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Purpose The aim of this study is to evaluate the safety and efficacy of ex vivo activated and expanded natural killer (NK) cell therapy (SNK01) plus pembrolizumab in a randomized phase I/IIa clinical trial.Materials and Methods Overall, 18 patients with advanced non–small cell lung cancer (NSCLC) and a programmed death ligand 1 tumor proportion score of 1% or greater who had a history of failed frontline platinum-based therapy were randomized (2:1) to receive pembrolizumab every 3 weeks +/– 6 weekly infusions of SNK01 at either 2×109 or 4×109 cells per infusion (pembrolizumab monotherapy vs. SNK01 combination). The primary endpoint was safety, whereas the secondary endpoints were the objective response rate (ORR), progression-free survival (PFS), overall survival, and quality of life.Results Since no dose-limiting toxicity was observed, the maximum tolerated dose was determined as SNK01 4×109 cells/dose. The safety data did not show any new safety signals when SNK01 was combined with pembrolizumab. The ORR and the 1-year survival rate in the NK combination group were higher than those in patients who underwent pembrolizumab monotherapy (ORR, 41.7% vs. 0%; 1-year survival rate, 66.7% vs. 50.0%). Furthermore, the median PFS was higher in the SNK01 combination group (6.2 months vs. 1.6 months, p=0.001).Conclusion Based on the findings of this study, the NK cell combination therapy may consider as a safe treatment method for stage IV NSCLC patients who had a history of failed platinum-based therapy without an increase in adverse events.

Platelet transfusion refractoriness (PTR), in which platelet counts do not increase after transfusion, occurs in many patients receiving platelet transfusions. PTR is a clinical condition that can harm patients. The causes of PTR can be divided into two types: immune and non-immune. Most cases of PTR are non-immune. Among immune causes, the most common is human leukocyte antigen (HLA) class I molecules. PTR caused by anti-HLA antibodies is usually managed by transfusing HLA-matched platelets. Therefore, it is important, especially for hemato-oncologists who frequently perform transfusion, to accurately diagnose whether the cause of platelet transfusion failure is alloimmune or non-immunological when determining the treatment direction for the patient. In this review, we discuss the definitions, causes, countermeasures, and prevention methods of PTR.

The number of ABO-incompatible solid organ transplantations (ABOi SOTs) has markedly increased worldwide since the early 2000s. We investigated the choice of ABO group for blood component transfusion in ABOi SOT. We conducted a survey by e-mailing a questionnaire to blood bank specialists at 77 major hospitals in Korea, among whom 34 responded to the survey. In major ABOi SOT, for red blood cells (RBCs), the recipient's type (70.6%) was the most common choice, followed by group O (29.4%); for platelets, group AB (50.0%) was the most common choice, followed by the donor type (38.2%); for plasma, group AB (55.9%) was the most common choice, followed by the donor type (32.4%). In bidirectional ABOi SOT, for RBCs, the recipient's type (55.9%) was the most common choice, followed by group O (44.1%); for platelets and plasma, group AB was the most common choice (94.1% and 97.1%, respectively). The policies for transfusion in ABOi SOT were diverse. We suggest a guideline on the choice of ABO group for transfusion in ABOi SOT to secure patient health and enable an efficient use of blood components.

Rapid, simple, and inexpensive diagnostic point-of-care tests (POCTs) are essential for controlling infectious diseases in resource-limited settings. In this study, we developed a new detection system based on nanoparticle–DNA aggregation (STat aggregation of tagged DNA, STAT-DNA) to yield a visual change that can be easily detected by the naked eye. This simplified optical detection system was applied to detect hepatitis C virus (HCV). Reverse transcription-polymerase chain reaction (RT-PCR) was performed using primers labeled with biotin and digoxigenin. Streptavidin-coated magnetic particles (1 μm) and anti-digoxigenin antibody-coated polystyrene particles (250–350 nm) were added to form aggregates. The limit of detection (LoD) and analytical specificity were analyzed. The STAT-DNA results were compared with those of the standard real-time PCR assay using serum samples from 54 patients with hepatitis C. We achieved visualization of amplified DNA with the naked eye by adding nanoparticles to the PCR mixture without employing centrifugal force, probe addition, incubation, or dilution. The LoD of STAT-DNA was at least 101 IU/mL. STAT-DNA did not show cross-reactivity with eight viral pathogens. The detection using STAT-DNA was consistent with that using standard real-time PCR.

