Cancer Stem Cells (CD44+/CD24-), RAD6, DDB2 Immunohistochemistry Expression and IHC-UNEDO Scoring System As Predictor of Ovarian Cancer Chemoresistance.

Backgrounds: Ovarian cancer is a deadly women cancer with many chemoresistance after standard treatment. Ovarian cancer tissues' CD44+/CD24- (CSCs), RAD6 overexpression and DDB2 underexpression are associated with chemoresistance, recurrence, and poor prognosis of the disease because of the existence of cancer stem cells (CSCs). We tried to analyze the expression of those three proteins while building a predictor scoring system to predict the ovarian cancer chemoresistance from the ovarian cancer tissue immunohistochemistry. Materials and Methods: We conducted a cohort study of 64 patients divided into two groups (32 patients in each group) at the Cipto Mangunkusumo, Tarakan, Dharmais, and Fatmawati Hospital which are located in Jakarta city, Indonesia. The patients underwent cytoreductive debulking and histopathological examination continued by six series of chemotherapy followed by six months of observation. We divided the groups into chemoresistant and chemosensitive by using Response Criteria in Solid Tumors (RECIST) criteria. Ovarian cancer tissue immunohistochemistry tests were then performed to count the CSCs, RAD6 and DDB2 expressions. Results: We found relationship between increased CSCs, RAD6 and reduced DDB2 (p < 0.05) expression in ovarian cancer tissue with the chemoresistance. A possible predictor scoring system named IHC-UNEDO scoring was built to aid the ovarian cancer chemoresistance prediction. Conclusions: The conclusion is that CSCs, RAD6 and DDB2 expressions are significantly associated with ovarian cancer chemoresistance, and IHC-UNEDO scoring should be considered as a tool to predict ovarian cancer chemoresistance.

Effect of cholecalciferol supplementation on hand grip strength, walking speed, and expression of vitamin D receptor, interleukin-6, and insulin-like growth factor-1 in monocyte in pre-frail older adults: A randomized double-blind placebo-controlled trial.

AIM: To investigate the effect of cholecalciferol supplementation on hand grip strength, walking speed, and expression of vitamin D receptor (VDR), interleukine-6 (IL-6) and insulin-like growth factor-1 (IGF-1) in monocyte in pre-frail older adults. METHODS: We conducted a randomized double-blinded placebo-controlled clinical trial for 12 weeks, involving 120 pre-frail older adults who were randomized to the cholecalciferol group (cholecalciferol 4000 IU/day) or the placebo group. All subjects were given calcium lactate 500 mg/day. Hand grip strength and walking speed, as primary outcomes, were analyzed using intention-to-treat analysis. The expression of VDR, IGF-1 and IL-6 in monocytes, as secondary outcomes, were analyzed using per-protocol analysis. RESULTS: After a 12-week intervention, there was a significant increase in serum 25(OH)D levels in both groups, with the increase being higher in the cholecalciferol group than in the placebo group (49.05 vs. 24.01 ng/mL; P < 0.001). No statistically significant differences were observed in hand grip strength (P = 0.228) and walking speed (P = 0.734) between the groups. There were no differences in the expression of VDR (P = 0.513), IL-6 (P = 0.509), and IGF-1 (P = 0.503) monocytes between the groups. CONCLUSIONS: Cholecalciferol supplementation for 12 weeks increased serum 25(OH)D levels among pre-frail older adults. However, it did not improve hand grip strength and walking speed, and nor did it change the expression of VDR, IL-6, and IGF-1 in monocytes. Geriatr Gerontol Int 2024; 24: 554-562.

Granulocyte Colony-stimulating Factor Improves Innate Immunity in Pediatric Pretransplant Patients.

