Differences in Clinical Outcomes Between Hydroxyurea-Resistant and -Intolerant Polycythemia Vera Patients.

BACKGROUND: Previous studies have suggested that patients with polycythemia vera (PV) who exhibit hydroxyurea-resistance (HU-R) and -intolerance (HU-I) may have distinct characteristics and clinical outcomes. However, to date, no studies have reported a comparison between these two groups or assessed prognostic factors in these patients. METHODS: The objective of this study was to evaluate clinical outcomes and identify prognostic factors among PV patients with HU-R or HU-I. We conducted a review of PV patients who received frontline treatment with HU from nine centers and identified 90 patients with HU-R or HU-I. RESULTS: The cumulative incidence of thrombosis after 7 years of HU-R/I was 21.4%, and the incidence of disease progression was 22.5%. Comparing the HU-R and HU-I groups, the HU-R group had a significantly higher rate of disease progression (36.7% vs. 0.56%, P = 0.009), while there was no significant difference in thrombosis incidence (19.0% vs. 22.9%, P = 0.463). Multivariate analysis revealed that HU-R was an independent prognostic factor for progression-free survival (hazard ratio, 6.27, 95% confidence interval, 1.83-21.47, P = 0.003). Additionally, higher lactate dehydrogenase levels, multiple cardiovascular risk factors, and prior thrombosis were identified as unfavorable predictors of overall survival. CONCLUSION: These findings suggest that patients with HU-R face a higher risk of hematological transformation, but have a comparable risk of thrombosis to patients with HU intolerance. These distinctions should guide decisions on second-line treatment options and clinical trials involving these patients.

Impact of the ACOSOG Z0011 trial on surgical practice in Asian patients: trends in axillary surgery for breast cancer from a Korean Breast Cancer Registry analysis.

BACKGROUND: Since the publication of the Z0011 trial, practice-changing clinical guidelines for breast surgery have been developed. Although recent studies confirmed the feasibility of the Z0011 strategy in Asian populations, there has been no study on the trends of axillary surgery in Asian cohort. This study aimed to investigate the time trend of axillary surgery for breast cancer from a Korean Breast Cancer Registry to understand the impact of the Z0011 trial in Asian patients. METHODS: We collected prospectively constructed data from the nationwide Korean Breast Cancer Registry (KBCR). We identified patients who underwent sentinel node biopsy followed by breast-conserving surgery from 2011 to 2018 and were found to have pathological stage T1-2N1-3M0 disease. Regression analyses were performed to compare the downward trend of axillary lymph node dissection (ALND) in Korean cohort with that previously reported in a Dutch cohort. RESULTS: From KBCR data, 7478 patients met the inclusion criteria. The proportion of ALND significantly decreased from 2011 (76.6%) to 2018 (47.5%). Multivariate analysis revealed that earlier years at diagnosis, larger tumor size, and lymphatic invasion were associated with a higher odds ratio of performing ALND. Compared to the Dutch cohort, the downward trend of ALND in Korea was significantly more gradual (annual percent change: 37.2 vs. 5.8%, p < 0.001). CONCLUSIONS: This study demonstrated a downward trend of ALND in Korean patients with breast cancer. However, the rate of decrease was significantly slower than that in the Dutch cohort.

A Comparative Study of the Accuracy of Dental CAD Programs in Designing a Fixed Partial Denture.

PURPOSE: Error testing at each stage of prosthetic manufacturing remains relatively underdeveloped for computer-aided design/computer-aided manufacturing methods, and no experimental studies have validated the computer-aided design programs. This study aimed to test the accuracy and trueness of the computer-aided design of a three-unit fixed prosthesis. MATERIALS AND METHODS: Three computer-aided design programs (Exocad, Dental System™, and inLab 16) were tested on the designs of a three-unit fixed partial denture, and a three-dimensional analysis program was used to calculate the internal clearance error for the computer-aided design prostheses. The Kruskal-Wallis and Dunn's post hoc tests were used to reveal significant differences in trueness between the three computer-aided design programs (α < 0.05). RESULTS: Dental System™ showed the lowest mean error values for #24 and #26 at the mesial margin (both 0 µm), mesial wall (0.10, 0.12 µm, respectively), occlusal surface (-0.05, 0.10 µm), distal wall (0.23, -0.02 µm), and distal margin (both 0 µm). In sum, except for the mesial margin and distal margin site of tooth #26, the mean error value of Dental System™ was statistically the lowest, followed by those of Exocad and inLab 16 (p < 0.003). CONCLUSIONS: The accuracy of computer-aided design differed according to the type of computer-aided design program. Dental System™ achieved the best trueness at the margins, axial walls, and occlusal surface, followed by Exocad and inLab 16.

