Development of blood demand prediction model using artificial intelligence based on national public big data.

Objective: Modern healthcare systems face challenges related to the stable and sufficient blood supply of blood due to shortages. This study aimed to predict the monthly blood transfusion requirements in medical institutions using an artificial intelligence model based on national open big data related to transfusion. Methods: Data regarding blood types and components in Korea from January 2010 to December 2021 were obtained from the Health Insurance Review and Assessment Service and Statistics Korea. The data were collected from a single medical institution. Using the obtained information, predictive models were developed, including eXtreme Gradient Boosting (XGBoost), Light Gradient Boosting Machine (LGBM), and category boosting (CatBoost). An ensemble model was created using these three models. Results: The prediction performance of XGBoost, LGBM, and CatBoost demonstrated a mean absolute error ranging from 14.6657 for AB+ red blood cells (RBCs) to 84.0433 for A+ platelet concentrate (PC) and a root mean squared error ranging from 18.5374 for AB+ RBCs to 118.6245 for B+ PC. The error range was further improved by creating ensemble models, wherein the department requesting blood was the most influential parameter affecting transfusion prediction performance for different blood products and types. Except for the department, the features that affected the prediction performance varied for each product and blood type, including the number of RBC antibody screens, crossmatch, nationwide blood donations, and surgeries. Conclusion: Based on blood-related open big data, the developed blood-demand prediction algorithm can efficiently provide medical facilities with an appropriate volume of blood ahead of time.

Frequency histograms of three high-sensitivity cardiac troponin assays in a reference population.

BACKGROUND: Cardiac troponin (cTn) values above the 99th percentile upper reference limit (URL) indicate myocardial injury. We established 99th percentile URLs for three high-sensitivity cTn (hs-cTn) assays (Beckman Coulter Access hs-cTnI, Abbott STAT hs-cTnI, and Roche Elecsys hs-cTnT) using a healthy population in Korea. METHODS: Each cTn value was measured by three assays and analyzed by dividing by gender and age. RESULTS: The frequency histograms of log-transformed cTn values for Beckman and Abbott assays exhibited a bell-shaped distribution. The 99th percentile URLs were 9.8, 17.4, and 17.3 ng/L in the total population; 10.9/9.0, 18.9/17.0, and 18.9/17.7 ng/L in the male/female population (p < 0.001 for all three assays); and 11.2/7.2, 19.9/14.5, and 22.7/9.3 ng/L in the older/younger population (p < 0.001 for all three assays) for Beckman, Abbott, and Roche assays, respectively. CONCLUSION: Among the three assays, bell-shaped distributions were observed in a frequency histogram of log-transformed cTn values for healthy population in Beckman and Abbott assays. Also, our findings show that the 99th percentile URLs for cTn levels vary not only by gender but age.

Comparison of ACCEL ELISA COVID-19 with Elecsys Anti-SARS-CoV-2 for Screening of COVID-19.

OBJECTIVE: Although real-time reverse transcription-PCR (RT-PCR) is the gold standard for diagnosing coronavirus disease 2019 (COVID-19), simpler and faster antibody detection tests can be complementary for diagnosis of COVID-19. To manage the COVID-19 pandemic, the need for serologic testing has increased. In this report, the newly developed antibody detection assays ACCEL ELISA COVID-19 (ACCEL) and Elecsys anti-SARS-CoV-2 (Elecsys) were evaluated. METHODS: Serum samples submitted for routine laboratory testing were analyzed (66 and 161 PCR-positive and PCR-negative samples). After the samples were aliquoted, antibody detection tests were performed using ACCEL and Elecsys assays. RESULTS: When detection of viral RNA using RT-PCR was set as the reference method for diagnosis of COVID-19, the sensitivity was 83.3% and 75.8, and the specificity was 96.9 and 99.4% in ACCEL and Elecsys, respectively. The true positivity rates of ACCEL and Elecsys assays were 57.1%/42.9%, 57.1%/28.6%, 77.8%/66.7%, and 97.1%/97.1% among the specimens collected ≤3, 4-7, 8-14, and >14 days after symptom onset, respectively. CONCLUSIONS: The ACCEL assay showed high sensitivity in samples collected within 7 days after symptom onset. Because many patients are asymptomatic in the early stage of SARS-CoV-2 infection, the ACCEL assay could be a good screening tool due to high sensitivity in the early stage of SARS-CoV-2 infection.