Background and objectives: The ABO antibody (Ab) titration tests are used in monitoring in ABO-incompatible (ABOi) solid organ transplantation (SOT). However, currently developed ABO Ab tests show Ab binding reactions. This study attempted to measure ABO Ab level using complement-dependent cytotoxicity (CDC). Materials and methods: We studied 93 blood group O serum samples from patients who underwent ABOi SOT from January 2019 to May 2021. Patients’ sera were incubated with A1 or B cells and added to a human complement solution. Supernatants were collected after centrifugation, and free hemoglobin (Hb) was measured by spectrophotometry. We converted plasma Hb value to hemolysis (%), which were compared with ABO Ab titer. Results: We found a mild correlation between hemolysis and ABO Ab titers. In simple regression analysis, the correlation coefficients were within 0.3660–0.4968 (p < 0.0001) before transplantation. In multiple linear regression analysis, anti-A hemolysis (%) was higher in immunoglobulin M (IgM) (β = 12.9) than in immunoglobulin G (IgG) (β = −3.4) (R2 = 0.5216). Anti-B hemolysis was higher in IgM (β = 8.7) than in IgG (β = 0.0) (R2 = 0.5114). There was a large variation in hemolysis within the same Ab titer. Conclusions: CDC can be used in a new trial for ABO Ab measurement. Furthermore, IgM rather than IgG seems to play a significant role in vivo activity, consistent with previous knowledge. Thus, this study may help in the development of the ABO Ab titration supplement test for post-transplant treatment policy establishment and pre-transplant desensitization.

Background Reference intervals defined for adults or children of other ethnicities cannot be applied in the evaluation of Korean pediatric patients. Pediatric reference intervals are difficult to establish because children are in their growing stage and their physiology changes continuously. We aimed to establish reference intervals for routine laboratory tests for Korean pediatric patients through retrospective multicenter data analysis. Methods Preoperative laboratory test results from 1,031 pediatric patients aged 0 month-18 years who underwent minor surgeries in four university hospitals were collected. Age- and sex-specific reference intervals for routine laboratory tests were defined based on the Clinical and Laboratory Standards Institute (CLSI) EP28-A3c guidelines. Results The pediatric reference intervals determined in this study were different from existing adult reference intervals and pediatric reference intervals for other ethnicities. Most tests required age-specific partitioning, and some of those required sex-specific partitioning for at least one age-partitioned subgroup. Erythrocyte sedimentation rate, monocyte percentage, basophil percentage, activated partial thromboplastin time, glucose, cholesterol, albumin, bilirubin, chloride, and C-reactive protein did not show any difference between age- or sex-partitioned subgroups. Conclusions We determined Korean pediatric reference intervals for hematology, coagulation, and chemistry tests by indirect sampling based on medical record data from multiple institutions. These reference intervals would be valuable for clinical evaluations in the Korean pediatric population.

The immunogenicity of a blood group antigen is a measure of its likelihood of inducing alloantibodies. Although the immunogenicity of blood group antigens has been analyzed in Caucasian populations, immunogenicity to date has not been analyzed in Asian subjects. The present study therefore evaluated the relative immunogenicity of blood group antigens in a Korean population.All available data of unexpected antibody identification tests performed at Asan Medical Center between 1997 and 2021 were analyzed. The relative immunogenicity of a blood group antigen relative to K antigen was calculated based on relative numbers of alloantibodies and the probabilities of antigen-negative recipients receiving antigen-positive RBC units.A total of 3898 antibody identification results were included, with 1632 (41.9 %) from male patients. The ranking of antigen immunogenicity was: E c e C K Jk(a) Lu(a) S Fy(a) Fy(b) Jk(b) Di(b) Di(a) in the total population and E c e C Jk(a) Fy(a) Fy(b) S K Lu(a) Jk(b) Di(b) Di(a) in male patients.The rank order of immunogenicity for blood group antigens in this study provides information about relative immunogenecity in Koreans. These findings also provide supporting evidence regarding antigen selection for extended antigen-matched transfusions in recipients of multiple transfusions.

