Phthalate and gallstones: the mediation of insulin.

Background: Exposure to a mixture of environmental chemicals may cause gallstone, but the evidence remains equivocal. The current study aims to investigate the association between phthalate metabolites and gallstones, and to explore their mediators. Methods: Data from the National Health and Nutrition Examination Survey 2017-2018 on U.S. adults (≥20 years) were analyzed to explore the association between phthalate metabolites and gallstones by employed survey-weighted logistic regression, restricted cubic spline (RCS), weighted quantile sum (WQS) regression, and Bayesian kernel machine regression (BKMR). Mediation analyses examined the role of oxidative stress markers, inflammatory markers, metabolic syndrome, body composition, diabetes, and insulin. Results: The current study included 1,384 participants, representing 200.6 million U.S. adults. Our results indicated a significant association between phthalate metabolites, particularly high molecular weight metabolites such as Di(2-ethylhexyl) phthalate (DEHP) and 1,2-Cyclohexane dicarboxylic acid diisononyl ester (DINCH), and gallstones. Furthermore, mediation analyses indicated that phthalate metabolites may play a role in the development of gallstones by influencing insulin secretion. Subgroup analyses did not reveal significant interaction. Conclusion: The association between exposure to phthalates and the occurrence of gallstones, potentially mediated by hyperinsulinemia from a nationally representative epidemiological perspective. These insights contribute to a better understanding of the potential health implications of plasticizers, emphasizing the need for proactive management measures.

Menopausal hormone therapy increases the risk of gallstones: Health Insurance Database in South Korea (HISK)-based cohort study.

OBJECTIVE: To determine whether menopausal hormone therapy (MHT) increases the risk of gallstones and gallbladder cancer. DESIGN: A retrospective cohort study. PATIENTS OR OTHER PARTICIPANTS: Data from the Korea National Health Insurance Corporation was obtained between January 1, 2002, and December 31, 2019. INTERVENTIONS: Participants were divided into MHT and non-MHT groups; the MHT group was analyzed in detail by dividing participants into tibolone, combined estrogen plus progestin by the manufacturer (CEPM) or physician (CEPP), oral estrogen alone, and topical estrogen subgroups. MAIN OUTCOME MEASURES: The incidence of gallstones and gallbladder cancer was compared between the two groups. RESULTS: This study enrolled 1,004,034 and 381,711 patients in the non-MHT and the MHT groups, respectively. The incidence of gallstones was 2.6% in the non-MHT group and 3.4%, 2.6%, 3.4%, 3.2%, and 4.4% in the tibolone, CEPM, oral estrogen alone, CEPP, and topical estrogen groups, respectively. Cox proportional hazard analysis revealed that all hormones increased the risk of gallstones ([tibolone] hazard ratio [HR]: 1.347, 95% confidence interval [CI]: 1.309-1.387, [CEPM] HR: 1.146, 95% CI: 1.1-1.19, [oral estrogen alone] HR: 1.241, 95% CI: 1.18-1.305, [CEPP] HR: 1.164, 95% CI: 1.01-1.341, [topical estrogen] HR: 1.602, 95% CI: 1.295-1.983). However, the risk of gallbladder cancer did not change with any hormone therapy. CONCLUSIONS: All types of MHT including tibolone, increased the risk of gallstones. This risk was the highest with topical estrogen, which may be a result of selection bias due to concerns regarding the adverse effects of CEE and MPA.

Associations of long-term exposure to particulate matter with gallstone risks in Chinese adults: A large cross-sectional study.

