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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 -
Surgical Infections May 2024species account for approximately 15% of hospital-associated infections, causing fatal consequences, especially in critically ill patients. This study aimed to...
species account for approximately 15% of hospital-associated infections, causing fatal consequences, especially in critically ill patients. This study aimed to evaluate invasive candidiasis (IC) risk factors in critically ill patients undergoing surgery. We retrospectively reviewed the medical records of 583 patients who underwent emergency surgery for complicated intra-abdominal infections between January 2016 and December 2021. Patients were divided into two groups according to the presence or absence of IC during their hospital stay. IC was defined as culture-proven candidemia and intra-abdominal candidiasis. This study included 373 patients for the final analysis, of whom 320 were discharged without IC (IC absent group) and 53 presented with IC (IC present group) during their hospital stay. The IC present group showed a higher in-hospital mortality rate (35.8 vs. 8.8%; p < 0.001), with 66.0% of the patients diagnosed within 10 days, whereas only 6.5% were diagnosed beyond 20 days after admission. Stomach (odds ratio [OR], 4.188; 95% confidence interval [CI], 1.204-14.561; p = 0.024) and duodenum (OR, 7.595; 95% CI, 1.934-29.832; p = 0.004) as infection origin, higher Acute Physiology and Chronic Health Evaluation II (APACHE II) score (OR, 1.097; 95% CI, 1.044-1.152; p < 0.001), and lower initial systolic blood pressure (OR, 0.983; 95% CI, 0.968-0.997; p = 0.018) were risk factors of IC after emergency gastrointestinal surgery. Patients who had stomach and duodenum as infection origin, higher APACHE II scores, and lower initial systolic blood pressure had a higher risk of developing IC during their hospital stay after emergency gastrointestinal surgery. Prophylactic antifungal agents can be carefully considered for critically ill patients with these features.
Topics: Humans; Male; Female; Risk Factors; Retrospective Studies; Middle Aged; Candidiasis, Invasive; Intraabdominal Infections; Critical Illness; Aged; Digestive System Surgical Procedures; Adult; Hospital Mortality; Aged, 80 and over
PubMed: 38634791
DOI: 10.1089/sur.2023.333 -
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 -
Surgery For Obesity and Related... Mar 2024Limited evidence exists on the patterns of medication use for hypertension, diabetes mellitus (DM), and dyslipidemia after bariatric surgery among Asian patients.
Discontinuation of blood pressure-lowering, glucose-lowering, and lipid-lowering medications after bariatric surgery in patients with morbid obesity: a nationwide cohort study in South Korea.
BACKGROUND
Limited evidence exists on the patterns of medication use for hypertension, diabetes mellitus (DM), and dyslipidemia after bariatric surgery among Asian patients.
OBJECTIVES
To investigate the patterns in the use of blood pressure-lowering, glucose-lowering, and lipid-lowering medications following BS in Korean patients with morbid obesity.
SETTING
This study is a retrospective cohort study using the Health Insurance Review and Assignment claims database of South Korea (from 2019 to 2021).
METHODS
We included patients who underwent BS between 2019 and 2020 in South Korea. We evaluated the treatment patterns of blood pressure-lowering, glucose-lowering, and lipid-lowering medications at 3-month intervals for 1-year following BS, including medication use, individual medication classes, and the number of medications prescribed. Furthermore, we estimated remission rates for each disorder based on patient characteristics by defining patients who discontinued their medications for at least 2 consecutive quarters as remission.
RESULTS
A total of 3810 patients were included in this study. For 1-year following BS, a marked decrease in the number of patients using blood pressure-lowering, glucose-lowering, and lipid-lowering medications was observed. The most remarkable decrease occurred in glucose-lowering medications, which decreased by approximately -75.1% compared with that at baseline. This tendency was consistently observed when analyzing both the number of medications prescribed and the specific medication classes. Regarding remission rates, patients who were female, younger, and received the biliopancreatic diversion-duodenal switch as their BS showed a relatively higher incidence of remission than other groups.
CONCLUSIONS
BS was associated with a decrease in the use of medications for hypertension, diabetes mellitus (DM), and dyslipidemia.
PubMed: 38631926
DOI: 10.1016/j.soard.2024.03.008 -
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