Machine Learning Predicts Pathologic Complete Response to Neoadjuvant Chemotherapy for ER+HER2- Breast Cancer: Integrating Tumoral and Peritumoral MRI Radiomic Features.

BACKGROUND: This study aimed to predict pathologic complete response (pCR) in neoadjuvant chemotherapy for ER+HER2- locally advanced breast cancer (LABC), a subtype with limited treatment response. METHODS: We included 265 ER+HER2- LABC patients (2010-2020) with pre-treatment MRI, neoadjuvant chemotherapy, and confirmed pathology. Using data from January 2016, we divided them into training and validation cohorts. Volumes of interest (VOI) for the tumoral and peritumoral regions were segmented on preoperative MRI from three sequences: T1-weighted early and delayed contrast-enhanced sequences and T2-weighted fat-suppressed sequence (T2FS). We constructed seven machine learning models using tumoral, peritumoral, and combined texture features within and across the sequences, and evaluated their pCR prediction performance using AUC values. RESULTS: The best single sequence model was SVM using a 1 mm tumor-to-peritumor VOI in the early contrast-enhanced phase (AUC = 0.9447). Among the combinations, the top-performing model was K-Nearest Neighbor, using 1 mm tumor-to-peritumor VOI in the early contrast-enhanced phase and 3 mm peritumoral VOI in T2FS (AUC = 0.9631). CONCLUSIONS: We suggest that a combined machine learning model that integrates tumoral and peritumoral radiomic features across different MRI sequences can provide a more accurate pretreatment pCR prediction for neoadjuvant chemotherapy in ER+HER2- LABC.

Characteristics of Korean BCR-ABL1-Negative Myeloproliferative Neoplasms Related to the 2016 WHO Criteria Revision.

BACKGROUND: We aimed to identify changes in the diagnosis and subtype classification of Korean patients with BCR-ABL1-negative MPN related to the revision of the WHO classification in 2016. METHODS: We evaluated 76 Korean patients with BCR-ABL1-negative MPN who underwent diagnostic work-ups, including bone marrow (BM) examinations and JAK2 V617F mutation analysis, from January 2013 to June 2018. Additionally, we reclassified the subtype of 43 patients who were diagnosed based on the WHO 2008 classification. RESULTS: From January 2013 to April 2016, 43 patients were diagnosed with BCR-ABL1-negative MPN (12 PV, 17 ET, 14 PMF) according to the 2008 WHO classification, and from May 2016 to June 2018, 33 patients were diagnosed according to the 2016 classification (15 PV, 11 ET, 7 PMF). With the application of 2016 classification, 3 cases of ET were reclassified as pre-PMF, and the proportion of PV increased from 27.9% to 45.5%. There were significant differences in CBC between pre-PMF and overt PMF, between ET and overt-PMF, but no difference between ET and pre-PMF. CONCLUSIONS: The overall characteristics of BCR-ABL1-negative MPN patients were not significantly different from those of previous reports. 'Masked PV', which could not be diagnosed according to the WHO 2008 classification, may have been diagnosed as PV since 2016 due to the increase in the diagnostic value of the BM findings and the lowering of the hemoglobin (Hb) threshold.

Heterogeneous genetic landscape of congenital neutropenia in Korean patients revealed by whole exome sequencing: genetic, phenotypic and histologic correlations.

Congenital neutropenia (CN) is a hematological disease heterogeneous in its genetic, phenotypic and histologic aspects. We aimed to identify the genetic etiology of Korean CN patients in the context of bone marrow (BM) histology and clinical phenotype. Whole-exome sequencing (WES) or targeted sequencing was performed on the BM or peripheral blood specimens of 16 patients diagnosed with CN based on BM exam from 2009 to 2018. Absolute count of myeloperoxidase (MPO)-positive cells was calculated using ImageJ software. Semi-quantitation of MPO-positive cells in BM sections was performed by MPO grading (grades 0-3). Comprehensive retrospective review on real-world data of 345 pediatric patients with neutropenia including 16 patients in this study during the same period was performed. Seven disease-causing variants were identified in ELANE, G6PC3 and CXCR4 in 7 patients. A novel homozygous G6PC3 variant (K72fs) of which the mechanism was copy-neutral loss of heterozygosity was detected in two brothers. A low myeloid-to-erythroid ratio (0.5-1.5) was consistently observed in patients with ELANE mutations, while MPO-positive cells (40%-50%) with MPO grade 1 or 2 were detected in myelokathexis caused by G6PC3 and CXCR4 mutations. Meanwhile, disease-causing variants were detected in ELANE, TAZ and SLC37A4 in 5 patients by retrospective review of medical records. Our results suggest that following the immunological study and BM exam, WES or an expanded next generation sequencing panel that covers genes related to immunodeficiency and other inherited bone marrow failures as well as CN is recommended for neutropenia patient diagnosis.

