Clinical practice of hepatitis B screening in patients starting with chemotherapy: A survey among Dutch oncologists.

OBJECTIVE: Screening for hepatitis B virus (HBV) before chemotherapy is recommended by international guidelines; still, the HBV screening rate is low, and patients remain at risk for HBV reactivation (HBVr). Because HBVr is a serious and preventable condition, we conducted a survey to evaluate the screening behaviour of oncologists in the Netherlands. METHODS: We conducted an anonymous digital survey by email to all practicing medical oncologists. The surveys were sent in two session, the first one in 2017 and the second one in 2019. Questions included HBV screening procedures, reasons for screening and experience with HBVr. RESULTS: Among the 110 respondents, 29 (27%) followed a standardised protocol. Overall, 13 (12%) oncologists screened all patients, 76 (70%) only screened patients they considered as high risk and 19 (18%) did not screen anyone. Fourteen percent of the respondents experienced a HBVr in one of their patients. CONCLUSION: This survey suggests that universal HBV screening is not common practice and usually patients considered as at risk for HBVr are screened, while this group is not always properly identified. Introduction of a national protocol for HBV screening and adjustment of the Dutch oncology guidelines might contribute to a reduction of HBVr during chemotherapy.

Dapagliflozin for prednisone-induced hyperglycaemia in acute exacerbation of chronic obstructive pulmonary disease.

The aim of the present study was to compare the effectiveness and safety of add-on treatment with dapagliflozin to placebo in patients with prednisone-induced hyperglycaemia during treatment for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). We enrolled 46 patients hospitalized for an AECOPD in a multicentre double-blind randomized controlled study in which add-on treatment with dapagliflozin 10 mg was compared with placebo. Glycaemic control and incidence of hypoglycaemia were measured through a blinded subcutaneous continuous glucose monitoring device. Participants in the dapagliflozin group spent 54 ± 27.7% of the time in target range (3.9-10 mmol/L) and participants in the placebo group spent 53.6 ± 23.4% of the time in target range (P = .96). The mean glucose concentration was 10.1 mmol/L in the dapagliflozin group and 10.4 mmol/L in the placebo group (P = .66). One participant using dapagliflozin and 2 participants using placebo experienced symptomatic hypoglycaemia. Treatment with dapagliflozin was safe and there was no difference in risk of hypoglycaemia compared with placebo. Dapagliflozin did not result in better glycaemic control compared with placebo in participants with prednisone-induced hyperglycaemia during AECOPD.

Impaired quality of life in treatment-seeking obese children of Dutch, Moroccan, Turkish and Surinamese descent.

OBJECTIVE: To determine the health-related quality of life (HRQOL) of overweight and obese multi-ethnic children compared with normal-weight children; and to investigate differences in HRQOL between self- and parent-proxy reports and ethnic groups. DESIGN: Prospective cross-sectional study. SETTING: Out-patient clinic where children and their parents filled out a validated HRQOL questionnaire (KIDSCREEN-52) and height, weight, waist circumference and fat percentage were measured. SUBJECTS: Overweight and obese children, aged 8-18 years (mean BMI Z-score 3·2 (sd 0·6)), from the obesity out-patient clinic. RESULTS: Three hundred and eight self- and 213 parent-proxy reported questionnaires were completed. Global HRQOL and the Physical Wellbeing, Moods & Emotions and Self-Perception subscales were markedly reduced in our multi-ethnic obese cohort, relative to the Dutch reference values. Parent proxies reported significantly lower on the global HRQOL and the Physical Wellbeing, Moods & Emotions and Bullying subscales. In Caucasian children, multivariate analyses showed that BMI was associated with the quality-of-life subscales Moods & Emotions, Self-Perception and Bullying. CONCLUSIONS: HRQOL was markedly reduced in our multi-ethnic overweight and obese out-patient clinic cohort, with significantly lower parent-proxy scores compared with self-reported scores. We believe intervention programmes aiming to improve HRQOL should be directed to both parents and children, while ethnic-specific programmes to enhance HRQOL seem of less importance.

