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Background Chronic lymphocytic leukemia (CLL) is the most common type of adult leukemia in Western countries but is rare in the East Asian countries. Due to its rarity and the lack of feasible novel agents and laboratory prognostic tools, there are limited data on the clinical outcomes of this disease in Asia. To clarify the current treatment status, we performed a multicenter retrospective analysis of patients with CLL in Korea. Methods The medical records of 192 eligible patients between 2008 and 2019 were reviewed for clinical characteristics, treatment courses, and outcomes. The first-line treatment regimens of the patients included in this analysis were as follows: fludarabine/cyclophosphamide/rituximab (FCR) (N=117, 52.7%), obinutuzumab plus chlorambucil (GC) (N=30, 13.5%), and chlorambucil monotherapy (N=24, 10.8%). Results The median progression-free survival (PFS) was 55.6 months, and the average 2-year PFS rate was 80.3%. PFS was not significantly different between the patients receiving FCR and those receiving GC; however, chlorambucil treatment was associated with significantly inferior PFS (P more...

Parapharyngeal space (PPS) tumors are extremely rare, composing only 0.5% of all head and neck tumors. The PPS is shaped like an inverted pyramid bounded by the skull base superiorly and hyoid bone inferiorly. Recently, we experienced a 55-year-old female patient who visited the clinic with a presumed PPS tumor that had been incidentally identified by neck MRI. The patient underwent surgery for the removal of tumor by transoral approach following tonsillectomy. However, contrary to the initial expectations, no tumors were visible at the operative field and only observed were the evidence of chronic inflammatory tissues within the removed tonsil. To date, chronic follicular tonsillitis mimicking a PPS tumor has not been reported in the literature. Therefore, we report this case with a brief discussion of points to consider supported by a review of relevant literature. more...

Pharyngocutaneous fistula is a readily encountered complication that occurs after surgery for laryngopharyngeal cancer. The development of pharyngocutaneous fistula increases hospitalization, delays postoperative adjuvant treatment, and can lead to serious complications such as wound infection and carotid artery rupture. Transoral robotic surgery (TORS) is actively being performed as a standard procedure for surgery of pharyngeal and laryngeal cancers. Many reports verified that TORS is advantageous in terms of perioperative outcomes such as decreased hospitalization and reduced rate of postoperative complications, free flap reconstruction, and tracheostomy or gastrostomy tube dependence relative to open surgery. However, careful selection of patients is mandatory and there are some critical points to consider in optimal treatment outcomes. Recently, we experienced a 47-year-old patient with tonsillar cancer who underwent lateral oropharyngectomy by TORS and radical neck dissection. Unfortunately, multiple pharyngocutaneous fistulae occurred following postoperative concurrent chemoradiotherapy (CCRT). Multiple phrayngocutaneous fistulae following TORS and postoperative CCRT have not been reported in the literature. Therefore, we report this case with a brief discussion supported by a review of the relevant literature. more...

Complete surgical excision within a margin of normal healthy bone is the treatment of choice for intraosseous hemangioma. A 56-year-old man visited with complaints of a firm, mildly tender, immovable, and palpable mass on the right forehead (size: 1.5× 1.5 cm). Non-contrast brain computed tomography performed preoperatively revealed a 1.5 cm heterogenous osteolytic lesion with suspected internal trabeculation in the right frontal bone. Under general anesthesia, a 2 cm transverse incision was made on the forehead skin rather than bicoronal incision. Full-thickness en bloc resection of the frontal bone including the mass was performed. The frontal bone was removed with care taken not to damage the frontal sinus mucosa. The frontal sinus was sealed with a collagen patch (Tachocomb) and a cranioplasty was performed using bone cement. At 6 months postoperative, a clean wound was confirmed without any complications, and there was no local recurrence. Surgical excision of intraosseous hemangioma in the frontal sinus bone can be performed via direct incision or the bicoronal approach. In this case, the direct incision approach was used to achieve smaller scars and faster recovery than the bicoronal approach. more...

Carfilzomib, lenalidomide, and dexamethasone (KRd) effectively improve survival in patients with relapsed and refractory multiple myeloma (RRMM). However, the outcome of KRd treatment in Asian patients reflecting a general RRMM population outside of a clinical trial has not been reported. Fifty-five RRMM patients who were treated with carfilzomib in combination with Rd from the time of the first approval of KRd in the Republic of Korea were analyzed. The median age was 61 years. The percentage of patients with an ECOG performance status ≥ 3, creatinine clearance < 50 mL/min, high-risk cytogenetics, and ≥ 4 lines of prior treatment were 9%, 22%, 31%, and 27%, respectively. Forty-one patients started treatment with KRd, whereas the remaining 14 patients (25%) were added carfilzomib during the Rd treatment. In the whole cohort, the overall response rate was 73% and progression-free survival was 8.8 months. The addition of carfilzomib in patients who were refractory or had disease progression during Rd treatment reattained a response in half of the patients. The advantage of carfilzomib with Rd was significant in patients in the first relapse. Toxicity profile was acceptable, excluding severe infections. Carfilzomib in combination with Rd is effective and has a reasonable adverse event rate in Asian patients with RRMM. more...

We compared efficacy and safety, according to frailty, of elderly patients with relapsed and refractory multiple myeloma (RRMM) treated with lenalidomide and dexamethasone (Rd), for whom bortezomib treatment had failed. Patients, 164 (52.9%) and 146 (47.1%), were classified as non-frail and frail using a simplified frailty scale. The overall response rates (ORR) and survival outcomes were lower in frail than in non-frail patients (ORR: 56.2% vs. 67.7%, P = 0.069; median progression free survival: 13.17 vs. 17.80 months, P = 0.033; median overall survival: 23.00 vs. 36.27 months, P = 0.002, respectively). The number of treatment emergent adverse events in grade 3 or worse was higher in frail than in non-frail patients (41.8% vs. 24.4%, P = 0.002, respectively). In frail patients, independent poor prognostic factors for survival were two or more Charlson comorbidity index (CCI) score, prior to exposure to both bortezomib and thalidomide, and achieved less than partial response In conclusion, frailty could predict clinical outcomes of Rd treatment in elderly patients with RRMM who had failed prior bortezomib. In frail patients, lower CCI in addition to less previous treatment exposure and deep response were associated with better survival. more...

We compared the efficacy and toxicity of busulfan and melphalan (BUMEL) and those of high-dose melphalan (HDMEL) as conditioning regimens for autologous stem cell transplantation (ASCT) in patients with multiple myeloma (MM) through a propensity score-matched analysis. No significant difference in the complete response and overall response rate after ASCT was observed between BUMEL and HDMEL. After a median follow-up of 37.3 months in the BUMEL group and 50.8 months in the HDMEL group, the median progression-free survival was calculated to be 32.9 months and 25.2 months ( more...

