Validation of the 2022 European LeukemiaNet risk stratification for acute myeloid leukemia.

This study aimed to validate the 2022 European LeukemiaNet (ELN) risk stratification for acute myeloid leukemia (AML). A total of 624 newly diagnosed AML patients from 1998 to 2014 were included in the analysis. Genetic profiling was conducted using targeted deep sequencing of 45 genes based on recurrent driver mutations. In total, 134 (21.5%) patients had their risk classification reassessed according to the 2022 ELN risk stratification. Among those initially classified as having a favorable risk in 2017 (n = 218), 31 and 3 patients were reclassified as having intermediate risk or adverse risk, respectively. Among the three subgroups, the 2022 ELN favorable-risk group showed significantly longer survival outcomes than the other groups. Within the 2017 ELN intermediate-risk group (n = 298), 21 and 46 patients were reclassified as having favorable risk or adverse risk, respectively, and each group showed significant stratifications in survival outcomes. Some patients initially classified as having adverse risk in 2017 were reclassified into the intermediate-risk group (33 of 108 patients), but no prognostic improvements were observed in this group. A multivariable analysis identified the 2022 ELN risk stratification, age, and receiving allogeneic hematopoietic cell transplantation as significant prognostic factors for survival. The 2022 ELN risk stratification enables more precise decisions for proceeding with allogeneic hematopoietic cell transplantation for AML patients.

Ultrahigh peroxidase-like catalytic performance of Cu-N4 and Cu-N4S active sites-containing reduced graphene oxide for sensitive electrochemical biosensing.

Carbon-based nanozymes possessing peroxidase-like activity have attracted significant interest because of their potential to replace native peroxidases in biotechnology. Although various carbon-based nanozymes have been developed, their relatively low catalytic efficiency needs to be overcome to realize their practical utilization. Here, inspired by the elemental uniqueness of Cu and the doped elements N and S, as well as the active site structure of Cu-centered oxidoreductases, we developed a new carbon-based peroxidase-mimicking nanozyme, single-atom Cu-centered N- and S-codoped reduced graphene oxide (Cu-NS-rGO), which preserved many Cu-N4 and Cu-N4S active sites and showed dramatically high peroxidase-like activity without any oxidase-like activity, yielding up to 2500-fold higher catalytic efficiency (kcat/Km) than that of pristine rGO. The high catalytic activity of Cu-NS-rGO might be attributed to the acceleration of electron transfer from Cu single atom as well as synergistic effects from both Cu-N4 and Cu-N4S active sites, which was theoretically confirmed by Gibbs free energy calculations using density functional theory. The prepared Cu-NS-rGO was then used to construct an electrochemical bioassay system for detecting choline and acetylcholine by coupling with the corresponding oxidases. Using this system, both target molecules were selectively determined with high sensitivity that was sufficient to clinically determine their levels in physiological fluids. Overall, this study will facilitate the development of nanocarbon-based nanozymes and their electrochemical biosensing applications, which can be extended to the development of miniaturized devices in point-of-care testing environments.

Exploring cellular immunotherapy platforms in multiple myeloma.

Despite major advances in therapeutic platforms, most patients with multiple myeloma (MM) eventually relapse and succumb to the disease. Among the novel therapeutic options developed over the past decade, genetically engineered T cells have a great deal of potential. Cellular immunotherapies, including chimeric antigen receptor (CAR) T cells, are rapidly becoming an effective therapeutic modality for MM. Marrow-infiltrating lymphocytes (MILs) derived from the bone marrow of patients with MM are a novel source of T cells for adoptive T-cell therapy, which robustly and specifically target myeloma cells. In this review, we examine the recent innovations in cellular immunotherapies, including the use of dendritic cells, and cellular tools based on MILs, natural killer (NK) cells, and CAR T cells, which hold promise for improving the efficacy and/or reducing the toxicity of treatment in patients with MM.

Prognostic analysis according to European LeukemiaNet 2022 risk stratification for elderly patients with acute myeloid leukemia treated with decitabine.