Evaluation of AdvanSure AlloScreen Max Panel With 92 Different Allergens for Detecting Allergen-Specific IgE.

OBJECTIVES: The objective of this study was to examine the performance of AdvanSure AlloScreen Max with 92 different allergens compared to Polycheck Allergy and ImmunoCAP. The relationship of serum IgE concentration with the number and the highest class/level of positive allergen-specific IgEs was also examined. METHODS: A total of 406 serum samples were included in this study. Discrepant cases between AdvanSure AlloScreen Max and Polycheck Allergy underwent ImmunoCAP testing for allergen-specific IgE. RESULTS: Total agreement of the two multiple allergen simultaneous tests (MAST) was 92.5%. Compared to ImmunoCAP, total agreement rate was higher with AdvanSure AlloScreen Max (60.8%) than that with Polycheck Allergy (39.2%). Serum IgE concentration showed a significant and positive correlation with the number and the highest class/level of positive allergen-specific IgEs. CONCLUSIONS: A MAST assay panel containing as many allergens as possible would be more helpful in the allergen screening for patients with high serum IgE concentration.

Comparison between creatine kinase MB, heart-type fatty acid-binding protein, and cardiac troponin T for detecting myocardial ischemic injury after cardiac surgery.

BACKGROUND: Heart-type fatty acid-binding protein (H-FABP) is a cytoplasmic protein and is released form necrotic cardiac myocytes, as well as ischemic cardiac myocytes. In this study, we compared creatine kinase MB (CK-MB), H-FABP, and cardiac troponin T (cTnT) after coronary artery bypass grafting (CABG), heart valve surgery, or septal defect surgery to evaluate the difference in detecting myocardial injury between three markers. METHODS: A total of 69 patients (CABG, 32; valve surgery, 27; and septal defect surgery, 10) were prospectively enrolled. Blood samples were taken at specific intervals. RESULTS: Mean amount (AUC0-72h) of CK-MB and cTnT released for 72 h in the patients with valve surgery were 2446 h·ng/ml and 93.2 h·ng/ml, which were significantly larger than those in the patients with CABG or septal defect surgery (p < .05). Mean amount (AUC0-72h) of H-FABP released for 72 h in the patients with CABG was 1939 h·ng/ml, which was significantly larger than that in the patients with septal defect surgery (700.1 h·ng/ml) (p < .05). CONCLUSION: H-FABP would be a more useful marker for detecting myocardial ischemic injury than CK-MB and cTnT. CK-MB and cTnT would be more sensitive to myocardial injury with surgical trauma than with ischemic injury in the patients with cardiac surgery.

A new strategy for calculating the risk of ovarian malignancy algorithm (ROMA).