Differences in the diagnosis and treatment of hematologic malignancies attributable to health insurance coverage.

ABSTRACT: Medical care should be equally provided to the public regardless of their financial capability. In the real world, expenditures directly out from the patient sector decide the medical journey, even in a country with national health insurance. The aim of this study was to investigate whether there are differences in the diagnostic and treatment processes in hematologic malignancies based on patient characteristics, such as health insurance status.Through the review of 5614 "CBCs with differential count" results with abnormal cells from 358 patients from January 2010 to June 2017, 238 patients without past medical histories of hematologic malignancies were enrolled. Excluding reactive cases, 206 patients with hematologic malignancy were classified into 8 disease categories: acute leukemia, myelodysplastic syndrome, myeloproliferative neoplasm (MPN), myelodysplastic syndrome/MPN, lymphoid neoplasm, plasma cell neoplasm, r/o hematologic malignancy, and cancer.The patients' age, sex, disease categories and follow-up durations showed associations with the clinical course. The "refusal of treatment" group was the oldest and had a relatively higher percentage of females, whereas those who decided to transfer to a tertiary hospital were younger. The age, clinical course, and follow-up durations were different across health insurance statuses. The medical aid group was the oldest, and the group whose status changed from a medical insurance subscriber to a medical aid beneficiary during treatment was the youngest. The majority of patients who refused treatment or wished to be transferred to a tertiary hospital were medical insurance subscribers. The percentage of patients who were treated in this secondary municipal hospital was higher in the medical-aid beneficiaries group than in the medical insurance group. Follow-up durations were longest in the status change group and shortest in the medical insurance group.Almost all medical aid beneficiaries with hematologic malignancies opted to continue treatment at this secondary/municipal hospitals, indicating that this category of medical institutions provides adequate levels and qualified healthcare services to those patients. The secondary municipal hospital provides qualified healthcare services for medical aid beneficiaries with hematologic malignancies.

Evaluation of Three Multiplex Real-time Reverse Transcription PCR Assays for Simultaneous Detection of SARS-CoV-2, Influenza A/B, and Respiratory Syncytial Virus in Nasopharyngeal Swabs.

BACKGROUND: In the coronavirus disease 2019 (COVID-19) pandemic era, the simultaneous detection of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), influenza virus (Flu), and respiratory syncytial virus (RSV) is important in the rapid differential diagnosis in patients with respiratory symptoms. Three multiplex real-time reverse transcription polymerase chain reaction (rRT-PCR) assays have been recently developed commercially in Korea: PowerChek™ SARS-CoV-2, Influenza A&B Multiplex Real-time PCR Kit (PowerChek; KogeneBiotech); STANDARD™ M Flu/SARS-CoV-2 Real-time Detection Kit (STANDARD M; SD BioSensor); and Allplex™ SARS-CoV-2/FluA/FluB/RSV Assay (Allplex; Seegene). We evaluated the analytical and clinical performances of these kits. METHODS: A limit of detection tests were performed and cross-reactivity analysis was executed using clinical respiratory samples. Ninety-seven SARS-CoV-2-positive, 201 SARS-CoV-2-negative, 71 influenza A-positive, 50 influenza B-positive, 78 RSV-positive, and 207 other respiratory virus-positive nasopharyngeal swabs were tested using the three assays. The AdvanSure™ respiratory viruses rRT-PCR assay (AdvanSure; LG Life Sciences) was used as a comparator assay for RSV. RESULTS: Except in influenza B, in SARS-CoV-2 and influenza A, there were no significant differences in detecting specific genes of the viruses among the three assays. All three kits did not cross-react with common respiratory viruses. All three kits had greater than 92% positive percent agreement and negative percent agreement and ≥ 0.95 kappa value in the detection of SARS-CoV-2 and flu A/B. Allplex detected RSV more sensitively than AdvanSure. CONCLUSION: The overall performance of three multiplex rRT-PCR assays for the concurrent detection of SARS-CoV-2, influenza A/B, and RSV was comparable. These kits will promote prompt differential diagnosis of COVID-19, influenza, and RSV infection in the COVID-19 pandemic era.

