Risk factors for carbapenem‐resistant Enterobacterales infection among hospitalized patients with previous colonization

BackgroundWe aimed to identify the risk factors for subsequent carbapenem‐resistant Enterobacterales (CRE) infections in patients with initial rectal colonization with CRE.MethodsWe conducted a retrospective case–control study on inpatients with rectal CRE colonization between January 2019 and December 2020. Clinical and microbiological data were extracted from hospital patients'' medical records and the clinical microbiology laboratory. Risk factors were assessed and compared between patients with CRE colonization who had subsequent infections and those who did not have infections.ResultsAmong 1064 patients screened for CRE, we enrolled 205 patients with rectal CRE colonization. Among the 205 colonized bacteria, 78.5% were Klebsiella pneumoniae, with 62.9% of them producing Klebsiella pneumoniae carbapenemase (KPC). Multivariate logistic regression analysis revealed that more than three times hospitalization (p = 0.026), being in a coma (p = 0.019), and exposure to carbapenems (p = 0.015) were independent risk factors for CRE clinical infection among CRE rectal carriers.ConclusionThis is the first study to report that more than three times hospitalization is an independent risk factor for subsequent CRE clinical infection in CRE intestinal carriers. Carbapenem‐resistant Klebsiella pneumoniae is the most important species isolated from hospitalized CRE rectal carriers and is the most common cause of subsequent infections.     

G‐CSF as a potential early biomarker for diagnosis of bloodstream infection

BackgroundCytokines play an important role in bacterial infection, and thus, we aim to find out cytokines that may be diagnostically significant in early stage of bacterial bloodstream infection.MethodsMice models infected with Staphylococcus aureus and Klebsiella pneumoniae were established. Then dynamic changes of nine serum cytokines were monitored within 48 hours after the infection. Cytokines with significant differences between the infected groups and control group were further analyzed. Clinical samples of patients who were suspected of bloodstream infection were collected. Then the diagnostic efficiency of screened cytokines was determined with receiver operating characteristic curve analysis.ResultsAs for mice models infected by Staphylococcus aureus and Klebsiella pneumoniae, six cytokines including IL‐1β, IL‐6, IL‐12p70, G‐CSF, IFN‐γ, and TNF‐α were significantly different (P < .05) between two bacterial infected groups. As for clinical samples, three cytokines including IL‐6, IL‐12p70, and G‐CSF showed significant differences between infection group (Staphylococcus aureus and Klebsiella pneumonia group) and negative control group. With the area under curve of 0.7350 and 0.6431 for G‐CSF and IL‐6, respectively, these two cytokines were significantly different between Staphylococcus aureus and Klebsiella pneumoniae infection groups. Combination of G‐CSF and IL‐6 could improve the AUC to 0.8136.ConclusionsG‐CSF cannot only identify bacterial bloodstream infection, but can also distinguish the infection of Staphylococcus aureus from Klebsiella pneumoniae. Further investigation should be performed concerning the diagnostic efficiency of G‐CSF in diagnosing different types of bacterial bloodstream infection.     

Characteristics of ST11 KPC‐2‐producing carbapenem‐resistant hypervirulent Klebsiella pneumoniae causing nosocomial infection in a Chinese hospital

BackgroundThe purpose of our study is to analyze the microbiological and clinical characteristics of carbapenem‐resistant hypervirulent Klebsiella pneumoniae (CR‐hvKP) that causes nosocomial infection.MethodsWe collected the carbapenem‐resistant K. pneumoniae (CRKP) strains that caused nosocomial infection in a hospital in China and collected the relevant clinical data. We characterized these strains for their antimicrobial and virulence‐associated phenotype and genotype and analyzed the clonal relatedness. We screened hypervirulent strains and compared them with non‐hypervirulent strains.ResultsWe retrospectively analyzed 62 CRKP strains that caused nosocomial infection in a tertiary hospital within 1 year, of which 41 (41/62, 66.1%) CRKP were considered as CR‐hvKP. All CR‐hvKP strains were multi‐drug resistance (MDR) and the vast majority of isolates (39/41, 95.1%) were ST11 KPC‐2‐producing strains. Two hypermucoviscous isolates and 4 capsular types were found in 41 CR‐hvKP. Twenty‐nine isolates (29/41, 70.7%) showed hypervirulence in Galleria mellonella infection model. PFGE showed that ST11‐KL47 CR‐hvKP and ST11‐KL64 CR‐hvKP exhibited a high degree of clonality, while non‐hypervirulent strains were not significant. CR‐hvKP had higher positive rates of bla _KPC‐2 and bla _CTX‐M‐65 and higher levofloxacin resistance (p < 0.001, p = 0.005 and p = 0.046, respectively) when compared to the non‐hypervirulent strains. There was no significant difference between the two groups in terms of in‐hospital mortality (7/41, 17.1% vs 5/21, 23.8%, p = 0.743).ConclusionOur research finds that ST11 KPC‐2‐producing CR‐hvKP is the main type of CRKP that caused nosocomial infection, and clonal spread has occurred. We provide more information about CR‐hvKP in health care.     

