-
Cureus Feb 2024A patient status post (s/p) renal transplantation in 2014 presented with an upper gastrointestinal bleed (UGIB). The source of the bleed was found to be a large mass in...
A patient status post (s/p) renal transplantation in 2014 presented with an upper gastrointestinal bleed (UGIB). The source of the bleed was found to be a large mass in the duodenum with histopathology from biopsies obtained during esophagogastroduodenoscopy revealing diffuse large B-cell lymphoma (DLBCL) of the duodenum. His mycophenolate was stopped, and the tacrolimus dose was reduced due to active malignancy. He was discharged and completed one cycle of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) before presenting back to ED with hemorrhagic shock from a large upper GI bleed requiring admission to the medical intensive care unit. Post-transplant lymphoproliferative disorders such as DBLCL can present 10 years from the transplant date. These malignancies are at high risk for bleed, especially after treatment with chemotherapy is initiated.
PubMed: 38516468
DOI: 10.7759/cureus.54555 -
World Journal of Gastroenterology Feb 2024In this editorial we comment on the article published "Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by...
In this editorial we comment on the article published "Clinical significance of programmed cell death-ligand expression in small bowel adenocarcinoma is determined by the tumor microenvironment". Small bowel adenocarcinoma (SBA) is a rare gastrointestinal neoplasm and despite the small intestine's significant surface area, SBA accounts for less than 3% of such tumors. Early detection is challenging and the reason arises from its asymptomatic nature, often leading to late-stage discovery and poor prognosis. Treatment involves platinum-based chemotherapy with a 5-fluorouracil combination, but the lack of effective chemotherapy contributes to a generally poor prognosis. SBAs are linked to genetic disorders and risk factors, including chronic inflammatory conditions. The unique characteristics of the small bowel, such as rapid cell renewal and an active immune system, contributes to the rarity of these tumors as well as the high intratumoral infiltration of immune cells is associated with a favorable prognosis. Programmed cell death-ligand 1 (PD-L1) expression varies across different cancers, with potential discrepancies in its prognostic value. Microsatellite instability (MSI) in SBA is associated with a high tumor mutational burden, affecting the prognosis and response to immunotherapy. The presence of PD-L1 and programmed cell death 1, along with tumor-infiltrating lymphocytes, plays a crucial role in the complex microenvironment of SBA and contributes to a more favorable prognosis, especially in the context of high MSI tumors. Stromal tumor-infiltrating lymphocytes are identified as independent prognostic indicators and the association between MSI status and a favorable prognosis, emphasizes the importance of evaluating the immune status of tumors for treatment decisions.
Topics: Humans; Tumor Microenvironment; B7-H1 Antigen; Ligands; Prognosis; Lymphocytes, Tumor-Infiltrating; Adenocarcinoma; Intestine, Small; Duodenal Neoplasms
PubMed: 38516246
DOI: 10.3748/wjg.v30.i8.794 -
Obesity Surgery May 2024Duodenal-jejunal bypass (DJB) is an experimental procedure in metabolic surgery that does not have a restrictive component. Changes in bile acid (BA) dynamics and...
INTRODUCTION
Duodenal-jejunal bypass (DJB) is an experimental procedure in metabolic surgery that does not have a restrictive component. Changes in bile acid (BA) dynamics and intestinal microbiota are possibly related to metabolic improvement after DJB. Our previous studies involving obese diabetic rats showed the crucial role of the biliopancreatic limb (BPL) in metabolic improvement after DJB caused by BA reabsorption. We established a new DJB procedure to prevent bile from flowing into the BPL and aimed to elucidate the importance of bile in the BPL after DJB.
METHODS
Otsuka Long-Evans Tokushima Fatty rats with diabetes were divided into three groups: two DJB groups and a sham group (n = 11). Duodenal-jejunal anastomosis was performed proximal to the papilla of Vater in the DJB group (n = 11). However, the DJB-D group (n = 11) underwent a new procedure with duodenal-jejunal anastomosis distal to the papilla of Vater for preventing bile flow into the BPL.
RESULTS
Glucose metabolism improved and weight gain was suppressed in the DJB group, but not in the DJB-D and sham groups. Serum BA level and conjugated BA concentration were elevated in the DJB group. The gut microbiota was altered only in the DJB group; the abundance of Firmicutes and Bacteroidetes decreased and that of Actinobacteria increased. However, the DJB-D group exhibited no apparent change in the gut microbiota, similar to the sham group.
