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Case Reports in Gastroenterology 2024Whipple's disease is a rare condition that can present with atypical and non-specific features requiring a high index of suspicion for diagnosis.
INTRODUCTION
Whipple's disease is a rare condition that can present with atypical and non-specific features requiring a high index of suspicion for diagnosis.
CASE PRESENTATION
We present a case of a man in his 40s with peripheral arthritis and bilateral sacro-ileitis for 4-5 years that was treated with an anti-tumour necrosis factor therapy, which led to worsening of his symptoms, elevation of the inflammatory markers, and the development of fever, night sweats, anorexia, and a significant weight loss. The patient had no abdominal pain, diarrhoea, or other gastrointestinal symptoms. An FDG-PET scan showed increased uptake in the stomach and caecum. Endoscopic examination showed inflammatory changes in the stomach and normal mucosa of the duodenum, jejunum, terminal ileum, caecum, and colon. Histopathology was inconclusive, but the diagnosis was confirmed with PCR testing. He had no neurological symptoms, but cerebrospinal fluid PCR was positive. He was treated with intravenous ceftriaxone 2 g daily for 4 weeks, followed by trimethoprim/sulfamethoxazole 160/800 mg twice daily for 1 year with close monitoring and follow-up.
CONCLUSION
This case presents an atypical and challenging presentation of Whipple's disease and the importance of proactive testing for neurological involvement.
PubMed: 38645407
DOI: 10.1159/000538462 -
Frontiers in Pharmacology 2024Tacrolimus is metabolized in the liver with the participation of the CYP3A4 and CYP3A5 enzymes. Proton pump inhibitors are used in kidney transplant patients to prevent...
Tacrolimus is metabolized in the liver with the participation of the CYP3A4 and CYP3A5 enzymes. Proton pump inhibitors are used in kidney transplant patients to prevent duodenal and gastric ulcer disease due to glucocorticoids. Omeprazole, unlike famotidine, is a substrate and inhibitor of the enzymes CYP2C19, CYP3A4, CYP3A5. The aim of this study was to compare the impact of omeprazole and famotidine on the pharmacokinetics of tacrolimus. A randomized, non-blinded study involving 22 stabilized adult kidney transplant patients was conducted. Patients received the standard triple immunosuppression regimen and omeprazole 20 mg (n = 10) or famotidine 20 mg (n = 12). The study material consisted of blood samples in which tacrolimus concentrations were determined using the Chemiluminescent Microparticle Immuno Assay method. A single administration of omeprazole increased tacrolimus concentrations at 2 h (day 2) = 11.90 ± 1.59 ng/mL vs. 2 h (day 1 - no omeprazole administration) = 9.40 ± 0.79 ng/mL ( = 0.0443). AUC amounted to 63.07 ± 19.46 ng × h/mL (day 2) vs. 54.23 ± 10.48 ng × h/mL (day 1), ( = 0.0295). AUC amounted to 44.32 ± 11.51 ng × h/mL (day 2) vs. 38.68 ± 7.70 ng × h/mL (day 1), ( = 0.0130). Conversely, no significant changes in values of pharmacokinetic parameters were observed for famotidine. Omeprazole significantly increases blood exposure of tacrolimus. The administration of famotidine instead of omeprazole seems safer for patients following kidney transplantation. clinicaltrials.gov, identifier NCT05061303.
PubMed: 38638867
DOI: 10.3389/fphar.2024.1352323 -
Cureus Mar 2024Peptic ulcer disease (PUD) is a surgical emergency that affects the mucosal lining of the stomach or proximal intestine. Complications of PUD include upper...
