Relationship among sleep, work features, and SARS-cov-2 vaccine antibody response in hospital workers.

STUDY OBJECTIVES: Immunity is influenced by sleep and the circadian rhythm. Healthcare workers are predisposed to both insufficient sleep and circadian disruption. This study aimed to evaluate the relationship between sleep and work characteristics and the antibody response to the mRNA SARS-CoV-2 vaccine BNT162b2. METHODS: The authors' prospective cohort study ("COVI3") evaluated the effect of a third (booster) dose of the BNT162b2 vaccine. A subset of participants provided information on anthropometric measures, sleep, stress and work characteristics including shift work and number of work hours per week. Blood samples for anti-S1-RBD IgG antibody levels were obtained 21 weeks following receipt of the third dose of the vaccine. RESULTS: In total, 201 healthcare workers (73% women) were included. After adjustment for age, body mass index (BMI), shift work, smoking status, and perceived stress, short sleep duration (<7 h per night) was associated with lower anti-S1-RBD IgG levels (Odds ratio 2.36 [95% confidence interval 1.08-5.13]). Participants who performed shift work had higher odds of lower anti-S1-RBD IgG levels compared to those who did not work in shifts [odds ratio = 2.99 (95% confidence interval 1.40, 6.39)] after accounting for age, short sleep duration, BMI, smoking status and perceived stress. CONCLUSIONS: Shift work and self-reported short sleep duration were associated with a lower antibody response following a booster dose of the SARS-CoV-2 vaccine. These findings suggest that the efficacy of vaccination, particularly among healthcare workers, may be augmented by addressing both sleep and circadian alignment.

Neutrophil Gelatinase-Associated Lipocalin for the Assessment of Reversible versus Persistent Renal Tubular Damage in ST-Segment Myocardial Infarction Patients.

BACKGROUND: Most studies investigated the value of neutrophil gelatinase-associated lipocalin (NGAL) as a marker of renal tubular injury only at a single time point. We investigated the possible utilization of NGAL level dynamics for the identification of different renal injury patterns in ST-elevation myocardial infarction (STEMI) patients. METHODS: Blood samples for plasma NGAL in 132 STEMI patients were drawn immediately before and 24 h following primary coronary intervention. Abnormal elevation of NGAL levels was defined using the cardiac surgery-associated NGAL score with NGAL levels ≥100 ng/mL suggesting renal tubular damage. According to NGAL levels at 0 and 24 h, patients were stratified into 3 groups: no tubular damage (NGAL <100 ng/mL in both exams), reversible tubular damage (NGAL >100 ng/mL at 0 h but <100 ng/mL at 24 h), and persistent tubular damage (NGAL >100 ng/mL at both 0 and 24 h). RESULTS: Mean age was 62 ± 13 years, and 78% were men. Of these patients, 29/132 (22%) demonstrated reversible tubular damage, and 36/132 (27%) persistent tubular damage. Only 13/132 patients (10%) progressed to clinical acute kidney injury during hospitalization, all of whom had persistent tubular injury. In multivariate regression model, symptom duration was independently associated with persistent tubular damage, both as continues variable (odds ratio [OR] 1.02, 95% confidence interval [CI] 1.01-1.04; p = 0.04) and for symptom duration >360 min (OR 2.66, 95% CI 1.07-6.63; p = 0.03). CONCLUSIONS: Renal tubular damage is common among STEMI patients. Dynamic NGAL measurement may differentiate between reversible and persistent tubular damage. Further trials are needed in order to assess the complex cardiorenal interactions.

Neutrophil Gelatinase-Associated Lipocalin for the Early Prediction of Acute Kidney Injury in ST-Segment Elevation Myocardial Infarction Patients Treated with Primary Percutaneous Coronary Intervention.

