Lactose after Roux-en-Y gastric bypass for morbid obesity, is it a problem?

BACKGROUND: Roux-en-Y gastric bypass (RYGB) can cause multiple food intolerances and gastrointestinal complaints are frequently reported after dairy consumption. We aimed to determine the prevalence of lactose malabsorption and intolerance, and complaints associated with dairy consumption in daily life, before and after RYGB. METHOD: The lactose breath test (LBT) and lactose tolerance test (LTT) was performed in 84 patients awaiting RYGB surgery and 84 patients after surgery. Gastrointestinal symptoms at baseline and after testing were recorded. Lactose malabsorption was defined as a positive LBT and/or LTT. Lactose intolerance as a positive test combined with an increase of gastrointestinal complains. Dairy consumption in daily life and successive gastrointestinal complaints were registered via a questionnaire. Results of preoperative and postoperative patients were compared. RESULTS: Lactose malabsorption was present in 15 (17.9%) of the preoperative patients and in 25 (29.8%) of the postoperative patients (OR 2.46; 95%CI: 1.08-5.59; p = .03). Of the preoperative patients 6 (7.1%) patients met the criteria for lactose intolerance, compared to 8 (9.5%) patients in the postoperative group (OR 1.48; 95%CI 0.48-4.57; p = .50). Twelve (14.3%) preoperative patients indicated to have gastrointestinal complaints after dairy consumption in daily life versus 45 (53.6%) postoperative patients (p < .01). CONCLUSION: This study shows no increase in patients with proven lactose intolerance after RYGB compared to preoperative patients. Gastrointestinal complaints after dairy consumption in daily life were far more frequently reported by RYGB patients. It is unlikely that all reported gastrointestinal complaints are actually caused by lactose. Other ingredients in dairy, like fat, are possibly contributory.

Introduction of routine hepatitis B screening for all patients receiving cancer treatment.

BACKGROUND: Patients with a chronic hepatitis B virus (HBV) infection or patients who have recovered from an HBV infection are at risk for HBV reactivation (HBVr), especially if they need treatment with chemotherapy. International guidelines recommend routine HBV screening for all patients starting with chemotherapy. This study evaluates the implementation of a routine HBV screening protocol. METHODS: A retrospective study was performed between January 2015 and October 2016 at the Medical Centre Slotervaart Amsterdam. All patients with a solid or hematological malignancy starting intravenous chemotherapy were included. In September 2015, a protocol for routine HBV screening was introduced. HBV screening results were evaluated before and after implementation of the screening protocol. RESULTS: In total, 184 patients were included, of which 129 patients were actually screened; 37 of the 70 (53%) patients were screened in the group before implementation of the protocol and 92 of the 114 (81%) after implementation. Before routine HBV screening, 8/37 (21.6%) patients tested anti-HBc positive; after introduction of routine screening, 13/92 (14.1%) patients tested anti-HBc positive. After implementation of the screening protocol, no HBVr occurred. CONCLUSION: Implementation of routine HBV screening in patients starting chemotherapy increases identification of the number of patients identified as at risk for HBVr and contributes to prevention of HBVr. A high prevalence of anti-HBc positive patients was found during routine HBV screening, indicating the importance of screening. Awareness and implementation of routine HBV screening, together with knowledge of existing guidelines is necessary to increase the HBV screening rate in patients treated with chemotherapy.

Dynamics of von Willebrand factor reactivity in sickle cell disease during vaso-occlusive crisis and steady state.