Increased Nucleated RBCs in Cord Blood: Not an Exclusion Criterion but a Quality Indicator for Hematopoietic Progenitor Cell Transplantation.

Increased nucleated red blood cell (NRBC) counts have been reported to be associated with adverse fetal outcomes, and cord blood units (CBUs) with increased NRBC counts require a 2nd questionnaire to determine their suitability for transplantation. However, a recent study demonstrated a positive correlation of NRBCs with CD34+ cells and total nucleated cells (TNCs). We evaluated the association between the NRBC count and hematopoietic progenitor cell (HPC) content (TNC and CD34+ cell counts) in Korean full-term newborn CBUs. In addition, we assessed whether an increased NRBC count is associated with newborn health problems that impair CBU safety. Among the 32,876 units processed from May 2006 to December 2018, a total of 23,385 CBUs with a TNC count ≥ 7 × 108 and reliable perinatal information were analyzed to assess the association of the NRBC count with CBU parameters, and the newborns associated with 457 CBUs that required the 2nd questionnaire due to an increased NRBC (≥ 15 NRBCs/100 WBCs) were assessed at one year for health problems that threatened CBU safety. The majority of the CBUs that required the 2nd questionnaire due to an increased NRBC count (96.9%) were determined to be suitable for transplantation. Those with an increased NRBC count showed significantly higher CD34+ cell and TNC counts and a higher rate of transplantation (P < 0.001, < 0.001 and 0.025, respectively). NRBCs showed a significant positive correlation with TNCs and CD34+ cells and a significant negative correlation with birth weight (all P < 0.001; adjusted r = 0.185, 0.369 and - 0.029, respectively). In the multiple linear regression analysis, NRBCs showed independent and positive correlations with TNCs and CD34+ cells after adjustments for birth weight and gestational age (all P < 0.001; ß = 0.182, adjusted R2 = 0.053 and ß = 0.367, adjusted R2 = 0.418). An increased NRBC count in full-term normal delivery is a surrogate marker of HPCs in CBUs rather than an exclusion criterion for CBU safety. Moreover, providing the NRBC count together with the NRBC-corrected TNC count will be useful for clinicians to select CBUs for transplantation.

The use of a borderline zone for the interpretation of interferon-gamma release assay results for serial screening of healthcare workers.

OBJECTIVE: An interferon-gamma release assay (IGRA) is used to screen for latent tuberculosis infection (LTBI). Among IGRAs, the QuantiFERON-TB Gold In-Tube (QFT-GIT) results are highly variable, so the borderline zone has been proposed to reduce unnecessary LTBI treatment. The aim of this study was to examine the proportion of the borderline zone of QFT-GIT in healthcare workers' (HCWs) serial IGRA and to retrospectively identify the utility of predicting tuberculosis (TB) in a moderate TB incidence setting. METHODS: The participants were HCWs who had undergone serial LTBI screening between June 2013 and June 2018. IGRA-positive HCWs underwent examinations that included low-dose computed tomography (LDCT) and TB culture, if necessary. Applying the borderline zone (0.2-<0.7 IU/mL), the results were classified as definite negative, borderline negative, borderline positive and definite positive. RESULTS: Through the follow-up of 477 HCWs, 441 (92.5%) invariant, 30 (6.3%) conversion, 2 (0.4%) reversion and 5 (1.0%) indeterminate results were observed with the manufacturer's cutoff. Applying the borderline zone, 419 (87.8%) invariant, 22 (4.6%) conversion, 1 (0.2%) reversion and 36 (7.5%) decision pending, including 5 (1.0%) indeterminate results, were observed. At the time of screening, five TB cases were identified. Chest X-ray (CXR) identified one TB case, and LDCT identified four additional TB cases. After one year, two TB cases were diagnosed, and their screening QFT-GIT results were definite positive and borderline negative. In the Cochran-Armitage trend test, the greater the maximum difference in the QFT-GIT grade with the borderline zone was, the higher the probability of developing TB (P-value <0.001). CONCLUSION: The application of the borderline zone lowered the conversion rate but increased the decision pending rate. Introducing the borderline zone requires a careful approach, and a thorough examination needs to be performed to rule out TB in converters. HCWs with borderline QFT-GIT results also need close observation.

