Association between umbilical cord vitamin D levels and adverse neonatal outcomes.

OBJECTIVE: We investigated the associations between cord blood concentration of 25-hydroxyvitamin D [25(OH)D], neonatal outcomes, and the risk of hospitalization during the first year of life. METHODS: A total of 402 newborn infants and their mothers were prospectively enrolled and divided in four groups according to season of the year. We determined 25(OH)D serum concentrations from maternal-neonatal pairs at delivery by electrochemiluminescence immunoassay. Cut-offs at 25, 50, and 75 nmol/L defined vitamin D status, corresponding to deficiency, insufficiency, and sufficiency, respectively. Crude odds ratio (cOR) and 95% confidence intervals (CI) were estimated using logistic regression. RESULTS: Vitamin D severe deficiency (i.e., <25 nmol/L) was present in 18% of newborns. Cord blood severe deficiency was associated with an increased risk of preterm birth (cOR 3.6, 95% CI: 1.1-12.2), neonatal respiratory distress syndrome (cOR 5.9, 95% CI: 1.1-33.2), and increased risk of hospitalization during the first year of life because of acute respiratory infection (cOR 3.9, 95% CI: 1.4-10.6) or acute gastroenterocolitis (cOR 5.2, 95% CI: 1.4-19.1). CONCLUSION: Cord blood vitamin D deficiency is associated with increased risk of preterm birth, neonatal respiratory distress syndrome, and hospitalization during the first year of life.

Could the immune response in the sentinel lymph nodes of gastric cancer patients be the key to tailored surgery?

BACKGROUND: Precise detection of downstream, nonsentinel lymph node metastases is the key to implementation of the sentinel lymph node concept in gastric cancer. To overcome the problem of complex lymphatic drainage, micrometastases, and skip metastases, we investigated the feasibility of tumor cell detection in sentinel lymph nodes, using flow cytometry as well as studied immune suppression in the sentinel lymph node as a potential marker of downstream lymph node metastases. METHODS: In 21 patients with gastric cancer, the sentinel lymph nodes extracted during operation subjected to frozen sections and flow cytometry. The tumor cells were defined with the cell surface markers CEACAM and EpCAM. Simultaneously, the cell densities of different subsets of T cells were determined. RESULTS: The sensitivity and specificity of the determination of nodal status with flow cytometry for tumor cell detection was 100% and 63%, respectively, as seen in frozen sections. Correlations with nonsentinel lymph node metastases were seen for CD127(low)CD25(high) and CD45(neg)CD127(low)CD25(high) cell densities, relative proportion of CD45RA(neg)CD127(low)CD25(high) cells, frozen sections results, lymphangial invasion, and tumor size (P ≤ .043 each). Multivariate analysis identified the relative proportions of CD45RA(neg)CD127(low)CD25(high) cells as the only significant predictor for downstream nonsentinel lymph node metastases (P = .028; 95% confidence interval, 1.107-5.780). The predictive value of combined detection of flow cytometry tumor cells and the relative proportion of CD45RA(neg)CD127(low)CD25(high) cells for nodal stage determination was 91%. CONCLUSION: Combined detection of tumor cells and CD45RA(neg)CD127(low)CD25(high) cells in sentinel lymph nodes with flow cytometry predicts accurately nonsentinel lymph node metastases.

High-dose cholecalciferol supplementation for vitamin D deficiency in haemodialysis patients.

Vitamin D deficiency, which is a recognized problem in haemodialysis (HD) patients, has been associated with higher all-cause mortality. There are no guidelines concerning vitamin D supplementation in HD patients. This study aimed to assess the effects of once-monthly supplementation with high-dose cholecalciferol (vitamin D(3)) in HD patients. Patients with 25-hydroxy vitamin D (25[OH]D) levels of < 75 nmol/l received 40,000 IU of cholecalciferol oncemonthly for 3 months in succession. Every 4 months, 25(OH)D levels were measured and, based on the findings, cholecalciferol therapy was continued for another cycle if necessary. Six cycles were completed in the 24-month study period. The majority of HD patients had mild or severe vitamin D deficiency at baseline. Monthly supplementation with cholecalciferol at 40,000 IU was well tolerated, safe and inexpensive. The treatment regime was effective for vitamin D insufficiency but did not prove to be enough to restore 25(OH)D levels in HD patients with mild or severe vitamin D deficiency.