Loss of Arabidopsis matrix metalloproteinase-5 affects root development and root bacterial communities during drought stress.

Matrix metalloproteinases (MMPs) are zinc-dependent endo-peptidases that in mammals are known to be involved in remodeling the extracellular matrix (ECM) in developmental and pathological processes. In this study, we report At5-MMP of Arabidopsis thaliana to be important for root development and root bacterial communities. At5-MMP is mainly localized in the root vasculature and lateral root, an At5-MMP T-DNA insertion mutant (mmp5 KO) showed reduced root growth and a lower number of root apexes, causing reduced water uptake from the soil. Subsequently, mmp5 KO is sensitive to drought stress. Inhibited auxin transport was accompanied with resistance to indole-3-acetic acid (IAA), 2, 4-dichlorophenoxyacetic acid (2, 4-D), and 1-naphthaleneacetic acid (NAA). The content of endogenous abscisic acid (ABA) was lower in roots of mmp5 KO than in wild type. Genes responsive to ABA as well as genes encoding enzymes of the proline biosynthesis were expressed to a lower extent in mmp5 KO than in wild type. Moreover, drought stress modulated root-associated bacterial communities of mmp5 KO: the number of Actinobacteria increased. Therefore, At5-MMP modulates auxin/ABA signaling rendering the plant sensitive to drought stress and recruiting differential root bacterial communities.

3D-Printed Load Cell Using Nanocarbon Composite Strain Sensor.

The development of a 3D-Printed Load Cell (PLC) was studied using a nanocarbon composite strain sensor (NCSS) and a 3D printing process. The miniature load cell was fabricated using a low-cost LCD-based 3D printer with UV resin. The NCSS composed of 0.5 wt% MWCNT/epoxy was used to create the flexure of PLC. PLC performance was evaluated under a rated load range; its output was equal to the common value of 2 mV/V. The performance was also evaluated after a calibration in terms of non-linearity, repeatability, and hysteresis, with final results of 2.12%, 1.60%, and 4.42%, respectively. Creep and creep recovery were found to be 1.68 (%FS) and 4.16 (%FS). The relative inferiorities of PLC seem to originate from the inherent hyper-elastic characteristics of polymer sensors. The 3D PLC developed may be a promising solution for the OEM/design-in load cell market and may also result in the development of a novel 3D-printed sensor.

Childbirth in young Korean women with previously treated breast cancer: The SMARTSHIP study.

PURPOSE: Alongside the modern trend of delaying childbirth, the high incidence of breast cancer among young women is causing significant pregnancy-related problems in Korea. We estimated the incidence of childbirth for young Korean breast cancer survivors compared with women who did not have breast cancer using a nationally representative dataset. METHODS: Using a database from the National Health Insurance Service in South Korea, we analyzed 109,680 women who were between 20 and 40 years old between 2007 and 2013. They were prospectively followed, and childbirth events were recorded until December 31, 2015. We compared childbirth rates and characteristics between the breast cancer survivors and the noncancer controls. RESULTS: Compared to 10,164 childbirths among 91,400 women without breast cancer (incidence rate: 22.3/1000), 855 childbirths occurred among 18,280 breast cancer survivors (incidence rate: 9.4/1000); the adjusted hazard ratio (HR) for childbirth was 0.41 (95% CI 0.38-0.44). Chemotherapy, endocrine therapy, and target therapy were associated with the decreasing childbirths among survivors, with corresponding adjusted HRs of 0.61 (0.53-0.70), 0.44 (0.38-0.51), and 0.62 (0.45-0.86), respectively. Breast cancer survivors had a lower probability of full-term delivery and a higher frequency of preterm labor than controls, with corresponding adjusted ORs of 0.78 (0.68-0.90) and 1.33 (1.06-1.65), respectively. CONCLUSIONS: We showed that a history of breast cancer has a negative effect on childbirth among young premenopausal women in Korea. Breast cancer survivors should be aware that they have a higher risk for preterm labor and are less likely to have a full-term delivery than women without a history of breast cancer.