Umbilical Cord Blood Units Cryopreserved in the Public Cord Blood Bank: A Breakthrough in iPSC Haplobanking?

The use of induced pluripotent stem cells (iPSCs) is an emerging therapeutic option for precision medicine. Cord blood (CB) cells with lower immunogenicity, fewer genomic changes, and persistent epigenetic memory might be ideal candidates for iPSC production. Based on the human leukocyte antigen (HLA) distribution of cord blood units (CBUs) in the public CB bank, we estimated the coverage of the Korean population with HLA-homozygous iPSCs to repurpose cryopreserved CBUs. We analyzed a total of 27,904 Korean CBUs donated to the public CB bank. Low-to-intermediate resolution typing was performed for HLA-A, -B, and -DRB1 alleles, and individuals possessing homozygous HLA haplotypes were identified by direct counting. Moreover, the matching probabilities for zero-mismatch transplantation were calculated for 27,904 CBUs and 50,000,000 potential Korean patients. Among the preserved CBUs, 15 HLA-A, 40 HLA-B, and 13 HLA-DRB1 alleles as well as 48 homozygous HLA-A-B-DRB1 haplotypes were identified at serological equivalents (2 digits). The 48 identified homozygous haplotypes cumulatively matched 78.18% of the 27,904 Korean CB donors as zero HLA-mismatch iPSC sources. Among the combinations of 1,699 haplotypes with frequencies greater than 0.001%, assuming a population of 50 million, those 48 haplotypes can provide a match for 78.37% of potential Korean recipients. A practicable number of HLA-A, -B, and -DRB1 homozygous iPSC lines derived from CBUs may be an efficient option in allogeneic iPSC therapy because this type of haplobanking may provide cell lines with optimal HLA matching for up to three-quarters of the Korean population.

Total nucleated cell counts are driving clinician's choice rather than cryopreservation period: Lesson for cord blood banks.

According to the increase in both the number of cryopreserved cord blood (CB) units and the cryopreservation period for each CB unit in the largest public CB bank in Korea, we are pursuing greater efficiency in CB bank management. Thus, we analyzed whether the cryopreservation period has a negative impact on the selection of CB units for CB transplantation (CBT). Until December 2019, 468 CB units were used for transplantation. The cryopreservation period, total nucleated cell (TNC), and CD34+ cell counts were analyzed among the CB units according to the CBT-year and the donation year. The results showed that the cryopreservation period was increased in recent CBT-year groups. The transplanted CB units showed similar TNC counts irrespective of the donation year, and the mean TNC count was 13.9 × 108/unit. CB units cryopreserved for a relatively long period were transplanted consistently. The mean TNC count of CB units cryopreserved for over 10 years was 16.4 × 108/unit. The mean CD34+ cell counts were not significantly different among the CB units transplanted after CBT-2013 and among the CB units donated after CBT-2011. Through an analysis of the CB units selected by clinicians for CBT, this study revealed that clinicians placed more weight on the TNC counts than on the cryopreservation period of cryopreserved CB units. Therefore, the minimum TNC count of CB units suitable for cryopreservation should be increased up to 13.0 × 108/unit to balance the satisfaction of clinicians' needs with the efficiency of the CB bank.

Fifteen new nucleotide substitutions in variants of human papillomavirus 18 in Korea : Korean HPV18 variants and clinical manifestation.