Introduction Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma and a heterogeneous disease with a variety of molecular aberrations and diverse clinical outcomes. BCL2 expression has been implicated for a poor prognosis among patients with DLBCL. However, there is no consensus regarding the interpretation of BCL2 expression in DLBCL. In previous studies, the range of BCL2-positive cases, determined by immunohistochemistry (IHC), was highly variable (24 - 80%) due to subjective and semiquantitative interpretation and the absence of the established cutoff value for BCL2 expression. Consequently, the prognostic impact of BCL2 varies between studies. In addition, only the proportion of BCL2 positive tumor cells are considered in determining the BCL2 positivity. We aimed to define BCL2 positivity by quantitative analysis integrating both the intensity and proportion of BCL2 expression. Methods We retrospectively collected formalin-fixed, paraffin-embedded (FFPE) diagnostic biopsies from 221 patients with de novo DLBCL between January 2007 and December 2012 at our institute. All patients were treated with R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone) as first-line treatment. A separate validation set included 111 patients with de novo DLBCL who received first-line R-CHOP at another tertiary hospital in South Korea. BCL2 expression was analyzed using the tumor-specific Automated Quantitative Analysis (AQUA) scoring system based on multiplex immunofluorescence. The tumor-specific quantified intensity information in pixels was converted to protein expression information on a cell basis using the AQUA scoring system. The AQUA scores for BCL2 was calculated as the signal intensities of BCL2 in the target compartment divided by the pixel area of the target compartment. Cell of origin (COO) was determined according to the Hans classification using IHC. Results Ninety-eight patients (44.3%) were > 60 years old of age, 126 patients (57.0%) were male and 81 patients (36.7%) had an International Prognostic Index of 3-5 in the training set. With a median follow-up duration of 59 months, the 5-year event-free survival (EFS) and overall survival (OS) rate were 62.2% and 69.0%, respectively. The BCL2 AQUA score of 41.47 was determined as the optimal cutoff value in the ROC analysis. A total of 86 patients (38.9%) were classified as high BCL2 AQUA score group according to the determined cutoff value. High BCL2 AQUA score was significantly associated with worse OS and EFS (P = 0.00015; OS, P = 0.00012; EFS) (Figure 1A, B). Multivariate analysis revealed that high BCL2 AQUA score was a significant poor prognostic factor for both OS and EFS independent of the IPI, and COO (P = 0.01; OS, P = 0.015; EFS). The high BCL2 AQUA score group in the validation set was also significantly associated with worse OS and EFS (P = 0.0075; OS, P = 0.0049; EFS) (Figure 1C, D). The poor prognostic impact of BCL2 AQUA score was also in good correlation with both OS and EFS in the entire cohort (P < 0.0001; OS, P < 0.0001; EFS) (Figure 1E, F). The adverse impact of high BCL2 AQUA score was identified within both low (IPI 0-2) and high IPI (IPI 3-5) groups (Figure 2A-D). The high BCL2 AQUA score was also associated with poor prognosis within both GCB (P = 0.0077; OS, P = 0.0055; EFS) and non-GCB type DLBCL (P = 0.059; OS, P = 0.04; EFS), although a marginal statistical significance was observed regarding OS in the non-GCB type (Figure 2E-H). Conclusion Our study demonstrated that BCL2 expression analyzed by AQUA scoring system, incorporating both intensity and proportion, is an independent prognostic factor for patients with DLBCL. Given the growing clinical implications of BCL2 and the therapeutic progress in targeting BCL2 in hematologic malignancies, the concrete definition of BCL2 positivity in DLBCL holds great promise for the study of the pathophysiology of DLBCL and could be used to establish new therapeutic strategies. Disclosures No relevant conflicts of interest to declare. more...

The clinical manifestations of diabetic kidney disease (DKD) are more heterogeneous than those previously reported, and these observations mandate the need for the recruitment of patients with biopsy-proven DKD in biomarker research. In this study, using the public gene expression omnibus (GEO) repository, we aimed to identify urinary mRNA biomarkers that can predict histological severity and disease progression in patients with DKD in whom the diagnosis and histologic grade has been confirmed by kidney biopsy. We identified 30 DKD-specific mRNA candidates based on the analysis of the GEO datasets. Among these, there were significant alterations in the urinary levels of 17 mRNAs in patients with DKD, compared with healthy controls. Four urinary mRNAs—LYZ, C3, FKBP5, and G6PC—reflected tubulointerstitial inflammation and fibrosis in kidney biopsy and could predict rapid progression to end-stage kidney disease independently of the baseline eGFR (tertile 1 vs. tertile 3; adjusted hazard ratio of 9.68 and 95% confidence interval of 2.85–32.87, p < 0.001). In conclusion, we demonstrated that urinary mRNA signatures have a potential to indicate the pathologic status and predict adverse renal outcomes in patients with DKD. more...

Background : : Online hemodiafiltration (OL-HDF) offers considerable advantages in clearance of molecules of various sizes. However, evidence of clinical effects of OL-HDF is scarce in Korea. In this study, we investigated changes in laboratory values over more than 12 months after switching to OL-HDF. Methods : : Adult patients with end-stage renal disease undergoing hemodialysis (HD) were prospectively enrolled in a K-cohort (CRIS no. KCT0003281) from 6 tertiary hospitals in South Korea. We recruited 435 patients, 339 of whom were on HD at enrollment. One hundred eighty-two patients were followed for more than 24 months. Among them, 44 were switched to OL-HDF for more than 12 months without conversion to HD. We used a paired t test to compare baseline and 24-month follow-up results. Results : : The mean age of the subjects was 61.2 ± 12.2 years, and 62.6% were male. The baseline hemoglobin level was not significantly different between HD and OL-HDF group (10.61 ± 1.15 vs. 10.46 ± 1.03 g/dL, P = 0.437). However, the baseline serum protein and albumin levels were significantly lower in the OL-HDF group (6.82 ± 0.49 vs. 6.59 ± 0.48 g/dL, P = 0.006; 3.93 ± 0.28 vs. 3.73 ± 0.29 g/dL, P < 0.001). In patients switched to OL-HDF, levels of hemoglobin and serum albumin significantly increased (10.46 ± 1.03 vs. 11.08 ± 0.82 g/dL, P = 0.001; 3.73 ± 0.29 vs. 3.87 ± 0.30 g/dL, P = 0.001). The normalized protein catabolic rate decreased after 24 months, but the change was not significant (1.07 ± 0.25 vs. 1.03 ± 0.21 g/kg/day, P = 0.433). Although the dose of erythropoiesis-stimulating agent was lower in patients who converted to HDF, it was not significantly different (-115.7 ± 189.7 vs. -170.5 ± 257.1 P = 0.206). Conclusion : : OL-HDF treatment over more than 12 months was associated with no harmful effects on anemia and nutritional status. more...

Patients with transplant‐ineligible relapsed and refractory multiple myeloma (RRMM) have a short life expectancy, especially when they have failed both the proteasome inhibitor and immunomodulator therapies. This study aimed to assess the efficacy and safety of pomalidomide, cyclophosphamide, and dexamethasone (PCd) in elderly patients with RRMM. This phase 2 clinical trial recruited 55 elderly patients with RRMM. The patients underwent a 28‐day treatment cycle: pomalidomide (4 mg/day on days 1‐21, administered orally) and cyclophosphamide (400 mg/day on days 1, 8, and 15; administered orally) plus dexamethasone. The median (range) age of the patients was 73.3 (64‐86) years, and 8 (14.5%) patients who were ≥ 80 years old. Eight (14.5%) and 31 (56.4%) patients exhibited stage III (revised international staging system) and frail status (simplified frailty scale), respectively. The overall response rate (ORR) and clinical benefit rate (CBR) of PCd therapy were 58.2% and 72.7%, respectively. The median PFS and median overall survival (OS) were 6.90 months (95% CI, 4.7‐9.0) and 18.48 months (95% CI, 9.4‐27.6), respectively. The incidence rate of grade ≥ 3 non‐hematological toxicities was 70.8%. In particular, the incidence rate of primary infection was 45.4%, including 21.8% for pneumonia, 9.0% for sepsis, and 14.6% for febrile neutropenia. In conclusion, PCd is an effective regimen for elderly patients with RRMM who had failed both bortezomib and lenalidomide treatments, but in whom the treatment‐associated infection is the main cause of morbidity and mortality. more...

