Serum cortisol and neuroticism for post-traumatic stress disorder over 2 years in patients with physical injuries.

AIM: This study aimed to explore the relationships between serum cortisol levels, personality traits, and the development of Post-Traumatic Stress Disorder (PTSD) over 2 years among individuals with physical injuries. METHODS: Participants were consecutively recruited from a trauma center and followed prospectively for 2 years. At baseline, serum cortisol levels were measured, and personality traits were categorized into five dimensions (Extraversion, Agreeableness, Conscientiousness, Neuroticism, and Openness), using the Big Five Inventory-10. The diagnosis of PTSD during follow-up (at 3, 6, 12, and 24 months post-injury) was determined using the Clinician-Administered PTSD Scale for DSM-5. Binary and multinomial logistic regression analyses were conducted to examine the interactions between cortisol levels, personality traits, and PTSD development. RESULTS: Among 923 patients analyzed, 112 (12.1%) were diagnosed with PTSD at some point during the study period, with prevalence rates decreasing from 8.8% at 3 months to 3.7% at 24 months post-injury. Direct associations between cortisol levels or personality traits and PTSD were not observed. However, a significant interaction between lower cortisol levels and higher Neuroticism in relation to PTSD risk was identified, especially during the early follow-up periods (3 to 6 months), but this association waned from the 12-month follow-up onward. CONCLUSION: Our findings reveal Neuroticism-dependent associations between serum cortisol levels and PTSD development, exhibiting temporal variations. These results suggest that PTSD development may be influenced by a complex, time-sensitive interplay of biological and psychosocial factors, underscoring the importance of considering individual differences in stress reactivity and personality in PTSD research and treatment.

Machine-learning model to predict the tacrolimus concentration and suggest optimal dose in liver transplantation recipients: a multicenter retrospective cohort study.

Titrating tacrolimus concentration in liver transplantation recipients remains a challenge in the early post-transplant period. This multicenter retrospective cohort study aimed to develop and validate a machine-learning algorithm to predict tacrolimus concentration. Data from 443 patients undergoing liver transplantation between 2017 and 2020 at an academic hospital in South Korea were collected to train machine-learning models. Long short-term memory (LSTM) and gradient-boosted regression tree (GBRT) models were developed using time-series doses and concentrations of tacrolimus with covariates of age, sex, weight, height, liver enzymes, total bilirubin, international normalized ratio, albumin, serum creatinine, and hematocrit. We conducted performance comparisons with linear regression and populational pharmacokinetic models, followed by external validation using the eICU Collaborative Research Database collected in the United States between 2014 and 2015. In the external validation, the LSTM outperformed the GBRT, linear regression, and populational pharmacokinetic models with median performance error (8.8%, 25.3%, 13.9%, and - 11.4%, respectively; P < 0.001) and median absolute performance error (22.3%, 33.1%, 26.8%, and 23.4%, respectively; P < 0.001). Dosing based on the LSTM model's suggestions achieved therapeutic concentrations more frequently on the chi-square test (P < 0.001). Patients who received doses outside the suggested range were associated with longer ICU stays by an average of 2.5 days (P = 0.042). In conclusion, machine learning models showed excellent performance in predicting tacrolimus concentration in liver transplantation recipients and can be useful for concentration titration in these patients.

Assessing the Predictive Validity of Early Post-injury CAPS-5 for Later Posttraumatic Stress Disorder Diagnosis.

Abstract.Objective: The Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) is a widely recognized tool with exceptional reliability and validity in evaluating and diagnosing PTSD. This study aimed to determine the predictive values of CAPS-5 assessed early postinjury for subsequent development of PTSD during a 2-year follow-up period.Methods: Patients with moderate to severe physical injuries were recruited from a trauma center at a university hospital in South Korea between June 2015 and January 2021. At baseline, 1,142 patients underwent evaluations using CAPS-5 for the diagnosis of acute stress disorder (ASD) along with total scores. They were followed up for PTSD using the CAPS-5 evaluations at 3, 6, 12, and 24 months post-baseline. Area under receiver operating curve (AUROC) analyses were conducted to identify predictive values of the CAPS-5 for later PTSD development.Results: CAPS-5 diagnosis of ASD at baseline displayed fair to failed performance (AUROCs: 0.555-0.722) for predicting follow-up PTSD. However, CAPS-5 scores of ≥15 exhibited good to fair predictive accuracy (AUROCs: 0.767-0.854) for later PTSD development. Notably, for patients with intentional injuries or a history of previous trauma, a higher CAPS-5 score of ≥16 showed improved predictive accuracy.Conclusion: A CAPS-5 score of ≥15 would be an effective and practical cutoff for early prediction of PTSD following physical injuries. In cases of intentional injuries or a documented trauma history, a cutoff of ≥16 may offer enhanced predictive precision. Future research in diverse settings and populations is needed to confirm the generalizability of our findings.

