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Objectives: Bilirubin is a potent endogenous antioxidant and immunomodulating substance, which is also implicated in both cell signalling and various metabolic pathways. Mild elevation of systemic bilirubin concentrations provides substantial protection against many diseases of civilization. Rare published reports have suggested that serum bilirubin might also be relevant to sports performance. The purpose of the current study was to evaluate serum bilirubin concentrations and the prevalence of Gilbert syndrome (GS) in elite athletes., Methods: The study was carried out in 536 consecutive healthy elite athletes and in 2594 individuals of the Czech post-MONICA study representing the general Czech population. Serum bilirubin concentrations, the prevalence of benign hyperbilirubinemia > 17 µmol/L (1 mg/dL, a phenotypic sign of GS), and a variant of the UGT1A1 gene promoter responsible for GS manifestation in Caucasians (rs81753472) were evaluated in study subjects., Results: Compared to the general Czech population, significantly higher serum bilirubin concentrations were found in elite athletes (9.6 vs. 11.6 µmol/L, p < 0.001), both in men (11.3 vs. 12.6 µmol/L, p < 0.001) and women (8.3 vs. 10.5 µmol/L, p < 0.001). Furthermore, the prevalence of GS was also significantly higher in elite athletes (9.6 vs. 22%, p < 0.001) together with the tendency to higher frequencies of the genotypes (TA) 7/7 and (TA) 6/7 UGT1A1., Conclusion: Elite athletes have significantly higher concentrations of serum bilirubin, the most potent endogenous antioxidant substance known. Simultaneously, the prevalence of GS syndrome is also much higher in elite athletes, suggesting that a mild elevation of serum bilirubin might predispose to better sports performance., (© 2022. The Author(s).)

Background: The aim of this study was to examine the diurnal and exercise-related changes in red blood cell variables which serve as indirect markers of doping in sports., Methods: Ten men and 7 women, all undoped highly trained endurance athletes aged 19-34 years, were included in the study. Before and on the day with single and repeated bouts of exercise, blood samples were collected at 07:00, 09:00, 13:00, 18:00, and 21:00, at least 2 hours after exercise. Hemoglobin (Hb), hematocrit (Hct), and the reticulocytes % (Ret%) were determined by flow cytometry. Changes in OFF-hr score were also calculated and repeated-measures ANOVA was used to compare diurnal differences., Results: In overall, the mean Hb decreased continuously by 4.5 and 3.3% (all P<0.001) over the day with single and repeated bouts of exercise, respectively. Corresponding values for the decline in Hct were 4.2 and 5.9% (all P<0.001). In contrast, the Ret% showed no apparent diurnal rhythm but single and repeated bouts of exercise increased the relative Ret% in the evening by 12.4 and 16.7% (P<0.01), respectively. Then the calculated OFF-hr score was reduced by 6.2 and 9.8% (all P<0.01) at the end of the day., Conclusions: These results confirmed the normal diurnal pattern in the examined red blood cell variables in response to exercise in highly trained athletes. Furthermore, they showed noticeable between-subject variability and the possible risk of a false suspicion of blood doping in undoped athletes after repeated bouts of exercise.

Background: Unwarranted administration of antibiotics in acute pancreatitis presents a global challenge. The clinical reasoning behind the misuse is poorly understood. Our aim was to investigate current clinical practices and develop recommendations that guide clinicians in prescribing antibiotic treatment in acute pancreatitis., Methods: Four methods were used. 1) Systematic data collection was performed to summarize current evidence; 2) a retrospective questionnaire was developed to understand the current global clinical practice; 3) five years of prospectively collected data were analysed to identify the clinical parameters used by medical teams in the decision making process, and finally; 4) the UpToDate Grading of Recommendations, Assessment, Development and Evaluation (GRADE) system was applied to provide evidence based recommendations for healthcare professionals., Results: The systematic literature search revealed no consensus on the start of AB therapy in patients with no bacterial culture test. Retrospective data collection on 9728 patients from 22 countries indicated a wide range (31-82%) of antibiotic use frequency in AP. Analysis of 56 variables from 962 patients showed that clinicians initiate antibiotic therapy based on increased WBC and/or elevated CRP, lipase and amylase levels. The above mentioned four laboratory parameters showed no association with infection in the early phase of acute pancreatitis. Instead, procalcitonin levels proved to be a better biomarker of early infection. Patients with suspected infection because of fever had no benefit from antibiotic therapy., Conclusions: The authors formulated four consensus statements to urge reduction of unjustified antibiotic treatment in acute pancreatitis and to use procalcitonin rather than WBC or CRP as biomarkers to guide decision-making., (Copyright © 2019 IAP and EPC. Published by Elsevier B.V. All rights reserved.)

