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Background: This study examined gender differences in occupational stress, depressive symptoms, and suicidal ideation by considering the potential moderating effect of grit on Korean employees., Methods: A total of 11,369 participants (7,735 men and 3,634 women) aged 19-65 years, employed across 18 private companies and local government organizations in Korea, completed questionnaires including the Short Grit Scale, Korean Occupational Stress Scale, and Center for Epidemiologic Studies Depression Scale between April 2020 and March 2022. Suicidal ideation was assessed based on its presence or absence. Mediation and moderation analyses were performed using the Statistical Package for the Social Sciences PROCESS macro., Results: Depressive symptoms partially mediated the relationship between occupational stress and suicidal ideation in male employees, whereas depressive symptoms fully mediated the relationship in female employees. Grit moderated the relationship between depressive symptoms and suicidal ideation in male employees but not in female employees. Furthermore, the moderated mediating effect of grit in male employees on the relationship between occupational stress and suicidal ideation provided less protection in cases of severe depression. The cross-sectional design does not allow for causal inferences., Conclusion: These findings contribute to understanding of the gender differences in the impact of depressive symptoms on the relationship between occupational stress and suicidal ideation, as well as the protective effect of grit. These findings highlight the need for gender-specific approaches to prevent suicidal ideation among employees., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Purpose: TP53 mutations are common in head and neck squamous cell carcinoma (HNSCC). We evaluated their clinical impact in patients treated with targeted agents or immunotherapy in the KCSG HN15-16 TRIUMPH trial., Materials and Methods: We analyzed clinical characteristics and outcomes of patients with TP53 mutations in the TRIUMPH trial, a multicenter, biomarker-driven umbrella trial in Korea. Patients were assigned to treatment groups based on genomic profiles: Group 1, alpelisib; Group 2, poziotinib; Group 3, nintedanib; and Group 4, abemaciclib. If there was no identifiable target, the patients were allocated to Group 5 (durvalumab ± tremelimumab)., Results: TP53 mutations were detected in 116/179 patients (64.8%), more frequently in HPV-negative and non-oropharyngeal cancers. Patients with TP53 mutations exhibited shorter progression-free survival (PFS) than TP53 wild-type in all the patients (1.7 vs. 3.8 months, p=0.002) and in those who received targeted treatments (2.5 vs. 7.3 months, p=0.009). Furthermore, TP53 mutations were strongly associated with poor overall survival than TP53 wild-type in all the patients (11.1 vs. 28.8 months, p=0.005) and in Group 5 (8.1 vs. 33.0 months, p=0.001)., Conclusion: TP53 mutations were associated with aggressive clinical characteristics and poor survival, particularly in HNSCC patients treated with immunotherapy.

Antipsychotic polypharmacy is commonly used in clinical settings, with a growing trend in using long-acting injections to mitigate many side effects of polypharmacy. A previous study demonstrated that long-acting aripiprazole once-monthly (AOM) injection increased treatment adherence, restored functionality, and improved symptoms. However, there is insufficient evidence to demonstrate the therapeutic effects of AOM in polypharmacy practice. This observational study aimed to investigate the real-world clinical benefits and effectiveness of AOM by assessing changes in drug dosage, the number of drugs, clinical functioning, psychotic symptoms, and the duration of drug efficacy. Study participants were recruited from eight study sites, with the baseline visit marking the initiation of drug treatment. Clinical and demographic data were collected from medical records at screening, baseline, and months 1, 3, 6, 9, and 12. Over 12 months, we analyzed changes in drug dosage, the number of drugs, and scores of the Positive and Negative Syndrome Scale-6 (PANSS-6), Global Assessment of Functioning (GAF), and Clinical Global Impression-Severity (CGIS). Data from 139 participants were analyzed. Total 12-month antipsychotic doses calculated in chlorpromazine equivalents (CPE) were reduced by 32.6%. A comparison of total monthly antipsychotic doses in CPE between the first and last months showed a 24.6% reduction in the dose. Additionally, the quantity of benzodiazepine tablets/capsules, total benzodiazepine doses calculated in lorazepam equivalents, and quantity of tablets/capsules of mood stabilizers, anticholinergics, and beta blockers were significantly reduced. GAF scores increased by 14.1% over 12 months, and PANSS-6 total scores reduced by 17.3% over 12 months, with significant differences observed from month 1 and baseline, respectively. The scores steadily improved until month 9 compared to those of the previous months, continuing to improve through month 12. The CGI-S score reduced by 14.3% over 12 months, showing a significant decrease from month 1 and a steady improvement until month 6, maintaining this improvement until month 12. In conclusion, this study demonstrated the early effectiveness of AOM in treating Korean patients with schizophrenia on polypharmacy. AOM improved function and clinical symptoms in patients with schizophrenia from treatment onset and caused a decrease in the quantity and dosage of drugs taken by the patients., Competing Interests: Declaration of competing interest The authors have no conflicts of interest to declare., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Purpose: The role of neoadjuvant chemotherapy in locally advanced sinonasal squamous cell carcinoma (SNSCC) has not been established prospectively. We conducted a phase II trial of neoadjuvant chemotherapy (NAC) with docetaxel/cisplatin/5-fluorouracil (TPF) in this population., Materials and Methods: Eligible patients had unresectable, locally advanced SNSCC, defined as T3/4 stage or potential compromise of critical organ function on surgery. Three TPF (docetaxel 75 mg/m2 and cisplatin 75 mg/m2 on day 1, 5-fluorouracil 1,000 mg/m2 on days 1-4 every 3 weeks) cycles were administered with prophylactic pegteograstim. The primary outcome was the overall response rate (ORR); the secondary outcomes included 2-year progression-free survival (PFS), eyeball preservation rate, and safety., Results: Among 28 patients screened, 25 were evaluable for efficacy (one screen-failure; two evaluable for safety only). The confirmed ORR was 72.0%. The definitive post-NAC treatment comprised chemoradiotherapy (n=15) and surgery (n=10). With a median follow-up of 25.5 months, median PFS was not reached and the 2-year PFS rate was 60.4%. Response to NAC was related to prolonged PFS (p=0.038). No patient underwent eyeball exenteration at the data cutoff point. Treatment-related adverse events of grade ≥3 were neutropenia (48.1%) including febrile neutropenia (14.8%), followed by acute kidney injury (22.2%), nausea/vomiting (11.1%), anemia (7.4%), thrombocytopenia (7.4%), and enterocolitis (3.7%)., Conclusion: TPF NAC showed a promising efficacy and might help preserve critical structures in this population, which needs to be validated in a large prospective trial (KCT0003377).

Background: Individuals with borderline personality traits are known to have disturbed representations of self and others. Specifically, an unstable self-identity and difficulties distinguishing between self and others can impair their mentalizing abilities in interpersonal situations. However, it is unclear whether these traits are linked to differences in neural representation of self and others., Methods: In this study involving 156 young adults, changes in neural function during self-other processing were measured using a Functional Near-Infrared Spectroscopy (fNIRS) task and a self-report survey. During the fNIRS task, participants were asked about their own traits, others' traits, how they believed others perceived them, and the basic meaning of words. The study aimed to determine whether the degree of neural differentiation between the task conditions was related to borderline personality traits., Result: The study found that traits indicative of identity instability could be predicted by similarities in task-dependent connectivity. Specifically, the neural patterns when individuals estimated how others perceived them were more similar to the patterns when they judged their own traits., Conclusions: These findings suggest that borderline personality traits related to identity issues may reflect difficulties in distinguishing between neural patterns when processing self and other information., Competing Interests: Declaration of competing interest The authors report no competing interests to declare., (Copyright © 2024 Elsevier B.V. All rights reserved.)

