Effect of Roselle Flower Extract (Hibiscus sabdariffa Linn.) on Reducing Steatosis and Steatohepatitis in Vitamin B12 Deficiency Rat Model.

Background and Objectives: Non-alcoholic Fatty Liver Disease (NAFLD) can occur as a result of micronutrient deficiencies. Hibiscus sabdarifa, a plant used in traditional medicine, contains ingredients that can help prevent this process. This study looked at the potency of Hibiscus sabdariffa Ethanol Extract (HSE) to prevent homocysteine-induced liver damage in animals that were deficient in vitamin B12. Materials and Methods: A comparative study of the effects of roselle extract is presented in an experimental design. Thirty Sprague-Dawley rats were divided into six groups using randomization. To demonstrate the absence of liver damage in the experimental animals under normal conditions, a control group was fed a normal diet without HSE. For the induction of liver damage in the experimental animals, the vitamin B12-restricted group was administered a vitamin B12-restricted diet. To test the effect of HSE on liver damage, the treatment group was given HSE along with a vitamin B12-restricted diet. Each group was given two treatment periods of eight and sixteen weeks. These results were compared with the results of the parameter examination between the vitamin B12 restriction group, with and without HSE, using an ANOVA statistic. The data were analyzed with licensed SPSS 20.0 software. Results: HSE significantly increased the blood levels of vitamin B12 while lowering homocysteine levels. The administration of HSE reduced liver damage based on the activity of liver function enzymes in the plasma due to a limitation of vitamin B12. HSE decreased Sterol Regulatory Element-Binding Protein-1c (SREBP1c) and Nuclear Factor Kappa B (NFkB) protein expressions in the liver tissue, but did not decrease Glucose-Regulated Protein 78 (GRP78) protein expression. Significantly, the levels of Tumor Necrosis Factor alpha (TNF-a) and IL-6 in the liver tissue were lower, while the levels of IL-10 and Nuclear factor-erythroid-2 Related Factor 2 (NRF2) were higher with HSE administration. HSE produced a better histopathological profile of the Hematoxylin and Eosin (H&E)-Masson tricrome for inflammation, fat and fibrosis in the liver. Conclusions: In this study, HSE was found to slow the development of liver damage in experimental animals that were given a vitamin B12-deficient diet.

The Association of Immune Cell Infiltration with Metastasis Location in De Novo Metastatic Triple Negative Breast Cancer: A Multicenter Cross-Sectional Study in Indonesia.

BACKGROUND: Triple-negative breast cancer (TNBC) is an aggressive cancer subtype, with limited treatments and a high metastasis risk. The varying location of metastasis in TNBC patients often leads to in prognosis in breast cancer. Therefore, this study aimed to investigate the potential association between immune cells profiles in the tumor microenvironment and metastatic patterns. METHODS: We conducted a multicenter cross-sectional study in 2022 to examine formalin-fixed paraffin-embedded (FFPE) and medical record data from 2015 to 2020 in de novo metastatic TNBC patients. The medical records provided crucial information about the sites of metastasis. Immunohistochemistry (IHC) analysis was carried out on primary breast tumor tissues to evaluate the expressions of cluster of differentiation (CD)4 T-cells, CD8 T-cells, CD163, FOXP3 Tregs, and programmed death-ligand 1 (PD-L1), along with immune cells ratios showing antitumor-to-protumor activity (CD4/FOXP3, CD8/FOXP3, CD4/CD163, CD8/CD163). Metastatic locations were grouped into bone-only, visceral, lung, liver, and brain metastasis.  Results: A total of 120 metastatic TNBC patients were documented for their metastatic location and IHC report. The clinical and histopathological characteristics showed that the majority of the patients were within the 40-65 years old group, and 34.2% had standard body mass index (BMI). Furthermore, the majority (89.22%) of the patients showed No Special Type (NST), (56.7%) had histopathology grade III, high Ki-67 ≥20% (85.8%), and positive PD-L1 expression (30.8%), with visceral metastasis indicating the highest proportion of 75.8%. Patients with a high CD8/FOXP3 and CD4/FOXP3 ratio were significantly prone to have bone-only metastasis compared to visceral metastasis (p= 0.028 and p=0.024, respectively).  Conclusion: The ratio of antitumor to protumor T-lymphocytes had a significant relevance in the metastatic location patterns in TNBC.

