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Topic Review
Promising Highly Targeted Therapies for Cholangiocarcinom
To overcome the poor prognosis of cholangiocarcinoma (CCA), highly targeted therapies, such as antibody-drug conjugates (ADCs), photodynamic therapy (PDT) with/without systemic chemotherapy, and experimental photoimmunotherapy (PIT), have been developed. Three preclinical trials have investigated the use of ADCs targeting specific antigens, namely HER2, MUC1, and glypican-1 (GPC1), for CCA. Trastuzumab emtansine demonstrated higher antiproliferative activity in CCA cells expressing higher levels of HER2. PDT is effective in areas where appropriate photosensitizers and light coexist. Its mechanism involves photosensitizer excitation and subsequent reactive oxygen species production in cancer cells upon irradiation. Hematoporphyrin derivatives, temoporfin, phthalocyanine-4, talaporfin, and chlorine e6 derivatives have mainly been used clinically and preclinically in bile duct cancer. PIT is the most novel anti-cancer therapy developed in 2011 that selectively kills targeted cancer cells using a unique photosensitizer called “IR700” conjugated with an antibody specific for cancer cells. PIT is currently in the early stages of development for identifying appropriate CCA cell targets and irradiation devices. Future human and artificial intelligence collaboration has potential for overcoming challenges related to identifying universal CCA cell targets. This could pave the way for highly targeted therapies for CCA, such as ADC, PDT, and PIT.
  • 641
  • 25 Jul 2023
Topic Review
Mechanisms of Relationship between NAFLD and Arterial Hypertension
Non-alcoholic fatty liver disease (NAFLD) and arterial hypertension (AH) are widespread noncommunicable diseases in the global population. Since hypertension and NAFLD are diseases associated with metabolic syndrome, they are often comorbid. In fact, many contemporary published studies confirm the association of these diseases with each other, regardless of whether other metabolic factors, such as obesity, dyslipidemia, and type 2 diabetes mellites, are present.
  • 640
  • 13 Sep 2023
Topic Review
Noninvasive Indices for Hepatic Fibrosis in Hemodialysis Patients
Hepatitis C virus (HCV) is a major health problem in hemodialysis patients, which leads to significant morbidity and mortality through progressive hepatic fibrosis or cirrhosis. Percutaneous liver biopsy is the gold standard to stage hepatic fibrosis. However, it is an invasive procedure with postbiopsy complications. Because uremia may significantly increase the risk of fatal and nonfatal bleeding events, the use of noninvasive means to assess the severity of hepatic fibrosis is particularly appealing to hemodialysis patients.
  • 639
  • 29 Sep 2022
Topic Review
Ileal Pouch–Anal Anastomosis and Pouchitis
Inflammatory bowel diseases, Crohn’s disease and ulcerative colitis, are life-long disorders characterized by the chronic relapsing inflammation of the gastrointestinal tract with the intermittent need for escalation treatment and, eventually, even surgery. The total proctocolectomy with ileal pouch–anal anastomosis (IPAA) is the surgical intervention of choice in subjects affected by ulcerative colitis (UC). Although IPAA provides satisfactory functional outcomes, it can be susceptible to some complications, including pouchitis as the most common.
  • 638
  • 18 Jul 2022
Topic Review
Juvenile Autoimmune Hepatitis
Juvenile autoimmune hepatitis (JAIH) is severe immune-mediated necro-inflammatory disease of the liver with spontaneous progression to cirrhosis and liver failure if left untreated. The diagnosis is based on the combination of clinical, laboratory and histological findings. Prothrombin ratio is a useful prognostic factor to identify patients who will most likely require a liver transplant by adolescence or early adulthood. JAIH treatment consists of immune suppression and should be started promptly at diagnosis to halt inflammatory liver damage and ultimately prevent fibrosis and progression to end-stage liver disease. The risk of relapse is high especially in the setting of poor treatment compliance.
  • 635
  • 06 Sep 2023
Topic Review
Relationship between Gut Microbiota and Cardiovascular Disease
Cardiovascular disease (CVD) is a leading cause of death and morbidity worldwide. Identification of possible preventive strategies is of central interest to avoid CVD onset and progression. In this regard, intensive medical and scientific activity is currently employed in the management of traditional risk factors, but despite maximum medical therapy, there is still a residual risk of undetermined etiology. The gut microbiota is gaining increasing interest as one of the potentially modifiable factors that are involved in the pathogenesis of several diseases, including CVD. A multitude of microorganisms lives symbiotically with the human host; 10–100 trillion microbes among bacteria, viruses, fungi, and helminths are located in the gut. They serve a multitude of functions, which include maintenance of intestinal homeostasis and defence against external aggressive agents, modulation of the immune response, and production of metabolites. 
