-
Indian Journal of Gastroenterology :... Feb 2023Abdominal tuberculosis is an ancient problem with modern nuances in diagnosis and management. The two major forms are tuberculous peritonitis and gastrointestinal... (Review)
Review
Abdominal tuberculosis is an ancient problem with modern nuances in diagnosis and management. The two major forms are tuberculous peritonitis and gastrointestinal tuberculosis (GITB), while the less frequent forms are esophageal, gastroduodenal, pancreatic, hepatic, gallbladder and biliary tuberculosis. The clinicians need to discriminate the disease from the close mimics: peritoneal carcinomatosis closely mimics peritoneal tuberculosis, while Crohn's disease closely mimics intestinal tuberculosis. Imaging modalities (ultrasound, computed tomography, magnetic resonance imaging and occasionally positron emission tomography) guide the line of evaluation. Research in diagnostics (imaging and endoscopy) has helped in the better acquisition of tissue for histological and microbiological tests. Although point-of-care polymerase chain reaction-based tests (e.g. Xpert Mtb/Rif) may provide a quick diagnosis, these have low sensitivity. In such situations, ancillary investigations such as ascitic adenosine deaminase and histological clues (granulomas, caseating necrosis, ulcers lined by histiocytes) may provide some specificity to the diagnosis. A diagnostic trial of antitubercular therapy (ATT) may be considered if all diagnostic armamentaria fail to clinch the diagnosis, especially in TB-endemic regions. Objective evaluation with clear endpoints of response is mandatory in such situations. Early mucosal response (healing of ulcers at two months) and resolution of ascites are objective criteria for early response assessment and should be sought at two months. Biomarkers, especially fecal calprotectin for intestinal tuberculosis, have also shown promise. For most forms of abdominal tuberculosis, six months of ATT is sufficient. Sequelae of GITB may require endoscopic balloon dilatation for intestinal strictures or surgical intervention for recurrent intestinal obstruction, perforation or massive bleeding.
Topics: Humans; Mycobacterium tuberculosis; Ulcer; Sensitivity and Specificity; Tuberculosis, Gastrointestinal; Polymerase Chain Reaction
PubMed: 36899289
DOI: 10.1007/s12664-023-01343-x -
The Cochrane Database of Systematic... Nov 2018Cardiovascular disease (CVD) remains an important cause of mortality and morbidity, and high levels of blood cholesterol are thought to be the major modifiable risk... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Cardiovascular disease (CVD) remains an important cause of mortality and morbidity, and high levels of blood cholesterol are thought to be the major modifiable risk factors for CVD. The use of statins is the preferred treatment strategy for the prevention of CVD, but some people at high-risk for CVD are intolerant to statin therapy or unable to achieve their treatment goals with the maximal recommended doses of statin. Ezetimibe is a selective cholesterol absorption inhibitor, whether it has a positive effect on CVD events remains uncertain. Results from clinical studies are inconsistent and a thorough evaluation of its efficacy and safety for the prevention of CVD and mortality is necessary.
OBJECTIVES
To assess the efficacy and safety of ezetimibe for the prevention of CVD and all-cause mortality.
SEARCH METHODS
We searched the CENTRAL, MEDLINE, Embase and Web of Science on 27 June 2018, and two clinical trial registry platforms on 11 July 2018. We checked reference lists from primary studies and review articles for additional studies. No language restrictions were applied.
SELECTION CRITERIA
We included randomised controlled trials (RCTs) that compared ezetimibe versus placebo or ezetimibe plus other lipid-modifying drugs versus other lipid-modifying drugs alone in adults, with or without CVD, and which had a follow-up of at least 12 months.
DATA COLLECTION AND ANALYSIS
Two review authors independently selected studies for inclusion, extracted data, assessed risk of bias and contacted trialists to obtain missing data. We performed statistical analyses according to the Cochrane Handbook for Systematic Reviews of Interventions and used the GRADE to assess the quality of evidence.