Power-Efficient Nonvolatile Ternary Content Addressable Memory with Flexible Search Scope Using Reconfigurable Match Line Segment and Selective Search Line.

This paper proposes a nonvolatile-based Ternary Content Addressable Memory (nvTCAM) with efficient dynamic power. The selective search line technique reduces the unnecessary power consumption by designating the search range according to the pattern of the stored data. The reconfigurable match line (ML) segment guarantees the optimal performance independent of the search pattern. Thanks to this technology, it shows a 21% reduction in data-driven power and a 46% reduction in ML-driven power. All those techniques are built in nvTCAM respectively. The test chip is fabricated using 180 nm CMOS technology, and functions are verified.

Bendamustine plus rituximab for relapsed or refractory diffuse large B cell lymphoma: a multicenter retrospective analysis.

Bendamustine plus rituximab (BR) showed efficacy and safety in indolent lymphomas and mantle cell lymphoma. However, there were limited experiences of real-world practice of BR in diffuse large B cell lymphoma (DLBCL). In this study, we report the Korean experiences with BR in relapsed or refractory DLBCL who are not eligible for intensive chemotherapy and autologous stem cell transplantation. This is an observational, multicenter, retrospective analysis. Between December 2011 and December 2015, a total of 58 patients with relapsed or refractory DLBCL were treated with BR in 11 tertiary hospitals in Korea. Patients received an intravenous (IV) infusion of rituximab at a dose of 375 mg/m2 on day 1. On days 2 and 3, patients received an IV infusion of bendamustine at doses of 120 or 90 mg/m2. Median age was 69 (range 18-86), 74.1% had stage III or IV disease, and 67.2% showed high-intermediate or high International Prognostic Index scores at diagnosis. In an intention-to-treat analysis, 18 patients (31.0%) showed a complete response and 14 (24.1%) showed a partial response, resulting in an overall response rate of 55.1%. The median duration of the response was 3.7 months (range 1.0-47.2 months). The median progression-free survival was 3.9 months (95% confidence interval [CI], 2.4-5.4 months), and the median overall survival was 6.7 months (95% CI, 4.7-8.7 months). The most common grade 3/4 adverse event was neutropenia (n = 40; 68.9%). Febrile neutropenia was observed in 11 patients (18.9%). Grade 3/4 thrombocytopenia was observed in 34 patients (58.6%). Our study confirmed the high efficacy and acceptable toxicity profile of BR in relapsed or refractory DLBCL patients. However, we need to closely observe the higher tendency of grade 3/4 hematological toxicities in Korean patients.

Development of a Spoke Type Torque Sensor Using Painting Carbon Nanotube Strain Sensors.

This study reports a hub-spoke type joint torque sensor involving strain gauges made of multiwalled carbon nanotubes (MWCNT). We developed the novel joint torque sensor for robots by means of MWCNT/epoxy strain sensors (0.8 wt%, gauge factor 2) to overcome the limits of conventional foil strain gauges. Solution mixing process was hired to fabricate a liquid strain sensor that can easily be installed on any complicated surfaces. We painted the MWCNT/epoxy mixing liquid on the hub-spoke type joint torque sensor to form the piezoresistive strain gauges. The painted sensor converted its strain into torque by mean of the installed hub-spoke structure after signal processing. We acquired sufficient torque voltage responses from the painted MWCNT/epoxy strain sensor.