BACKGROUND: Epidemiological evidence regarding the relation of exposure to ambient particulate matter (PM) with gallstone disease (GSD) risk remains lacking. We tested the hypothesis that long-term exposure to PM is related to the development of GSD and that dyslipidemia can mediate the effect of PM-associated GSD formation. METHODS: We extracted related information on the basis of the baseline survey of the China Multi-Ethnic Cohort Study. The exposure levels of PM (PM1, PM2.5, and PM10) were assessed by validated spatiotemporal models. The relation of exposure to ambient PM with GSD risks was analyzed by non-conditional logistic regression models. Additionally, mediation analysis was conducted to assess whether dyslipidemia was related to the relation of PM exposure with GSD risks. RESULTS: A total of 72,893 participants were included. Increased ambient PM exposure was positively associated with a higher GSD risk, with ORs (and 95% CI) of 1.17 (1.06, 1.28), 1.10 (1.05, 1.15), and 1.07 (1.04, 1.10) for every 10 µg/m3 increment in PM1, PM2.5, and PM10, separately. The association was more remarkable in males, drinkers, and central obesity participants. Dyslipidemia significantly mediated the association between PM and GSD, with mediating proportions of 5.37%, 9.13%, and 7.66% in PM1, PM2.5, and PM10, respectively. CONCLUSION: Exposure to PM may relate to the increased risk of GSD in Chinese adults, especially among males, drinkers, and central obesity participants. Dyslipidemia may partially mediate the effect of PM-associated GSD development. Our results might provide epidemiological evidence for the progression of GSD related to PM and give new insights into GSD prevention and screening priorities.

Complicaciones por pseudolitiasis vesicular y nefrolitiasis asociada a ceftriaxona. Reporte de caso / No disponible

INTRODUCCIÓN: La ceftriaxona es un antibiótico de amplio espectro frecuentemente utilizado en pediatría. La pseudolitiasis vesicular es un efecto adverso bien conocido que se presenta en un 15 a 57% de los casos. En cambio, la litiasis renal es extremadamente infrecuente, con muy pocas publicaciones al respecto. CASO CLÍNICO: Se presenta el caso de un paciente de 9 años que, durante tratamiento con ceftriaxona por una apendicitis aguda complicada, desarrolla pseudolitiasis vesicular y urinaria. Durante la misma internación el paciente presenta una pancreatitis leve y una ureterohidro-nefrosis bilateral, con insuficiencia renal aguda, como complicaciones de las pseudolitiasis. COMENTARIOS: La sospecha de la formación de litiasis renal y/o vesicular asociada al uso de ceftriaxona es fundamental para un diagnóstico temprano y prevención de complicaciones como las reportadas en este paciente, siendo fundamental la suspensión precoz del fármaco como inicio del tratamiento

INTRODUCTION: Ceftriaxone is a wide-spectrum antibiotic frequently used in pediatrics. Biliary pseudolithiasis is a well-known side-effect occurring in 15-57% of cases. However, nephrolithiasis is extremely infrequent, with very few related publications. CASE REPORT: We present the case of a 9-year-old patient with ceftriaxone-treated complicated acute appendicitis who developed biliary pseudolithiasis and nephrolithiasis. During hospitalization, the patient presented with pseudolithiasis complications such as mild pancreatitis and bilateral ureterohydronephrosis with acute renal failure. REMARKS: Suspecting ceftriaxone-associated biliary pseudolithiasis and/or nephrolithiasis is key to achieve an early diagnosis and prevent complications such as those reported in this patient. Early discontinuation is essential as an initial treatment measure

A novel GPER antagonist protects against the formation of estrogen-induced cholesterol gallstones in female mice.

Many clinical studies and epidemiological investigations have clearly demonstrated that women are twice as likely to develop cholesterol gallstones as men, and oral contraceptives and other estrogen therapies dramatically increase that risk. Further, animal studies have revealed that estrogen promotes cholesterol gallstone formation through the estrogen receptor (ER) α, but not ERß, pathway. More importantly, some genetic and pathophysiological studies have found that G protein-coupled estrogen receptor (GPER) 1 is a new gallstone gene, Lith18, on chromosome 5 in mice and produces additional lithogenic actions, working independently of ERα, to markedly increase cholelithogenesis in female mice. Based on computational modeling of GPER, a novel series of GPER-selective antagonists were designed, synthesized, and subsequently assessed for their therapeutic effects via calcium mobilization, cAMP, and ERα and ERß fluorescence polarization binding assays. From this series of compounds, one new compound, 2-cyclohexyl-4-isopropyl-N-(4-methoxybenzyl)aniline (CIMBA), exhibits superior antagonism and selectivity exclusively for GPER. Furthermore, CIMBA reduces the formation of 17ß-estradiol-induced gallstones in a dose-dependent manner in ovariectomized mice fed a lithogenic diet for 8 weeks. At 32 µg/day/kg CIMBA, no gallstones are found, even in ovariectomized ERα (-/-) mice treated with 6 µg/day 17ß-estradiol and fed the lithogenic diet for 8 weeks. In conclusion, CIMBA treatment protects against the formation of estrogen-induced cholesterol gallstones by inhibiting the GPER signaling pathway in female mice. CIMBA may thus be a new agent for effectively treating cholesterol gallstone disease in women.