Essentials The role of von Willebrand Factor (VWF) in the pathophysiology of sickle cell disease is unclear. We assessed markers of VWF during admission for vaso-occlusive crisis (VOC) and steady state. VWF reactivity was higher during VOC and was associated with inflammation and neutrophil activation. Hyper-adhesive VWF may promote VOC in sickle cell disease. SUMMARY: Background Endothelial activation plays a central role in the pathophysiology of vaso-occlusion in sickle cell disease (SCD), facilitating adhesive interactions with circulating blood cells. Upon activation, various adhesive molecules are expressed, including von Willebrand factor (VWF). Increased VWF levels have been observed in patients with SCD during steady state. However, the role of VWF in the pathogenesis of SCD vaso-occlusion is unclear. Objectives To longitudinally assess the quantity and reactivity of VWF and its regulating protease ADAMTS-13 during vaso-occlusive crisis (VOC). Methods In this observational study, we obtained sequential blood samples in adult SCD patients during VOC. Results VWF reactivity was significantly higher during VOC (active VWF, VWF glycoprotein Ib-binding activity, and high molecular weight multimers), whereas platelet count and levels of ADAMTS-13 antigen and ADAMTS-13 activity were concomitantly lower than during steady state. Levels of VWF antigen, VWF propeptide (VWF:pp) and ADAMTS-13 specific activity did not change during VOC. VWF reactivity correlated strongly with markers of inflammation and neutrophil activation, and was inversely correlated with the platelet count. In patients who developed acute chest syndrome, levels of VWF, VWF:pp and active, hyperadhesive VWF were significantly higher, whereas ADAMTS-13 activity was lower, than in patients without this complication. Conclusions We provide the first evidence that VOC in SCD is associated with increased reactivity of VWF, without a pronounced ADAMTS-13 deficiency. This hyper-reactivity may be explained by resistance of VWF to proteolysis, secondary to processes such as inflammation and oxidative stress. Hyperadhesive VWF, scavenging blood cells in the microcirculation, may thereby amplify and sustain VOC in SCD.

Gastrointestinal symptoms and food intolerance 2 years after laparoscopic Roux-en-Y gastric bypass for morbid obesity.

BACKGROUND: Laparoscopic Roux-en-Y gastric bypass (LRYGB) is an effective treatment for morbid obesity, but might aggravate gastrointestinal complaints and food intolerance. The long-term prevalence of these symptoms has not been well studied. METHODS: In a cross-sectional study, all patients who underwent primary LRYGB from May to October 2012 were approached 2 years after surgery to complete a general health questionnaire, the Gastrointestinal Symptom Rating Scale (GSRS), and a food intolerance questionnaire. The results were compared with those for a control group of morbidly obese patients. RESULTS: A total of 249 patients were included for analysis, representing a response rate of 93·9 per cent. Mean(s.d.) total weight loss was 30·8(8·7) per cent. The total mean GSRS score was higher in patients who had LRYGB (median 2·19 versus 1·75 in unoperated patients; P < 0·001); the difference in symptoms of indigestion was most notable (P < 0·001). Food intolerance for specific products was reported by 70·7 (95 per cent c.i. 64·8 to 76·0) per cent of the postoperative patients, for a median of 4 foods. There was a positive correlation between food intolerance and score on the GSRS. There was no correlation between either food intolerance or the total mean GSRS score and weight loss, but there was a correlation between weight loss and abdominal pain. CONCLUSION: At 2 years after surgery, patients undergoing LRYGB for morbid obesity have more gastrointestinal complaints than obese controls. Food intolerance is a common side-effect of LRYGB independent of degree of weight loss or the presence of other abdominal symptoms.

Employment-related concerns of HIV-positive people in the Netherlands: input for a multidisciplinary guideline.

PURPOSE: Finding and keeping employment is difficult for people with HIV. To improve supportive care for people with HIV and employment-related problems, a multidisciplinary guideline was developed in the Netherlands in 2010/2011. To identify the employment-related concerns of people with HIV and to formulate the key questions for the guideline, we conducted a qualitative study. The results of this study are described in this article. METHODS: This study was performed in three HIV-treatment centers in the Netherlands. In total 18 participants participated in three focus-group interviews and nine participants were interviewed individually. The data were transcribed ad verbatim and were analyzed according to the principle of constant comparison. RESULTS: Our findings indicate that people with HIV in the Netherlands face many work-related concerns. The themes which emerged from this study were disclosure, stigma and discrimination, knowledge about HIV, physical and psychological factors, working conditions, absenteeism, reintegration, and dismissal and counselling. CONCLUSIONS: This study provides insight into employment-related concerns for people with HIV living in a Western country. It formed the basis for the key questions which were addressed in a multidisciplinary, evidence-based guideline "HIV and work". Finally, it gives leads for further scientific research and opportunities for improving the vocational guidance of people with HIV.

The impact of surgical complications as a main risk factor for venous thromboembolism: a multicenter study.