Although lenalidomide plus dexamethasone (RD) is a therapeutic option for relapsed/refractory multiple myeloma (RRMM), limited real-world clinical data exist. The purpose of this study was to estimate efficacy and safety of RD in RRMM patients of the clinical practice. Data from patients at 25 university hospitals in South Korea between October 2009 and December 2016 were collected retrospectively. We report the effectiveness and safety of RD in 546 RRMM patients in routine clinical practice in South Korea. Patients (median age, 65 years) typically received median 7 cycles of RD, and 184 (33.7%) patients were treated with 10 or more cycles of RD. Patients with renal impairment (CLCr more...

Limited-stage (Ann Arbor stage I or II) mantle cell lymphoma (MCL) is an extremely rare disease. Thus, there is little data on the clinical features and treatment outcomes of patients with early-stage MCL. We examined consecutive stage I or II MCL 41 cases diagnosed between 2000 and 2016 in 16 institutions of the Consortium for Improving Survival of Lymphoma group. All cases were pathologically confirmed and systemic evaluation was performed for staging. The clinical features were reviewed, and the treatment outcomes were analyzed. The median age of patients was 66 years (range 19–85 years); there were more men (n = 31, 75.6%) than women. Most patients (n = 28, 68.3%) had stage 2 disease, and 29 (70.7%) were symptomatic. The elevation of lactate dehydrogenase (n = 2, 4.9%) was not common; thus, 39 patients (95.1%) had a low-risk score (0 or 1) for the International Prognostic Index, and 28 (68.3%) had a low-risk score (1–3) for the MCL International Prognostic Index. Most patients (n = 37, 90.1%) received chemotherapy as the first therapeutic strategy, while some received radiotherapy (n = 2), surgical resection (n = 1), or no treatment (n = 1). Of the patients who received chemotherapy, 23 (56.9%) received a rituximab-containing regimen, and R-CHOP (n = 17) and R-bendamustine (n = 5) were commonly used. The best response was noted in 97.4% (n = 38) of patients, including 32 who showed a complete response (78%). With a median follow-up duration of 40.6 months, the 42 months relapse-free survival was 59.1%, and the 5-year overall survival rate was 80.4%. Limited-state MCL showed indolent clinical and low-risk prognostic features. Chemotherapy could be effective for controlling localized MCL lesions, with high complete response rates. more...

Background Several factors had been suggested to contribute to the development of hypertension in chronic glomerulonephritis (GN). This study was conducted to find the association of baseline blood pressure (BP) with pathophysiologic findings and later renal progression in chronic GN. Methods Clinico-pathological findings including serum creatinine (Cr), proteinuria, pathological findings, and urinary Na excretion were analyzed in a total of 233 patients with IgA nephropathy from The Kyung-Hee Cohort of GN. Glomerular surface area (GSA) was measured by imaging analysis and urine angiotensinogen (AGT) concentrations by human ELISA kits. Results Systolic BP was ≥130mmHg in 124 patients (53%). Systolic BP was negatively correlated with follow-up eGFR (r=-0.32, p more...

Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin’s lymphomas with poor clinical outcomes. Pralatrexate showed efficacy and safety in recurrent or refractory PTCLs. The purpose or this study was to investigate the efficacy and safety of pralatrexate in relapsed or refractory PTCLs in real-world practice. This was an observational, multicenter, retrospective analysis. Between December 2012 and December 2016, a total of 38 patients with relapsed or refractory PTCLs were treated with pralatrexate at 10 tertiary hospitals in Korea. Patients received an intravenous infusion of pralatrexate at a dose of 30 mg/m2/week for 6 weeks on a 7-week schedule. Modified dosing and/or scheduling was allowed according to institutional protocols. Median patient age was 58 years (range, 29–80 years) and the most common subtype was peripheral T-cell lymphoma, not otherwise specified (n = 23, 60.5%). The median dosage of pralatrexate per administration was 25.6 mg/m2/wk (range, 15.0–33.0 mg/m2/wk). In intention-to-treat analysis, 3 patients (7.9%) showed a complete response and 5 patients (13.2%) showed a partial response, resulting in an overall response rate (ORR) of 21.1%. The median duration of response was 7.6 months (range, 1.6–24.3 months). The median progression-free survival (PFS) was 1.8 months (95% confidence interval [CI], 1.7–1.8 months) and the median overall survival was 7.7 months (95% CI, 4.4–9.0 months). The most common grade 3/4 adverse events were thrombocytopenia (n = 13, 34.2%), neutropenia (n = 7, 23.7%), and anemia (n = 7, 18.4%). Our study showed relatively lower ORR and shorter PFS in patients with recurrent or refractory PTCLs treated with pralatrexate in real-world practice. The toxicity profile was acceptable and manageable. We also observed significantly lower dose intensity of pralatrexate in real-world practice. more...

Background/aims Membranous nephropathy (MN) is the most common primary glomerular disease diagnosed in older patients. Few reports describe the clinical outcomes in older patients with idiopathic MN. Methods The outcomes of 135 patients with histologically proven MN were analyzed. 'Older' was defined as 60 years of age or older at the time of the renal biopsy. The rates of complete remission (CR), progression to end-stage renal disease (ESRD) and infection were compared between older and younger patients. Results The cumulative event rate for achieving CR was inferior (p = 0.012) and that for requiring renal replacement was higher (p = 0.015) in older patients, and they had a greater risk of infection (p = 0.005). Older age was a significant predictor of a lower rate of CR (adjusted odds ratio [OR], 0.51; 95% confidence interval [CI], 0.26 to 0.98), and was a robust predictor of infection (adjusted OR, 5.27; 95% CI, 1.31 to 21.20). Conservative treatment was associated with a lower remission rate (p = 0.036) and corticosteroid treatment was less effective in achieving CR (p = 0.014), in preventing progression to ESRD (p = 0.013) and in reducing infection (p = 0.033) in older patients. Cyclosporine treatment had similar clinical outcomes with regard to CR, ESRD progression, and infection in older patients. Conclusion Older age was independently associated with inferior rates of CR and greater risk of infection. Treatment modalities affected the outcomes of older patients differently in that cyclosporine treatment is predicted to be more useful than corticosteroids. more...

One year after COVID-19 was declared a pandemic, the management of the disease in kidney transplant patients remains uncertain. The interruption of immunosuppressive therapy is frequently suggested in kidney transplant recipients with COVID-19; however, such an interruption potentially increases the risk of allograft rejection and hyperimmune response. We here report the successful treatment of COVID-19 pneumonia in a kidney transplant recipient who received a sirolimus-based regimen. The course of COVID-19 management was favorable for maintaining sirolimus treatment. Nevertheless, the patient showed signs of extreme overexposure to sirolimus because of drug interaction with antiviral treatment. This case illustrates the advantages and related adverse events of sirolimus-based immunosuppression in the management of COVID-19 in kidney transplant recipients. more...