In recent years, gastroenterologists focused their interest on finding the genetic background of inflammatory bowel disease and colon cancer. NOD2/ CARD15 gene is still the most investigated gene of all known genes and its mutations can explain approximately 20% of genetic predisposition to Crohns disease. From later identified genes that play an important role in the etiology of Crohns disease, the IL23R and ATG16L1 genes have a perspective place. In the case of hereditary colorectal cancer, we can select by the help of genetic diagnostics, the group of patients with high risk of colon cancer, which requires more intensive monitoring. The aim is to find out the colon cancer in the early, treatable stage. In practical terms, genetic diagnostics of inflammatory bowel disease and colon cancer has no screening and only poor prognostic importance. It is pleasant, that the Slovak genetic workplaces are interested in this issue and in accordance with modern trends they try to expand its diapason.

For the primary prophylaxis of variceal bleeding endoscopic band ligation has been shown to be as effective as non-selective beta-blockers (carvedilol), but variceal injection sclerotherapy is not generaly recommended in this setting because of higher rate of complications and lower effect in reducing either bleeding or mortality. Endoscopic management of acutely bleeding gastroesophageal varices includes injection sclerotherapy, rubber band ligation, and variceal obturation with tissue adhesives. Variceal injection sclerotherapy remains a quick, simple and cheap technique for the control of active bleeding from esophageal varices, but is associated with more rebleeding than variceal band ligation, which is now preferred also for lower rate of complications. Endoscopic sclerotherapy has increasingly been replaced by ligation also in secondary prophylaxis of variceal bleeding. The studies showed that band ligation can eradicate varices in fewer sessions, re-bleeding and complications were fewer in comparison with variceal injection sclerotherapy. Because of the reduced efficacy, severe complications, and the high mortality associated with using conventional sclerosants in acute bleeding gastric varices, the technique of injecting tissue adhesives has been studied, described and used despite numerous complications. Endoscopic injection sclerotherapy of esophageal varices remains usable as an oldest method in arresting of this hemorrhage only in rare cases when the band ligation is not available.

Background: Comparative data regarding different regimens of oral mesalazine (mesalamine) for maintaining remission in ulcerative colitis are limited., Aim: To evaluate whether 3.0 g mesalazine once-daily (OD) is superior to the standard treatment of 0.5 g mesalazine three times daily (t.d.s.) and to prove the therapeutic equivalence of OD vs. t.d.s. dosing of total 1.5 g mesalazine for remission maintenance in patients with ulcerative colitis., Methods: A 1-year, multicentre, double-blind, double-dummy study was undertaken in patients with endoscopically and histologically confirmed ulcerative colitis in remission. Patients were randomised to oral mesalazine 3.0 g OD, 1.5 g OD or 0.5 g t.d.s. The primary efficacy endpoint was the proportion of patients still in clinical remission at the final visit, with clinical relapse being defined as CAI score >4 and an increase of ≥3 from baseline., Results: The primary efficacy endpoint occurred in 162/217 3.0 g OD patients (75%), 129/212 1.5 g OD patients (61%) and 150/218 0.5 g t.d.s. patients (69%) in the intention-to-treat population, and in 152/177 (86%), 121/182 (67%) and 144/185 (78%) in the per protocol population respectively; 3.0 g OD was superior to both low-dose regimens for the primary endpoint (i.e. P < 0.001, 3.0 g OD vs. 1.5 g OD; P = 0.024, 3.0 g OD vs. 0.5 g t.d.s.; superiority test, per protocol population). Safety analysis, including comprehensive renal monitoring, revealed no concern in any treatment group., Conclusion: Mesalazine 3.0 g once daily was the most effective dose for maintenance of remission in ulcerative colitis of the three regimens assessed, with no penalty in terms of safety., (© 2010 Blackwell Publishing Ltd.)