OBJECTIVES: This study aimed to evaluate the prognostic significance of the revised European LeukemiaNet (ELN)-2022 risk stratification model for 123 elderly acute myeloid leukemia (AML) patients treated with decitabine chemotherapy. RESULTS: Based on the ELN-2022 risk stratification, 15 (12.2%), 51 (41.5%), and 57 (46.3%) patients were classified as having favorable, intermediate, and high-risk AML, respectively. In comparison with the ELN-2017 risk stratification, the ELN-2022 risk stratification re-assigned 26 (21.1%) and three (2.4%) patients to the adverse and favorable risk groups, respectively. Survival analysis revealed distinctive overall survival (OS) outcomes among the ELN-2022 risk groups (6-month OS rate: 73.3%, 52.9%, and 47.7% for favorable, intermediate, and adverse risk, respectively; P = 0.101), with a parallel trend observed in the event-free survival (EFS) (6-month EFS rate: 73.3%, 52.9%, and 45.6% for favorable, intermediate, and adverse risk, respectively; P = 0.049). Notably, both OS and EFS in the favorable risk group were significantly superior in comparison to that of the adverse risk group (OS: P = 0.040, EFS: P = 0.030). Although the ELN-2022 C-index (0.559) was greater than the ELN-2017 C-index (0.539), the result was not statistically significant (P = 0.059). Based on the event net reclassification index, we consistently observed significant improvements in the ELN-2022 risk stratification for overall survival (0.21 at 6 months). CONCLUSION: In conclusion, the revised ELN-2022 risk stratification model may have improved the risk classification of elderly AML patients treated with hypomethylating agents compared to the ELN-2017 risk stratification model.

Prognostic Significance Of Sequential 18f-fdg Pet/Ct During Frontline Treatment Of Peripheral T Cell Lymphomas.

BACKGROUND/AIMS: The prognostic significance of 18F-fluorodeoxyglucose (FDG)-positron emission tomography-computed tomography (PET/CT) in peripheral T-cell lymphomas (PTCLs) are controversial. We explored the prognostic impact of sequential 18F-FDG PET/CT during frontline chemotherapy of patients with PTCLs. METHODS: In total, 143 patients with newly diagnosed PTCLs were included. Sequential 18F-FDG PET/CTs were performed at the time of diagnosis, during chemotherapy, and at the end of chemotherapy. The baseline total metabolic tumor volume (TMTV) was calculated using the the standard uptake value with a threshold method of 2.5. RESULTS: A baseline TMTV of 457.0 cm3 was used to categorize patients into high and low TMTV groups. Patients with a requirehigh TMTV had shorter progression-free survival (PFS) and overall survival (OS) than those with a low TMTV (PFS, 9.8 vs. 26.5 mo, p = 0.043; OS, 18.9 vs. 71.2 mo, p = 0.004). The interim 18F-FDG PET/CT response score was recorded as 1, 2-3, and 4-5 according to the Deauville criteria. The PFS and OS showed significant differences according to the interim 18F-FDG PET/CT response score (PFS, 120.7 vs. 34.1 vs. 5.1 mo, p < 0.001; OS, not reached vs. 61.1 mo vs. 12.1 mo, p < 0.001). CONCLUSION: The interim PET/CT response based on visual assessment predicts disease progression and survival outcome in PTCLs. A high baseline TMTV is associated with a poor response to anthracycline-based chemotherapy in PTCLs. However, TMTV was not an independent predictor for PFS in the multivariate analysis.

Real-world outcome of patients with extensively pretreated multiple myeloma who were treated with selinexor and dexamethasone: a Korean multicenter retrospective analysis.

The outcomes of patients with myeloma after exposed to penta-classes are extremely poor. Selinexor is the first approved exportin inhibitor for those patients, but intractable toxicities may limit its use. This retrospective study evaluated the real-world efficacy and safety of selinexor plus dexamethasone (XD) and involved 48 patients with multiple myeloma, who were treated from November 2020 to October 2022. Their median age was 64 years, and the median number of prior lines of therapy was 6. The overall response rate was 25%, and the median progression-free survival (PFS) was 2.1 months (95% confidence interval (CI), 1.7-2.5). Patients on a reduced initial dose, delayed treatment, and dose reduction had better PFS. After XD treatment failure, 17 patients received subsequent therapy and had a median PFS of 2.4 months. The median overall survival was 4.6 months (95% CI, 2.3-6.9). Among the patients, 12 (25%) and 17 (35%) experienced dose reduction and delayed treatment, respectively. Our data show that the real-world efficacy of XD treatment in heavily pretreated patients was modest and that improving treatment adherence through reducing initial doses or delaying treatments may improve patient outcomes.

Incidence of invasive fungal diseases in inflammatory bowel disease patients: A nationwide study in South Korea.