Background: Suicide remains a significant global public health challenge, with hanging as the most prevalent suicide method in South Korea. This study aimed to determine diagnostic markers confirming suicidal hanging-associated deaths., Methods: In this prospective study, hemorrhages at the periosteal-clavicular origin of the sternocleidomastoid (SCM) muscles were compared among suicidal hanging, manual strangulation, and ligature strangulation cases. This study included 211 cases of suicide by hanging, and a control group of 50 individuals who underwent cardiopulmonary resuscitation but died of other causes. Additionally, nine cases of ligature strangulation and six cases of manual strangulation were analyzed. Postmortem examinations were conducted, and clavicular hemorrhages were histologically evaluated. Statistical analyses were performed using the χ² test., Results: Hemorrhages at the periosteal-clavicular origin of the SCM were observed in 178 of the 211 hanging cases (84.4%). The highest frequency of clavicular hemorrhage was found in typical hanging cases with complete suspension. Among the 50 control cases, only three showed hemorrhages in the clavicular region, but these were extravasations in the adjoining soft tissue, not in the periosteum. In cases of manual and ligature strangulation, SCM hemorrhages were found within the muscle tissue and were not of periosteal-clavicular origin., Conclusion: Hemorrhage at the periosteal-clavicular origin of the SCM is a significant finding in suicidal hanging and serves as a potential pathognomonic marker for confirming cases of suicidal hanging. The study revealed a statistically significant association between the type of hanging, completeness of body suspension, and the occurrence of these hemorrhages. Cardiopulmonary resuscitation does not cause a hemorrhage at this location., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: Overexposure to ultraviolet (UV) radiation accelerates skin aging, resulting in wrinkle formation, reduced skin elasticity, and hyperpigmentation. UV irradiation induces increased matrix metalloproteinases (MMPs) that degrade collagen in the extracellular matrix. Skin aging is also accompanied by epigenetic alterations such as promoter methylation by DNA methyltransferases, leading to the activation or suppression of gene expression. Although carnitine acetyltransferase (CRAT) is implicated in aging, the effect of UV on the expression of CRAT and regulatory mechanisms of UV-induced MMP-1 expression remain unknown., Objective: We investigated changes in CRAT expression upon UV irradiation and its effect on MMP-1 expression., Methods: Primary human dermal fibroblasts were UV irradiated with either control or 5-AZA-dC. CRAT knockdown or overexpression was performed to investigate its effect on MMP-1 expression. The mRNA level was analyzed by quantitative real-time PCR, and protein level by western blotting., Results: The expression of CRAT was decreased in UV-irradiated human skin in vivo and in human dermal fibroblasts in vitro. CRAT was downregulated upon UV irradiation by hypermethylation, and treatment with 5-Aza-2'-deoxycytidine, a DNA methyltransferase inhibitor, reversed UV-induced downregulation of CRAT. CRAT knockdown activated the JNK, ERK, and p38 MAPK signaling pathways, which increased MMP-1 expression. Stable overexpression of CRAT alleviated UV-induced MMP-1 induction., Conclusion: CRAT downregulation caused by promoter hypermethylation may play an important role in UV-induced skin aging via upregulation of MMP-1 expression., Competing Interests: Declaration of Competing Interest The authors have no conflict of interest to declare., (Copyright © 2024 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.)

Purpose: Benign prostatic hyperplasia (BPH) is a urinary tract disorder that primarily affects geriatric males. Natural materials have been developed to treat and prevent symptoms of BPH. However, a few natural functional foods has been conclusively proven to cure or prevent symptoms of BPH. The study aimed to investigate the anti-proliferative mechanism of Curcumae Radix (CR) and Syzygium aromaticum (SA) extracts using RWPE-1 cells and testosterone propionate (TP)-induced BPH rats., Materials and Methods: In vitro experiments were performed to assess the synergistic anti-proliferative effects of an equal mixture of CR and SA extracts on TP-treated RWPE-1 cells. In animal experiments, TP-induced BPH rats were administrated with saline, CR and SA extracts at 50, 100, and 200 mg/kg or finasteride at 1 mg/kg daily for 6 weeks. Body weight, prostate weight, dihydrotestosterone (DHT), androgen receptor (AR), and prostate-specific antigen (PSA) levels were measured. Additionally, extracellular signal-regulated kinase and NF-κB levels, oxidative stress, and inflammatory stress responses in the prostate were also analyzed., Results: In this study, the combination of CR and SA extracts synergistically inhibited cell proliferation compared with the effect of each extract in TP-treated RWPE-1 cells. CR and SA extracts inhibited increasing of prostate weight, thickness of prostate epithelium, the level of PSA and DHT in serum. The expression of protein and gene of PSA and AR in prostate of TP-induced BPH rats were also suppressed by the administration of CR and SA extracts. Furthermore, reactive oxygen species and inflammation axis, NOX4-iNOS-COX2 and its associated representative inflammatory cytokine, interleukin-8 were also reduced in the CR and SA extracts-administered BPH rats., Conclusions: The results suggest that the combination of CR and SA extracts improves BPH through its anti-inflammatory and anti-oxidative effects, demonstrating great potential as an anti-BPH medicine., Competing Interests: The authors have nothing to disclose., (Copyright © 2024 Korean Society for Sexual Medicine and Andrology.)

Purpose: In this study, we evaluated 66 patients diagnosed with adenoid cystic carcinoma (ACC) enrolled in two Korean Cancer Study Group trials to investigate the response and progression patterns in recurrent and/or metastatic ACC treated with vascular endothelial growth factor receptor tyrosine kinase inhibitors (VEGFR-TKIs)., Materials and Methods: We evaluated 66 patients diagnosed with ACC who were enrolled in the Korean Cancer Study Group trials. The tumor measurements, clinical data, treatment outcomes, and progression patterns of therapy were analyzed., Results: In the 66 patients (53 receiving axitinib and 13 receiving nintedanib), the disease control rate was 61%, and three patients achieved partial response. The median follow-up, median progression-free survival (PFS), overall survival, and 6-month PFS rate were 27.6%, 12.4%, and 18.1% months and 62.1%, respectively. Among 42 patients who experienced progression, 27 (64.3%) showed target lesion progression. Bone metastasis was an independent poor prognostic factor., Conclusion: Overall, most patients demonstrated stable disease with prolonged PFS; however, prominent target lesion progression occurred in some patients. Thus, PFS may capture VEGFR-TKI efficacy better than the objective response rate.

Background: The aim of this study was to evaluate the impact of intravenous palonosetron compared to ondansetron on hypotension induced by spinal anesthesia in women undergoing cesarean section., Methods: Fifty-four women scheduled for elective cesarean section were, randomly allocated to ondansetron group (n = 27) or palonosetron group (n = 27). Ten minutes prior to the administration of spinal anesthesia, participants received an intravenous injection of either ondansetron or palonosetron. A prophylactic phenylephrine infusion was initiated immediately following the intrathecal administration of bupivacaine and fentanyl. The infusion rate was titrated to maintain adequate blood pressure until the time of fetal delivery. The primary outcome was total dose of phenylephrine administered. The secondary outcomes were nausea or vomiting, the need for rescue antiemetics, hypotension, bradycardia, and shivering. Complete response rate, defined as the absence of postoperative nausea and vomiting and no need for additional antiemetics, were assessed for up to 24 hours post-surgery., Results: No significant differences were observed in the total dose of phenylephrine used between the ondansetron and palonosetron groups (387.5 μg [interquartile range, 291.3-507.8 μg versus 428.0 μg [interquartile range, 305.0-507.0 μg], P = 0.42). Complete response rates also showed no significant differences between the groups both within two hours post-spinal anesthesia (88.9% in the ondansetron group versus 100% in the palonosetron group; P = 0.24) and at 24 hours post-surgery (81.5% in the ondansetron group versus 88.8% in the palonosetron group; P = 0.7). In addition, there was no difference in other secondary outcomes., Conclusion: Prophylactic administration of palonosetron did not demonstrate a superior effect over ondansetron in mitigating hemodynamic changes or reducing phenylephrine requirements in patients undergoing spinal anesthesia with bupivacaine and fentanyl for cesarean section., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2024 Kim et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

Background/aims: Optimal risk stratification based on simplified geriatric assessment to predict treatment-related toxicity and survival needs to be clarified in older patients with diffuse large B-cell lymphoma (DLBCL)., Methods: This multicenter prospective cohort study enrolled newly diagnosed patients with DLBCL (≥ 65 yr) between September 2015 and April 2018. A simplified geriatric assessment was performed at baseline using Activities of Daily Living (ADL), Instrumental ADL (IADL), and Charlson's Comorbidity Index (CCI). The primary endpoint was event-free survival (EFS)., Results: The study included 249 patients, the median age was 74 years (range, 65-88), and 125 (50.2%) were female. In multivariable Cox analysis, ADL, IADL, CCI, and age were independent factors for EFS; an integrated geriatric score was derived and the patients stratified into three geriatric categories: fit (n = 162, 65.1%), intermediate-fit (n = 25, 10.0%), and frail (n = 62, 24.9%). The established geriatric model was significantly associated with EFS (fit vs. intermediate-fit, HR 2.61, p < 0.001; fit vs. frail, HR 4.61, p < 0.001) and outperformed each covariate alone or in combination. In 87 intermediate-fit or frail patients, the relative doxorubicin dose intensity (RDDI) ≥ 62.4% was significantly associated with worse EFS (HR, 2.15, 95% CI 1.30-3.53, p = 0.002). It was related with a higher incidence of grade ≥ 3 symptomatic non-hematologic toxicities (63.2% vs. 27.8%, p < 0.001) and earlier treatment discontinuation (34.5% vs. 8.0%, p < 0.001) in patients with RDDI ≥ 62.4% than in those with RDDI < 62.4%., Conclusion: This model integrating simplified geriatric assessment can risk-stratify older patients with DLBCL and identify those who are highly vulnerable to standard dose-intensity chemoimmunotherapy.