Novel retinal findings in ß-thalassemia major: older age and higher ferritin level as the risk factors.

PURPOSE: To investigate retinal changes in ß-thalassemia major patients and identify their association with systemic risk factors. METHODS: In this prospective study, 120 ß-thalassemia major patients received complete ophthalmic examinations (best-corrected visual acuity, contrast sensitivity, color vision, and indirect ophthalmoscopy) and retinal imaging using color fundus photography and fundus autofluorescence imaging. Patients were grouped according to the presence of thalassemia-related retinal changes. The association between systemic risk factors (age, type and duration of iron chelator use, history of splenectomy, hemoglobin level, and ferritin level) and thalassemia-related retinal changes was investigated using logistic regression analysis. RESULTS: Thalassemia-related retinal changes were identified in 36.7% of patients. Several distinct retinal changes were observed, including retinal refractile bodies in 10% of patients and retinal hemorrhage in 5.8% of patients. Fundus autofluorescence imaging showed abnormal patterns in 36.3% of patients with thalassemia-related retinal changes and 18.4% of patients without thalassemia-related retinal changes. Age (odds ratio [OR] = 1.10, 95% confidence interval [CI] 1.03-1.18) and ferritin level (OR 1.16, 95% CI 1.01-1.33) were associated with thalassemia-related retinal changes. CONCLUSION: Novel retinal changes were observed in ß-thalassemia major patients. This study identified older age and higher ferritin level as risk factors for thalassemia-related retinal changes.

Serious fungal disease incidence and prevalence in Indonesia.

BACKGROUND: Indonesia is a tropical country, warm and humid, with numerous environmental fungi. Data on fungal disease burden help policymakers and clinicians. OBJECTIVES: We have estimated the incidence and prevalence of serious fungal diseases. METHODS: We found all published and unpublished data and estimated the incidence and prevalence of fungal diseases based on populations at risk. HIV data were derived from UNAIDS (2017), pulmonary tuberculosis (PTB) data from 2013-2019, data on chronic pulmonary aspergillosis (CPA) were used to estimate CPA prevalence and likely deaths, COPD data from Hammond (2020), lung cancer incidence was from Globocan 2018, and fungal rhinosinusitis was estimated using community data from India. RESULTS: Overall ~7.7 million Indonesians (2.89%) have a serious fungal infection each year. The annual incidence of cryptococcosis in AIDS was 7,540. Pneumocystis pneumonia incidence was estimated at 15,400 in HIV and an equal number in non-HIV patients. An estimated 1% and 0.2% of new AIDS patients have disseminated histoplasmosis or Talaromyces marneffei infection. The incidence of candidaemia is 26,710. The annual incidence of invasive aspergillosis was estimated at 49,500 and the prevalence of CPA is at 378,700 cases. Allergic bronchopulmonary aspergillosis prevalence in adults is estimated at 336,200, severe asthma with fungal sensitisation at 443,800, and fungal rhinosinusitis at 294,000. Recurrent vulvovaginal candidiasis is estimated at 5 million/year (15-50 years old). The incidence of fungal keratitis around 40,050. Tinea capitis prevalence in schoolchildren about 729,000. CONCLUSIONS: Indonesia has a high burden of fungal infections.

Randomised, controlled, double-blind study of combination therapy of oral tranexamic acid and topical hydroquinone in the treatment of melasma.

BACKGROUND/OBJECTIVES: Melasma is a common pigmentary disorder for which oral tranexamic acid has shown some efficacy in previous studies. The aim of this study was to assess the effectiveness of oral tranexamic acid in combination with hydroquinone cream in the treatment of melasma. METHODS: Subjects with moderate-to-severe melasma were enrolled. Group A received hydroquinone 4% cream, sunscreen and oral tranexamic acid, while Group B received hydroquinone 4% cream, sunscreen and placebo capsules for 3 months. All subjects had an additional 3-month follow-up visit on sunscreen alone. The primary outcome measure was change in modified Melasma Area and Severity Index (mMASI) score. In addition, the melanin index was measured using a mexameter. RESULTS: Fifty subjects were enrolled, and all completed the study. There was a 55% reduction in mMASI after 3 months from mean 8.96 (SD 2.45) to 4.0 (SD 1.6) in Group A compared to 10.9% from mean 8.53 (SD 2.04) to 7.6 (SD 2.0) in Group B. Three months after oral and topical therapy was discontinued, there was a 42% decrease in mMASI compared to baseline in Group A (mean 5.1 SD 1.7) vs. 4.7% in Group B (mean 8.1 SD 2.0). No serious adverse events were observed. CONCLUSIONS: A combination of oral tranexamic acid and topical hydroquinone is more effective than hydroquinone alone in the treatment of melasma.

