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JAMA Network Open Aug 2023Accurate risk prediction models using routinely measured biomarkers-eg, carbohydrate antigen 19-9 (CA19-9) and bilirubin serum levels-for pancreatic cancer could...
IMPORTANCE
Accurate risk prediction models using routinely measured biomarkers-eg, carbohydrate antigen 19-9 (CA19-9) and bilirubin serum levels-for pancreatic cancer could facilitate early detection of pancreatic cancer and prevent potentially unnecessary diagnostic tests for patients at low risk. An externally validated model using CA19-9 and bilirubin serum levels in a larger cohort of patients with pancreatic cancer or benign periampullary diseases is needed.
OBJECTIVE
To assess the discrimination, calibration, and clinical utility of a prediction model using readily available blood biomarkers (carbohydrate antigen 19-9 [CA19-9] and bilirubin) to distinguish early-stage pancreatic cancer from benign periampullary diseases.
DESIGN, SETTING, AND PARTICIPANTS
This diagnostic study used data from 4 academic hospitals in Italy, the Netherlands, and the UK on adult patients with pancreatic cancer or benign periampullary disease treated from 2014 to 2022. Analyses were conducted from September 2022 to February 2023.
EXPOSURES
Serum levels of CA19-9 and bilirubin from samples collected at diagnosis and before start of any medical intervention.
MAIN OUTCOMES AND MEASURES
Discrimination (measured by the area under the curve [AUC]), calibration, and clinical utility of the prediction model and the biomarkers, separately.
RESULTS
The study sample comprised 249 patients in the development cohort (mean [SD] age at diagnosis, 67 [11] years; 112 [45%] female individuals), and 296 patients in the validation cohort (mean [SD] age at diagnosis, 68 [12] years; 157 [53%] female individuals). At external validation, the prediction model showed an AUC of 0.89 (95% CI, 0.84-0.93) for early-stage pancreatic cancer vs benign periampullary diseases, and outperformed CA19-9 (difference in AUC [ΔAUC], 0.10; 95% CI, 0.06-0.14; P < .001) and bilirubin (∆AUC, 0.07; 95% CI, 0.02-0.12; P = .004). In the subset of patients without elevated tumor marker levels (CA19-9 <37 U/mL), the model showed an AUC of 0.84 (95% CI, 0.77-0.92). At a risk threshold of 30%, decision curve analysis indicated that performing biopsies based on the prediction model was equivalent to reducing the biopsy procedure rate by 6% (95% CI, 1%-11%), without missing early-stage pancreatic cancer in patients.
CONCLUSIONS AND RELEVANCE
In this diagnostic study of patients with pancreatic cancer or benign periampullary diseases, an easily applicable risk score showed high accuracy for distinguishing early-stage pancreatic cancer from benign periampullary diseases. This model could be used to assess the added diagnostic and clinical value of novel biomarkers and prevent potentially unnecessary invasive diagnostic procedures for patients at low risk.
Topics: Adult; Humans; Female; Child; Male; CA-19-9 Antigen; Pancreatic Neoplasms; Bilirubin; Carbohydrates
PubMed: 37639271
DOI: 10.1001/jamanetworkopen.2023.31197 -
Hypertension (Dallas, Tex. : 1979) Oct 2018
Review
Topics: Bilirubin; Cardiovascular Diseases; Humans; Metabolic Diseases; Myocardium; Signal Transduction
PubMed: 30354722
DOI: 10.1161/HYPERTENSIONAHA.118.11130 -
Biomolecules & Therapeutics Nov 2023Bile pigment, bilirubin, and biliverdin concentrations may change as a results of biliary tract cancer (BTC) altering the mechanisms of radical oxidation and heme...