The development of a multidisciplinary, evidence-based guideline for "HIV and employment".

The objective of this study was to develop a multidisciplinary guideline that supports the care and vocational rehabilitation of HIV-infected people with employment-related problems. The guideline was developed according to the "evidence-based guideline development" method developed by the Dutch Institute for Health Care Improvement. This method consists of the following steps: forming a multidisciplinary core group and an expert panel, formulating key questions, searching and appraising the available literature, formulating considerations and recommendations, peer reviewing the draft guideline, and authorizing the final guideline. All relevant professional associations were represented in the core group that was assembled to develop the guideline, i.e., HIV doctors, HIV nurses, general practitioners, occupational health physicians, psychologists, social workers, occupational health nurses, vocational experts, and insurance physicians. Five key questions for the guideline were formulated with the following themes: determinants of employment, disclosure and stigma, self-management, interventions, and the organization of care. In the literature review on these topics, 45 studies met the inclusion criteria. The methodological quality of the included articles was poor. Factors such as patient preferences and medical/ethical issues were considered. The recommendations in the guideline are a weighting of the scientific evidence and the considerations of the core group. The guideline, as well as its summary for daily practice, clarifies the most important barriers and facilitators to people with HIV either staying at work or returning to work, and it constitutes a clinical, easy-to-use guideline for health-care providers and how they can support people with HIV who want to work.

High prevalence of vitamin D insufficiency/deficiency in Dutch multi-ethnic obese children.

Vitamin D insufficiency/deficiency is common among non-white children; however, little is known about the prevalence of vitamin D insufficiency/deficiency in non-white obese children living in the Netherlands. Therefore, a retrospective analysis was performed on data from multi-ethnic Dutch children and adolescents 6­18 years who visited the obesity outpatient clinic in 2012­2013. We performed anthropometric measurements, oral glucose tolerance test, and measured 25(OH)D and lipid levels. Vitamin D insufficiency was defined as 25(OH)D levels 37.5- <50 nmol/L and vitamin D deficiency as 25(OH)D <37.5 nmol/L. In total, data from 387 children were obtained (mean age 11.6 years, 41.1 % boys, 10.3 % Dutch native, 25.6 % Turkish, 24.5 % Moroccan, 7.5 % African Surinamese, and 7.0 % West African). The median 25(OH)D level was 34 (range 12­105) nmol/L. In total, 17.8 % were vitamin D sufficient, 24.5 % with vitamin D insufficiency, and 57.6 % with vitamin D deficiency. Obese ethnic children showed the highest (87.5 %) and normal weight white children showed the lowest (20.0 %) prevalence of vitamin D insufficiency/deficiency . Conclusion: Vitamin D insufficiency and deficiency is extremely prevalent in treatment-seeking obese ethnic children. However, there was no evidence of an effect of vitamin D status on various components of the metabolic syndrome in our cohort.

Intermittent fasting during Ramadan causes a transient increase in total, LDL, and HDL cholesterols and hs-CRP in ethnic obese adolescents.

UNLABELLED: The radical change of lifestyle during Ramadan fast has shown to affect cardiometabolic risk variables in adults. In youth, however, no studies are available. We aimed to evaluate the effect of Ramadan fast on Body Mass Index (BMI) and the cardiometabolic profile of obese adolescents. A prospective cohort study was conducted. We measured weight, height, body composition, blood pressure, heart rate, glucose, insulin, total cholesterol, low-density lipoprotein (LDL) cholesterol and high-density lipoprotein (HDL) cholesterol, triglycerides, and high sensitivity C-reactive protein (hs-CRP) levels before, during the last week of and at 6 weeks after Ramadan. Twenty-five obese adolescents were included. BMI and glucose metabolism did not change after Ramadan or at 6 week after cessation of Ramadan. At the end of Ramadan, a significant decrease in body fat percentage was observed, while significant increases in heart rate, total cholesterol, LDL cholesterol, HDL cholesterol, and hs-CRP were found (all P < 0.05). Six weeks after Ramadan, all parameters returned to baseline levels. CONCLUSION: In this sample of 25 ethnic obese adolescents transient cardiometabolic changes were observed during Ramadan fasting. Since most of these changes were reversible within 6 weeks, there seems no harm or benefit for obese adolescents to participate in Ramadan.