High-risk human papillomavirus (HPV) infection is an essential factor for the development of cervical cancer. HPV18 is the second most common carcinogenic HPV type following HPV16, but the lineages of HPV18 have been less well studied than those of HPV 16. The purpose of this study was to analyze the nucleotide variants in the E6, E7, and L1 genes of HPV18, to assess the prevalence of HPV18 variants in Korea and to explore the relationship between HPV18 genetic variants and the risk for cervical cancer.A total of 170 DNA samples from HPV18-positive cervical specimens were collected from women admitted to a secondary referral hospital located in Seoul. Among them, the lineages of the 97 samples could be successfully determined by historical nomenclature.All the studied HPV 18 variants were lineage A. Sublineages A1 and A4 comprised 91.7% (89/97) and 1.0% (1/97), respectively. Sublineages other than A1 or A4 comprised 7.2% (7/97). We identified 15 new nucleotide substitutions among 44 nucleotide substitutions: C158T, T317G, T443G, A560G, A5467G, A5560C, A5678C, A6155G, G6462A, T6650G, G6701A, T6809C, A6823G, T6941C and T6953C. Among them, 6 substitutions at positions 317, 443, 5467, 5560, 6462, and 6823 resulted in amino acid changes (E6: F71L and N113K; L1: H13R, H44P, A345T, and N465S, respectively). The pathologic results were classified as normal in 25.8% (25/97) of the women, atypical squamous cells of undermined significance (ASCUS) in 7.2% (7/97), cervical intraepithelial neoplasia (CIN) 1 in 36.1% (35/97), CIN2/3 in 19.6% (18/97), and carcinoma in 12.4% (12/97). There was no significant association between the HPV18 sublineages and the severity of pathologic lesion or the disease progression.This study is the first to analyze the distribution of HPV18 variants in Korean and to associate the results with pathologic findings. Although the HPV18 variants had no significant effect on the degree and progression of the disease, the newly discovered nonsynonymous mutation in L1 might serve as a database to determine vaccine efficacy in Korean women.

Patient-reported Goal Achievement after Treating Male Benign Prostatic Hyperplasia with Alpha-adrenergic Antagonist: A 12-week Prospective Multicenter Study.

PURPOSE: The study was designed to assess and predict patient-reported goal achievement after treatment of benign prostatic hyperplasia (BPH) patients with tamsulosin. MATERIALS AND METHODS: From November 2013 to October 2015, 272 patients initially diagnosed with BPH were prospectively enrolled in nine different centers. Before the treatment, subjective final goals were recorded by all patients. Every four weeks, the treatment outcomes were evaluated using international prostate symptom score (IPSS) and uroflowmetry, and adverse events were recorded. Patient-reported goal achievements were assessed after 12 weeks of treatment. RESULTS: Of the enrolled patients, 179 patients completed the study. The pretreatment patients' goals included the frequency improvement, nocturia improvement, residual urine sense improvement, well voiding, hesitancy improvement, weak urine stream improvement, urgency improvement, and voiding-related discomfort improvement. Of the 179 patients, 129 patients (72.1%) reported that they achieved their primary goals after three months of medical therapy. Logistic regression analysis revealed that pretreatment quality of life (OR = 8.621, 95% CI: 2.154-9.834), and improvement of quality of life (OR = 6.740, 95% CI: 1.908-11.490) were independent predictors of patient-reported goal achievement after tamsulosin monotherapy. CONCLUSION: Overall patient-reported goal achievement after medical therapy for BPH was high and the scores of pretreatment quality of life and improvement of quality of life can be important factors to predict the achievement of treatment goals.

Single nucleotide polymorphisms in the TGF-ß1 gene are associated with polycystic ovary syndrome susceptibility and characteristics: a study in Korean women.