Background: Patients with multiple myeloma exhibit malignant osteolytic bone disease due to excessive osteoclast formation and function. We recently identified that osteoclastogenic stimulator selenoprotein W (SELENOW) is upregulated via ERK signaling and downregulated via p38 signaling during receptor activator of nuclear factor (NF)-κΒ ligand (RANKL)-induced osteoclast differentiation. In the intrinsic physiological process, RANKL-induced downregulation of SELENOW maintains proper osteoclast differentiation; in contrast, forced overexpression of SELENOW leads to overactive osteoclast formation and function., Methods and Results: We observed that SELENOW is highly expressed in multiple myeloma-derived peripheral blood mononuclear cells (PBMCs) and mature osteoclasts when compared to healthy controls. Also, the level of tumor necrosis factor alpha (TNFα), a pathological osteoclastogenic factor, is increased in the PBMCs and serum of patients with multiple myeloma. ERK activation by TNFα was more marked and sustained than that by RANKL, allowing SELENOW upregulation. Excessive expression of SELENOW in osteoclast progenitors and mature osteoclasts derived from multiple myeloma facilitated efficient nuclear translocation of osteoclastogenic transcription factors NF-κB and NFATc1, which are favorable for osteoclast formation., Conclusion: Our findings suggest a possibility that feedforward signaling of osteoclastogenic SELENOW by TNFα derived from multiple myeloma induces overactive osteoclast differentiation, leading to bone loss during multiple myeloma., (© 2024. The Author(s).)

Objectives: This study aimed to investigate whether genetic alterations in PI3KCA and the cell cycle pathways influence the efficacy of durvalumab, an immune checkpoint inhibitor, in patients with head and neck squamous cell carcinoma (HNSCC) who had previously failed platinum-based treatment., Materials and Methods: We obtained data from a phase II umbrella trial of patients with HNSCC who failed platinum-based treatment (TRIUMPH, NCT03292250). Patients receiving durvalumab treatment comprised those with PIK3CA alterations (Group A), those with cell cycle pathway alterations such as CDKN2A (Group B), and those with no druggable genetic alterations (Group C). We analyzed the overall response rate (ORR), progression-free survival (PFS), and overall survival (OS) in each group and evaluated the potential predictive factors for durvalumab., Results: We analyzed the data of 87 patients: 18, 12, and 57 in groups A, B, and C, respectively. The ORRs were 27.8 %, 8.3 %, and 15.8 % in Groups A, B, and C, respectively (P = 0.329), and the median PFS for each group was 2.3, 1.6, and 1.7 months, respectively, with no significant differences between the groups (P = 0.24). Notably, patients with lower neutrophil-lymphocyte ratio (NLR) (≤5.8) had longer PFS (median, 2.8 vs 1.6 months, P < 0.001), while those with lower platelet-lymphocyte ratio (PLR) (≤491.2) exhibited longer PFS (median, 1.8 vs 1.2 months, P < 0.001)., Conclusion: Durvalumab's efficacy was similar, irrespective of the presence of PIK3CA or cell cycle pathway genetic alterations in patients with platinum-resistant HNSCC. The NLR and PLR may be promising predictive biomarkers., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: The authors certified that they have no conflict of interest (COI) directly related to this report. Broad information about their COI is presented. BK received research funding from MSD, AstraZeneca and Ono Pharmaceutical Co., Ltd., and has served as an advisor for Handok, NeoImmuneTec, Trialinformatics and ImmuneOncia outside of the current work., (Copyright © 2024 Elsevier Ltd. All rights reserved.)

Purpose: A precise oncologic approach for head and neck squamous cell carcinoma (HNSCC) is necessary. We performed a genomic profile-based umbrella trial for the patients with platinum-refractory recurrent and/or metastatic HNSCC., Methods: In this multicenter, open-label, single-arm phase II trial, we performed targeted next-generation sequencing (NGS). Patients were assigned to each treatment arm on the basis of their matching genomic profiles: arm 1, alpelisib, a PIK3CA inhibitor; arm 2, poziotinib, an epidermal growth factor receptor/HER2 inhibitor; arm 3, nintedanib, an fibroblast growth factor receptor inhibitor; and arm 4, abemaciclib, a CDK4/6 inhibitor. If there was no matching target, patients were allocated to arm 5, duvalumab ± tremelimumab, anti-PD-L1/cytotoxic T-cell lymphocyte-4 inhibitor. When progressive disease (PD) occurred in arms 1-4, cross over to arm 5 was allowed. The primary end point was disease control rate (DCR) in arm 1 and overall response rate (ORR) in arms 2-5 by investigator assessment., Results: Between October 2017 and August 2020, 203 patients were enrolled, including crossover. In arm 1, the ORR was 21.2% and DCR was 65.6%. The ORR was 0% for arm 2, 42.9% for arm 3, 0% for arm 4, and 15.6% for arm 5. In the case of PD with durvalumab, tremelimumab was added, and the ORR for durvalumab + tremelimumab was 2.2%. The median progression-free survival was 3.4, 3.2, 5.6, 1.6, and 1.7 months for each arm, respectively. The median overall survival was 12.4, 6.1, 11.1, 9.1, and 12.7 months, respectively. Overall, the toxicity profiles were manageable, and there were no treatment-related deaths., Conclusion: To our knowledge, this study is the first biomarker-driven umbrella trial for platinum-refractory HNSCC using matched molecular targeted agents. We found that NGS-based genomic phenotyping was methodologically feasible and applicable.

Objective: This study aimed to identify the correlation between digital capacity, health promotion participation, and active aging of older people living in rural areas in South Korea to assess the factors influencing participation in programs for health promotion and active aging., Methods: Data were collected through a 1:1 face-to-face survey using a structured questionnaire from 13 February to 24 February 2023 during the older individuals' visits in the senior citizen welfare centers and senior citizen centers in the region. The Measuring Digital Skills questionnaire used to assess the digital competence of South Korean individuals was employed in this study. To confirm the structural relationship between digital capacity and health promotion participation and active aging in the older population aged 65 years and older based on the collected data, a structural equation modeling analysis was performed., Results: Active health promotion participation had a positive effect on active aging. The pathway that older adults in Korea can led to participation in health promotion and active aging in the current situation is not mainly through the digital competency whereas mobile internet skill showed positive influneces., Conclusions: In the digital era and super-aged society, various programs are provided to older individuals to enhance the utilization of smartphones. However, education and programs for strengthening digital capacity should be organized to explain the advantages of digital use and to inform of the dangers of addiction to ensure healthy aging through social participation and exchange both online and offline., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2024.)

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., Competing Interests: The authors have no potential conflicts of interest to disclose., (© 2024 The Korean Academy of Medical Sciences.)

Background: This study analyzed the predictive value of artificial intelligence (AI)-powered tumor-infiltrating lymphocyte (TIL) analysis in recurrent or metastatic (R/M) adenoid cystic carcinoma (ACC) treated with axitinib., Methods: Patients from a multicenter, prospective phase II trial evaluating axitinib efficacy in R/M ACC were included in this study. H&E whole-side images of archival tumor tissues were analyzed by Lunit SCOPE IO, an AI-powered spatial TIL analyzer., Results: Twenty-seven patients were included in the analysis. The best response was stable disease, and the median progression-free survival (PFS) was 11.1 months (95% CI, 9.2-13.7 months). Median TIL densities in the cancer and surrounding stroma were 25.8/mm 2 (IQR, 8.3-73.0) and 180.4/mm 2 (IQR, 69.6-342.8), respectively. Patients with stromal TIL density >342.5/mm 2 exhibited longer PFS (p = 0.012)., Conclusions: Cancer and stromal area TIL infiltration were generally low in R/M ACC. Higher stromal TIL infiltration was associated with a longer PFS with axitinib treatment., (© 2023 Wiley Periodicals LLC.)