Background: Vascular adhesion protein-1 (VAP-1) is an oxidative enzyme of primary amines that facilitates the transmigration of inflammatory cells. Its oxidative and inflammatory effects are prominently increased in pathological conditions, such as metabolic, atherosclerotic, and cardiac diseases. However, the clinical significance of circulating VAP-1 levels in hemodialysis (HD) patients is unclear.Methods: A total of 434 HD patients were enrolled in a prospective multicenter cohort study between June 2016 and April 2019. Plasma VAP-1 levels were measured at the time of data entry, and the primary endpoint was defined as a composite of cardiovascular (CV) and cardiac events.Results: Circulating VAP-1 levels were positively correlated with plasma levels of cardiac remodeling markers, including brain natriuretic peptide, galectin-3, and matrix metalloproteinase-2. Multivariable logistic regression analysis revealed that patients with higher circulating VAP-1 levels were more likely to have left ventricular diastolic dysfunction [odds ratio, 1.40; 95% confidence interval [CI], 1.04–1.88]. The cumulative event rate of the composite of CV events was significantly greater in VAP-1 tertile 3 than in VAP-1 tertiles 1 and 2 (P = 0.009). Patients in tertile 3 were also associated with an increased cumulative event rate of cardiac events (P = 0.015), with a 2.06-fold higher risk each for CV (95% CI, 1.10–3.85) and cardiac (95% CI, 1.03–4.12) events after adjusting for multiple variables.Conclusions: Plasma VAP-1 levels were positively associated with left ventricular diastolic dysfunction and the risk of incident CV and cardiac events in HD patients. Our results indicate that VAP-1 may aid clinicians in identifying HD patients at a high risk of CV events. more...

Background: Neprilysin inhibition has demonstrated impressive benefits in heart failure treatment, and is the current focus of interest in cardiovascular (CV) and kidney diseases. However, the role of circulating neprilysin as a biomarker for CV events is unclear in hemodialysis (HD) patients.Methods: A total of 439 HD patients from the K-cohort were enrolled from June 2016 to April 2019. The plasma neprilysin level and echocardiographic findings at baseline were examined. The patients were prospectively followed up to assess the primary endpoint (composite of CV events and cardiac events).Results: Plasma neprilysin level was positively correlated with left ventricular (LV) mass index, LV end-systolic volume, and LV end-diastolic volume. Multivariate linear regression analysis revealed that neprilysin level was negatively correlated with LV ejection fraction (β = −2.14; p = 0.013). The cumulative event rate of the composite of CV events was significantly greater in neprilysin tertile 3 (p = 0.049). Neprilysin tertile 3 was also associated with an increased cumulative event rate of cardiac events (p = 0.016). In Cox regression analysis, neprilysin tertile 3 was associated with a 2.61-fold risk for the composite of CV events [95% confidence interval (CI), 1.37–4.97] and a 2.72-fold risk for cardiac events (95% CI, 1.33–5.56) after adjustment for multiple variables.Conclusions: Higher circulating neprilysin levels independently predicted the composite of CV events and cardiac events in HD patients. The results of this study suggest the importance of future studies on the effect of neprilysin inhibition in reducing CV events. more...

When reconstructing a lateral alar defect of the nose, satisfactory aesthetic and functional results are difficult to achieve through a single-stage surgery alone. Here the authors describe a new innovative surgical technique using a superiorly based folded nasolabial flap through a single-stage surgery alone. An 85-year-old male patient visited plastic surgery clinic with sudden enlargement of a mass 3 or 4 days before the visit. On the basis of the biopsy test results, a diagnosis of basal cell carcinoma on the right lateral alar was made. A full-thickness lateral alar resection was performed while maintaining the shape of the right alar rim (outer skin defect: 2.2 × 2 cm2 and inner mucosal defect: 1.4 × 1.3 cm2). Next, a single-stage reconstruction with a superiorly based folded turnover nasolabial flap was performed for the full-thickness lateral alar defect. Six months after the reconstructive surgery, no wound complication and nostril collapse occurred. The surgical method used in this case has many advantages. First, the authors' method is performed only in a single stage. Second, the flap is based on a rich vascular supply from the angular artery, which eliminates the possibility of flap necrosis through multiple turnovers. Third, because the turnover nasolabial flap is a construct of the epidermis, dermis, and subcutaneous fat, the flap is quite stiff thus reducing the possibility of nostril collapse. Fourth, the procedure leaves no scars in the superior area of the nose other than the nasolabial fold scar. more...

Background Natural killer/T-cell lymphoma (NKTCL) is a disease with limited treatment options and poor outcomes. Daratumumab monotherapy demonstrated clinical activity in a single-patient case report. We present data from the primary analysis of a phase 2 study of daratumumab monotherapy in relapsed or refractory (R/R) NKTCL. Methods This phase 2 study with Simon’s two-stage design evaluated daratumumab in patients with histologically confirmed extranodal NKTCL, nasal type, per WHO classification that was refractory to or relapsed after ≥ 1 line of chemotherapy, who were not candidates for other treatment modalities. All patients received daratumumab 16 mg/kg intravenously once weekly for Cycles 1 and 2, every other week for Cycles 3 through 6, and every 4 weeks thereafter until progression or unacceptable toxicity; all cycles were 28 days. The primary end point was objective response rate (ORR) based on blinded independent central review per Revised Criteria for Response Assessment of Hodgkin and non-Hodgkin Lymphoma (Lugano classification). Results In total, 32 Asian patients received daratumumab. The ORR was 25.0% (95% confidence interval [CI] 11.5–43.4); all 8 responders had a partial response; and the median duration of response was 55.0 days (95% CI 29–339). At 10.2 months of median follow-up, median progression-free survival (PFS) was 53.0 days (95% CI 43–106); the 4-month PFS rate was 13.0%. Median overall survival (OS) was 141.0 days (95% CI 94–438); the 6-month OS rate was 42.9%. Nineteen (59.4%) patients had grade 3/4 treatment-emergent adverse events (TEAEs); the most common was thrombocytopenia (25.0%; n = 8). TEAEs leading to death occurred in 4 patients (death, respiratory failure, septic shock, and pneumonia); all were unrelated to daratumumab. Conclusions In patients with R/R NKTCL, daratumumab monotherapy was well tolerated with no new safety concerns and achieved an ORR of 25.0%. However, no patients achieved complete response, and duration of response was short. Trial registration ClinicalTrials.gov, NCT02927925. Registered 7 October 2016. more...

The C-reactive protein-to-albumin ratio (CAR) has not been assessed in diffuse large B cell lymphoma (DLBCL, the most common non-Hodgkin lymphoma). This retrospective study evaluated the prognostic value of CAR in 186 DLBCL patients. A CAR value of 0.158 was selected as the most discriminative cut-off for identifying patients with high CAR values (73/141 patients, 51.8%). During a median follow-up of 32.5 months, the high CAR group had significantly poorer complete response to induction therapy (64.4% vs. 92.6%; p 0.158 also showed worse 3-year OS (47.9% vs. 87.2%, p = 0.0035) and 3-year PFS (36.1% vs. 82.1%, p = 0.0011). A high CAR remained significantly associated with poor outcomes for > 60-year-old patients (OS: p = 0.0038, PFS: p = 0.0015) and younger patients (OS: p = 0.0041, PFS: p = 0.0044). Among older patients, a high CAR value also predicted non-relapse mortality (p = 0.035). Therefore, the CAR might complement the International Prognostic Index in DLBCL cases. more...