INTRODUCTION AND OBJECTIVE: Neutrophil gelatinase-associated lipocalin (NGAL), a glycoprotein released by renal tubular cells, can be used as a marker of early tubular damage. We evaluated plasma NGAL level utilization for the identification of acute kidney injury (AKI) among ST-elevation myocardial infarction (STEMI) patients undergoing primary coronary intervention (PCI). METHODS: 131 STEMI patients treated with PCI were prospectively included. Plasma NGAL levels were drawn prior to PCI (0 h) and 24 h afterwards. AKI was defined per KDIGO criteria of serum creatinine increase. Receiver-operating characteristic (ROC) methods were used to identify optimal sensitivity and specificity for the observed NGAL range. RESULTS: Overall AKI incidence was 14%. NGAL levels were significantly higher for patients with AKI at both 0 h (164 ± 42 vs. 95 ± 30; p < 0.001) and 24 h (142 ± 41 vs. 93 ± 36; p < 0.001). Per ROC curve analysis, an optimal cutoff value of NGAL (>120 ng/mL) predicted AKI with 80% sensitivity and specificity (AUC 0.881, 95%, CI 0.801-0.961, p < 0.001). In a multivariate logistic regression model, NGAL levels were independently associated with AKI at 0 h (OR 1.044, 95% CI 1.013-1.076; p = 0.005) and 24 h (OR 1.018, 95% CI 1.001-1.036; p = 0.04). CONCLUSIONS: Elevated NGAL levels, suggesting renal tubular damage, are independently associated with AKI in STEMI patients undergoing primary PCI.

Elevated Neutrophil Gelatinase-Associated Lipocalin for the Assessment of Structural versus Functional Renal Damage among ST-Segment Elevation Myocardial Infarction Patients.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is an early marker of renal tubular damage. We investigated the incidence and possible implications of elevated NGAL levels (suggesting renal damage) compared to both functional and damage markers (manifested as serum creatinine [sCr] elevation) and no NGAL/sCr change, among -ST-elevation myocardial infarction (STEMI) patients treated with primary percutaneous coronary intervention (PCI). METHODS: We included 131 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn 24 h following PCI. We used the terms NGAL(-) or NGAL(+) with levels ≥100 ng/mL suggesting renal tubular damage and the terms. sCr(-) or sCr(+) to consensus diagnostic increases in sCr defining acute kidney injury. Patients were also assessed for in hospital-adverse outcomes. RESULTS: Of the study patients, 56 (42%) were NGAL(-)/sCr(-), 58 (44%) NGAL(+)/sCr(-), and 18 (14%) were both NGAL(+)/sCr(+). According to the 3 study groups, there was a stepwise increase in the proportion of left ventricular ejection fraction ≤45% (43 vs. 60. vs. 72%; p = 0.04), in-hospital adverse outcomes (9 vs. 14 vs. 56%; p < 0.001) and their combination. Specifically, more NGAL(+)/sCr(-) patients developed the composite endpoint when compared to NGAL(-)/sCr(-) patients (64 vs. 46%; OR 2.1, [95% CI 1.1-4.5], p = 0.05). A similar and consistent increase was observed in peak sCr, length of hospital stay, and C-reactive protein levels. CONCLUSIONS: Elevated NGAL levels suggesting renal tubular damage, increased inflammation, or both are common among STEMI patients and are associated with adverse outcomes even in the absence of diagnostic increase in sCr.

Elevated neutrophil gelatinase-associated lipocalin levels before contrast media administration among ST-segment elevation myocardial infarction patients treated with primary percutaneous coronary intervention.