BACKGROUND: Studies suggest that postoperative complications are a risk factor for venous thromboembolism (VTE) after bariatric surgery. Knowledge of factors associated with a higher risk of VTE after bariatric surgery may be essential to select patients who may benefit from either prolonged or intensified thrombosis prophylaxis. The aim of this study is to determine the relationship between postoperative complications and VTE after bariatric surgery and other classical risk factors. METHODS: A retrospective multicenter case-control study was performed in patients who had bariatric surgery between January 2008 and September 2011. VTE until 6 months after surgery was registered, and patients were contacted to ascertain the results. For every case of VTE after surgery, 6 control patients were selected who were matched for gender, age, participating center and type of surgery. Risk factors for VTE before and after surgery and postoperative complications were registered. RESULTS: A total of 2,064 surgeries were included. In 12 patients, VTE occurred within 6 months after bariatric surgery (incidence 0.58 %, 95 % confidence interval (CI) = 0.25-0.93). There was a strong association of complications after surgery (cases 91.7 %, controls 15.3 %, odds ratio (OR) 61.0; 95 % CI = 7.1-521.3) or intensive care admission (cases 50.0 %, controls 11.1 %, OR = 8.0; 95 % CI = 2.1-30.8) with VTE. The majority of postoperative complications were anastomotic leak, abdominal abscess, and infection. We could not detect an association between classical thrombosis risk factors and postoperative VTE. CONCLUSIONS: The incidence of VTE is low after bariatric surgery using thrombosis prophylaxis. However, there is a strong association between postoperative complications and VTE. These patients may benefit from more intensive thrombosis prophylaxis.

High levels of procoagulant factors mediate the association between free thyroxine and the risk of venous thrombosis: the MEGA study.

BACKGROUND: Thyroid hormone affects the coagulation system, but its effect on clinical disease is not clear. We determined the associations of levels of free thyroxine (FT4), thyroid-stimulating hormone (TSH) and anti-thyroid peroxidase antibodies (antiTPO) with levels of coagulation factors and the risk of venous thrombosis. METHODS: In a large population based case-control study (Multiple Environmental and Genetic Assessment of risk factors for venous thrombosis study) on the etiology of venous thrombosis, we determined the levels of FT4, TSH, antiTPO, factor FII, FVII, FVIII, FIX, FX, von Willebrand factor (VWF), antithrombin, protein C, protein S and fibrinogen in 2177 cases and 2826 controls. RESULTS: High levels of FT4 were associated with increased concentrations of procoagulant factors, and not with levels of anticoagulant factors. High levels of FT4 were also associated with the risk of venous thrombosis, up to an odds ratio (OR) of 2.2 (95% confidence interval [CI] 1.0-4.6) for levels above 24.4 pm relative to FT4 levels between 15.5 and 18.9 pm. In 11 cases and one control, clinical hyperthyroidism had been diagnosed within a year of the thrombotic event, leading to an OR of 17.0 (95% CI 2.2-133.0) for thrombosis. The ORs approached unity after adjustment for FVIII and VWF, which suggests that the effect was mediated by these factors. Low TSH levels were also, but less evidently, associated with thrombosis, whereas there was no association between antiTPO and venous thrombosis risk. CONCLUSIONS: High levels of FT4 increase the concentrations of the procoagulant proteins FVIII, FIX, fibrinogen, and VWF, and by this mechanism increase the risk of venous thrombosis.

The effect of levothyroxine on expression of inflammation-related genes in healthy subjects: a controlled randomized crossover study.

An excess of thyroid hormone leads to a prothrombotic state; however, the underlying pathophysiological mechanisms remain unknown. As evidence points towards an extensive "cross-talk" between the inflammatory and coagulation cascade, inflammation has been claimed as a possible mechanism through which different risk factors trigger venous thrombus formation. We aimed to study changes in expression of inflammation-related genes of the leukocyte RNA expression profile in healthy subjects in response to supraphysiological doses of levothyroxine. In a randomized single-blinded crossover design, 12 healthy volunteers (aged 18-40 years) received levothyroxine and no medication, both for 14 days with a wash-out period of at least 28 days between the periods. Blood was sampled at baseline and day 14 of each study period. MRNA was isolated from whole blood and used for multiplex ligation-dependent probe amplification to study the expression of inflammation-related genes. Compared to the control situation no significant changes were found in the expression of proinflammatory cytokines and mediators after the intake of levothyroxine. The results of this study show that high thyroid hormone levels do not lead to an altered inflammatory profile. This provides evidence against a major role of the inflammatory system as mediator in the effect of thyroid hormone on the coagulation system. The mechanisms by which thyroid hormone may influence coagulation proteins remain to be elucidated.

