[The diagnostic accuracy of anti-citrullin antibody assessment in the diagnosis of patients suspected of rheumatoid arthritis by a general practitioner]. / De diagnostische accuratesse van de anticitrullinebepaling voor het vaststellen van reumatoïde artritis door de huisarts.

OBJECTIVE: To determine whether assessment of antibodies directed against citrullin provides additional value in the diagnosis of rheumatoid arthritis (RA) in general practice. DESIGN: Retrospective. METHODS: In a 6-month period in 2004 (May-December), all sera sent to our laboratory for assessment of rheumatoid factor (RF-IgM), were also analysed for the presence of antibodies directed against citrullinated fibrinogen (anti-citrullin). We analysed 691 sera sent in by general practitioners using a homemade assay. To determine the disease classification, general practitioners were asked to provide information pertaining to the American College of Rheumatology disease classification criteria. The response was 97.6%. For patients who were referred to a rheumatologist in the last 2 years (December 2004-December 2006), the diagnosis of the rheumatologist was also considered in the analysis. RESULTS: A total of 28 patients (4%) were diagnosed with rheumatoid arthritis. Only 25% of these patients were positive for anti-citrullin, and only 25% were positive for RF-IgM. These 2 groups only partially overlapped. The positive and negative predictive values of anti-citrullin were 36 and 96%, respectively. CONCLUSION: The presence of anti-citrullin provided no additional value compared to rheumatoid factor in classifying RA in a general practice population.

Improved and more effective algorithms to screen for nutrient deficiencies after bariatric surgery.

BACKGROUND/OBJECTIVES: Most bariatric guidelines recommend frequent lab monitoring of patients to detect nutrient and vitamin deficiencies as early as possible. The aim of this study was to optimize the cost effectiveness of the nutrient panel, by developing an algorithm, which detects nutrient deficiencies at lower costs. SUBJECTS/METHODS: In this retrospective study, 2055 patients who had undergone Laparoscopic Roux-Y Gastric Bypass (LRYGB) and Laparoscopic Sleeve Gastrectomy (LSG) surgery at Catharina Hospital Eindhoven between January 2009 and December 2013 were included. Perioperative biochemical measurements (7 days before and 127 days after surgery) and measurements >549 days before surgery were excluded. For analysis, the most recent preoperative and postoperative measurements were selected for each biochemical parameter separately. First, the amount of moderate and severe deficiencies were calculated. Second, we investigated whether each variable (vitamins A, B1, B6, B12, D, folate, ferritin, zinc and magnesium) could predict the presence of deficiency. RESULTS: In total, 561 (LRYGB) and 831 (LSG) patients had at least preoperative and postoperative values of vitamin A, B1, B6, B12, D, folate, ferritin, zinc or magnesium. The algorithm reduces vitamin D, B12, B6, B1 and ferritin examinations by 15, 11, 28, 28 and 38%, respectively, without missing clinically relevant deficiencies. The corresponding potential cost savings was 14%. CONCLUSIONS: This study identified substantial cost savings in laboratory test for both LRYGB and LSG procedures. The potential cost reduction of 14% might even be increased to 42% when less frequent moderate deficiencies are not screened anymore, whereas >99.0 of moderate deficiencies will be detected.

Cut-off values to rule out urinary tract infection should be gender-specific.

The diagnosis of urinary tract infection (UTI) by urine culture is an expensive and time-consuming procedure. Using a screening method, to identify negative samples, would improve the procedure and reduce costs. In this study, urine flow cytometry, of over 7000 urine samples, was assessed by retrospective analysis. With a cut-off value of >200bacteria/µl, we obtained a sensitivity of 93.0%, a specificity of 63.5%, and a negative predictive value (NPV) of 96.2%. As a result the culturing of 49% of all samples could be avoided. In addition, the data was retrospectively analyzed to determine if the introduction of gender-specific cut-off values could improve screening results. The obtained receiver operator curves are indeed significantly different when gender specific cut-offs were used. When a NPV of 95% is considered acceptable the unisex cut-off value of >200bacteria/µl can be used for women (NPV 94.9%), but the cut-off value for men could be raised to >400bacteria/µl without diminishing the NPV (NPV 95.0%).

Comparison Between Different Intramuscular Vitamin B12 Supplementation Regimes: a Retrospective Matched Cohort Study.

BACKGROUND: The incidence of vitamin B12 deficiency after bariatric surgery can range from 26 to 70 %. There is no consensus on optimal vitamin B12 supplementation in postbariatric patients. The objective of this study was to compare three different regimes. METHODS: In this retrospective matched cohort study, we included 63 patients with methylmalonic acid (MMA) levels ≥300 nmol/L. Group A (n = 21) received 6 intramuscular (im) vitamin B12 injections including a loading dose, group B (n = 21) received 3 im vitamin B12 injections without loading dose and group C (n = 21) received no im vitamin B12 injections. RESULTS: The total post-bariatric patient population consisted of 14 males (22.2 %) and 49 women (77.8 %) with a mean current body mass index of 30.6 ± 8.0 kg/m2. There was no significant difference in vitamin B12 and MMA levels between 3 groups at baseline. There was a significant difference in follow-up vitamin B12 levels of group A compared to group B (p = 0.02) and group A compared to group C (p = 0.03). In the follow-up results, there is also a significant decrease in MMA levels of group A compared to group B (p = 0.02), group A compared to group C (p < 0.001), and group B compared to group C (p < 0.01). CONCLUSIONS: In this study, a shorter injection regime is probably not sufficient to treat a vitamin B12 deficiency. An injection regime with 6 injections recovered all vitamin B12 deficiencies biochemically. MMA levels cannot recover spontaneously over time without additional im injection regime.