Gait training for paraplegic patients is effective in preventing various complications due to prolonged sitting. In these patients, the use of powered exoskeletal-gait-orthosis (EGO) consumes lower energy than traditional training methods using non-powered EGO, such as a reciprocating-gait-orthosis (RGO). Thus, long-term training is possible and effective in increasing the activity level of the trunk muscles. However, more than 60% of paraplegic patients have incomplete injuries with residual function, which is inversely related to the functional role of the orthosis. We hypothesized that the gait ability in incomplete paraplegia could be improved by knee joint activation, and we developed a lightweight knee-actuated EGO (KAEGO). We verified its effectiveness in one patient with an incomplete spinal cord injury by comparing the metabolic cost of transport (COT) measured by a six minute walk test to a traditional non-powered EGO. We found that with increasing assist torque to the knee joint, the COT decreased by up to 24.5%, and the gait performance, including walking speed and travel distance, significantly improved up to 37% compared to that of the non-powered EGO. Future studies should verify the KAEGO system&rsquo, s effectiveness in a larger number of patients with various injury levels. more...

Background As in younger recipients, post-transplant infection is a frequent and devastating complication after kidney transplantation (KT) in older recipients. However, few studies have analyzed characteristics of post-transplant infection in older kidney recipients. In this study of a nation-wide cohort of older kidney recipients, we investigated the current epidemiology, risk factors, and clinical impacts of early post-transplant infection, which was defined as infectious complications requiring hospitalization within the first 6 months after KT. Methods Three thousand seven hundred thirty-eight kidney recipients registered in the Korean Organ Transplantation Registry between 2014 and 2017 were enrolled. Recipients were divided into two groups, younger (n = 3081) and older (n = 657), with a cutoff age of 60 years. We observed characteristics of early post-transplant infection, and investigated risk factors for the development of infection. We also analyzed the association of early post-transplant infection with clinical outcomes including cardiac events, rejection, graft loss, and all-cause mortality. Results The incidence of early post-transplant infection was more frequent in older recipients (16.9% in younger group and 22.7% in older group). Bacteria were the most common causative pathogens of early post-transplant infection, and the most frequent site of infection was the urinary tract in both older and younger recipients. Older recipients experienced more mycobacterial infections, co-infections, and multiple site infections compared with younger recipients. In older recipients, female sex (HR 1.398, 95% CI 1.199–1.631), older donor age (HR 1.010, 95% CI 1.004–1.016), longer hospitalization after KT (HR 1.010, 95% CI 1.006–1.014), and experience of acute rejection (HR 2.907, 95% CI 2.471–3.419) were independent risk factors for the development of early post-transplant infection. Experiencing infection significantly increases the incidence of rejection, graft loss, and all-cause mortality. Conclusion Our results illustrate current trends, risk factors, and clinical impacts of early post-transplant infection after KT in older recipients. Considering the poor outcomes associated with early post-transplant infection, careful screening of recipients at high risk for infection and monitoring of recipients who experience infection are advised. In addition, since older recipients exhibit different clinical characteristics than younger recipients, further studies are needed to establish effective strategies for treating older recipients. more...

Introduction: A recent study showed that early renal tubular injury is ameliorated in Nod-like receptor pyrin domain-containing protein 3 (NLRP3) KO mice with rhabdomyolysis-induced acute kidney injury (RIAKI). However, the precise mechanism has not been determined. Therefore, we investigated the role of NLRP3 in renal tubular cells in RIAKI. Methods: Glycerol-mediated RIAKI was induced in NLRP3 KO and wild-type (WT) mice. The mice were euthanized 24 h after glycerol injection, and both kidneys and plasma were collected. HKC-8 cells were treated with ferrous myoglobin to mimic a rhabdomyolytic environment. Results: Glycerol injection led to increase serum creatinine, aspartate aminotransferase (AST), and renal kidney injury molecule-1 (KIM-1) level, renal tubular necrosis, and apoptosis. Renal injury was attenuated in NLRP3 KO mice, while muscle damage and renal neutrophil recruitment did not differ between NLRP3 KO mice and WT mice. Following glycerin injection, increases in cleaved caspase-3, poly (ADP-ribose) polymerase (PARP), and a decrease in the glutathione peroxidase 4 (GPX-4) level were observed in the kidneys of mice with RIAKI, and these changes were alleviated in the kidneys of NLRP3 KO mice. NLRP3 was upregulated, and cell viability was suppressed in HKC-8 cells treated with ferrous myoglobin. Myoglobin-induced apoptosis and lipid peroxidation were significantly decreased in siNLRP3-treated HKC-8 cells compared to ferrous myoglobin-treated HKC-8 cells. Myoglobin reduced the mitochondrial membrane potential and increased mitochondrial fission and reactive oxygen species (ROS) and lipid peroxidation levels, which were restored to normal levels in NLRP3-depleted HKC-8 cells. Conclusions: NLRP3 depletion ameliorated renal tubular injury in a murine glycerol-induced acute kidney injury (AKI) model. A lack of NLRP3 improved tubular cell viability via attenuation of myoglobin-induced mitochondrial injury and lipid peroxidation, which might be the critical factor in protecting the kidney. more...

Background Cognitive decline is common in older adults. Similarly, the prevalence of renal dysfunction is also increased in the elderly population. We conducted this study to clarify the relationship between renal dysfunction and decline of cognitive function in community-dwelling elderly population. Methods A cross-sectional analysis was performed using data from the Korean Frailty and Aging Cohort Study, a nationwide cohort study. Total 2847 (1333 men, 1514 women) eligible participants were enrolled for this study. The estimated glomerular filtration rate (eGFR, mL/min/1.73m2) was calculated using the Chronic Kidney Disease Epidemiology Collaboration equation. Global cognitive function was assessed with the Mini-mental State Examination-Korean version. Other domains of cognitive function were tested with the Consortium to Establish a Registry for Alzheimer’s disease and the Frontal Assessment Battery. Results The mean age of all participants was 76.0 ± 3.9 years and eGFR (all in mL/min/1.73 m2) was 77.5 ± 14.3. And the mean eGFR was 91.7 ± 3.2 in quartile 1, 84.9 ± 1.8 in quartile 2, 76.1 ± 3.7 in quartile 3, and 57.2 ± 10.8 in quartile 4. In baseline characteristics, participants with lower eGFR tend to have lower cognitive function scores than participant with higher eGFR. In linear regression analysis, eGFR was correlated with the word list memory (β = 0.53, P = 0.005), word list recall (β = 0.86, P P = 0.030) after adjustment of confounding variables. Moreover, after multivariate adjustment the association with cognitive impairment in quartile 2 was stronger (adjusted OR: 1.535, 95% CI: 1.111–2.120, P = 0.009), and the ORs of cognitive impairment were 1.501 (95% CI: 1.084–2.079, P = 0.014) in quartile 3 and 1.423 (95% CI: 1.022–1.983, P = 0.037) in quartile 4. Conclusion In older adults, the immediate, recent memory, and recognition domains were significantly related to renal function. Also, the mild renal dysfunction was independently associated with impairment of global cognitive function. These results suggest that the early stages of renal dysfunction could be an effective target to prevent worsening of cognitive impairment. Therefore, regular monitoring and early detection of mild renal dysfunction in elderly population might be needed. more...

The clinical symptoms of glomus tumors are pain, tenderness, nail discoloration, and cold intolerance. The only treatment for subungual glomus tumors is surgical removal. In this clinical study, we present an eponychium preserving method as a new innovative surgical approach for subungual glomus tumor. We retrospectively reviewed the data of 27 patients with subungual glomus tumors who underwent tumor resection using the eponychial flap elevation method between March 2010 and 2019. After the excision of the subungual glomus tumor using the eponychial flap elevation method, wound problems, severe pain, and nail deformity other than a minimal scar were not noted. The innovative eponychial flap elevation method is a simple and straightforward method for the management of subungual glomus tumors; the tumors can be sufficiently exposed and completely excised using this method while avoiding secondary nail dystrophy. This method can be another option among several methods of subungual glomus tumor removal. more...