  • 633
  • 01 Jun 2023
Topic Review
MicroRNAs in Hepatic Ischemia–Reperfusion Injury
Hepatic ischemia–reperfusion injury (IRI) is one of the main factors for early allograft dysfunction (EAD), which may lead to graft rejection, graft loss, or shortened graft life in liver transplantation. Hepatic IRI appears to be inevitable during the majority of liver procurement and transportation of donor organs, resulting in a cascade of biological changes. The activation of signaling pathways during IRI results in the up- and downregulation of genes and microRNAs (miRNAs). miRNAs are ~21 nucleotides in length and well-characterized for their role in gene regulations; they have recently been used for therapeutic approaches in addition to their role as biomarkers for many diseases. Various miRNAs have been identified in association with hepatic IRI that either exaggerate or ameliorate the hepatic IRI. Altering targeted miRNA expression has great potential to reduce early graft dysfunction and improve patient outcome. Strategies to implement this approach have been studied using hepatic cell lines subjected to oxygen deprived conditions in vitro, as well as animal models after induction of hepatic IRI through warm ischemia in vivo. By studying the mechanisms of specific miRNAs, the up- or downregulation during hepatic IRI reveals whether that miRNA can ameliorate or exaggerate the metabolism and functions of the liver. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels can be used to indicate when liver injury is present and improve diagnosis accuracy along with miRNA biomarkers. The manipulation of miRNAs could have an influence on the inflammatory and oxidative stress pathways associated with hepatic IRI.
  • 632
  • 15 Apr 2022
Topic Review
Management of Pediatric Feeding Disorder
Pediatric feeding disorder (PFD) is defined as impaired oral intake that is not age appropriate and is associated with at least one dysfunctional domain: medical; nutritional; feeding skills; and psychosocial  Feeding difficulties take time to resolve and are best managed in progressive phases. A series of short-term goals are typically developed that can lead to complex interdisciplinary coordination of care. Using a stepwise treatment approach to PFD is important because, even though feeding problems are relatively common—occurring in up to 45% of children in the general population—the condition is severe enough to warrant intensive intervention in about 10%. A stepwise approach ensures that feeding problems are not overlooked or treated inappropriately.
  • 631
  • 03 Mar 2023
Topic Review
Management of Cholestatic Liver Diseases
Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are two chronic cholestatic liver diseases affecting bile ducts that may progress to biliary cirrhosis.
  • 630
  • 07 May 2021
Topic Review
Sphingosine 1-Phosphate Modulation in Inflammatory Bowel Diseases
Inflammatory bowel diseases (IBDs), including ulcerative colitis (UC) and Crohn’s disease (CD), are chronic, disabling conditions affecting the gastrointestinal tract and characterized by an abnormal immune response to intestinal microflora in genetically susceptible individuals. For their progressive behavior, the recommended management involves optimal and early treatment, in order to prevent complications such as corticosteroids’ need, hospitalization, surgery and disability and dysplasia/cancer. Most S1P modulators are reported to be safe and effective in the treatment of both UC and CD. High and satisfactory rates of clinical remission as well as endoscopic improvement and remission can be achieved with these molecules. Safety alarms remain rather low, although the S1P binding to two of its G protein-coupled receptors, 2 and 3 (S1PR2 and S1PR3), may be associated with cardiovascular risks.
  • 630
  • 08 Aug 2022
Topic Review
Methods of Measuring Pancreatic Cystic Lesion Size
The incidence of pancreatic cystic lesions (PCLs) has been rising due to improvements in imaging. Of these, intraductal papillary mucinous neoplasms (IPMNs) are the most common and are thought to contribute to almost 20% of pancreatic adenocarcinomas. All major society guidelines for the management of IPMNs use size defined by maximum diameter as the primary determinant of whether surveillance or surgical resection is recommended. However, there is no consensus on how these measurements should be obtained or whether a single imaging modality is superior. Furthermore, the largest diameter may fail to capture the complexity of PCLs, as most are not perfectly spherical.
  • 629
  • 14 Sep 2023
Topic Review
Diet and Nutritional Interventions in Early Life
The infant gut microbiome plays a key role in the healthy development of the human organism and appears to be influenced by dietary practices through multiple pathways. First, maternal diet during pregnancy and infant nutrition significantly influence the infant gut microbiota. Moreover, breastfeeding fosters the proliferation of beneficial bacteria, while formula feeding increases microbial diversity. The timing of introducing solid foods also influences gut microbiota composition. In preterm infants the gut microbiota development is influenced by multiple factors, including the time since birth and the intake of breast milk, and interventions such as probiotics and prebiotics supplementation show promising results in reducing morbidity and mortality in this population.
  • 628
  • 27 Feb 2024
Topic Review
HER2 in Metastatic Colorectal Cancer
HER2 is an emerging biomarker in colorectal cancer (CRC). This oncogene plays an essential role in regulating cell proliferation, differentiation, migration, and, more in general, tumorigenesis and tumor progression. The most frequent types of HER2 alterations in CRC include gene amplification and missense mutations in 7–8% of CRC, often being mirrored by HER2 protein overexpression, representing founder events in solid tumors, including CRC.