Peptic ulcer disease (PUD) is a surgical emergency that affects the mucosal lining of the stomach or proximal intestine. Complications of PUD include upper gastrointestinal hemorrhage, perforation, and obstruction. The primary management approach for perforated peptic ulcers is surgery, but conservative management can be conducted in selected cases. A 54-year-old female was referred to the surgical unit with a history of severe upper abdominal pain and repeated vomiting. No other symptoms were reported and there was no significant medical or family history except the history of non-steroidal anti-inflammatory drugs. Examination revealed that the patient had a medical condition. was vitally stable with tenderness in the upper abdomen, in particular the epigastric and right hypochondrial, but no signs of generalized peritonitis. Her white cell count was elevated at 24,000x10^3/UL, and a C-reactive protein of 45.5 mg/dL. An upright CXR revealed the classic gas under the diaphragm. Abdominal CT with oral gastrograffin identified the diagnosis of perforated duodenal ulcer without ulcer leak. The case was treated by conservative management started with resuscitation, nil per os, IV fluid, IV antibiotics, and close observation and the patient was stable with no complications and completed the nonoperative management successfully till discharge after 10 days of hospital stay. The case illustrates that although this condition is uncommon to be treated without surgical intervention, there are some factors and criteria for successful NOM. Peptic ulcer perforation is a life-threatening surgical emergency. Surgery is the standard treatment for PPU and NOM can be conducted safely and successfully in highly selected cases. the surgeon should keep a wide safety window while providing nonstandard management with readiness to operate at any time. We believe that the main factor in successful nonsurgical management of our case is being fasted for a long time before perforation.
PubMed: 38638727
DOI: 10.7759/cureus.56491 -
Clinical Case Reports Apr 2024Duodenal GISTs are rare and challenging tumors. Acute life-threatening upper GI bleeding is a possible presentation of duodenal GISTs. Surgery is the standard treatment...
KEY CLINICAL MESSAGE
Duodenal GISTs are rare and challenging tumors. Acute life-threatening upper GI bleeding is a possible presentation of duodenal GISTs. Surgery is the standard treatment for localized duodenal GISTs. Imatinib is an effective adjuvant therapy for duodenal GISTs.
ABSTRACT
GIST is the most common mesenchymal neoplasm of the gastrointestinal tract, accounting for 1%-2% of gastrointestinal tumors. They originate from the interstitial cells of Cajal and are rare in patients younger than 30 years. The stomach is the most common site, followed by the small intestine and colon. GISTs are caused by a gain-of-function mutation in the proto-oncogene receptor tyrosine kinase, with activating mutations in KIT being the most common. Most GISTs are asymptomatic. Even if gastrointestinal bleeding is the most common complication life-threatening hemorrhage is extremely uncommon. We present a case of a 31-year-old male patient presented with massive active hematemesis and melena with hemorrhagic shock. The patient presented with massive hematemesis and melena of 1 h duration. Endoscopy showed pulsating active bleeding from the third part of the duodenum which was difficult to manage via endoscopy. Histopathologic evaluation showed spindle cell type GIST. Intraoperatively, there was a nodular mass with active bleeding on the third part of the duodenum. Duodenectomy with end-to-end anastomosis was done. Discharged with no postoperative complication and was put on imatinib. There are considerable challenges that arise in the diagnosis and treatment of duodenal gastrointestinal stromal tumors (GISTs) when they present with life-threatening upper gastrointestinal hemorrhage. In order to achieve the best possible outcomes for patients, it is crucial to have a comprehensive understanding of the clinical presentation, diagnostic methods, and treatment approaches.
PubMed: 38634092
DOI: 10.1002/ccr3.8796 -
Cureus Mar 2024Due to the advances in endoscopic technology, surgery for duodenal ulcer (DU) bleeding has decreased, although surgery is still necessary for more complicated cases. The...
Due to the advances in endoscopic technology, surgery for duodenal ulcer (DU) bleeding has decreased, although surgery is still necessary for more complicated cases. The concept of damage control surgery (DCS) has been established in the field of trauma, and a simple surgical approach may be preferable in serious cases such as uncontrolled DU bleeding. We present a successful case of bleeding with massive hematoma and perforation of the duodenum due to an over-the-scope clip that was treated by a less invasive surgical approach with consideration of the DCS.