Comprehensive evaluation of the revised international staging system in multiple myeloma patients treated with novel agents as a primary therapy.

The revised International Staging System (R-ISS) has recently been developed to improve the risk stratification of multiple myeloma (MM) patients over the ISS. We assessed the R-ISS in MM patients who were treated with novel agents as a primary therapy and evaluated its discriminative power and ability to reclassify patients from the ISS. A total of 514 newly diagnosed MM patients treated with novel agents including thalidomide, bortezomib, and lenalidomide as a primary therapy were included in this retrospective analysis. With a median follow-up duration of 42.3 months (range, 40.5-44.1), the median overall survival (OS) was 61.0 months. There was a significant difference in median OS (not reached, 60.9, and 50.1 months for stages 1, 2, and 3, respectively, P < 0.001) among the three stages of R-ISS. The C-statistic was significantly greater for R-ISS than for ISS (0.769 vs. 0.696, P < 0.001). The event NRI was -0.08 (95% confidence interval [CI], -0.18-0.01) and the non-event NRI was 0.05 (95% CI, -0.03-0.10), resulting in a total NRI of -0.03 (95% CI, -0.14-0.08, P = 0.602). The R-ISS performs well and has significantly better discriminative power than the ISS in MM patients treated with novel agents as a primary therapy. However, it does not better reclassify patients from the ISS, suggesting that there is still room to improve the staging system. Moreover, new statistical measures for assessing and quantifying the risk prediction of new prognostic models are necessary in future studies.

Oral mucormycosis in patients with haematologic malignancies in a bone marrow transplant unit.

Mucormycosis is an aggressive and life-threatening opportunistic fungal infection, which predominantly affects immunocompromised patients. It typically manifests in rhinocerebral, pulmonary or disseminated forms in patients with immunosuppressive conditions. Mucormycosis limited to the oral cavity is rare, and to the best of our knowledge only seven cases have previously been reported in English literature. We present five consecutive cases of oral mucormycosis in patients with leukaemia, and provide a literature review.

The role of the addition of ovarian suppression to tamoxifen in young women with hormone-sensitive breast cancer who remain premenopausal or regain menstruation after chemotherapy (ASTRRA): study protocol for a randomized controlled trial and progress.

BACKGROUND: Ovarian function suppression (OFS) has been shown to be effective as adjuvant endocrine therapy in premenopausal women with hormone receptor-positive breast cancer. However, it is currently unclear if addition of OFS to standard tamoxifen therapy after completion of adjuvant chemotherapy results in a survival benefit. In 2008, the Korean Breast Cancer Society Study Group initiated the ASTRRA randomized phase III trial to evaluate the efficacy of OFS in addition to standard tamoxifen treatment in hormone receptor-positive breast cancer patients who remain or regain premenopausal status after chemotherapy. METHODS: Premenopausal women with estrogen receptor-positive breast cancer treated with definitive surgery were enrolled after completion of neoadjuvant or adjuvant chemotherapy. Ovarian function was assessed at the time of enrollment and every 6 months for 2 years by follicular-stimulating hormone levels and bleeding history. If ovarian function was confirmed as premenopausal status, the patient was randomized to receive 2 years of goserelin plus 5 years of tamoxifen treatment or 5 years of tamoxifen alone. The primary end point will be the comparison of the 5-year disease-free survival rates between the OFS and tamoxifen alone groups. Patient recruitment was finished on March 2014 with the inclusion of a total of 1483 patients. The interim analysis will be performed at the time of the observation of the 187th event. DISCUSSION: This study will provide evidence of the benefit of OFS plus tamoxifen compared with tamoxifen only in premenopausal patients with estrogen receptor-positive breast cancer treated with chemotherapy. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT00912548 . Registered May 31 2009. Korean Breast Cancer Society Study Group Register KBCSG005 . Registered October 26 2009.

Substitution of methotrexate with corticosteroid for acute graft-versus-host disease prevention in transplanted patients who develop methotrexate toxicity.