BACKGROUND: Neutrophil gelatinase-associated lipocalin (NGAL) is a glycoprotein released by renal tubular cells upon nephrotoxic or ischemic events and is considered an early marker of tubular damage. We aimed to demonstrate the presence of early renal injury detected by elevated NGAL levels taken before contrast administration in ST-segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI). PATIENTS AND METHODS: We prospectively included 88 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn immediately before PCI (baseline NGAL; NGAL1) and 24 h after PCI (NGAL2). Abnormal elevations in NGAL levels were defined using the cardiac surgery associated NGAL score (NGAL score) with NGAL levels at least 100 ng/ml, suggesting renal tubular damage. Patients were also assessed for the dynamics between NGAL2 and NGAL1 levels. RESULTS: The mean age of the patients was 62 ± 13 years and 78% were men. A total of 50/88 (56%) patients had baseline NGAL level of at least 100, suggesting possible tubular damage before PCI. Only 10 patients progressed to clinical acute kidney injury during hospitalization, all of whom had baseline NGAL level of at least 100 (P < 0.001). Among patients with baseline NGAL at least 100, 28/50 (56%) showed a decrease in the NGAL level within 24 h, whereas only 9/50 (18%) showed an elevation in the NGAL level. In contrast, only 7/38 (19%) patients with baseline NGAL level less than 100 showed an elevation in NGAL levels within 24 h. CONCLUSION: Elevated NGAL levels before primary PCI suggesting renal tubular damage are common among STEMI patients. Further trials are needed to assess the complex cardio-renal interactions.

The value of cerebrospinal fluid lactate levels in diagnosing CSF infections in pediatric neurosurgical patients.

PURPOSE: Diagnosis of cerebrospinal fluid (CSF) infections in patients following neurosurgical procedures can be challenging. CSF lactate (LCSF) has been shown to assist in differentiating bacterial from non-bacterial meningitis in non-neurosurgical patients. The use of lactate in diagnosing CSF-related infections following neurosurgical procedures has been described in adults. The goal of this study was to describe the role of LCSF levels in diagnosing CSF-related infections among neurosurgical children. METHODS: We retrospectively collected data for all pediatric patients treated at a large tertiary pediatric neurosurgical department, for whom CSF samples were collected over a 2-year period. Lactate levels were correlated with other CSF parameters, surgical parameters, presence of CSF infection, and source of CSF sample (lumbar, ventricular, or pseudomeningocele). RESULTS: A total of 215 CSF samples from 162 patients were analyzed. We found a correlation between lactate levels and other CSF parameters. Lactate levels displayed an inconsistent correlation with infection depending on sample origin. Irrespective of the CSF source, lactate levels could not sufficiently discriminate between those with or without infection. Lactate levels were correlated with recent surgery, and, in some of the subgroups, to the extent of blood in CSF. CONCLUSIONS: LCSF levels are influenced by many factors, including the source of sample, recent surgery, and the presence of subarachnoid or ventricular blood secondary to surgery. The added value of LCSF for diagnosing CSF infections in children with a history of neurosurgical procedures is unclear and may be influenced by the extent of blood in the CSF.

Characteristics of apparently healthy individuals with a very low C-reactive protein.

BACKGROUND: The importance of the inflammatory processes and C-reactive protein (CRP) evaluation was observed. Only few studies used cut-off value <1 mg/L. We sought to evaluate the association between very low CRP (vlCRP) and health status, to describe the repetition of vlCRP and to identify predictors for repetition. METHODS: A historical cohort study of all participants who underwent a routine annual check-up between January 2002 and July 2018 at the Tel Aviv Sourasky medical center. CRP test was evaluated in all participants. Individuals who use statins or with CRP >10 mg/L were excluded. CRP ≤0.12 mg/L was considered as vlCRP. RESULTS: The final study cohort included 14,161 individuals. Of them, 5065 were females and mean age was 43.4 years (SD 10.6). vlCRP at first check-up was observed in 1299 (9.2%) of the participants. In multivariable analysis, older age, hyperlipidemia, hypertension and smoking were significantly associated with lower probability of vlCRP. At the second check-up, 50.1% vlCRP repetition was observed with no significant predictor from previous visit. CONCLUSION: vlCRP is associated with younger age, non-smoking, and absence of hyperlipidemia and of hypertension. However, it may also be part of the individual physiology.

Dipeptidyl peptidase 4-deficient rats have improved bile secretory function in high fat diet-induced steatosis.

