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Despite a high prevalence of dementia in older adults hospitalized with severe acute respiratory syndrome coronavirus 2 infection (COVID-19), research investigating association between preexisting diagnoses of dementia and prognosis of COVID-19 is scarce. We explored a nationwide cohort with a total of 2,800 subjects older than 50 years who were diagnosed with COVID-19 between January and April 2020. Among them, 223 patients had underlying dementia (dementia group). We matched 1:1 for each dementia-non-dementia group pair yielding 223 patients without dementia (no dementia group) using propensity score matching. The primary outcome measure was group difference in mortality after COVID-19. Mortality rate after COVID-19 were significantly higher in dementia group than in no dementia group (33.6% vs. 20.2%, p=0.002). In addition, dementia group had higher proportion of patients requiring invasive ventilatory support than no dementia group (34.1% vs. 22.0%, p=0.006). Multivariable analysis showed that dementia group had a higher risk of mortality than no dementia group (odds ratio=3.05, p

Objective No previous study examined impact of dementia in the outcome of allogeneic hematopoietic stem cell transplantation (HSCT). We aimed to investigate overall survival (OS) of patients with dementia after receiving HSCT. Methods Among 8,230 patients who underwent HSCT between 2002 and 2018, 5,533 patients younger than 50 years were first excluded. Remaining patients were divided into those who were and were not diagnosed with dementia before HSCT (dementia group: n = 31; no dementia: n = 2,666). Thereafter, among 2,666 participants without dementia, 93 patients were selected via propensity-matched score as non-dementia group. Patients were followed from the day they received HSCT to the occurrence of death or the last follow-up day (December 31, 2018), whichever came first. Results With median follow-up of 621 days for dementia group and 654 days for non-dementia group, 2 year-OS of dementia group was lower than that of non-dementia group (53.3% [95% confidence interval, 95% CI, 59.0-80.2%] vs. 68.8% [95% CI, 38.0-68.2%], p = 0.076). In multivariate analysis, dementia had significant impacts on OS (hazard risk = 2.539, 95% CI, 1.166-4.771, p = 0.017). Conclusion Our results indicated that patients diagnosed with dementia before HSCT have 2.539 times higher risk of mortality after transplantation than those not having dementia. With number of elderly needing HSCT is increasing, further work to establish treatment guidelines for the management of HSCT in people with dementia is needed.

The Philadelphia-negative myeloproliferative neoplasms (MPNs) are divided in three major groups: polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The 2016 WHO classification incorporates also prefibrotic PMF (pre-PMF) and overt PMF. This study aimed to discriminate the clinical features, genetic alterations, and outcomes in patients with prefibrotic, overt PMF, and secondary MF (SMF). This study included 229 patients with diagnosed myelofibrosis (MF). Among 229 patients, 67 (29%), 122 (53%), and 40 (18%) were confirmed as SMF, overt PMF, and pre-PMF, respectively. The JAK2 V617F mutation was differentially distributed in SMF and PMF, contradictory to CALR and MPL mutations. Regarding nondriver mutations, the occurrence of ASXL1 mutations differed between PMF and SMF or pre-PMF. The three-year overall survival was 91.5%, 85.3%, and 94.8% in SMF, overt PMF, and pre-PMF groups. Various scoring systems could discriminate the overall survival in PMF but not in SMF and pre-PMF. Still, clinical features including anemia and thrombocytopenia were poor prognostic factors throughout the myelofibrosis, whereas mutations contributed differently. Molecular grouping by wild-type SF3B1 and SRSF2/RUNX1/U2AF1/ASXL1/TP53 mutations showed inferior progression-free survival (PFS) in PMF, SMF, and pre-PMF. We determined the clinical and genetic features related to poor prognosis in myelofibrosis.

In this work, polyacrylic acid-functionalized MCM-41 was synthesized, which was made to interact with calcium ions, in order to realize enhanced pH-responsive nanocarriers for sustained drug release. First, mesoporous silica nanoparticles (MSNs) were prepared by the sol-gel method. Afterward, a (3-trimethoxysilyl)propyl methacrylate (TMSPM) modified surface was prepared by using the post-grafting method, and then the polymerization of the acrylic acid was performed. After adding a calcium chloride solution, polyacrylic acid-functionalized MSNs with calcium-carboxyl ionic bonds in the polymeric layer, which can prevent the cargo from leaking out of the mesopore, were prepared. The structure and morphology of the modified nanoparticles (PAA-MSNs) were characterized by X-ray diffraction (XRD), Fourier-transform infrared (FT-IR) spectroscopy, transmission electron microscopy (TEM), and N2 adsorption–desorption analysis, etc. The controlled release of guest molecules was studied by using 5-fluorouracil (5-FU). The drug molecule-incorporated nanoparticles showed different releasing rates under different pH conditions. It is considered that our current materials have the potential as pH-responsive nanocarriers in the field of medical treatment.