Effects of Liraglutide Compared With Placebo on Events of Acute Gallbladder or Biliary Disease in Patients With Type 2 Diabetes at High Risk for Cardiovascular Events in the LEADER Randomized Trial.

OBJECTIVE: To explore gallbladder- and biliary tract-related events reported for the liraglutide and placebo groups in the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial. RESEARCH DESIGN AND METHODS: LEADER was an international, randomized, double-blind, controlled cardiovascular (CV) outcomes trial. Participants with type 2 diabetes at high risk for CV events (n = 9,340) were randomized 1:1 to receive either liraglutide (≤1.8 mg daily; n = 4,668) or placebo (n = 4,672), with both groups also receiving standard care (treatment period: 3.5-5 years). Acute gallstone disease was a medical event of special interest. This post hoc analysis categorized captured events of acute gallbladder or biliary disease into four groups: uncomplicated gallbladder stones, complicated gallbladder stones, cholecystitis, and biliary obstruction. Time to first event by treatment group was analyzed using Cox regression. RESULTS: There was an increased risk of acute gallbladder or biliary disease with liraglutide versus placebo (n = 141 of 4,668 vs. n = 88 of 4,672 patients, respectively; hazard ratio [HR] 1.60; 95% CI 1.23, 2.09; P < 0.001). Similar trends were observed for each of the four categories of gallbladder- or biliary tract-related events. Cholecystectomy was performed more frequently in liraglutide-treated patients (HR 1.56; 95% CI 1.10, 2.20; P = 0.013) but for similar proportions of the patients who experienced gallbladder- or biliary tract-related events (57% with liraglutide vs. 59% with placebo). CONCLUSIONS: Although LEADER was not specifically designed to assess acute gallbladder or biliary disease, the trial showed an increased risk of gallbladder- or biliary tract-related events with liraglutide versus placebo, which appeared to be consistent across four categories of these events. Further studies should investigate the relevant mechanisms.

Experimental verification of factors influencing calcium salt formation based on a survey of the development of ceftriaxone-induced gallstone-related disorder.

Ceftriaxone (CTRX) forms salts with calcium (Ca) in the gall bladder and bile duct, and induces the formation of gallstones. In this study, factors of CTRX-induced gallstone formation were extracted from the results of a retrospective survey using the Japanese Adverse Drug Event Report (JADER), and the causal relationship between the factors and gallstone formation was investigated. From JADER, 136 patients who developed 'gallstone-related disorder' with CTRX as a suspected drug were extracted. The incidence of gallstone-induced adverse effects was high in patients treated with CTRX at a dose exceeding the normal daily dose and in children younger than 10 years old, suggesting that CTRX at a high level is a factor for gallstone formation. Thus, after mixing CTRX and Ca2+ at different concentrations under different pH condition, the number of particles in the solutions was measured using a Coulter counter. As a result, the number of minute particles significantly increased at all pH values when Ca2+ and CTRX were mixed at a concentration of 10 mEq/L or higher and 1.5 g/L or higher, respectively. At pH 6.5 or 7.0, visible crystals were detected when 25 mEq/L of Ca2+ and 2.0 g/L of CTRX were mixed. Based on these findings, attention should be sufficiently paid to the development of 'gallstone-related disorder' in pediatric patients and in patients treated with CTRX at a dose exceeding the normal dose. Furthermore, gallstone formation and growth may be promoted when CTRX and Ca2+ coexist at high concentrations under low pH conditions.

Obeticholic acid may increase the risk of gallstone formation in susceptible patients.