Background & Aims: Comparative data on budesonide vs mesalamine for the treatment of mild-to-moderately active Crohn's disease (CD) are sparse. We assessed the efficacy and safety of each therapy in patients with mildly to moderately active CD., Methods: We performed a randomized, double-blind, double-dummy, 8-week, multicenter study in which 309 patients with mildly to moderately active CD received pH-modified-release oral budesonide (9 mg/day once daily or 3 mg/day 3 times daily) or Eudragit-L-coated oral mesalamine (4.5 g/day)., Results: The primary efficacy variable, clinical remission (defined as Crohn's Disease Activity Index ≤150), at the final visit occurred in 69.5% (107 of 154) of patients given budesonide vs 62.1% (95 of 153) of patients given mesalamine (difference, 7.4%; 95% repeated confidence interval, -4.6% to 18.0%; P = .001 for noninferiority). Clinical remission rates did not differ significantly between the 2 budesonide groups. Treatment response, defined as Crohn's Disease Activity Index of 150 or less and/or a decrease of 70 or more (Δ70) or 100 or more (Δ100) points from baseline to final visit, did not differ significantly between patients given budesonide vs mesalamine (Δ70, P = .11; Δ100, P = .15), or between the 2 budesonide groups (Δ70, P = .38; Δ100, P = .78). No other efficacy end points differed significantly between groups. Discontinuation because of adverse events occurred in 3% and 5% of budesonide- and mesalamine-treated patients, respectively. There were no clinically relevant differences in adverse events between the 2 budesonide groups., Conclusions: Budesonide (9 mg/day) was numerically, but not statistically, more effective than Eudragit-L-coated mesalamine (4.5 g/day) in patients with mildly to moderately active CD. Budesonide (9 mg/day), administered once daily, was as effective as the standard (3 times daily) regimen., (Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.)

Involvement of genetic factors in the aetiology of inflammatory bowel disease (IBD) has been known for a long time. Our aim was to investigate the prevalence of polymorphisms in NOD2, ICAM-1 and CCR5 genes in Czech and Slovak patients with IBD in comparison with healthy controls. The frequency of well-known mutations (R702W, G908W and 1007fs in the NOD2 gene; K469E in the ICAM-1 gene, and Delta32 in the CCR5 gene) involved in IBD was tested in 45 patients with CD and 22 patients with UC. The allele frequency of these mutations was determined and genotype-phenotype correlation was specified. Isolated DNA was genotyped, and allele frequency was counted and statistically verified. Significant differences between the healthy control group and CD patients were observed in mutation 1007fs of the NOD2 gene (P = 0.0203). We also associated allele E469 of the ICAM-1 gene with CD (P = 0.0024). No significant association between other alleles and CD was found, and no gene variation was linked to UC. The number of mutations and mutated genes was higher among patients with CD than among patients with UC. Our results support previous findings about participation of mutations of NOD2 and ICAM-1 genes in IBD. We confirmed that both CD and UC are polygenic diseases with a genedosage effect. This observation strengthens the opinion that genetic factors play a more important role in CD than in UC.

Background: There are no comparative studies of coated mesalazine., Aim: To compare the efficacy and tolerability of Eudragit-L- and ethylcellulose-coated mesalazine tablets in patients with mild to moderately active ulcerative colitis., Methods: A double-blind, double-dummy, randomized parallel group trial was performed across 18 centres in Australia, and 20 in Eastern Europe. Patients were treated with 3 g mesalazine for 8 weeks with the primary efficacy end point being clinical remission., Results: Of 215 patients, 69% achieved clinical remission in both treatment groups (P < 0.001; chi-square test) with no differences in frequency of adverse events. In the Australian cohort (n = 63), the Eudragit-L group had a higher remission rate (73% vs. 36%) and responded 13 days faster, compared with those in the European group (67% vs. 84%, and 2 days respectively). No clear reasons for differences in treatment responses were identified., Conclusions: Eudragit-L and ethylcellulose-coated mesalazine tablets are well tolerated and equally effective in achieving remission in mild-moderately active ulcerative colitis over 8 weeks.