Kidney function estimating equations in patients with chronic kidney disease.

BACKGROUND: The current guidelines emphasise the need to assess kidney function using predictive equations rather than just serum creatinine. The present study compares serum cystatin C-based equations and serum creatinine-based equations in patients with chronic kidney disease (CKD). METHODS: Seven hundred and sixty-four adult patients with CKD were enrolled. In each patient serum creatinine and serum cystatin C were determined. Their glomerular filtration rate (GFR) was estimated using three serum creatinine-based equations [Cockcroft-Gault (C&G), modification of diet in renal disease (MDRD) and the Chronic Kidney Disease Epidemiology Collaboration equation (CKD-EPI)] and two serum cystatin C-based equations [our own cystatin C formula (GFR=90.63 × cystatin C(-1.192) ) and simple cystatin C formula (GFR=100/cystatin C)]. The GFR was measured using (51) CrEDTA clearance. RESULTS: Statistically significant correlation between (51) CrEDTA clearance with serum creatinine, serum cystatin C and all observed formulas was found. The receiver operating characteristic curve analysis (cut-off for GFR 60 ml/min/1.73m(2)) showed that serum cystatin C and both cystatin C formulas had a higher diagnostic accuracy than C&G formula. Bland and Altman analysis for the same cut-off value showed that all formulas except simple cystatin C formula underestimated measured GFR. The accuracy within 30% of estimated (51) CrEDTA clearance values differs according to stages of CKD. Analysis of ability to correctly predict patient's GFR below or above 60 ml/min/1.73m(2) showed statistically significant higher ability for both cystatin C formulas compared to MDRD formula. CONCLUSION: Our results indicate that serum cystatin C-based equations are reliable markers of GFR comparable with creatinine-based formulas.

Serum cystatin C-based equation compared to serum creatinine-based equations for estimation of glomerular filtration rate in patients with chronic kidney disease.

Estimation of the glomerular filtration rate (GFR) is essential for the evaluation of patients with chronic kidney disease (CKD). The Cockcroft-Gault (CG) and modification of diet in renal disease (MDRD) formulas are serum creatinine-based equations, and the most widely used tests for renal function. Recently, serum cystatin C-based equations were proposed as markers for estimation of GFR. The present study compares our serum cystatin C-based equation (cystatin C formula) and serum creatinine-based equations for a large group of patients with CKD. In this study, 592 adult patients with CKD were enrolled. In each patient, serum creatinine was determined and creatinine clearance was calculated using the CG and MDRD formulas. The serum cystatin C was determined by an immunonephelometric method and our own cystatin C formula (GFR = 90.63 x cystatin C-1.192) for estimation of GFR was developed. GFR was measured using 51CrEDTA clearance, and the correlation, accuracy, bias and precision were determined. Ability to correctly estimate the patient's GFR with different equations compared to gold standard below and above 60 ml/min/1.73 m2; was analyzed. The mean 51CrEDTA clearance was 47 ml/min/1.73 m2, the mean serum creatinine was 269 micromol/l and the mean serum cystatin C was 2.68 mg/l. Statistically significant correlation between 51CrEDTA clearance with the CG (r = 0.861) and MDRD (r = 0.909) formulas and the cystatin C formula (r = 0.899) was found. The receiver operating characteristic (ROC) curve analysis (cut-off for GFR 60 ml/min/1.73 m2) showed that the cystatin C formula had a significantly higher diagnostic accuracy than the CG formula (p < 0.003). All equations underestimated the measured GFR and lacked precision. Analysis of ability to correctly predict the patient's GFR below or above 60/ml/min/1.73 m2 showed a higher prediction for the cystatin C formula than the MDRD formula (91.6 versus 84.1%, p < 0.0005) and a higher prediction trend than the CG formula (91.6 versus 88.3%, p = 0.078). Our results indicate that serum cystatin C-based equation is a reliable marker of GFR with a very high diagnostic accuracy and ability to predict patients with CKD and GFR under 60/ml/min/1.73 m2.

Erythropoietic protoporphyria patients in Slovenia.