BACKGROUND & AIMS: The nuclear farnesoid X receptor (FXR) agonist obeticholic acid (OCA) has been developed for the treatment of liver diseases. We aimed to determine whether OCA treatment increases the risk of gallstone formation. METHODS: Twenty patients awaiting laparoscopic cholecystectomy were randomized to treatment with OCA (25 mg/day) or placebo for 3 weeks until the day before surgery. Serum bile acids (BAs), the BA synthesis marker C4 (7α-hydroxy-4-cholesten-3-one), and fibroblast growth factor 19 (FGF19) were measured before and after treatment. During surgery, biopsies from the liver and the whole bile-filled gallbladder were collected for analyses of gene expression, biliary lipids and FGF19. RESULTS: In serum, OCA increased FGF19 (from 95.0 ±â€¯8.5 to 234.4 ±â€¯35.6 ng/L) and decreased C4 (from 31.4 ±â€¯22.8 to 2.8 ±â€¯4.0 nmol/L) and endogenous BAs (from 1,312.2 ±â€¯236.2 to 517.7 ±â€¯178.9 nmol/L; all p <0.05). At surgery, BAs in gallbladder bile were lower in patients that received OCA than in controls (OCA, 77.9 ±â€¯53.6 mmol/L; placebo, 196.4 ±â€¯99.3 mmol/L; p <0.01), resulting in a higher cholesterol saturation index (OCA, 2.8 ±â€¯1.1; placebo, 1.8 ±â€¯0.8; p <0.05). In addition, hydrophobic OCA conjugates accounted for 13.6 ±â€¯5.0% of gallbladder BAs after OCA treatment, resulting in a higher hydrophobicity index (OCA, 0.43 ±â€¯0.09; placebo, 0.34 ±â€¯0.07, p <0.05). Gallbladder FGF19 levels were 3-fold higher in OCA patients than in controls (OCA, 40.3 ±â€¯16.5 ng/L; placebo, 13.5 ±â€¯13.1 ng/ml; p <0.005). Gene expression analysis indicated that FGF19 mainly originated from the gallbladder epithelium. CONCLUSIONS: Our results show for the first time an enrichment of FGF19 in human bile after OCA treatment. In accordance with its murine homolog FGF15, FGF19 might trigger relaxation and filling of the gallbladder which, in combination with increased cholesterol saturation and BA hydrophobicity, would enhance the risk of gallstone development. LAY SUMMARY: Obeticholic acid increased human gallbladder cholesterol saturation and bile acid hydrophobicity, both decreasing cholesterol solubility in bile. Together with increased hepatobiliary levels of fibroblast growth factor 19, our findings suggest that pharmacological activation of the farnesoid X receptor increases the risk of gallstone formation. Clinical trial number: NCT01625026.

Biliary stone disease in patients receiving somatostatin analogs for neuroendocrine neoplasms. A retrospective observational study.

BACKGROUND: Somatostatin analogs are the backbone of neuroendocrine neoplasms treatment. Biliary stone disease is a potentially severe adverse event of somatostatin analogs: an increased incidence has been reported in somatostatin analogs-treated acromegalic patients, but studies on patients with neuroendocrine neoplasms are lacking. AIMS: To evaluate biliary stone disease incidence and associated factors in a large series of patients treated with somatostatin analogs for neuroendocrine neoplasms. METHODS: A prospectively-collected database of patients with a diagnosis of neuroendocrine neoplasms of any grade and site, treated with somatostatin analogs at our Institution between 1995 and 2017, was retrospectively analyzed. Patients' demographics and disease characteristics were analyzed to evaluate the incidence and the factors related to biliary stone disease. RESULTS: Three-hundred patients were included; 101 (33.7%) patients underwent cholecystectomy before starting somatostatin analogs. Among 164 patients with gallbladder in situ and no history of stone disease, 60 (36.6%) developed gallstones after a mean of 36.7 months (range 1-239) from treatment start with a mean yearly incidence of 8.73%. Previous cholecystectomy was associated with a lower rate of development of gallstones (p < 0.001) or related complications (p = 0.017). CONCLUSION: We observed a high incidence of biliary stone disease in patients treated with somatostatin analogs-treated for neuroendocrine neoplams. Previous cholecystectomy was the only factor associated with a lower occurrence of biliary stone disease.

Association between cholesterol gallstones and testosterone replacement therapy in a patient with primary hypogonadism. / Asociación de colelitiasis y terapia de reemplazo de testosterona en un paciente con hipogonadismo primario.