BACKGROUND: Limited reports exist regarding invasive fungal diseases (IFDs) in inflammatory bowel disease (IBD) patients. OBJECTIVES: This study aims to investigate the incidence and risk factors of IFDs, specifically invasive candidiasis, aspergillosis and pneumocystosis, in IBD patients in South Korea using nationwide data. PATIENTS/METHODS: A population-based retrospective cohort of 42,913 IBD patients between January 2010 and December 2018 was evaluated using the Health Insurance Review and Assessment database. The primary outcome was the incidence of IFDs, including invasive candidiasis, aspergillosis and pneumocystosis, while the secondary outcome involved analysing the risk factors associated with each specific infection. RESULTS: The study included a total of 42,913 IBD patients, with 29,909 (69.7%) diagnosed with ulcerative colitis (UC) and 13,004 (30.3%) diagnosed with Crohn's disease (CD). IFDs occurred in 166 IBD patients (0.4%), with 93 cases in UC patients and 73 cases in CD patients. The incidence rates of invasive candidiasis, aspergillosis and pneumocystosis in IBD patients were 0.71 per 1000 person-years (PYs), 0.15 per 1000 PYs and 0.12 per 1000 PYs, respectively. The cumulative incidence of invasive candidiasis (adjusted p-value <.001) and Pneumocystosis (adjusted p-value = .012) was found to be higher in CD patients than in UC patients. Each IFD had different risk factors, including IBD subtypes, age at diagnosis, anti-tumour necrotic factor agents or the Charlson comorbidity index. CONCLUSION: Based on nationwide data in South Korea, this study shows that IFDs occur consistently in patients with IBD, albeit with a low frequency.

Outcome of Multiple Myeloma Patients With Hepatitis B Surface Antigen: Korean Multiple Myeloma Working Party 2103 Study.

BACKGROUND: Hepatitis B virus reactivation (HBVr) is a well-known complication of systemic chemotherapy for particularly hematologic malignancies in HBV carriers. We performed a multicenter retrospective study to investigate the incidence and risk factors of HBVr in patients with hepatitis B surface antigen (HBsAg)-positive multiple myeloma (MM). METHODS: We included 123 patients with HBsAg-positive MM who had received systemic therapy. The primary objective of the study was to evaluate the incidence of HBVr in patients with HBsAg-positive MM. RESULTS: The median age was 59 years, and 72 patients were male. With a median follow-up duration of 41.4 months, there were 43 instances of HBVr in 35 patients (28.5%): 29 treatment-related HBVr occurred during 424 treatments. Treatments containing antiviral prophylaxis were associated with a significantly lower incidence of HBVr compared to those without (14.4% vs. 1.9%, P < 0.001). Moreover, treatment with cyclophosphamide (P = 0.002) and doxorubicin (P = 0.053) were risk factors for HBVr; stem cell transplantation was not associated with HBVr. There was no significant difference in overall survival between patients with and without HBVr (P = 0.753) and myeloma progression was the major cause of death. CONCLUSION: Considering the low incidence of HBVr in patients who had received antiviral prophylaxis, HBsAg-positivity should not impede patients from receiving optimal antimyeloma treatment or participating in clinical trials.

Efficacy of natural killer cell therapy combined with chemoradiotherapy in murine models of head and neck squamous cell carcinoma.

BACKGROUND AIMS: Natural killer (NK) cell-based cancer immunotherapy is effective when combined with other treatment modalities such as irradiation and chemotherapy. NK cell's antitumor function to treat solid tumor, including head and neck squamous cell carcinoma (HNSCC), has been targeted recently. This study assessed NK cell recruitment in response to chemoradiation therapy (CRT) in HNSCC. METHODS: Ex vivo expansion of NK cell, flow cytometry, cell viability assay, cytotoxicity assay, immunohistochemistry, and animal model were performed. RESULTS: Mouse NK cells were recruited to the tumor site by CRT in a nude mouse model. Furthermore, expanded and activated human NK cells (eNKs) were recruited to the tumor site in response to CRT, and CRT enhanced the anti-tumor activity of eNK in an NOD/SCID IL-2Rγnull mouse model. Various HNSCC cancer cell lines exhibited different NK cell ligand activation patterns in response to CRT that correlated with NK cell-mediated cytotoxicity. CONCLUSIONS: Identifying the activation patterns of NK cell ligands during CRT might improve patient selection for adjuvant NK cell immunotherapy combined with CRT. This is the first study to investigate the NK cell's antitumor function and recruitment with CRT in HNSCC mouse model.