BACKGROUND: There are only scarce epidemiological data on the prevalence of erythropoietic protoporphyria (EPP) in a given population. The aim of this study was to assess the prevalence of EPP within the Slovenian population. MATERIALS AND METHODS: The patients were selected by routine examination of photosensitive patients and by studying hospital records. A quantitative spectrophotometric method was used to assess protoporphyrin, with values larger than 530 nm/l considered elevated. RESULTS: 32 EPP patients were detected, which allows us to estimate the prevalence of EPP in Slovenia at 1.75 per 100,000 inhabitants.

Accelerated atherosclerosis in pre-menopausal female patients with rheumatoid arthritis.

Increased mortality due to cardiovascular disease in rheumatoid arthritis (RA) patients was reported. Using B-mode ultrasonography we compared intima-media thickness (IMT) and plaque occurrence (indicators of asymptomatic atherosclerosis) in the carotid arteries in 70 pre-menopausal, female RA patients and 40 controls. Correlations with different risk factors were evaluated. The IMT values were higher in RA patients (0.59 mm vs. 0.47 mm, P < 0.0001) and they had more plaques (P = 0.023). In RA patients higher levels of sensitive CRP (P < 0.0001), ICAM (P < 0.0001), VCAM (P < 0.0001), IL-2 (P < 0.001), IL-6 (P = 0.009) and TNF-alfa (P < 0.01) were found. A correlation between IMT and triglycerides (P = 0.018) and a negative correlation between IMT and HDL cholesterol (P = 0.037) were found. With multiple regression analysis the association between IMT and sensitive CRP (P = 0.027) and presence of plaques and apolipoprotein B (P = 0.028) was established. The results indicate that even pre-menopausal, female RA patients had accelerated atherosclerosis. Chronic systemic inflammation may play an important role in atherogenesis.

Serum cystatin C as an endogenous marker of renal function in the elderly.

The glomerular filtration rate (GFR) is the main indicator of kidney function. In clinical practice the GFR is often estimated from serum creatinine. In the elderly, serum creatinine is notoriously unreliable as an estimator of GFR. Recently, serum cystatin C has been proposed as a new endogenous marker of glomerular filtration rate. A total of 144 patients, aged more than 60 years (mean age 70.4 years), who had undergone 51CrEDTA clearance, were enrolled in our study. In each patient serum creatinine and serum cystatin C were determined. The reciprocal of serum creatinine, the reciprocal of serum cystatin C and creatinine clearance (from Cockcroft and Gault formula) were calculated. Serum cystatin C was measured with the particle-enhanced immunonephelometric method. The mean 51CrEDTA clearance was 34.5+/-25.55 ml/min/1.73 m2, the mean serum creatinine was 312+/-210 micromol/l and the mean serum cystatin C 3.15 mg/l+/-1.62 mg/l. We found a significant correlation between 51CrEDTA clearance and serum creatinine, serum cystatin C, the reciprocal of serum creatinine and the reciprocal of serum cystatin C as well as with creatinine clearance. In comparison of the correlation coefficients we found that the correlation between 51CrEDTA clearance and serum cystatin C was significantly better than that with serum creatinine (p < 0.05). The correlation between 51CrEDTA clearance and the reciprocal of serum cystatin C was superior to that with the reciprocal of serum creatinine (p < 0.003) and calculated creatinine clearance (p < 0.003). Our results indicate that serum cystatin C is a more reliable marker of GFR in the elderly than serum creatinine or creatinine clearance.

Ultrasonographic assessment of celiac disease in children: comparison with antiendomysium antibodies and histology.