QuantiFERON monitor predicts early cytomegalovirus infection and viral burden in allogeneic hematopoietic stem cell transplantation.

INTRODUCTION: Cytomegalovirus (CMV) infection is a major cause of transplantation-related morbidity and mortality. This study assessed the utility of the QuantiFERON monitor (QFM; Qiagen) for the prediction of early CMV infection and viral burden. METHODS: QuantiFERON-CMV (QF-CMV; Qiagen) and QFM were measured at the post-allogeneic hematopoietic stem cell transplantation (HSCT) week 4. CMV DNA was measured at every visit until post-HSCT week 24. The QFM cutoff specific to CMV infection was established. RESULT: At the post-HSCT week 4, the QFM cutoff predicting CMV infection was 86.95 IU/mL. While QF-CMV results at the post-HSCT week 4 were associated with high-level CMV infection (CMV DNA ≥ 5,000 IU/mL) but not with CMV infection (CMV DNA ≥ 500 IU/mL), QFM was associated with both CMV infection and high-level CMV infection. Both indeterminate QF-CMV and nonreactive QFM were associated with increased peak CMV DNA. CONCLUSION: Low QFM is a risk factor for CMV infection and increased CMV viral loads. QFM at post-HSCT week 4 can be utilized as an assay to predict the risk and burden of early CMV infection in HSCT recipients, in conjunction with other risk factors.

Delayed effects of alcohol consumption on the association between serum BDNF levels and post-traumatic stress disorder development over two-years.

BACKGROUNDS: This study aimed to examine the individual and combined effects of serum BDNF (sBDNF) levels and alcohol consumption status, assessed shortly after a physical injury, on the development of post-traumatic stress disorder (PTSD) over two years. METHODS: Participants were consecutively recruited from a trauma center and followed prospectively for two years. At baseline, sBDNF levels and alcohol consumption history were assessed. A range of socio-demographic and clinical covariates were also collected. PTSD diagnosis during follow-up (3, 6, 12, and 24 months post-injury) was established using the Clinician-Administered PTSD Scale for DSM-5. Binary and multinomial logistic regression analyses were employed to investigate the relationships between sBDNF levels, alcohol consumption status, and PTSD onset. RESULTS: Out of 923 participants analyzed, 112 (12.1%) developed PTSD at some point during the study, with prevalence rates of 8.8% at 3 months, 7.6% at 6 months, 4.8% at 12 months, and 3.7% at 24 months. The study found no individual associations between sBDNF levels or alcohol consumption status and PTSD development. However, lower sBDNF levels significantly predicted PTSD in individuals who consumed alcohol, a relationship not observed in non-drinkers, with significant interaction terms. This pattern was consistent at later follow-up points from 12 to 24 months, but not at earlier assessments at 3 and 6 months. LIMITATIONS: The study's reliance on participants from a single trauma center with moderate to severe injuries may limit the generalizability of the findings. CONCLUSIONS: A significant interaction between sBDNF levels and alcohol consumption in relation to PTSD development was observed, particularly in the long term. These findings highlight the necessity of considering both sBDNF levels and alcohol consumption in strategies aimed at preventing PTSD among individuals with physical injuries, underscoring the need for tailored approaches based on these factors.

Unique immune characteristics and differential anti-PD-1-mediated reinvigoration potential of CD8+ TILs based on BRCA1/2 mutation status in epithelial ovarian cancers.