PURPOSE: Although many hypotheses regarding the pathogenesis of polycystic ovary syndrome (PCOS) have been generated, genetic studies have not identified specific genes that play a role in PCOS etiopathogenesis. This study aimed to investigate the relationship between TGF-ß1 gene polymorphism and PCOS in Koreans. METHOD: A total of 51 Korean women with PCOS and 69 healthy women were enrolled. We analyzed 4 single nucleotide polymorphisms (SNPs) of the TGF-ß1 gene (rs11466313, rs1800469, rs2317130, and rs4803457). We also analyzed laboratory measurements, such as free testosterone, glucose, and cholesterol. RESULTS: The frequencies of rs1800469T allele negativity, rs4803457T allele negativity, the rs1800469CC genotype, and the rs4803457CC genotype showed positive associations with PCOS (P = 0.003, P = 0.027, P = 0.009, and P=0.031, respectively), whereas the haplotypes rs1800469C-rs4803457T and rs1800469T-rs4803457T showed negative associations with PCOS. A strong protective effect of the "rs1800469CT-rs4803457TT" combination (OR = 0.09) and a strong risk effect of "rs1800469CC-rs4803457CC" (OR = 6.23) for PCOS were observed. The rs1800469C/T and rs2317130C/T SNPs exhibited associations with several laboratory measurements with various levels of significance. CONCLUSION: The results demonstrated an association of TGF-ß1 gene polymorphisms with the development and/or characteristics of PCOS in the Korean population.

Association of human papillomavirus type 16 and its genetic variants with cervical lesion in Korea.

Persistent human papillomavirus type 16 (HPV16) is the major risk factor for cervical cancer. HPV16 intratypic variants differ in their geographical distribution and oncogenic potential. This study aimed to analyze the distribution of HPV16 variants and their association with cervical lesion histopathology in Korean women. In total, 133 HPV16-positive cervical samples from women admitted to Seoul National University Boramae Hospital were analyzed by sequencing E6, E7, and L1 genes and the long control region (LCR), and the variant distribution according to cervical lesion grade was determined. Isolates were grouped into a phylogenetic lineage, and A1-3, A4, C, and D sublineages were detected in 54.1, 37.8, 0.7, and 7.4% of samples, respectively. The most commonly observed LCR variations were 7521G>A (91.5%), 7730A>C (59.6%), and 7842G>A (59.6%). Furthermore, A4 or D sublineage-positive women had a higher risk for cervical cancer than women who were positive for A1-3. Among HPV phylogenetic clusters, A1-3 was the predominant sublineage, and within A1-3, the 350G polymorphism was highly frequent. These results differed from those of previous studies in Korea and other Asian countries. The findings suggest that cervical neoplasia incidence in HPV16-infected patients could be affected by the distribution of HPV16 variants in the population.

Frequency of the moyamoya-related RNF213 p.Arg4810Lys variant in 1,516 Korean individuals.

BACKGROUND: Moyamoya disease (MMD) is a progressive steno-occlusive vasculopathy that involves large intracranial arteries accompanied by abnormal collateral vessels. Recently, RNF213 was identified as a susceptibility gene for MMD and p.Arg4810Lys (rs112735431) is the most common variant in East Asian MMD patients. Interestingly, many studies have reported that a certain proportion of the general population in Japan, Korea, and China also has this variant. In this study, we investigated the frequency of this variant and estimated an odds ratio of MMD using two different Korean populations. METHODS: A total of 1,516 anonymous DNA samples, 799 from an umbilical cord blood bank and 717 from routine health-checked adults, were genotyped using targeted Sanger sequencing. RESULTS: The p.Arg4810Lys variant was detected at genotype frequencies of 2.25% (18/799; 95% confidence interval (CI), 1.43-3.53%) in cord blood samples and 2.65% (19/717; 95% CI, 1.70-4.10%) in adult samples, respectively. This variant showed a strong association with MMD (P < 0.001), giving an odds ratio of 162.7 (95% CI, 65.5-403.9) and 137.8 (95% CI, 55.8-339.9) based on the cord blood and adults samples, respectively. CONCLUSIONS: These results confirm that the RNF213 p.Arg4810Lys variant is not uncommon in the general Korean population and provide reference data for the association of this variant and MMD.

A case of spitzoid melanoma.

Spitzoid melanoma is a subtype of melanoma that, clinically and histologically, resembles a Spitz nevus. Clinically, spitzoid melanomas usually evolve from amelanotic nodular lesions, growing to 1 cm or more in diameter. They often remain clinically undiagnosed because of their wide variety of clinical appearances and a lack of pigmentation. Distinguishing a Spitz nevus from a spitzoid melanoma can be extremely difficult. Features that favor the diagnosis of a spitzoid melanoma are asymmetrical shape, diameter greater than 1 cm, a lesion with a deep invasive component, and a high degree of cytologic atypia. There have been only rare reports in the literature of the presence of giant cells in malignant melanoma, and the presence of these cells may result in its misdiagnosis as a histiocytic tumor. We present a case of spitzoid melanoma on the right ankle of a 22-year-old-woman.