Corpus callosum index correlates with brain volumetry and disability in multiple sclerosis patients.

OBJECTIVE: To analyze the correlation between corpus callosum index (CCI), brain volumetry, and disability in multiple sclerosis (MS) patients. The brain volumetry consists of the corpus callosum, cortical gray matter, subcortical gray matter, and white matter volumes. METHODS: This was a retrospective cross-sectional study from October 2018 to February 2019 of 30 patients with MS aged 20 to 61 years old. Brain volumetry was performed using FreeSurfer software. The CCI were measured manually using conventional best mid-sagittal T1W brain MRI. The anterior, posterior, and medium segments were measured and divided to its greatest anteroposterior diameter. Higher CCI values indicated greater corpus callosum volumes. Clinical evaluation was comprised of MS subtype, age of onset, relapse frequency and Expanded Disability Status Scale (EDSS). RESULTS: Thirty MS patients with median of age 22 years were included. Relapsing-remitting (RRMS) subtype were 73.3%. Very significant correlations were shown between the CCI and corpus callosum volume (CCV) (r=0.79; p<0.0001) and cerebral white matter volume (r=0.81; p<0.0001). Significant correlations were shown between the CCI and cortical gray matter volume (r=0.64; p<0.0001) and subcortical gray matter volume (r=0.69; p<0.0001). The CCI was positively correlated with age of onset and inversely with EDSS. The CCV and CCI were smaller in secondary progressive MS (SPMS). CONCLUSION: The CCI is easy and fast to obtain in conventional MRI and significantly correlated with brain volumetry, age of onset and disability in MS patients.

Minimal apparent diffusion coefficient value of the solid component to differentiate borderline and malignant ovarian epithelial tumours: a preliminary report.

PURPOSE: Ovarian tumours are the second most common cause of death from gynaecological cancer. There are three types of ovarian cancer based on histopathological examination: benign, borderline, and malignant. However, it is difficult to distinguish the borderline and malignant tumours. Several studies used the apparent diffusion coefficient value to distinguish the ovarian tumour types, with various results. This preliminary report focused more on the use of the minimal ADC (mADC) value on the solid component, to differentiate borderline and malignant ovarian tumours. MATERIAL AND METHODS: In 21 cases of borderline ovarian tumours, of which 11 were regarded as malignant and 10 were regarded as borderline following histopathological examination, the mADC value was measured by two different radiologists by using free-hand technique. The intraclass correlation coefficient (ICC) was used to measure the reliability and agreement between the two radiologists. Receiver-operating characteristic (ROC) curves were then calculated to determine the optimum cut-off point. RESULTS: There were statistically significant (p = 0.001) of the mADC value between the borderline and malignant tumours. The intraclass correlation coefficient value showed excellent reliability and agreement between the examiners. The ROC curve showed the optimum cut-off point at 0.628 × 10-3 mm2/s (p = 0.001), which yielded 100% sensitivity and 80% specificity. CONCLUSIONS: The use of free-hand technique to measure the mADC value on the solid component can be valuable in differentiating borderline and malignant ovarian epithelial tumours. This result may assist clinicians in considering further treatment approaches.

The Role of Serum Expression Levels of Microrna-21 on Bone Mineral Density in Hypostrogenic Postmenopausal Women with Osteoporosis: Study on Level of RANKL, OPG, TGFß-1, Sclerostin, RANKL/OPG Ratio, and Physical Activity.