BACKGROUND/AIMS: Rodent obesity models have been shown to display impaired bile secretory functions. We have shown that glucagon-like peptide 1 (GLP-1) attenuates hepatic lipogenesis, and in the present study we investigated whether GLP-1 also improves high fat diet-associated cholestatic injury. METHODS: Wild type (WT) and dipeptidyl peptidase 4-deficient rats (DPP4-) with chronic elevated serum levels of active GLP-1 were fed regular chow and a Western diet for 2 months. Primary hepatocytes were used to assess GLP-1 effects on mRNA expression and transcription of genes encoding bile acid synthesis enzymes and transporters. RESULTS: DPP4- exhibited attenuated liver injury as expressed by lower serum AST and ALT after 2 months of a Western diet. In addition, DPP4- had better insulin sensitivity, lower serum triglycerides, cholesterol and bile acids. Hepatic expression of cyp7A1, the rate limiting enzyme in conversion of cholesterol into bile acids, was strongly attenuated in DPP4- fed with a Western diet. Moreover, hepatic expression of bile transporter, ABCB11, was increased, facilitating a higher rate of bile secretion. Mechanistically, we showed that GLP-1 directly reduced basal and LXR-induced cyp7A1 mRNA expression and suppressed cyp7A1 transcription in transient transfection assays in primary hepatocytes. However, GLP-1 and its analog exendin 4 also induced mRNA expression of bile acid transporter ABCC3 in primary rat hepatocyte cultures. CONCLUSIONS: Our data suggest that GLP-1 analogs may serve as a novel therapeutic drug to alleviate obesity-induced liver injury by reducing bile acid synthesis and improving liver bile secretory function.

The association between adipocytokines and biomarkers for nonalcoholic fatty liver disease-induced liver injury: a study in the general population.

BACKGROUND AND AIM: Leptin and adiponectin have been implicated in the development of nonalcoholic fatty liver disease (NAFLD). However, the usefulness of adipocytokines as a screening tool for nonalcoholic steatohepatitis (NASH) and fibrosis could not be evaluated in the general population due to the invasive nature of liver biopsy. The aim was to evaluate the association between adipocytokines and presumed liver injury in the general population using noninvasive biomarkers. METHODS: A cross-sectional study of 375 individuals, sampled from the National Health Survey was conducted. The exclusion criterion was any known secondary etiology for liver disease. Anthropometrics, serum leptin, adiponectin, insulin, lipids, and FibroMax were measured. RESULTS: Three hundred and thirty-eight individuals met the inclusion criteria and had valid FibroMax. Fibrosis diagnosed by the FibroTest was found in 25.7% of the patients, of whom 12.8% had significant fibrosis. Steatohepatitis was diagnosed by the NASH test in 0.9% and borderline NASH in 31.4% of the patients. Adiponectin was an independent negative correlate of borderline NASH [odds ratio (OR): 0.92; 95% confidence interval (CI): 0.86-0.98/1 µg/ml] together with high-density lipoprotein, and leptin was a positive correlate (OR: 1.03; CI: 1.01-1.06/1 ng/ml), together with abdominal obesity, serum triglycerides, and HbA1C. The OR for borderline NASH was 20.7 (CI: 7.5-57.5) when both high leptin (upper quartile) and suboptimal adiponectin were present, adjusting for age and sex. The FibroTest was not associated with leptin and adiponectin. The strongest predictors for fibrosis were age, sex, abdominal obesity, and insulin. CONCLUSION: Low adiponectin and high leptin and the combination of both have a strong independent association with presumed early-stage NASH. However, early-stage fibrosis cannot be predicted by these adipocytokines.

An animal model for chemotherapy-associated steatohepatitis and its prevention by the oral administration of fatty acid bile acid conjugate.