Plasma CC-chemokine ligand 28 level is correlated with hematopoietic stem cells in human cord blood.

BACKGROUND: CC-chemokine ligand 28 (CCL28) was previously identified as a novel growth factor in vitro for hematopoietic stem cells (HSCs) from cord blood (CB). However, there is no report on the relationship between CCL28 and HSCs in a human body. STUDY DESIGN AND METHODS: To reveal the effect of CCL28 on hematopoietic cells in human CB at birth, we measured CCL28 in frozen CB plasma, which was preserved as a reference sample for cryopreserved CB units for HSC transplantation. We also evaluated the correlation of CCL28 level with CB components. RESULTS: A total of 81 cryopreserved nonconforming CB units for transplantation were selected. The level of CCL28 was 2540 ± 377 pg/mL. The CCL28 levels correlated with the number of CD34+ cells (r = 0.222, p = 0.047) and white blood cells (r = 0.254, p = 0.022) in the CB units. The CCL28 levels also correlated with hemoglobin levels (r = 0.221, p = 0.048) in fresh CB. CONCLUSION: This finding of positive correlation between CCL28 level and CD34+ cell numbers in vivo, together with the previous report that CCL28 influences the proliferation of hematopoietic cells in CB in vitro, may give a clue for better understanding the variability in HSC content in CB that is cryopreserved for HSC transplantation.

Regulatory T cells and TGF-ß1 in clinically localized renal cell carcinoma: Comparison with age-matched healthy controls.

PURPOSE: We investigated the proportion of regulatory T cells (Treg cells) in the peripheral blood (PB) and among tumor-infiltrating lymphocytes (TILs) of patients with renal cell carcinoma (RCC) compared with age-matched healthy controls (HCs). We also assessed the presence of several immunomodulatory cytokines in these patients. METHODS: The proportion of Treg cells in the PB of 59 patients with clinically localized RCC and 65 HCs, as well as the prevalence of Treg cells among TILs and lymphocytes in normal kidney tissue, were evaluated by flow cytometry using specific monoclonal antibodies recognizing CD4(+), CD25(+), and Foxp3(+) markers. In addition, the levels of transforming growth factor (TGF)-ß1, interleukin-6, tumor necrosis factor-α, and interferon-γ were determined using standard enzyme-linked immunosorbent assay. RESULTS: There was no difference between the mean percentage of Treg cells in the PB of patients with RCC and HCs (P = 0.148). However, the proportion of Treg cells showed a significant positive correlation with tumor size (r = 0.295, P = 0.029), with the percentage of PB Treg cells significantly higher in patients with RCC with large tumors (≥7 cm) than in HCs (4.6 ± 5.8% vs. 1.9 ± 2.6%, P = 0.023). There was no statistically significant difference in the percentage of Treg cells among TILs and lymphocytes in normal kidney tissue (P = 0.629). The mean TGF-ß1 level in patients with RCC was statistically significantly higher than in HCs (P<0.001). CONCLUSIONS: In this study, we provide evidence for an increased proportion of Treg cells in the PB of clinically localized patients with RCC with substantial tumor burden and a higher level of TGF-ß1 compared with age-matched HCs.

The likelihood of having a serum PSA level of ≥2.5 ng/mL according to the degree of fatty liver disease in a screened population.

