AB016. Intracranial tumor characteristics and the incidence of cachexia: a cross-sectional study.

BACKGROUND: Intracranial tumors constitute a significant burden on global morbidity and disability, posing a risk for the development of cachexia. Cancer cachexia is a multi-organ syndrome of systemic inflammation and negative energy balance which may lead to diminished treatment efficacy and reduced survival rates. The association between intracranial tumor features and incidence of cachexia remains unknown. The purpose of this study is to investigate the association between the characteristics of intracranial tumors and the incidence of cachexia in patients. METHODS: We conducted a retrospective cross-sectional study to observe hospitalized intracranial tumor patients at Dr. Cipto Mangunkusumo Hospital. This study described the prevalence and the percentage of baseline characteristics, the diagnosis of cachexia was based on Evans criteria. Kolmogorov-Smirnov for the normality test. Bivariate analysis was done using the Chi-square test for qualified categorical variables, the Fischer test for unqualified categorical variables, and the Mann-Whitney test for ordinal variables. RESULTS: Our study revealed of 36 subjects with intracranial tumor diagnosis, the incidence of cachexia was higher in secondary brain tumors compared to primary brain tumors [odds ratio (OR) 5.5; 95% confidence interval (CI): 1.28-23.69; P=0.02]. Cancer cachexia occurs through inflammation, autonomic, and neuroendocrine pathways, leading to increased energy expenditure and decreased energy intake. The burden of secondary brain tumor amplifies the overall metabolic demands and systemic inflammation thus contributing to cachexia progression, which is identified by significant weight loss in patients with secondary brain tumor groups compared to primary tumors (P=0.01). Patients with cachexia tend to experience malnutrition and fatigue (P=0.04), which may interfere with their survival rates and quality of life. The most common neurological deficit observed in our subjects is headache (72.2%), while patients presenting with clinical manifestations of extremity weakness were more likely to develop cachexia (OR 6.4; 95% CI: 1.23-35.44; P=0.04). There were no significant differences in age distribution, gender, and brain tumor location among the subject groups. CONCLUSIONS: Patients with secondary brain tumors and extremity weakness are more likely to develop cachexia. The severity of cachexia can help distinguish between primary and secondary brain tumors. Clinicians should pay attention to neurological deficits, particularly extremity weakness, as it can worsen cachexia.

AB032. The effect of high-dose dexamethasone on systemic immune-inflammation index (SII) in patients with brain tumor, a retrospective study in tertiary hospital in Indonesia.

BACKGROUND: Inflammation plays an important role in proliferation, migration, and invasion of tumor cells; therefore, many research has been done to investigate inflammation parameters including systemic immune-inflammatory index (SII). Dexamethasone, a strong anti-inflammatory, is still widely used as the main treatment in vasogenic edema. High-dose administration (16 mg/day) is recommended in patients with brain tumors with increased intracranial pressure. We performed this retrospective study to determine SII profile, dexamethasone use, and the effect of high-dose dexamethasone on SII in patients with brain tumors. METHODS: We performed a retrospective study on patients with brain tumors in 2022-2023 period who were treated with intravenous high-dose dexamethasone. Patient demographics, clinical characteristics of the brain tumor, concurrent infection, as well as dexamethasone dose and duration were recorded. Platelet, neutrophil, and lymphocyte count obtained prior to dexamethasone administration, and on the fifth to seventh day were also collected. SII was calculated by the following formula: neutrophil × platelet counts/lymphocyte. Data were then analyzed using Microsoft Excel 2019 and SPSS 29.0.2.0. RESULTS: We enrolled 56 patients with brain tumors, age 47±13.5 years, 78.6% were female, 69.6% had malignant brain tumors (brain metastases and high-grade primary brain tumors) and 26.8% had concurrent infection. High-dose dexamethasone was administered with average dose of 16.8±3.3 mg/day for average duration of 4.8±1.8 days. SII was significantly higher in malignant compared to benign brain tumors both in prior and after dexamethasone administration (P=0.02, P=0.01). SII was significantly higher in metastasis brain tumor compared to primary brain tumor (P=0.005). High-dose dexamethasone significantly increased SII and decreased lymphocyte count (P=0.006, P=0.04). CONCLUSIONS: SII was found higher in malignant brain tumor and brain metastasis. High-dose dexamethasone was administered with average dose of 16.81±3.37 mg/day for average duration of 4.78±1.84 days. SII was found to be higher after high-dose dexamethasone, due to a decrease of lymphocyte counts in peripheral blood.

