrhea; gastrointestinal illness; lipopolysaccharide; innate immune system
Online: 26 March 2019 (09:31:44 CET)
Cyanobacterial blooms occur with increasing frequency in freshwater ecosystems, posing a hazard to human and environmental health. Exposure of human to cyanobacterial metabolites occurs mostly via accidental ingestion through contaminated drinking water or during recreational activities and, most frequently, results in gastrointestinal symptoms. Despite the clinical manifestation, cyanobacterial metabolites are rather investigated for their toxicity towards specific organs or tissues, especially hepato-, nephro- and neurotoxicity, then for effects on the gastrointestinal tract and the associated lymphoid tissue. The aim of this review was to systematically summarize available literature on the effects on the gastrointestinal tract and the mucosal innate immune system and compile the data from both, in vitro and in vivo studies, focusing on human-health relevant models. Our systematic literature review revealed significant data gaps in the understanding on metabolites breaching the gastrointestinal barrier and the role of the immune system in the establishment of clinical symptoms. Microcystins and cylindrospermopsin were linked to gastrointestinal symptoms, immune system effects or both. Furthermore, implications for cyanobacterial bloom lipopolysaccharides in gastrointestinal inflammation were reported in several cases, while other metabolites received only minor attention. The collected data indicate the need for a reassessment of potential enterotoxicity of microcystins and cylindrospermopsin. Additionally, the carcinogenic potential of cyanotoxins, especially microcystins, has to be clarified, as an increasing amount of epidemiological studies show correlations between cyanobacterial blooms and gastrointestinal cancer incidence. Furthermore, other, often highly abundant bioactive metabolites like aeruginosins, have to be toxicologically evaluated at levels also accounting for (sub-)chronic exposure to low concentrations and in combination with naturally co-occurring metabolites, as can be expected in drinking water supplies. studies, focusing on human-health relevant models. Our systematic literature review revealed significant data gaps in the understanding on metabolites breaching the gastrointestinal barrier and the role of the immune system in the establishment of clinical symptoms. Microcystins and cylindrospermopsin were linked to gastrointestinal symptoms, immune system effects or both. Furthermore, implications for cyanobacterial bloom lipopolysaccharides in gastrointestinal inflammation were reported in several cases, while other metabolites received only minor attention. The collected data indicate the need for a reassessment of potential enterotoxicity of microcystins and cylindrospermopsin. Additionally, the carcinogenic potential of cyanotoxins, especially microcystins, has to be clarified, as an increasing amount of epidemiological studies show correlations between cyanobacterial blooms and gastrointestinal cancer incidence. Furthermore, other, often highly abundant bioactive metabolites like aeruginosins, have to be toxicologically evaluated at levels also accounting for (sub-)chronic exposure to low concentrations and in combination with naturally co-occurring metabolites, as can be expected in drinking water supplies.
ARTICLE | doi:10.20944/preprints202012.0784.v1
Subject: Life Sciences, Biochemistry Keywords: Bacillus subtilis; flow cytometry; gastrointestinal health; peripheral blood mononuclear cells (PBMC); probiotic; short chain fatty acid
Online: 31 December 2020 (09:46:43 CET)
Probiotics make up a large and growing segment of the commercial market of dietary supplements and are touted as offering a variety of human health benefits. Some of the purported positive impacts of probiotics include, but are not limited to, stabilization of the gut microbiota, prevention of gastrointestinal disorders and modulation of the host immune system. Current research suggests that the immunomodulatory effects of probiotics are strain specific and vary in mode of action. Here, we examined the immunomodulatory properties of Bacillus subtilis strain DE111 in a healthy human population. In a randomized, double blind, placebo-controlled four-week intervention, we examined peripheral blood mononuclear cells (PBMCs) at basal levels pre- and post-treatment as well as in response to stimulation with bacterial lipopolysaccharide (LPS). We observed an anti-inflammatory effect of B. subtilis, manifested as a decrease in immune cell populations within the basal state along with an increase in anti-inflammatory immune cells in response to LPS stimulation. Overall gastrointestinal health, microbiota, and circulating and fecal markers of inflammation and gut barrier function were largely unaffected by DE111 treatment. These data suggest that the novel probiotic B. subtilis DE111 may have clinical applications in modulating immune homeostasis via anti-inflammatory mechanisms.