CONCLUSION
BAs are essential in the BPL for metabolic improvement after DJB; they can improve the gut microbiota in these processes.
Topics: Rats; Animals; Bile; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Obesity, Morbid; Jejunum; Duodenum; Bile Acids and Salts; Blood Glucose; Gastric Bypass
PubMed: 38512643
DOI: 10.1007/s11695-024-07176-7 -
Frontiers in Veterinary Science 2024Bioactive plants such as , , and might improve intestinal health as an alternative to antibiotic growth promoters. The objective of this study was to determine the...
Bioactive plants such as , , and might improve intestinal health as an alternative to antibiotic growth promoters. The objective of this study was to determine the effect of the ethanolic extracts (EEs) of these plants on the intestinal health of broiler chickens. Cobb 500 chickens ( = 352) were distributed into eight treatments with four replicates and 11 chickens each. T1 received a base diet, and T2 received a base diet with 0.005% zinc bacitracin. T3, T5, and T7 were supplemented with 0.005% of , , and EE in the diet while T4, T6, and T8 with 0.01% of the extract. The EEs were supplemented with drinking water from 1 to 26 days of age. The following parameters were evaluated: hematological profiles at 28 days of age, blood metabolites profiles at 14, 21, and 28 days; , , and sp. abundance in the ileum mucosa and content at 21 and 28 days, and histomorphometry of the duodenum, jejunum, and ileum mucosa at 14, 21, and 28 d. Final weight (FW), weight gain (WG), feed intake (FI), and feed conversion rate (FCR) were evaluated at seven, 21, and 33 days of age. and EE at 0.01% increased blood glucose levels at 21 and 28 days of age, respectively, and and EE at 0.01% increased triglycerides at 28 days of age; in addition, this EE did not have any effect on the AST and ALT profiles. The depths of the Lieberkühn crypts and the villi length to the crypt's depth ratio increased with age on supplementation with 0.01% and EE at 21 days of age ( < 0.05). In addition, the depth of the crypts increased at 28 days of age ( < 0.05) in chickens supplemented with 0.01% EE. The 0.01% EE in diet decreased in the population in the ileal microbiota ( < 0.05). The FW and WG during the fattening and in the three stages overall increased, and the FCR decreased; however, the FI and the carcass yield did not change in the broiler chickens supplemented with 0.01% EE ( < 0.05). Conclusively, the EE at 0.01% of the diet improved intestinal health and thus the performance indices of the broiler chickens and did not have a detrimental effect on any of the parameters evaluated, so it is postulated as a potential alternative to AGP in poultry.
PubMed: 38511194
DOI: 10.3389/fvets.2024.1286152 -
Diabetologia Jul 2024Protein kinase CK2 acts as a negative regulator of insulin expression in pancreatic beta cells. This action is mainly mediated by phosphorylation of the transcription...
AIMS/HYPOTHESIS
Protein kinase CK2 acts as a negative regulator of insulin expression in pancreatic beta cells. This action is mainly mediated by phosphorylation of the transcription factor pancreatic and duodenal homeobox protein 1 (PDX1). In pancreatic alpha cells, PDX1 acts in a reciprocal fashion on glucagon (GCG) expression. Therefore, we hypothesised that CK2 might positively regulate GCG expression in pancreatic alpha cells.
METHODS
We suppressed CK2 kinase activity in αTC1 cells by two pharmacological inhibitors and by the CRISPR/Cas9 technique. Subsequently, we analysed GCG expression and secretion by real-time quantitative RT-PCR, western blot, luciferase assay, ELISA and DNA pull-down assays. We additionally studied paracrine effects on GCG secretion in pseudoislets, isolated murine islets and human islets. In vivo, we examined the effect of CK2 inhibition on blood glucose levels by systemic and alpha cell-specific CK2 inhibition.
RESULTS
We found that CK2 downregulation reduces GCG secretion in the murine alpha cell line αTC1 (e.g. from 1094±124 ng/l to 459±110 ng/l) by the use of the CK2-inhibitor SGC-CK2-1. This was due to a marked decrease in Gcg gene expression through alteration of the binding of paired box protein 6 (PAX6) and transcription factor MafB to the Gcg promoter. The analysis of the underlying mechanisms revealed that both transcription factors are displaced by PDX1. Ex vivo experiments in isolated murine islets and pseudoislets further demonstrated that CK2-mediated reduction in GCG secretion was only slightly affected by the higher insulin secretion after CK2 inhibition. The kidney capsule transplantation model showed the significance of CK2 for GCG expression and secretion in vivo. Finally, CK2 downregulation also reduced the GCG secretion in islets isolated from humans.