Objective We compared the clinical outcomes of recipients of ABO-incompatible (ABOi) kidney transplantation (KT) according to the blood group of the plasma transfused. Materials and Methods We retrospectively analyzed the data of 60 recipients of ABOi-KT with blood type O and A or B donors. Demographic and clinical characteristics were compared between 2 groups of recipients: 1 group received AB plasma regardless of the donor’s blood type (n = 30), and the other group received donor-type plasma (n = 30). Results There were no significant differences between the groups in terms of demographic characteristics. Transfusion of donor-type plasma was noninferior to transfusion of type AB plasma in terms of both rejection-free survival and rejection rate (P = .455, P = .335). Conclusion There was no significant prognostic difference between the 2 groups. In terms of blood supply and inventory management, we suggest that the blood group of the plasma should match the donor’s type.

Background Recent advances in desensitization techniques and immunosuppressive therapy have led to improved outcomes after ABO-incompatible (ABO-i) kidney transplantation (KT). However, questions remain unanswered, particularly regarding which type of ABO isoagglutinin-immunoglobulin M (IgM) or immunoglobulin M (IgG)-is significantly involved in antibody-mediated rejection (AMR). Study design and methods We retrospectively analyzed data from 120 patients who underwent ABO-i KT between 2012 and 2014. Preoperative plasma exchange was performed until the IgM isoagglutinin titer was 4 or less, regardless of the IgG titer. Clinical data were compared between patient groups with pre-KT IgG isoagglutinin titer 16 or greater (high IgG; titer range, 16-256; n = 39) and 8 or less (low IgG; titer range, -8; n = 81). Results The median follow-up periods were 59 (high IgG) and 55 (low IgG) months. Patient survival at 5 years (p = 0.314) was 100% (high IgG) and 97.4% (low IgG). Graft survival at 5 years (p = 0.480) was 100% (high IgG) and 98.7% (low IgG). AMR by anti-ABO antibody occurred in only one patient in the low-IgG group. Conclusion Patients with high pre-KT IgG isoagglutinin titers had equally successful outcomes as those with low IgG titers. ABO-i KT can be successfully performed by reducing the pre-KT IgM isoagglutinin titer to 4 or less, as determined by the immediate spin tube method.

ABO antibodies occur naturally and usually exist as alloantibodies. They are the most clinically significant in cases of transfusions. However, there are very few reports on auto-anti-A or B. A 58-year-old man visited our hospital for evaluation of an inguinal mass. Blood typing was performed, while preparing the patient for an excisional biopsy. Forward and reverse typing showed a typical AB and A pattern. Results of the direct antiglobulin and unexpected antibody screening tests were negative. The serum did not react with AB3 cells. The biopsy revealed a diffuse large B-cell lymphoma. After completing four cycles of R-CHOP chemotherapy, the patient achieved complete remission. There were no anti-B antibodies found on repeat ABO typing. This report shares our experience on unexpected anti-B antibody findings in a patient with an A1B blood type. To the best of our knowledge, this is the first report of anti-B antibodies in a patient with an A1B blood type in Korea.

Objective We designed a study to compare the efficacy of cryoprecipitate-reduced plasma (CRP) and fresh frozen plasma (FFP), at the level of individual sessions, for treating refractory thrombotic microangiopathy (TMA) with therapeutic plasma exchange (TPE). Materials and Methods Platelet counts (× 10³/μL) and lactate dehydrogenase (LD; IU/L) levels were measured before and after each session. We compared the mean-percentage and absolute changes in platelet count and LD after each TPE session. Results The data from 33 patients treated for TMA between 2009 and 2018 were collected for this study. Both absolute and percentage increases in the platelet count were statistically significant (P = .003 and P = .011, respectively) when CRP was used. However, when patients were divided into subgroups according to specific diagnosis, no significant differences were found among the groups, except in terms of the absolute platelet count increase in the thrombotic thrombocytopenic purpura group (P Conclusion The platelet count increase was higher when patients received CRP than when they received FFP. We found that CRP may be a rescue option for patients with refractory TMA.