BACKGROUND: Preoperative chemotherapy for hepatic resection of colorectal liver metastases is associated with the development of chemotherapy-associated steatohepatitis (CASH). This increases the risk of perioperative morbidity and mortality. To the authors' knowledge, an animal model for CASH has not been described previously. It has been established that fatty acid bile acid conjugates (FABACs) prevent the formation of diet-induced fatty liver. The current study was designed to establish an animal model of CASH and to use that model to study the effect of FABACs on its occurrence. METHODS: C57BL/6 mice were given different doses of oxaliplatin and irinotecan. Oxaliplatin administered once weekly at a dose of 6 mg/kg for a total dose of 24 mg/kg was tolerated best and was associated most consistently with CASH. Thus, that dose was chosen as the induction model for CASH. Subsequently, mice were divided into a control group (no treatment), an oxaliplatin group, and a CASH-prevention group, which received oxaliplatin and C20-FABAC at a dose of 150 mg/kg daily. The animals were killed after 28 days. RESULTS: Liver fat content was significantly lower (P < .0001) in the control group (51.63 mg/g) and the prevention group (62.13 mg/g) compared with the oxaliplatin group (95.35 mg/g). This difference was mainly because of the accumulation of liver triglycerides in the oxaliplatin group. CONCLUSIONS: The current results indicated that C57BL/6 mice receiving weekly oxaliplatin can be used as a model for CASH. Oral FABAC therapy reduced the development of CASH in animals that received oxaliplatin. To the authors' knowledge, this report is the first description of a model and a potential preventive treatment for CASH.

Inhibition of immune-mediated concanavalin a-induced liver damage by free-radical scavengers.

BACKGROUND/AIMS: The aims of the present study were to elucidate whether oxidative stress has a role in Con A-induced hepatitis and to examine if antioxidants may protect against liver damage in this model. METHODS: Hepatitis was induced in Balb/c mice by administration of Con A (18 mg/kg) to the tail vein. Liver enzymes and histology were determined 24 h after Con A injection. Tumor necrosis factor alpha (TNFalpha) and interleukin-10 (IL-10) levels were assayed 2 h after Con A injection. Hepatic malondialdehyde levels were measured at 1, 3, 8, 12, 18, and 24 h after Con A injection in order to examine the timing of free-radicals formation. Nuclear factor kappa B (NF-kappabeta) activation was determined by electrophoresis mobility shift assay (EMSA) 1 and 2 h after Con A injection. In separate experiments, mice were pretreated with either dimethylsulfoxide or dimethylthiourea before Con A inoculation. The antioxidant and NF-kappabeta inhibitor pyrrolidine dithiocarbamate (PDTC) was used as positive control. RESULTS: Hepatic malondialdehyde levels increased 12, 18, and 24 h after Con A inoculation but not earlier. Serum levels of liver enzymes and TNFalpha, hepatic malondialdehyde, and protein carbonyls and the histologic necroinflammatory score were significantly reduced in the antioxidants-treated mice, while IL-10 levels were increased. Dimethylsulfoxide, dimethylthiourea, and PDTC inhibited oxidative stress, but only PDTC inhibited Con A-induced NF-kappaB activation. CONCLUSIONS: Reactive oxygen species play a role in immune-mediated Con A-induced hepatitis probably secondary to immune-mediated liver damage. Scavenging of reactive oxygen species by antioxidants prevents hepatitis independently of NF-kappaB inhibition and may be a new therapeutic target in this experimental model.

Role of leisure-time physical activity in nonalcoholic fatty liver disease: a population-based study.

UNLABELLED: Physical activity (PA) is commonly recommended for nonalchoholic fatty liver disease (NAFLD) patients. However, there is limited evidence on the independent role of PA in NAFLD. The aim of this study was to examine the association between PA and NAFLD. We conducted a cross-sectional study of a subsample (n = 375) of the Israeli National Health and Nutrition Survey. Exclusion criteria were any known etiology for liver disease. Participants underwent an abdominal ultrasound examination; biochemical tests, including leptin, adiponectin, and resistin; and the noninvasive biomarker SteatoTest and anthropometric evaluations. A semiquantitative food frequency questionnaire and a detailed PA questionnaire were administered. Three hundred forty-nine patients (52.7% men, 30.9% primary NAFLD) were included. The NAFLD group engaged in less aerobic, resistance, or other kinds of PA (P

[Innovations in the medical treatment of gallstones and fatty liver: FABACs (Fatty Acid Bile Acid Conjugates)].