Psychologists' evaluation of bariatric surgery candidates influenced by patients' attachment representations and symptoms of depression and anxiety.

This study examines whether patients self-reported attachment representations and levels of depression and anxiety influenced psychologists' evaluations of morbidly obese patients applying for bariatric surgery. A sample of 250 patients (mean age 44, 84 % female) who were referred for bariatric surgery completed questionnaires to measure adult attachment and levels of depression and anxiety. Psychologists rated patients' suitability for bariatric surgery using the Cleveland Clinic Behavioural Rating System (CCBRS), unaware of the results of the completed questionnaires. Attachment anxiety (OR = 2.50, p = .01) and attachment avoidance (OR = 3.13, p = .001) were found to be associated with less positive evaluations on the CCBRS by the psychologists, and symptoms of depression and anxiety mediated this association. This study strongly supports the notion that patients' attachment representations influence a psychologist's evaluation in an indirect way by influencing the symptoms of depression and anxiety patients report during an assessment interview. The clinical implications of these findings are discussed.

Nucleosomes and neutrophil activation in sickle cell disease painful crisis.

Activated polymorphonuclear neutrophils play an important role in the pathogenesis of vaso-occlusive painful sickle cell crisis. Upon activation, polymorphonuclear neutrophils can form neutrophil extracellular traps. Neutrophil extracellular traps consist of a meshwork of extracellular DNA, nucleosomes, histones and neutrophil proteases. Neutrophil extracellular traps have been demonstrated to be toxic to endothelial and parenchymal cells. This prospective cohort study was conducted to determine neutrophil extracellular trap formation in sickle cell patients during steady state and painful crisis. As a measure of neutrophil extracellular traps, plasma nucleosomes levels were determined and polymorphonuclear neutrophil activation was assessed measuring plasma levels of elastase-α1-antitrypsin complexes in 74 patients in steady state, 70 patients during painful crisis, and 24 race-matched controls using Enzyme Linked Immunosorbent Assay. Nucleosome levels in steady state sickle cell patients were significantly higher than levels in controls. During painful crisis levels of both nucleosomes and elastase-α1-antitrypsin complexes increased significantly. Levels of nucleosomes correlated significantly to elastase-α1-antitrypsin complex levels during painful crisis, (Sr = 0.654, P<0.001). This was seen in both HbSS/HbSß(0)-thalassemia (Sr=0.55, P<0.001) and HbSC/HbSß(+-)thalassemia patients (Sr=0.90, P<0.001) during painful crisis. Levels of nucleosomes showed a correlation with length of hospital stay and were highest in patients with acute chest syndrome. These data support the concept that neutrophil extracellular trap formation and neutrophil activation may play a role in the pathogenesis of painful sickle cell crisis and acute chest syndrome.

RT-PCR detection of respiratory pathogens in newborn children admitted to a neonatal medium care unit.

BACKGROUND: This study aimed to determine the prevalence of respiratory pathogens among newborns admitted to a neonatal medium care unit (NMCU) and to identify clinical predictors. METHODS: A 1-y observational study was performed of neonates admitted to an NMCU in Amsterdam, The Netherlands. Nasopharyngeal samples were collected for the detection of respiratory viruses and bacteria by real-time PCR (RT-PCR). Cycle threshold (Ct) values were provided to estimate viral load. Predictors for the presence of study pathogens were identified. RESULTS: From October 2010 through September 2011, 334 neonates (median age 1.3 d, 53.6% male) were included. Overall, 37 respiratory pathogens were detected in 34 children (10.2%): parainfluenza-1 (n = 9), human rhinovirus (n = 7), parainfluenza-3 (n = 6), respiratory syncytial virus (RSV, n = 6), Streptococcus pneumoniae (n = 3), adenovirus (n = 2), human coronavirus (n = 2), influenza A (n = 1), and bocavirus (n = 1). Neonates with higher viral loads (Ct <35; n = 11) were more often clinically ill than those with lower viral loads (Ct ≥35; n = 23). Two variables significantly contributed to the detection of study pathogens: age (odds ratio (OR) 1.21 for each day older; 95% confidence interval 1.12-1.30) and rhinorrhea (OR 6.71; 95% confidence interval 1.54-29.21). CONCLUSION: Respiratory pathogens seem to play a role in neonates admitted to an NMCU. The influence of respiratory pathogen detection on clinical management remains to be determined.