INTRODUCTION: We sought to investigate the impact of fatty liver disease (FLD) on prostate cancer (PCa) screening by estimating the odds of having a prostate-specific antigen (PSA) value over the cutoff used to prompt for the recommendation of prostate biopsy. METHODS: Between 2007 and 2013, 18 533 native Korean men eligible to receive a serum PSA test, liver profiles, and abdominal ultrasonography were recruited. Logistic regression was used to estimate the odds of an abnormal PSA (≥2.5 ng/mL) in these men (age 45-75 years, PSA≤10 ng/mL) in relation to FLD. The FLD status was categorized as normal, mild, moderate, and severe grade by abdominal sonography. RESULTS: A total of 16 563 men (89.4%) were included in the study after applying the inclusion criteria. Liver profiles were negatively correlated with the serum PSA level. After controlling for age and obesity, there was a statistically significant trend towards a lower likelihood of having a serum PSA level of ≥2.5 ng/mL with severe FLD, having a 34.7% lower likelihood (odds ratio 0.653, 95% confidence interval 0.477-0.88; p<0.01) compared to men in the normal group. CONCLUSIONS: Severe FLD is an independent predictor of a lower likelihood of having abnormal PSA level. Further studies are needed to better define these results in clinical biopsy practice.

Attached segment has higher CD34+ cells and CFU-GM than the main bag after thawing.

A contiguous segment attached to the cord blood unit (CBU) is required for verifying HLA types, cell viability, and, possibly, potency before transplantation since such a segment is considered to be representative of the CBU. However, little is known regarding the characteristics of contiguous segments in comparison to main bag units due to the difficulty experienced in accessing a large number of cryopreserved CBUs. In this study, we used 245 nonconforming CBUs for allogeneic transplantation. After thawing the cryopreserved CBU, the number of total nucleated cells (TNCs), CD34(+) cells, and CFUs in CB from main bags and segments, as well as cell viability and apoptosis, were examined. The comparative analysis showed that the number of TNCs was significantly higher in CB from main bags, whereas the numbers of CD34(+) cells and CFU-GM were significantly higher in CB from segments. While the cell viability of TNCs in segments was higher, the proportion of apoptotic TNCs was also higher. In contrast, no difference was observed between the proportion of apoptotic CD34(+) cells in main bags and segments. In the correlation analysis, the numbers of TNCs, CD34(+) cells, and CFU-GM in main bags were highly correlated with those in segments, indicating that CB from segments is indeed representative of CB in main bags. Taken together, we conclude that segments have higher CD34(+) cells and CFU-GM and lower TNCs than the main cryopreserved bag, although the two compartments are highly correlated with each other.

Measuring the improvement in health-related quality of life using King's health questionnaire in non-obese and obese patients with lower urinary tract symptoms after alpha-adrenergic medication: a preliminary study.

BACKGROUND: The efficacy of medical treatment among obese men with lower urinary tract symptoms (LUTS) has been less clear, especially regarding the improvement of QoL. We aimed to investigate the difference in efficacy and consequent satisfaction of life quality after medical treatment of male LUTS according to obesity. METHODS: An 8-week prospective study was performed for a total of 140 patients >50 years old with International Prostate Symptom Scores (IPSS) > 12 points and prostate volume > 20 mL. Obesity was determined by either body mass index (BMI) or waist circumference (WC). Patients were divided into 2 groups according to BMI or WC. Patients received tamsulosin at a dose of 0.4 mg daily for 8 weeks. The changes from baseline in the IPSS, maximal urinary flow rate (Qmax), post-void residual volume, questionnaire of quality of life (QoL), and King's Health Questionnaire (KHQ) were analyzed. RESULTS: Of the 150 enrolled patients, 96 completed the study. Seventy-five patients (78.1%) had BMI ≥ 23 kg/m2, and 24 (25.0%) had WC > 90 cm. Overall, the IPSS, IPSS QoL, and total KHQ showed significant improvement. Obese (BMI ≥ 23 kg/m2) and non-obese (BMI < 23 kg/m2) both showed improvement of the IPSS and IPSS QoL scores, but only the obese (BMI ≥ 23 kg/m2) group showed improvement of the total KHQ score (P < 0.001 vs. P = 0.55). Only the obese (WC > 90 cm) group showed improvement of the IPSS and total KHQ scores (P < 0.001). CONCLUSIONS: Our preliminary study showed the different efficacy of an alpha-blocker for improvement of LUTS and life quality according to obesity. Obese patients, defined by BMI or WC, showed the tendency toward a more favorable improvement of LUTS and life quality. TRIAL REGISTRATION: Current Controlled Trials 2010-058. Registered 2 September 2010 in Soonchunhyang University Hospital.