BACKGROUND: MiR-21 is known to play a role in osteoclast proliferation and differentiation, but the role of serum miR-21 expression in osteoporosis remains unclear. Previous research found that serum miR-21 expression was positively correlated with bone mineral density in postmenopausal osteoporosis patients, but other factors involved in postmenopausal osteoporosis still unknown. This study aimed to determine the role of serum miR-21 expression, concentration of RANKL, OPG, TGF-ß1, sclerostin and serum calcium, RANKL/OPG ratio, and physical activity on bone mineral density of spine in hypoestrogenic postmenopausal women with osteoporosis (PMOP) compared with no osteoporosis (PMNOP), with point of interest on the expression of serum miR-21. METHODS: this study was conducted by comparative cross-sectional design. The subjects were divided into 2 groups of PMOP and PMNOP. We used an absolute quantification real-time PCR method to determine serum miR-21 expressions level. RESULTS: Median of serum miR-21 expression at the PMOP group was significantly higher compared to PMNOP group (p = 0.001). Serum miR-21 expression, RANKL, RANKL/OPG ratio, and physical activity were significantly correlated with BMD values in the PMOP group. Moderate physical activity was significantly negatively correlated with serum miR-21 expression. We also obtained a linear regression equation BMD = 1.373-0.085*Ln.miR-21-0.176*Log10.RANKL (R2 = 52.5%). CONCLUSION: serum miR-21 expression in PMOP was higher compared with PMNOP. Serum miR-21 expression proved to have a negative effect on spinal BMD values in hypoestrogenic postmenopausal women with osteoporosis of 8.5%. Obtained equation of BMD = 1.373-0.085*Ln.miR-21-0.176*Log10.RANKL can explain the value of spinal BMD by 52.5%.

Effect of Metformin on Handgrip Strength, Gait Speed, Myostatin Serum Level, and Health-related Quality of Life: A Double Blind Randomized Controlled Trial among Non-diabetic Pre-frail Elderly Patients.

BACKGROUND: sarcopenia contributes to the development of frailty syndrome. Frailty syndrome is potentially improved by modifying insulin resistance, inflammation, and myostatin level. This study is aimed to investigate the effect of metformin on handgrip strength, gait speed, myostatin serum level, and health-related quality of life (HR-QoL) among non-diabetic pre-frail elderly patients. METHODS: a double blind randomized controlled trial study was conducted on non-diabetic elderly outpatients aged ≥ 60 years with pre-frail status based on phenotype and/ or index criteria (Cardiovascular Health Study and/ or Frailty Index 40 items) consecutively recruited from March 2015 to June 2016 at Cipto Mangunkusumo Hospital. One-hundred-twenty subjects who met the research criteria were randomized and equally assigned into 3 x 500 mg metformin or placebo group. The study outcomes were measured at baseline and after 16 weeks of intervention. RESULTS: out of 120 subjects, 43 subjects in metformin group and 48 subjects in placebo group who completed the intervention. There was a significant improvement on the mean gait speed of metformin group by 0.39 (0.77) second or 0.13 (0.24) meter/second that remained significant after adjusting for important prognostic factors (p = 0.024). There was no significant difference on handgrip strength, myostatin serum level, and HR-QoL between both groups. CONCLUSION: 3 x 500 mg metformin for 16 weeks was statistically significant and clinically important in improving usual gait speed as one of the HR-QoL dimensions, but did not significantly improve the EQ-5D index score, handgrip strength, nor myostatin serum level.

The Role of Cytotoxic T-lymphocyte-associated Protein 4 (CTLA-4) Gene, Thyroid Stimulating Hormone Receptor (TSHR) Gene and Regulatory T-cells as Risk Factors for Relapse in Patients with Graves Disease.

BACKGROUND: graves' disease (GD) is the most common condition of thyrotoxicosis. The management of GD is initiated with the administration of antithyroid drugs; however, it requires a long time to achieve remission. In reality more than 50% of patients who had remission may be at risk for relapse after the drug is stopped. This study aimed to evaluate the role of clinical factors such as smoking habit, degree of ophtalmopathy, degree of thyroid enlargement; genetic factors such as CTLA-4 gene on nucleotide 49 at codon 17 of exon 1, CTLA-4 gene of promotor -318, TSHR gene polymorphism rs2268458 of intron 1; and immunological factors such as regulatory T cells (Treg) and thyroid receptor antibody (TRAb); that affecting the relapse of patients with Graves' disease in Indonesia. METHODS: this was a case-control study, that compared 72 subjects who had relapse and 72 subjects without relapse at 12 months after cessation of antithyroid treatment, who met the inclusion criteria. Genetic polymorphism examination was performed using PCR-RFLP. The number of regulatory T cells was counted using flow cytometry analysis and ELISA was used to measure TRAb. The logistic regression was used since the dependent variables were categorical variables. RESULTS: the analysis of this study demonstrated that there was a correlation between relapse of disease and family factors (p=0.008), age at diagnosis (p=0.021), 2nd degree of Graves' ophthalmopathy (p=0.001), enlarged thyroid gland, which exceeded the lateral edge of the sternocleidomastoid muscles (p=0.040), duration of remission period (p=0.029), GG genotype of CTLA-4 gene on the nucleotide 49 at codon 17 of exon 1 (p=0.016), CC genotype of TSHR gene on the rs2268458 of intron 1 (p=0.003), the number of regulatory T cells (p=0.001) and TRAb levels (p=0.002). CONCLUSION: genetic polymorphisms of CTLA-4 gene on the nucleotide 49 at codon 17 of exon 1, TSHR gene SNP rs2268458 of intron 1, number of regulatory T cells and TRAb levels play a role as risk factors for relapse in patients with Graves' disease.