Bile pigment, bilirubin, and biliverdin concentrations may change as a results of biliary tract cancer (BTC) altering the mechanisms of radical oxidation and heme breakdown. We explored whether changes in bile pigment components could help distinguish BTC from benign biliary illness by evaluating alterations in patients with BTC. We collected bile fluid from 15 patients with a common bile duct stone (CBD group) and 63 individuals with BTC (BTC group). We examined the bile fluid's bilirubin, biliverdin reductase (BVR), heme oxygenase (HO-1), and bacterial taxonomic abundance. Serum bilirubin levels had no impact on the amounts of bile HO-1, BVR, or bilirubin. In comparison to the control group, the BTC group had considerably higher amounts of HO-1, BVR, and bilirubin in the bile. The areas under the curve for the receiver operating characteristic curve analyses of the BVR and HO-1 were 0.832 (<0.001) and 0.891 (<0.001), respectively. Firmicutes was the most prevalent phylum in both CBD and BTC, according to a taxonomic abundance analysis, however the Firmicutes/Bacteroidetes ratio was substantially greater in the BTC group than in the CBD group. The findings of this study showed that, regardless of the existence of obstructive jaundice, biliary carcinogenesis impacts heme degradation and bile pigmentation, and that the bile pigment components HO-1, BVR, and bilirubin in bile fluid have a diagnostic significance in BTC. In tissue biopsies for the diagnosis of BTC, particularly for distinguishing BTC from benign biliary strictures, bile pigment components can be used as additional biomarkers.
PubMed: 37558633
DOI: 10.4062/biomolther.2023.010 -
Revista Da Associacao Medica Brasileira... Jul 2020The increase in bilirubin levels in newborns can cause toxic effects on the auditory system, which can lead to hearing loss. This review aimed to verify the impact of... (Review)
Review
The increase in bilirubin levels in newborns can cause toxic effects on the auditory system, which can lead to hearing loss. This review aimed to verify the impact of hyperbilirubinemia in the hearing of newborns, relating audiological findings to serum levels of bilirubin. A literature review was conducted during October 2017, using the terms "hyperbilirubinemia", "jaundice", "infant", "newborn" and "hearing loss", on databases CAPES journals, MEDLINE and BIREME (SciELO, BBO). 827 studies were identified and 59 were selected for full-text reading, resulting in the selection of seven articles that met the inclusion criteria and were considered relevant to the sample of this study. All the reviewed studies performed brainstem auditory evoked potential as the main test for audiological evaluation. Changes in the audiological findings of neonates with hyperbilirubinemia were observed in all studies. There was no consensus on the serum bilirubin levels that may cause auditory changes; however, the relationship between hearing disorders and blood levels of bilirubin was positive. We identify the need to establish reference values for bilirubin levels considered critical for the occurrence of hearing disorders as well as the audiological follow-up of neonates with hyperbilirubinemia.
Topics: Audiometry; Bilirubin; Evoked Potentials, Auditory, Brain Stem; Hearing Loss; Humans; Hyperbilirubinemia; Infant, Newborn
PubMed: 32844928
DOI: 10.1590/1806-9282.66.7.1002 -
International Journal of Molecular... Jun 2022Heme oxygenase (HO) has both beneficial and detrimental effects via its metabolites, including carbon monoxide (CO), biliverdin or bilirubin, and ferrous iron. HO-1 is... (Review)
Review
Heme oxygenase (HO) has both beneficial and detrimental effects via its metabolites, including carbon monoxide (CO), biliverdin or bilirubin, and ferrous iron. HO-1 is an inducible form of HO that is upregulated by oxidative stress, nitric oxide, CO, and hypoxia, whereas HO-2 is a constitutive form that regulates vascular tone and homeostasis. In brains injured by trauma, ischemia-reperfusion, or Alzheimer's disease (AD), the long-term expression of HO-1 can be detected, which can lead to cytotoxic ferroptosis via iron accumulation. In contrast, the transient induction of HO-1 in the peri-injured region may have regenerative potential (e.g., angiogenesis, neurogenesis, and mitochondrial biogenesis) and neurovascular protective effects through the CO-mediated signaling pathway, the antioxidant properties of bilirubin, and the iron-mediated ferritin synthesis. In this review, we discuss the dual roles of HO-1 and its metabolites in various neurovascular diseases, including age-related macular degeneration, ischemia-reperfusion injury, traumatic brain injury, Gilbert's syndrome, and AD.
