Derivation, validation, and comparison of a new prognostic scoring system for acute lower gastrointestinal bleeding

\ua9 2023 The Authors. DEN Open published by John Wiley & Sons Australia, Ltd on behalf of Japan Gastroenterological Endoscopy Society.Objectives: Lower gastrointestinal bleeding is a common presentation with little data concerning risk factors for adverse outcomes. The aim was to derive and validate a scoring system to stratify risk in lower gastrointestinal bleeding and compare it to the Oakland score. Methods: A total of 2385 consecutive patients (mean age 65 years, 1140 males) were used to derive the score using multivariate logistic regression modeling then internally and externally validated. The Oakland score was applied and area under receiver operating characteristic (AUROC) curves were calculated and compared. A score of <1 was compared with an Oakland score of <9 to assess 30-day rebleeding and mortality rates. Results: Rebleeding was associated with age, inpatient bleeding, syncope, malignancy, tachycardia, hypotension, lower hemoglobin and mortality with age, inpatient bleeding, liver/gastrointestinal disease, tachycardia, and hypotension. The area under the receiver operating characteristic curves was 0.742 for rebleeding and 0.802 for mortality. A score <1 was associated with rebleeding (0.0%–2.2%) and mortality (0%). The Oakland score had a significantly lower area under the receiver operating characteristic curve for rebleeding of 0.687 but not for mortality; 0.757. A score <1 was associated with a lower 30-day rebleeding risk compared to an Oakland score <9 (4/379 vs. 15/355, p = 0.009) but not mortality (0/365 vs. 1/355, p = 0.493). Conclusions: Our score predicts 30-day rebleeding and mortality rate with low scores associated with very low risk. The Aberdeen score is superior to the Oakland score for predicting rebleeding. Prospective evaluation of both scores is required

Prevalence of inflammatory bowel disease among coeliac disease patients in a Hungarian coeliac centre

BACKGROUND: Celiac disease, Crohn disease and ulcerative colitis are inflammatory disorders of the gastrointestinal tract with some common genetic, immunological and environmental factors involved in their pathogenesis. Several research shown that patients with celiac disease have increased risk of developing inflammatory bowel disease when compared with that of the general population. The aim of this study is to determine the prevalence of inflammatory bowel disease in our celiac patient cohort over a 15-year-long study period. METHODS: To diagnose celiac disease, serological tests were used, and duodenal biopsy samples were taken to determine the degree of mucosal injury. To set up the diagnosis of inflammatory bowel disease, clinical parameters, imaging techniques, colonoscopy histology were applied. DEXA for measuring bone mineral density was performed on every patient. RESULTS: In our material, 8/245 (3,2 %) coeliac disease patients presented inflammatory bowel disease (four males, mean age 37, range 22-67), 6/8 Crohn's disease, and 2/8 ulcerative colitis. In 7/8 patients the diagnosis of coeliac disease was made first and inflammatory bowel disease was identified during follow-up. The average time period during the set-up of the two diagnosis was 10,7 years. Coeliac disease serology was positive in all cases. The distribution of histology results according to Marsh classification: 1/8 M1, 2/8 M2, 3/8 M3a, 2/8 M3b. The distribution according to the Montreal classification: 4/6 Crohn's disease patients are B1, 2/6 Crohn's disease patients are B2, 2/2 ulcerative colitis patients are S2. Normal bone mineral density was detected in 2/8 case, osteopenia in 4/8 and osteoporosis in 2/8 patients. CONCLUSIONS: Within our cohort of patients with coeliac disease, inflammatory bowel disease was significantly more common (3,2 %) than in the general population

To retain or remove the syndesmotic screw: a review of literature

Introduction: Syndesmotic positioning screws are frequently placed in unstable ankle fractures. Many facets of adequate placement techniques have been the subject of various studies. Whether or not the syndesmosis screw should be removed prior to weight-bearing is still debated. In this study, the recent literature is reviewed concerning the need for removal of the syndesmotic screw. Materials and methods: A comprehensive literature search was conducted in the electronic databases of the Cochrane Library, Pubmed Medline and EMbase from January 2000 to October 2010. Results: A total of seven studies were identified in the literature. Most studies found no difference in outcome between retained or removed screws. Patients with screws that were broken, or showed loosening, had similar or improved outcome compared to patients with removed screws. Removal of the syndesmotic screws, when deemed necessary, is usually not performed before 8-12 weeks. Conclusion: There is paucity in randomized controlled trials on the absolute need for removal of the syndesmotic screw. However, current literature suggests that it might be reserved for intact screws that cause hardware irritation or reduced range of motion after 4-6 months

Fecal pancreatic elastase-1 levels in older individuals without known gastrointestinal diseases or diabetes mellitus