Total body irradiation (TBI) is included in the conditioning regimen for allogeneic hematopoietic stem cell transplantation (HSCT), with unique advantages such as uniform distribution over the whole body and decreased exposure to cytotoxic chemotherapeutic agents. For individuals who lack matched sibling or matched unrelated donors, the use of haploidentical donors has been increasing despite challenges such as graft rejection and graft-versus-host disease (GVHD). Although a limited number of studies have been performed to assess the clinical role of TBI in haploidentical HSCT, TBI-based conditioning showed comparable results in terms of survival outcomes, rate of relapse, and GVHD in diverse hematologic malignancies such as leukemia, lymphoma, and multiple myeloma. Advances in supportive care, along with recent technical improvements such as restriction of maximum tolerated dose, appropriate fractionation, and organ shielding, help to overcome diverse adverse events related to TBI. Post-transplantation cyclophosphamide was used in most studies to reduce the risk of GVHD. Additionally, it was found that post-transplantation rituximab may improve outcomes in TBI-based haploidentical HSCT, especially in patients with B-cell lymphoma. Along with the advances of techniques and strategies, the expansion of age restriction would be another important issue for TBI-based haploidentical HSCT considering the current tendency toward increasing age limitation and lack of matched donors. This review article summarizes the current use and future perspectives of TBI in haploidentical HSCT., Graphical Abstract more...

We aimed to investigate the association between Korean medicine (KM) treatment and the risk of Parkinson&rsquo, s Disease (PD) in patients with inflammatory bowel disease (IBD) in South Korea. This study analyzed data from the National Health Insurance Service-Senior cohort in South Korea. The 1816 IBD patients enrolled in the analysis comprised 411 who received only conventional treatment (monotherapy group) and 1405 who received both conventional and KM treatments (integrative therapy group). The risk of PD in patients with IBD was significantly lower in the integrative therapy group than in the monotherapy group after adjusting for confounding variables (adjusted hazard ratio (HR), 0.56, 95% confidence interval (CI) = 0.34&ndash, 0.92). In the mild Charlson Comorbidity Index (CCI) group, the risk of PD in patients with IBD in the integrative therapy group was 0.39 times lower (adjusted HR, 95% CI = 0.20&ndash, 0.77) than that in the monotherapy group. However, there was no significant difference in the risk of PD in patients with IBD between the integrative therapy and monotherapy groups among individuals with severe CCI (adjusted HR, 0.90, 95% CI = 0.41&minus, 1.96). IBD patients are at a decreased risk of PD when they receive integrative therapy. KM treatment may prevent PD in IBD patients. more...

Background and objectives The purpose of this study was to evaluate the efficacy of revision cochlear implant (CI) surgery for better speech comprehension targeting patients with low satisfaction after first CI surgery. Subject and methods Eight patients who could not upgrade speech processors because of an too early CI model and who wanted to change the whole system were included. After revision CI surgery, we compared speech comprehension before and after revision CI surgery. Categoies of Auditory Performance (CAP) score, vowel and consonant confusion test, Ling 6 sounds, word and sentence identification test were done. Results The interval between surgeries ranged from eight years to 19 years. Same manufacturer's latest product was used for revision surgery in six cases of eight cases. Full insertion of electrode was possible in most of cases (seven of eight). CAP score (p-value=0.01), vowel confusion test (p-value=0.041), one syllable word identification test (p-value=0.026), two syllable identification test (p-value=0.028), sentence identification test (pvalue=0.028) had significant improvement. Consonant confusion test (p-value=0.063), Ling 6 sound test (p-value=0.066) had improvement but it is not significant. Conclusions Although there are some limitations of our study design, we could identify the effect of revision (upgrade) CI surgery indirectly. So we concluded that if patient complain low functional gain or low satisfaction after first CI surgery, revision (device upgrade) CI surgery is meaningful even if there is no device failure. more...

Background Peripheral blood stem cell (PBSC) collection is important for successful hematopoietic stem cell transplantation. This study aimed to investigate the laboratory parameters associated with the optimal timing of autologous PBSC collection from lymphoma and multiple myeloma patients. Methods We retrospectively evaluated data from 1105 PBSC apheresis procedures performed on 379 adult patients at the National Cancer Center between June 2005 and December 2019. Laboratory parameters, including cutoff values for the number of hematopoietic progenitor cells (HPCs) and circulating CD34+ cells, were analyzed to determine their association with CD34+ cell yield. Results The pre-apheresis HPC and CD34+ cell count were statistically significant variables associated with harvested CD34+ cell in lymphoma and MM patients. The optimal cutoff values were 18 × 106 /L for pre-HPC count (66.8% sensitivity, 66.4% specificity) and 11/μL for pre-CD34+ cell count (85.8% sensitivity, 87.2% specificity), to achieve CD34+ cell yields ≥ 1.0 × 106 /kg for each apheresis procedure. Moreover, the optimal cutoff values were 23 × 106 /L for pre-HPC count (71.0% sensitivity, 69.0% specificity) and 18/μL for pre-CD34+ cell count (87.5% sensitivity, 86.3% specificity) to achieve CD34+ cell yields ≥ 2.0 × 106 /kg for each apheresis procedure. Conclusion HPC count is a potential surrogate marker for monitoring the starting time for PBSC collection. Applying cutoff values for the number of HPC and CD34+ cells may be clinically useful for optimizing the timing of PBSC collection. more...

Background and Aims Low physical performance in patients undergoing maintenance hemodialysis is associated with a high mortality rate. We investigated the clinical relevance of gait speed and handgrip strength, the two most commonly used methods to assess physical performance. Method We obtained data regarding gait speed and handgrip strength from 277 hemodialysis patients and evaluated their relationship with baseline parameters, mental health, plasma inflammatory markers, and major adverse clinical outcomes. Low physical performance was defined by the recommendations suggested by the Asian Working Group on Sarcopenia. Results The prevalence of low gait speed and handgrip strength were 28.2% and 44.8%, respectively. Old age, low serum albumin levels, high comorbidity index, and impaired cognitive functions were associated with low physical performance. Patients with isolated low gait speed exhibited a general trend for worse quality of life than those with isolated low handgrip strength. Gait speed and handgrip strength showed very weak correlations with had different determinant factors (older age, the presence of diabetes, and lower serum albumin for low gait speed, and lower body mass index, and the presence of previous cardiovascular events for low handgrip strength). Patients with low gait speed and handgrip strength had elevated levels of plasma endocan and matrix metalloproteinase-7 and the highest risk of all-cause mortality and cardiovascular events among the groups (adjusted hazard ratio of 2.72, p = 0.024). Conclusion Gait speed and handgrip strength reflected distinctive aspects of patient characteristics and that their combination improved the prediction of adverse clinical outcomes in hemodialysis patients. Gait speed seems to be a better indicator for poor patient outcomes compared with handgrip strength. more...