BACKGROUND: Reliable quantitative measurements of HE4 and CA125 levels are required to calculate the risk of ovarian malignancy algorithm (ROMA) value. We suggest a new reporting strategy for interpreting ROMA values based on analytical measurement range (AMR) and qualified-intervals of the HE4 and CA125 results. METHODS: HE4 and CA125 assays from Abbott and Roche were used. The AMRs and the qualified-intervals were as follows: Architect HE4 assay, 20-1500 and 17.2-2637.8 pmol/L; Architect CA125 II assay, 1-1000 and 3.9-14,163.0 U/mL; Elecsys HE4 assay, 15-1500 and 28.8-3847 pmol/L; Elecsys CA125 II assay, 0.6-5000 and 6.5-5000 U/mL. These values were used to simulate the ROMA values. RESULTS: Reporting algorithm for the ROMA value could be classified into three categories. (1) If quantitative HE4 and CA125 levels are reliable, the numerical ROMA value can be reported. (2) If HE4 value is <20 and <28.8 for Abbott and Roche in premenopausal woman, the ROMA value should be reported as "low risk" regardless of the CA125 result. In postmenopausal woman, however, it should be reported as "low risk" (CA125<203.0 and <165.8 for Abbott and Roche) or "undetermined" (vice-versa value). (3) If CA125 value is <3.9 and <6.5 for Abbott and Roche, it should be reported as "low risk" (premenopausal HE4<51.5 and <62.2, postmenopausal HE4<323.0 and <281.5 for Abbott and Roche) or "undetermined" (vice-versa value). CONCLUSIONS: New reporting strategy will provide more informative reporting of ROMA values in clinical practice.

Evaluation of a novel point-of-care test kit, ABSOGEN™ PCT, in semi-quantitative measurement of procalcitonin in whole blood.

BACKGROUND: In response to inflammation, procalcitonin plasma concentrations increase more rapidly than other acute-phase reactants and higher values are associated with severe disease. Procalcitonin measurements assist in determining whether antibiotic therapy should be used. point-of-care testing (POCT) is performed for early decision making about additional testing or therapy. The ABSOGEN™ PCT (Bumyoungbio, Inc., Suwon, Korea) is a rapid novel semi-quantitative immunochromatographic PCT assay that analyses whole blood samples. We compared the patient quantitative test results to ABSOGEN™ PCT test results. METHODS: Whole blood was loaded onto an ABSOGEN™ PCT cartridge and incubated for 10 minutes. The color intensity of the band of the cartridge was measured using an accompanying device and with the naked eye. The results were graded as negative (<0.1 ng/mL), low (0.1 to <1.0 ng/mL), middle (1.0-2.0 ng/mL), and high (>2.0 ng/mL). A total of 158 specimens with procalcitonin levels measured from 0 to 18.96 ng/mL were used for comparison study. RESULTS: The concordance rate between ABSOGEN™ PCT using the reader and quantitative assay, between ABSOGEN™ PCT using naked eyes and quantitative assay, and between ABSOGEN™ PCT using the reader and naked eyes for the same category was 83.5% (P=.040), 78.5% (P<.001), and 82.3% (P=.001), respectively. The concordance rates for the ±1 categories were all 100%. CONCLUSION: ABSOGEN™ PCT is an accurate assay. It is easy to use, simple, fast, portable. The assay has potential value in clinical applications, especially in emergency care.

Usefulness of biological variation in the establishment of delta check limits.

BACKGROUND: Biological variation is used in the calculation of reference change values (RCVs) for a delta check. In this study, we examined the correlation between intra-individual biological coefficients of variation (CVI) and delta check limits according to population distribution. METHODS: A total of 1,533,359 paired test results of nine routine chemistry tests were used to make the population distributions of delta percent changes. Their 0.5th, 2.5th, 97.5th, and 99.5th percentiles were then used for delta check limits. RESULTS: A large difference was observed between the chemistry tests in the percentage exceeding the delta check limits according to the RCVs. The mean percentage of test results of each test item exceeding the delta check limits of RCV95% ranged from 12.3% to 40.6%. Delta percent changes of protein, albumin, sodium (Na), potassium (K) and chloride (Cl) showed a symmetric distribution. However, an asymmetric distribution was observed in the delta percent changes of glucose, aspartate transaminase (AST), alanine aminotransferase (ALT) and creatinine. A good correlation was observed between CVI and the delta check limits according to population distribution and a closer correlation was observed when using the test items with CVI of <5.0%. CONCLUSIONS: Intra-individual biological coefficients of variation (CVI) would be useful for the establishment of delta check limits.

Evaluation of Isothermal Target and Probe Amplification (iTPA) for the Detection of Mycobacterium Tuberculosis.