Prediction model of subacromial pain syndrome in assembly workers using shoulder range of motion and muscle strength based on support vector machine.

Subacromial pain syndrome (SAPS) is the most common upper-extremity musculoskeletal problem among workers. In this study, a machine learning model was built to predict and classify the presence or absence of SAPS in assembly workers with shoulder joint range of motion (ROM) and muscle strength data using support vector machine (SVM). Permutation importance was used to determine important variables for predicting workers with or without SAPS. The accuracy of the support vector classifier (SVC) polynomial model for classifying workers with SAPS was 82.4%. The important variables in model construction were internal rotation and abduction of shoulder ROM and internal rotation of shoulder muscle strength. It is possible to accurately perform SAPS classification of workers with relatively easy-to-obtain shoulder ROM and muscle strength data using this model. In addition, preventing SAPS in workers is possible by adjusting the factors affecting model building using exercise or rehabilitation programs.Practitioner summary: This study aimed to create a machine learning model that can predict and classify SAPS using shoulder ROM and muscle strength and identify the variables that are of high importance in model construction. This model could be used to predict or classify workers' SAPS and manage or prevent SAPS.

The Prevalence and Risk Factors of Clostridioides difficile Infection in Inflammatory Bowel Disease: 10-Year South Korean Experience Based on the National Database.

BACKGROUND: Few studies evaluate the epidemiology and risk factors of Clostridioides difficile infection (CDI) in Asian patients with inflammatory bowel disease (IBD). We investigated the year-end prevalence, cumulative incidence and risk factors of CDI in Asian patients with IBD using a large-scale population-based cohort in Korea. METHODS: Using the National Health Insurance Service database, we identified patients with IBD and sex- and age-matched controls without IBD between 2008 and 2018. The year-end prevalence and cumulative incidence of CDI were compared among patients with Crohn's disease (CD) and ulcerative colitis (UC) with controls. The risk factors for CDI were evaluated. RESULTS: Among the 54,836 patients with IBD and 109,178 controls, CDI occurred in 293 patients with IBD and 87 controls. The annual year-end prevalence of CDI in patients with IBD increased from 8.6/10,000 persons in 2008 to 22.3/10,000 persons in 2018. The risk of CDI was higher in both patients with CD and UC than that in the matched controls (hazard ratio [HR], 7.285; 95% confidence interval [CI], 5.388-9.851; P < 0.001 and HR, 7.487; 95% CI, 5.796-9.670; P < 0.001, respectively). Among patients with IBD, the risk factors for CDI included older age, female sex, high Charlson comorbidity index score, and IBD-related medications including oral 5-aminosalicylic acid, immunomodulatory agents, biologics, and steroids used for > 90 days. CONCLUSION: The risk of CDI in Korean patients with IBD was approximately seven times higher than that in controls without IBD, and the annual year-end prevalence of CDI continuously increased from 2008 to 2018.

Adoptive NK Cell Therapy - a Beacon of Hope in Multiple Myeloma Treatment.

Major advances in the treatment of multiple myeloma (MM) have been achieved by effective new agents such as proteasome inhibitors, immunomodulatory drugs, or monoclonal antibodies. Despite significant progress, MM remains still incurable and, recently, cellular immunotherapy has emerged as a promising treatment for relapsed/refractory MM. The emergence of chimeric antigen receptor (CAR) technology has transformed immunotherapy by enhancing the antitumor functions of T cells and natural killer (NK) cells, leading to effective control of hematologic malignancies. Recent advancements in gene delivery to NK cells have paved the way for the clinical application of CAR-NK cell therapy. CAR-NK cell therapy strategies have demonstrated safety, tolerability, and substantial efficacy in treating B cell malignancies in various clinical settings. However, their effectiveness in eliminating MM remains to be established. This review explores multiple approaches to enhance NK cell cytotoxicity, persistence, expansion, and manufacturing processes, and highlights the challenges and opportunities associated with CAR-NK cell therapy against MM. By shedding light on these aspects, this review aims to provide valuable insights into the potential of CAR-NK cell therapy as a promising approach for improving the treatment outcomes of MM patients.