Background: Mesalazine as the treatment standard for ulcerative colitis can be applied in different galenical preparations., Aim: A novel formulation of mesalazine pellets with delayed and prolonged release characteristics was compared with conventional Eudragit L-coated tablets. Furthermore, the effect of mesalazine dose escalation on nonresponders was evaluated in both treatment groups., Methods: A total of 233 patients with mild to moderately active ulcerative colitis were randomized to receive either mesalazine (1.5 g/day in three doses) as pellets (n = 115) or tablets (n = 118) for 8 weeks. At insufficient response, the dose was increased to 3.0 g., Results: The clinical remission rate (clinical activity index < or = 4) for pellets was 67% vs. 68% for tablets which statistically proved to be not inferior (significance level alpha = 2.5%). In patients without dose increase, the remission rate was 47% (pellets) vs. 42% (tablets). Endoscopic improvement was observed in 80% (pellets) vs. 83% (tablets), and histological improvement in 48% (pellets) vs. 52% (tablets) of patients., Conclusions: Mesalazine pellets are as effective as tablets in the treatment of mild to moderately active ulcerative colitis. Dose escalation to 3.0 g/day is a valid option for nonresponders to a starting dose of 1.5 g/day.

Background: Reactive types of oxygen play an important part also in carcinogenesis. Antioxidant enzymes are the primary defence against their damage. The objective of the present work was to glutathione peroxidase in the mucosa and polyps of the colon in subjects with colorectal adenoma and idiopathic proctocolitis., Methods and Results: The authors examined 18 controls, 43 patients with colorectal adenoma and 12 subjects with idiopathic proctocolitis. During endoscopy bioptic specimens of the mucosa and from polyps were taken for histological and enzymological examination: Cu/Zn superoxide dismutase, catalase, glutathione peroxidase. In subjects with colorectal adenoma a raised glutathione peroxidase activity was found in the colon and an elevated activity of superoxide dismutase in the adenoma. In patients with idiopathic proctocolitis in the stage of clinical remission in the mucosa a lower glutathione peroxidase activity was found but a high activity of all enzymes was recorded in the inflamed polyps., Conclusions: The cause of elevated activities of antioxidant enzymes in subjects with colorectal adenoma in the colonic mucosa and in adenomas is not known and calls for further studies. In patients with idiopathic proctocolitis the increased level of antioxidant enzymes in the mucosa is probably produced by a higher production of reactive oxygen types by activated leucocytes in the inflamed tissues.

Background: The etiopathogenic relationship of Helicobacter pylori (HP) infection to chronic active antrumgastritis and peptic ulcer disease has been confirmed by a number of studies. The key role in the development of peptic lesions belongs to hypergastrinemia. This is supposed to be related to ammonium synthesis in the antral area influenced (promoted by HP and resulting in interruption) weakening of the negative feedback mechanism maintaining intraluminal acidity., Objectives: In our present study we focus our attention to the effectiveness of triple antimicrobial therapy in HP positive patients with chronic active antrumgastritis residing in the lowering of the level of serum gastrin., Methods: There was a group of 15 patients in our current study with HP positivity as well as chronic active antrumgastritis documented by endoscopy, histology, microbiology and serology respectively. Endoscopical and histological findings were classified according to "The Sydney System". The whole group was evaluated on an ambulatory basis, those with active ulcer, endocrinopathy and biliary tract disorders were excluded. The basal level of serum gastrin was evaluated by RIA-test-gastrin before and after successful antimicrobial therapy., Results: In our group of 15 patients with HP infection in coexistence with chronic active antrumgastritis we have found a significant decrease in the basal level of serum gastrin (p = 0,01) after successful therapy., Conclusion: The decrease in the basal level of serum gastrin after eradication of HP confirms the importance of HP infection in the pathogenesis of peptic lesions in stomach and duodenum. We consider the antimicrobial therapy in chronic active antrumgastritis in HP positive patients to be a fully indicated therapeutic approach. (Tab. 1, Fig. 1, Ref. 10.).

Most colon carcinomas are preceded by an adenomatous polyp--adenoma-carcinoma sequence. Active oxygen species (AOS) can play a role in the pathogenesis of this process. Antioxidant enzymes (AE) are the primary defense against the deleterious effect of AOS. Activities of AE in 56 individuals with colorectal adenoma (CA), 29 individuals with colorectal carcinoma (CC) and in 24 control subjects were examined. Biopsy specimens from the non-neoplastic colonic mucosa and from the CA and CC were taken during colonoscopy for histological and enzymological analysis. Activities of following AE were estimated: CuZn-superoxide dismutase (CuZn-SOD), catalase (CAT) and glutathione peroxidase (GPx). It was found that individuals with CA and CC were characterized by: (1) increased activities of CAT and GPx in non-neoplastic mucosa, that persisted in some of the patients even after removal of tumors; (2) increased activities of CuZn-SOD, CAT and PGx in CA and CC tissues. It can be inferred that the accumulation of peroxides in the non-neoplastic colonic mucosa induced higher activities of CAT and GPx. The reasons of high activities of all AE in the tissues of CA and CC and their relation to carcinogenesis are not clear and require further studies.