BACKGROUND: We aimed to investigate the distinct immunological characteristics of the tumor immune microenvironment in epithelial ovarian cancer (EOC) according to BRCA1/2 mutations status and differential PD-1 expression levels. METHODS: Tumor-infiltrating lymphocytes (TILs) were collected from patients with newly diagnosed advanced-stage EOC (YUHS cohort, n=117). This YUHS cohort was compared with The Cancer Genome Atlas (TCGA) data for ovarian serous cystadenocarcinoma (n=482), in terms of survival outcomes and immune-related gene profiles according to BRCA1/2 status. We used multicolor flow cytometry to characterize the immune phenotypes and heterogeneity of TILs with or without BRCA1/2 mutations. In vitro functional assays were conducted to evaluate the reinvigorating ability of CD8+ TILs on anti-PD-1 treatment. RESULTS: We found that EOC patients with BRCA1/2 mutations (BRCA1/2mt) exhibited better survival outcomes and significantly higher tumor mutation burden (TMB), compared with BRCA1/2 non-mutated (BRCA1/2wt) patients. Furthermore, CD8+ TILs within BRCA1/2mt tumors displayed characteristics indicating more severe T-cell exhaustion than their BRCA1/2wt counterparts. Notably, the capacity for anti-PD-1-mediated reinvigoration of CD8+ TILs was significantly greater in BRCA1/2wt tumors compared with BRCA1/2mt tumors. Additionally, within the BRCA1/2wt group, the frequency of PD-1highCD8+ TILs was positively correlated with the reinvigoration capacity of CD8+ TILs after anti-PD-1 treatment. CONCLUSION: Our results highlight unique immune features of CD8+ TILs in EOC and a differential response to anti-PD-1 treatment, contingent on BRCA1/2 mutation status. These findings suggest that immune checkpoint blockade may be a promising frontline therapeutic option for selected BRCA1/2wt EOC patients.

ETV6::ABL1 fusion: from overlooked minor clone in myeloproliferative neoplasm to major player in leukemic transformation.

The ETV6::ABL1 fusion defines a subgroup of myeloid/lymphoid neoplasms with eosinophilia and tyrosine kinase gene fusions. We report a case of extramedullary involvement and leukemic transformation in myeloproliferative neoplasm (MPN), where ETV6::ABL1 was initially overlooked but later detected in the blast phase. ETV6::ABL1 burden was very low during the MPN phase but increased substantially during the blast phase. This correlation between ETV6::ABL1 burden and disease phenotype indicated that an immature leukemic clone is the sole carrier of ETV6::ABL1, suggesting that ETV6::ABL1 is not the primary driver of the MPN phase. Moreover, only the blast phase revealed somatic mutations in RUNX1 and STAG2, or complex karyotype, while the MPN phase revealed no molecular and cytogenetic abnormalities. Therefore, it remains uncertain whether the small clone of ETV6::ABL1 influenced the manifestation of MPN or if another underlying driver was responsible for the MPN phase, necessitating further research.

Toxicity Evaluation of a Non-Pain Pharmacopuncture Extract Using a Bacterial Reverse Mutation Test.

Objectives: The objective of this study was to assess the genotoxicity of a no-pain pharmacopuncture (NPP) extract developed in 2022 using a bacterial reverse mutation assay, aiming to further substantiate the safety profile of NPP. Methods: The genotoxicity evaluation involved a bacterial reverse mutation assay to assess the mutagenic potential of NPP extracts with and without metabolic activation. Histidine-requiring Salmonella typhimurium strains (TA98, TA100, TA1535, and TA1537) and tryptophan-requiring Escherichia coli strains (WP2uvrA) were used in the assay. Results: The NPP extract did not induce a revertant colony count exceeding two times that of the negative control at any dose level in any of the tested strains, both with and without metabolic activation. Additionally, no growth inhibition or precipitation was observed in the presence of NPP. Conclusion: Based on the findings, it can be concluded that the NPP extract exhibited no mutagenic potential in the in vitro genotoxicity tests conducted.

INSPIRE, a publicly available research dataset for perioperative medicine.

We present the INSPIRE dataset, a publicly available research dataset in perioperative medicine, which includes approximately 130,000 surgical operations at an academic institution in South Korea over a ten-year period between 2011 and 2020. This comprehensive dataset includes patient characteristics such as age, sex, American Society of Anesthesiologists physical status classification, diagnosis, surgical procedure code, department, and type of anaesthesia. The dataset also includes vital signs in the operating theatre, general wards, and intensive care units (ICUs), laboratory results from six months before admission to six months after discharge, and medication during hospitalisation. Complications include total hospital and ICU length of stay and in-hospital death. We hope this dataset will inspire collaborative research and development in perioperative medicine and serve as a reproducible external validation dataset to improve surgical outcomes.

Differential predictors of early- and delayed-onset post-traumatic stress disorder following physical injury: a two-year longitudinal study.