Novel π-Extended Indolocarbazole-Based Deep-Blue Fluorescent Emitter with Remarkably Narrow Bandwidth for Solution-Processed Organic Light-Emitting Diodes.

In solution-processed organic light-emitting diodes (OLEDs), achieving high color purity and efficiency is as important as that in vacuum processes. Emitters suitable for solution processing must have excellent solubility in organic solvents, high molecular weight, and compatibility with the host materials. In this study, we synthesized a deep-blue emitter that satisfies the above conditions by introducing a 1,4-bis(indolo[3,2,1-jk]carbazol-2-yl)benzene-based planar emitting core (DICz) structure and four 3,6-di-tert-butyl-9-phenyl-9H-carbazole (tCz) peripheral units, namely, 4tCz-DICz. A comparative compound, 4Hex-DICz, incorporating hexyl phenyl groups was synthesized. In contrast to 4Hex-DICz, 4tCz-DICz exhibited exceptional solubility in organic solvents and superior film-forming properties attributed to the presence of tCz units. Additionally, in the film state, the effective encapsulation of the emitting core (DICz) by the tCz units in 4tCz-DICz helps prevent undesirable molecular aggregation. The solution-processed OLEDs employing the CH-2D1 film, doped with 5 wt % 4tCz-DICz as the emitting layer, exhibited a deep-blue emission at 424 nm, characterized by a narrow bandwidth of 22 nm, and achieved a maximum external quantum efficiency (EQE) of approximately 4.0%. In contrast, the 4Hex-DICz-based device demonstrated an EQE of 2.91%. Consequently, we have successfully demonstrated that the introduction of four bulky tCz units into the DICz core is a promising molecular design strategy for the development of soluble indolocarbazole-based emitters, especially those used in high-performance deep-blue fluorescent OLEDs.

Open-labeled, multicenter phase II study of prophylactic administration of pegylated granulocyte colony-stimulating factor in relapsed or refractory multiple myeloma who received pomalidomide-based regimens (KMM170).

Introduction: Pegylated granulocyte colony-stimulating factor (G-CSF) has been widely used for preventing febrile neutropenia in various types of cancer treatment. In the present study, we prospectively evaluated the safety and efficacy of pegfilgrastim as a primary prophylaxis of febrile neutropenia and infection among patients with relapsed refractory multiple myeloma (RRMM) treated with pomalidomide-based regimens. Methods: Thirty-three patients with RRMM who received pomalidomide and dexamethasone (Pd) with or without cyclophosphamide (PCd) were enrolled in this study. Twenty-eight patients were treated with PCd and 5 patients were treated with Pd. All patients were given pegfilgrastim subcutaneously with a single administration performed on the first day of each cycle as primary prophylaxis until the fourth cycle. Results: The median age of the patients was 75 (range 56-85), and the median prior line of therapy was 2 (range 2-6). Seventeen patients (51.5%) had any grade of neutropenia and 20 (60.6%) had any grade of thrombocytopenia before starting pomalidomide treatment. During the 4 cycles of treatment, grade 3 or more neutropenia occurred in 17 patients (51.5%), and 4 (12.1%) experienced grade 3 or more febrile neutropenia. Grade 3 or more infections occurred in 5 patients (15.2%). Interestingly, the patients with markedly increased ANC of more than 2 x 109/L compared to baseline ANC after 7 days of pegfilgrastim at 1st cycle of treatment showed a significantly lower incidence of grade 3-4 neutropenia. The most common adverse event of pegfilgrastim was fatigue, and all the adverse events caused by pegfilgrastim were grade 1 or 2. And there was no significant change in the immune cell population and cytokines during the administration of pegfilgrastim. Discussion: Considering that this study included elderly patients with baseline neutropenia, pegylated G-CSF could be helpful to prevent severe neutropenia, febrile neutropenia, or infection in patients with RRMM.

Busulfan plus melphalan versus high-dose melphalan as a conditioning regimen for autologous stem cell transplantation in multiple myeloma with high-risk features (KMM 2015).