Background - Structural changes occur in the pancreas as a part of the natural aging process. With aging, also the incidence of maldigestive symptoms and malnutrition increases, raising the possibility that these might be caused at least in part by inadequate pancreatic enzyme secretion due to degenerative processes and damage of the gland. Fecal elastase-1 is a good marker of pancreatic exocrine secretion. The aim of this study was to investigate the fecal elastase-1 levels among over 60 years old Finnish and Polish healthy individuals without any special diet, known gastrointestinal disease, surgery or diabetes mellitus. Methods - A total of 159 patients participated in this cross-sectional study. 106 older individuals (aged 60-92 years) were recruited from outpatient clinics and elderly homes. They were divided to three age groups: 60-69 years old (n = 31); 70-79 years old (n = 38) and over 80 years old (n = 37). 53 young subjects (20-28 years old) were investigated as controls. Inclusion criteria were age over 60 years, normal status and competence. Exclusion criteria were any special diet, diabetes mellitus, any known gastrointestinal disease or prior gastrointestinal surgery. Fecal elastase-1 concentration was measured from stool samples with an ELISA that uses two monoclonal antibodies against different epitopes of human elastase-1. Results - Fecal elastase-1 concentrations correlated negatively with age (Pearson r = -0,3531, P < 0.001) and were significantly lower among subjects over 70 years old compared to controls (controls vs. 70-79 years old and controls vs. over 80 years old, both P < 0.001). Among the over 60 years old subjects, the fecal elastase-1 concentrations were below the cut off level of 200 μg/g in 23 of 106 (21.7%) individuals [mean 112 (86-138) μg/g] indicating pancreatic exocrine insufficiency. Of those, 9 subjects had fecal elastase-1 level below 100 μg/g as a marker of severe pancreatic insufficiency. Conclusion - In our study one fifth of healthy older individuals without any gastrointestinal disorder, surgery or diabetes mellitus suffer from pancreatic exocrine insufficiency and might benefit from enzyme supplementation therapy.peerReviewe

Insulin Concentration Modulates Hepatic Lipid Accumulation in Mice in Part via Transcriptional Regulation of Fatty Acid Transport Proteins

Fatty liver disease (FLD) is commonly associated with insulin resistance and obesity, but interestingly it is also observed at low insulin states, such as prolonged fasting. Thus, we asked whether insulin is an independent modulator of hepatic lipid accumulation.In mice we induced, hypo- and hyperinsulinemia associated FLD by diet induced obesity and streptozotocin treatment, respectively. The mechanism of free fatty acid induced steatosis was studied in cell culture with mouse liver cells under different insulin concentrations, pharmacological phosphoinositol-3-kinase (PI3K) inhibition and siRNA targeted gene knock-down. We found with in vivo and in vitro models that lipid storage is increased, as expected, in both hypo- and hyperinsulinemic states, and that it is mediated by signaling through either insulin receptor substrate (IRS) 1 or 2. As previously reported, IRS-1 was up-regulated at high insulin concentrations, while IRS-2 was increased at low levels of insulin concentration. Relative increase in either of these insulin substrates, was associated with an increase in liver-specific fatty acid transport proteins (FATP) 2&5, and increased lipid storage. Furthermore, utilizing pharmacological PI3K inhibition we found that the IRS-PI3K pathway was necessary for lipogenesis, while FATP responses were mediated via IRS signaling. Data from additional siRNA experiments showed that knock-down of IRSs impacted FATP levels.States of perturbed insulin signaling (low-insulin or high-insulin) both lead to increased hepatic lipid storage via FATP and IRS signaling. These novel findings offer a common mechanism of FLD pathogenesis in states of both inadequate (prolonged fasting) and ineffective (obesity) insulin signaling

Nonsense-mediated mRNA decay controls the changes in yeast ribosomal protein pre-mRNAs levels upon osmotic stress

The expression of ribosomal protein (RP) genes requires a substantial part of cellular transcription, processing and translation resources. Thus, the RP expression must be tightly regulated in response to conditions that compromise cell survival. In Saccharomyces cerevisiae cells, regulation of the RP gene expression at the transcriptional, mature mRNA stability and translational levels during the response to osmotic stress has been reported. Reprogramming global protein synthesis upon osmotic shock includes the movement of ribosomes from RP transcripts to stress-induced mRNAs. Using tiling arrays, we show that osmotic stress yields a drop in the levels of RP pre-mRNAs in S. cerevisiae cells. An analysis of the tiling array data, together with transcription rates data, shows a poor correlation, indicating that the drop in the RP pre-mRNA levels is not merely a result of the lowered RP transcription rates. A kinetic study using quantitative RT-PCR confirmed the decrease in the levels of several RP-unspliced transcripts during the first 15 minutes of osmotic stress, which seems independent of MAP kinase Hog1. Moreover, we found that the mutations in the components of the nonsense-mediated mRNA decay (NMD), Upf1, Upf2, Upf3 or in exonuclease Xrn1, eliminate the osmotic stress-induced drop in RP pre-mRNAs. Altogether, our results indicate that the degradation of yeast RP unspliced transcripts by NMD increases during osmotic stress, and suggest that this might be another mechanism to control RP synthesis during the stress response