Skin photoaging induced by ultraviolet (UV) irradiation contributes to the formation of thick and coarse wrinkles. Humans are exposed to UV light throughout their lives. Therefore, it is crucial to determine the time-sequential effects of UV on the skin. In this study, we irradiated the mouse back skin with UV light for eight weeks and observed the changes in gene expressions via microarray analysis every week. There were more downregulated genes (514) than upregulated genes (123). The downregulated genes had more functional diversity than the upregulated genes. Additionally, the number of downregulated genes did not increase in a time-dependent manner. Instead, time-dependent kinetic patterns were observed. Interestingly, each kinetic cluster harbored functionally enriched gene sets. Since collagen changes in the dermis are considered to be a major cause of photoaging, we hypothesized that other gene sets contributing to photoaging would exhibit kinetics similar to those of the collagen-regulatory genes identified in this study. Accordingly, co-expression network analysis was conducted using 11 well-known collagen-regulatory seed genes to predict genes with similar kinetics. We ranked all downregulated genes from 1 to 504 based on their expression levels, and the top 50 genes were suggested to be involved in the photoaging process. Additionally, to validate and support our identified top 50 gene lists, we demonstrated that the genes (FN1, CCDC80, PRELP, and TGFBR3) we discovered are downregulated by UV irradiation in cultured human fibroblasts, leading to decreased collagen levels, which is indicative of photoaging processes. Overall, this study demonstrated the time-sequential genetic changes in chronically UV-irradiated skin and proposed 50 genes that are involved in the mechanisms of photoaging., Competing Interests: The authors have declared that no competing interests exist., (Copyright: © 2023 Jin et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)

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., Competing Interests: The authors declare that this study received funding from the Kyowa Kirin Korea Co, Ltd. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article or the decision to submit it for publication., (Copyright © 2023 Song, Lee, Moon, Kim, Kim, Kim, Mun, Lee, Do, Lee, Jung and Kim.)

Background: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematologic disorder characterized by uncontrolled terminal complement activation. Eculizumab, a monoclonal antibody C5 inhibitor was introduced in Korea in 2009 and has been the standard treatment option for PNH., Methods: This study assessed the long-term efficacy/safety of eculizumab in PNH using real-world data from the Korean Health Insurance Review and Assessment Service. Eighty patients who initiated eculizumab from 2009-2020 were enrolled., Results: At eculizumab initiation, the median age was 51.5 years, lactate dehydrogenase (LDH) 6.8 × upper limit of normal, and granulocyte clone size 93.0%. All patients had at least one PNH-related complication before eculizumab initiation, including renal failure (n = 36), smooth muscle spasm (n = 24), thromboembolism (n = 20), and pulmonary hypertension (n = 15). The median (range) duration of eculizumab treatment was 52.7 (1.0, 127.3) months (338.6 total treated patient-years). Despite high disease activity in the study population before treatment initiation, overall survival was 96.2% and LDH levels were stabilized in most patients during treatment. PNH-related complications at treatment initiation were resolved in 44.4% of patients with renal failure, 95.8% with smooth muscle spasm, 70.0% with thromboembolism, and 26.7% with pulmonary hypertension. Extravascular hemolysis occurred in 28.8% of patients (n = 23; 0.09 per patient-year) and breakthrough hemolysis in 18.8% (n = 15; 0.06 per patient-year). No treatment discontinuation cases related to eculizumab were observed., Conclusion: These data provided evidence for the long-term efficacy and safety of eculizumab in Korean PNH patients with high disease burdens., Competing Interests: Jin Seok Kim has received honoraria and consulting fees from Handok Inc. Jun Ho Jang has received research support from Alexion, AstraZeneca Rare Disease. Sung-Soo Yoon has received research funding from Chong Kun Dang Pharm, JW Pharmaceutical, Kyowa Kirin, Roche-Genentech, and Yuhan Pharmaceutical; has served on the advisory board for Amgen, Antengene, Astellas, Celgene, Janssen, Merck, Novartis, and Takeda; and has received consulting fees from Ticaros Therapeutics. BokJin Hyun, HyunSun Nam, and Eunhye Kim are employees of Handok Inc. Min Joo Kwak and Yong Kyun Won were an employee of Handok Inc. at the time of study. Jong Wook Lee has served on advisory boards and has received honoraria and research grants from Alexion, AstraZeneca Rare Disease. Deog-Yeon Jo, Seo-Yeon Ahn, Je-Hwan Lee, Sung-Hyun Kim, Chul Won Choi, Ho-Jin Shin, Min-Kyoung Kim, Jae Hoon Lee, Yeung-Chul Mun, and Jee Hyun Kong have no potential conflicts of interest to disclose., (© 2023 The Korean Academy of Medical Sciences.)

Workplace bullying is a prevalent issue with a significant impact on employees' mental health. This study aimed to explore the relationship between workplace bullying and the prevalence of depression, with a particular focus on the role of gender. A total of 12,344 Korean employees aged 19-65 years were included in the study. They completed the Center for Epidemiologic Studies Depression Scale (CES-D) and a score of 16 or higher in CES-D indicated depression. The association between workplace bullying and depression was analyzed using logistic regression analyses. The average CES-D scores were higher for both male and female employees who experienced bullying than for those who did not ( p < 0.001). The association between the experience of workplace bullying and the prevalence of depression was statistically significant for both genders, with a stronger correlation observed among male employees ( p for interaction < 0.001). Organizations are urged to address workplace bullying, particularly for male employees, through the implementation of anti-bullying strategies and policies, as well as the provision of mental health resources and support.

Background: The present study investigated an interpersonal model of development of depressive symptoms in employees, where occupational stress affects burnout, which in turn affects risk for depression, and whether this mediation is moderated by grit., Methods: A total of 11,421 participants, aged 19 to 65 years, who were employees of 18 private companies and local government organizations in Korea were included. They completed questionnaires, including the Korean version of occupational stress scale, Oldenburg Burnout Inventory, Center for Epidemiologic Studies Depression scale and Grit scale. Mediation and moderation analyses were carried out in the Statistical Package for the Social Sciences PROCESS macro., Results: The association between occupational stress and depressive symptoms was mediated by exhaustion (b = -0.256, 95 % CI [0.244, 0.268]) and disengagement (b = -0.052, 95 % CI [0.039, 0.065]). Moreover, the effect of exhaustion on depressive symptoms was moderated by each grit, with the effect being stronger for employees with low grit (b = 0.939, p < 0.001 for passion and b = 0.629, p < 0.001 for perseverance) than for those with high grit (b = 0.944, p < 0.001 for passion and b = 0.686, p < 0.001 for perseverance)., Limitations: The cross-sectional design of the study does not allow causal inferences., Conclusions: These findings contribute to the understanding of how occupational stress predicts depressive symptoms in the workplace and provide practical implications for preventing burnout and nurturing grit to protect employees' mental health in the workplace., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2023. Published by Elsevier B.V.)

The analgesia nociception index (ANI) has emerged as a potential measurement for objective pain assessment during general anesthesia. This systematic review and meta-analysis aimed to evaluate the accuracy and effectiveness of ANI in assessing intra- and post-operative pain in patients undergoing general anesthesia. We conducted a comprehensive search of Ovid-MEDLINE, Ovid-EMBASE, Cochrane Central Register of Controlled Trials, Google Scholar, public clinical trial databases (ClinicalTrials and Clinical Research Information Service), and OpenSIGLE to identify relevant studies published prior to May 2023 and included studies that evaluated the accuracy and effectiveness of ANI for intra- or post-operative pain assessment during general anesthesia. Among the 962 studies identified, 30 met the eligibility criteria and were included in the systematic review, and 17 were included in the meta-analysis. For predicting intra-operative pain, pooled sensitivity, specificity, diagnostic odds ratio (DOR), and area under curve of ANI were 0.81 (95% confidence interval [CI] = 0.79-0.83; I 2 = 68.2%), 0.93 (95% CI = 0.92-0.93; I 2 = 99.8%), 2.32 (95% CI = 1.33-3.30; I 2 = 61.7%), and 0.77 (95% CI = 0.76-0.78; I 2 = 87.4%), respectively. ANI values and changes in intra-operative hemodynamic variables showed statistically significant correlations. For predicting post-operative pain, pooled sensitivity, specificity, and DOR of ANI were 0.90 (95% CI = 0.87-0.93; I 2 = 58.7%), 0.51 (95% CI = 0.49-0.52; I 2 = 99.9%), and 3.38 (95% CI = 2.87-3.88; I 2 = 81.2%), respectively. ANI monitoring in patients undergoing surgery under general anesthesia is a valuable measurement for predicting intra- and post-operative pain. It reduces the use of intra-operative opioids and aids in pain management throughout the perioperative period.