We report that the grain size of an extruded Mg–6Zn–0.5Zr alloy is significantly reduced by the addition of Ca. The grain size was reduced from 4.2 to 1.6 µm by the addition of 0.2 wt% Ca, leading to an increase in the yield strength to as high as 65 MPa. Microstructural analysis indicated that adding Ca to the alloy results in the co-presence of MgZn2 and Ca2Mg6Zn3 particles within the α-Mg matrix and the co-segregation of Zn and Ca at the grain boundaries. The factors responsible for such remarkable changes in the microstructure and tensile properties are also discussed.

Background Plasma cell myeloma (PCM) is a genetically heterogeneous disease. The genetic spectrum of PCM has been expanded to mutations such as KRAS, NRAS, and BRAF genes in the RAS-RAF-MAPK pathway. In this study, we have evaluated the frequency of these mutations and their significance, including baseline characteristics and clinical outcomes. Methods We explored 50 patients who were newly diagnosed with PCM between 2009 and 2012 at a single Korean institute. Clinical and laboratory parameters were gathered through careful review of medical records. Mutation analysis was carried out using DNA from the bone marrow at the time of diagnosis. Pyrosequencing was performed to detect KRAS G12V, KRAS G13D, and NRAS G61R. BRAF V600E was analyzed by allele-specific real- time PCR. Comparison of clinical and laboratory parameters was carried out according to those mutations. Results We identified 14 patients (28%) with activating mutations in the RAS-RAF-MAPK pathway (RAS/RAF mutations): KRAS (N=3), NRAS (N=4), BRAF (N=7), and both KRAS and BRAF (N=1). RAS/RAF mutations were more frequently observed in patients with complex karyotypes and showed poorer progression free survival (PFS). Specifically, the BRAF V600E mutation had a significantly negative impact on median PFS. Conclusion We first showed the frequency of RAS/RAF mutations in Korean patients with PCM. Screening of these mutations could be considered as a routine clinical test at the time of diagnosis and follow-up due to their influence on clinical outcome, as well as its potential as a therapeutic target.

Studies investigating association of depression with overall survival (OS) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) yielded conflicting results. A nationwide cohort study, which included all adult patients [n = 7,170; depression group, 13.3% (N = 956); non-depression group, 86.7% (N = 6,214)] who received allo-HSCT from 2002 to 2018 in South Korea, analyzed risk of pre-transplant depression in OS of allo-HSCT. Subjects were followed from the day they received allo-HSCT, to occurrence of death, or last follow-up day (December 31, 2018). Median age at allo-HSCT for depression and non-depression groups were 50 and 45 (p p p p = 0.04), and to having both depression and anxiety disorder (aHR = 1.202, CI: 1.038–1.393, p = 0.014) groups. Pre-transplant anxiety (anxiety only) did not have significant influence in OS. Additional medical and psychiatric care might be necessary in patients who experienced depression, especially with anxiety, before allo-HSCT.