Topics: Bilirubin; Biliverdine; Heme Oxygenase (Decyclizing); Heme Oxygenase-1; Iron
PubMed: 35806040
DOI: 10.3390/ijms23137041 -
Cells Aug 2022Bilirubin-induced neurological damage (BIND) has been a subject of studies for decades, yet the molecular mechanisms at the core of this damage remain largely unknown.... (Review)
Review
Bilirubin-induced neurological damage (BIND) has been a subject of studies for decades, yet the molecular mechanisms at the core of this damage remain largely unknown. Throughout the years, many in vivo chronic bilirubin encephalopathy models, such as the Gunn rat and transgenic mice, have further elucidated the molecular basis of bilirubin neurotoxicity as well as the correlations between high levels of unconjugated bilirubin (UCB) and brain damage. Regardless of being invaluable, these models cannot accurately recapitulate the human brain and liver system; therefore, establishing a physiologically recapitulating in vitro model has become a prerequisite to unveil the breadth of complexities that accompany the detrimental effects of UCB on the liver and developing human brain. Stem-cell-derived 3D brain organoid models offer a promising platform as they bear more resemblance to the human brain system compared to existing models. This review provides an explicit picture of the current state of the art, advancements, and challenges faced by the various models as well as the possibilities of using stem-cell-derived 3D organoids as an efficient tool to be included in research, drug screening, and therapeutic strategies for future clinical applications.
Topics: Animals; Bilirubin; Brain; Humans; Induced Pluripotent Stem Cells; Mice; Organoids; Rats; Rats, Gunn; Trauma, Nervous System
PubMed: 36078055
DOI: 10.3390/cells11172647 -
Turk Patoloji Dergisi 2021The aim of the study is to do a clinicopathologic study of post mortem kidney biopsies with significant deposition of bilirubin pigment within tubular epithelial cells...
OBJECTIVE
The aim of the study is to do a clinicopathologic study of post mortem kidney biopsies with significant deposition of bilirubin pigment within tubular epithelial cells and in the lumen of distal tubules as a bile cast.
MATERIAL AND METHOD
All post mortem specimens with acute tubular necrosis, with the presence of bile casts in tubules or bile pigment deposition in the tubular epithelium during the period 2015-2018 were examined for gross and histopathology along with biochemical parameters and viral markers.
RESULTS
Bile casts with sloughed renal tubular epithelial cells and occasional macrophages were present in the distal convoluted tubule in 78.6% of biopsies (11/14). The plugging of distal convoluted tubule with casts was similar to that seen in myeloma and myoglobin cast nephropathies. Bilirubin pigment deposition was present in 35.7% (5/14) of cases. The frequency of bile casts in each biopsy was variable and it did not have any association with serum bilirubin levels or etiology of liver dysfunction. A striking difference from earlier studies is the high number of toxin-induced liver damage including six cases of paraquat and 2 cases of yellow phosphorus poisoning.
CONCLUSION
This study proves importance of the bile cast nephropathy as a reason for kidney injury, especially with varied hepatotoxic etiologies, especially paraquat and yellow phosphorus.
Topics: Adolescent; Adult; Aged; Autopsy; Bile; Bilirubin; Child; Hepatorenal Syndrome; Humans; Kidney Diseases; Liver Diseases; Middle Aged; Nephrosis; Paraquat; Phosphorus
PubMed: 34514566
DOI: 10.5146/tjpath.2021.01532 -
Transplantation Reviews (Orlando, Fla.) Oct 2018In patients with end-stage renal disease, kidney transplantation has been associated with numerous benefits, including increased daily activity, and better survival... (Review)
Review
In patients with end-stage renal disease, kidney transplantation has been associated with numerous benefits, including increased daily activity, and better survival rates. However, over 20% of kidney transplants result in rejection within five years. Rejection is primarily due to a hypersensitive immune system and ischemia/reperfusion injury. Bilirubin has been shown to be a potent antioxidant that is capable of potentially reversing or preventing damage from reactive oxygen species generated from ischemia and reperfusion. Additionally, bilirubin has several immunomodulatory effects that can dampen the immune system to promote organ acceptance. Increased bilirubin has also been shown to have a positive impact on renal hemodynamics, which is critical post-transplantation. Lastly, bilirubin levels have been correlated with biomarkers of successful transplantation. In this review, we discuss a multitude of potentially beneficial effects that bilirubin has on kidney acceptance of transplantation based on numerous clinical trials and animal models. Exogenous bilirubin delivery or increasing endogenous levels pre- or post-transplantation may have therapeutic benefits.