PubMed: 38633969
DOI: 10.7759/cureus.56359 -
Redox Biology Jun 2024Iron overload can lead to oxidative stress and intestinal damage and happens frequently during blood transfusions and iron supplementation. However, how iron overload...
Differentiation of intestinal stem cells toward goblet cells under systemic iron overload stress are associated with inhibition of Notch signaling pathway and ferroptosis.
Iron overload can lead to oxidative stress and intestinal damage and happens frequently during blood transfusions and iron supplementation. However, how iron overload influences intestinal mucosa remains unknown. Here, the aim of current study was to investigate the effects of iron overload on the proliferation and differentiation of intestinal stem cells (ISCs). An iron overload mouse model was established by intraperitoneal injection of 120 mg/kg body weight iron dextran once a fortnight for a duration of 12 weeks, and an iron overload enteroid model was produced by treatment with 3 mM or 10 mM of ferric ammonium citrate for 24 h. We found that iron overload caused damage to intestinal morphology with a 64 % reduction in villus height/crypt depth ratio, and microvilli injury in the duodenum. Iron overload mediated epithelial function by inhibiting the expression of nutrient transporters and enhancing the expression of secretory factors in the duodenum. Meanwhile, iron overload inhibited the proliferation of ISCs and regulated their differentiation into secretory mature cells, such as goblet cells, through inhibiting Notch signaling pathway both in mice and enteroid. Furthermore, iron overload caused oxidative stress and ferroptosis in intestinal epithelial cells. In addition, ferroptosis could also inhibit Notch signaling pathway, and affected the proliferation and differentiation of ISCs. These findings reveal the regulatory role of iron overload on the proliferation and differentiation of ISCs, providing a new insight into the internal mechanism of iron overload affecting intestinal health, and offering important theoretical basis for the scientific application of iron nutrition regulation.
Topics: Animals; Ferroptosis; Mice; Goblet Cells; Iron Overload; Signal Transduction; Stem Cells; Cell Differentiation; Receptors, Notch; Oxidative Stress; Intestinal Mucosa; Cell Proliferation; Disease Models, Animal; Male
PubMed: 38631120
DOI: 10.1016/j.redox.2024.103160 -
Trials Apr 2024Liver disease is within the top five causes of premature death in adults. Deaths caused by complications of cirrhosis continue to rise, whilst deaths related to other...
BACKGROUND
Liver disease is within the top five causes of premature death in adults. Deaths caused by complications of cirrhosis continue to rise, whilst deaths related to other non-liver disease areas are declining. Portal hypertension is the primary sequelae of cirrhosis and is associated with the development of variceal haemorrhage, ascites, hepatic encephalopathy and infection, collectively termed hepatic decompensation, which leads to hospitalisation and mortality. It remains uncertain whether administering a non-selective beta-blocker (NSBB), specifically carvedilol, at an earlier stage, i.e. when oesophageal varices are small, can prevent VH and reduce all-cause decompensation (ACD).
METHODS/DESIGN
The BOPPP trial is a pragmatic, multicentre, placebo-controlled, triple-blinded, randomised controlled trial (RCT) in England, Scotland, Wales and Northern Ireland. Patients aged 18 years or older with cirrhosis and small oesophageal varices that have never bled will be recruited, subject to exclusion criteria. The trial aims to enrol 740 patients across 55 hospitals in the UK. Patients are allocated randomly on a 1:1 ratio to receive either carvedilol 6.25 mg (a NSBB) or a matched placebo, once or twice daily, for 36 months, to attain adequate power to determine the effectiveness of carvedilol in preventing or reducing ACD. The primary outcome is the time to first decompensating event. It is a composite primary outcome made up of variceal haemorrhage (VH, new or worsening ascites, new or worsening hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP), hepatorenal syndrome, an increase in Child-Pugh grade by 1 grade or MELD score by 5 points, and liver-related mortality. Secondary outcomes include progression to medium or large oesophageal varices, development of gastric, duodenal, or ectopic varices, participant quality of life, healthcare costs and transplant-free survival.