Co‐infection of Klebsiella pneumonia,Cytomegalovirus, Aspergillus and Zygomycete in a patient with SARS‐CoV‐2

Co‐infection between severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and other pathogens has become a serious threat. There are the reports of fungal, bacterial, and viral co‐infections with SARS‐CoV‐2. We report the unusual case of concomitant aspergillosis, mucormycosis, cytomegalovirus pneumonia, and also klebsiella pneumoniae empyema as the complication of SARS‐CoV‐2.     

Combined procalcitonin and hemogram parameters contribute to early differential diagnosis of Gram‐negative/Gram‐positive bloodstream infections

BackgroundHemogram parameters and procalcitonin (PCT) play auxiliary roles in the diagnosis and outcome of sepsis. However, it is not clear whether these indicators can quickly distinguish bacterial classification or guide the choice of empirical antibiotics.MethodsWe retrospectively enrolled 381 patients with bloodstream infections (BSI), divided into Gram‐positive bloodstream infections (GP‐BSI) and Gram‐negative bloodstream infections (GN‐BSI). Demographic parameters, hemogram parameters, and PCT were recorded and compared between the two groups.ResultsThe mean platelet volume (MPV), platelet distribution width (PDW), and PCT in the GN‐BSI group were significantly higher than those in the GP‐BSI group, while the platelet count (PLT), plateletcrit, platelet count‐to‐white blood cell count ratio (PWR), platelet count‐to‐neutrophil count ratio (PNR), platelet count‐to‐PCT ratio (PLT/PCT), and mean platelet volume‐to‐PCT ratio (MPV/PCT) were significantly lower in the GN‐BSI group. Multivariate stepwise logistic regression analysis revealed that the independent predictors of GN‐BSI were MPV, PWR, and PCT. The areas under the curve (AUC) for this prediction model was 0.79, with sensitivity =0.75 and specificity =0.71.ConclusionsThere were significant differences in terms of PCT, platelet parameters, and platelet‐related index‐PCT ratio between GN‐BSI and GP‐BSI. Combined PCT and hemogram parameters are more conducive to the early differential diagnosis of bacterial classification of BSI.     

Biomarkers of connective tissue disease‐associated interstitial lung disease in bronchoalveolar lavage fluid: A label‐free mass spectrometry‐based relative quantification study

BackgroundThe pathogenesis of connective tissue disease‐associated interstitial lung disease (CTD‐ILD) is unclear. This study aims to identify differentially expressed proteins (DEPs) in CTD‐ILD to determine the potential role of these DEPs that may play in the pathogenesis of CTD‐ILD and to offer potential therapeutic targets.MethodsBronchoalveolar lavage fluid (BALF) samples were collected from four patients with CTD‐ILD and four patients without CTD‐ILD. Label‐free mass spectrometry‐based relative quantification was used to identify the DEPs. Bioinformatics were used to determine the potential biological processes and signaling pathways associated with these DEPs.ResultsWe found 65 upregulated DEPs including SFTPD, CADM1, ACSL4, TSTD1, CD163, LUM, SIGLEC1, CPB2, TGFBI and HGD, and 67 downregulated DEPs including SGSH, WIPF1, SIL1, RAB20, OAS3, GMPR2, PLBD1, DNAJC3, RNASET2 and OAS2. The results of GO functional annotation for the DEPs showed that the DEPS were mainly enriched in the binding, cellular anatomical entity, cellular processes, and biological regulation GO terms. The results of KEGG analyses showed that the pathways most annotated with the DEPs were complement and coagulation cascades, metabolic pathways, pathways in cancer, and PPAR signaling pathway. COG analyses further informed the functions associated with these DEPs, with most focused on signal transduction mechanisms; posttranslational modification, protein turnover, chaperones; intracellular trafficking, secretion, and vesicular transport; amino acid transport and metabolism; and lipid transport and metabolism.ConclusionsDEPs identified between patients with vs. without CTD‐ILD may play important roles in the development of CTD‐ILD and are potential new biomarkers for early diagnosis of CTD‐ILD.     