Background: Children with decompensated cirrhosis (DC) awaiting LT suffer from infection linked to high pediatric end-stage liver disease (PELD) scores and mortality. Granulocyte colony-stimulating factor (G-CSF) therapy has shown promising results in adult DC. Our study investigated G-CSF as an optimizing treatment for pre-transplant DC, exploring its effect on cytokine activity. Methods: An open-label, randomized controlled trial included DC patients aged 3 months-12 years. The intervention group (n=26) received 12 G-CSF courses injected subcutaneously (5 µg/kg/day) plus DC standard medical treatment (SMT). The control group (n = 24) received SMT. We obtained PELD scores, tumor necrosis factor (TNF)-α, interleukin (IL)-10, hepatocyte growth factor (HGF), CD34+ mobilization, liver function, leukocyte and neutrophil counts. Infection and side effects were documented. Results: There was no significant difference in PELD scores between the groups after 3 months G-CSF treatment. Decreased TNF-α (p < 0.001) and increased IL-10 and HGF (p = 0.003 for both markers) were shown 1 month following G-CSF treatment. Alanine aminotransferase (ALT) levels improved significantly (p = 0.038). Significant increase in leucocyte and neutrophil counts (p < 0.001) and a lower incidence of sepsis (p = 0.04) were shown after intervention. There was no significant difference in survival (p = 0.372). Conclusion: Following 3 months of G-CSF treatment, PELD scores did not show significant improvement. G-CSF reversed the cytokine profiles in DC, resulting in reduced TNF-α and increased IL-10. HGF significantly improved, indicating hepatic regeneration. Significantly decreased occurrence of sepsis following G-CSF treatment indicated improved clinical outcome.

TNFα induces Caspase-3 activity in hematopoietic progenitor cells CD34+, CD33+, and CD41 + of myelodysplastic syndromes.

BACKGROUND: Cytopenia is the primary feature of Myelodysplastic Syndrome, even in the presence of hypercellular bone marrow. TNFα is recognized as both a proinflammatory, and proapoptotic cytokine with a well established role in promoting apoptosis in MDS. Therefore, TNFα has the potential to be a valuable biomarker for predicting the progression of cytopenia in MDS. This study aims to establish the role of TNFα exposure in triggering apoptosis through caspase-3 activity in CD34+, CD33+, and CD41 + cells in MDS. METHODS: This study is an in vitro comparative experimental research. Bone marrow mononuclear cells were isolated as the source of hematopoietic progenitor cells. Subsequently, CD34+, CD33+, and CD41 + cells were exposed to rhTNFα, and the caspase-3 activity was measured using flowcytometry. RESULTS: In MDS CD33 + and CD41 + caspase-3 activity of rhTNFα exposed cells was significantly higher than without exposed cells. The opposite result was found in CD34 + cells, where the caspase-3 activity without rhTNFα exposed cells was significantly higher than rhTNFα exposed cells. CONCLUSION: rhTNFα exposure led to an elevation in caspase-3 activity in MDS progenitor cells, especially in those that had differentiated into myeloid cell CD33 + and megakaryocyte cell CD41+, as opposed to the early progenitor cells CD34+.

Efficacy of LL-37 cream in enhancing healing of diabetic foot ulcer: a randomized double-blind controlled trial.

Wound healing in DFU (diabetic foot ulcer) has prolonged inflammation phase and defective granulation tissue formation. LL-37 has antimicrobial property, induces angiogenesis, and keratinocyte migration and proliferation. This study analyzes the efficacy of LL-37 cream in enhancing wound healing rate and decreasing the levels of IL-1α, TNF-α, and the number of aerobic bacteria colonization in DFU with mild infection. This study was conducted from January 2020 to June 2021 in Jakarta. Subjects were instructed to apply either LL-37 cream or placebo cream twice a week for 4 weeks. Wounds were measured on days 7, 14, 21, and 28 and processed with ImageJ. The levels of LL-37, IL-1α, and TNF-α from wound fluid were measured using ELISA. The number of aerobic bacteria colonization was counted from the isolate grown in culture. The levels of LL-37 in DFU at baseline were equally low in both groups which were 1.07 (0.37-4.96) ng/mg protein in the LL-37 group and 1.11 (0.24-2.09) ng/mg protein in the placebo group. The increase in granulation index was consistently greater in the LL-37 group on days 7, 14, 21, and 28 (p = 0.031, 0.009, 0.006, and 0.037, respectively). The levels of IL-1α and TNF-α increased in both groups on days 14 and 21 (p > 0.05). The decrease in the number of aerobic bacteria colonization was greater in the LL-37 group on days 7, 14 and 21, but greater in the placebo group on day 28 (p > 0.05). In conclusion, LL-37 cream enhanced the healing rate of DFU with mild infection, but did not decrease the levels of IL-1α and TNF-α and the number of aerobic bacteria colonization. This trial is registered at ClinicalTrials.gov, number NCT04098562.

Vitamin D Levels in Pre-frail Older Adults and Its Correlation with Hand Grip Strength.