A comprehensive map of the Kir2.1 interactome was generated using the proximity-labeling approach BioID. The map encompasses 218 interactions, the vast majority of which are novel, and explores the variations in the interactome profiles of Kir2.1WT versus Kir2.1Δ314-315, a trafficking deficient ATS1 mutant, thus uncovering molecular mechanisms whose malfunctions may underlie ATS1 disease. PKP4, one of the BioID interactors, is validated as a modulator of Kir2.1-controlled inward rectifier potassium currents., Graphical Abstract Highlights • Generation using BioID of a map of the Kir2.1 interactome with 218 interactions. • Identification of Kir2.1WT- versus Kir2.1Δ314-315-preferred interactors. • Identification of the desmosome protein PKP4 as a new modulator of IKir2.1 currents., Kir2.1, a strong inward rectifier potassium channel encoded by the KCNJ2 gene, is a key regulator of the resting membrane potential of the cardiomyocyte and plays an important role in controlling ventricular excitation and action potential duration in the human heart. Mutations in KCNJ2 result in inheritable cardiac diseases in humans, e.g. the type-1 Andersen-Tawil syndrome (ATS1). Understanding the molecular mechanisms that govern the regulation of inward rectifier potassium currents by Kir2.1 in both normal and disease contexts should help uncover novel targets for therapeutic intervention in ATS1 and other Kir2.1-associated channelopathies. The information available to date on protein-protein interactions involving Kir2.1 channels remains limited. Additional efforts are necessary to provide a comprehensive map of the Kir2.1 interactome. Here we describe the generation of a comprehensive map of the Kir2.1 interactome using the proximity-labeling approach BioID. Most of the 218 high-confidence Kir2.1 channel interactions we identified are novel and encompass various molecular mechanisms of Kir2.1 function, ranging from intracellular trafficking to cross-talk with the insulin-like growth factor receptor signaling pathway, as well as lysosomal degradation. Our map also explores the variations in the interactome profiles of Kir2.1WTversus Kir2.1Δ314-315, a trafficking deficient ATS1 mutant, thus uncovering molecular mechanisms whose malfunctions may underlie ATS1 disease. Finally, using patch-clamp analysis, we validate the functional relevance of PKP4, one of our top BioID interactors, to the modulation of Kir2.1-controlled inward rectifier potassium currents. Our results validate the power of our BioID approach in identifying functionally relevant Kir2.1 interactors and underline the value of our Kir2.1 interactome as a repository for numerous novel biological hypotheses on Kir2.1 and Kir2.1-associated diseases.

Context and Objectives This study aimed to assess the effects of hormone replacement therapy (HRT) on bone mineral density (BMD) in young women who underwent allogeneic hematopoietic stem cell transplantation (HSCT). Participants and Methods This retrospective cohort included 234 female patients with premature ovarian insufficiency (POI) who underwent allogeneic HSCT between April 2009 and April 2016 at Seoul St. Mary’s Hospital in Seoul, Korea. Inclusion criteria included adult patients who were age 40 years or younger at the time of transplantation and were followed for at least 3 years after HSCT. Results At the first and second years after HRT, there was a significant increase in the BMD of the lumbar spine of the HRT group (n = 170) compared to that of the non-HRT group (n = 64) (P = .033 and P = .047, respectively). The BMD of the lumbar spine significantly increased from baseline by 4.16 ± 4.39% and 5.42 ± 5.86% after 1 and 2 years of HRT, respectively (P = .037 and P = .021). The BMD of the femoral neck and total hip also showed a significant percentage increase from baseline after 2 years of HRT. These changes were significant even in the presence of graft-versus-host disease or steroid exposure. For HRT that was initiated within 12 months after HSCT, the increase in BMD in the lumbar spine was greatest after 2 years of HRT. Conclusions These results support that early and active hormonal therapy might be beneficial for BMD in female HSCT recipients with POI.

We report that the corrosion resistance of a Mg–Sn-based alloy with Mg2Sn precipitates can be considerably improved by surface modification using pulsed electron beam treatment. The alloy subjected to a pulse electron beam treatment showed a modified surface layer with a thickness of ∼12 µm, appearing more resistant to corrosion attack than the bare surface of the alloy. In 0.6 M NaCl solution, the alloys with and without the surface modification exhibited average corrosion rates of 4.3 and 8.1 mm y −1, respectively. The improved corrosion resistance was attributed to reduced cathodic activation, resulting from the surficial reduction of relatively noble Mg2Sn precipitates.

We evaluated the prognostic efficiency of the European Leukemia Net (ELN) 2017 criteria on the post-transplant outcomes of 174 patients with intermediate (INT; n = 108, 62%) or adverse (ADV) risk (n = 66, 38%) of acute myeloid leukemia; these patients had received the first allogeneic hematopoietic stem-cell transplantation (HSCT) at remission. After a median follow-up period of 18 months, the 2 year OS, RFS, and CIR after HSCT were estimated to be 58.6% vs. 64.4% (p = 0.299), 50.5% vs. 53.7% (p = 0.533), and 26.9% vs. 36.9% (p = 0.060) in the INT and ADV risk groups, respectively. Compared to the ELN 2017 stratification, pre-HSCT WT1 levels (cutoff: 250 copies/104 ABL) more effectively segregated the post-HSCT outcomes of INT risk patients compared to ADV risk patients regarding their 2 year OS (64.2% vs. 51.5%, p = 0.099), RFS (59.4% vs. 32.4%, p = 0.003), and CIR (18.9% vs. 60.0% p < 0.001). Indeed, high WT1 levels were more prominent in INT risk patients than in ADV risk patients. Notably, FLT3-ITD had the greatest impact on post-HSCT outcomes among all the ELN 2017 criteria components; patients in the FLT3-ITD mutant subgroups exhibited the worst outcomes regardless of their allelic ratios or NPM1 status compared to the pre-HSCT WT1 level of other INT and ADV risk patients.