Topics: Antioxidants; Bilirubin; Graft Rejection; Humans; Kidney Transplantation
PubMed: 29983261
DOI: 10.1016/j.trre.2018.06.003 -
Archives of Razi Institute Apr 2022The liver and kidney are the most important organs in the body, and they both act as target structures for drug-induced injury as a consequence of their functions in...
The liver and kidney are the most important organs in the body, and they both act as target structures for drug-induced injury as a consequence of their functions in metabolisms, detoxifications, storage, elimination of medications, and their metabolites. The present study aimed to examine the role of the natural and free radical scavenger "CoQ10" against diclofenac-induced hepatic and renal tissue injury. In total, 36 adult Wistar rats were randomly divided into three equal groups (n=12). The animals in the control group did not receive any medication or treatments, and the second group included animals that received intramuscular (IM) injection of Diclofenac (DF) (at a dose of 10 mg/kg once daily for 14 days). Moreover, the third group was given the IM injection of DF (at a dose of 10 mg/kg once daily for 14 days) +CoQ10. After 14 days, DF prompted signified hepatic and renal injury indicated by elevated biochemical parameters, such as total serum bilirubin, alkaline phosphatase, aspartate aminotransferase, alanine aminotransferase, blood urea nitrogen, creatinine, and uric acid, compared to the control and the third group. However, the group that received Diclofenac+CoQ10 had significantly lower hepatic and renal dysfunctions, compared to the second treated group. DF toxic effects could be the consequences of mitochondrial dysfunction and free radical effects. Remarkably, therapeutic supplementation of CoQ10 diminished the DF-induced toxic oxidative injury and apoptotic cell death. The protective effects of CoQ10 were attributed to its antioxidants and free radical scavenger activity.
Topics: Rats; Animals; Diclofenac; Alanine Transaminase; Free Radical Scavengers; Creatinine; Uric Acid; Alkaline Phosphatase; Rats, Wistar; Aspartate Aminotransferases; Bilirubin
PubMed: 36284948
DOI: 10.22092/ARI.2022.357210.1998 -
American Journal of Physiology.... Jun 2018The buildup of fat in the liver (hepatic steatosis) is the first step in a series of incidents that may drive hepatic disease. Obesity is the leading cause of... (Review)
Review
The buildup of fat in the liver (hepatic steatosis) is the first step in a series of incidents that may drive hepatic disease. Obesity is the leading cause of nonalcoholic fatty liver disease (NAFLD), in which hepatic steatosis progresses to liver disease. Chronic alcohol exposure also induces fat accumulation in the liver and shares numerous similarities to obesity-induced NAFLD. Regardless of whether hepatic steatosis is due to obesity or long-term alcohol use, it still may lead to hepatic fibrosis, cirrhosis, or possibly hepatocellular carcinoma. The antioxidant bilirubin and the enzyme that generates it, biliverdin reductase A (BVRA), are components of the heme catabolic pathway that have been shown to reduce hepatic steatosis. This review discusses the roles for bilirubin and BVRA in the prevention of steatosis, their functions in the later stages of liver disease, and their potential therapeutic application.
Topics: Bilirubin; Disease Progression; Fatty Liver; Humans; Liver Cirrhosis; Oxidoreductases Acting on CH-CH Group Donors; Protective Agents
PubMed: 29494209
DOI: 10.1152/ajpgi.00026.2018