ARTICLE | doi:10.20944/preprints202004.0542.v1
Subject: Keywords: Cytokine storm; IL-1 and IL-6 production via SARS-CoV-2; gastrointestinal H4R receptor antagonists
Online: 30 April 2020 (17:14:34 CEST)
The premise regarding COVID-19 disease is that it is a spectrum which begins with infection with viral SARS-CoV-2 exposure via airborne or oral virus particles. The individual response to it depends on many factors including co-morbid conditions. An important aspect of SARS-CoV-2 virus infection is the cytokine storm that develops after the infection. The immuno-chemical chaos created in this cytokine storm is to the benefit of the virus. In this meta analysis the authors explore ways to let the cytokine storm die down by looking into the role of histamine. Histamine is a metabolic product of the essential aminoacid histidine. Histamine has 4 known receptors: H1, H2, H3 and H4. The immunoglobulines IgE and IgM are indicative for a COVID-19 infection. This immune response is related to inflammation. Inflammation, in turn, runs mainly via histamine after e.g. virus inoculation. The goal of the meta-study is to gather evidence to primarily block the H4 receptor (H4R) in gastrointestinal cells to diminish the cytokine overproduction in the $\approx$ 30\% of the patients suffering from gastrointestinal problems caused by SARS-CoV-2. Our concept is as follows. If we can strike a careful balance between hampering the gastrointestinal spreading of the virus and histamine antagonists to tackle the cytokine storm, then the natural immunity can later on come on line again and attack the virus without being led astray by cytokine chaos. We will concentrate on H4R but also look at H1R and H2R related effects. The proposed substances in our systemic approach can be balanced for an effective early treatment. The nature of our work is by its method and results theoretical. In that respect we also may note the structural chemistry indol skeleton resemblance among a number of different drugs.
REVIEW | doi:10.20944/preprints202205.0014.v2
Subject: Life Sciences, Molecular Biology Keywords: COVID-19; SARS-CoV-2; Diabetes; Neurological dysfunction; Cardiovascular complications; Pulmonary dysfunction; Renal dysfunction; bone loss; Eye disease; Gastrointestinal complications
Online: 23 May 2022 (11:00:06 CEST)
Since the discovery of the Coronavirus disease 2019 (COVID-19) outbreak, a vast majority of studies have been carried out that confirmed the worst outcome of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in people with preexisting health conditions, including diabetes, obesity, hypertension, cancer, and cardiovascular diseases. Likewise, diabetes itself is one of the leading causes of global public health concerns that impose a heavy global burden on public health as well as socio-economic development. Both diabetes and SARS-CoV-2 infection have their independent ability to induce the pathogenesis and severity of multi-system organ dysfunction, while the co-existence of these two culprits can accelerate the pathophysiology and magnify the severity of the diseases. However, the exact pathophysiology of multi-system organ failure in diabetic patients after SARS-CoV-2 infection is still obscure. This review summarized the organ-specific possible molecular mechanisms of SARS-CoV-2 and diabetes-induced pathophysiology of several diseases of multiple organs, including the lungs, heart, kidney, brain, eyes, gastrointestinal system, and bones, and subsequent manifestation of multi-system organ failure.
REVIEW | doi:10.20944/preprints202001.0171.v1
Subject: Medicine & Pharmacology, Nutrition Keywords: Dipeptidyl peptidase-4; Fibroblast growth factor; Gastrointestinal peptide; Glucagon-like peptide 1; Glucagon receptor; Peroxisome proliferator-activated receptor; Sodium glucose cotransporter
Online: 16 January 2020 (11:44:49 CET)
Liver related diseases are the 3rd leading causes (9.3%) of mortality in type 2 diabetes mellitus (T2DM) in Japan. T2DM is closely associated with nonalcoholic fatty liver disease (NAFLD) which is the most prevalent chronic liver disease worldwide. Nonalcoholic steatohepatitis (NASH), a severe form of NAFLD, can lead to hepatocellular carcinoma (HCC) and hepatic failure. There are no established pharmacotherapies for NASH patients with T2DM. Though vitamin E is established as a 1st line agent in NASH without T2DM, its efficacy was recently denied in NASH with T2DM. The effects of pioglitazone on NASH histology with T2DM have extensively been established, but several concerns exist such as body weight gain, fluid retention, cancer incidence, and bone fracture. Glucagon-like peptide 1 (GLP-1) receptor agonists and sodium/glucose cotransporter 2 (SGLT2) inhibitors are expected to ameliorate NASH (LEAN study, LEAD trial, and E-LIFT study). Among a variety of SGLT2 inhibitors, dapagliflozin have already entered phase 3 trials (DEAN study). A key clinical question is what kinds of anti-diabetic drugs are the most appropriate for the treatment of NASH to prevent progression of hepatic fibrosis resulting in HCC/liver-related mortality without increasing risk at cardiovascular or renal events. The combination therapies such as glucagon receptor agonist/GLP-1 or gastrointestinal peptide /GLP-1 will be under development. This review focuses on antidiabetic agents and future perspectives on the view of the treatment of NAFLD with T2DM.