Identification of sacrococcygeal and pelvic abscesses infected with invasive Mycoplasma hominis by MALDI‐TOF MS

Background Mycoplasma hominis is the smallest prokaryotic microorganism with no cell wall, high pleomorphism, and slower reproduction than bacteria. It is difficult for clinical technicians to find M. hominis through the negative Gram staining of specimens. Therefore, it is likely to miss detection in routine clinical smear etiological examination. M. hominis is generally considered to be a common colonizing bacterium in urogenital tract with low pathogenicity, and it is usually difficult to invade submucosal tissue and enter the bloodstream.MethodsThe abscesses of the patient were examined histopathologically, and the pus in the abscesses was extracted for etiological examination. MALDI‐TOF MS was used to identify and confirmed the pathogens in the specimens. The commercial Mycoplasma isolation, culture, and drug sensitivity kit was used to determine antibiotic susceptibility.ResultsNo pathogens were found after pathological and smear microscopic examination of the puncture fluid from the sacrococcygeal and pelvic abscesses. Until 48 h later, small, translucent, and gray‐white colonies were observed in the blood plate culture results. The laboratory physician ultimately determined that the pathogen was M. hominis by MALDI‐TOF MS.ConclusionWe report a case of extra‐urogenital cystic abscesses infected by M. hominis, in order to improve clinicians’ comprehensive understanding of the pathogenicity of Mycoplasma. In addition, the clinical laboratory technician should pay attention to the role of Wright–Giemsa staining of puncture fluid smear in the preliminary detection and the application of MALDI‐TOF MS in identification of uncommon pathogenic microorganisms.     

Clinical outcomes of post‐renal transplant patients with COVID‐19 infection in the ICU: A single‐center case series

Most of the post‐renal transplant patients are taking immunosuppressive medications, including calcineurin inhibitors, anti‐proliferative agents, and steroids. This case series highlights the clinical characteristics and outcomes of eight post‐renal transplant patients with severe COVID‐19 infection admitted to the intensive care unit.     

The study of routine laboratory factors in children with mycoplasma pneumoniae pneumonia: serum uric acid may have anti‐inflammatory effect

BackgroundHigh uric acid levels are a risk factor for cardiovascular disorders, and metabolic diseases; however, the role of serum uric acid (sUA) during the mycoplasma pneumoniae pneumonia (MPP) of children is poorly known. This study aimed to clarify the effects of sUA during the MPP of children.MethodsThis was a prospective cohort study of children with MPP from multi‐center inpatient departments from September 2019 to August 2020. Routine laboratory characteristics analyzed including ALT, AST, BUN, CREA, UA, LDH, CK‐MB, WBC, N%, PLT, and CRP. Subjects were divided into 3 groups: non‐MPP, mild MPP (MMPP), and severe MPP (SMPP).Results949 subjects were enrolled, including 207 in non‐MPP, 565 in MMPP, and 177 in SMPP. The optimal cutoff value for sUA is 239 μmmol/L in receiver operating characteristic (ROC) curves analysis. Multivariate logistic regression showed that WBC and sUA had significance for protective effects between non‐MPP and SMPP, but CRP did not have significance between the two groups, N and PLT had significance for risk factors; WBC and sUA did not have significance for the protective effects between non‐MPP and MMPP, CRP had significance between the two groups, N and PLT had significance for the risk effects. Similarly, binary logistic regression showed UA, WBC, and CRP had significance for the protective effects between non‐MPP and MPP, but N and PLT had significance for the risk effects between the two groups.ConclusionBoth multivariate and binary logistic regression demonstrated that sUA displayed a protective effect during the MPP of children, which meant sUA is anti‐inflammatory.     