A 16-year-old boy had a past medical history of primary hypogonadism, due to bilateral anorchia. He presented with gallstones located in the gallbladder and a mild dilatation of the intrahepatic biliary tree. The histology study reported cholesterol gallstones. The patient had been treated with testosterone replacement therapy since infancy. We suggest a possible correlation between testosterone replacement therapy and the presence of cholesterol gallstones.

Gallstones were associated with the gastrointestinal adverse events of cinacalcet in hemodialysis patients with secondary hyperparathyroidism.

This study aimed to investigate the association of gastrointestinal (GI) adverse events of cinacalcet with gallstones in the hemodialysis (HD) patients with secondary hyperparathyroidism (SHPT). A total of 23 HD patients under the treatment with cinacalcet and 101 control patients were enrolled in this cross-sectional study. We investigated the prevalence of gallstones and the association of GI adverse events of cinacalcet with gallstones. The prevalence of gallstones was significantly higher in the HD patients with cinacalcet compared with the controls (47.8% vs. 15.8%). The longer time on HD, hypercalcemia, hyperphosphatemia and elevated parathyroid hormone level were observed in the HD patients with cinacalcet. Besides, GI adverse events of cinacalcet were observed more frequently in the HD patients with gallstones compared with those without gallstones (odds ratio 13.5, 95% CI: 1.80-101). Therefore, screening for gallstones before dosing cinacalcet may reduce the risk of GI adverse events in SHPT patients.

Is the oral contraceptive or hormone replacement therapy a risk factor for cholelithiasis: A systematic review and meta-analysis.

BACKGROUND: Association between exogenous estrogen intake and cholelithiasis risk has been reported in several epidemiological studies, including oral contraceptive (OC) and hormone replacement therapy (HRT), while the results were controversial. This study aimed to perform a comprehensive meta-analysis of this issue. METHODS: PUBMED, EMBASE, and Cochrane library database were searched up to October 2016. Two reviewers independently extracted data from eligible studies, relative risks (RRs), and/or odds ratios (ORs) with 95% confidence intervals (95% CIs) for the highest versus lowest categories of intake were adopted. Either a fixed- or a random-effects model was adopted to estimate overall RRs or ORs. Besides, subgroup and publication bias analyses were applied to explain the heterogeneity. An original study was also conducted to verify our conclusion. RESULTS: A total of 19 studies with approximately 556,620 participants were included in this meta-analysis. The pooled RR of cholelithiasis for the highest versus the lowest categories was 1.59 (95% CI: 1.44-1.75), indicating that exogenous estrogen was positive associated with the intake of exogenous estrogen. However, the pooled RR of OC intake and cholelithiasis risk was 1.19 (95% CI: 0.97-1.45), and the RR for HRT was 1.79 (95% CI: 1.61-2.00). CONCLUSION: The HRT was positively associated with the cholelithiasis risk, and the OC will not increase the risk of cholelithiasis.

Organochloride pesticides induced hepatic ABCG5/G8 expression and lipogenesis in Chinese patients with gallstone disease.

BACKGROUND: Organochlorine pesticides (OCPs) are one kind of persistent organic pollutants. Although they are reported to be associated with metabolic disorders, the underlying mechanism is unclear. We explored the association of OCPs with gallstone disease and its influence on hepatic lipid metabolism. MATERIALS AND METHODS: OCPs levels in omentum adipose tissues from patients with and without gallstone disease between 2008 and 2011 were measured by GC-MS. Differences of gene expression involved in hepatic lipid metabolism and hepatic lipids content were compared in liver biopsies between groups with high and low level of OCPs. Using HepG2 cell lines, the influence on hepatic lipid metabolism by individual OCP was evaluated in vitro. RESULTS: In all patients who were from non-occupational population, there were high levels of ß-hexachlorocyclohexane (ß-HCH) and p',p'-dichloroethylene (p',p'-DDE) accumulated in adipose tissues. Both ß-HCH and p', p'-DDE levels were significantly higher in adipose tissues from patients with gallstone disease (294.3± 313.5 and 2222± 2279 ng/g of lipid) than gallstone-free controls (282.7± 449.0 and 2025±2664 ng/g of lipid, P< 0.01) and they were strongly related with gallstone disease (P for trend = 0.0004 and 0.0138). Furthermore, higher OCPs in adipose tissue led to increase in the expression of hepatic cholesterol transporters ABCG5 and G8 (+34% and +27%, P< 0.01) and higher cholesterol saturation index in gallbladder bile, and induced hepatic fatty acids synthesis, which was further confirmed in HepG2 cells. CONCLUSIONS: OCPs might enhance hepatic secretion of cholesterol into bile via ABCG5/G8 which promoting gallstone disease as well as lipogenesis.