Newly diagnosed multiple myeloma (NDMM) frequently results in renal impairment (RI), and its natural course has not been fully elucidated in the era of novel agents. We aimed to identify the dynamics of renal function after autologous stem cell transplantation (ASCT) following induction treatment using a novel agent in transplantation-eligible NDMM patients with RI (estimated glomerular filtration rate [eGFR] ≤50 mL/min/1.73 m

Both the tumor and tumor microenvironment (TME) are crucial for pathogenesis and chemotherapy resistance in multiple myeloma (MM). Bortezomib, commonly used for MM treatment, works on both MM and TME cells, but innate and acquired resistance easily develop. By single-cell RNA sequencing (scRNA-seq), we investigated bone marrow aspirates of 18 treatment-naïve MM patients who later received bortezomib-based treatments. Twelve plasma and TME cell types and their subsets were identified. Suboptimal responders (SORs) to bortezomib exhibited higher copy number alteration burdens than optimal responders (ORs). Forty-four differentially expressed genes for SORs based on scRNA-seq data were further analyzed in an independent cohort of 90 treatment-naïve MMs, where 24 genes were validated. A combined model of three clinical variables (older age, low absolute lymphocyte count, and no autologous stem cell transplantation) and 24 genes was associated with bortezomib responsiveness and poor prognosis. In T cells, cytotoxic memory, proliferating, and dysfunctional subsets were significantly enriched in SORs. Moreover, we identified three monocyte subsets associated with bortezomib responsiveness and an MM-specific NK cell trajectory that ended with an MM-specific subset. scRNA-seq predicted the interaction of the GAS6-MERTK, ALCAM-CD6, and BAG6-NCR gene networks. Of note, tumor cells from ORs and SORs were the most prominent sources of ALCAM on effector T cells and BAG6 on NK cells, respectively. Our results indicate that the complicated compositional and molecular changes of both tumor and immune cells in the bone marrow (BM) milieu are important in the development and acquisition of resistance to bortezomib-based treatment of MM.

Our study investigated the incidence of secondary nonhematologic malignancies in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-SCT) and explored its risk compared to the general population. A population-based case cohorts with adult patients who received allo-SCT between January 2002 and December 2018 and a control cohort with matched general population were extracted from the Korean National Health Insurance Service database. Each case and control cohort included 5177 patients. With a median follow-up of 2374 days for the case cohort and 2269 days for the control cohort, the 10-year cumulative incidence rate of nonhematologic malignancy was significantly higher in the case cohort compared to the control cohort (4.23% vs 2.3%, hazard ratio [HR] 1.73, 95% confidence interval [CI] 1.32-2.25, P .001). The sub-class analysis according to cancer-site revealed significantly higher risks of 10-year cumulative incidence for cancers of head, neck and esophagus (HR 3.19, 95% CI 1.34-7.59, P = .003); cancers involving upper gastrointestinal tract (HR 3.74, 95% CI 1.58-8.85, P .001), colorectal cancer (HR 2.02, 95% CI 1.04-3.91, P = .029), thyroid cancer (HR 2.09, 95% CI 1.1-3.97, P = .012), gynecological cancer (HR 2.69, 95% CI 1.04-6.96, P = .048) in the case cohort compared to the control cohort. No significant differences were detected for cancers involving lung, mediastinum and heart, breast cancer in female, cancers of the hepatobiliary and pancreatic system and cancers associated with urological system. These findings suggest the need for enhanced screening for nonhematologic malignancies in allo-SCT recipients compared to the general population.