Review: Viral infections and mechanisms of thrombosis and bleeding.

Viral infections are associated with coagulation disorders. All aspects of the coagulation cascade, primary hemostasis, coagulation, and fibrinolysis, can be affected. As a consequence, thrombosis and disseminated intravascular coagulation, hemorrhage, or both, may occur. Investigation of coagulation disorders as a consequence of different viral infections have not been performed uniformly. Common pathways are therefore not fully elucidated. In many severe viral infections there is no treatment other than supportive measures. A better understanding of the pathophysiology behind the association of viral infections and coagulation disorders is crucial for developing therapeutic strategies. This is of special importance in case of severe complications, such as those seen in hemorrhagic viral infections, the incidence of which is increasing worldwide. To date, only a few promising targets have been discovered, meaning the implementation in a clinical context is still hampered. This review discusses non-hemorrhagic and hemorrhagic viruses for which sufficient data on the association with hemostasis and related clinical features is available. This will enable clinicians to interpret research data and place them into a perspective.

Alterations in coagulation and fibrinolysis after levothyroxine exposure in healthy volunteers: a controlled randomized crossover study.

BACKGROUND: Several hemostatic abnormalities have been reported in hyperthyroidism, but the overall effect of thyroid hormone excess on coagulation and fibrinolysis is unclear. OBJECTIVE: Our aim was to assess whether the use of supraphysiological doses of levothyroxine leads to coagulation activation and inhibition of fibrinolysis. PATIENTS AND METHODS: Healthy volunteers were randomized to receive levothyroxine or no medication for 14 days with a washout period of at least 28 days in a crossover design. To study the effects of different degrees of thyroid hormone excess, 16 participants received levothyroxine in a dose of 0.3 mg per day, and 12 received levothyroxine 0.45 or 0.6 mg per day depending on body weight. Several variables of coagulation and fibrinolysis were measured. RESULTS: Levels of von Willebrand factor activity (VWF:RiCo) and antigen (VWF:Ag), factor (F) VIII, plasminogen activator inhibitor-1 (PAI-1) and clot-lysis time were slightly higher after levothyroxine 0.3 mg per day than after the control situation, but only levels of VWF showed a significant increase from baseline. After levothyroxine 0.45 or 0.6 mg per day, levels of fibrinogen increased by 17%, VWF activity by 24%, VWF antigen by 26%, FVIII by 19%, FIX by 14%, FX by 7%, PAI-1 by 116% and clot-lysis time by 14%, and activated partial thromboplastin time decreased by 3%; all were significant changes compared with the control situation. We did not observe clear evidence of coagulation activation. CONCLUSIONS: Our data suggest that thyroid hormone excess increases coagulation factor levels and inhibits fibrinolysis in a dose-dependent fashion. This implies an increased risk of venous thrombosis during hyperthyroidism.

Procalcitonin as a potent marker of bacterial infection in febrile Afro-Caribbean patients at the emergency department.

Procalcitonin (PCT) has been shown to be of additional value in the work-up of a febrile patient. This study is the first to investigate the additional value of PCT in an Afro-Caribbean febrile population at the emergency department (ED) of a general hospital. Febrile patients were included at the ED. Prospective, blinded PCT measurements were performed in patients with a microbiologically or serologically confirmed diagnosis or a strongly suspected diagnosis on clinical grounds. PCT analysis was performed in 93 patients. PCT levels differentiated well between confirmed bacterial and confirmed viral infection (area under the curve [AUC] of 0.82, sensitivity 85%, specificity 69%, cut-off 0.24 ng/mL), between confirmed bacterial infection and non-infectious fever (AUC of 0.84, sensitivity 90%, specificity 71%, cut-off 0.21 ng/mL) and between all bacterial infections (confirmed and suspected) and non-infectious fever (AUC of 0.80, sensitivity 85%, specificity 71%, cut-off 0.21 ng/mL). C-reactive protein (CRP) levels were shown to be less accurate when comparing the same groups. This is the first study showing that, in a non-Caucasian febrile population at the ED, PCT is a more valuable marker of bacterial infection than CRP. These results may improve diagnostics and eventually decrease antibiotic prescriptions in resource-limited settings.