MAIN RESULTS
We included 26 RCTs randomising 23,499 participants. All included studies assessed effects of ezetimibe plus other lipid-modifying drugs compared with other lipid-modifying drugs alone or plus placebo. Our findings were driven by the largest study (IMPROVE-IT), which had weights ranging from 41.5% to 98.4% in the different meta-analyses.Ezetimibe with statins probably reduces the risk of major adverse cardiovascular events compared with statins alone (risk ratio (RR) 0.94, 95% confidence interval (CI) 0.90 to 0.98; a decrease from 284/1000 to 267/1000, 95% CI 256 to 278; 21,727 participants; 10 studies; moderate-quality evidence). Trials reporting all-cause mortality used ezetimibe with statin or fenofibrate and found they have little or no effect on this outcome (RR 0.98, 95% CI 0.91 to 1.05; 21,222 participants; 8 studies; high-quality evidence). Adding ezetimibe to statins probably reduces the risk of non-fatal myocardial infarction (MI) (RR 0.88, 95% CI 0.81 to 0.95; a decrease from 105/1000 to 92/1000, 95% CI 85 to 100; 21,145 participants; 6 studies; moderate-quality evidence) and non-fatal stroke (RR 0.83, 95% CI 0.71 to 0.97; a decrease 32/1000 to 27/1000, 95% CI 23 to 31; 21,205 participants; 6 studies; moderate-quality evidence). Trials reporting cardiovascular mortality added ezetimibe to statin or fenofibrate, probably having little or no effect on this outcome (RR 1.00, 95% CI 0.89 to 1.12; 19457 participants; 6 studies; moderate-quality evidence). The need for coronary revascularisation might be reduced by adding ezetimibe to statin (RR 0.94, 95% CI 0.89 to 0.99; a decrease from 196/1000 to 184/1000, 95% 175 to 194; 21,323 participants; 7 studies); however, no difference in coronary revascularisation rate was observed when a sensitivity analysis was limited to studies with a low risk of bias.In terms of safety, adding ezetimibe to statins may make little or no difference in the risk of hepatopathy (RR 1.14, 95% CI 0.96 to 1.35; 20,687 participants; 4 studies; low-quality evidence). It is uncertain whether ezetimibe increase or decrease the risk of myopathy (RR 1.31, 95% CI 0.72 to 2.38; 20,581 participants; 3 studies; very low-quality evidence) and rhabdomyolysis, given the wide CIs and low event rate. Little or no difference in the risk of cancer, gallbladder-related disease and discontinuation due to adverse events were observed between treatment groups. For serum lipids, adding ezetimibe to statin or fenofibrate might further reduce the low-density lipoprotein cholesterol (LDL-C), total cholesterol and triglyceride levels and likely increase the high-density lipoprotein cholesterol levels; however, substantial heterogeneity was detected in most analyses.None of the included studies reported on health-related quality of life.
AUTHORS' CONCLUSIONS
Moderate- to high-quality evidence suggests that ezetimibe has modest beneficial effects on the risk of CVD endpoints, primarily driven by a reduction in non-fatal MI and non-fatal stroke, but it has little or no effect on clinical fatal endpoints. The cardiovascular benefit of ezetimibe might involve the reduction of LDL-C, total cholesterol and triglycerides. There is insufficient evidence to determine whether ezetimibe increases the risk of adverse events due to the low and very low quality of the evidence. The evidence for beneficial effects was mainly obtained from individuals with established atherosclerotic cardiovascular disease (ASCVD, predominantly with acute coronary syndrome) administered ezetimibe plus statins. However, there is limited evidence regarding the role of ezetimibe in primary prevention and the effects of ezetimibe monotherapy in the prevention of CVD, and these topics thus requires further investigation.