Arsenic trioxide (ATO) is the standard treatment for relapsed acute promyelocytic leukemia (APL). However, consensus on post-remission therapies is still lacking.We evaluated 52 patients who experienced relapse following initial treatment of APL between 2000 and 2019 at Catholic Hematology Hospital. Among them, 41 patients received reinduction treatment, 30 with ATO-based regimen, whereas 11 with conventional intensive chemotherapy (IC).The ATO reinduction group showed a significantly higher second molecular complete remission (mCR2) rate, superior neutrophil and platelet recovery, and a lower infection rate than the IC reinduction group. No significant differences were observed in survival outcomes after post-remission treatment among the ATO-based (N=19), autologous (N=12), and allogeneic (N=6) hematopoietic stem cell transplantation (HSCT) groups. In the ATO-based and autologous HSCT groups, among patients with mCR2 after ATO reinduction, nine and five patients experienced a second relapse, respectively (50.7% vs. 41.7%,Post-remission treatment outcomes of patients with relapsed APL were not significantly different, regardless of the treatment option, suggesting the feasibility of ATO-based treatment without HSCT in mCR2. Allogeneic HSCT may be an effective salvage treatment modality for patients with a second relapse. Owing to a few cases of relapsed APL, multicenter prospective studies may help elucidate the efficacy of each post-remission treatment.

The highly conserved Notch pathway transmits signals between neighboring cells to elicit distinct downstream transcriptional programs. In given contexts, Notch is a major regulator of cell fate specification, proliferation, and apoptosis, such that aberrant Notch signaling leads to a pleiotropy of human diseases, including developmental disorders and cancers. The canonical pathway signals through the transcription factor CSL (RBPJ in mammals), which forms a transcriptional activation complex with the intracellular domain of the Notch receptor and the coactivator Mastermind. CSL can also function as a transcriptional repressor by forming complexes with one of several different corepressor proteins, such as FHL1 or SHARP in mammals and Hairless in Drosophila. Recently, we identified the malignant brain tumor (MBT) family member L3MBTL3 as a bona fide RBPJ binding corepressor that recruits the repressive lysine demethylase LSD1/KDM1A to Notch target genes. Here we define the RBPJ-interacting domain (RBP-ID) of L3MBTL3 and report the 2.06 Å crystal structure of the complex formed between RBPJ, the RBP-ID of L3MBTL3 and DNA. The structure reveals the molecular interactions underlying L3MBTL3 complexation with RBPJ, which we comprehensively analyze with a series of L3MBTL3 and RBPJ mutations that span the binding interface. Compared to other RBPJ-binding proteins, we find that L3MBTL3 interacts with RBPJ via an unusual binding motif, which is sensitive to mutations throughout its RBPJ-interacting region. We also show that these disruptive mutations affect RBPJ and L3MBTL3 function in cells, providing further insights into Notch mediated transcriptional regulation.

Resilient modulus (MR) is a key factor in the Mechanistic Empirical Pavement Design Guide (MEPDG) which was adopted by INDOT in January 2009. The resilient modulus can be determined in new pavement projects from subgrade soil samples collected at the site. However, for a pavement rehabilitation project, it becomes difficult to obtain soil information, and coring for samples may not be feasible because of traffic. The literature is rich with correlations between the MR of the subgrade obtained in the laboratory with that estimated from FWD tests in the field. However, the review conducted shows very contradictory and inconsistent findings, thus existing correlations seem to apply only to the cases investigated, i.e., they are ad hoc correlations and cannot be generalized. To improve the interpretation of the FWD data and enhance the reliability of the results in Indiana, FWD and GPR tests were performed at five different road construction projects at the same locations where soil samples were collected and tested in the laboratory for resilient modulus. The selected sites included roads with rigid pavement and treated subgrade and flexible pavement with untreated subgrade. The study showed that (1) FWD backcalculation is greatly affected by pavement thickness; (2) GPR can provide actual thicknesses and can identify discrepancies between as-built and design pavement thickness; (3) for flexible pavements, a one-to-one correlation exists between FWD modulus and laboratory resilient modulus values for untreated subgrade soils; (4) MODTAG or ELMOD codes can both be used to estimate the resilient modulus of the subgrade in flexible pavements; (5) for rigid pavements, results of FWD backcalculation analysis using ELMOD or MODTAG greatly overestimate the resilient modulus of the soil, with backcalculated moduli 1.3 to 6 times higher than laboratory results; (6) ELMOD is recommended for routine analysis of FWD data, while MODTAG is recommended for research or to evaluate the quality of the data, when needed.