  • 627
  • 09 Feb 2023
Topic Review
Virally Infected Donor Grafts
The ideal management for end stage liver disease, acute liver failure, and hepatocellular carcinoma (HCC), within specific criteria, is liver transplantation (LT). Due to continuous increase in LT cases, there has been consideration to increase utilization of organs from donor livers which were previously discarded, including virally infected donor livers. 
  • 624
  • 07 Jan 2022
Topic Review
Laparoscopic Proximal Gastrectomy and Laparoscopic Subtotal Gastrectomy
Laparoscopic proximal gastrectomy (LPG) and laparoscopic distal gastrectomy with a small remnant stomach, namely laparoscopic subtotal gastrectomy (LsTG), are alternative function-preserving procedures for laparoscopic total gastrectomy (LTG) of early proximal gastric cancer.
  • 624
  • 16 Jan 2023
Topic Review
TGF-β, Activin and Follistatin in Inflammatory Bowel Disease
Inflammatory bowel disease (IBD) is an immune-mediated inflammatory condition predominantly affecting the gastrointestinal (GI) tract. An increasing prevalence of IBD has been observed globally. The pathogenesis of IBD includes a complex interplay between the intestinal microbiome, diet, genetic factors and immune responses. The consequent imbalance of inflammatory mediators ultimately leads to intestinal mucosal damage and defective repair. Growth factors, given their specific roles in maintaining the homeostasis and integrity of the intestinal epithelium, are of particular interest in the setting of IBD. Furthermore, direct targeting of growth factor signalling pathways involved in the regeneration of the damaged epithelium and the regulation of inflammation could be considered as therapeutic options for individuals with IBD. Several members of the transforming growth factor (TGF)-β superfamily, particularly TGF-β, activin and follistatin, are key candidates as they exhibit various roles in inflammatory processes and contribute to maintenance and homeostasis in the GI tract. 
  • 624
  • 05 May 2023
Topic Review
Endoscopic Transpapillary/Endoscopic Ultrasound-Guided Gallbladder Drainage of Acute Cholecystitis
A percutaneous cholecystostomy tube (PCT) is the conventionally favored nonoperative intervention for treating acute cholecystitis. However, PCT is beset by high adverse event rates, need for scheduled reintervention, and inadvertent dislodgement, as well as patient dissatisfaction with a percutaneous drain. Recent advances in endoscopic therapy involve the implementation of endoscopic transpapillary drainage (ETP-GBD) and endoscopic ultrasound-guided gallbladder drainage (EUS-GBD), which are increasingly preferred over PCT due to their favorable technical and clinical success combined with lower complication rates. 
  • 624
  • 28 Feb 2024
Topic Review
Hepatic Arterial Infusion Chemotherapy for Advanced Hepatocellular Carcinoma
Systemic therapeutic agents, including combination immunotherapy, could promote a change in the treatment strategy in patients with advanced hepatocellular carcinoma (HCC). Hepatic arterial infusion chemotherapy (HAIC) is highly effective in patients with vascular invasion compared with sorafenib.
  • 622
  • 02 Jun 2023
Topic Review
Non-Coding RNAs in Hepatocellular Carcinoma Progression
Hepatocellular carcinoma (HCC) is a predominant malignancy with increasing incidences and mortalities worldwide. In Western countries, the progressive affirmation of Non-alcoholic Fatty Liver Disease (NAFLD) as the main chronic liver disorder in which HCC occurrence is appreciable even in non-cirrhotic stages, constitutes a real health emergency. In light of this, a further comprehension of molecular pathways supporting HCC onset and progression represents a current research challenge to achieve more tailored prognostic models and appropriate therapeutic approaches. RNA non-coding transcripts (ncRNAs) are involved in the regulation of several cancer-related processes, including HCC. When dysregulated, these molecules, conventionally classified as “small ncRNAs” (sncRNAs) and “long ncRNAs” (lncRNAs) have been reported to markedly influence HCC-related progression mechanisms. 
  • 622
  • 01 Nov 2023
Topic Review
Non-Alcoholic Fatty Liver Disease and Metabolic Syndrome
Metabolic syndrome (MetS) is characterized by an association of cardiovascular and diabetes mellitus type 2 risk factors. Although the definition of MetS slightly differs depending on the society that described it, its central diagnostic criteria include impaired fasting glucose, low HDL-cholesterol, elevated triglycerides levels and high blood pressure. Insulin resistance (IR) is believed to be the main cause of MetS and is connected to the level of visceral or intra-abdominal adipose tissue, which could be assessed either by calculating body mass index or by measuring waist circumference. Studies revealed that IR may also be present in non-obese patients, and considered visceral adiposity to be the main effector of MetS’ pathology. Visceral adiposity is strongly linked with hepatic fatty infiltration also known as non-alcoholic fatty liver disease (NAFLD), therefore, the level of fatty acids in the hepatic parenchyma is indirectly linked with MetS, being both a cause and a consequence of this syndrome.
  • 621
  • 23 Feb 2023
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