[Four cases of ceftriaxone-associated biliary pseudolithiasis].

We report four cases of ceftriaxone-associated biliary pseudolithiasis. All cases were treated conservatively without cholecystectomy or endoscopic retrograde cholangiopancreatography. Because conservative treatment is the preferred treatment, clinicians should be aware that biliary pseudolithiasis is possible in patients who have abdominal pain associated with gallbladder stones on imaging. Regardless of whether we are treating adults or children, it is necessary to check for a history of ceftriaxone treatment before symptom onset.

Absence of Elovl6 attenuates steatohepatitis but promotes gallstone formation in a lithogenic diet-fed Ldlr(-/-) mouse model.

Nonalcoholic steatohepatitis (NASH) is a progressive form of nonalcoholic fatty liver disease (NAFLD) that can develop into liver cirrhosis and cancer. Elongation of very long chain fatty acids (ELOVL) family member 6 (Elovl6) is a microsomal enzyme that regulates the elongation of C12-16 saturated and monounsaturated fatty acids (FAs). We have previously shown that Elovl6 plays an important role in the development of hepatic insulin resistance and NASH by modifying FA composition. Recent studies have linked altered hepatic cholesterol homeostasis and cholesterol accumulation to the pathogenesis of NASH. In the present study, we further investigated the role of Elovl6 in the progression of lithogenic diet (LD)-induced steatohepatitis. We showed that the absence of Elovl6 suppresses hepatic lipid accumulation, plasma total cholesterol and total bile acid (BA) levels in LDL receptor-deficient (Ldlr(-/-)) mice challenged with a LD. The absence of Elovl6 also decreases hepatic inflammation, oxidative stress and liver injury, but increases the formation of cholesterol crystals in the less dilated gallbladder. These findings suggest that Elovl6-mediated changes in hepatic FA composition, especially oleic acid (C18:1n-9), control handling of hepatic cholesterol and BA, which protects against hepatotoxicity and steatohepatitis, but promotes gallstone formation in LD-fed Ldlr(-/-) mice.

Association of Meloxicam Use with the Risk of Acute Pancreatitis: A Case-Control Study.

BACKGROUND AND OBJECTIVE: No sufficient research has focused on the relationship between meloxicam use and acute pancreatitis. This study aimed to explore this issue in Taiwan. METHODS: This case-control study was conducted using the database of the Taiwan National Health Insurance Program. In all, there were 6780 cases aged 20-84 years who were newly diagnosed with acute pancreatitis during the period 1998-2011, and 21,393 control subjects without acute pancreatitis. Cases and controls were matched for sex, age and comorbidities. Odds ratios (ORs) and 95% confidence intervals (CIs) were measured to explore the associations between acute pancreatitis, meloxicam use and comorbidities, using a multivariable unconditional logistic regression model. RESULTS: After controlling for potential confounding factors, the adjusted OR for acute pancreatitis was 1.76 (95% CI 1.30-2.40) for subjects with current use of meloxicam, in comparison with subjects who had never used meloxicam. The adjusted OR decreased to 1.29 (95% CI 0.82-2.03) for subjects with late use of meloxicam, but without statistical significance. CONCLUSIONS: Current use of meloxicam is associated with increased odds of acute pancreatitis. Clinicians should consider the potential risk of acute pancreatitis when prescribing meloxicam.

Intraductal infusion of taurocholate followed by distal common bile duct ligation leads to a severe necrotic model of pancreatitis in mice.