Serum amyloid a,C‐reactive protein,and procalcitonin levels in children with Mycoplasma pneumoniae infection

Background Mycoplasma pneumoniae (MP) is a common pathogen of community‐acquired pneumonia in children. In the present study, serum amyloid A (SAA), C‐reactive protein (CRP), and procalcitonin (PCT) levels in children with MP infection were analyzed and the differential diagnoses of MP evaluated.MethodsThe study included 152 children with MP infection hospitalized in Tai’an Central Hospital in Shandong Province and 50 healthy children as controls. SAA, CRP, and PCT, as well as serum immunoglobulins and T lymphocyte subsets were analyzed during the acute and convalescent phases. Among the MP‐infected children, 30 cases were selected to monitor the SAA, immunoglobulins, and T lymphocyte subset levels for a week.ResultsThe SAA, CRP, PCT, IgA, and IgM levels were significantly higher in the MP‐infected group than in the control group (F _(SAA) = 83.91, p < 0.05; F _(CRP) = 40.79, p < 0.05; F _(PCT) = 60.58, p < 0.05; F _(IgA) = 43.45, p < 0.05; F _(IgM) = 233.88, p < 0.05). In addition, the levels of these factors were significantly higher in the acute phase than in the convalescent phase (p < 0.05). However, significant difference was not observed in the IgG level between these two groups (p > 0.05). The CD3⁺ and CD4⁺ levels in the MP‐infected group were lower than in the control group ( F _(CD3+)= 60.58, P < 0.05; F _(CD4+) = 89.05, p < 0.05), and the CD8⁺ level was higher than in the control group ( F _(CD8+)= 96.96, p < 0.05). The CD3⁺, CD4⁺, and CD8⁺ levels were significantly different between the acute phase and the convalescent phase (CD3⁺: acute phase vs. convalescent phase, q = 2.79, p < 0.05; CD4⁺: acute phase vs. convalescent phase, q = 2.83, p < 0.05; CD8⁺: acute phase vs. convalescent phase, q = 3.15, p < 0.05). The changes in serum SAA levels in the MP‐infected group positively correlated with the changes in IgA, IgM, and CD8⁺ levels and negatively correlated with CD3⁺, CD4⁺, and CD4⁺/CD8⁺.ConclusionSAA, CRP, and PCT were specific markers for diagnosing early MP infection in children. These findings are important in the differential diagnosis of MP infection and clinical guidance for MP treatment.     

The effect of smoking on COVID‐19–linked biomarkers in hospitalized patients with COVID‐19

BackgroundThe coronavirus pandemic, an infection (coronavirus disease 2019—COVID‐19), caused by severe acute respiratory disease coronavirus 2 (SARS‐CoV‐2), continues to have a strong influence worldwide. Although smoking is a major known risk factor for respiratory infectious disease, the effects of smoking on COVID‐19 are unclear. In this study, we aimed to evaluate the relationship between smoking and important hematologic (lymphocyte count, neutrophil count, platelet count, neutrophil‐lymphocyte ratio [NLR], platelet‐lymphocyte ratio [PLR]), inflammatory, and biochemical biomarkers in the prognosis of hospitalized patients with COVID‐19.MethodsIn a COVID‐19 pandemic hospital between June and August 2020, 200 adult patients aged over 18 years were hospitalized with COVID‐19 inflammatory and hematologic biomarkers at their first admission and smoking data were selected for this study.ResultsThe rate of smokers was much higher among men (91.5%) than in women (8.5%) (p = 0.001). Neutrophil counts were evaluated and was significantly higher in current smokers (p < 0.001) and ex‐smokers (p = 0.001), and NLR (p = 0.008) and ferritin (p = 0.004) levels were higher than in never smokers. The saturation of patients had a negative significant linear correlation of NLR, PLR, and pack years of smoking. Compared with never smokers, current smokers had higher neutrophil counts (OR = 0.828 [0.750–0.915]; p = 0.041), NLR values (OR = 0.948 [0.910–0.987]; p = 0.009), and CRP levels (OR = 0.994 [0.990–0.999]; p = 0.019).ConclusionSerum neutrophil, NLR, and ferritin levels, which are widely used in determining the prognosis of COVID‐19, were found higher in current smokers/ex‐smokers. These results support the view that a poor prognosis of COVID‐19 is associated with smoking.     

Recurrent urinary tract infection with antibiotic‐resistant Klebsiella pneumoniae in a patient with Crohn's disease: A case report

Recurrent urinary tract infections with resistant strains of Klebsiella pneumoniae are a potential complication of the long‐term use of immunosuppressive therapy in patients with Crohn''s disease.     