Purpose: This phase II, open-label, multicenter study aimed to investigate the efficacy and safety of a rituximab intensification for the 1st cycle with every 21-day of rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone (R-CHOP-21) among patients with previously untreated advanced-stage or bulky diffuse large B-cell lymphoma (DLBCL)., Materials and Methods: Ninety-two patients with stage III/IV or bulky DLBCL from 21 institutions were administered 8 cycles of R-CHOP-21 with an additional one dose of rituximab intensification on day 0 of the 1st cycle (RR-CHOP). The primary endpoint was a complete response (CR) rate after 3 cycles of chemotherapy., Results: Among the 92 DLBCL patients assessed herein, the response rate after 3 cycles of chemotherapy was 88.0% (38.0% CR+50.0% partial response [PR]). After the completion of 8 cycles of chemotherapy, the overall response rate was observed for 68.4% (58.7% CR+9.8% PR). The 3-year progression-free survival rate was 64.0%, and the 3-year overall survival rate was 70.4%. Febrile neutropenia was one of the most frequent grade 3 adverse events (40.0%) and 5 treatment-related deaths occurred. Compared with the clinical outcomes of patients who received R-CHOP chemotherapy as a historical control, the interim CR rate was higher in male patients with RR-CHOP (20.5% vs. 48.8%, p=0.016)., Conclusion: Rituximab intensification on days 0 to the 1st cycle of the standard 8 cycles R-CHOP-21 for advanced DLBCL yielded favorable response rates after the 3 cycles of chemotherapy and acceptable toxicities, especially for male patients. ClinicalTrials.gov ID: NCT01054781.

Background: Although brachial plexus block in volar plating surgery for distal radius fractures is reportedly associated with lower postoperative pain scores, rebound pain has been reported to occur after the initial block wears off. Dexamethasone can be used in multimodal strategies for antiemesis and to control pain postoperatively. Although prior studies have suggested that anesthesia can be prolonged by adding dexamethasone to regional blocks, no randomized trials we are aware of have ascertained whether doing so will make a clinically important difference in pain after surgery for distal radius fractures., Questions/purposes: Do patients who receive supplemental dexamethasone in a brachial plexus block for volar plating of unstable distal radius fractures have (1) better pain scores at 4, 8, 24, and 48 hours postoperatively than patients who have not received dexamethasone, and (2) lower fentanyl consumption and administration of antiemetic drugs without change in serum blood glucose, as well as a longer analgesic duration from the block after surgery than patients who have not received dexamethasone?, Methods: This randomized, double-blind trial included 69 patients undergoing surgery for distal radius fractures under ultrasound-guided supraclavicular brachial plexus blocks who were randomly allocated into two groups: a nondexamethasone group receiving a brachial plexus block with 0.5% ropivacaine and a dexamethasone group receiving 0.5% ropivacaine and 5 mg of dexamethasone. Thirty-four patients were allocated to the dexamethasone group and 35 were allocated to the nondexamethasone group. Nine patients (four in the dexamethasone group and five in the nondexamethasone group) were excluded after randomization because local anesthetics were used during their surgical procedures owing to an incomplete block or they requested patient-controlled analgesia after surgery. The treatment groups did not differ in any important ways, including age, gender, BMI, hand dominance, and AO/Orthopaedic Trauma Association classification. All patients received the same surgical procedure and perioperative care protocol, except for the injected agents during their brachial plexus block. The primary outcome was postoperative pain, evaluated using a 10-mm VAS at 4, 8, 12, 24, and 48 hours after surgery. The minimum clinically important difference for the VAS score was 2 of 10 points. Secondary outcome variables included fentanyl administration as a rescue analgesic, the number of patients receiving antiemetic medications because of fentanyl administration, and the duration of brachial plexus block. Serum blood glucose was measured 1 day before, immediately after, and 24 hours after surgery. Patients, surgeons, and outcome assessors were blinded to treatment allocation., Results: The only clinically important between-group difference in VAS pain scores was at 8 hours, favoring the group that received dexamethasone over the group that did not (1.9 ± 1.6 versus 4.7 ± 2.7; mean difference -2.8 [95% CI -3.9 to -1.6]; p < 0.001). After brachial plexus block, the most severe pain score in both groups was reported at 12 hours postoperatively and gradually diminished over time. There was no between-group difference in fentanyl use between those who received dexamethasone and those who did not (21 ± 38 mcg versus 31 ± 29 mcg; mean difference -10 [95% CI -27.4 to 7.4]; p = 0.26). Furthermore, the use of antiemetics did not differ between the groups (27% [eight of 30] versus 37% [11 of 30]; odds ratio 1.6 [95% CI 0.5 to 4.8]; p = 0.41). Baseline and 24-hour postoperative serum blood glucose level did not differ between the groups. However, the immediately postoperative serum blood glucose level was higher in the dexamethasone group than in the nondexamethasone group (121 ± 29 versus 104 ± 20; mean difference 16 [95% CI 3.3 to 28.8]; p = 0.02). The brachial plexus block duration was 3 hours longer (95% CI 0.8 to 5.2 hours) in the dexamethasone group than that in the nondexamethasone group (11 ± 5 hours versus 8 ± 3 hours; p = 0.01)., Conclusion: The postoperative pain level in patients who received supplemental dexamethasone in a regional block was not clinically different from that of patients who received conventional brachial plexus block anesthesia when undergoing volar plating for distal radius fractures. However, patients who received a brachial plexus block with dexamethasone experienced slight prolongation of their block and decrease in pain 8 hours after surgery., Level of Evidence: Level I, therapeutic study., Competing Interests: Each author certifies that there are no funding or commercial associations (consultancies, stock ownership, equity interest, patent/licensing arrangements, etc.) that might pose a conflict of interest in connection with the submitted article related to the author or any immediate family members. All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research® editors and board members are on file with the publication and can be viewed upon request., (Copyright © 2023 by the Association of Bone and Joint Surgeons.)

Background: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. The high positivity rate for human epidermal growth factor receptor 2 (HER2) led to an investigation of the efficacy of HER2-targeted agents. Docetaxel-PM (polymeric micelle) is a low-molecular-weight, nontoxic, biodegradable, and docetaxel-loaded micellar formulation. Trastuzumab-pkrb is a biosimilar to trastuzumab., Methods: This was a multicenter, single-arm, open-label phase 2 study. Patients with HER2-positive (immunohistochemistry [IHC] score of ≥2+ and/or HER2/chromosome enumeration probe 17 [CEP17] ratio of ≥2.0) advanced SDCs were enrolled. Patients received docetaxel-PM (75 mg/m 2 ) and trastuzumab-pkrb (8 mg/kg in the first cycle and 6 mg/kg in subsequent cycles) every 3 weeks. Primary end point was objective response rate (ORR)., Results: A total of 43 patients were enrolled. The best objective responses were partial response in 30 (69.8%) patients and stable disease in 10 (23.3%) patients, leading to an ORR of 69.8% (95% confidence interval [CI], 53.9-82.8) and a disease control rate of 93.0% (80.9-98.5). Median progression-free survival, duration of response, and overall survival were 7.9 (6.3-9.5), 6.7 (5.1-8.4), and 23.3 (19.9-26.7) months, respectively. Patients with HER2 IHC score of 3+ or HER2/CEP17 ratio ≥2.0 demonstrated better efficacies compared to those with HER2 IHC score of 2+. Thirty-eight (88.4%) patients experienced treatment-related adverse events (TRAE). Because of TRAE, nine (20.9%), 14 (32.6%), and 19 (44.2%) patients required temporary discontinuation, permanent discontinuation, or dose reduction, respectively., Conclusions: The combination of docetaxel-PM and trastuzumab-pkrb demonstrated promising antitumor activity with a manageable toxicity profile in HER2-positive advanced SDC., Plain Language Summary: Salivary duct carcinoma (SDC) is uncommon but is the most aggressive subtype of salivary gland carcinomas. SDC shares morphological and histological similarities with invasive ductal carcinoma of breast, which led to an investigation of hormonal receptor and human epidermal growth factor receptor 2 (HER2)/neu expression status in SDC. In this study, patients with HER2-positive SDC were enrolled and treated with combination of docetaxel-polymeric micelle and trastuzumab-pkrb. Promising antitumor activities were shown with objective response rate of 69.8%, disease control rate of 93.0%, median progression-free survival of 7.9 months, median duration of response of 6.7 months, and median overall survival of 23.3 months., (© 2023 American Cancer Society.)