Despite the development of effective agents for multiple myeloma (MM), the management of patients with high-risk MM (HRMM) is challenging. High-dose treatment followed by autologous stem cell transplantation (ASCT) is regarded as upfront treatment for transplant-eligible patients with HRMM. In the present study, we retrospectively investigated the efficacies of two conditioning regimens for upfront ASCT in newly diagnosed patients with MM and high-risk features: high-dose melphalan (HDMEL; 200 mg/m2) and busulfan plus melphalan (BUMEL). In total, 221 patients underwent ASCT between May 2005 and June 2021; among these 221 patients, 79 had high-risk cytogenetic abnormalities. In patients with high-risk cytogenetics, BUMEL showed a tendency toward longer overall survival (OS) and progression-free survival (PFS) compared to HDMEL (median OS; not reached vs. 53.2 months; P = 0.091, median PFS; not reached vs. 31.7 months; P = 0.062). Additionally, multivariate analysis revealed that BUMEL was significantly associated with PFS (hazard ratio = 0.37, 95% confidence interval = 0.15-0.89, P = 0.026). We compared BUMEL with HDMEL in patients with other high-risk features, such as high lactate dehydrogenase level, extramedullary disease, and poor response to frontline therapy. Notably, among patients with less than very good partial response (VGPR) to frontline therapy, median PFS was significantly longer in the BUMEL group than in the HDMEL group (55.1 vs. 17.3 months, respectively; P = 0.011). These findings indicate that BUMEL may be an effective conditioning regimen for upfront ASCT in MM patients with high-risk cytogenetics; BUMEL may be more appropriate than HDMEL for patients with less than VGPR to frontline therapy.

Risk Factors for the Occurrence and Severity of Vertebral Fractures in Inflammatory Bowel Disease Patients: A Nationwide Population-Based Cohort Study.

BACKGROUND: The risk of vertebral fractures is increased in inflammatory bowel disease (IBD) patients. However, whether the severity of vertebral fractures differs between IBD patients and the general population, or between patients with Crohn's disease (CD) and ulcerative colitis (UC), is unknown. METHODS: We investigated risk factors associated with the occurrence and severity of vertebral fractures in IBD patients using The National Healthcare Insurance Service (NHIS) database. We defined the patients who underwent vertebroplasty or kyphoplasty after being diagnosed with a vertebral fracture as having a severe vertebral fracture than those with only diagnosis codes. RESULTS: From 2008 to 2018, there were 33,778 patients with IBD (24,370 UC patients and 9,408 CD patients) and 101,265 patients in the reference population. The incidence rate ratio of vertebral fractures in the IBD patients was 1.27 per 1,000 person-years (95% confidence interval [CI], 1.26-1.27). The risk of vertebral fracture was higher in CD and UC patients than in the matched reference group (hazard ratio [HR], 1.59; 95% CI, 1.31-1.92; P < 0.001 and HR, 1.26; 95% CI, 1.14-1.41; P < 0.001, respectively). In a multivariate analysis, the occurrence of vertebral fracture was associated with CD (HR, 1.31; 95% CI, 1.08-1.59; P = 0.006), older age (CD: HR, 1.09; 95% CI, 1.08-1.09; P < 0.001 and UC: HR, 1.09; 95% CI, 1.08-1.09; P < 0.001), female sex (CD: HR, 1.81; 95% CI, 1.63-2.01; P < 0.001 and UC: HR, 2.02; 95% CI, 1.83-2.22; P < 0.001), high Charlson Comorbidity Index (CCI) score (CD: HR, 1.42; 95% CI, 1.23-1.63; P < 0.001 and UC: HR, 1.46; 95% CI, 1.29-1.65, P < 0.001), and long-term steroid use (CD: HR, 3.71; 95% CI, 2.84-3.37; P < 0.001 and UC: HR, 3.88; 95% CI, 3.07-4.91; P < 0.001). The severity of vertebral fractures was associated with IBD (CD: HR, 1.82; 95% CI, 1.17-2.83; P = 0.008 and UC: HR, 1.49; 95% CI, 1.17-1.89; P < 0.001) and older age (HR, 1.06; 95% CI, 1.05-1.07; P < 0.001). CONCLUSION: Vertebral fractures occur frequently and more severely in IBD patients, particularly those with CD. Therefore, we suggest monitoring of bone density, regular vitamin D supply, and reducing the use of corticosteroids to prevent vertebral fractures in IBD patients who are older, female, or have comorbidities.

The prognostic impact of reduced variant burden in elderly patients with acute myeloid leukemia treated with decitabine.

