Can a semi-quantitative method replace the current quantitative method for the annual screening of microalbuminuria in patients with diabetes? Diagnostic accuracy and cost-saving analysis considering the potential health burden.

OBJECTIVES: Diabetes is a global epidemic, and the high cost of annually and quantitatively measuring urine albumin excretion using the turbidimetric immunoassay is challenging. We aimed to determine whether a semi-quantitative urinary albumin-creatinine ratio test could be used as a screening tool for microalbuminuria in diabetic patients. METHODS: We assessed the diagnostic accuracy of the semi-quantitative method. The costs of false results in the semi-quantitative method were calculated based on the annual probability of disease progression analyzed through a systematic literature review and meta-analysis. The pooled long-term cost-saving effect of the semi-quantitative method compared with the quantitative test was assessed using a Markov model simulating a long-term clinical setting. Diagnostic accuracy and the cost-saving effect were also validated in an independent external cohort. RESULTS: Compared with the quantitative test, the semi-quantitative method had sensitivities of 93.5% and 81.3% and specificities of 61.4% and 63.1% in the overall sample of diabetic patients (n = 1,881) and in diabetic patients with eGFR ≥60 ml/min/1.73 m2 and a negative dipstick test (n = 1,110), respectively. After adjusting for direct and indirect medical costs, including the risk of disease progression, which was adjusted by the meta-analyzed hazard ratio for clinical outcomes, it was determined that using the semi-quantitative method could save 439.4 USD per person for 10 years. Even after adjusting the result to the external validation cohort, 339.6 USD could be saved for one diabetic patient for 10 years. CONCLUSIONS: The semi-quantitative method could be an appropriate screening tool for albuminuria in diabetic patients. Moreover, it can minimize the testing time and inconvenience and significantly reduce national health costs.

Amino Acid-Based Formula in Premature Infants with Feeding Intolerance: Comparison of Fecal Calprotectin Level.

PURPOSE: We investigated fecal calprotectin (FC) levels in preterm infants with and without feeding intolerance (FI), and compared the FC levels according to the type of feeding. METHODS: The medical records of 67 premature infants were reviewed retrospectively. The fully enteral-fed infants were classified into two groups; the FI group (29 infants) and the control group (31 infants). Seven infants with necrotizing enterocolitis, sepsis, and perinatal asphyxia were excluded. If breast milk (BM) or preterm formula (PF) could not be tolerated by infants with FI, amino acid-based formula (AAF) was tried temporarily. Once FI improved, AAF was discontinued, and BM or PF was resumed. We investigated the FC levels according to the type of feeding. RESULTS: Significant differences were found in gestational age, birth weight, age when full enteral feeding was achieved, and hospital stay between the FI and control group (p<0.05). The FC levels in the FI group were significantly higher than those in the control group (p<0.05). The FC levels in the AAF-fed infants with FI were significantly lower than those in the BM- or PF-fed infants (p<0.05). The growth velocities (g/d) and z scores were not significantly different between the FI and control group (p>0.05). CONCLUSION: The FC levels in AAF-fed infants with FI showed significantly lower than those in the BM- or PF-fed infants with FI. The mitigation of gut inflammation through the decrease of FC levels in AAF-fed infants with FI could be presumed.

The relationship between anti-C-reactive protein and disease activity in patients with systemic lupus erythematosus.

Background/Aims: Anti-C-reactive protein (CRP) antibody has been introduced as a potential biologic marker in Systemic lupus erythematosus (SLE). The aim of study is to evaluate the level of anti-CRP antibody in patients with SLE. METHODS: This study investigated the relationship between levels of anti-CRP antibodies and disease activity markers, such as complement, anti-double-stranded DNA antibody, and SLE disease activity index in 34 patients with SLE. RESULTS: The serum anti-CRP antibody levels of the patients with SLE were significantly higher than those of the healthy controls (11.3 ± 5.6 µg/mL vs. 9.1 ± 2.8 µg/mL). The percentages of the positive anti-CRP antibody were 52.9% in SLE and 27.8% in controls. Disease duration of SLE showed significant correlation with the anti-CRP antibody (r = 0.234, p = 0.026). However no significant relationship was observed between the levels of anti-CRP antibodies and disease activity markers. Conclusions: These data show that the anti-CRP antibody levels of the patients with SLE were significantly higher than those of healthy controls. We observed that the presence of the anti-CRP anti-CRP antibody was not associated with disease activity of SLE.

Increased urinary neutrophil gelatinase-associated lipocalin in very-low-birth-weight infants with oliguria and normal serum creatinine.