AB037. Association between systemic immune-inflammation index with hypercoagulable state in primary brain tumor: a retrospective study in Dr. Cipto Mangunkusumo Hospital, Jakarta, Indonesia.

BACKGROUND: Hypercoagulable state is considered a common complication in brain tumors, which increases the risk of thromboembolic events, leading to mortality and morbidities. Detecting hypercoagulability typically requires expensive tests, such as D-dimer and fibrinogen, which are not accessible in many healthcare facilities in Indonesia. The systemic immune-inflammation index (SII) is known as an inflammation marker that contributes to hypercoagulability in many conditions. SII tests are more affordable and widely available, but there is still not much study that investigates the association between SII and hypercoagulable state in primary brain tumors. This preliminary study aimed to find an association between SII with hypercoagulable state in primary brain tumor conditions. METHODS: We collected data from inpatients diagnosed with primary brain tumors from 2021 to 2023 in Dr. Cipto Mangunkusumo Hospital. Hypercoagulable states were established from high D-dimer serum testing (>660 µg/L). SII was calculated by the following formula: neutrophil counts × platelet counts/lymphocyte counts. Both D-dimer and SII were collected at first admission to the hospital. The receiver operating characteristic (ROC) curve were used to determine the SII cut-off value. Bivariate and multivariate logistic analyses were performed to confirm the association with the incidence of hypercoagulable state. RESULTS: This study enrolled 65 patients with primary brain tumors, 73.8% subjects with hypercoagulable state. A total of 61.5% were female, mean age 47.54±2.02 years. High-grade tumors exhibited a higher prevalence than low-grade tumors (53.8% vs. 46.2%). SII cut-off value determined at 1,343.50 (sensitivity 56.9%, specificity 57.1%). We found no significant association between SII and hypercoagulable state. Multivariate analyses show that duration of brain tumor before 6 months (P=0.04), and history of brain tumor surgery (P=0.02) were significantly associated with the incidence of hypercoagulable state in primary brain tumor. CONCLUSIONS: Based on the findings in this investigation, we find 73.8% subjects with hypercoagulable states in primary brain tumor. No significant relationship between high SII and hypercoagulable states but significant association of duration brain tumor before 6 months and history of brain tumor surgery with hypercoagulable state in primary brain tumor.

AB069. Type of personality and cancer-related pain in central nervous system (CNS) tumor patients: a cross-sectional study.