A group of patients younger than 40 years of age, who had been subdued to endoscopic large intestine adenoma polypectomy were compared with the rest of the patients regarding the adenoma occurrence according to sex, localisation, histologic character, frequency of recurrence, and carcinoma formation in the large intestine in the site of previous polypectomy. The compared groups of patients differed merely in time of recurrence. In patients over 40 years of age the adenomas reoccurred most frequently in the first and fifth years following the primary polypectomy. In patients after primary polypectomy regular colonoscopic controls were suggested, namely after the first year and subsequently after every two years. This scheme is appropriate also for patients under the age of 40 years. Therefore the recommended intervals of colonoscopic controls at this age category do not require to be subdued to alteration. (Tab. 14, Ref. 5.)

Background: The primary defense against oxidation damage of tissues are anti-oxidant enzymes, e.g. superoxide dismutase, catalase and glutathione peroxidase. Some non-enzymatic substances have a significant anti-oxidant action (e.g. vitamin C, E, beta-carotene and others). The objective of the present work was to follow up the Cu/Zn superoxide dismutase activity, catalase and glutathione peroxidase (anti-oxidant enzymes of the gastric mucosa) in subjects with the risk of developing gastric cancer, e.g. those suffering from atrophic gastritis, hyperplastic polyps and gastric adenoma., Methods and Results: The authors examined 80 subjects (50 men and 30 women) aged 25 - 71 years. In all during endoscopic examination bioptic specimens of the mucosa were taken at standard sites of the gastric corpus and antrum for histological and enzymological examination. Enzymological examination: activity of Cu/Zn-superoxide dismutase (Randox Lab. Ltd. GB kit), catalase activity (modified method of Cavarocchia et al.) and glutathione peroxidase activity (method according to Paglia and Valentine). The Cu/Zn-superoxide dismutase activity was elevated in the group of patients with gastritis after gastrectomy (67%) and with gastric adenoma (35%), the catalase activity in patients with gastritis after gastrectomy (40%) and the glutathione peroxidase activity in patients with the diagnosis of gastritis after gastrectomy (185%), atrophic gastritis (46%) hyperplastic polyp (50%) and gastric adenoma (50%)., Conclusions: The increased activity of anti-oxidant enzymes was due to a higher concentration of the superoxide anion radical, hydrogen peroxide and organic peroxides (lipoperoxides); the source of active types of oxygen are phagocytic leucocytes in the chronically inflamed gastric mucosa.

In a prospective study based on contemporary knowledge of the problem of gastrooesophageal varices the authors submit the algorithm of the therapeutic procedure. Sclerotization treatment holds a dominant position, as it can be used in all stages of the disease and in all three groups of patients classified according to Child. In case of gastric varicosities which cannot be treated by sclerotization the method of choice in patients of groups Child A, B are ablative operations and selective portosystemic anastomoses, in concurrent hypersplein: azygo-portal separation.

The authors present their experience with the outcome of gastrofibroscopic sclerotherapy of oesophageal varices, performed in a total of 70 patients with portal hypertension. All patients were classified in classes B and C according to Child's criteria, and 68 of them had variceal bleeding before receiving sclerotherapy. Acute bleeding was successfully arrested in seven cases, and elective sclerotherapy in between bleeding episodes was carried out in 60 cases. To date, complete obliteration has been noted in 34 patients. An effect of previous sclerotherapy was observed during the next therapeutic session in 18, and eight patients died from progressive hepatic insufficiency. In the discussion section, the authors analyse current concepts on the technique of sclerotherapy related to complications, on instrumentarium and sclerosing solutions, and on the significance of prophylactic, acute and elective sclerotherapy, with the importance of endoscopic sclerotherapy of oesophageal varices perceived mainly in comparison with the results of surgery from the point of view of long-term patient survival.