BACKGROUND: This study compared the diagnostic power of isothermal target and probe amplification (iTPA) with the existing real-time PCR for the detection of Mycobacterium tuberculosis (MTB). METHOD: The two molecular methods were performed using DNA extracted directly from lower respiratory tract samples, not from the culture broth. A total of 174 non-consecutive patients with suspected pulmonary tuberculosis were enrolled in this study. Acid-fast bacilli (AFB) stain and liquid culture with the BACTEC MGIT 960 system (Becton Dickinson Diagnostic, USA) were performed. Real-time PCR and iTPA methods were performed with the AdvanSure TB/NTM TaqMan assay (LG Lifescience, Korea) and the RapiDx® MTB test (RapleGene, Korea). RESULTS: Among 174 patients, 49 of 52 isolates were identified as MTB and 3 of 52 isolates were identified as non-tuberculous mycobacteria NTM. Based on the culture results, the sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 95.9%, 90.1%, 81.3%, and 98.2% for iTPA, and 95.7%, 91.0%, 80.4%, and 98.2% for real-time PCR, respectively. The agreement of iTPA was 83.0% with the AFB stain, 92.4% with the MGIT culture, and 94.2% with real-time PCR. Disagreement between the two molecular methods occurred in 10 patients. CONCLUSIONS: This study is the first to report the evaluation of iTPA conducted from direct specimens. Both iTPA and real-time PCR proved to be rapid, sensitive, and specific tools for the detection of MTB in clinical samples. The iTPA method for the MTB detection revealed a high concordance rate with real-time PCR.

Accuracy Assessment of Three Different Lots of the LABGEO PT Hemoglobin A1c Test Using Reference Materials.

BACKGROUND: Both accurate measurement of HbA1c and minimal reagent lot-to-lot variability are essential for point-of-care HbA1c assays. The accuracy of three different cartridge lots of the Samsung LABGEO PT HbA1c Test was investigated to determine whether the results can be used for follow-up and screening of patients with diabetes. METHODS: The LABGEO PT10 device and three different lots of the LABGEO PT HbA1c Test cartridge were used. Seven levels of reference materials were measured using each cartridge in a duplicate manner for 3 days. The bias, within-laboratory precision, and total error were calculated. The medical decision point analysis was performed. RESULTS: The mean absolute bias, within-laboratory precision, and total error of each cartridge were 3.3%, 2.5%, and 8.1% for Lot1; 1.9%, 2.6%, and 7.1% for Lot2; and 2.7%, 2.8%, and 8.1% for Lot3. The predicted value (95% confidence interval) of each cartridge at an HbA1c of 6.5% was 6.74% (6.66, 6.83) for Lot1, 6.60 (6.51, 6.70) for Lot2, and 6.51 (6.39, 6.63) for Lot3. CONCLUSIONS: Our data suggest that the LABGEO PT HbA1c Test can be used to monitor patients with diabetes and perform diabetes screening when false-positive results are obtained in the doctor's office.

Polymorphisms of the heart-type fatty acid-binding protein as a prognostic factor in patients with atherosclerosis.

The amount of heart-type fatty acid-binding protein (FABP3) in cardiomyocytes may affect the prognosis of patients with coronary atherosclerosis. In this study, we examined whether single nucleotide polymorphisms (SNPs) of the FABP3 gene were prognostic factors in patients with coronary atherosclerosis. We enrolled 100 patients with myocardial infarction and coronary atherosclerosis and 100 healthy individuals to assess the genotypes of four SNPs of the FABP3 gene (RS2271072, RS16834408, RS2279885, and RS10914367). The MI patients with coronary atherosclerosis exhibited a higher frequency (16%) of the C/G-G/G haplotype of RS2271072 and RS10914367 than healthy individuals (7%). Koreans with the C/G-G/G haplotype for these SNPs had a higher risk of MI than did Koreans with the G/G-A/A haplotype. We calculated an odds ratio of 2.83 (95% confidence interval: 1.01-7.96). In conclusion, the C/G-G/G haplotype at RS2271072 and RS10914367 SNPs of FABP3 might be a prognostic factor in patients with coronary atherosclerosis.