Objectives Rh(D)-incompatible (Rh-i) solid organ transplantations are not considered for organ matching, but no consensus guidelines exist regarding the need for anti-D immunoglobulin (RhIG) prophylaxis. Methods We reviewed 35 Rh(D)-negative patients who had received Rh-i solid organ transplantation. We divided the patients into a RhIG-administered group and a nonadministered group. All patients also underwent an antibody screening test to assess Rh alloimmunization. Graft function was monitored with serum creatinine or bilirubin and kidney or liver biopsy whenever a rejection was suspected. Overall survival was also assessed. Results The median (range) age of transplant recipients was 48.5 (4-69) years, and 73.5% of patients were male. Median (range) follow-up time after transplantation was 60 (2-246) months. In the RhIG nonadministered group (n = 16), anti-D was not detected in any of the patients. More rejection episodes occurred in the RhIG-administered group among those undergoing kidney transplant (P = .0278). Conclusions The low rate of Rh(D) alloimmunization is associated with the immunosuppressive state of the patients. RhIG prophylaxis seems to have no clinical benefit in Rh-i solid organ transplantation.

To ensure safe red blood cell (RBC) transfusion practice, it is important to comply with storage and transport requirements of RBC units. We conducted a comprehensive survey on the practice of RBC transport and storage to explore the awareness of and compliance with the 30-minute rule, the current status of RBC unit transport, and possible utility of temperature indicators (TIs) to reduce RBC wastage.From June to August of 2019, 64 blood bank physicians (14 questions) in 64 secondary- and tertiary-care hospitals and 673 nurses (13 questions) in 42 tertiary-care hospitals replied to a questionnaire survey. The results of the survey were analyzed with descriptive statistics.Among the physicians surveyed, 97.0% (N=62) of hospitals had transfusion guidelines in place. The RBC wastage in 2018 ranged from less than five units to more than 200 units. Among the nurses surveyed, 99.4% (N=669) were aware of and complied with the 30-minute rule; 13.5% (N=91) of the nurses had experience of RBC wastage due to violation of the 30-minute rule. Both physicians (67%, N=43) and nurses (83.1%, N=559) responded that TIs would help reduce RBC wastage.This is the first survey on the practices related to RBC transport and storage in Korea. This study provides fundamental data on current practice for the blood cold chain, insights into RBC wastage, and highlights the utility of TIs.

BACKGROUND AND OBJECTIVES Temperature indicators (TIs) are used to monitor the surface temperature of red blood cell (RBC) units. We compared the utility of a newly developed time-temperature indicator (TTI) prototype, Freshzone TTI (FZTTI) (Freshzone, Seoul, South Korea) and two US Food and Drug Administration-approved TIs, Safe-T-Vue 10 (STV10; Temptime Corporation, Morris Plains, NJ) and Blood Temp 10 (BT10; Timestrip UK Ltd, Cambridge, UK). MATERIALS AND METHODS FZTTI, STV10 and BT10 were attached to 91 RBC units after issue (including eight units that were stored in refrigerators in the ward before transfusion). The time for colour change (CC) was monitored based on the 30-min rule. The CC of FZTTI indicated the total time elapsed since the temperature of RBC units exceeded 10°C, and the CC of STV10 and BT10 indicated that the temperature of RBC units exceeded 10°C. RESULTS In 83 units, the median time for CC differed significantly between FZTTI and the TIs (51.4 min in FZTTI vs. 13.9 min in STV10 and 10.5 min in BT10, both at p

Affordable point-of-care (POC) CD4 + T lymphocyte counting techniques have been developed as alternatives to flow cytometry-based instruments caring for patients with human immunodeficiency virus (HIV)-1. However, POC CD4 enumeration technologies can be inaccurate. Here, we developed a microparticle-based visual detector of CD4 + T lymphocytes (ImmunoSpin) using microparticles conjugated with anti-CD4 antibodies, independent of microfluidic or fluorescence detection systems. Visual enumeration of CD4 + T cells under conventional light microscope was accurate compared to flow cytometry. Microparticle-tagged CD4 + T cells were well-recognized under a light microscope. ImmunoSpin showed very good precision (coefficients of variation of ImmunoSpin were ≤ 10%) and high correlation with clinical-grade flow cytometry for the enumeration of CD4 + T cells (y = 0.4232 + 0.9485 × for the %CD4 + T cell count, R2 = 0.99). At thresholds of 200 and 350 cells/µL, there was no misclassification of the ImmunoSpin system compared to the reference flow cytometry. ImmunoSpin showed clear differential classification of CD4 + T lymphocytes from granulocytes and monocytes. Because non-fluorescence microparticle-tags and cytospin slides are used in ImmunoSpin, they can be applied to an automatic digital image analyzer. Slide preparation allows long-term storage, no analysis time limitations, and image transfer in remote areas. Graphical abstract

Bisphenol A (BPA) is an endocrine-disrupting chemical thought to mimic the action of oestrogens. There have been reports suggesting an association between BPA exposure and infertility in hu...