BACKGROUND: In infants, oliguria is defined as a urine output of <1.5 mL/kg/h. The aim of our study was to assess the impact of oliguria on urinary neutrophil gelatinase-associated lipocalin (NGAL) and serum cystatin C (CysC) levels in very-low-birth-weight infants (VLBWIs) with a normal serum creatinine (Cr) level. METHODS: Fifty-seven VLBWIs were enrolled in the study. Urinary NGAL, serum CysC and Cr levels and urinary NGAL/Cr ratios were measured. Infants with Apgar scores of >5 at 5 min and/or a serum Cr level of >1.5 mg/dL or those treated for patent ductus arteriosus were excluded. In case of antibiotic treatment, blood and urine samples were collected at ≥48 h after discontinuation of antibiotic treatment. RESULTS: There was a significant difference in gestational age between infants with oliguric episodes during hospitalization and those without, but not in birth weight, perinatal or postnatal factors. Gestational age was negatively correlated with urinary NGAL and serum CysC levels and urinary NGAL/Cr ratio (p < 0.05), whereas postnatal age was negatively correlated with serum Cr level and urinary NGAL/Cr ratio (p < 0.05). Of the 117 urine and blood samples collected, 25 (21.4%) were obtained from neonates with oliguric episodes. After adjusting for gestational age and postnatal age, comparison of samples collected in infants with and without oliguric episodes revealed significant differences in the mean level of urinary NGAL and in the urinary NGAL/Cr ratio, but not in mean serum CysC or serum Cr levels. The urinary NGAL level [area under the curve (AUC) 0.886, 95% confidence interval (CI) 0.814-0.937] and urinary NGAL/Cr ratio (AUC 0.853, 95% CI 0.775-0.911) showed significantly greater discrimination for oliguria than serum CysC (AUC 0.610, 95% CI: 0.515-0.699) or serum Cr (AUC 0.747, 95%CI 0.659-0.823) levels. CONCLUSIONS: Urinary NGAL level and urinary NGAL/Cr ratio were more sensitive markers for the presence of oliguria in VLBWIs with normal serum Cr levels than serum CysC level.

[A case of partial trisomy 15q25.3-qter].

A 15q25-qter partial trisomy characterized by pre or postnatal overgrowth, tall stature, macrocephaly and craniosynostosis has rarely been reported. The cause of overgrowth has been thought to be the triplication of the insulin-like growth factor 1 receptor (IGF1R) gene located on the 15q26.3. We report a patient with partial trisomy 15q25.3-qter showing mental retardation, developmental delay, macrocephaly, long narrow face, ptosis, high palate arch, scoliosis, clinodactyly and overgrowth. Additional material located on terminal 2q was found in karyotyping analysis. In bacterial artificial chromosome (BAC) clone-based-array comparative genomic hybridization (aCGH) analysis, a gain of 31 clones on 15q25.3-qter and a loss of 2 clones on 2q37.3 were observed. An extra copy of IGF1R gene was observed on derivative chromosome 2 in FISH analysis. In conclusion, the patient was diagnosed to have de novo 46,XX,der(2)t(2;15)(q37.3;q25.3) chromosome complement. Adequate genetic counseling and regular follow-ups would be needed for the patient.

[A RhD negative patient failed to produce detectable anti-D after transfusion of 35 units of RhD positive red blood cells].

In the present day, pretransfusion tests include ABO and RhD grouping, antibody screening, antibody identification, and cross matching. Although error rates for these tests have decreased compared to those in the past, clerical errors still occur. When exposed to RhD positive RBCs, a RhD negative person can produce anti-D that causes a severe hemolytic disease of the fetus and the newborn in addition to hemolytic transfusion reactions. Therefore, administration of RhD positive RBCs to a RhD negative person should be avoided. We experienced a RhD negative patient who had been misidentified as positive and transfused 35 units of RhD positive RBCs eight years ago, but did not have detectable anti-D in present. The red cells of the patient showed no agglutination with the anti-D reagent and a negative result in the standard weak D test. The multiplex PCR with sequence-specific priming revealed that the patient was RhD negative.

mRNA expression and RNA editing (2451 C-to-U) of IL-12 receptor beta2 in adult atopic patients.

Interleukin (IL)-12 activates T helper (Th) 1 cells to produce interferon (IFN)-gamma which inhibits atopic inflammation. IL-12 acts through interaction with its receptor, especially beta(2) subunit. In several studies, the low production of IFN-gamma in peripheral mononuclear cells of atopic patients on response to IL-12 stimulation has been reported. Therefore we investigated the IL-12 receptor beta(2) (IL-12R beta(2)) mRNA expression and RNA editing, nucleotide 2451 C-to-U conversion, to find the cause of low responsiveness to IL-12 in atopy. Quantitative real time PCR for mRNA expression and sequence analysis for RNA editing were performed in 80 atopic patients and 54 healthy controls. The expression of IL-12R beta(2) mRNA was significantly lower in atopic patients than healthy controls (p<0.05). In sequence analysis, RNA editing on nucleotide 2451 was not found from either atopic patients or healthy controls. In additional evaluation, there was no relationship between expression of IL-12R beta(2) mRNA and serum total IgE or blood eosinophil count. Reduced IL-12R beta(2) mRNA expression in atopic patients indicate the reduced capacity to respond to IL-12 which induce IFN-gamma production and this may contribute to Th2-skewed immune response in atopy.