The authors performed from 1983 86 gastrofiberoscopic diathermocoagulations and 132 colonoscopic polypectomies. The finding of the high number of adenomas in the stomach - 22.35%/63.15% in diameter to 10 mm/-is surprising. As to complications they recorded in one case mucosal bleeding after gastrofiberoptic polypectomy and in one case a covered perforation of the sigmoid at the site of colonoscopic polypectomy. The discussion is devoted to the present views of the importance of the endoscopic polypectomy in the diagnosis and treatment of polyps in the gastrointestinal tract with the accentuation of the problems of the endoscopic polypectomy from the proximal part of the digestive tube. The authors state the necessity to keep this method for removal of the gastric hyperplasiogenous polyps and the polyps to 10 mm in diameter. Finally, the advantages of the endoscopic polypectomy: unpretentiousness, no risk for patient, high diagnostic and therapeutic value and the economy, as compared with transabdominal surgical approach, are stressed.

The authors performed a total of 288 successful endoscopic gastroduodenal polypectomy procedures in 129 patients. Drawing on literary data and the results of follow-up of their own patients, they regard endoscopic gastroduodenal polypectomy as a successful and relatively low-risk method for secondary prevention of gastric cancer. Recurrence of adenomas, with malignant degeneration in 6-75%, was noted, only in the first year after primary polypectomy, in 8% of patients. Four percent of patients after adenoma polypectomy developed gastric carcinoma. Removal of gastroduodenal adenomas by endoscopy represents a final therapeutic procedure significantly reducing the possibility of these originally benign variants transforming into malignant ones. Even polyps smaller than 10 mm in diameter may be adenomas possessing a rather high malignant potential. The authors regard endoscopic polypectomy of hyperplastic polyps as a justified procedure since the literary data compiled and their own experience suggest polyp susceptibility to development of dysplasia. While this tendency gets manifest only rarely, it would be medically wrong to dismiss it as negligible. In case of removal of an early polypoid gastric carcinoma, endoscopic polypectomy is a therapeutic procedure only in clearly defined and histologically well classified cases. In other cases involving prominence of the gastroduodenal mucosa, it is an invaluable diagnostic method whose benefit is that it removes an entire polyp for histologic examination.

The authors report on their experience with endoscopic treatment of choledocholithiasis. Out of a total of 363 successful procedures of endoscopic papillosphincterotomy (EPS), choledocholithiasis was the indication for EPS in 270 patients (74.4%). Most often, EPS and extraction were performed in patients after cholecystectomy (79.6%) and those with choledocholithiasis and an in situ gallbladder, but free of stones (13.4%). In patients with concomitant cholecystolithiasis, EPS was carried out only in those cases in which surgery was contraindicated. EPS was performed in four cases of acute biliary pancreatitis. Removal of stones from the choledochus was successful in 95.5%. Of the total of 363 successful EPS's, complications were observed in 17 cases (4.7%), with a mortality of 1.1% (4 deaths). Most frequently, the causes included bleeding (1.9%) and perforation (1.1%). Of other complications, the authors noted acute pancreatitis, acute cholangitis and impaction of stone in the hepatocholedochus in two cases each. The complications required emergency surgery in six patients (35.3%).

Background: Studies about the association between bilirubin and migraine were few. Therefore, the purpose of this study was to investigate the association between serum total bilirubin and the prevalence of severe headaches or migraine., Methods: A multivariable logistic regression was used to assess the association between serum total bilirubin concentration and severe headaches or migraine. We also performed stratified analyses, interaction analyses and multiple interpolations in the sensitivity analysis., Results: This cross-sectional study included 12,552 adults from the National Health and Nutrition Examination Survey (NHANES) from 1999 to 2004. The overall incidence of migraine was 19.99% (2,509/12,552). With every 1 mg/dl increase in bilirubin, the prevalence of migraine decreased by 23% (95% CI: 0.64, 0.93) after adjustment of all related covariates. Similarly, the risk of migraine was reduced by 17% (95% CI: 0.72, 0.97) in the Q4 group (the fourth quartile, highest serum total bilirubin level) compared with the Q1 group (the lowest level). Furthermore, interaction effects by age groups were significant in this relationship (P for interaction = 0.0004). In the Q4 group compared with Q1, inverse associations were observed in those aged ≥40 years (OR: 0.71,95% CI: 0.59, 0.85) in the stratified analysis., Conclusion: These findings support an association between serum total bilirubin and severe headaches or migraine, revealing an inverse association between serum total bilirubin quartiles and severe headaches or migraine in American adults. Age could play an important role in this association., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)