UNLABELLED: Several attempts have been made to identify accurate screening tests for celiac disease (CD) with the aim to reduce the need for biopsy or obtaining appropriate selection criteria prior to intestinal biopsy. In this context we evaluated the usefulness of screening for endomysial antibodies (EMA) in the diagnosis of CD in children in comparison with CD-related changes detected by ultrasound (US) or biopsy. PATIENTS: We studied 35 children (1-15 years, 22 girls and 13 boys, mean age 8 years) with untreated CD (N = 15), treated CD (N = 10) and controls (N = 10), undergoing small bowel biopsy as a diagnostic procedure. METHODS: US of the small bowel was performed prior to mucosa biopsy using a 4- or 7-MHz transducer of a computed sonography device. The thickness of the intestinal wall and small bowel motility were recorded. Simultaneously, all children had serum routinely sampled for IgA EMA. RESULTS: All controls had histologically normal small bowel mucosa, US showed a small bowel wall thickness of 1 mm with normal motility in 9 children and non-specific wall changes in 1 child. EMA was weakly positive in 1 of these, and negative in all other controls. Of 15 children with untreated CD, severe enteropathy and strongly positive EMA were found in 10 cases; in 5 children moderate enteropathy and positive EMA were detected. Severe US changes were found in all of these children (1.6 mm thickness of the intestinal wall, hyperperistalsis and abundant fluid in the bowel). Mild enteropathy was found in 10 children with treated CD (3 months of a gluten-free diet). EMA was positive in 2 children and weakly positive in 8. Non-specific US changes were found in 6 children. In conclusion, our results indicate that US provides valuable information on small-bowel wall structure and can help in decision making on the necessity of small bowel biopsy. The present study confirms a stronger correlation between EMA and CD than between US and CD.

Hemodialysis vascular access thrombosis and lipoprotein(a).

Background. Vascular access remains the Achilles's heel of successful hemodialysis and thrombosis is the leading cause of vascular access failure. Elevated lipoprotein(a) (Lp(a)) levels in hemodialysis patients were reported, and in some studies were also associated with hemodialysis vascular access thrombosis. Patients and methods. In our study 84 hemodialysis patients with native arteriovenous fistula were included. Two groups of patients were defined: group A including 61 patients with their vascular access either never or only once thrombosed, and group B including 23 patients with two or more thromboses of their vascular access. We determined serum concentrations of Lp(a) in all our patients. Results. Average serum Lp(a) concentration for all the patients included in the study was 0.273 +/- 0.31 g/l. No relationship was found between serum Lp(a) concentrations and age, gender and duration of dialysis treatment. Serum Lp(a) concentrations were higher in group A than in group B patients (0.301 g/l versus 0.198 g/l), but the difference was not statistically significant. There was also no statistically significant difference between group A and group B regarding age, gender and duration of hemodialysis treatment. The use of a cut-off value for Lp(a) of 0.3 g/l and 0.57 g/l also failed to provide a significant difference between group A and B patients. Conclusion. We found no significant differences in Lp(a) concentrations between group A (thrombosis-non-prone) and group B (thrombosis-prone) patients. Our results suggest that Lp(a) is not an independent risk factor for vascular access occlusion in hemodialysis patients.

The clinical significance of antinuclear antibodies in connective tissue disease.

Antinuclear antibodies (ANA) are often present in connective tissue diseases. In 279 non-selected patients with connective tissue disease, inflammatory and degenerative joint disease, in some patients with chronic infectious diseases and malignancies and in the presence of some unclear pathologic conditions in patients whose serum reacted positively to ANA, we analyzed the type of immunofluorescence and the presence of extractable antinuclear antibodies (ENA). In systemic lupus erythematosus, the prevailing immunofluorescence is type H (homogenous) (60.6%), anti-Ro/SS-A appears in 24.2%, anti-Sm and anti-RNP in 12.1%. In Sjögren's syndrome, type S prevails (47.6%), anti- Ro/SS-A and anti-La/SS-B are present in 52.4%, only anti-Ro/SS-A in 28.6%. In systemic sclerosis, the prevailing immunofluorescence is type S (37.5%), in 75% a positive anti-Scl-70 antibody is present. In mixed connective tissue disease, anti-RNP appears in 85.7%. In dermatopolymyositis, the anti-Jo-1 antibody is present in 33.3%. In undifferentiated connective tissue disease, type S immunofluorescence appears in 70%. In rheumatoid arthritis the prevailing immunofluorescence is type H (homogenous) (46.4%) and type S (speckled) (41.0%), while the presence of ENA is rare (anti-Ro/SS-A in 4.6%). In spondylarthritis, type S immunofluorescence appears most often (62.5%). Patients with chronic infectious disease, malignancies, undefined conditions and degenerative joint disease present with various types of immunofluorescence; the presence of ENA is extremely rare in these patients. The results of this study underline the significance of ANA and, particularly ENA, in the diagnosis of connective tissue disease. These antibodies however, can also be identified in various infectious and malignant diseases as well as in inflammatory and degenerative joint diseases.