BACKGROUND: Vitamin D deficiency is frequent in older adults and associated with poor musculoskeletal function. The prevalence of pre-frailty is also high in older persons, who may proceed to a frail state. This study aimed to determine the vitamin D levels in pre-frail older adults and its correlation with hand grip strength. METHODS: A cross-sectional study was conducted on older adults (age > 60 years) with a pre-frail condition who were visiting the outpatient geriatric clinic at Cipto Mangunkusumo Hospital in Jakarta, Indonesia. Serum levels of vitamin D, measured as 25(OH)D, were determined by enzyme-linked immunosorbent assay (ELISA), and hand grip strength was measured using a Jamar hydraulic dynamometer. Correlations between vitamin D levels and hand grip strength were evaluated by Spearman's rank correlation coefficient. Multiple linear regression analysis was carried out to assess contribution of variables that influence hand grip strength. RESULTS: Of 95 pre-frail older adults (mean age 70.08 ± 5.35 years), 67.4% were female,  and the median vitamin D level was 17.91 (interquartile range/IQR 13.68-26.36) ng/mL. Overall, 11.6% of the participants had normal vitamin D levels, whereas 34.7% and 53.7% had insufficient and deficient levels, respectively. Females were more likely to have inadequacy of vitamin D than males.  Those with vitamin D deficiency tended to have a higher body mass index (BMI) and lower vitamin D intake than normal levels. A significant correlation between serum vitamin D levels and hand grip strength was observed (r = 0.283; P = 0.006). After adjusting for age, comorbidities, nutritional status, functional status, BMI, protein intake, and sun exposure score, regression analysis between hand grip strength and vitamin D levels gave standard coefficient beta = 0.255 (P = 0.013). CONCLUSION: In this study, pre-frail older adults had a high proportion of deficient and insufficient vitamin D levels, and a significant correlation was found between serum vitamin D levels and hand grip strength.

The Expressions of NF-κB, COX-2, Sp1, and c-Jun in Pancreatic Ductal Adenocarcinoma and Their Associations with Patient Survival.

Chronic inflammation is a crucial driver of carcinogenesis in pancreatic ductal adenocarcinoma (PDAC). Several studies have investigated the prognostic significance of cyclooxygenase-2 (COX-2) expression in PDAC patients, obtaining conflicting results. Nuclear factor kappa-B (NF-κB), specificity protein 1 (Sp1), and c-Jun are known as the transcription factors of the COX2 gene. This exploratory observational study investigated the association of the NF-κB, COX-2, Sp1, and c-Jun expressions with patient survival in PDAC. We used the immunohistochemical method to detect the PDAC tissue expressions of NF-κB (RelA/p65), COX-2, Sp1, and c-Jun. The expressions of these proteins were correlated with the overall survival (OS) and other clinicopathological characteristics of PDAC patients. We obtained 53 PDAC specimens from resections and biopsies. There were significant correlations between the four proteins' expressions in the PDAC tissues. The expression of the cytoplasmic (aHR = 0.31; 95% CI 0.11-0.90; p = 0.032) or nuclear NF-κB (aHR = 0.22; 95% CI 0.07-0.66; p = 0.007) was independently associated with a better prognosis in the PDAC patients. COX-2, Sp1, and c-Jun showed no significant association with a prognosis in the PDAC patients. The PDAC patients who expressed NF-κB had a better prognosis than the other patients, which suggests that the role of inflammation in PDAC is more complex than previously thought.

The effect of early radiofrequency turbinate reduction, intranasal steroid, and antihistamine H-1 on persistent allergic rhinitis: a randomized clinical trial

Abstract Objective: We aimed to evaluate the effect of radiofrequency turbinate reduction as an initial treatment on clinical improvement, inflammatory mediators, and remodeling process. Methods: Between July 2018- February 2020, 32 patients with moderate-severe persistent AR were randomly divided into 2 groups. Intervention group received radiofrequency turbinate reduction followed by intranasal steroid and Antihistamine H-1 (AH-1), control group received intranasal steroid and AH-1. Both groups were evaluated for clinical improvement (using visual analogue scale based on total nasal symptoms score, peak nasal inspiratory flow, and turbinate size using imageJ) after 4 and 8 weeks of treatment. Inflammatory mediators (ELISA from nasal secretions was performed to measure ECP, IL-5, and HSP-70) and remodeling markers (nasal biopsy followed by immunohistochemistry examination was performed to evaluate MMP-9, TIMP-1, and PAI-1) were evaluated in week 4. Results: Three patients dropped out of the study, resulting in 16 patients in intervention group and 13 patients in control group. At week 4, clinical response improved significantly in the intervention group compared to control group (Chi-Square test, p<0.05). Compared to control, intervention group experienced a reduction of IL-5 and no significant change in ECP level (Mann Whitney test, p>0.05). Reduction in the ratio of MMP-9/TIMP-1 were significantly higher in intervention group (unpaired t-test, p< 0,05). Meanwhile, increase in HSP-70 in the intervention group was slightly lower than in control group, but the difference with control group was not significant (Mann Whitney test, p>0.05). Conclusion: Early radiofrequency turbinate reduction followed by pharmacotherapy given to persistent moderate-severe AR patients give more improvement only in early clinical symptoms and reduce MMP-9/TIMP-1 ratio, thus it might be suggested as one of the adjuvant therapies for the management of moderate-severe persistent AR. However, further investigation with a larger sample size and longer follow-up period is needed. Level of evidence: 1B.