Improving Bariatric Patient Aftercare Outcome by Improved Detection of a Functional Vitamin B12 Deficiency.

BACKGROUND: Vitamin B12 deficiency is common after bariatric surgery. Vitamin B12 is a poor predictor of functional vitamin B12 status, since deficiencies might even occur within the reference limits. Therefore, vitamin B12 deficiencies with serum vitamin B12 levels are between 140 and 200 pmol/L remain undetected. Methylmalonic acid (MMA), however, will detect these deficiencies as accumulates due to functional intracellular vitamin B12 deficiencies. MMA is a relative expensive analysis and is therefore not generally available. To lower the costs, we only request MMA when vitamin B12 levels are between these levels. As a result, more biochemical deficiencies are found. However, it was not known whether bariatric patients with vitamin B12 levels between 140 and 200 pmol/L would benefit from supplementation. METHOD: Bariatric patients with vitamin B12 levels between 140 and 200 pmol/L with (n = 45) and without (n = 45) intramuscular hydroxocobalamin injections were compared. RESULTS: Treated patients showed a significant increase of vitamin B12 levels (P < 0.001) and a significant decrease in MMA levels (P < 0.001). Biochemical improvement occurs in both patients with and without clinical symptoms. The control group showed a significant increase of MMA levels (P < 0.001). To examine whether biochemical benefits of vitamin B12 supplementation are correlated with clinical improvement, patient records were checked for complaints. Complaints were disappeared after treatment, while no improvement was seen in untreated patients. CONCLUSION: This study shows that all bariatric patients with vitamin B12 levels between 140 and 200 pmol/L benefit clinical and biochemical from vitamin B12 supplementation, regardless the MMA levels.

Effects of overexpression of the SH2-containing inositol phosphatase SHIP on proliferation and apoptosis of erythroid AS-E2 cells.

Previous studies have demonstrated that SH2-containing inositol phosphatase (SHIP) is involved in the control of B cell, myeloid cell and macrophage activation and proliferation. The goal of the present study was to examine the role of SHIP during proliferation and apoptosis in cells of the erythroid lineage. Wild-type and catalytically inactive SHIP proteins were overexpressed in the erythropoietin (EPO)-dependent cell line AS-E2. Stable overexpression of catalytically inactive SHIP decreased proliferation and resulted in prolonged activation of the extracellular signal-regulated protein kinases ERK1/2 and protein kinase B (PKB), while wild-type SHIP did not affect EPO-mediated proliferation or phosphorylation of ERK and PKB. When AS-E2 cells were EPO deprived a significant increase in apoptosis was observed in clones overexpressing wild type. Mutational analysis showed that this increase in apoptosis was independent of the enzymatic activity of SHIP. The enhanced apoptosis due to overexpression of SHIP was associated with an increase in caspase-3 and -9 activity, without a distinct effect on caspase-8 activity or mitochondrial depolarization. Moreover, in cells overexpressing SHIP apoptosis could be reduced by a caspase-3 inhibitor. These data demonstrate that in the erythroid cell line AS-E2 overexpression of catalytically inactive SHIP reduced proliferation, while overexpression of wild-type SHIP had no effect. Furthermore, overexpression of SHIP enhanced apoptosis during growth factor deprivation by inducing specific caspase cascades, which are regulated independently of the 5-phosphatase activity of SHIP.

Urine flow cytometry can rule out urinary tract infection, but cannot identify bacterial morphologies correctly.

The diagnosis of urinary tract infection (UTI) by urine culture is a time-consuming and costly procedure. Usage of a screening method, to identify negative samples, would therefore affect time-to-diagnosis and laboratory cost positively. Urine flow cytometers are able to identify particles in urine. Together with the introduction of a cut-off value, which determines if a urine sample is subsequently cultured or not, the number of cultures can be reduced, while maintaining a low level of false negatives and a high negative predictive value. Recently, Sysmex developed additional software for their urine flow cytometers. Besides measuring the number of bacteria present in urine, information is given on bacterial morphology, which may guide the physician in the choice of antibiotic. In this study, we evaluated this software update. The UF1000i classifies bacteria into two categories: 'rods' and 'cocci/mixed'. Compared to the actual morphology of the bacterial pathogen found, the 'rods' category scores reasonably well with 91% chance of classifying rod-shaped bacteria correctly. The 'cocci/mixed' category underperforms, with only 29% of spherical-shaped bacteria (cocci) classified as such. In its current version, the bacterial morphology software does not classify bacteria, according to their morphology, well enough to be of clinical use in this study population.