Background Krebs von den Lungen 6 (KL-6) is a sensitive marker for diagnosing, monitoring, and predicting the prognoses of interstitial lung diseases (ILDs). This study aimed to evaluate the performance of the Nanopia KL-6 assay (Sekisui Medical, Tokyo, Japan) and to test the relationship between KL-6 concentrations and clinical results. Methods In total, 230 patients diagnosed as having ILDs were enrolled. All underwent high-resolution computed tomography (HRCT) followed by the pulmonary function test (PFT). We also enrolled 116 disease controls and 200 healthy controls. Evaluation of the Nanopia KL-6 assay involved determination of precision, linearity, and limit of quantification (LOQ). Results from the Nanopia KL-6 assay were compared with those from ELISA and correlated with the HRCT and PFT results. Results The within-laboratory precisions were

Introduction Chimerism is defined as coexistence of different cell lines in an individual. 46,XX/46,XY chimerism is very rare and exhibits broad range of clinical phenotypes. Most cases are detected at infancy or younger age due to disorders of sex development, while phenotypically normal cases are incidentally discovered through abnormal blood grouping results or multiple genotypes in HLA. Objective Aim was to determine the genetic expression of numerous HLA alleles detected in phenotypically normal 46,XX/46,XY chimerism. Materials and methods A patient was admitted for lung transplantation due to end-stage pulmonary disease. Pre-transplantation work-up included blood group typing and HLA DNA typing analyses. Peripheral blood and hair follicle specimens were used to confirm unusual tri-allelic results by high-resolution PCR-SBT. Cytogenetic analyses of karyotyping, FISH and chromosomal microarray were done. Flowcytometry crossmatch analysis was conducted using lymphocytes and anti-HLA sera defined by Luminex panel reactive antibody test (One Lambda, Inc., Canoga Park, CA), to determine antigen expression of HLA alleles. Results 46,XX/46,XY chimerism was confirmed through series of cytogenetic analyses. HLA typing of the patient revealed three alleles from HLA-A, -B and -DRB1 loci. Antigen expression of all 3 HLA alleles was confirmed by flow cytometry crossmatch. Discussion A case of normal phenotype 46,XX/46,XY chimerism was detected for the first time in Korean patient admitted for lung transplantation. Cytogenetic results were confirmatory for chimerism and HLA typing using PCR-SBT method was able to detect the presence of 3 HLA alleles. Flowcytometry crossmatch was proven sensitive for detecting antigen expression of different cell lines of small proportions.

Background The Automated Fluorescent Immunoassay System (AFIAS) rotavirus assay (Boditech Med Inc., Chuncheon, Korea) is a new rapid antigen test for rotavirus detection. We evaluated the performance of this assay for detecting rotaviruses and their specific genotypes in clinical stool samples. Methods AFIAS rotavirus assay was performed in 103 rotavirus-positive and 103 rotavirus-negative stool samples (confirmed by both PCR and ELISA), and its results were compared with those of PCR, ELISA, and immunochromatographic assay (ICA). We evaluated diagnostic sensitivity/specificity, the detectability of rotavirus subtypes, lower limit of detection (LLOD), reproducibility, cross-reactivity, and interference of AFIAS rotavirus assay. Results Based on PCR and ELISA results, diagnostic sensitivity and specificity of the AFIAS rotavirus assay were both 99.0%. LLOD results showed that the AFIAS assay had sensitivity similar to or greater than ICA and ELISA. High reproducibility was confirmed, and no cross-reactivity or interference was detected. This assay could detect genotypes G1P[8], G2P[4], G3P[8], G4P[6], G4P[8], G8P[4], G8P[8], G9P[4], and G9P[8]. Conclusions The AFIAS rotavirus assay showed high reproducibility, sensitivity, and specificity as well as excellent agreement with ELISA, PCR, and ICA. It detected the most common as well as unusual genotypes of rotavirus prevalent in Korea. It could be a useful on-site assay for rapid, convenient, and cost-effective detection of rotavirus infection.