CONCLUSIONS/INTERPRETATION
These novel findings not only indicate an important function of protein kinase CK2 for proper GCG expression but also demonstrate that CK2 may be a promising target for the development of novel glucose-lowering drugs.
Topics: Casein Kinase II; Animals; Glucagon; Mice; Humans; Glucagon-Secreting Cells; Homeodomain Proteins; Trans-Activators; Male; Cell Line; Insulin
PubMed: 38503901
DOI: 10.1007/s00125-024-06128-1 -
Scientific Reports Mar 2024To evaluate the efficacy and nutrition of single-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) in Chinese obese patients in the first postoperative...
To evaluate the efficacy and nutrition of single-anastomosis duodenal-ileal bypass with sleeve gastrectomy (SADI-S) in Chinese obese patients in the first postoperative year. Clinical data of 66 obese patients who underwent SADI-S surgery at China-Japan Union Hospital of Jilin University from November 2018 to May 2022 were retrospectively collected. The weight, body mass index (BMI), percentage of excess weight loss (%EWL), and percentage of total weight loss (%TWL) were recorded at 3, 6, and 12 months after surgery. Moreover, metabolic disease remission and nutrient deficiencies were assessed at 1 year postoperatively. Overall, 66 patients (38 males and 28 females) were recruited, with a mean age of 35 (18-61) years and an average preoperative BMI of 42.94 kg/m. Before surgery, 38 patients had type 2 diabetes mellitus (T2DM), 46 patients had hyperuricemia (HUA), 45 patients had hypertension (HTN), 35 patients had hyperlipidemia, 12 patients had hypercholesterolemia, 12 patients had hyper-low-density lipoproteinemia, and 14 patients had gastroesophageal reflux disease symptoms (GERD). All patients had undergone a DaVinci robotic or laparoscopic SADI-S surgery, and none converted to laparotomy or died. Four patients developed postoperative complications and were cured and discharged after conservative treatment or surgical treatment. At 3, 6 and 12 months, the average %EWL was 62.07 ± 26.56, 85.93 ± 27.92, and 106.65 ± 29.65%, %TWL was 22.67 ± 4.94, 32.10 ± 5.18, and 40.56 ± 7.89%, respectively. Fasting blood glucose (FBG), glycated hemoglobin (HbA1c), uric acid (UA), triglycerides (TG), blood pressure (BP), and other indexes were significantly lower after one year post-surgery compared with the preoperative period (P < 0.05). The remission rates of T2DM, HUA, HTN, hypertriglyceridemia, hypercholesterolemia, and hyper-low-density lipoproteinemia 1 year after surgery were 100, 65.2, 62.2, 94.3, 100, and100%, respectively. One year after surgery, the remission rate of GERD was 71.4% (10/14), the rate of new occurrence of GERD was 12.1% (8/66), and the overall incidence rate was 18.2% (12/66). Except for vitamin B12(vit B12), the other nutrient indexes were significantly decreased after 1 year of surgery relative to levels before surgery (P < 0.05). The deficiency rates for vitamin A (vit A), vitamin E (vit E), zinc ion (Zn), and folic acid (FA) were higher (45.5, 25.8, 24.2, and 16.7%, respectively); however, there were no related clinical symptoms. SADI-S had significant effects on weight loss and metabolic disease remission. The main nutrient deficiencies after SADI-S were vit A, vit E, Zn, and FA deficiencies. The long-term efficacy and safety of SADI-S warrant further follow-up.
Topics: Male; Female; Humans; Adult; Obesity, Morbid; Diabetes Mellitus, Type 2; Retrospective Studies; Hypercholesterolemia; Ileum; Obesity; Anastomosis, Surgical; Gastrectomy; Hypertension; Weight Loss; Gastroesophageal Reflux; Gastric Bypass; Treatment Outcome
PubMed: 38499796
DOI: 10.1038/s41598-024-57289-3 -
Gut Jun 2024Ultra-short coeliac disease (USCD) is defined as villous atrophy only present in the duodenal bulb (D1) with concurrent positive coeliac serology. We present the first,...