Increasing thyroid-stimulating hormone is associated with impaired glucose metabolism in euthyroid obese children and adolescents.

BACKGROUND: Contrasting data exist regarding the relationship between thyroid-stimulating hormone (TSH) and obesity-related risk factors in children. In the present study, we investigated the association between TSH, free T4 (fT4) and cardiometabolic risk factors in euthyroid obese children and adolescents. METHODS: A retrospective analysis of patient records was performed on data from 703 multi-ethnic obese children and adolescents who visited an obesity-outpatient clinic. We performed anthropometric measurements, an oral glucose tolerance test, and measured serum TSH, fT4 and lipid levels. RESULTS: A positive association between TSH and the standard deviation score of the body mass index (BMI-Z) was found. After adjustment for ethnicity, sex, pubertal stage and BMI-Z, logistic regression analysis showed significant associations between TSH levels and impaired fasting glucose, impaired glucose tolerance, high total cholesterol, high low-density lipoprotein cholesterol and high triglycerides. No significant associations between fT4 levels and cardiometabolic risk factors were found in linear/logistic regression analysis. CONCLUSION: In our multi-ethnic cohort of euthyroid obese children and adolescents increasing TSH was associated with impaired glucose metabolism and dyslipidemia.

Genetic glucocorticoid receptor variants differ between ethnic groups but do not explain variation in age of diabetes onset, metabolic and inflammation parameters in patients with type 2 diabetes.

Aims: The effect of excess glucocorticoid receptor (GR) stimulation through glucocorticoid medication or cortisol on glucose metabolism is well established. There are genetic GR variants that result in increased or decreased GR stimulation. We aimed to determine the prevalence of genetic GR variants in different ethnic groups in a cohort of patients with type 2 diabetes, and we aimed to determine their association with age of diabetes onset and metabolic and inflammation parameters. Methods: A cross-sectional analysis was performed in a multiethnic cohort (n = 602) of patients with established type 2 diabetes. Polymorphisms in the GR gene that have previously been associated with altered glucocorticoid sensitivity (TthIIII, ER22/23EK N363S, BclI and 9ß) were determined and combined into 6 haplotypes. Associations with age of diabetes onset, HbA1c, hs-CRP and lipid values were evaluated in multivariate regression models. Results: The prevalence of the SNPs of N363S and BclI was higher in Dutch than in non-Dutch patients. We observed a lower prevalence of the SNP 9ß in Dutch, South(East) Asian and Black African patients versus Turkish and Moroccan patients. We did not detect an association between SNPs and diabetes age of onset or metabolic parameters. We only found a trend for lower age of onset and higher HbA1c in patients with 1 or 2 copies of haplotype 3 (TthIIII + 9ß). Conclusions: The prevalence of genetic GR variants differs between patients of different ethnic origins. We did not find a clear association between genetic GR variants and age of diabetes onset or metabolic and inflammation parameters. This indicates that the clinical relevance of GR variants in patients with established type 2 diabetes is limited.

Increased efflux of oxidized glutathione (GSSG) causes glutathione depletion and potentially diminishes antioxidant defense in sickle erythrocytes.