Topics: Aged; Aged, 80 and over; Anticholesteremic Agents; Cardiovascular Diseases; Cause of Death; Cholesterol; Cholesterol, LDL; Drug Therapy, Combination; Ezetimibe; Fenofibrate; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Middle Aged; Myocardial Infarction; Randomized Controlled Trials as Topic; Simvastatin; Stroke; Triglycerides
PubMed: 30480766
DOI: 10.1002/14651858.CD012502.pub2 -
Frontiers in Immunology 2023Programmed cell death (PCD) refers to cell death in a manner that depends on specific genes encoding signals or activities. PCD includes apoptosis, pyroptosis, autophagy... (Review)
Review
Programmed cell death (PCD) refers to cell death in a manner that depends on specific genes encoding signals or activities. PCD includes apoptosis, pyroptosis, autophagy and necrosis (programmed necrosis). Among these mechanisms, pyroptosis is mediated by the gasdermin family and is accompanied by inflammatory and immune responses. When pathogens or other danger signals are detected, cytokine action and inflammasomes (cytoplasmic multiprotein complexes) lead to pyroptosis. The relationship between pyroptosis and cancer is complex and the effect of pyroptosis on cancer varies in different tissue and genetic backgrounds. On the one hand, pyroptosis can inhibit tumorigenesis and progression; on the other hand, pyroptosis, as a pro-inflammatory death, can promote tumor growth by creating a microenvironment suitable for tumor cell growth. Indeed, the NLRP3 inflammasome is known to mediate pyroptosis in digestive system tumors, such as gastric cancer, pancreatic ductal adenocarcinoma, gallbladder cancer, oral squamous cell carcinoma, esophageal squamous cell carcinoma, in which a pyroptosis-induced cellular inflammatory response inhibits tumor development. The same process occurs in hepatocellular carcinoma and some colorectal cancers. The current review summarizes mechanisms and pathways of pyroptosis, outlining the involvement of NLRP3 inflammasome-mediated pyroptosis in digestive system tumors.
Topics: Humans; Carcinoma, Pancreatic Ductal; Digestive System; Esophageal Squamous Cell Carcinoma; Gallbladder Neoplasms; Inflammasomes; Neoplasms; Pyroptosis; Squamous Cell Carcinoma of Head and Neck; Stomach Neoplasms; Carcinoma, Hepatocellular; Colorectal Neoplasms
PubMed: 37081882
DOI: 10.3389/fimmu.2023.1074606 -
Journal of Cancer 2021A deep and comprehensive understanding of factors that contribute to cancer initiation, progression, and evolution is of essential importance. Among them, the... (Review)
Review
A deep and comprehensive understanding of factors that contribute to cancer initiation, progression, and evolution is of essential importance. Among them, the serine/threonine and tyrosine kinase-like kinases, also known as receptor interacting proteins (RIPs) or receptor interacting protein kinases (RIPKs), is emerging as important tumor-related proteins due to its complex regulation of cell survival, apoptosis, and necrosis. In this review, we mainly review the relevance of RIP to various malignant digestive neoplasms, including esophageal cancer, gastric cancer, colorectal cancer, hepatocellular carcinoma, gallbladder cancer, cholangiocarcinoma, and pancreatic cancer. Consecutive research on RIPs and its relationship with malignant digestive neoplasms is required, as it ultimately conduces to the etiology and treatment of cancer.
PubMed: 34093836
DOI: 10.7150/jca.57076 -
Aging Jul 2023Gallbladder carcinoma is a malignant epithelial tumor of gallbladder with a high degree of malignancy. However, relationship between KNTC1 and MCM2 and gallbladder...
BACKGROUND
Gallbladder carcinoma is a malignant epithelial tumor of gallbladder with a high degree of malignancy. However, relationship between KNTC1 and MCM2 and gallbladder cancer is unclear.
METHODS
GSE139682 and GSE202479 were downloaded from gene expression omnibus (GEO). Differentially expressed genes (DEGs) were screened. Functional enrichment analysis and gene set enrichment analysis (GSEA) were performed. Protein-protein interaction (PPI) Network was constructed and analyzed. Gene expression heat map was drawn. Comparative toxicogenomics database (CTD) analysis was performed to find diseases most related to core genes. TargetScan was performed for screening miRNAs that regulated central DEGs.