OBJECTIVE: The most common etiology of acute pancreatitis results from the impaction of gallstones or sludge in the distal common bile duct (CBD). The result is pancreatic duct obstruction, diversion of bile into the pancreas, or cholestasis. In the current study, we examined whether combining both aspects, that is, infusion of the bile acid taurocholate (TC) followed by bile duct ligation (BDL), could yield a more severe form of pancreatitis that mimics biliary pancreatitis. METHODS: In mice, after laparotomy, the CBD was infused with either normal saline (NS) or TC. Subsequently, the CBD was ligated at the ampulla. RESULTS: Mice receiving TC infusion followed by BDL (TC + BDL) had higher mortality compared with animals receiving intraductal NS with BDL (NS + BDL). The TC + BDL arm developed more severe and diffuse pancreatic necrosis. In addition, serum amylase, IL-6, and bilirubin were significantly higher. However, pancreatic edema as well as lung and liver injury were unchanged between TC + BDL and NS + BDL. CONCLUSIONS: In summary, the combination of bile infusion into the pancreas followed by BDL causes a more severe, necrotizing pancreatitis. We believe that this novel model of pancreatitis is useful because it can be used in transgenic mice and recapitulates several aspects of biliary pancreatitis.

Cálculos biliares asociados al uso de ceftriaxona en niños / Gallstones in association with the use of ceftriaxone in children

INTRODUCCIÓN: La pseudocolelitiasis asociada a ceftriaxona en niños es un evento frecuente pero pocas veces tenido en cuenta; ocurre en el 15 al 57% de los que la reciben y en la mayoría de los casos cursa asintomática y autorresolutiva. PACIENTES Y MÉTODOS: Estudio prospectivo, observacional y descriptivo. Se incluyeron pacientes de 1 mes a 18 años que recibieron ceftriaxona. Se realizó ecografía de hígado y vesícula biliar al inicio del tratamiento y cada 5 días hasta finalizarlo. A los pacientes con anormalidades ecográficas se les realizó seguimiento clínico y ecográfico semanalmente hasta la resolución completa. Se buscó asociación con los factores de riesgo descritos en la literatura. RESULTADOS: Fueron incluidos 73 pacientes, 57,5% femeninos, con edad entre 4 meses y 17 años (x = 4,2 años). Se presentó pseudocolelitiasis en 31 pacientes (42,5%) y en este grupo se documentó al día 5 en el 96,8% (n = 30). El tamaño de los cálculos estuvo entre 4 y 14 mm (x = 8,1). La duración de la pseudocolelitiasis estuvo entre 9 y 55 días (x = 24,1 días). El 22,6% (n = 7) presentó síntomas y se presentó una complicación grave. En el análisis multivariado el lactato de Ringer como líquido de dilución tuvo 1,86 veces más riesgo (p = 0,019). No se encontró relación con la edad, duración ni dosis del antibiótico, ayuno, uso de suplementos de calcio, nutrición parenteral o uso de otros antibióticos. CONCLUSIÓN: Se presenta pseudocolelitiasis asociado a ceftriaxona en 4 de cada 10 niños que la reciben, sin relación con factores de riesgo tradicionales. La evolución es hacia la auto resolución aunque cerca del 20% presentan síntomas

INTRODUCTION: Ceftriaxone associated pseudolithiasis is fairly frequent in children, but rarely taken into account. It occurs in 15% to 57% of children, and in most cases is asymptomatic and resolves spontaneously. PATIENTS AND METHODS: A prospective, observational, and descriptive study was conducted that included patients aged 1 month to 18 years-old who received ceftriaxone. Liver and gallbladder ultrasound was performed at the start of treatment, and every 5 days until it was completed. Patients with abnormal ultrasound findings were followed up clinically every week until they were resolved. The findings were compared with risk factors described in the literature. RESULTS: A total of 73 patients aged between 4 months and 17 years (mean = 4.2 years) were included, of whom 57.5% were female. Pseudolithiasis was present in 31 patients (42.5%) and was documented in 96.8% (n = 30) of this group on day 5. The stone size was between 4 and 14 mm (mean = 8.1 mm). The duration of pseudolithiasis was between 9 and 55 days (mean = 24.1 days).Symptoms were present in 22.6% (n = 7) and 1 had a serious complication. In the multivariate analysis, Ringer's Lactate as fluid dilution was 1.86 times higher risk (P = 0.019). No relationship was found with age, duration and dose of antibiotic, fasting, use of calcium supplements, parenteral nutrition, or use of other antibiotics. CONCLUSION: Pseudocolelitiasis associated with ceftriaxone take place in 4 of 10 children who receive, unrelated to traditional risk factors. The trend is towards self resolution although about20% have symptoms