Background: Clonal hematopoiesis of indeterminate potential (CHIP) has been reported to be associated with increased cardiovascular disease, aging and insulin resistance. Despite the debate of causal contribution of CHIP on metabolic diseases, we want to explore whether CHIP is related to diabetic peripheral neuropathy (DPN). Methods: This study analyzed the prevalence of CHIP in patients with type 2 diabetes classified according to DPN status. Logistic regression analysis was used to evaluate the association between CHIP and DPN. Results: CHIP was more prevalent in subjects without DPN than those with DPN (19.9% vs. 8.8%, respectively; P=0.013). Individuals having any CHIP, or DNA methyltransferase 3A (DNMT3A) CHIP were less likely to have any abnormality shown in DPN test; the adjusted odds ratio were 0.85 (95% confidence interval [CI], 0.73 to 1.00) and 0.70 (95% CI, 0.56 to 0.89), respectively. Interestingly, DNMT3A CHIP showed the negative association, but Tet methylcytosine dioxygenase 2 (TET2) CHIP showed the positive association with abnormal feet electrochemical skin conductance level. Conclusion On the contrary to expectations, CHIP was negatively associated with DPN. Functional linking between the mutation in hematopoietic cells and DPN, and the opposite role of DNMT3A and TET2 should be investigated.

Development of transfusion-related acute lung injury (TRALI), a non-cardiogenic pulmonary edema, after blood transfusion, is a rare but potentially leading cause of mortality from blood transfusion. We report on a case of TRALI in a 51-year male with acute calculous cholecystitis and liver cirrhosis. As preoperative treatment, he was given ten units of fresh frozen plasma (FFP) for 3 days before the operation. During the transfusion of the 10th unit of FFP, he experienced a sudden onset of hemoptysis, tachypnea, tachycardia, and cyanosis. Bilateral pulmonary infiltration not observed on the chest X-ray at the visit was newly developed. There was no evidence of volume overload but severe hypoxemia. Blood transfusion was stopped and he recovered fully after 8 days of oxygen therapy through a nasal cannula. Although HLA and HNA antibodies were not detected in the donor's blood, HLA antibodies (A2, B57, B58) were detected in the patient's blood. We reported this meaningful case of TRALI that occurred after transfusion of only fresh frozen plasma which did not contain human leukocyte antibody in a patient with HLA antibody.
Acute Lung Injury* ; Anoxia ; Antibodies ; Blood Transfusion ; Catheters ; Cholecystitis ; Cyanosis ; Hemoptysis ; Humans ; Leukocytes ; Liver Cirrhosis ; Male ; Mortality ; Oxygen ; Plasma* ; Pulmonary Edema ; Tachycardia ; Tachypnea ; Thorax

BACKGROUND/AIMS: To evaluate and select microRNAs relevant to acute myeloid leukemia (AML) pathogenesis, we analyzed differential microRNA expression by quantitative small RNA next-generation sequencing using duplicate marrow samples from individual AML patients. METHODS: For this study, we obtained paired marrow samples at two different time points (initial diagnosis and first complete remission status) in patients with AML. Bone marrow microRNAs were profiled by next-generation small RNA sequencing. Quantification of microRNA expression was performed by counting aligned reads to microRNA genes. RESULTS: Among 38 samples (32 paired samples from 16 AML patients and 6 normal marrow controls), 27 were eligible for sequencing. Small RNA sequencing showed that 12 microRNAs were selectively expressed at higher levels in AML patients than in normal controls. Among these 12 microRNAs, mir-181, mir-221, and mir-3154 were more highly expressed at initial AML diagnosis as compared to first complete remission. Significant correlations were found between higher expression levels of mir-221, mir-146, and mir-155 and higher marrow blast counts. CONCLUSIONS: Our results demonstrate that mir-221 and mir-181 are selectively enriched in AML marrow and reflect disease activity. mir-3154 is a novel microRNA that is relevant to AML but needs further validation.
Bone Marrow ; Diagnosis ; Humans ; Leukemia, Myeloid, Acute* ; MicroRNAs* ; RNA* ; Sequence Analysis, RNA*