There are limited data on second stem cell transplantation (SCT2) outcomes with alternative donors for relapsed AML after the first stem cell transplantation (SCT1). We analyzed the outcomes of 52 adult AML patients who received SCT2 from haploidentical donors (HIT, N = 32) and double-cord blood (dCBT, N = 20) between 2008 and 2021. The HIT group received T-cell-replete peripheral blood stem cells after reduced-toxicity conditioning with anti-thymocyte globulin (ATG), while the dCBT group received myeloablative conditioning. For a median follow-up of 64.9 months, the HIT group, compared to the dCBT group, had earlier engraftment, superior 2-year overall survival (OS), disease-free survival (DFS), and non-relapse mortality (NRM) with similar relapse. Multivariate analysis demonstrated that HIT was significantly associated with better OS, DFS, and lower NRM than dCBT. Both longer remission duration after SCT1 and complete remission at SCT2 were significantly associated with a lower relapse rate. In addition, bone marrow WT1 measurable residual disease (MRD) positivity was significantly associated with inferior OS and higher relapse. This study suggests that T-cell-replete HIT with ATG-based GVHD prophylaxis may be preferred over dCBT as SCT2 for relapsed AML and that WT1-MRD negativity may be warranted for better SCT2 outcomes.

This study analyzed taste and odor profiles in broccoli stems with different methods of thermal processing using electronic tongue and electronic nose. In electronic tongue analysis, umami and bitterness were obviously changed upon thermal processing, however, saltiness, sweetness, and sourness showed slight variations. Between raw and thermally processed broccolis, microwaved broccoli showed the highest changes of tastes based on raw broccoli, however, blanched broccoli showed similar tastes to raw broccoli compared with the others. In electronic nose analysis, a total of 21 volatiles in broccolis were analyzed. Sulfur-containing volatiles were changed via thermal steps, and the generation and reduction of sulfur-containing compounds have occurred (i.e. methnaethiol, 2,4,5-trimethylthiazole). In addition, some of the thermal steps (oven-heating, microwave heating, air-frying) have occurred Maillard reaction, and thus pyridine was generated. Therefore, this study can provide flavor data in broccoli, and contribute to further research for flavor characteristics in broccoli using electronic sensors.

Background/Aims: Idiopathic multicentric Castleman disease (iMCD) comprises approximately 30% of all cases of Castleman disease. It is characterized by con stitutional symptoms, enlarged lymph nodes at multiple anatomical sites, and laboratory test abnormalities, which are primarily related to the overproduction of interleukin 6 (IL-6). Siltuximab is a human-mouse chimeric immunoglobulin G1κ monoclonal antibody against human IL-6. In view of the limited treatment options for iMCD, this study aimed to evaluate the efficacy and safety of siltux imab in the management of this condition. Methods: In this real-world retrospective study, we administered siltuximab to 15 patients with iMCD who previously received conventional chemotherapy and/or steroid pulse therapy. The median time to a durable symptomatic response was 22 days (range, 17 to 56). The serum hemoglobin and albumin levels and erythrocyte sedimentation rates significantly normalized after the first 3 months of siltux imab treatment. Lymph node involution, assessed using imaging, was relatively gradual, demonstrating a complete or partial response at 6 months. Results: On an average, the improvements in clinical, laboratory, and radiologic parameters of iMCD in responders were observed after one, three, and eight cy cles of siltuximab treatment, respectively. Siltuximab demonstrated a favorable safety profile, and prolonged treatment was well-tolerated. Conclusions: Despite the small sample size of the present study, the results are encouraging and demonstrate the potential of siltuximab as the first-line treat ment of iMCD. Further large multicenter studies are needed to evaluate the clini cal outcomes and adverse events associated with siltuximab.

In 27% of diffuse large B cell lymphoma (DLBCL) cases, bone marrow (BM), assessed by BM biopsy, is involved. BM involvement, an extranodal site involvement, affects the International Prognostic Index (IPI) score adversely. However, chromosomal abnormalities are neither included as a prognostic factor nor are they considered in the IPI risk classification category. We retrospectively analyzed 600 DLBCL patients at diagnosis for BM involvement (by both BM biopsy immunohistochemistry [BMI] with karyotyping and 18-fluorodeoxyglucose-positron emission tomography [FDG-PET] high uptake [BMP]). The BM-involved DLBCL patients identified by both BMI and BMP showed significantly inferior survival outcomes. Chromosomal abnormalities, especially complex karyotype (CK) of the involved BM, are related to much worse survival outcomes due to the inadequate treatment response including frontline auto-hematopoietic stem cell transplantation (HSCT). Therefore, CK population should either be considered for more aggressive treatment modalities, such as frontline allo-HSCT, or those further clinical trials are explored for alternative or novel treatment approaches. Furthermore, if the FDG-PET shows high possibility of marrow involvement, bilateral BM biopsy with cytogenetic evaluation should be incorporated into the routine workup for newly diagnosed DLBCL patients. This is to look for other markers of poor-risk factors, such as CK or further genetic mutations.