Objectives: This study aimed to investigate the predictors of both early- and delayed-onset PTSD over a 2-year period following physical injuries. Methods: Patients were recruited from a trauma center at a university hospital in South Korea (June 2015 ~ January 2021). At baseline, 1142 patients underwent comprehensive assessments including socio-demographic, pre-trauma, trauma-related, and peri-trauma evaluations. Diagnoses of acute stress disorder (ASD) and subthreshold ASD were also determined using the Clinician-administered PTSD Scale (CAPS). Follow-up assessments at three months included diagnoses of PTSD and subthreshold PTSD using CAPS, and stressful life events (SLEs), with additional evaluations at 6, 12, and 24 months. The analyzed sample comprised 1014 patients followed up at least once after the baseline and 3-month evaluations. PTSD diagnoses were categorized into early-onset (within the first six months after trauma) and delayed-onset (more than six months after trauma). Logistic regression models identified predictors for each group. Results: Early-onset and delayed-onset PTSD were diagnosed in 79 and 35 patients, respectively. Early-onset PTSD was predicted by previous psychiatric disorders, previous traumatic events, ASD and subthreshold ASD diagnoses, and higher anxiety levels. In contrast, delayed-onset PTSD was linked to higher education, higher injury severity, and subthreshold PTSD and SLEs at 3-month follow-up. Conclusion: Distinct predictors were found for early-onset and delayed-onset PTSD. The findings underscore the heterogeneous factors influencing the temporal development of PTSD post-trauma, and may provide valuable guidance for more targeted interventions and improved patient outcomes.

Moderating role of functioning level on the association between suicidal ideation and delayed-onset post-traumatic stress disorder.

OBJECTIVES: This study aimed to investigate the relationship between suicidal ideation at baseline and the development of post-traumatic stress disorder (PTSD) in individuals who have experienced physical injuries, with a specific focus on how this relationship is moderated by the patient's functioning level. METHODS: Participants were consecutively recruited from a trauma center and prospectively followed for two years. At baseline, suicidal ideation was assessed using the Brief Psychiatric Rating Scale, and functioning level was evaluated using the Social and Occupational Functioning Assessment Scale. During the follow-up, PTSD diagnosis was established using the Clinician-Administered PTSD Scale for DSM-5. Binary and multinomial logistic regression analyses were employed to examine the associations between suicidal ideation, functioning level, and PTSD. RESULTS: Of the 1014 participants analyzed, 114 (11.2%) developed PTSD, with early-onset observed in 79 (7.8%) and delayed-onset in 35 (3.5%) cases. Suicidal ideation at baseline was significantly associated with both early- and delayed-onset PTSD. Notably, higher functioning individuals with baseline suicidal ideation had an increased likelihood of developing delayed-onset PTSD, while this association was not significant in lower functioning individuals, with significant interaction terms. Additionally, suicidal ideation was a consistent predictor of early-onset PTSD across all functioning levels. CONCLUSION: The impact of baseline suicidal ideation on PTSD varies depending on the individual's functioning level, with higher functioning individuals being more vulnerable to delayed-onset PTSD. These findings underscore the importance of considering functional status in the assessment and intervention of PTSD following physical trauma.

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.

Impact of suicidality on delayed-onset post-traumatic stress disorder is modified by age: A two-year longitudinal study.

OBJECTIVES: This study aimed to investigate the relationship between early suicidality and post-traumatic stress disorder (PTSD) onset in patients with physical injuries, focusing on age as a modifying factor. METHODS: At baseline, 1014 patients were evaluated for suicidality, age divided into younger (<60 years) vs. older (≥60 years) groups, and potential covariates. PTSD was diagnosed at follow-up at 3, 6, 12, and 24 months, and then were categorized into early-onset (within the first six months after trauma) and delayed-onset (more than six months after trauma). Logistic regression models were used after adjusting for covariates. RESULTS: Presence of suicidality at baseline was significantly associated with delayed-onset PTSD in older but not younger patients with significant interaction terms, whereas it was significantly associated with early-onset PTSD across all age groups. CONCLUSION: Age-specific associations were found between suicidality and PTSD onset. The findings highlight the importance of early suicidality assessment, especially in older patients for ongoing monitoring and support, and underscore the critical need for early PTSD identification and intervention for all ages.

Effect of hyperbilirubinemia on the accuracy of continuous non-invasive hemoglobin measurements in liver transplantation recipients.