BACKGROUND: We evaluated the outcomes of serum galactomannan (GM) assay for the screening of invasive pulmonary aspergillosis (IPA) in allogeneic hematopoietic stem cell transplantation (alloHSCT) recipients while on primary antifungal prophylaxis (PAP). METHODS: This study included patients with hematologic disorders who underwent alloHSCT from January 2013 to November 2015. Patients received routine PAP with fluconazole before 2014 and micafungin after 2014; serum GM tests were performed and retrospectively analyzed. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of serum GM tests for detection of probable/proven IPA were evaluated. The serial change of serum GM levels was illustrated on a time series plot. RESULTS: A total of 136 alloHSCT recipients at Seoul National University Hospital were included in the study. Fluconazole was administered in 72 patients for PAP, while micafungin was administered in the remaining 64 patients. The overall sensitivity, specificity, and NPV of serum GM assays were 95.8% (95% confidence interval [CI] 78.9–99.9%), 93.8% (95% CI 91.7–95.5%), and 99.8% (95% CI 99.1–100.0%), respectively. However, the PPV of GM tests was relatively low at 35.4% (95% CI 23.9–48.2%). The serial change in serum GM levels differed according to the antifungal agents used. With effective PAP using micafungin, serial serum GM levels showed zero order kinetics during the neutropenic period. CONCLUSION: Although the serum GM assay is a sensitive and specific test for detecting IPA in alloHSCT recipients, its role for routine surveillance in an era of effective PAP with micafungin is limited.
Antifungal Agents ; Fluconazole ; Hematology ; Hematopoietic Stem Cell Transplantation ; Humans ; Invasive Pulmonary Aspergillosis* ; Kinetics ; Mass Screening* ; Retrospective Studies* ; Sensitivity and Specificity ; Seoul ; Stem Cell Transplantation* ; Stem Cells*

Accounting ; Adenolymphoma ; Anesthesia, General ; Biopsy, Fine-Needle ; Lymphocytes ; Parotid Gland ; Parotid Neoplasms ; Physical Examination ; Salivary Glands

Zosteriform metastasis from malignant melanoma is a rare type of skin metastasis that shows cutaneous lesions including patches, plaques, and nodules along with dermatomes, and thus needs to be distinguished from herpes zoster skin infection. Although some authors have explained the mechanism of zosteriform metastasis, its pathogenesis remains unknown. Herein, we describe an 85-year-old woman with zosteriform metastasis of malignant melanoma arising in a medium-sized congenital melanocytic nevus.
Aged, 80 and over ; Female ; Herpes Zoster ; Humans ; Melanoma* ; Neoplasm Metastasis* ; Nevus, Pigmented* ; Skin*

PURPOSE: Vascular endothelial growth factor (VEGF)-A, VEGF165b, interleukin (IL)-1beta, and transforming growth factor (TGF)-beta1 are known to influence tumor angiogenesis. Clinical implications of these cytokines need to be elucidated. MATERIALS AND METHODS: Using clinical data and baseline serum samples of 140 consecutive patients with advanced non-small cell lung cancer who received platinum-based combination chemotherapy, we investigated the association among serum cytokine levels, treatment outcomes, as well as leukocyte and platelet counts. RESULTS: The median age of patients was 64 years (range, 26 to 86 years). The male to female ratio was 104:36. High TGF-beta1 and IL-1beta levels were associated with shorter progression-free survival, and high VEGF-A and IL-1beta levels were associated with shorter overall survival in the univariate analysis. VEGF165b was not related to the treatment outcomes. Leukocytosis and thrombocytosis were associated with shorter overall survival. The multivariate analysis demonstrated that VEGF-A, IL-1beta, and leukocytosis were significant prognostic factors (p=0.0497, p=0.047, and p<0.001, respectively). Leukocytosis was not associated with recent pneumonia (p=0.937) and correlated with VEGF-A (p<0.001) and TGF-beta1 (p=0.020) levels. CONCLUSION: Serum VEGF-A, TGF-1beta, and IL-1beta levels, in addition to leukocyte and platelet counts, are shown to be associated with clinical outcomes. Leukocyte and platelet counts are correlated with serum VEGF-A and TGF-beta1 levels.
Blood Platelets ; Carcinoma, Non-Small-Cell Lung* ; Cytokines ; Disease-Free Survival ; Drug Therapy, Combination ; Female ; Humans ; Interleukin-1beta ; Interleukins ; Leukocytes ; Leukocytosis ; Male ; Multivariate Analysis ; Platelet Count ; Pneumonia ; Thrombocytosis ; Transforming Growth Factor beta1* ; Transforming Growth Factors ; Vascular Endothelial Growth Factor A*