Although 18 F-fluorodeoxyglucose positron emission tomography (18 F-FDG PET) is commonly used for initial staging and therapeutic response evaluation in aggressive lymphomas, its prognostic utility for mantle cell lymphoma (MCL) is controversial. Therefore, we retrospectively evaluated the correlations of interim PET (iPET) and end-of-treatment PET (ePET) response with survival outcomes in 89 consecutive advanced MCL patients treated with frontline R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine and prednisolone). iPET positivity was strongly associated with inferior five-year overall survival (OS) [hazard ratio (HR) 7·84, P

Ibrutinib is highly effective in patients with relapsed or refractory mantle cell lymphoma (MCL) in major clinical trials. Although there has been a dramatic improvement in survival outcomes in the salvage setting, nonresponders to ibrutinib have a bleak prognosis. Therefore, this retrospective study was conducted to identify the most appropriate therapeutic strategy and prognosis‐related factors to predict the response of patients with relapsed or refractory MCL to ibrutinib monotherapy. Thirty‐three consecutive refractory or relapsed MCL patients treated with ibrutinib were analyzed in this study. The median overall survival (OS) and progression‐free survival (PFS) after initiation of ibrutinib were 35.1 months and 27.4 months, respectively. Risk factor analysis showed that high risk according to the Mantle Cell Lymphoma International Prognostic Index (MIPI) and nonresponse to ibrutinib at the first three cycles were significantly associated with inferior OS. Poor PFS was associated with high‐risk biologic MIPI, prior bendamustine exposure, and nonresponse to ibrutinib during the first three cycles. After ibrutinib failure, primary nonresponders had poorer OS and PFS than inconsistent responders. The overall response rate for the first salvage therapy was only 33%, with a median TTP of 3.2 months. There was no effective therapeutic strategy except for allogeneic hematopoietic stem cell transplantation (allo‐HSCT). Although ibrutinib responders exhibited favorable survival outcomes, nonresponders had a dismal prognosis. To overcome these limitations, it may be necessary to modify therapeutic strategies, such as selecting inconsistent responders for earlier allo‐HSCT., Although ibrutinib responders exhibited favorable survival outcomes, nonresponders had a dismal prognosis. To overcome these limitations, it may be necessary to modify therapeutic strategies.

In adult patients with relapsed or refractory (R/R) Philadelphia chromosome‐negative (Ph‐negative) B‐cell presursor acute lymphoblastic leukemia (BCP‐ALL), complete remission (CR) and overall survival (OS) rates are poor. We analyzed treatment outcomes and prognostic factors for 32 adult patients with R/R Ph‐negative BCP‐ALL who received blinatumomab at first salvage. Patients who achieved CR proceeded to allogeneic hematopoietic cell transplantation (allo‐HCT). At the time of blinatumomab treatment, 11 patients (34.3%) were primary refractory, 10 (31.4%) had relapsed with first CR duration (CRD1) ≥12 months, and 11 (34.3%) had relapsed with CRD1, Blinatumomab is effective for achieving good quality CR and bridging to allo‐HCT for adult patients with R/R Ph‐negative BCP‐ALL in first salvage. The role of blinatumomab in relapsed patients with short CR duration, extramedullary disease, and high tumor burden should be cautiously considered due to poor response.