Background: Anaplastic thyroid cancer (ATC) is a rare but aggressive type of thyroid carcinoma. BRAF V600E-mutation, which is found in 10%-50% of ATCs, is associated with poor prognosis. A recent clinical trial reported a substantial clinical benefit of concomitant treatment of dabrafenib ( BRAF inhibitor) and trametinib (MEK inhibitor) for treating BRAF V600E-mutant ATC. However, reports on patients with ATC treated with this regimen following surgery are lacking., Case Summary: We report the case of a 63-year-old female patient diagnosed with BRAF V600E-mutant ATC. Following three surgeries-total thyroidectomy, total laryngectomy, and neck dissection-she was diagnosed with lung metastasis during follow-up. The metastatic ATC was successfully treated with dabrafenib and trametinib. The patient achieved a complete response at the 32-mo follow-up., Conclusion: Adjuvant chemotherapy with dabrafenib plus trametinib is efficacious for treatment and prevention of recurrent ATC with BRAF mutation following surgery., Competing Interests: Conflict-of-interest statement: The authors have nothing to disclose pertaining to this article., (©The Author(s) 2023. Published by Baishideng Publishing Group Inc. All rights reserved.)

As global temperatures have steadily increased over past decades, studying of the impacts of heat stress on morpho-physiological traits and economic yields of horticultural crops have been increasingly gained attentions by many scientists and farmers. Hot pepper (Capsicum annuum L.) is an important vegetable crop mostly grown in open-fields in South Korea. In this study, the impacts of prolonged heat stress on three hot pepper genotypes differing by levels of stress susceptibility were evaluated. The study was conducted in two different temperature-controlled greenhouses for 75 days. 48 days old plants were grown in control and heat-treated greenhouses where the temperatures had been set at 30 °C and 35 °C during the day for 75 days, respectively. Morphological, physiological, and nutrient characteristics of three accessions were measured. All hot pepper accessions were enabled to recover from prolonged heat stress exposures within approximately a month. The phenomenon of recovery was observed in some significant morphological and physiological characteristics. For example, the plant growth rate and photosynthesis rate significantly increased after 40th days of heat treatment. The heat stress sensitivity varied between genotypes. The plants that produced more fruits over biomass at early stage of heat treatment had relatively slow recovery, resulting in the largest yield loss. This key morphological characteristic can be used for future breeding program to adapt the prolonged heat stress., (© 2023. Springer Nature Limited.)

Introduction: Upfront autologous stem cell transplantation (ASCT) has been recommended for patients who are newly diagnosed with peripheral T-cell lymphoma (PTCL), and CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisone), an anthracycline-based chemotherapy has been the frontline chemotherapy for PTCL. However, it is not clear whether anthracycline-based chemotherapies such as CHOP could be standard induction therapy for PTCL., Methods: We conducted a randomized phase II study to compare CHOP with fractionated ifosfamide, carboplatin, etoposide, and dexamethasone (ICED) for patients eligible for ASCT. The primary endpoint was progression-free survival (PFS) and secondary endpoints included objective response rate, overall survival (OS), and safety profiles., Results: Patients were randomized into either CHOP (n = 69) or ICED (n = 66), and the characteristics of both arms were not different. PTCL-not otherwise specified (NOS, n = 60) and angioimmunoblastic T-cell lymphoma (AITL, n = 53) were dominant. The objective response rate was not different between CHOP (59.4%) and ICED (56.1%), and the 3-year PFS was not different between CHOP (36.7%) and ICED (33.1%). In AITL patients, CHOP was favored over ICED whereas ICED was associated with more cytopenia and reduced dose intensity. Patients who received upfront ASCT after achieving complete response to CHOP or ICED showed 80% of 3-year OS., Discussion: In summary, our study showed no therapeutic difference between CHOP and ICED in terms of response and PFS. Thus, CHOP might remain the reference regimen especially for AITL based on its better outcome in AITL, and upfront ASCT could be recommended as a consolidation of complete response in patients with PTCL., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2023 Kim, Jo, Yoon, Yang, Yoon, Lee, Kong, Park, Kang, Lee, Oh, Shin, Lee, Choi, Jeong, Kim, Kang, Yi, Lim, Yhim, Do, Yun, Eom, Lee, Suh and Kim.)

Self-compassion (SC) involves taking an emotionally positive attitude towards oneself when suffering. Although SC has positive effects on mental well-being as well as a protective role in preventing symptoms in healthy individuals, few studies on white matter (WM) microstructures in neuroimaging studies of SC has been studied. Brain imaging data were acquired from 71 healthy participants. WM regions of mirroring network were analyzed using tract-based spatial statistics. After the WM regions associated with SC were extracted, exploratory correlation analysis with the self-forgiveness scale, the coping scale, and the world health organization quality of life scale abbreviated version was performed. We found that self-compassion scale total scores were negatively correlated with the fractional anisotropy (FA) values of the superior longitudinal fasciculus (SLF) in healthy individuals. The self-kindness and mindfulness subscale scores were also negatively correlated with FA values of the same regions. These FA values were negatively correlated with the total scores of self-forgiveness scale, and self-control coping strategy and confrontation coping strategy. Our findings suggest levels of SC may be associated with WM microstructural changes of SLF in healthy individuals. These lower WM microstructures may be associated with positive personal attitudes, such as self-forgiveness, self-control and active confrontational strategies., (© 2023. The Author(s).)

Abnormalities in the extracellular matrix (ECM) caused by ultraviolet (UV) radiation are mediated by epigenetic mechanisms. Enhancer of zeste homolog 2 (EZH2) is a histone methyltransferase that is implicated in inflammation, immune regulation, and senescence. However, its role in controlling UV-induced ECM alterations in the skin remains elusive. Here, we investigated the role of EZH2 in UV-induced expression of matrix metalloproteinase (MMP)-1 and type I procollagen. We found that UV induced EZH2 expression in human skin in vivo and in human dermal fibroblasts (HDFs). EZH2 knockdown reduced the expression and promoter activity of MMP-1 and increased those of type I procollagen, whereas EZH2 overexpression had the opposite effects. Mechanistically, EZH2 increased NF-κB activity, and p65 and p50 expression and promoter activity. Intriguingly, chromatin immunoprecipitation assays revealed that the EZH2/p65/p50 complex was recruited and bound to the MMP-1 promoter after UV irradiation, independent of its histone methyltransferase activity. In contrast, EZH2-induced DNA methyltransferase 1 (DNMT1) formed a complex with EZH2 and enhanced the enrichment of H3K27me3 on the COL1A2 promoter following UV irradiation. These findings indicate that EZH2 plays a dual role in regulating MMP-1 and type I procollagen expression and improve our understanding of how this epigenetic mechanism contributes to UV-induced skin responses and photoaging. This study shows that inhibiting EZH2 is a potential anti-aging strategy for preventing UV-induced skin aging by reducing MMP-1 expression and inducing type I procollagen expression., Competing Interests: Declaration of Competing Interest All authors have no conflict of interest to declare., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Purpose: We conducted a nationwide, multicenter, prospective registry study for newly diagnosed patients with peripheral T-cell lymphoma (PTCL) to better define the clinical characteristics, treatment patterns, survival outcomes, and the role of upfront autologous stem cell transplantation (ASCT) in these patients., Materials and Methods: Patients with PTCL receiving chemotherapy with curative intent were registered and prospectively monitored. All patients were pathologically diagnosed with PTCL., Results: A total of 191 patients with PTCL were enrolled in this prospective registry study. PTCL, not otherwise specified (PTCL-NOS) was the most common pathologic subtype (n=80, 41.9%), followed by angioimmunoblastic T-cell lymphoma (AITL) (n=60, 31.4%). With a median follow-up duration of 3.9 years, the 3-year progression-free survival (PFS) and overall survival (OS) rates were 39.5% and 60.4%, respectively. The role of upfront ASCT was evaluated in patients who were considered transplant-eligible (n=59). ASCT was performed as an upfront consolidative treatment in 32 (54.2%) of these patients. There were no significant differences in PFS and OS between the ASCT and non-ASCT groups for all patients (n=59) and for patients with PTCL-NOS (n=26). However, in patients with AITL, the ASCT group was associated with significantly better PFS than the non-ASCT group, although there was no significant difference in OS., Conclusion: The current study demonstrated that the survival outcomes with the current treatment options remain poor for patients with PTCL-NOS. Upfront ASCT may provide a survival benefit for patients with AITL, but not PTCL-NOS.