RESULTS
230 DEGs were identified. According to GObp analysis, they were mainly concentrated in regulation of ossification, regulation of spindle microtubule and centromere attachment, cytoskeleton tissue of cortical actin. According to GOcc analysis, they are mainly concentrated in plasma membrane part, cell junction, plasma membrane region and anterior membrane. According to GOmf analysis, they are mainly enriched in protein homodimerization activity, proximal promoter sequence-specific DNA binding and sulfur compound binding. KEGG showed that target genes were mainly enriched in Hippo signal pathway, p53 signal pathway and cancer pathway. KIFC2, TUBG1, RACGAP1, CHMP4C, SFN and MYH11 were identified as core genes. Gene expression heat map showed that KNTC1, MCM2, CKAP2, RACGAP1, CCNB1 were highly expressed in gallbladder carcinoma samples. CTD analysis showed that KNTC1, MCM2, CKAP2, RACGAP1, CCNB1 were associated with head and neck squamous cell carcinoma, necrosis, inflammation and hepatomegaly.
CONCLUSIONS
KNTC1 and MCM2 are highly expressed in gallbladder cancer. Higher expression level correlates with worse prognosis.
Topics: Humans; Gene Expression Profiling; Gallbladder Neoplasms; Gene Regulatory Networks; Protein Interaction Maps; Head and Neck Neoplasms; Computational Biology; Gene Expression Regulation, Neoplastic; Biomarkers, Tumor; Microtubule-Associated Proteins; Cell Cycle Proteins; Minichromosome Maintenance Complex Component 2
PubMed: 37480569
DOI: 10.18632/aging.204889 -
World Journal of Gastroenterology Jun 2020The advent of lumen apposing metal stents (LAMS) has revolutionized the management of many complex gastroenterological conditions that previously required surgical or... (Review)
Review
The advent of lumen apposing metal stents (LAMS) has revolutionized the management of many complex gastroenterological conditions that previously required surgical or radiological interventions. These procedures have garnered popularity due to their minimally invasive nature, higher technical and clinical success rate and lower rate of adverse events. By virtue of their unique design, LAMS provide more efficient drainage, serve as conduit for endoscopic access, are associated with lower rates of leakage and are easy to be removed. Initially used for drainage of pancreatic fluid collections, the use of LAMS has been extended to gallbladder and biliary drainage, treatment of luminal strictures, creation of gastrointestinal fistulae, pancreaticobiliary drainage, improved access for surgically altered anatomy, and drainage of intra-abdominal and pelvic abscesses as well as post-surgical fluid collections. As new indications of endosonographic techniques and LAMS continue to evolve, this review summarizes the current role of LAMS in the management of these various complex conditions and also highlights clinical pearls to guide successful placement of LAMS.
Topics: Drainage; Endoscopy; Endosonography; Fluoroscopy; Gastrointestinal Diseases; Humans; Stents
PubMed: 32550749
DOI: 10.3748/wjg.v26.i21.2715 -
International Journal of Surgery Case... 2015Symptomatic biliary disease in children and young adults requiring surgical intervention are uncommon. However even rarer is the occurrence of a spontaneous gallbladder...
INTRODUCTION
Symptomatic biliary disease in children and young adults requiring surgical intervention are uncommon. However even rarer is the occurrence of a spontaneous gallbladder necrosis in a child. We report a case of spontaneous necrosis in a child with no apparent causative factors.
CASE
Fit and well 16 year-old boy presented with acute generalized lower abdominal pain. Examination revealed mild epigastric pain with rebound tenderness and guarding of the right iliac fossa. Diagnostic laparoscopy showed a necrotic gallbladder and incidental finding of a Meckel's diverticulum. He had a cholecystectomy and Meckel's diverticulum resection. Patient recovered uneventfully and was discharged home. He was reviewed 2 months later and recovered well with no evidence of any post-operative complication. He was discharged without any further follow up.