Differential Deployment of REST and CoREST Promotes Glial Subtype Specification and Oligodendrocyte Lineage Maturation

The repressor element-1 (RE1) silencing transcription factor/neuron-restrictive silencer factor (REST/NRSF) is a master transcriptional regulator that binds to numerous genomic RE1 sites where it acts as a molecular scaffold for dynamic recruitment of modulatory and epigenetic cofactors, including corepressor for element-1-silencing transcription factor (CoREST). CoREST also acts as a hub for various cofactors that play important roles in epigenetic remodeling and transcriptional regulation. While REST can recruit CoREST to its macromolecular complex, CoREST complexes also function at genomic sites independently of REST. REST and CoREST perform a broad array of context-specific functions, which include repression of neuronal differentiation genes in neural stem cells (NSCs) and other non-neuronal cells as well as promotion of neurogenesis. Despite their involvement in multiple aspects of neuronal development, REST and CoREST are not believed to have any direct modulatory roles in glial cell maturation.We challenged this view by performing the first study of REST and CoREST in NSC-mediated glial lineage specification and differentiation. Utilizing ChIP on chip (ChIP-chip) assays, we identified distinct but overlapping developmental stage-specific profiles for REST and CoREST target genes during astrocyte (AS) and oligodendrocyte (OL) lineage specification and OL lineage maturation and myelination, including many genes not previously implicated in glial cell biology or linked to REST and CoREST regulation. Amongst these factors are those implicated in macroglial (AS and OL) cell identity, maturation, and maintenance, such as members of key developmental signaling pathways and combinatorial transcription factor codes.Our results imply that REST and CoREST modulate not only neuronal but also glial lineage elaboration. These factors may therefore mediate critical developmental processes including the coupling of neurogenesis and gliogenesis and neuronal-glial interactions that underlie synaptic and neural network plasticity and homeostasis in health and in specific neurological disease states

Mortality and pulmonary complications in patients undergoing surgery with perioperative SARS-CoV-2 infection: an international cohort study

Background: The impact of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on postoperative recovery needs to be understood to inform clinical decision making during and after the COVID-19 pandemic. This study reports 30-day mortality and pulmonary complication rates in patients with perioperative SARS-CoV-2 infection. Methods: This international, multicentre, cohort study at 235 hospitals in 24 countries included all patients undergoing surgery who had SARS-CoV-2 infection confirmed within 7 days before or 30 days after surgery. The primary outcome measure was 30-day postoperative mortality and was assessed in all enrolled patients. The main secondary outcome measure was pulmonary complications, defined as pneumonia, acute respiratory distress syndrome, or unexpected postoperative ventilation. Findings: This analysis includes 1128 patients who had surgery between Jan 1 and March 31, 2020, of whom 835 (74·0%) had emergency surgery and 280 (24·8%) had elective surgery. SARS-CoV-2 infection was confirmed preoperatively in 294 (26·1%) patients. 30-day mortality was 23·8% (268 of 1128). Pulmonary complications occurred in 577 (51·2%) of 1128 patients; 30-day mortality in these patients was 38·0% (219 of 577), accounting for 81·7% (219 of 268) of all deaths. In adjusted analyses, 30-day mortality was associated with male sex (odds ratio 1·75 [95% CI 1·28–2·40], p\textless0·0001), age 70 years or older versus younger than 70 years (2·30 [1·65–3·22], p\textless0·0001), American Society of Anesthesiologists grades 3–5 versus grades 1–2 (2·35 [1·57–3·53], p\textless0·0001), malignant versus benign or obstetric diagnosis (1·55 [1·01–2·39], p=0·046), emergency versus elective surgery (1·67 [1·06–2·63], p=0·026), and major versus minor surgery (1·52 [1·01–2·31], p=0·047). Interpretation: Postoperative pulmonary complications occur in half of patients with perioperative SARS-CoV-2 infection and are associated with high mortality. Thresholds for surgery during the COVID-19 pandemic should be higher than during normal practice, particularly in men aged 70 years and older. Consideration should be given for postponing non-urgent procedures and promoting non-operative treatment to delay or avoid the need for surgery. Funding: National Institute for Health Research (NIHR), Association of Coloproctology of Great Britain and Ireland, Bowel and Cancer Research, Bowel Disease Research Foundation, Association of Upper Gastrointestinal Surgeons, British Association of Surgical Oncology, British Gynaecological Cancer Society, European Society of Coloproctology, NIHR Academy, Sarcoma UK, Vascular Society for Great Britain and Ireland, and Yorkshire Cancer Research