Evaluation of enzymatic BM Test HbA1c on the JCA-BM6010/C and comparison with Bio-Rad Variant II Turbo, Tosoh HLC 723 G8, and AutoLab immunoturbidimetry assay.

BACKGROUND: A novel enzymatic HbA1c assay was introduced for use in an automated chemistry analyzer. With this unique method, HbA1c and plasma glucose can be measured from the same EDTA tube. We evaluated the analytical performance of this enzymatic HbA1c assay in a JCA-BM6010/C analyzer and compared the HbA1c values with the results from other widely used methodological instruments. METHODS: The imprecision, linearity, carry-over and concordance rate of the enzymatic HbA1c test (BM Test HbA1c) using the JCA-BM6010/C analyzer were evaluated. Three hundred and seventy-seven specimens with HbA1c concentrations from 16 to 133 mmol/mol were used for a comparison study with two high performance liquid chromatography methods: Variant II Turbo and Tosoh HLC 723 G8 and the AutoLab Hemoglobin A1c immunoturbidimetry reagent using a Hitachi 7600-110. Forty specimens were used for the glucose method comparison. RESULTS: The HbA1c coefficients of variation of the within-run imprecision for low and high levels were 0.6% and 0.4%, respectively. The linearity of the BM Test HbA1c using the JCA-BM6010/C analyzer was excellent in the range between 31 mmol/mol and 143 mmol/mol. The carry-over rate was 0.2%. The relationships between the BM test and the other three methods were 0.916×Tosoh G8+3.644, r=0.986; 0.887×Bio-Rad Variant II+1.896, r=0.972; and 0.941×AutoLab+4.532, r=0.977. The concordance rates using a cut-off of 48 mmol/mol were 91.5% with Tosoh G8, 82.8% with Bio-Rad Variant II, and 91.0% with AutoLab. The simultaneously assayed plasma glucose with HbA1c was 1.002×Routine plasma glucose+0.625, r=1.000 CONCLUSIONS: The enzymatic BM Test HbA1c in the JCA-BM6010/C analyzer showed excellent precision and linearity, and a minimal carry-over rate. The simultaneously assayed plasma glucose analysis showed good performance.

Comparison of the AdvanSure HBV real-time PCR test with three other HBV DNA quantification assays.

BACKGROUND: We compared the AdvanSure hepatitis B virus real-time polymerase chain reaction (AdvanSure HBV) kit with three other HBV DNA quantification assays and evaluated its performance. METHODS: The AdvanSure HBV real-time PCR assay was compared with the Abbott RealTime HBV Quantification Kit, the COBAS TaqMan HBV Test, and the VERSANT HBV branched DNA 3.0 assay. The precision, linearity, accuracy, limit of detection (LOD), cross reactivity, and genotype inclusivity of the assays were compared, and any influence of the sampling tube type was evaluated. RESULTS: The AdvanSure HBV PCR showed good correlations with the three other HBV DNA assays. The R(2) coefficients were 0.944, 0.939, and 0.921 with the Abbott RealTime HBV Quantification Kit, the COBAS TaqMan HBV Test, and the VERSANT bDNA 3.0 assay, respectively. Linearity was good in the tested range of 1.15-8.45 log10 IU/ml. The lower LOD result was consistent with the 18 IU/ml claimed by the manufacturer. HBV genotypes A-F were all correctly amplified, and no cross reactivity was found in samples with high HCV RNA levels or high protein concentrations. The results were not influenced by the sample preparation tube (i.e. plain tube, SST, and EDTA containing tubes). CONCLUSION: The AdvanSure HBV real-time PCR assay is a reliable method for quantifying HBV DNA levels in routine laboratory testing.

Automated heart-type fatty acid-binding protein assay for the early diagnosis of acute myocardial infarction.