Background and Aims Although obesity is a well-known risk factor for chronic kidney disease (CKD), previous epidemiologic studies have produced mixed results. This study was purposed to investigate the relationship between obesity and CKD occurrence in the healthy middle-aged Korean population. Method We used a prospective, longitudinal data from the Korean Genome and Epidemiology Study (KoGES), a population-based, epidemiology study in South Korea (2001-2014). A total of 6,678 participants aged 40-69 who were free of diabetes, hypertension, and CKD at baseline were followed-up biennially. CKD was defined as at least two-time occurrence of estimated glomerular filtration rate < 60 mL/min/1.73m2 using CKD-EPI equation during the follow-up period. Results A total of 433 participants (6.5%) developed CKD. We divided the participants into 5 groups by BMI: underweight (BMI < 18.5), normal-weight (BMI 18.5-22.0), overweight 1 (BMI 23.0-24.9), overweight 2 (BMD 25-29.9), and obesity (BMI >30). Compared to the normal-weight group, hazard ratio of CKD occurrence was elevated in overweight 2 (HR=1.43, p=0.01) and obesity (HR=1.73, p=0.03) in multivariate-adjusted regression analysis (variates: age, newly developed hypertension, newly developed diabetes, fasting glucose > 126mg/dL, 2hours glucose > 200mg/dL, systolic blood pressure > 140mmHg, physical activity, alcohol consumption, smoking). When dividing the participants into three age groups: the 40s, 50s, and 60s, only the 60s group showed a significant correlation of BMI with CKD occurrence (overweight 2: HR=1.93, p=0.05, obesity: HR=3.94, p=0.03). Conclusion The risk of CKD was significantly high for those in their 60s who were overweight or obese despite free of underlying diseases in the Korean population. more...

Background and Aims Proprotein convertase subtilisin/kexin type 9 (PCSK9) is a promising new target for prevention of cardiovascular (CV) events. However, the clinical significance of circulating PCSK9 is unclear in hemodialysis (HD) patients. Method A total of 353 HD patients were prospectively enrolled from June 2016 to May 2018 in a K-cohort. Plasma PCSK9 level was measured at the time of study enrollment. Patients were classified into three groups based on PCSK9 tertile. The primary endpoint was defined as composite of CV event and death from any cause. Results Plasma PCSK9 level was positively correlated with total cholesterol level in patients with statin treatment. However, PCSK9 was not related to plasma inflammatory (high-sensitivity C-reactive peptide, monocyte chemoattractant protein-1, interleukin-6) or calcification-related markers (osteoprotegerin and receptor activator of nuclear factor kappa-Β ligand). Multivariate linear regression analysis revealed that baseline statin treatment and serum glucose, albumin, and total cholesterol were independent determinants of circulating PCSK9 levels. In Cox-regression analysis, PCSK9 tertile 3 was associated with a 1.99-fold risk for composite events (95% CI, 1.08–3.66), and it was associated with a 2.26-fold risk for CV events (95% CI, 1.11–4.62) after adjustment for multiple variables. PCSK9 tertile 3 provides additional prognostic power to predict composite events in subgroups with higher levels of high-sensitivity C-reactive peptide and LDL. Conclusion In conclusion, higher circulating PCSK9 level independently predicted CV events and death in HD patients. These results suggest the importance of future studies regarding the effect of PCSK9 inhibition on reduction of CV events. more...

Purpose To evaluate topographic changes in choroidal thickness during development of choroidal neovascularization (CNV) in treatment-naive age-related macular degeneration (AMD) and to test the value of such changes as a predictive tool of CNV development. Methods This retrospective cohort included 86 eyes that developed CNV from intermediate AMD, 43 eyes with intermediate AMD, and 36 eyes without AMD. Patients with intermediate AMD underwent spectral domain optical coherence tomography using enhanced depth imaging mode every 6 months until CNV was detected. Choroidal neovascularization was localized to one of the subfields of Early Treatment of Diabetic Retinopathy Study grid on fluorescein angiography. Average choroidal thickness of each subfield was calculated. Results Choroidal thickness of the subfield where CNV developed at first clinical detection significantly increased compared with that 6 months before (P = 0.000 for central, P = 0.001 for superior parafoveal, P = 0.002 for temporal parafoveal, P = 0.002 for inferior parafoveal, and P = 0.001 for nasal parafoveal subfield). In eight patients who visited unexpectedly 3 months before CNV development in central subfield, choroidal thickness of central subfield increased significantly compared with that 6 months before CNV development (P = 0.001). Conclusion Choroidal neovascularization development accompanied choroidal thickening of the corresponding subfield. Regular measurement of choroidal thickness may assist in prediction of CNV. more...

Background: Peripheral T cell lymphoma (PTCL) is a heterogeneous entity with poor survival. We evaluated the neutrophil-to-lymphocyte ratio (NLR), absolute lymphocyte count (ALC), and platelet count as new prognostic factors for PTCL. Patients and Methods: We retrospectively analyzed 77 patients with PTCL initially treated with anthracycline-based chemotherapy. Survival curves were compared between groups with different initial NLR (iNLR), end-point NLR (eNLR), initial ALC, and platelet counts. Cox regression was used to analyze the risk factor for survival. Results: Patients with a higher eNLR (≥3), lymphopenia (< 1,000/μL), and thrombocytopenia (< 150 K/μL) had an inferior progression-free survival (PFS) and overall survival (OS) compared to their counterparts, while a higher iNLR (≥3) was predictive of a shorter OS but not PFS. Among these, thrombocytopenia was an independent poor prognostic factor for both PFS and OS, with a hazard ratio of 2.42 (p = 0.012) for PFS and 4.21 (p = 0.006) for OS. The presence of thrombocytopenia further stratified patients with a worse prognosis within overlapping risk-groups by the prognostic index for PTCL. Conclusions: Our study showed that thrombocytopenia at diagnosis was an independent prognostic factor for survival in patients with PTCL. more...

Background/Aims This study was conducted to evaluate the recent prevalence and trend of anti-tuberculosis (TB) drug resistance with a focus on multidrug-resistance (MDR) and fluoroquinolone resistance in South Korea. Methods We retrospectively reviewed the drug susceptibility testing results of culture-confirmed Mycobacterium tuberculosis isolates collected from 2010 to 2014 at seven tertiary hospitals in South Korea. Results A total of 5,599 cases were included: 4,927 (88.0%) were new cases and 672 (12.0%) were previously treated cases. The MDR rate has significantly decreased from 6.0% in 2010 to 3.0% in 2014 among new cases, and from 28.6% in 2010 to 18.4% in 2014 among previously treated cases (p < 0.001 and p = 0.027, respectively). The resistance rate to any fluoroquinolone was 0.8% (43/5,221) in non-MDR-TB patients, as compared to 26.2% (99/378) in MDR-TB patients (p < 0.001). There was no significant change in the trend of fluoroquinolone resistance among both nonMDR-TB and MDR-TB patients. Among the 43 non-MDR-TB patients with fluoroquinolone resistance, 38 (88.4%) had fluoroquinolone mono-resistant isolates. Conclusions The prevalence of MDR-TB has significantly decreased from 2010 to 2014. The prevalence of fluoroquinolone resistance among non-MDR-TB patients was low, but the existence of fluoroquinolone mono-resistant TB may be a warning on the widespread use of fluoroquinolone in the community. more...

Background/Aims: Mucosa-associated lymphoid tissue (MALT) lymphoma of the stomach is an uncommon disease. Bone marrow involvement is reported even in patients with only a mucosal lesion. We evaluated the prevalence and risk factors of marrow involvement and its implications for diagnosis and treatment. Methods: In total, 132 patients who were diagnosed with gastric MALT lymphoma at the National Cancer Center in Korea between January 2001 and December 2016 were enrolled in the study. The patient data were collected and analyzed retrospectively. Results: Of the 132 patients, 47 (35.6%) were male, with a median age of 52 years (range, 17 to 81 years). The median follow-up duration was 48.8 months (range, 0.5 to 169.9 months). Helicobacter pylori infection was detected in 82 patients (62.1%). Most patients (80.3%) had stage IE1 according to the modified Ann Arbor staging system. Ninety-two patients underwent bone marrow evaluation, and four patients (4.3%) had marrow involvement. Of these patients, one presented with abdominal lymph node involvement, while the other three had stage IE1 disease if marrow involvement was disregarded. All three patients had no significant symptoms and were monitored after local treatment without evidence of disease aggravation. Conclusions: Bone marrow involvement was found in 4.3% of the patients with gastric MALT lymphoma. Bone marrow examination may be deferred because marrow involvement does not change the treatment options or outcome in gastric MALT lymphoma confined to the stomach wall. (Gut Liver 2018;12:278-287) more...