Methotrexate (MTX) toxicity can hamper the administration of all planned doses in acute graft-versus-host disease (GVHD) prophylaxis following allogeneic hematopoietic stem cell transplantation. Reduction or omission of MTX doses results in an increased risk of acute GVHD. In this prospective observational study, we compared the incidence of GVHD and the transplant outcomes between patients who received the full treatment course of MTX (group 1), patients in whom MTX doses were omitted if MTX toxicity developed (group 2), and patients receiving corticosteroid instead of MTX if MTX toxicity developed (group 3). The cumulative incidence of grades II-IV acute GVHD at 100 days post-transplantation was 22.2 % in group 1, 43.6 % in group 2, and 25.0 % in group 3 (P = 0.132). The risk of grades II-IV acute GVHD in group 2 was higher than that in group 1 (hazard ratio (HR) 3.262, P = 0.016), but the risk in group 3 was similar to that in group 1 (HR 0.960, P = 0.890). Group 3 also showed a trend towards a lower risk of chronic GVHD compared to the other groups. The cumulative risk of chronic GVHD at 2 years was 73.9, 71.6, and 33.3 % in groups 1, 2, and 3, respectively (P = 0.084). However, a likely higher relapse incidence and infection-related mortality in group 3 produced a trend towards the lowest relapse-free survival (2-year RFS, 46.3, 49.3, and 25.0 % in groups 1, 2, and 3, respectively; P = 0.329) and overall survival (2-year OS, 45, 52.3, and 25 %, respectively; P = 0.322) in group 3. Although the substitution of MTX with corticosteroid ameliorates the increased risk of GVHD in patients in which it is imperative to omit its dose, its negative impact on relapse and infection risk does not result in favorable transplant outcomes.

A Spray-On Carbon Nanotube Artificial Neuron Strain Sensor for Composite Structural Health Monitoring.

We present a nanocomposite strain sensor (NCSS) to develop a novel structural health monitoring (SHM) sensor that can be easily installed in a composite structure. An NCSS made of a multi-walled carbon nanotubes (MWCNT)/epoxy composite was installed on a target structure with facile processing. We attempted to evaluate the NCSS sensing characteristics and benchmark compared to those of a conventional foil strain gauge. The response of the NCSS was fairly good and the result was nearly identical to the strain gauge. A neuron, which is a biomimetic long continuous NCSS, was also developed, and its vibration response was investigated for structural damage detection of a composite cantilever. The vibration response for damage detection was measured by tracking the first natural frequency, which demonstrated good result that matched the finite element (FE) analysis.

The prevalence and spectrum of BRCA1 and BRCA2 mutations in Korean population: recent update of the Korean Hereditary Breast Cancer (KOHBRA) study.

The Korean Hereditary Breast Cancer (KOHBRA) study was established to evaluate the prevalence and spectrum of BRCA1/2 mutations in Korean breast cancer patients at risk for hereditary breast and ovarian cancer. A total of 2953 subjects (2403 index patients and 550 family members of affected carriers) from 36 centers participated in this study between May 2007 and December 2013. All participants received genetic counseling and BRCA genetic testing. In total, 378 mutation carriers among 2403 index patients were identified. The prevalence of BRCA mutations in specific subgroups was as follows: 22.3 % (274/1228) for breast cancer patients with a family history of breast/ovarian cancers, 8.8 % (39/441) for patients with early-onset (<35 years) breast cancer without a family history, 16.3 % (34/209) for patients with bilateral breast cancer, 4.8 % (1/21) for male patients with breast cancer, and 37.5 % (3/8) for patients with both breast and ovarian cancer. From an analysis of the mutation spectrum, 63 BRCA1 and 90 BRCA2 different mutations, including 44 novel mutations, were identified. The c.7480 (p.Arg2494Ter) mutation in BRCA2 (10.1 %) was the most commonly identified in this cohort. The KOHBRA study is the largest cohort to identify BRCA mutation carriers in Asia. The results suggest that the prevalence of BRCA mutations in familial breast cancer patients is similar to that among Western cohorts. However, some single risk factors without family histories (early-onset breast cancer, male breast cancer, or multiple organ cancers) may limit the utility of BRCA gene testing in the Korean population.