BACKGROUND: Pain is the most common complaint experienced by central nervous system (CNS) tumor patients. Pain, especially cancer pain, involves the whole aspect of a person, such as personality, cognition, and behavior. Personality characteristics play an important role in how a person perceives pain rate and deals with painful situation. This study aimed to describe types of personality and investigate relationship between types of personality and cancer-related pain in CNS patients. METHODS: This study was conducted at Cipto Mangunkusumo General Hospital from January to December 2023, that was determined by random sampling. The analysis included a total of 99 subjects from inpatient settings. In depth interview was used to assess type of personality and Numeric Rating Scale (NRS) was used to assess intensity of pain. Data analyses were carried out using the Chi-squared and Fisher's exact test to assess the relationship between types of personality and cancer-related pain in CNS patients. RESULTS: There were 99 subjects with mean age of 48.37±12.96 years, mostly women (60.6%). The results showed that in patients with CNS tumor, the most common neurological deficit was cancer pain (93.9%), consisting of no-mild pain (30.3%) and moderate-severe pain (69.7%). The prevalence of narcissistic personality was 73.7%, followed by histrionic personality 15.2%, and other personality (11.1%) such as borderline, obsessive-compulsive, and avoidant personality. Narcissistic personality traits were found in 48.5% of patients with moderate-severe pain. However, bivariate analysis showed that there was no significant relationship between types of personality and intensity of pain in CNS tumor patients (P=0.60). CONCLUSIONS: Although there was no significant relationship, cluster B personality (narcissistic, histrionic, and borderline) was found in a large percentage of CNS tumor patients. Research findings showed that intensity of pain was caused by biological components of pain and may be influenced by the patient's perception of pain itself, not solely due to personality. Therefore, it's important for health workers to pay attention and give optimal management to every patient's pain complaint, and not to ignore or minimize it. Psychiatrists can be involved by giving psychotherapy so that patients can deal with their pain in a more adaptive way.

AB068. Psychiatric disorder in central nervous system tumor patients and its related factors.

BACKGROUND: Patients of central nervous system (CNS) tumors have a potential to develop psychiatric disorder. These may present resulting from tumor mass, edema, or patient's failure to adapt to their illness and treatment. The presence of psychiatric disorders may cause disability, decreased daily functioning, reduced quality of life, and even death. In order to provide adequate treatment to patients with CNS tumors, it's important to evaluate the type of psychiatric disorder in patients with spinal and brain tumors. This study aimed to investigate the prevalence of psychiatric disorder dan related factors that exist in patients with brain and spinal tumors. METHODS: In a study conducted at Cipto Mangunkusumo General Hospital from January to December 2023, factors associated with psychiatric disorders in patients with CNS tumors were investigated. The analysis included a total of 161 subjects from inpatient settings. In depth interview was utilized to assess psychiatric disorder. Data analyses were carried out using the Chi-square and Fisher's exact test to assess the relationship between locations of tumor, neurological deficits, and psychiatric disorders. RESULTS: There were 161 subjects with mean age of 48.86±13.13 years, mostly women (59.0%). Patients with spinal tumor have more psychiatric disorders compared to their counterpart with intracranial tumor (79.1% and 76.3% respectively), while the most common psychiatric disorder was adjustment disorder. There is no significant relationship between tumor location and psychiatric disorder. In both patients with intracranial and spinal tumors, the most common neurological deficit was cancer pain (88.2%). However, bivariate analysis showed that among the neurological deficits found in the CNS tumor patients, dysphagia (P=0.02) and incontinence (P=0.02) have significant relationship with depression, while pain (P=0.02) and cognitive dysfunction (P=0.01) have significant relationship with adjustment disorder. It also showed that pain (P<0.001), cognitive dysfunction (P=0.002), and seizure (P=0.03) have significant relationship with organic mental disorder. CONCLUSIONS: Dysphagia, incontinence, pain, cognitive disfunction, and seizure were identified as risk factors for psychiatric disorders in intracranial and spinal tumor patients. The finding underscores the importance of screening and comprehensive psychiatric evaluations in patients with CNS tumors, as psychiatric symptoms may significantly impact their quality of life and treatment outcomes.

Effectiveness of transcranial direct current stimulation (tDCS) as adjunctive treatment for chronic headache in adults with clinically stable systemic lupus erythematosus (SHADE): a randomised double-blind multiarm sham controlled clinical trial.