The Effect of Enhanced External Counterpulsation Therapy and Improvement of Functional Capacity in Chronic Heart Failure patients: a Randomized Clinical Trial.

AIM: to investigate the efficacy of enhanced external counterpulsation (EECP) therapy to improve functional capacity in patients with chronic heart failure (CHF). METHODS: a double-blind random clinical trial was performed in 99 patients with CHF who had received EECP therapy at Jade Cardiovascular Clinic, Manado, North Sulawesi, Indonesia between January 2014 and June 2015. Subjects were categorized into 2 groups, i.e. 49 subjects had sham EECP therapy and 50 subjects had EECP therapy. All subjects performed six-minute walking test (6MWT) before and after receiving EECP therapy. RESULTS: there was no significant difference between both groups regarding the basic characteristics of patients with CHF. The 6MWT result before EECP therapy showed that there were 30 patients (61.2%) with walk distance of <300 meter in the sham EECP group; while in the group receiving EECP therapy, we found 34 patients (68%); p=0.24. Post-EECP therapy, there were 33 patients (67.3%) with walk distance of <300 meters in EECP sham group; while in the group receiving EECP alone, there was only 1 patient (2%); p<0.01.The 6MWT walk distance in sham group before EECP therapy was 252.65 (SD 97.55) meters and it was 243.65 (SD 86.96) meters following the EECP therapy; p=0.18. In EECP group, the 6MWT walk distance before therapy was 256.88 (SD 85.56) meters and after EECP therapy the walk distance was 449.46 (SD 92.08) meters; p<0.01. CONCLUSION: EECP therapy is effective to improve functional capacity in patients with CHF.

Evaluating resistance to acetyl salicylic acid using platelet function test in patients with ischemic stroke at Cipto Mangunkusumo Hospital.

AIM: to identify the prevalence of laboratoric ASA resistance using platelet function tests in patients with ischemic stroke at Cipto Mangunkusumo Hospital and its associated factors. METHODS: this study was a cross-sectional study involving 50 patients with ischemic stroke who only received ASA treatment. Evaluation of resistance to ASA was performed using Verifynow® platelet function test. ASA resistance was defined as ASA reaction unit (ARU) 550. RESULTS: there were 7 patients with ASA resistance. The mean age of subjects in ASA resistance group was 51.3±9.2 years; while in ASA responsive group was 57.8±9.7 years. In ASA resistance group, there were 85.7% male patients, 57.1% active smoker and 100% subjects with hypertension. CONCLUSION: the prevalence of laboratoric ASA resistance in patients with ischemic stroke evaluated using platelet function test at Cipto Mangunkusumo Hospital is 14%. The prevalence is more likely to occur in male patients who were active smoker, at younger age and with comorbidity of hypertension.

Risk of dysphagia in a population of infants born pre-term: characteristic risk factors in a tertiary NICU.