DISCUSSION
The BOPPP trial aims to investigate the clinical and cost-effectiveness of carvedilol in patients with cirrhosis and small oesophageal varices to determine whether this non-selective beta-blocker can prevent or reduce hepatic decompensation. There is clinical equipoise on whether intervening in cirrhosis, at an earlier stage of portal hypertension, with NSBB therapy is beneficial. Should the trial yield a positive result, we anticipate that the administration and use of carvedilol will become widespread with pathways developed to standardise the administration of the medication in primary care.
ETHICS AND DISSEMINATION
The trial has been approved by the National Health Service (NHS) Research Ethics Committee (REC) (reference number: 19/YH/0015). The results of the trial will be submitted for publication in a peer-reviewed scientific journal. Participants will be informed of the results via the BOPPP website ( www.boppp-trial.org ) and partners in the British Liver Trust (BLT) organisation.
TRIAL REGISTRATION
EUDRACT reference number: 2018-002509-78. ISRCTN reference number: ISRCTN10324656. Registered on April 24 2019.
Topics: Adult; Humans; Adrenergic beta-Antagonists; Ascites; Carvedilol; Esophageal and Gastric Varices; Gastrointestinal Hemorrhage; Hepatic Encephalopathy; Hypertension, Portal; Liver Cirrhosis; Multicenter Studies as Topic; Randomized Controlled Trials as Topic; Pragmatic Clinical Trials as Topic
PubMed: 38627804
DOI: 10.1186/s13063-024-08063-3 -
PloS One 2024Gestational diabetes mellitus (GDM) in human patients disrupts glucose metabolism post-pregnancy, affecting fetal development. Although obesity and genetic factors...
Gestational diabetes mellitus (GDM) in human patients disrupts glucose metabolism post-pregnancy, affecting fetal development. Although obesity and genetic factors increase GDM risk, a lack of suitable models impedes a comprehensive understanding of its pathology. To address this, we administered streptozotocin (STZ, 75 mg/kg) to C57BL/6N mice for two days before pregnancy, establishing a convenient GDM model. Pregnant mice exposed to STZ (STZ-pregnant) were compared with STZ-injected virgin mice (STZ-virgin), citrate buffer-injected virgin mice (CB-virgin), and pregnant mice injected with citrate buffer (CB-pregnant). STZ-pregnant non-obese mice exhibited elevated blood glucose levels on gestational day 15.5 and impaired glucose tolerance. They also showed fewer normal fetuses compared to CB-pregnant mice. Additionally, STZ-pregnant mice had the highest plasma C-peptide levels, with decreased pancreatic islets or increased alpha cells compared to CB-pregnant mice. Kidneys isolated from STZ-pregnant mice did not display histological alterations or changes in gene expression for the principal glucose transporters (GLUT2 and SGLT2) and renal injury-associated markers. Notably, STZ-pregnant mice displayed decreased gene expression of insulin-receiving molecules (ISNR and IGFR1), indicating heightened insulin resistance. Liver histology in STZ-pregnant mice remained unchanged except for a pregnancy-related increase in lipid droplets within hepatocytes. Furthermore, the duodenum of STZ-pregnant mice exhibited increased gene expression of ligand-degradable IGFR2 and decreased expression of GLUT5 and GLUT12 (fructose and glucose transporters, respectively) compared to STZ-virgin mice. Thus, STZ-pregnant mice displayed GDM-like symptoms, including fetal abnormalities, while organs adapted to impaired glucose metabolism by altering glucose transport and insulin reception without histopathological changes. STZ-pregnant mice offer a novel model for studying mild onset non-obese GDM and species-specific differences in GDM features between humans and animals.
Topics: Female; Pregnancy; Mice; Humans; Animals; Diabetes, Gestational; Streptozocin; Mice, Inbred C57BL; Insulin; Diabetes Mellitus, Experimental; Obesity; Glucose; Phenotype; Citrates; Blood Glucose
PubMed: 38626157
DOI: 10.1371/journal.pone.0302041