Effects of co‐infection with Clonorchis sinensis on the sex hormones levels in male patients with chronic hepatitis B

ObjectiveWe evaluated the levels of sex hormones in male hepatitis B patients co‐infected with Clonorchis sinensis (C. sinensis).MethodsA total of 136 male individuals were enrolled in this study, including 27 healthy controls, 28 patients with C. sinensis mono‐infection, 19 patients with only chronic hepatitis B, 18 patients with post‐hepatitis B liver cirrhosis, 26 chronic hepatitis B patients co‐infected with C. sinensis, and 18 post‐hepatitis B liver cirrhosis patients coinfected with C. sinensis. Serum levels of progesterone (P), luteinizing hormone (LH), estradiol (E2), testosterone (T), prolactin (PRL), and follicle stimulating hormone (FSH) in these groups were measured.ResultsThe results showed that compared with the LC group, the LC⁺ C. sinensis co‐infected group had an increase in E2 but decrease in T and FSH. The levels of E2 in CHB⁺ C. sinensis co‐infected patients were significantly higher than those in CHB mono‐infected patients, but the significantly lower levels of T were observed. Compared with HCs group, the LC group showed significant increase in all terms of sex hormones, except PRL. By contrast, the CHB mono‐infected group presented an apparent decrease in E2, T, and PRL than the HCs group. However, there were no significant differences in sex hormone levels between the C. sinensis mono‐infected patients and HCs.ConclusionThis study suggests that C. sinensis co‐infection aggravates the sex hormone disturbance in HBV patients at both chronic hepatitis and cirrhosis stages, providing evidences for potential strategies in disease prevention and treatment.     

Clinical response in metastatic castration‐resistant prostate cancer (mCRPC) cases treated with supra‐physiological doses of testosterone: Bipolar androgen therapy

Androgen deprivation therapy is a standard of care for metastatic prostate cancer. A paradoxical approach utilizing high doses of testosterone in castration‐resistant prostate cancer patients demonstrated clinical responses. Here, we report on four heavily pretreated Japanese patients (including one patient on hemodialysis) successfully treated with supra‐physiological doses of testosterone.     

Establishment of a time‐resolved immunoassay for acute kidney injury based on the detection of Kim‐1

AimTo establish a highly sensitive time‐resolved fluorescence immunoassay (TRFIA) of kidney injury molecule‐1 (Kim‐1) and evaluate its clinical value in acute kidney injury (AKI).MethodsThe Kim‐1‐TRFIA was established by the double‐antibody sandwich method, and the method was evaluated. The established Kim‐1‐TRFIA was used to detect the concentration of Kim‐1 in the serum of healthy controls and patients with AKI.ResultsThe optimal coating antibody concentration and optimal Eu³⁺‐labeled antibody dilution ratio for Kim‐1‐TRFIA are 1 μg/ml and 1:140, respectively. The linear range is 42.71–4666.69 pg/ml. The intra‐ and inter‐assay coefficients of variation are <10%. The specificity of our Kim‐1‐TRFIA is acceptable. The recovery is between 95.14% and 102.84%. The concentration of Kim‐1 in the serum of patients with AKI is 126.50 ± 67.99 pg/ml, which is significantly higher than that in the serum of healthy controls (49.72 ± 16.40 pg/ml, p < 0.001). Staging patients with AKI by glomerular filtration rate shows that the serum concentration of Kim‐1 increases significantly with increasing disease severity (p < 0.05).ConclusionA highly sensitive Kim‐1‐TRFIA was established. With this immunoassay, a good differential diagnosis can be made, and healthy people and AKI patients can be differentiated by detecting the concentration of Kim‐1 in the serum. Moreover, the severity of AKI patients can be determined.     

Effect of artificial skin membrane on the expression of miR‐155 and miR‐506‐3p in patients with second‐degree burns

ObjectiveTo investigate the effect of artificial skin on the expression of miR‐155 and miR‐506‐3p in patients with second‐degree burns.MethodsThe study subjects included 50 patients with second‐degree burns treated from July 2019 to July 2021. The control group received routine nursing, while the research group received both routine and artificial skin intervention simultaneously. The changes in wound tissue fibrosis and prognosis were observed. The expression levels of miR‐155 and miR‐506‐3p and their downstream regulatory factors were detected and correlated with the rehabilitation of patients after artificial skin treatment.ResultsAfter treating second‐degree burns with artificial skin membranes, the patient''s wound tissue fibrosis and inflammation level improved. At the same time, the expression levels of miR‐155 and miR‐506‐3p in related tests were higher than those in patients with available treatment.ConclusionThe effect of artificial skin membrane on the wound healing of second‐degree burn patients may be realized by influencing the expression levels of miR‐155 and miR‐506‐3p and their related signaling pathways.     