One-year epidemiology of fever at the Emergency Department.

BACKGROUND: Although fever is recognised as a major presentation symptom at Emergency Departments (EDs) and is often used as a rationale for the institution of antibiotics, few studies describing patients with fever as the sole inclusion criterion at the ED of a general hospital have been performed. The objective of this study is to describe epidemiology of non-surgical febrile patients at the ED and to identify risk factors for adverse outcome. METHODS: Blood, sputum, urine and faeces cultures, urine sediments and throat swaps for viral diagnostics were obtained from febrile ED patients. Outcome parameters were bacterial/viral infection, non-bacterial/non-viral infection, non-infectious febrile disease; mortality, hospital admission, admission to the intensive care unit (ICU) and length of hospital stay. RESULTS: 213 Patients were included (87.8% were hospitalised, 8.5% were admitted to ICU, 4.2% died). In 75 patients (35.2%), bacterial infection was confirmed; in 78 patients (36.6%) bacterial infection was suspected. In nine patients (4.2%), viral diagnosis was confirmed; in six patients (2.8%), a viral condition was suspected. The most frequently encountered infection was bacterial pneumonia (58 patients, 27.2%). Only older age was correlated with mortality (ρ=0.176, p=0.01). CONCLUSION: A majority of the febrile patients were admitted to the hospital, mostly for bacterial infection. An overall mortality rate of 4.2% was registered. Only a few risk factors for adverse outcome could be identified in this cohort. Overall, the outcome of patients presenting with fever at the ED is rather benign.

Systematic review on the effect of glucocorticoid use on procoagulant, anti-coagulant and fibrinolytic factors.

BACKGROUND: Whether glucocorticoid use contributes to a hypercoagulable state, and thereby enhances the thrombotic risk, is controversial. OBJECTIVE: We aimed to examine the effects of glucocorticoid use on coagulation and fibrinolysis. METHODS: MEDLINE and EMBASE databases were searched to identify published studies comparing glucocorticoid treatment with a glucocorticoid-free control situation. Subjects could be either patients or healthy volunteers. Two investigators independently performed study selection and data extraction. Results were expressed as standardized mean difference, if possible; data were pooled with a random-effects model. RESULTS: Of the 1967 identified publications, 36 papers were included. In healthy volunteers, a clear rise in factor (F)VII, VIII and XI activity was observed after glucocorticoid treatment, but these data alone provided insufficient evidence to support hypercoagulability. However, during active inflammation, glucocorticoids significantly increased levels of plasminogen activator inhibitor-1 (PAI-1), whereas levels of von Willebrand factor (VWF) and fibrinogen decreased. Peri-operative use of glucocorticoids inhibited the increase in tissue-type plasminogen activator induced by surgery. CONCLUSIONS: The present study showed differential effects of glucocorticoids depending on the clinical situation in which it is given, most likely as a result of their disease modifying properties. Clinical outcome studies are needed to adequately assess the risk-benefit of glucocorticoid use per population when thrombotic complication is the focus.

The diagnostic role of procalcitonin and other biomarkers in discriminating infectious from non-infectious fever.

Fever is not only observed in the course of a bacterial or viral infection, but can be a symptom of, for instance, auto-immune, malignant or thromboembolic disease. Determining the etiology of fever in a fast and reliable way is of pivotal importance, as different causes of fever may ask for different therapies. Neither clinical signs and symptoms, nor traditional biomarkers, such as CRP, leukocytes and ESR have sufficient sensitivity and specificity to guide treatment decisions. In this review we focus on the value of traditional and newer biomarkers in non-infectious febrile diseases. Procalcitonin (PCT) seems to be the most helpful laboratory marker for the differentiation of causes of fever, particularly in autoimmune, autoinflammatory and malignant diseases.