Gallstones and fatty liver are common disorders in the Western world, largely due to dietary and life style factors. Currently, laparoscopic cholecystectomy is the main treatment option for gallbladder stones. Surgery is, however, expensive and may cause morbidity and even mortality. An effective medical treatment would be desirable, especially in patients with mild to moderate symptoms or high surgical risk. Currently, the bile acid UDCA (Ursodeoxycholic acid) is used for oral dissolution treatment and for the prevention of cholelithiasis in selected cases. However, the major limitations of this treatment are its low efficacy, slow action and stone recurrence. Recently, phospholipids rather than bile salts were realized to be the major natural cholesterol solubilizers in bile. They also possess anti-crystallizing activity. The sn-2 fatty acid of the phospholipids molecule was found to be particularly important. This was the background for the development of FABACs (Fatty Acid and Bile Acid Conjugates), which are novel synthetic lipid molecules. These molecules are composed of fatty acids (with chain lengths from C-14 to C-22), that are linked to cholic acid, by an amide bond at position 3. In vitro and in vivo studies (in mice) have shown that FABACs can prevent the formation of cholesterol crystals and dissolve existing ones. C20-FABAC, when given orally, is absorbed and secreted into bile. It was also found to have a series of beneficial effects on cholesterol metabolism. The main treatment for patients with fatty liver consists of lifestyle and diet modifications, which are associated with low compliance. Currently there is no effective medical treatment for this disease. In the FABAC studies on the prevention and dissolution of gallstones in laboratory animals, it was observed that this treatment also prevents the formation of diet induced fatty liver. Further prospective studies found that FABACs indeed prevent/decrease the formation of fatty liver induced by high fat diet. This influence was observed in all the fatty liver parameters (histology as well as chemical analysis), and in different animal strains. Based on these findings, FABACs seem to be good candidates for the medical treatment of hepatobiliary disorders, in particular gallstones and fatty liver disease.

Prevention of liver cirrhosis in rats by curcumin.

BACKGROUND AND AIM: Curcumin, the major polyphenolic compound in turmeric, has been shown to attenuate hepatic damage in several animal models of liver injury. The aim of the present study was to examine the efficacy of curcumin in preventing thioacetamide-induced cirrhosis and to unravel the mechanism of curcumin's effect on hepatic fibrosis in rats. METHODS: Liver cirrhosis was induced by thioacetamide (TAA; 200 mg/kg, i.p.) twice weekly for 12 weeks. One group of rats concomitantly received curcumin (300 mg/kg/day, by gavage for 12 weeks); the control group received the solvent at identical amounts and duration. RESULTS: TAA administration induced liver cirrhosis, which was inhibited by curcumin. Liver histopathology, hydroxyproline levels and spleen weights were significantly lower in the rats treated with TAA+curcumin compared with TAA only (P<0.001). Immunohistochemical studies and in situ hybridization demonstrated inhibition of hepatic stellate cell (alpha smooth muscle actin-positive) activation and collagen alpha1 (I) gene expression in the livers of the TAA+curcumin-treated rats. Curcumin reduced oxidative stress as shown by the decreased hepatic nitrotyrosine staining in the curcumin+TAA-treated rats. Curcumin treatment had no effect on pre existing liver cirrhosis. As determined by in vitro studies using the rat HSC-T6 cell line, curcumin had no direct inhibitory effect on collagen alpha1 (I) messenger RNA expression. Further studies in these cells using reverse transcriptase-polymerase chain reaction demonstrated that curcumin had no effect on the expression of PDGF-induced TIMP-1 and TIMP-2, TGFbeta1, TGFbeta2 and MCP-1 but significantly inhibited tumor necrosis factor alpha expression. Curcumin had no effect on hepatic stellate cells proliferation. Zymography showed that curcumin had no effect on matrix metalloproteinase-2 activity. CONCLUSIONS: Curcumin inhibited the development of TAA-induced liver cirrhosis mainly due to its anti-inflammatory activities and not by a direct anti-fibrotic effect. As curcumin ingestion is safe in humans, it may be reasonable to assess in clinical studies the beneficial effect of curcumin in slowing the development of liver cirrhosis.