DISCUSSION
Gall bladder necrosis is a rare cause of an acute abdomen. We present the first reported case of a spontaneous gallbladder necrosis with no apparent cause. Literature review showed various causes of gall bladder necrosis including trauma, acalculous cholecystitis, gallbladder torsion, gangrenous cholecystitis and etc.
CONCLUSION
We report a case of spontaneous gallbladder necrosis in a young healthy male with no family history of thrombotic disorders or any history of sepsis, intervention, trauma and no obvious underlying anatomical or histological abnormalities. This is an exceedingly rare pathology and one would be forgiven for not including it on the list of a differential diagnosis in such circumstance. However it is important to send tissue sample to exclude any underlying histological aetiological factors.
PubMed: 26657530
DOI: 10.1016/j.ijscr.2015.11.002 -
Cureus Apr 2020Aneurysmal ruptures are a life-threatening pathology, and while the aorta is the principal location, any aneurysmal rupture can be fatal. Most result from chronic...
Aneurysmal ruptures are a life-threatening pathology, and while the aorta is the principal location, any aneurysmal rupture can be fatal. Most result from chronic diseases, such as hypertension, diabetes, and vasculitis. Nevertheless, a rupture can result in acute decompensation and must be recognized and addressed quickly to limit morbidity and mortality. The authors describe a case of a 66-year-old female who presented to the emergency department (ED) for abdominal pain and syncope. Even though imaging did not explicitly show the specific site of rupture of the hepatic artery, the positive Rapid Ultrasound for Shock and Hypotension (RUSH) exam and aortic dissection on computed tomography angiography along with her clinical picture (hypotension, abdominal pain, decreased capillary refill, grey skin) raised our suspicions for critical pathology. Exploratory laparotomy revealed a ruptured hepatic artery aneurysm. Her hospital course was complicated by ischemic necrosis of the gallbladder, spleen, and liver, requiring cholecystectomy, splenectomy, and partial hepatectomy, but she was discharged to rehabilitation and expected to make a recovery. This case displays the importance of using ultrasonography early to aid in expedited diagnosis and treatment as well as maintaining a high suspicion for vascular pathology in the setting of hemorrhagic shock.
PubMed: 32431993
DOI: 10.7759/cureus.7715 -
Journal of Clinical Medicine Nov 2020Endoscopic ultrasound (EUS)-guided interventions provide easy access to structures adjacent to the gastrointestinal tract, effectively targeting them for therapeutic... (Review)
Review
Endoscopic ultrasound (EUS)-guided interventions provide easy access to structures adjacent to the gastrointestinal tract, effectively targeting them for therapeutic purposes. They play an important role in the management of pancreatic fluid collections (PFC) and bile duct (BD) and pancreatic duct (PD) drainage in cases of failed endoscopic retrograde cholangiopancreatography (ERCP) or gallbladder (GB) drainage. Specially designed stents and delivery systems for EUS-guided transluminal interventions allow various new applications and improve the efficacy and safety of these procedures. In fact, EUS-guided drainage has emerged as the treatment of choice for the management of PFC, and recent innovations such as fully covered metal stents (including lumen-apposing metal stents) have improved outcomes in patients with walled-off necrosis. Similarly, EUS-guided BD and PD drainage with specially designed stents can be beneficial for patients with failed ERCP due to an inaccessible papilla, gastric outlet obstruction, or surgically altered anatomy. EUS-guided GB drainage is also performed using dedicated stents in patients with acute cholecystitis who are not fit for surgery. Although the field of dedicated stents for interventional EUS is rapidly advancing with increasing innovations, the debate on the most appropriate stent for EUS-guided drainage has resurfaced. Furthermore, some important questions remain unaddressed, such as which stent improves clinical outcomes and safety in EUS-guided drainage. Herein, the current status and problems of the available stents are reviewed, including the applicable indications, long-term clinical outcomes, comparison between each stent, and their future prospects.
PubMed: 33171627
DOI: 10.3390/jcm9113595