Although the clinical outcome of newly diagnosed multiple myeloma has improved with maintenance therapy, maintenance with novel agents is not always available depending on medical expenses or drug accessibility. We intended to investigate the efficacy and toxicity of thalidomide/dexamethasone maintenance in Korean patients. In this multicenter phase 2 study, patients with newly diagnosed myeloma who underwent induction chemotherapy followed by autologous stem cell transplantation (ASCT) were enrolled to receive maintenance treatment of 100mg thalidomide daily for 28 days and 40mg dexamethasone daily for 4 days each cycle. Maintenance was given up to 12 cycles. The primary endpoint was a 1-year event free survival (EFS) rate. It was assumed that EFS at 1-year would be 91% with thalidomide and 1-year EFS below 82% would be of no effect. A total of 43 patients were consecutively enrolled (median age, 58 years [range, 34 – 65]; male, n = 31). With a median follow-up duration of 17.3 months (range, 1.1 – 32.2), EFS at 1 year was 65.1% (95% confidence interval [CI], 48.9 – 77.3). PFS and OS at 1 year was 85.6% (95% CI, 70.7 – 93.3) and 90.4 (95% CI, 76.3 – 96.3), respectively. In terms of side effects, 39 patients (90.7%) experienced adverse events (AEs) of any grade, and 14 patients (32.6%) experienced grade 3 or 4 adverse events. 15 patients (34.9%) failed to complete 12 cycles of maintenance, and the most common reason for premature termination was AEs (n = 6). In Korean patients the benefits of thalidomide maintenance does not seem to outweigh the toxicity of thalidomide, especially in high-risk MM. Considering the long clinical course of MM, preservation of quality of life and finances might be more beneficial for subsequent MM treatment. more...

Background JAK2 V617F is the most common mutation in myeloproliferative neoplasms (MPNs) and is a major diagnostic criterion. Mutation quantification is useful for classifying patients with MPN into subgroups and for prognostic prediction. Droplet digital PCR (ddPCR) can provide accurate and reproducible quantitative analysis of DNA. This study was designed to verify the correlation of ddPCR with pyrosequencing results in the diagnosis of MPN and to investigate clinical implications of the mutational burden. Methods Peripheral blood or bone marrow samples were obtained from 56 patients newly diagnosed with MPN or previously diagnosed with MPN but not yet indicated for JAK2 inhibitor treatment between 2012 and 2016. The JAK2 V617F mutation was detected by pyrosequencing as a diagnostic work-up. The same samples were used for ddPCR to determine the correlation between assays and establish a detection sensitivity cut-off. Clinical and hematologic aspects were reviewed. Results Forty-two (75%) and 46 (82.1%) patients were positive for JAK2 V617F by pyrosequencing and ddPCR, respectively. The mean mutated allele frequency at diagnosis was 37.5±30.1% and was 40.7±31.2% with ddPCR, representing a strong correlation (r=0.9712, P more...

Purpose Regional differences in the incidence of lymphoid malignancies have been reported worldwide, but there has been no large-scale epidemiologic analysis in Korea. The aim of this study was to provide a nationwide population-based statistical analysis of Korean patients with lymphoid malignancies. Materials and Methods The Korea Central Cancer Registry analyzed the incidence and survival of patients with lymphoid malignancies from the Korean National Cancer Incidence Database. Diseases were grouped by clinically relevant categories based on the 2008 World Health Organization classification. Results Overall 65,948 lymphoid diseases were identified between 1999 and 2012. The incidence of most subtypes increased with age, except for precursor cell neoplasms. Male predominance (male:female ratio=1.28:1) was observed. In 2012, annual age-standardized incidence rates per 100,000 persons of Hodgkin’s lymphoma, mature B-cell neoplasm, mature T/natural killer (NK)–cell neoplasm, and precursor cell neoplasm were 0.46, 6.60, 0.95, and 1.50, respectively, and they increased yearly from 1999. Composite Hodgkin’s and non-Hodgkin’s lymphomas were extremely rare. Survival improvement estimated using 5-year relative survival rate was observed in patients with Hodgkin’s lymphoma (71.1%-83.0%), diffuse large B-cell lymphoma (49.5%-61.5%), plasma cell neoplasms (20.2%-36.9%), and lymphoblastic lymphoma/leukemia (41.5%-56.3%) between 1993 and 2012. However, survival rates of T/NK-cell lymphoma (excluding cutaneous T-cell lymphoma) ranged from 40.5%-43.5% during the study period. Survival rates decreased with age in most subtypes. Conclusion This report presented the subtype-specific statistical analysis of lymphoid malignancies in the Korean population, showing increasing incidences and survival rates in most subtypes. more...

Background: We examined the relationship and combined effect of vascular calcification (VC) and left ventricular hypertrophy (LVH) on deaths and cardiovascular events (CVEs) in hemodialysis (HD) patients. Methods: Maintenance HD patients (n=341) were included. Echocardiography data and plain chest radiographs were used to assess LVH and aortic arch VC. Results: VC was found in 100 patients (29.3%). LVH was more prevalent in patients with VC compared with those without VC (70% vs. 50.2%, P=0.001). VC was independently associated with a 2.42-fold increased risk of LVH (95% CI, 1.26-4.65). In multivariate analysis, compared with patients with neither VC nor LVH, the coexistence of VC and LVH was independently associated with CVE (HR, 2.01; 95% CI, 1.09-3.72), whereas VC or LVH alone was not. Patients with both VC and LVH had the highest risk for a composite event of deaths or CVE (HR, 1.88; 95% CI, 1.15-3.06). Significant synergistic interaction was observed between VC and LVH (P for interaction=0.039). Conclusions: VC was independently associated with LVH. The coexistence of VC and LVH was associated with higher risk of deaths and CVEs than either factor alone. VC and LVH showed a synergistic interaction for the risk of deaths and CVEs. more...

Background. Chemotherapy-induced peripheral neuropathy (CIPN) is a common adverse effect in cancer patients. The aim of this review was to assess the effectiveness of herbal medicine in preventing and treating CIPN. Methods. Randomised controlled trials were included in this review. Extracting and assessing the data independently, two authors searched 13 databases. Results. Twenty-eight trials involving 2174 patients met the inclusion criteria. Although there were some exceptions, the methodological quality was typically low. Seventeen trials reported the incidence rate of CIPN assessed by various tools and 14 showed a significant difference regarding the decrease of the incidence rate between the two groups. For clinical improvement, 12 trials reported it using various tools and 10 showed a significant difference between two groups. Two cases of adverse events occurred in one trial; the other nine trials reported no adverse events. Conclusions. We found that herbal medicines in combination with and/or without other therapies potentially have preventive or therapeutic effects on CIPN. However, conclusions cannot be drawn because of the generally low quality of the methodology, the clinical heterogeneity, and the small sample size for each single herbal medicine. Trials that are more rigorous and report sufficient methodological data are needed. more...