Apolipoprotein-E genotype and the risk of developing cholelithiasis following bariatric surgery: a clue to prevention of routine prophylactic cholecystectomy.

BACKGROUND: Obesity and especially rapid weight loss following bariatric surgery are known risk factors for cholelithiasis. Since the risk may be high, prophylactic cholecystectomy has been advocated. Apolipoprotein (Apo) E, an important carrier protein in cholesterol metabolism and trafficking, is believed to play a role in gallstone pathogenesis. In particular, the Apo E4 allele has been suggested to be associated with cholesterol cholelithiasis. The aim of this study was to assess the incidence of postoperative cholelithiasis in our patient population and to determine a possible correlation with the Apo-E genotype. METHODS: 134 morbidly obese patients undergoing gastric restrictive surgery [laparoscopic assisted gastric banding (LAGB) or silastic ring vertical gastroplasty (SRVG)] had abdominal ultrasound before and 6 to 12 months after operation, to determine the presence of gallstones. None of the patients enrolled in the study had gallstones before surgery. They did not have a prophylactic cholecystectomy or receive bile salt treatment. Apo-E genotypes were determined by Polymerase Chain Reaction restriction enzyme analysis. RESULTS: 10 patients (7.5%) developed postoperative cholelithiasis. The incidence of cholelithiasis in each ApoE genotype was: E2/E3--1/20 (5%), E3/E3--3/91 (3%), E3/E4--6/21 (29%), and E4/E4--0/2. ApoE allele frequencies in the study population were identical to those of a healthy control population. The mean BMI dropped from 43.6 to 29.4 kg/m2. CONCLUSIONS: The occurrence of postoperative gallstones was low in our population. However, in subjects with the Apo-E3/E4 genotype, the incidence is of practical significance. These data suggest that Apo-E genotyping may be useful in selecting patients for gallstone prevention (surgical or medical) when undergoing bariatric surgery. Further testing in larger patient populations may be able to give more definite guidelines in the future.

Dissolution of cholesterol gallstones in mice by the oral administration of a fatty acid bile acid conjugate.

Gallstones, mostly cholesterol stones, affect some 15% of the population. Oral bile salts dissolve human cholesterol gallstones, but with low efficacy, and surgery remains the main therapeutic option. Fatty acid bile acid conjugates (FABACs) were shown to prevent formation of cholesterol gallstones in experimental animals. The aim of this study was to test whether these compounds could dissolve preexisting cholesterol gallstones via oral administration. Inbred, gallstone-susceptible C57J/L mice were given a lithogenic diet for 2 months, and the presence of gallstones was ascertained. The mice were then switched to a regular diet while part of them were given in addition C20-FABAC, by gavage, at a dose of 0.5 or 3 mg per animal per day. All mice tested had cholesterol gallstones after 2 months on the lithogenic diet. In study I, after 2 months on the regular diet, 3 of 4 (75%) of the controls had gallstones, whereas none of the 6 FABAC-fed animals (3 mg/d) had stones (P =.033). In study II, evaluating 2 FABAC doses, after 2 months on the regular diet, 8 of 8 (100%) of the controls had gallstones, which were found in 2 of 7 (28%) and 1 of 8 (12%) of the mice supplemented with 0.5 mg/d (P =.007) or 3 mg/d (P =.001) FABAC, respectively. On a molar basis, the dose of 0.5 mg FABAC is equivalent to 14 mg/kg/d of a bile acid. In conclusion, FABACs given orally can dissolve preexisting cholesterol gallstones in mice. This was accomplished with a dose of FABAC equivalent to the dose of bile acids used in human gallstone dissolution.