Erythrocytes are both an important source and target of reactive oxygen species in sickle cell disease. Levels of glutathione, a major antioxidant, have been shown to be decreased in sickle erythrocytes and the mechanism leading to this deficiency is not known yet. Detoxification of reactive oxygen species involves the oxidation of reduced glutathione (GSH) into glutathione-disulfide (GSSG) which is actively transported out of erythrocyte. We questioned whether under oxidative conditions, GSSG efflux is increased in sickle erythrocytes. Erythrocytes of 18 homozygous sickle cell patients and 9 race-matched healthy controls were treated with 2,3-dimethoxy-l,4-naphthoquinone, which induces intracellular reactive oxygen species generation, to stimulate GSSG production. Intra- and extracellular concentrations of GSH and GSSG were measured at baseline and during 210-minute 2,3-dimethoxy-l,4-naphthoquinone stimulation. While comparable at baseline, intracellular and extracellular GSSG concentrations were significantly higher in sickle erythrocytes than in healthy erythrocyte after 210-minute 2,3-dimethoxy-l,4-naphthoquinone stimulation (69.9 ± 3.7 µmol/l vs. 40.6 ± 6.9 µmol/l and 25.8 ± 2.7 µmol/l vs. 13.6 ± 1.7 µmol/l respectively, P<0.002). In contrast to control erythrocytes, where GSH concentrations remained unchanged (176 ± 8.4 µmol/l vs. 163 ± 13.6 µmol/l, NS), GSH in sickle erythrocytes decreased significantly (from 167 ± 8.8 µmol/l to 111 ± 11.8 µmol/l, P<0.01) after 210-minute 2,3-dimethoxy-l,4-naphthoquinone stimulation. Adding multidrug resistance-associated protein-1 inhibitor (MK571) to erythrocytes blocked GSSG efflux in both sickle and normal erythrocytes. GSSG efflux, mediated by multidrug resistance-associated protein-1, is increased in sickle erythrocytes, resulting in net loss of intracellular glutathione and possibly higher susceptibility to oxidative stress.

Increasing levels of free thyroxine as a risk factor for a first venous thrombosis: a case-control study.

A hypercoagulable state exists in hyperthyroidism, but the association with venous thrombosis (VT) is not fully explored. We aimed to investigate VT risk for different plasma levels of thyroid hormones and thyroid antibodies. We used a case-control study on leg vein thrombosis conducted between September 1999 and August 2006 at the Academic Medical Center, Amsterdam, The Netherlands. Parameters of thyroid function were assessed in 190 cases (mean age, 57 years; range, 19-90 years) and 379 sex-matched controls (mean age, 56 years; range, 18-93 years). Odds ratios (ORs) and 95% confidence intervals (CIs) for VT risk were estimated according to several cutoff levels derived from plasma levels observed in controls. We found the risk of VT to gradually rise with increasing levels of free thyroxine (FT(4)). In the absence of traditional acquired risk factors, FT(4) levels above 17 pmol/L yielded a sex- and age-adjusted OR of 2.2 (95% CI, 1.2-4.2) for deep VT, which further increased up to an OR of 13.0 (95% CI, 1.1-154.1) for FT(4) levels above reference range. Our data suggest increasing levels of FT(4) to be a risk factor for VT and may have implications for both the prevention and management of this disease.

N-acetylcysteine reduces oxidative stress in sickle cell patients.

Oxidative stress is of importance in the pathophysiology of sickle cell disease (SCD). In this open label randomized pilot study the effects of oral N-acetylcysteine (NAC) on phosphatidylserine (PS) expression as marker of cellular oxidative damage (primary end point), and markers of hemolysis, coagulation and endothelial activation and NAC tolerability (secondary end points) were studied. Eleven consecutive patients (ten homozygous [HbSS] sickle cell patients, one HbSß(0)-thalassemia patient) were randomly assigned to treatment with either 1,200 or 2,400 mg NAC daily during 6 weeks. The data indicate an increment in whole blood glutathione levels and a decrease in erythrocyte outer membrane phosphatidylserine exposure, plasma levels of advanced glycation end-products (AGEs) and cell-free hemoglobin after 6 weeks of NAC treatment in both dose groups. One patient did not tolerate the 2,400 mg dose and continued with the 1,200 mg dose. During the study period, none of the patients experienced painful crises or other significant SCD or NAC related complications. These data indicate that N-acetylcysteine treatment of sickle cell patients may reduce SCD related oxidative stress.