This retrospective study compared the mortality and short-term complications according to the choice of general anesthesia or regional anesthesia in patients who underwent a total knee arthroplasty (TKA). We searched the Korean National Health Insurance Service National Sample Cohort database to analyze data from patients who received a TKA between January 2002 and December 2015. Before comparing the general and the regional anesthesia groups, the bias was reduced by propensity score matching. After matching, the mortality and complications occurring within 30 days after a TKA were compared between the 2 groups. In the database, 6491 primary TKA cases were identified. Nine hundred forty-three patients (14.5%) had a TKA performed under general anesthesia, and 5548 (85.5%) had a TKA performed under regional anesthesia. After propensity score matching, the data of 1886 patients were analyzed, with 943 patients in each group. There was no significant difference in mortality (0.32% vs 0.00%), transfusion rate (84.52% vs 84.73%, P = .8989), and length of hospital stay (50 vs 53, P = .5391) between the general and regional anesthesia groups. Most of the complications were not significantly different, but the major complications, including myocardial infarction (1.70% vs 0.64%, P = .0414) and acute renal failure (0.85% vs 0.11%, P = .0391), were higher in the general anesthesia group than in the regional anesthesia group. Also, admission to the intensive care unit (8.48% vs 2.33%, P < .0001) and total cost (₩8067, 400 vs ₩7487, 940, P = .0002) were higher in the general anesthesia group than in the regional anesthesia group. Our study found that regional anesthesia for TKA is associated with a decrease in major complications, including myocardial infarction and acute renal failure, and medical costs., Competing Interests: The authors have no funding and conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

Several guidelines classify autologous stem cell transplantation (ASCT) as a low to intermediate risk group for infection. In a nationwide population-based study, using the Korean Health Insurance Review and Assessment Service database, patients with lymphoma and multiple myeloma (MM) who underwent ASCT from 2002 to 2016 were retrospectively analyzed. Cumulative incidence rates (CIRs) and risk factors of opportunistic infections were investigated. CIRs of fungal, Varicella zoster virus (VZV), cytomegalovirus (CMV), and Pneumocystis jirovecii infections in lymphoma were 7.9%, 16.0%, 7.4%, and 5.1%, respectively, and CIRs in MM were 6.3%, 19.1%, 4.2%, and 5.6%, respectively. Fungal infection was significantly higher in patients with previous infection (Hazard ratio (HR) 2.003, p = 0.005) in lymphoma. Incidence of CMV infection was significantly higher in patients with prior CMV infection: HR 4.920, p < 0.001 (lymphoma); HR 3.022, p = 0.030 (MM). VZV infection was significantly lower in patients receiving prophylaxis: HR 0.082, p < 0.001 (lymphoma); HR 0.096, p < 0.001 (MM). For P. jirovecii infection, busulfex and melphalan conditioning (HR 1.875, p = 0.032) and previous P. jirovecii infection (HR 4.810, p < 0.001) had a higher incidence in MM. Patients who underwent ASCT should receive VZV prophylaxis and prophylaxis for fungal and P. jirovecii may be considered in patients with previous same infection., (© 2023. The Author(s).)

We aimed to compare treatment modalities and outcomes by gender in patients with locally advanced head and neck squamous cell carcinoma (LA-HNSCC). We characterized the sex-specific differences and compared the overall survival (OS) between male and female patients in a multicenter cohort of LA-HNSCC. To minimize the observed confounding, propensity score matching was utilized. The study included 445 patients; 385 (86.5%) were men and 60 (13.5%) were women. In terms of age, smoking habits, drinking habits, and primary tumor locations, there was a significant imbalance in sex before the matching. Propensity score matching yielded 60 patient pairs, with no statistical difference between the sexes in terms of their characteristics. As for the treatment strategies, there were no significant differences between the sexes before ( p = 0.260) and after ( p = 0.585) the propensity score matching. When comparing the survival probabilities between the sexes, OS was not significantly different in the overall (HR 1.02; 95% CI 0.59-1.76; p = 0.938) and propensity-score-matched population (HR 1.46; 95% CI 0.68-3.17; p = 0.331). These results suggest that there was no difference in prognosis by gender in the treatment modalities and outcomes of LA-HNSCC in real-world practice.

Purpose: Diffuse large B-cell lymphoma (DLBCL) is the most common hematologic malignancy worldwide. Although substantial improvement has been achieved by the frontline rituximab-based chemoimmunotherapy, up to 40%-50% of patients will eventually have relapsed or refractory disease, whose prognosis is extremely dismal., Materials and Methods: We have carried out two prospective cohort studies that include over 1,500 DLBCL patients treated with rituximab plus CHOP (#NCT01202448 and #NCT02474550). In the current report, we describe the outcomes of refractory DLBCL patients. Patients were defined to have refractory DLBCL if they met one of the followings, not achieving at least partial response after 4 or more cycles of R-CHOP; not achieving at least partial response after 2 or more cycles of salvage therapy; progressive disease within 12 months after autologous stem cell transplantation., Results: Among 1,581 patients, a total of 260 patients met the criteria for the refractory disease after a median time to progression of 9.1 months. The objective response rate of salvage treatment was 26.4%, and the complete response rate was 9.6%. The median overall survival (OS) was 7.5 months (95% confidence interval, 6.4 to 8.6), and the 2-year survival rate was 22.1%±2.8%. The median OS for each refractory category was not significantly different (p=0.529)., Conclusion: In line with the previous studies, the outcomes of refractory DLBCL patients were extremely poor, which necessitates novel approaches for this population.

The International Myeloma Working Group has recently revised the diagnostic criteria for primary plasma cell leukemia (PCL) to circulating plasma cells (CPCs) ≥ 5% in a peripheral blood smear. The present study validated new criteria in patients with multiple myeloma or PCL diagnosed using the previous diagnostic criteria, who were administered immunomodulatory drugs or proteasome inhibitors as induction therapy. We analyzed the medical records of 1357 patients from eight hospitals in South Korea. The median age of the all patients was 64 years, and 187 (13.8%) had CPCs at diagnosis. Only 79 (5.8%) of the patients had ≥ 5% CPCs. The median overall survival (OS) of patients with CPCs ≥ 5% and ≥ 20% was similar, but had significantly inferior median progression-free survival (PFS) and median OS than those with CPCs < 5% (13.1 vs. 21.5 months, P < 0.001, and 21.5 vs. 60.9 months, P < 0.001, respectively). Primary PCL diagnosed using the revised criteria presented with higher total calcium levels and serum creatinine levels, lower platelet counts and frequent organomegaly and plasmacytoma at diagnosis. Univariate and multivariate analyses demonstrated that the presence of plasmacytoma and elevated serum β2-microglobulin were significantly associated with OS in primary PCL. In conclusion, the revised criterion of CPCs ≥ 5% in a peripheral blood smear is appropriate for PCL diagnosis., (© 2022. The Author(s).)

Scientific regulatory systems with suitable analytical methods for monitoring quality, safety, and efficacy are essential in medicinal plant drug discovery. There have been only few attempts to adopt the analytical quality by design (AQbD) strategy in medicinal plants analysis over the last few years. AQbD is a holistic method and development approach that understands analytical procedure, from risk assessment to lifecycle management. The enhanced AQbD approach reduces the time and effort necessary to develop reliable analytical methods, leads to flexible change control through the method operable design region (MODR), and lowers the out-of-specification (OOS) results. However, it is difficult to follow all the AQbD workflow steps in the field of medicinal plants analysis, such as defining the analytical target profiles (ATPs), identifying critical analytical procedure parameters (CAPPs), among others, because the complexity of chemical and biological properties in medicinal plants acts as a barrier. In this review, various applications of AQbD to medicinal plant analytical procedures are discussed. Unlike the analysis of a single compound, medicinal plant analysis is characterized by analyzing multiple components contained in biological materials, so it will be summarized by focusing on the following points: Analytical methods showing correlations within analysis parameters for the specific medicinal plant analysis, plant raw material diversity, one or more analysis targets defined for multiple phytochemicals, key analysis attributes, and analysis control strategies. In addition, the opportunities available through the use of design-based quality management techniques and the challenges that coexist are also discussed.