Erythrodermic flare‐up of psoriasis with COVID‐19 infection: A report of two cases and a comprehensive review of literature focusing on the mutual effect of psoriasis and COVID‐19 on each other along with the special challenges of the pandemic

The COVID‐19 pandemic has been extra challenging for patients with chronic diseases. Psoriasis is one of the chronic conditions that its treatment mostly relies on immunosuppressants. In this study, we report two cases with a long history of psoriasis that COVID‐19 infection caused them to undergo erythrodermic psoriasis.     

The prognostic values of serum markers in hepatocellular carcinoma after invasive therapies based on real‐world data

Background and aimsHepatocellular carcinoma (HCC) is one of the most common malignancy with poor prognosis, and the mortality rate remains high. More than 70% of HCC patients have recurrence within 5 years after treatment. The purpose of this study is to evaluate the prognostic values of serum markers with retrospective data.MethodsWe applied real‐world data (RWD) to analyze the prognostic values of six serum markers for HCC patients after treatment, including α‐fetoprotein (AFP), α‐fetoprotein‐L3 (AFP‐L3), Golgi protein73 (GP73), alanine aminotransferase (ALT), albumin (ALB), and total bilirubin (TBil). A total of 268 cases were enrolled to analyze recurrence‐free survival (RFS), and 104 cases were used to analyze overall survival (OS).ResultsOur results demonstrated that patients with higher AFP and AFP‐L3 had shorter RFS (p = 0.016 and 0.004), while higher GP73, ALT, and TBil experienced longer RFS (p = 0.000, 0.020, and 0.019). Patients with high‐level GP73, ALT, TBil, and low‐level ALB had significantly higher mortality rate (p=0.035, 0.008, 0.010, and 0.005). Multivariate analysis revealed that GP73 (HR = 1.548, p = 0.001) and ALT (HR = 1.316, p = 0.046) were identified as independent prognostic factors for RFS, ALB (HR = 0.127, p = 0.007), and ALT (HR = 0.237, p = 0.01) were identified as independent prognostic factors for OS. Subgroups analysis showed that GP73 had better prognostic values than other serum markers in early‐stage HCC (p = 0.023).ConclusionsOur study demonstrates that AFP, AFP‐L3, and GP73 can be used as prognostic indicators for predicting the recurrence of HCC, while liver function tests have better survival prediction values. GP73 can act as a promising prognostic marker for early‐stage HCC.     

Lung abscess due to Streptococcus intermedius associated with SARS CoV‐2 infection in pregnancy: Unusual presentation and complication of a commensal bacteria during pregnancy

Streptococcus intermedius is a commensal bacterium reported in a few cases as the causative agent of brain and lung abscesses, pneumonia, and endocarditis. Lung abscesses due to Streptococcus intermedius are rare, especially in pregnancy. We describe the first case of lung abscess due to Streptococcus intermedius in a pregnant woman.     

A study of the moving rate of positive results for use in a patient‐based real‐time quality control program on a procalcitonin point‐of‐care testing analyzer

ObjectiveTo establish an applicable and highly sensitive patient‐based real‐time quality control (PBRTQC) program based on a data model constructed with patients’ results of a procalcitonin point‐of‐care testing (POCT) analyzer.MethodsPatients’ results were retrospectively collected within one year. The Excel software was used to establish quality control (QC) programs of the moving average (MA) and the moving rate of positive results (MR). A Monte Carlo simulation was used to introduce positive and negative biases between 0.01 and 1 ng/ml at random points of the testing data set. Different parameters were used to detect the biases, and the detection efficiency was expressed using the median number of patient samples affected until error detection (MNPed). After comparing the MNPeds of different programs, MA and MR programs with appropriate parameters were selected, and validation plots were generated using MNPeds and maximum number of the patient samples affected (MAX). β curves were generated using the power function of the programs, the performances were compared with that of the conventional QC program.ResultsNeither the conventional QC nor MA program was sensitive to small bias, While MR program can detect the minimum positive bias of 0.06 ng/ml and negative of 0.4 ng/ml at an average daily run size of 10 specimens, with FRs < 1.0%, βs < 1%.ConclusionThe MR program, which is more sensitive to small biases than conventional QC and MA programs, with low FR and β. As such, it can be used as a PBRTQC program with high performance.