This study evaluated the effect of hyperbilirubinemia on the accuracy of continuous non-invasive hemoglobin (SpHb) measurements in liver transplantation recipients. Overall, 1465 SpHb and laboratory hemoglobin (Hb) measurement pairs (n = 296 patients) were analyzed. Patients were grouped into normal (< 1.2 mg/dL), mild-to-moderate (1.2-3.0 mg/dL), and severe (> 3.0 mg/dL) hyperbilirubinemia groups based on the preoperative serum total bilirubin levels. Bland-Altman analysis showed a bias of 0.20 (95% limit of agreement, LoA: - 2.59 to 3.00) g/dL, 0.98 (95% LoA: - 1.38 to 3.35) g/dL, and 1.23 (95% LoA: - 1.16 to 3.63) g/dL for the normal, mild-to-moderate, and severe groups, respectively. The four-quadrant plot showed reliable trending ability in all groups (concordance rate > 92%). The rates of possible missed transfusion (SpHb > 7.0 g/dL for Hb < 7.0 g/dL) were higher in the hyperbilirubinemia groups (2%, 7%, and 12% for the normal, mild-to-moderate, and severe group, respectively. all P < 0.001). The possible over-transfusion rate was less than 1% in all groups. In conclusion, the use of SpHb in liver transplantation recipients with preoperative hyperbilirubinemia requires caution due to the positive bias and high risk of missed transfusion. However, the reliable trending ability indicated its potential use in clinical settings.

Characteristics of Hirayama Disease in Young South Korean Soldiers.

BACKGROUND AND PURPOSE: The purpose of this study was to describe the clinical presentation and features in electrodiagnostic and imaging investigations of young South Korean males diagnosed with Hirayama disease (HD). METHODS: We reviewed the electronic medical records of South Korean enlisted soldiers who were diagnosed with HD and discharged from military service during 2011-2021. We investigated the clinical characteristics and results of electrodiagnostic and magnetic resonance imaging (MRI) investigations. We analyzed laterality and identified the involved muscles using needle electromyography (EMG). Loss of lordosis, localized cervical cord atrophy, loss of attachment between the posterior dura and subjacent lamina, asymmetric flattening of the cord, crescent-shaped mass in the posterior epidural space, and noncompressive intramedullary T2-weighted high signal intensity were investigated using neutral- or flexion-position MRI. RESULTS: Forty-two male patients aged 20.2±0.8 years (mean±standard deviation) were identified. All patients complained of hand weakness, and 10 complained of hand tremor (23.8%). Four patients (9.5%) had symptoms in both upper limbs, and five (11.9%) had sensory disturbances. Needle EMG revealed that muscles in the C7-T1 myotome were commonly involved, and C5-C6 involvement of the deltoid (10.5%) and biceps brachii (12.5%) was also observed. In cervical MRI, localized cord atrophy (90.0%) was the most characteristic finding, and cord atrophy was most severe at the C5-C6 level (58.3%). CONCLUSIONS: This is the first description of a large number of patients with HD in South Korea. The clinical presentation and features found in electrodiagnostic and imaging investigations will improve the understanding of HD in the young South Korean male population.

Clinical relevance of vaginal natural orifice transluminal endoscopic surgery (vNOTES) in gynecology.

This study reviews the progress and recent advances in vaginal natural orifice transluminal endoscopic surgery (vNOTES) as a minimally invasive gynecologic procedure. The proposed advantages of vaginal natural orifice transluminal surgery include enhanced cosmesis due to a scarless procedure, better exposure compared with the pure vaginal approach, tolerable pain scores, fewer perioperative complications, and a shorter hospital stay. Recent advances in surgical instrumentation and technology have improved the feasibility of vNOTES as an innovative treatment option for gynecological conditions. However, technical challenges and training issues must be overcome before its widespread use. As a promising surgical innovation, further randomized comparative studies are required to clarify the safety and effectiveness of vNOTES in gynecology.

Genetic Characteristics of Patients with Young-Onset Myelodysplastic Neoplasms.

Myelodysplastic neoplasm (MDS) is a heterogeneous group of myeloid neoplasms affected by germline and somatic genetic alterations. The incidence of MDS increases with age but rarely occurs at a young age. We investigated the germline and somatic genetic alterations of Korean patients with young-onset MDS (<40 years). Among the thirty-one patients, five (16.1%) had causative germline variants predisposing them to myeloid neoplasms (three with GATA2 variants and one each with PGM3 and ETV variants). We found that PGM3 deficiency, a subtype of severe immunodeficiency, predisposes patients to MDS. Somatic mutations were identified in 14 patients (45.2%), with lower rates in patients aged < 20 years (11.1%). Nine (29%) patients had U2AF1 S34F/Y mutations, and patients with U2AF1 mutations showed significantly worse progression-free survival (p < 0.001) and overall survival (p = 0.006) than those without U2AF1 mutations. A UBA1 M41T mutation that causes VEXAS syndrome was identified in a male patient. In conclusion, a germline predisposition to myeloid neoplasms occurred in ~16% of young-onset MDS patients and was largely associated with primary immunodeficiencies, including GATA2 deficiency. Furthermore, the high frequency of somatic U2AF1 mutations in patients with young-onset MDS suggests the presence of a distinct MDS subtype.