BACKGROUND
Ultra-short coeliac disease (USCD) is defined as villous atrophy only present in the duodenal bulb (D1) with concurrent positive coeliac serology. We present the first, multicentre, international study of patients with USCD.
METHODS
Patients with USCD were identified from 10 tertiary hospitals (6 from Europe, 2 from Asia, 1 from North America and 1 from Australasia) and compared with age-matched and sex-matched patients with conventional coeliac disease.
FINDINGS
Patients with USCD (n=137, median age 27 years, IQR 21-43 years; 73% female) were younger than those with conventional coeliac disease (27 vs 38 years, respectively, p<0.001). Immunoglobulin A-tissue transglutaminase (IgA-tTG) titres at index gastroscopy were lower in patients with USCD versus conventional coeliac disease (1.8×upper limit of normal (ULN) (IQR 1.1-5.9) vs 12.6×ULN (IQR 3.3-18.3), p<0.001).Patients with USCD had the same number of symptoms overall (median 3 (IQR 2-4) vs 3 (IQR 1-4), p=0.875). Patients with USCD experienced less iron deficiency (41.8% vs 22.4%, p=0.006).Both USCD and conventional coeliac disease had the same intraepithelial lymphocytes immunophenotype staining pattern; positive for CD3 and CD8, but not CD4.At follow-up having commenced a gluten-free diet (GFD) (median of 1181 days IQR: 440-2160 days) both USCD and the age-matched and sex-matched controls experienced a similar reduction in IgA-tTG titres (0.5 ULN (IQR 0.2-1.4) vs 0.7 ULN (IQR 0.2-2.6), p=0.312). 95.7% of patients with USCD reported a clinical improvement in their symptoms.
INTERPRETATION
Patients with USCD are younger, have a similar symptomatic burden and benefit from a GFD. This study endorses the recommendation of D1 sampling as part of the endoscopic coeliac disease diagnostic workup.
Topics: Humans; Celiac Disease; Female; Male; Adult; Case-Control Studies; Duodenum; Young Adult; Transglutaminases; Immunoglobulin A; GTP-Binding Proteins; Atrophy; Diet, Gluten-Free; Intestinal Mucosa; Protein Glutamine gamma Glutamyltransferase 2; Gastroscopy; Middle Aged
PubMed: 38499339
DOI: 10.1136/gutjnl-2023-330913 -
Cureus Feb 2024Small bowel malignancies are relatively rare, accounting for only 3% of all gastrointestinal cancers. Duodenum is the most common location among small bowel cancers,...
Small bowel malignancies are relatively rare, accounting for only 3% of all gastrointestinal cancers. Duodenum is the most common location among small bowel cancers, followed by Jejunum and then Ileum. Duodenal adenocarcinoma produces vague symptoms, leading to late presentation and a poor prognosis compared to similarly staged colon cancer. It is rare to have brain metastasis in duodenal adenocarcinoma, and not many case reports have been reported. Only approximately 6% of patients with gastrointestinal malignancy have brain metastasis. Here, we present a case of a 64-year-old female patient diagnosed initially with stage IV duodenal adenocarcinoma presenting with duodenal mass, abdominal lymphadenopathy, and liver metastasis. She had excellent systemic control for over two years with systemic chemotherapy, with a close to complete response on follow-up imaging. She presented with a 2 cm left frontal mass biopsy consistent with duodenal adenocarcinoma metastasis. She underwent resection of the left frontal tumor and gamma knife to the resection cavity. She continues to have good systemic control of disease. This case highlights the rare possibility of brain metastasis with duodenal adenocarcinoma, especially in patients who have good systemic control with chemotherapy.
PubMed: 38496115
DOI: 10.7759/cureus.54202 -
International Journal of Veterinary... 2024Stress in poultry production is energy-demanding. Nucleotides and yeast cell-wall products are essential nutrients for broiler performance, gut function, and immune...
Impact of dietary-nucleotides and Saccharomyces cerevisiae-derivatives on growth-performance, antioxidant-capacity, immune-response, small-intestine histomorphometry, caecal-, and litter-hygiene of broiler-chickens treated with florfenicol.