OBJECTIVE: To examine the prevalence and characteristics of dysphagia and suck-swallow-breath incoordination as phenotypes of oral feeding difficulties. METHOD: A cross-sectional study with secondary data collected consecutively over 2 years from October 2020 to October 2022 to measure the prevalence of swallowing and oral feeding difficulty in preterm infants using Flexible endoscopic evaluation of swallowing examination at the tertiary Integrated Dysphagia Clinic. RESULTS: The prevalence of swallowing disorders was 25 % and the prevalence of suck-swallow-breath incoordination was 62.5 %. The significant risk factor that may show a possible correlation with oral feeding difficulty was mature post-menstrual age (p = 0.006) and longer length of stay (p = 0.004). The dominant percentage of upper airway abnormality and disorder were retropalatal collapse (40 %), laryngomalacia (42.5 %), paradoxical vocal cord movement (12.5 %), and gastroesophageal reflux disease (60 %). The dominant characteristic of oral motor examination and flexible endoscopic evaluation of swallowing examination was inadequate non-nutritive sucking (45 %), inadequate postural tone (35 %), and inadequate nutritive sucking (65 %). CONCLUSION: Dysphagia in preterm infants is mostly observed in those with mature post-menstrual age, longer length of stay, and the presence of gastroesophageal reflux disease with inadequate non-nutritive sucking and nutritive sucking abilities. Suck-swallow-breath incoordination is primarily observed in those with immature post-menstrual age, a higher prevalence of cardiopulmonary comorbidity, and a higher prevalence of upper airway pathologies (laryngomalacia, paradoxical vocal cord movement) with inadequate nutritive sucking ability.

Analyze, design, develop, implement, and evaluate approach to develop a pelvic floor muscle training guidebook to treat stress urinary incontinence in women.

OBJECTIVE: Stress urinary incontinence (SUI) is a common problem that affects the quality of life of women worldwide. Pelvic floor muscle training (PFMT) is an effective conservative first-line treatment for SUI. However, low compliance with PFMT is one of the main reasons for therapeutic failure. Indirect supervision using a guidebook may improve PFMT outcomes. To develop a PFMT guidebook using the analyze, design, development, implementation, and evaluation (ADDIE) method. METHODS: A guidebook was developed from July 2020 to April 2021 using the ADDIE method. This prospective study used mixed methods, namely qualitative analysis, focus group discussions, and in-depth interviews, and involved various experts from urogynecology, urology, medical rehabilitation, and physiotherapy departments. A pilot study was conducted on patients with SUI to evaluate the effectiveness of the guidebook. RESULTS: The ADDIE method was successfully implemented to develop the PFMT guidebook. The formative evaluation of the ADDIE steps mainly focused on the PFMT technique, content clarity, illustration, design, and color choice of the book. After the pilot study, the guidebook significantly improved Incontinence Impact Questionnaire, Short Form, 1-hour pad test, and perineometer scores. However, the pilot study showed no significant improvement in Urogenital Distress Inventory, Short Form scores. CONCLUSION: The PFMT guidebook developed using the ADDIE method improved outcomes in patients with SUI.

The relationship between high ratios of CD4/FOXP3 and CD8/CD163 and the improved survivability of metastatic triple-negative breast cancer patients: a multicenter cohort study.

BACKGROUND: Triple-negative breast cancer (TNBC) has been documented as the most aggressive subtype of breast cancer. This study aimed to analyze antitumor and protumor immune activities, and their ratios as significant prognostic biomarkers in metastatic TNBC (mTNBC). METHODS: A multicenter cohort study was conducted among 103 de novo mTNBC patients. The expression of CD8 and CD163 was evaluated using immunohistochemistry staining, CD4 and FOXP3 using double-staining immunohistochemistry, and PD-L1 using immunohistochemistry and RT-PCR. RESULTS: Multivariate analysis revealed that high CD4/FOXP3 (HR 1.857; 95% CI 1.049-3.288; p = 0.034) and the CD8/CD163 ratio (HR 2.089; 95% CI 1.174-3.717; p = 0.012) yield significantly improved 1 year overall survival (OS). Kaplan-Meier analysis showed that high levels of CD4 (p = 0.023), CD8 (p = 0.043), CD4/FOXP3 (p = 0.016), CD8/FOXP3 (p = 0.005), CD8/CD163 (p = 0.005) ratios were significantly associated with higher rate of 1 year OS. Furthermore, 1 year OS was directly correlated with antitumor CD4 (R = 0.233; p = 0.018) and CD8 (R = 0.219; p = 0.026) and was indirectly correlated with protumor CD163 and FOXP3 through CD4/FOXP3 (R = 0.282; p = 0.006), CD4/CD163 (R = 0.239; p = 0.015), CD8/FOXP3 (R = 0.260; p = 0.008), and CD8/CD163 (R = 0.258; p = 0.009). CONCLUSION: This is the first study to demonstrate that high levels of CD4/FOXP3 and CD8/CD163 significantly improved the 1 year OS in de novo mTNBC patients. Thus, we recommend the application of these markers as prognosis determination and individual treatment decision.