The posaconazole tablet formulation was developed to have improved bioavailability compared to the oral suspension. Here, we compared posaconazole plasma concentration (PPC) with the posaconazole oral suspension versus the tablet in Korean patients undergoing remission induction chemotherapy for hematologic malignancies. PPC was measured at 3, 8, and 15 days of treatment with the oral suspension (174 patients) or the tablet (40 patients). At all time-points, mean PPC was significantly higher with the tablet compared to the oral suspension. Our findings suggest that posaconazole tablets generate an optimal PPC earlier and in more patients than the oral suspension among Korean patients.
Antifungal Agents ; Biological Availability ; Dosage Forms ; Drug Therapy ; Hematologic Neoplasms* ; Humans ; Plasma* ; Remission Induction ; Tablets

PURPOSE: Primary effusion lymphoma (PEL) is a type of body cavity–based lymphoma (BCBL). Most patients with PEL are severely immunocompromised and seropositive for human immunodeficiency virus (HIV). We investigated the distinctive clinicopathologic characteristics of BCBL in a country with low HIV burden. MATERIALS AND METHODS: We retrospectively collected data on the clinicopathologic characteristics, treatments, and outcomes of 17 consecutive patients with BCBL at nine institutions in Korea. RESULTS: Latency-associated nuclear antigen 1 (LANA1) immunostaining indicated that six patients had PEL, six patients had human herpesvirus 8 (HHV8)-unrelated BCBL, and five patients had HHV8-unknown BCBL. The patients with PEL exhibited no evidence of immunodeficiency except for one who was HIV positive. One (20%) and four (80%) patients with PEL and six (100%) and zero (0%) patients with HHV8-unrelated BCBL were positive for CD20 and CD30 expression, respectively. The two patients with PEL (one HIV-positive and one HIV-negative patient) with the lowest proliferation activity as assessed by the Ki-67 labeling index survived for > 1 and > 4 years without chemotherapy, respectively, in contrast to the PEL cases in the literature, which mostly showed a high proliferation index and poor survival. CONCLUSION: PEL mostly occurred in ostensibly immunocompetent individuals and had a favorable outcome in Korea. A watchful waiting approach may be applicable for managing HIV-seronegative patients with PEL with a low Ki-67 labeling index. A possible trend was detected among LANA1, CD20, and CD30 expression in BCBL.
Drug Therapy ; Herpesvirus 8, Human ; HIV ; Humans ; Korea ; Lymphoma ; Lymphoma, Primary Effusion ; Prevalence ; Retrospective Studies ; Watchful Waiting

Purpose: Febrile neutropenia (FN) can cause suboptimal treatment and treatment-related mortality (TRM) in diffuse large B-cell lymphoma (DLBCL) patients treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP). Materials and methods: We conducted a prospective cohort study to evaluate the effectiveness of pegfilgrastim prophylaxis in DLBCL patients receiving R-CHOP, and we compared them with the PROCESS cohort (n=485). Results: Since January 2015, 986 patients with DLBCL were enrolled. Pegfilgrastim was administered at least once in 930 patients (94.3%), covering 90.3% of all cycles. FN developed in 137 patients (13.9%) in this cohort (23.7% in the PROCESS cohort, p<0.001), and 4.2% of all cycles (10.2% in the PROCESS cohort, p<0.001). Dose delay was less common (≥3 days: 18.1% vs. 23.7%, p=0.015; ≥5 days: 12.0% vs. 18.3%, p=0.023) in this cohort than in the PROCESS cohort. The incidence of TRM (3.2% vs. 5.6%, p=0.047) and infection-related death (1.8% vs. 4.5%, p=0.004) was lower in this cohort than in the PROCESS cohort. The 4-year overall survival (OS) and progression-free survival (PFS) rates of the two cohorts were not different (OS: 73.0% vs. 71.9%, p=0.545; PFS: 69.5% vs. 68.8%, p=0.616). However, in patients aged ≥75 years, the 4-year OS and PFS rates were higher in this cohort than in the PROCESS cohort (OS: 49.6% vs. 33.7%, p=0.032; PFS: 44.2% vs. 30.3% p=0.047). Conclusion Pegfilgrastim prophylaxis is effective in the prevention of FN and infection-related death in DLBCL patients receiving R-CHOP, and it also improves OS in patients aged ≥75 years.