Background Criteria for selection of FFP blood type has not been clearly established and use of group AB plasma is preferred by numerous transplantation protocols. Aims This study assesses the safety and efficacy of alternative group A or B plasma in ABO incompatible solid organ transplantation. Materials & methods Alternative use of group A or B plasma (incompatible plasma) was inevitable during the shortage of group AB plasma. Experience from select number of patients during the period of extreme group AB plasma shortage is described. Results The result of alternative use of group A or B plasma was within expectation, showing effective reduction of isoagglutinin titers for pre-operative desensitization and efficacy for treatment of post-operative patients. No immediate hemolytic transfusion reaction was reported. Discussion While validation in a larger cohort of patients is necessary, our limited experience have shown satisfactory clinical outcomes without adverse events. Conclusions Use of incompatible group A or B plasma is a viable option when group AB plasma is limited.

Bioavailable vitamin D and vitamin D metabolite ratio (VMR) have emerged as potential novel vitamin D markers. We developed a multiplex liquid chromatography-tandem mass spectrometry (LC-MS/MS) method to determine all elements necessary for the calculation of bioavailable vitamin D and VMR, including 25-hydroxyvitamin D [25-(OH)D] and 24,25-dihydroxyvitamin D

Background Anti-blood group antibody titers (ABTs) reported in titer values are variable depending on the testing method used. The introduction of new test methods such as automated methods requires proper method comparison. In this study, the automated blood bank system and manual tube method for ABT were compared using a log-transformed dataset to evaluate the alternative statistical approach. Methods ABT was conducted using specimens referred for solid organ transplantation. Methods for comparison were conventional manual tube method and IH-500 automated blood bank system using column agglutination (CAT). Criteria for agreement were exact match and 1-titer match. Measured titer values were log-transformed into interval scale for Deming regression analysis. Results From the comparison of the tube and CAT methods using titer values and the two criteria, the exact and 1-titer match were 15.9–41.5 % and 65.9–97.6 %, respectively. Deming regression was used to demonstrate the presence of both proportional and constant difference between the two methods. Conclusion The method comparison using conventional statistical approaches had limits due to the semi-quantitative value of the test. Log-transformed interval scale values for comparison were useful for interpretation of method comparison datasets. This alternative statistical approach could contribute to a more accurate comparison between assays and standardization of ABT testing.

Background The urinary albumin/creatinine ratio (ACR) is an important indicator of albuminuria. We aimed to estimate ACR uncertainty and its impact on test results and proposed imprecision quality goals based on the estimated uncertainty. Methods The combined ACR uncertainty was calculated using the individual uncertainties of urinary albumin and creatinine. ACR confidence intervals (CIs) were estimated based on the expanded uncertainty. When the CI contained the ACR category boundary (30 or 300 mg/g), the cases were considered ambiguous. Quality goals for ACR were suggested using the number of ambiguous cases among actual patient results. Results The number of ambiguous cases resulting from the combined ACR uncertainty was higher than expected based on biological variation (BV) quality goals. When the ACR met BV quality specifications, we estimated that 4.8-15.5% of the results may have been misclassified. To minimize the number of ambiguous results, the minimum, desirable, and optimum quality goals were set at 34.0%, 18.0%, and 4.5%, respectively. Conclusions We expressed ACR uncertainty using the uncertainties of urinary albumin and creatinine and assessed the impact of this combined uncertainty on the test results. Subsequently, we proposed imprecision quality goals for ACR based on ambiguous results.

Objectives We reanalyzed the data from proficiency testing (PT) to assess the effect of the geometric mean in the statistical analysis of immunohematologic data. Methods Using the five most recent anti–blood group antibody titer participant summary results, the geometric mean (GM) ±2 × geometric standard deviation (GSD) was used as the comparative consensus criterion to mode ±2 titers. Results Using the PT evaluation criterion of mode ±2 titers, the mean percentages of participants with acceptable results were 97.5% and 97.8% for anti-A and anti-D, respectively. When applying GM ±2 GSD, the mean percentages of acceptable results were 96.1% (anti-A) and 96.1% (anti-D). The percentages of responses included in each consensus criterion were lower using GM ±2 GSD, with a few exceptions. Conclusions Geometric means are more robust and precise in visualizing the central tendency. This method can improve the statistical robustness of PT evaluations.