Diagnostic accuracy of diffusion weighted imaging compared to magnetic resonance spectroscopy in differentiation of benign and malignant breast lesions: A systematic review and meta-analysis.

OBJECTIVE: To compare the sensitivity and specificity of diffusion weighted imaging (DWI) and magnetic resonance spectroscopy (MRS) in the differentiation of benign and malignant breast lesions. METHODS: Scopus, PubMed, and other registries were searched up to April 2023. We included diagnostic studies with DWI and MRS as index tests and histopathologic examination as the reference standard for differentiating benign and malignant breast lesions in adult females. We excluded studies involving healthy women, only breast cancer patients, and non-comparative diagnostic accuracy studies on either index test. The sensitivity and specificity of DWI and MRS were investigated and pooled using random-effect bivariate meta-analysis. Risk of bias was assessed using QUADAS-2. Evidence quality was summarized using GRADE. RESULTS: Eight eligible studies involving 632 females and 687 breast lesions were identified. The pooled sensitivity and specificity of DWI were 92% (CI 85-96%) and 88% (CI 75-94%), respectively. The pooled sensitivity and specificity of MRS were 85% (CI 66-94%) and 85% (CI 77-91%), respectively. No significant difference was noted in the sensitivity (7%, CI -8-22%) and specificity (3%, CI -9-14%) between DWI and MRS. CONCLUSIONS: In low to moderate quality evidence, DWI and MRS show comparable sensitivity and specificity in differentiating benign and malignant breast lesions.

Dynamic contrast-enhanced magnetic resonance imaging parameter changes as an early biomarker of tumor responses following radiation therapy in patients with spinal metastases: a systematic review.

PURPOSE: This systematic review aims to assess and summarize the clinical values of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) parameter changes as early biomarkers of tumor responses following radiation therapy (RT) in patients with spinal metastases. MATERIALS AND METHODS: A systematic search was conducted on five electronic databases: PubMed, Scopus, Science Direct, Cochrane, and Embase. Studies were included if they mentioned DCE-MRI parameter changes before and after RT in patients with spinal metastases with a correlation to tumor responses based on clinical and imaging criteria. The Quality Assessment of Diagnostic Accuracy Studies 2 was used to assess study quality. RESULTS: This systematic review included seven studies involving 107 patients. All seven studies evaluated the transfer constant (Ktrans), six studies evaluated the plasma volume fraction (Vp), three studies evaluated the extravascular extracellular space volume fraction, and two studies evaluated the rate constant. There were variations in the type of primary cancer, RT techniques used, post-treatment scan time, and median follow-up time. Despite the variations, however, the collected evidence generally suggested that significant differences could be detected in DCE-MRI parameters between before and after RT, which might reflect treatment success or failures in long-term follow-up. Responders showed higher reduction and lower values of Ktrans and Vp after RT. DCE-MRI parameters showed changes and detectable recurrences significantly earlier (up to 6 months) than conventional MRI with favorable diagnostic values. CONCLUSION: The results of this systematic review suggested that DCE-MRI parameter changes in patients with spinal metastases could be a promising tool for treatment-response assessment following RT. Lower values and higher reduction of Ktrans and Vp after treatment demonstrated good prediction of local control. Compared to conventional MRI, DCE-MRI showed more rapid changes and earlier prediction of treatment failure.

Deeper look into feedback practice in an Indonesian context: exploration of factors in undergraduate clinical settings.

PURPOSE: The practice of feedback is influenced by the characteristics of students, teachers, and the clinical environment. Most studies on feedback have been conducted in Western settings with different sociocultural backgrounds to Indonesia. This study explores feedback in Indonesian clinical clerkship using a sociocultural lens and aims to provide an exemplar of adaptive practice relevant to non-Western settings. METHODS: This qualitative study was conducted using an interpretive phenomenology approach. Data were collected through focus groups with students and teachers and interviews with program coordinators. Data were transcribed verbatim and grouped according to data sources, coded, and analyzed thematically. RESULTS: Themes identified from the focus group discussions and interviews were categorized as student, teacher, and environmental factors. Student factors include dependence on feedback, tendencies to use a group approach, difficulties recognizing social rules, a perceived lack of resilience, and tendencies to doubt praise. Factors related to teachers include a high level of expertise, being extremely busy, having a strong commitment, and being unsure of students' acceptance of feedback. Clinical environment factors influence interactions between teachers and learners and include high power distance and collectivistic values. A safe environment is needed to ensure effective feedback interactions. CONCLUSION: High power distance, collectivism, and generational characteristics of students likely impact feedback practice in clinical settings. Designing a safe environment is essential for effective feedback practice.