A new 15-valent pneumococcal conjugate vaccine (PCV15) against serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 11A, 14, 18C, 19A, 19F, 22F, and 23F has been developed using aluminum phosphate as an adjuvant. Using the rabbit model, immunogenicity of each serotype was evaluated by measuring antigen specific antibodies and functional antibody titers and comparing them to a control vaccine, Prevnar13®. Among the shared serotypes in both PCV15 and Prevnar13®, Type 3 and 23F in PCV15 exhibited a lower opsonic index than Prevnar13®. Conversely, the other types showed greater or nearly the same immunogenic effects. Type 11A and 22F are two additional serotypes included in PCV15, and only 22F showed a reasonable opsonic index compared with other types. Type 11A exhibited a basal level fold-increase in OPA; thus, we further optimized 11A as well as 3 and 23F by controlling the polysaccharide-to-protein conjugation ratio as a variable. Antibody levels and functional antibody activities were evaluated by ELISA and OPA, and improved levels of immunogenic activities were observed for all three serotypes. In this study, we propose a new PCV15 candidate, in which the common 13 serotypes and a licensed control vaccine have equivalent efficacy while two additional serotypes showed adequate immunogenicity in the rabbit model.

Highly transparent organic-inorganic hybrid UV-curable coating formulations were obtained using silica particles with different functional groups, such as methyl group, long alkyl chain, benzene ring, isobutyl group, and fluorine group. Their surface chemical structures were analyzed by attenuated total reflection-flourier transform infrared spectroscopy and X-ray photoelectron spectroscopy. The surface morphology of the hybrid UV-curable coating formulated materials was observed by atomic force microscopy and high-resolution scanning electron microscopy. The hydrophobic and oleophobic properties were investigated by contact angle measurements using water, hexadecane, and artificial fingerprint solution. The prepared hybrid UV-curable coating materials exhibited excellent transparency, good hydrophobic, and oleophobic properties in addition to the high thermal stability and high pencil hardness up to 8H. In particular, the hybrid UV-curable coating materials with a small amount of fluorine-functionalized silica showed balanced coating performance, such as high pencil hardness (6 H) and good amphiphobic properties (static contact angles in water (135°), oil (100°), and artificial fingerprint solution (114°)), as well as excellent transparency of more than 95% of transmittance.

Objectives This study aimed to identify the natural course of cytomegalovirus (CMV)/Epstein-Barr virus (EBV) after rabbit antithymocyte globulin and cyclosporine (rATG-CsA) for aplastic anemia (AA). Methods In 113 prospectively observed AA patients treated with rATG-CsA, the CMV/EBV cohort was classified into two groups by baseline viremic status: no viremia (CMV-G1, n = 112; EBV-G1, n = 98) and the presence of viremia (CMV-G2, n = 1; EBV-G2, n = 13). Results In CMV-G1, the mean CMV load increased up to 3 months but was completely resolved from 6 months. The mean EBV load of EBV-G1 showed a peak at 1 month and then gradually decreased over time but remained detectable throughout the observation period. EBV-G2 showed fluctuating EBV dynamics. With reactivation rates of 38.4% in CMV-G1 and 62.2% in EBV-G1, a longer time to rATG-CsA from diagnosis and a lower absolute lymphocyte count at 1 month from rATG-CsA were significantly associated with CMV and EBV reactivation, respectively. The mean peak CMV and EBV loads of patients with CMV-related (3.5%) and EBV-related (0.9%) diseases were evidently higher than those of the remaining patients without CMV and EBV diseases in the respective cohort. Conclusion Considering frequent reactivation and distinct courses of CMV/EBV, virologic surveillance is recommended after rATG-CsA for AA.

Acute promyelocytic leukemia (APL) is generally held to have favorable risk, but we have observed a high incidence of early deaths caused by fatal bleeding and differentiation syndrome (DS). We retrospectively analyzed 259 APL patients from 2002 to 2014 who all received all-trans retinoic acid (ATRA) with the support of sufficient transfusions, followed by 4 days of idarubicin. High-risk status was determined as a diagnostic leukocyte count (WBCdx) >10 × 109/L (Sanz criteria). For patients with hyperleukocytosis, we sometimes conducted leukapheresis and also used hydroxyurea and prophylactic dexamethasone. Because we frequently observed patient fatalities from progressive hyperleukocytosis, we also checked the maximum leukocyte count (WBCmax) and stratified patients by their incremental ratios. The 8-week cumulative incidence of early death and DS was 13.5% and 17.8%, respectively. We found that WBCmax correlated better with early death and DS, even in the low-risk group, than WBCdx. Among the patients with WBCdx 9/L, a WBCmax >43 × 109/L correlated with early death (26.7%) and DS (40.0%). Also, having a WBCdx of 10 to 43 × 109/La that increased to a WBCmax >43 × 109/L correlated with increased early death (33.3%). The multivariate analysis revealed that a WBCmax >43 × 109/L correlated significantly with both early death and DS.