Myelodysplastic syndrome evolving from aplastic anemia treated with immunosuppressive therapy: efficacy of hematopoietic stem cell transplantation.

A proportion of patients with aplastic anemia who are treated with immunosuppressive therapy develop clonal hematologic disorders, including post-aplastic anemia myelodysplastic syndrome. Many will proceed to allogeneic hematopoietic stem cell transplantation. We identified 123 patients with post-aplastic anemia myelodysplastic syndrome who from 1991 through 2011 underwent allogeneic hematopoietic stem cell transplantation, and in a matched-pair analysis compared outcome to that in 393 patients with de novo myelodysplastic syndrome. There was no difference in overall survival. There were no significant differences with regard to 5-year probabilities of relapse, non-relapse mortality, relapse-free survival and overall survival; these were 14%, 40%, 46% and 49% for post-aplastic anemia myelodysplastic syndrome, and 20%, 33%, 47% and 49% for de novo myelodysplastic syndrome, respectively. In multivariate analysis, relapse (hazard ratio 0.71; P=0.18), non-relapse mortality (hazard ratio 1.28; P=0.18), relapse-free survival (hazard ratio 0.97; P=0.80) and overall survival (hazard ratio 1.02; P=0.88) of post-aplastic anemia myelodysplastic syndrome were similar to those of patients with de novo myelodysplastic syndrome. Cytogenetic risk was independently associated with overall survival in both groups. Thus, transplant success in patients with post-aplastic anemia myelodysplastic syndrome was similar to that in patients with de novo myelodysplastic syndrome, and cytogenetics was the only significant prognostic factor for post-aplastic anemia myelodysplastic syndrome patients.

Is Helicobacter Pylori associated with Her2/neu Overexpression in Gastric Cancer Patients who Underwent Curative Resection?

BACKGROUND/AIMS: Human epidermal growth factor receptor 2 (Her2/neu) is an important target for treatment of gastric cancer using trastuzumab and Helicobacter pylori is a well-known risk factor of gastric cancer. We investigated the association of Her2/neu overexpression with Helicobacter pylori and other clinicopathologic factors in gastric cancer patients who underwent curative resection. METHODOLOGY: Her2/neu immunohistochemistry was performed in gastric cancer patients who underwent curative gastrectomy or endoscopic submucosal dissection. Analysis about its associations with clinicopathologic features such as Lauren histologic types, differentiation, Helicobacter pylori infection, location, depth of invasion, lymph node metastasis, and AJCC tumor stage was performed retrospectively. RESULTS: The incidence of Her2/neu 3+, 2+, 1+ and 0 was 8.9%, 22.1%, 4.4% and 64.6% respectively. Intestinal type of gastric cancer showed higher incidence of Her2/neu 3+ than diffuse type. The score 2+ and 3+ was more common in Helicobacter pylori-positive patients than Helicobacter pylori-negative patients (p = 0.024). 7th American joint Cancer Committee Tumor stage, depth of tumor invasion and lymph node metastasis did not show correlation with the level of Her2/neu expression. CONCLUSIONS: Helicobacter pylori-positive gastric cancer showed more Her2/neu overexpression. Helicobacter pylori eradication may be necessary to avoid Her2/neu overexpression.

Bilateral Sudden Hearing Loss in Iron Deficiency Anemia.

The present study describes an unusual case of bilateral sudden hearing loss associated with iron deficiency anemia. Although hematologic disorders such as anemia or leukemia have been reported to be associated with sudden hearing loss, bilateral sudden hearing loss, which was presented as the first manifestation of iron deficiency anemia, has not been reported. A 74-year-old man presented with simultaneous bilateral sudden hearing loss without vertigo. A complete blood count test revealed a hemoglobin level of 6.4 g/dL and a ferritin level of 14.5 mg/mL, indicating iron deficiency anemia. Postcontrast 3D FLAIR MRI showed enhancement of the bilateral cochlea, vestibules, and lateral semicircular and posterior semicircular canals. After treatment, the patient's hearing loss partially improved.