Screening of Major Depression Disorder in Patients With Epilepsy in Indonesian National Referral Hospital.

Background and Objectives: Major depressive disorder (MDD) is a common psychiatric disorder in patients with epilepsy (PWE). The Neurological Disorders Depression Inventory for Epilepsy (NDDI-E) is one of the MDD screening tools used in PWE. This study aims to determine the accuracy of the valid and reliable NDDI-E Indonesian version as an MDD screening tool in PWE and investigate the prevalence and risk factors for the development of MDD in PWE. Methods: A diagnostic cross-sectional study was conducted at Cipto Mangunkusumo National Referral Hospital, Indonesia. Patients were PWE aged 18 years or older who visited the epilepsy outpatient clinic. The valid and reliable NDDI-E Indonesian version and Mini International Neuropsychiatric Interview (MINI) International Classification of Disease, 10th Revision (ICD-10) were used to diagnose MDD. In phase II of the study, diagnostic accuracy was evaluated using the receiver operative characteristic (ROC) curve method to obtain the area under the curve (AUC) and diagnostic 2 x 2 table to determine the cutoff point, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV). During phase III of the study, eligible individuals were screened for MDD using the NDDI-E Indonesian version. Demographic and clinical data were collected. Data analysis was performed using the χ2 test, Mann-Whitney test, and multivariate logistic regression analysis. Results: A total of 105 individuals were involved, and only 23 of them were found to experience MDD based on MINI ICD-10. The best cutoff point for the NDDI-E Indonesian version was ≥11, with a sensitivity of 91.3%, specificity 89%, PPV 70%, and NPV 97.3%. The AUC obtained from ROC analysis was 97.5% (95% CI 95-99%, p < 0.001). Then, the survey was completed by 79 individuals, predominantly male, mostly within the age range of 26-45 years. The prevalence of MDD in PWE was 50.6%, and the significant risk factors were seizure frequency ≥8 times a year and the presence of chronic diseases (p < 0.001). Discussion: The NDDI-E Indonesian version was a screening tool with a high diagnostic accuracy to detect MDD in PWE at a cutoff point of 11. Poor seizure control and the presence of other chronic diseases were the risk factors correlated with MDD development in PWE.

Risk factors of prolonged diarrhea in children under 2 years old.

BACKGROUND: Prolonged diarrhea, defined as diarrhea lasting longer than 7 days, is known to negatively impact children's growth and development. However, studies of the risk factors of prolonged diarrhea remain limited. PURPOSE: This study aimed to analyze the risk factors for prolonged diarrhea in children under 2 years of age with acute diarrhea. METHODS: This 1-year nested case-control study was conducted at Fatmawati General Hospital in 2021-2022. Participants were selected using a consecutive sampling method from among children under 2 years of age with acute diarrhea within the previous 2-4 days. Children with diarrhea that lasted 7 days were considered positive for prolonged diarrhea, whereas those with acute diarrhea were considered negative. Children with comorbidities such as malnutrition were excluded. Clinical information including age, breastfeeding history, antibiotic exposure history, and nutritional status was recorded. Complete blood count, blood zinc levels, Rotavirus, adenovirus, and norovirus serology, alpha-1 antitrypsin (AAT) levels, and stool analysis were acquired as laboratory data. RESULTS: There were 62 subjects in the study and control groups. Overall, the median age was 12 months (6-24 months); most patients were boys. A history of antibiotic use (odds ratio [OR], 15.860; 95% confidence interval [CI], 5.286-47.591; P<0.001), zinc deficiency (OR, 4.758; 95% CI, 1.711-13.229; P=0.003), and elevated fecal AAT levels (OR, 2.677; 95% CI, 1.046-6.850; P=0.040) were the main risk factors for prolonged diarrhea in children under 2 years of age with acute diarrhea. CONCLUSION: A history of antibiotic use, zinc deficiency, and elevated fecal AAT levels were the main risk factors for prolonged diarrhea in children under 2 years of age with acute diarrhea. Thorough testing and appropriate antibiotic use are required to prevent prolonged diarrhea in children under 2 years of age.