Prolactin and venous thrombosis: indications for a novel risk factor?

OBJECTIVE: Several acquired risk factors for venous thrombosis (VT) are associated with high prolactin levels. Our goal was to investigate VT risk for different levels of prolactin. METHODS AND RESULTS: We used data of a case-control study on leg vein thrombosis conducted between September 1999 and August 2006 at the Academic Medical Center, Amsterdam, the Netherlands. Prolactin was assessed in 187 cases (mean age, 57 years; range, 19 to 90) and 374 gender-matched controls (mean age, 57 years; range, 18 to 93). Odds ratios and 95% CI for VT risk were estimated based on several cutoff levels derived from prolactin levels in controls. Odds ratios for VT risk clearly increased with higher prolactin levels. For prolactin levels above the 75th percentile (8 µg/L), we found an odds ratio of 1.7 (95% CI 1.0 to 2.7) as compared with levels below the 50th percentile (6 µg/L). This further increased up to an odds ratio of 4.7 (95% CI 1.8 to 11.8) for prolactin levels above the 97.5th percentile (16 µg/L). The risk was most pronounced in premenopausal women. CONCLUSIONS: Our data suggest that prolactin levels are associated with VT in a dose-dependent fashion. Future studies are needed to evaluate the causality of this relationship.

Low attack rate of novel influenza A (H1N1) virus infection among healthcare workers: a prospective study in a setting with an elaborated containment plan.

PURPOSE: This study aimed to determine incidence rates of novel influenza A (H1N1) infection among healthcare personnel with different exposure risks during the 2009 H1N1 pandemic. METHODS: From August 2009 until April 2010, 66 healthcare workers from a 410 bed teaching hospital in Amsterdam were monitored. The following three different exposure groups were created: a high- (n = 26), intermediate- (n = 20), and low-risk group (n = 20). Throat swabs were collected each week and analyzed by real-time reverse transcriptase-polymerase chain reaction (RT-PCR) in order to detect the H1N1 virus. Blood was drawn at study enrollment and once monthly thereafter, and serum specimens were tested with an H1N1-specific hemagglutination-inhibition serologic assay. Influenza-like signs and symptoms were assessed weekly. RESULTS: One of 26 high-risk group participants proved H1N1 positive once by RT-PCR. This corresponds to an incidence rate in the high-risk group of 5.7/1,000 person weeks (95% CI 0-17/1,000). None of the intermediate- and low-risk group participants proved H1N1 positive by RT-PCR. Significant antibody titer rises in convalescent sera were demonstrated in three participants: one was a confirmation of the case that had proved H1N1 positive by RT-PCR; the others occurred in two asymptomatic participants belonging to the low- and high-risk groups. An influenza-like illness was assumed in four participants from the high- (n = 1), intermediate- (n = 1) and low-risk (n = 2) groups; these findings were not confirmed by positive results from either diagnostic test. CONCLUSIONS: This study demonstrates a low incidence rate of influenza A (H1N1) infection among healthcare workers during the 2009 H1N1 pandemic in a setting with high hygiene standards.

Characterization of 2009 H1N1 pandemic influenza in a population of Dutch children with influenza-like signs and symptoms.