We compared an automated quantitative heart-type fatty acid-binding protein (H-FABP) assay with other cardiac-marker assays to examine its usefulness as an early diagnostic marker of acute myocardial infarction (AMI). Serum samples for cardiac troponin T (cTnT), creatine kinase-MB isozyme (CK-MB), myoglobin, and H-FABP were obtained from 64 patients with AMI and 53 patients with other conditions (control group). H-FABP was measured by using 2 immunoassays, the H-FABP enzyme-linked immunosorbent assay (ELISA; Biocheck, Foster City, CA) and the H-FABP latex turbidimetric immunoassay (LTIA; HBI, Anyang, Korea). Sensitivities of assays for cTnT, CK-MB, myoglobin, H-FABP (by ELISA), H-FABP (by LTIA), and electrocardiogram (ECG) for the diagnosis of AMI at hospital admission were 39.1%, 59.4%, 64.1%, 68.7%, 70.3%, and 54.7%, respectively. Specificities of cTnT, CK-MB, myoglobin, H-FABP (by ELISA), H-FABP (by LTIA), and ECG were 98.1%, 71.7%, 81.1%, 77.4%, 90.6%, and 92.5%, respectively. The automated H-FABP (by LTIA) is superior to cTnT, CK-MB, myoglobin, and H-FABP (by ELISA) tests for the diagnosis of AMI in patients admitted within 4 hours from the onset of chest pain.

[Comparison of quantitative results among two automated Rapid Plasma Reagin (RPR) assays and a manual RPR test].

BACKGROUND: We compared two automated Rapid Plasma Reagin (RPR) assay kits with a manual RPR assay kit to evaluate the possibility of using the two automated RPR assays as an alternative to the manual RPR assay for a quantitative monitoring. METHODS: One hundred eighty-five samples were analyzed, including 16 sera from patients with primary, secondary, and latent syphilis. Measured RPR unit (R.U.) values of two automated RPR assay kits, Mediace RPR (Sekisui Chemical Co., Ltd, Japan) and HBi Auto RPR (HBI Co., Ltd, Korea), were compared with the RPR titers of Macro-Vue RPR card test (Becton Dickinson BD Microbiology systems, USA). As a confirmatory test, Anti-Treponema pallidum EUROLINE WB (IgG) and Anti-Treponema pallidum EUROLINE WB (IgM) (Euroimmun, Germany) were used. RESULTS: There was a prozone effect with Mediace RPR at RPR titer (card test) of 1:16, but not with HBi Auto RPR. The R.U. values of the two automated RPR assays did not show proportional increase to the RPR titer. Agreement between manual RPR and two automated RPR assay kits, Mediace RPR assay and HBi Auto RPR assay, were 83.8% and 83.2%, respectively. CONCLUSIONS: The two automated RPR assay kits could not be used as an alternative to manual RPR test for quantitative analysis of RPR titer. As Mediace RPR shows a prozone effect at relatively low RPR titer, caution is needed in the interpretation of the measured values.

The comparison of parathyroid hormone degradation effect by various protease inhibitors in blood specimen.

BACKGROUND: The objective of this study was to evaluate the role of proteases on the degradation of parathyroid hormone (PTH) in blood samples. METHODS: Protease inhibitors with specificity against serine proteases (aprotinin), cysteine proteases (E-64), serine and cysteine proteases (leupeptin), metalloproteases (EDTA), or a protease inhibitor cocktail with a broad spectrum of inhibitory activity were added to blood samples. After storage at room temperature (0-48 hr), PTH levels were measured. RESULTS: PTH levels in samples with the protease inhibitor cocktail did not change significantly after 48 hr of storage at room temperature, but the average PTH levels decreased by 40.7% and 20.1%, in samples stored at room temperature and stored at 4 degrees C without protease inhibitors, respectively. PTH levels in samples with leupeptin were stable for up to 24 hr. After 48 hr, the mean PTH levels decreased by 17.1%, 16.0%, 26.2%, and 32.1%, with 500 KIU/mL aprotinin, 100 micromol/L leupeptin, 10 micromol/L E-64, and 10 micromol/L EDTA, respectively, in the samples stored at room temperature. CONCLUSIONS: The decrease in PTH levels in blood samples seemed to be due to the degradation of PTH by proteases. Various proteases, including especially serine proteases, would act together to degrade PTH in blood specimen. The PTH degradation may be inhibited in blood specimen with protease inhibitor cocktail.