BACKGROUND/AIMS: We evaluated the role of next-generation sequencing (NGS)-based disease monitoring for elderly patients diagnosed with acute myeloid leukemia (AML) who received decitabine therapy. METHODS: A total of 123 patients aged > 65 years with AML who received decitabine were eligible. We analyzed the dynamics of variant allele frequency (VAF) in 49 available follow-up samples after the fourth cycle of decitabine. The 58.6% VAF clearance (Δ, [VAF at diagnosis - VAF at follow-up] × 100 / VAF at diagnosis) was the optimal cut-off for predicting overall survival (OS). RESULTS: The overall response rate was 34.1% (eight patients with complete remission [CR], six of CR with incomplete hematologic recovery, 22 with partial responses, and six with morphologic leukemia-free status). Responders (n = 42) had significantly better OS compared with non-responders (n = 42) (median, 15.3 months vs. 6.5 months; p < 0.001). Of the 49 patients available for follow-up targeted NGS analysis, 44 had trackable gene mutations. The median OS of patients with ΔVAF ≥ 58.6% (n=24) was significantly better than that of patients with ΔVAF < 58.6% (n = 19) (20.5 months vs. 9.8 months, p = 0.010). Moreover, responders with ΔVAF ≥ 58.6% (n = 20) had a significantly longer median OS compared with responders with VAF < 58.6% (n = 11) (22.5 months vs. 9.8 months, p = 0.004). CONCLUSION: This study suggested that combining ΔVAF ≥ 58.6%, a molecular response, with morphologic and hematologic responses can more accurately predict OS in elderly AML patients after decitabine therapy.

Graphitic carbon nitride metal-free photocatalyst for the simultaneous removal of emerging pharmaceutical pollutants in wastewater.

The presence of pharmaceutical pollutants in water has emerged as a significant public health concern due to their potential adverse impacts, including the development of antibiotic resistance. Consequently, advanced oxidation processes based on photocatalysis have garnered considerable attention for treating pharmaceutical contaminants in wastewater. In this study, graphitic carbon nitride (g-CN), a metal-free photocatalyst, was synthesized by the polymerization of melamine and assessed as a potential candidate for the photodegradation of acetaminophen (AP) and carbamazepine (CZ) in wastewater. Under alkaline conditions, g-CN demonstrated high removal efficiencies of 98.6% and 89.5% for AP and CZ, respectively. The relationships between degradation efficiency and catalyst dosage, initial pharmaceutical concentration, and photodegradation kinetics were investigated. Increasing the catalyst dose facilitated the removal of antibiotic contaminants, with an optimum catalyst dose of 0.1 g, achieving a photodegradation efficiency of 90.2% and 82.7% for AP and CZ, respectively. The synthesized photocatalyst removed over 98% of AP (1 mg/L) within 120 min, with a rate constant of 0.0321 min-1, 2.14 times faster than that of CZ. Quenching experiments revealed that g-CN was active under solar light and generated highly reactive oxidants such as hydroxyl (•OH) and superoxide (•O2-). The reuse test confirmed the good stability of g-CN for treating pharmaceuticals during three repeated cycles. Finally, the photodegradation mechanism and environmental impacts were discussed. This study presents a promising approach for treating and mitigating pharmaceutical contaminants in wastewater.

Assessment of Fatigue and Associated Factors in Patients with Inflammatory Bowel Disease: A Questionnaire-Based Study.

Although fatigue is common in patients with inflammatory bowel disease (IBD), it often goes unrecognized and untreated. We investigated the degree of fatigue and associated factors in patients with IBD. A multicenter study involving 147 IBD patients was conducted at five academic hospitals from August 2019 to December 2021. Fatigue was evaluated using the validated Korean version of the Multidimensional Fatigue Inventory (MFI-K). Among 97 ulcerative colitis patients and 50 Crohn's disease patients, the mean total MFI-K score was 59.0 ± 5.5, which corresponded to a moderate-to-severe level of fatigue. Moderate-to-severe disease activity was found to be significantly associated with a higher general and physical fatigue subscale MFI-K score compared to remission-to-mild disease activity (17.6 ± 1.7 vs. 16.7 ± 2.0, p = 0.009), while the use of biologics was associated with a lower total MFI-K score (57.3 ± 5.0 vs. 59.5 ± 5.5, p = 0.031). In multiple linear regression, the total MFI-K score was positively correlated with a history of surgery for IBD, while it was negatively correlated with the use of biologics. Depression was positively correlated with the reduced motivation subscale score. The degree of fatigue in patients with IBD was high. Disease activity, the use of biologics, a history of surgery for IBD, and depression were associated with fatigue.