BACKGROUND: Chronic headache is a 'silent' neuropsychiatric systemic lupus erythematosus symptom with heterogeneous prevalence, potentially reaching 54.4%. It may reduce quality of life by increasing the likelihood of depression and sleep disturbance. While pharmacotherapy remains the first-line treatment, the current management is still challenging and needs other non-invasive modalities. An effective, tolerable and disease-specific treatment modality including transcranial direct current stimulation (tDCS) is considered to reduce the frequency of chronic headaches, including in SLE. Until recently, there was no standard protocol for tDCS in treating headaches. METHODS AND ANALYSIS: SHADE is a single-centre randomised double-blind multiarm sham-controlled trial for adults with clinically stable SLE, chronic headaches and without history of traumatic brain injury, brain infection, stroke or brain tumour. Random allocation is conducted to 88 subjects into 3 treatment groups (administration at primary motor, primary sensory and dorsolateral prefrontal cortex) and control group in 1:1:1:1 ratio. The primary endpoint is reduced number of headache days after adjunctive tDCS. The secondary endpoints are reduced headache intensity, increased quality of life, increased sleep quality, decreased depression and reduced analgesics use. The outcome is measured monthly until 3-month postintervention using headache diary, 36-Item Short Form Survey, Chronic Headache Quality of Life Questionnaire, Pittsburgh Sleep Quality Index and Mini International Neuropsychiatry Interview version 10 (MINI ICD 10). Intention-to-treat analysis will be performed to determine the best tDCS electrode placement. ETHICS AND DISSEMINATION: Ethical approval had been obtained from the local Institutional Review Board of Faculty of Medicine Universitas Indonesia. Results will be published through scientific relevant peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05613582.

Dual-Function Semaphorin 4D Released by Platelets: Suppression of Osteoblastogenesis and Promotion of Osteoclastogenesis.

Effects of the antiosteoblastogenesis factor Semaphorin 4D (Sema4D), expressed by thrombin-activated platelets (TPs), on osteoblastogenesis, as well as osteoclastogenesis, were investigated in vitro. Intact platelets released both Sema4D and IGF-1. However, in response to stimulation with thrombin, platelets upregulated the release of Sema4D, but not IGF-1. Anti-Sema4D-neutralizing monoclonal antibody (mAb) upregulated TP-mediated osteoblastogenesis in MC3T3-E1 osteoblast precursors. MC3T3-E1 cells exposed to TPs induced phosphorylation of Akt and ERK further upregulated by the addition of anti-sema4D-mAb, suggesting the suppressive effects of TP-expressing Sema4D on osteoblastogenesis. On the other hand, TPs promoted RANKL-mediated osteoclastogenesis in the primary culture of bone-marrow-derived mononuclear cells (BMMCs). Among the known three receptors of Sema4D, including Plexin B1, Plexin B2 and CD72, little Plexin B2 was detected, and no Plexin B1 was detected, but a high level of CD72 mRNA was detected in RANKL-stimulated BMMCs by qPCR. Both anti-Sema4D-mAb and anti-CD72-mAb suppressed RANKL-induced osteoclast formation and bone resorptive activity, suggesting that Sema4D released by TPs promotes osteoclastogenesis via ligation to a CD72 receptor. This study demonstrated that Sema4D released by TPs suppresses osteogenic activity and promotes osteoclastogenesis, suggesting the novel property of platelets in bone-remodeling processes.

A novel method of sampling gingival crevicular fluid from a mouse model of periodontitis.

Using a mouse model of silk ligature-induced periodontal disease (PD), we report a novel method of sampling mouse gingival crevicular fluid (GCF) to evaluate the time-dependent secretion patterns of bone resorption-related cytokines. GCF is a serum transudate containing host-derived biomarkers which can represent cellular response in the periodontium. As such, human clinical evaluations of PD status rely on sampling this critical secretion. At the same time, a method of sampling GCF from mice is absent, hindering the translational value of mouse models of PD. Therefore, we herein report a novel method of sampling GCF from a mouse model of periodontitis, involving a series of easy steps. First, the original ligature used for induction of PD was removed, and a fresh ligature for sampling GCF was placed in the gingival crevice for 10min. Immediately afterwards, the volume of GCF collected in the sampling ligature was measured using a high precision weighing balance. The sampling ligature containing GCF was then immersed in a solution of PBS-Tween 20 and subjected to ELISA. This enabled us to monitor the volume of GCF and detect time-dependent changes in the expression of such cytokines as IL-1b, TNF-α, IL-6, RANKL, and OPG associated with the levels of alveolar bone loss, as reflected in GCF collected from a mouse model of PD. Therefore, this novel GCF sampling method can be used to measure various cytokines in GCF relative to the dynamic changes in periodontal bone loss induced in a mouse model of PD.