Occurrence and mechanisms of amikacin resistance and its association with beta-lactamases in Pseudomonas aeruginosa: a Korean nationwide study.

OBJECTIVES: We investigated the occurrence and mechanism of amikacin resistance and its association with various beta-lactamase genes in Pseudomonas aeruginosa isolates. METHODS: Of the total 250 consecutive, non-duplicated isolates of P. aeruginosa, 55 isolates showed amikacin resistance. PCR amplification of genes for aminoglycoside (AG)-modifying enzymes [aac(3)-I, aac(3)-II/VI, aac(3)-III/IV, aac(6')-I, aac(6')-II, ant(2'')-I, ant(4')-II and aph(3')-VI], 16S rRNA methylases (rmtA, rmtB, rmtC and armA) and class 1 integrons was performed. In addition, we analysed the association of AG resistance genes with various beta-lactamase genes. RESULTS AND CONCLUSIONS: In Korea, the amikacin resistance rate in P. aeruginosa was high (22%), and it varied among provinces (3.8% to 40%). Four types of AG-modifying enzyme genes [aph(3')-VI, ant(2'')-I, aac(6')-I and aac(3)-II/VI] were found in 48 isolates. Thirty-six strains harboured two or more types of enzymes, of which a combination of aph(3')-VI and ant(2'')-I was the most frequent (24/36 isolates, 66.7%). None harboured aac(3)-I, aac(3)-III/IV, aac(6')-II, ant(4')-II, rmtA, rmtB, rmtC or armA. Forty-two isolates co-harboured beta-lactamase genes (mostly bla(OXA-10)). A class 1 integron was detected in all but one, and all the ant(2'')-I and 26/29 bla(OXA-10) were found in it. In contrast, aph(3')-VI was not found to be associated with the class 1 integron. Considering the possibility of co-selection and dissemination, constant monitoring of resistance evolution is necessary.

Methylation of p16(INK4A) and p57(KIP2) are involved in the development and progression of gastric MALT lymphomas.

p16(INK4A) and p57(KIP2) are inhibitors of cyclin-dependent kinases and their inactivation by methylation has been reported as a major tumorigenic mechanism in tumors. To examine whether methylation of p16(INK4A) and p57(KIP2) is involved in the development and progression of gastric MALT lymphomas, 24 gastric low-grade lymphomas of MALT, 11 diffuse large B-cell lymphomas, and 10 each case of gastric lymphoid follicles with and without Helicobacter pylori infection were studied. H. pylori infection was positive in 85.7% of the gastric lymphomas. In the gastric lymphoid follicles positive for H. pylori, methylation of p16(INK4A) was detected in 10% of cases, while methylation of p57(KIP2) was not detected. In low-grade MALT lymphomas, p16(INK4A) and p57(KIP2) were methylated in 41.7 and 29.2% of the cases, respectively. In diffuse large B-cell lymphomas, methylation of p16(INK4A) and p57(KIP2) was found in 72.7 and 36.4% of the cases, respectively. All but one case with p16(INK4A) and p57(KIP2) methylation was H. pylori positive and most of them were stage I. Our results indicate that methylation of p16(INK4A) followed by p57(KIP2) methylation involves during the tumorigenesis of gastric MALT lymphomas associated with H. pylori infection. As methylation of these two genes was more frequent in the higher grade (P<0.05), it may contribute to the malignant progression of gastric MALT lymphomas.