AIM: To determine causative respiratory pathogens and describe epidemiological and clinical characteristics in a paediatric population with influenza-like illness during the 2009 H1N1-pandemic. METHODS: Observational study of 412 children visiting an outpatient clinic of a Dutch teaching hospital. RESULTS: From August to December 2009, 412 children were tested at the clinic; 32% proved H1N1-positive, confirmed by reverse-transcriptase-polymerase-chain-reaction (RT-PCR). Pathogens were detected in 65% of samples. Influenza A(H1N1) (n = 132), human rhinovirus (n = 55), respiratory syncytial virus (n = 45) and adenovirus (n = 34) were mostly identified. Co-infections were seen in 34 children (8.3%). Mean age was 6.8 and 4.2 years in H1N1-positive and H1N1-negative cases, respectively (p < 0.01). H1N1-positive outpatient children reported fever, cough and rhinorrhoea more frequently than their H1N1-negative counterparts. Of 72 hospitalized children, 31% proved H1N1-positive; all showed a relatively mild clinical illness. None of the children had been admitted to an intensive care unit or died. Oseltamivir treatment was initiated in 72 children and discontinued in 42 (63%) when RT-PCR results turned negative. CONCLUSION: The 2009 H1N1-pandemic showed a mild clinical course in a Dutch paediatric outpatient clinic population. Respiratory pathogens were detected in the majority of children with influenza-like illness and influenza A(H1N1) virus was identified in one-third. Testing symptomatic children during an influenza pandemic has effectively limited the use of oseltamivir.

Microbiome-derived ethanol in nonalcoholic fatty liver disease.

To test the hypothesis that the gut microbiota of individuals with nonalcoholic fatty liver disease (NAFLD) produce enough ethanol to be a driving force in the development and progression of this complex disease, we performed one prospective clinical study and one intervention study. Ethanol was measured while fasting and 120 min after a mixed meal test (MMT) in 146 individuals. In a subset of 37 individuals and in an external validation cohort, ethanol was measured in portal vein blood. In an intervention study, ten individuals with NAFLD and ten overweight but otherwise healthy controls were infused with a selective alcohol dehydrogenase (ADH) inhibitor before an MMT. When compared to fasted peripheral blood, median portal vein ethanol concentrations were 187 (interquartile range (IQR), 17-516) times higher and increased with disease progression from 2.1 mM in individuals without steatosis to 8.0 mM in NAFL 21.0 mM in nonalcoholic steatohepatitis. Inhibition of ADH induced a 15-fold (IQR,1.6- to 20-fold) increase in peripheral blood ethanol concentrations in individuals with NAFLD, although this effect was abolished after antibiotic treatment. Specifically, Lactobacillaceae correlated with postprandial peripheral ethanol concentrations (Spearman's rho, 0.42; P < 10-5) in the prospective study. Our data show that the first-pass effect obscures the levels of endogenous ethanol production, suggesting that microbial ethanol could be considered in the pathogenesis of this highly prevalent liver disease.

Plasma levels of pentraxin-3, an acute phase protein, are increased during sickle cell painful crisis.

The painful crisis accounts for the majority of sickle cell disease (SCD) related hospital admissions. The prototypic long pentraxin 3 (PTX3), an acute phase protein, is elevated in patients with inflammatory and ischemic states. As the sickle cell painful crisis is associated with both inflammation and tissue ischemia, we questioned whether plasma PTX3 levels are increased during and associated with painful crisis severity. Furthermore, since PTX3 up-regulates endothelial expression of tissue factor we studied PTX levels in relation to markers of endothelial and coagulation activation. Plasma levels of PTX3, ultra-sensitive C-reactive protein (US-CRP), prothrombin fragment 1+2, thrombin-antithrombin (TAT) complexes, von Willebrand Factor antigen and soluble vascular adhesion molecule-1 were determined in 105 asymptomatic sickle cell patients, 33 patients during painful crisis and 30 race matched healthy controls. Plasma PTX3 levels were comparable between patients in asymptomatic state and healthy controls, but significantly higher during painful crisis (P<0.01). US-CRP levels were higher in asymptomatic patients compared to controls (P<0.0001) and increased further during painful crisis (P<0.0001). PTX3 levels at presentation with painful crisis correlated significantly with the duration of subsequent hospital admission (r(s) = 0.43; P = 0.013), whereas US-CRP levels did not. PTX3 levels did not correlate with markers of hypercoagulability. The increase of PTX3 levels during painful crisis and their relation to the duration of subsequent hospital stay suggest that PTX3 might serve both as a diagnostic and severity marker of the painful sickle cell crisis.