Aims: 4-1BB is a member of the tumor necrosis factor receptor superfamily that mainly expressed on activated T-cells and plays important roles in cell proliferation and survival of T-cells and natural killer cells. The roles of 4-1BB in immune cells have been intensively studied, whereas little is known about the expression and roles of 4-1BB in cancer cells., Main Methods: In the present study, we investigated 4-1BB expression in colorectal cancer tissues from human patients and established colorectal cancer cells, using mRNA expression, FACS, and immunostaining. Cancer cell proliferation and metastasis regulated by transfected 4-1BB was evaluated by cell growth rate, colony forming assay, cell migration, and Western blot with antibodies which are involved in epithelial-mesenchymal transition and anti-apoptosis. Expression of 4-1BB was knockdown by 4-1BB shRNA to prove that 4-1BB was involved in the cell proliferation. In vivo, 4-1BB transfected cancer cells were injected into mice, to induce tumor local region or lung., Key Findings: We found that colorectal cancer tissues from human patients and established colorectal cancer cells expressed 4-1BB at the high level. The higher expression of 4-1BB proliferated faster. In addition, we identified two forms of 4-1BB detected in colorectal cancer cells: full length form that was located on the plasma membrane and a short soluble form in the cytosol. The soluble form was also detected in the plasma from the mice with tumor xenografts expressed 4-1BB., Significance: Tumor-mediated 4-1BB expression in the colorectal cancer cells showed effects on cancer cell proliferation, invasion, and metastasis., Competing Interests: Declaration of competing interest The authors declare no competing of interest., (Copyright © 2022. Published by Elsevier Inc.)

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

External beam radiotherapy is effective for stage I orbital mucosa-associated lymphoid tissue lymphoma (MALToma). Hence, very-low-dose radiotherapy is increasingly being investigated. We conducted a single-center prospective phase II trial to evaluate the effectiveness of very-low-dose radiotherapy of 4 Gy (2 Gy × 2 fractions) in pathologically confirmed stage I orbital MALToma. In this first prospective trial, patients with complete response were observed after 3-6 months of follow-up. For patients without complete remission, a radiation dose of 24 Gy/12 fractions was additionally delivered. The primary endpoint was complete response rate; secondary endpoints were overall survival, local control, and progression-free survival. Seventeen patients were screened and three patients refused enrollment during October 2018-October 2021. Thus, 14 patients (17 eyes) were analyzed (median follow-up, 28.2 months). The overall response rate was 100% (complete remission: 11 lesions; partial remission: six lesions). In all lesions with residual disease, additional radiation therapy (dose: 24 Gy) was performed. One local failure was observed. Therefore, 4 Gy ultralow-dose radiation therapy for orbital MALToma was safely performed with a planned second-line treatment in patients without complete remission. This is the first prospective study to report the effectiveness of ultralow-dose radiotherapy of 4 Gy for stage I orbital MALToma treatment.

Refractory thin endometrium and recurrent implantation failure are among the most challenging infertility-related factors hindering successful pregnancy. Several adjuvant therapies have been investigated to increase endometrial thickness and the pregnancy rate, but the treatment effect is still minimal, and for many patients, these treatment methods can be quite costly and difficult to approach. Platelet-rich plasma (PRP) is an autologous concentration of platelets in plasma and has recently been elucidated as a better treatment option for these patients. PRP is rich in cytokines and growth factors, which are suggested to exert a regenerative effect at the level of the injured tissue. Another advantage of PRP is that it is easily obtained from the patient's own blood. We aimed to review the recent findings of PRP therapy used for patients with refractory thin endometrium and recurrent implantation failure.

Alzheimer's disease (AD) is the most-common cause of neurodegenerative dementia, and it is characterized by abnormal amyloid and tau accumulation, which indicates neurodegeneration. AD has mostly been diagnosed clinically. However, ligand-specific positron emission tomography (PET) imaging, such as amyloid PET, and cerebrospinal fluid (CSF) biomarkers are needed to accurately diagnose AD, since they supplement the shortcomings of clinical diagnoses. Using biomarkers that represent the pathology of AD is essential (particularly when disease-modifying treatment is available) to identify the corresponding pathology of targeted therapy and for monitoring the treatment response. Although imaging and CSF biomarkers are useful, their widespread use is restricted by their high cost and the discomfort during the lumbar puncture, respectively. Recent advances in AD blood biomarkers shed light on their future use for clinical purposes. The amyloid β (Aβ)42/Aβ40 ratio and the concentrations of phosphorylated tau at threonine 181 and at threonine 217, and of neurofilament light in the blood were found to represent the pathology of Aβ, tau, and neurodegeneration in the brain when using automatic electrochemiluminescence technologies, single-molecule arrays, immunoprecipitation coupled with mass spectrometry, etc. These blood biomarkers are imminently expected to be incorporated into clinical practice to predict, diagnose, and determine the stage of AD. In this review we focus on advancements in the measurement technologies for blood biomarkers and the promising biomarkers that are approaching clinical application. We also discuss the current limitations, the needed further investigations, and the perspectives on their use., Competing Interests: The authors have no potential conflicts of interest to disclose., (Copyright © 2022 Korean Neurological Association.)

Background: Nilotinib is a tyrosine kinase inhibitor approved by the Ministry of Food and Drug Safety for frontline and 2nd line treatment of Philadelphia chromosome-positive chronic myeloid leukemia (Ph+ CML). This study aimed to confirm the safety and efficacy of nilotinib in routine clinical practice within South Korea., Methods: An open-label, multicenter, single-arm, 12-week observational post-marketing surveillance (PMS) study was conducted on 669 Korean adult patients with Ph+ CML from December 24, 2010, to December 23, 2016. The patients received nilotinib treatment in routine clinical practice settings. Safety was evaluated by all types of adverse events (AEs) during the study period, and efficacy was evaluated by the complete hematological response (CHR) and cytogenetic response., Results: During the study period, AEs occurred in 61.3% (410 patients, 973 events), adverse drug reactions (ADRs) in 40.5% (271/669 patients, 559 events), serious AEs in 4.5% (30 patients, 37 events), and serious ADRs in 0.7% (5 patients, 8 events). Furthermore, unexpected AEs occurred at a rate of 6.9% (46 patients, 55 events) and unexpected ADRs at 1.2% (8 patients, 8 events). As for the efficacy results, CHR was achieved in 89.5% (442/494 patients), and minor cytogenetic response or major cytogenetic response was achieved in 85.8% (139/162 patients)., Conclusion: This PMS study shows consistent results in terms of safety and efficacy compared with previous studies. Nilotinib was well tolerated and efficacious in adult Korean patients with Ph+ CML in routine clinical practice settings.

Although mesoporous silica materials have been widely investigated for many applications, most silica materials are made by calcination processes. We successfully developed a convenient method to synthesize mesoporous materials at room temperature. Although the silica materials made by the two different methods, which are the calcination process and the room-temperature process, have similar specific surface areas, the silica materials produced with the room-temperature process have a significantly larger pore volume. This larger pore volume has the potential to attach to functional groups that can be applied to various industrial fields such as CO 2 adsorption. This mesoporous silica with a larger pore volume was analyzed by TEM, FT-IR, low angle X-ray diffraction, N 2 -adsorption analysis, and CO 2 adsorption experiments in comparison with the mesoporous silica synthesized with the traditional calcination method.

Histone deacetylases (HDACs) remove acetyl groups from lysine chains on histones and other proteins and play a crucial role in epigenetic regulation and aging. Previously, we demonstrated that HDAC4 is consistently downregulated in aged and ultraviolet (UV)-irradiated human skin in vivo . Cellular senescence is a permanent cell cycle arrest induced by various stressors. To elucidate the potential role of HDAC4 in the regulation of cellular senescence and skin aging, we established oxidative stress- and UV-induced cellular senescence models using primary human dermal fibroblasts (HDFs). RNA sequencing after overexpression or knockdown of HDAC4 in primary HDFs identified candidate molecular targets of HDAC4. Integrative analyses of our current and public mRNA expression profiles identified DNA damage-inducible transcript 4 (DDIT4) as a critical senescence-associated factor regulated by HDAC4. Indeed, DDIT4 and HDAC4 expressions were downregulated during oxidative stress- and UV-induced senescence. HDAC4 overexpression rescued the senescence-induced decrease in DDIT4 and senescence phenotype, which were prevented by DDIT4 knockdown. In addition, DDIT4 overexpression reversed changes in senescence-associated secretory phenotypes and aging-related genes, suggesting that DDIT4 mediates the reversal of cellular senescence via HDAC4. Collectively, our results identify DDIT4 as a promising target regulated by HDAC4 associated with cellular senescence and epigenetic skin aging.