TRAP-positive osteoclast precursors mediate ROS/NO-dependent bactericidal activity via TLR4.

Osteoclastogenesis was induced by RANKL stimulation in mouse monocytes to examine the possible bactericidal function of osteoclast precursors (OCp) and mature osteoclasts (OCm) relative to their production of NO and ROS. Tartrate-resistant acid phosphatase (TRAP)-positive OCp, but few or no OCm, phagocytized and killed Escherichia coli in association with the production of reactive oxygen species (ROS) and nitric oxide (NO). Phagocytosis of E. coli and production of ROS and NO were significantly lower in TRAP+ OCp derived from Toll-like receptor (TLR)-4 KO mice than that derived from wild-type (WT) or TLR2-KO mice. Interestingly, after phagocytosis, TRAP+ OCp derived from wild-type and TLR2-KO mice did not differentiate into OCm, even with continuous exposure to RANKL. In contrast, E. coli-phagocytized TRAP+ OCp from TLR4-KO mice could differentiate into OCm. Importantly, neither NO nor ROS produced by TRAP+ OCp appeared to be engaged in phagocytosis-induced suppression of osteoclastogenesis. These results suggested that TLR4 signaling not only induces ROS and NO production to kill phagocytized bacteria, but also interrupts OCm differentiation. Thus, it can be concluded that TRAP+ OCp, but not OCm, can mediate bactericidal activity via phagocytosis accompanied by the production of ROS and NO via TLR4-associated reprograming toward phagocytic cell type.

miR-584 expressed in human gingival epithelial cells is induced by Porphyromonas gingivalis stimulation and regulates interleukin-8 production via lactoferrin receptor.

BACKGROUND: MicroRNAs (miRNAs) are short, non-coding RNAs that are involved in post-transcriptional regulation of gene expression. Differential miRNA expression in innate and acquired immunity has been shown to regulate immune cell development and function. miRNA expression has been demonstrated to affect pathophysiology of inflammatory diseases, such as rheumatoid arthritis and lupus. As such, this study explores the role of miRNA in the context of pathophysiology of destructive periodontitis. Specifically, this investigation profiles the differentially expressed miRNA of Porphyromonas gingivalis (Pg)-stimulated human gingival epithelial cells (HGECs). METHODS: The specific miRNAs differentially expressed in Pg-stimulated OBA-9, immortalized HGECs, were analyzed using microarray. Real-time polymerase chain reaction (PCR) and Western blotting were performed to confirm the level of miRNA expression and determine target production of miRNA in OBA-9. The production of interleukin (IL)-8 was measured to determine the bioactivity of target protein regulated by miRNA. RESULTS: miR-584, which targets lactoferrin receptor (LfR), was 3.39-fold upregulated by Pg stimulation. This upregulation of miR-584 was confirmed by real-time PCR. Pg stimulation resulted in the suppression of LfR at mRNA and protein levels. The transfection of the miR inhibitor for miR-584 in OBA-9 recovered Pg-induced suppression of LfR. The addition of human lactoferrin (hLf) had a suppressive effect on IL-8 production in Pg-stimulated OBA-9. However, hLf also decreased IL-8 production strongly in Pg-stimulated OBA-9 in the presence of the miR inhibitor for miR-584. CONCLUSION: These findings suggest that the upregulation of miR-584 by Pg in OBA-9 inhibits the anti-inflammatory effects of hLf via the suppression of LfR.