Stress in poultry production is energy-demanding. Nucleotides and yeast cell-wall products are essential nutrients for broiler performance, gut function, and immune response. Antibiotics, like florfenicol, negatively affect the immune system. A total of 600 one-d-old broiler chickens (Cobb-500) were weighed and randomly allotted into four groups with three replicates each. The control group (G1) received the basal diet, G2 received a diet supplemented with a combination of nucleotides and derivatives (250 g/Ton), G3 received the basal diet and medicated with florfenicol (25 mg/Kg body weight) in drinking water for 5 days, while G4 received a combination of nucleotides and -derivatives (250 g/Ton) and medicated with florfenicol in drinking water. Growth performance criteria were recorded weekly. Blood, intestinal contents, small-intestine sections, and litter samples were collected to measure birds' performance, carcass yields, leukocytic counts, antioxidant capacity, antibody titres, phagocytic index, caecal , intestinal histomorphometry, and litter hygiene. Nucleotide-supplemented groups (G2 and G4) revealed significant ( ≤ 0.05) improvements in feed conversion, and body weight, but not for carcass yields in comparison to the control. Dietary nucleotides in G2 elevated blood total proteins, leucocytic count, antioxidant capacity, and phagocytic index, while they lowered blood lipids and litter moisture and nitrogen ( ≤ 0.05). Dietary nucleotides in G4 ameliorated the immunosuppressive effect of florfenicol ( ≤ 0.05) indicated in reducing caecal , improving duodenal and ileal villi length, and increasing blood albumin and globulin levels, and phagocytosis%. Supplementing diets with nucleotides and yeast products has improved the immune system and provided a healthier gut for broilers.
PubMed: 38487499
DOI: 10.1080/23144599.2024.2324411 -
Neurobiology of Disease May 2024A dysfunctional gut microbiota-brain axis is emerging as a potential pathogenic mechanism in epilepsy, particularly in pediatric forms of epilepsy. To add new insights...
A dysfunctional gut microbiota-brain axis is emerging as a potential pathogenic mechanism in epilepsy, particularly in pediatric forms of epilepsy. To add new insights into gut-related changes in acquired epilepsy that develops early in life, we used a multi-omics approach in a rat model with a 56% incidence of epilepsy. The presence of spontaneous seizures was assessed in adult rats (n = 46) 5 months after status epilepticus induced by intra-amygdala kainate at postnatal day 13, by 2 weeks (24/7) ECoG monitoring. Twenty-six rats developed epilepsy (Epi) while the remaining 20 rats (No-Epi) did not show spontaneous seizures. At the end of ECoG monitoring, all rats and their sham controls (n = 20) were sacrificed for quantitative histopathological and immunohistochemical analyses of the gut structure, glia and macrophages, as well as RTqPCR analysis of inflammation/oxidative stress markers. By comparing Epi, No-Epi rats, and sham controls, we found structural, cellular, and molecular alterations reflecting a dysfunctional gut, which were specifically associated with epilepsy. In particular, the villus height-to-crypt depth ratio and number of Goblet cells were reduced in the duodenum of Epi rats vs both No-Epi rats and sham controls (p < 0.01). Villus height and crypt depth in the duodenum and jejunum (p < 0.01) were increased in No-Epi vs both Epi and sham controls. We also detected enhanced Iba1-positive macrophages, together with increased IL1b and NFE2L2 transcripts and TNF protein, in the small intestine of Epi vs both No-Epi and sham control rats (p < 0.01), denoting the presence of inflammation and oxidative stress. Astroglial GFAP-immunostaining was similar in all experimental groups. Metagenomic analysis in the feces collected 5 months after status epilepticus showed that the ratio of two dominant phyla (Bacteroidota-to-Firmicutes) was similarly increased in Epi and No-Epi rats vs sham control rats. Notably, the relative abundance of families, genera, and species associated with SCFA production differed in Epi vs No-Epi rats, describing a bacterial imprint associated with epilepsy. Furthermore, Epi rats showed a blood metabolic signature characterized by changes in lipid metabolism compared to both No-Epi and sham control rats. Our study provides new evidence of long-term gut alterations, along with microbiota-related metabolic changes, occurring specifically in rats that develop epilepsy after brain injury early in life.
Topics: Humans; Child; Rats; Animals; Gastrointestinal Microbiome; Epilepsy; Status Epilepticus; Seizures; Inflammation
PubMed: 38485093
DOI: 10.1016/j.nbd.2024.106469