Correlation P2Y12 Genetic Polymorphism As Risk Factor of Clopidogrel Resistance in Indonesian Stroke Patients.

Background: Stroke is one of the highest causes of disability and mortality in several countries worldwide. Secondary prevention is important in the management of stroke. Clopidogrel is widely used in Asia as secondary prevention for ischemic stroke, even though several studies in Western show limited data related to clopidogrel resistance in Asia. This study aims to determine the correlation between P2Y12 genetic polymorphism and clopidogrel resistance in Indonesia. Methods: This study was conducted on one-year duration, the subjects were chosen through the consecutive sampling method, all subjects were examined for genetics and resistance to clopidogrel. The data were analyzed through statistical analysis, a bivariate analysis was conducted to determine the correlation between several variables and the resistance variable. This study employed resistance diagnostic methods with VerifyNow. Polymorphism of receptor P2Y12 was tested with the Polymerase Chain Reaction method (PCR) and analysis of restriction fragment length polymorphism (RFLP). The genes tested in this study were G52T and C34T. Results: The number of participants in this study was 112. Examination of gene P2Y12 showed that the majority was homozygote, wild-type C34T allele (67%), and G52T (66.1%). There was no significant correlation between clopidogrel resistance and gene G52T and C34T of P2Y12 (p > 0.05). Hb levels significantly correlated with P2Y12 G52T (p = 0.024). Meanwhile, Fatty Liver significantly correlated with P2Y12 C34T (p = 0.037). Conclusion: Indonesia showed a low clopidogrel resistance rate and a very low C34T and G52T allele P2Y12 gene mutation, meaning that Indonesia had low mutations in the P2Y12. This is the cause of clopidogrel resistance in this study only 15%. Therefore, in a region with less clopidogrel resistance, examination of the P2Y12 gene would not give significant results.

The role of the glucocorticoid receptor and its impact on steroid response in moderate-severe COVID-19 patients.

The effect of corticosteroid therapy in COVID-19 patients is mediated by its suppressive effect on the regulations of inflammatory response. However, its clinical outcome is often unpredictable. This study aimed to explore the role of glucocorticoid receptors in corticosteroid response in Moderate-Severe COVID-19 patients. In this cross-sectional study, we attempted to find the relationship between the expression of the glucocorticoid receptor (encoded by NR3C1), the variation of glucocorticoid receptors isoform, and the mutations of glucocorticoid receptors exon with clinical response to corticosteroids. In addition, the relationship between glucocorticoid receptors expression and the expression of IκBα (encoded by NFKBIA) and glucocorticoid-induced leucine zipper protein (GILZ; encoded by TSC22D3) as steroid pathways was also evaluated. Thirty-four COVID-19 patients were studied. Blood was drawn before and on day 5 of corticosteroid treatment. Glucocorticoid receptors expression, isoform, and mutation were determined by RNA sequencing from white blood cells. Based on the improvement of clinical and oxygen status, patients were classified into responder and non-responder groups. Of thirty-four patients, 23 (67.6%) showed excellent responses to corticosteroids, and 11 (32.4%) were non-responders. The NR3C1 gene expression was significantly higher in the responsive group at baseline and after five days of glucocorticoid treatment. Isoform variant and mutation of glucocorticoid receptors did not correlate with clinical response. The expression of IκBα and GILZ correlated positively with glucocorticoid receptors expression. This study elucidates the relationship between glucocorticoid receptor expression with therapeutic responses to corticosteroids in moderate-severe COVID-19.

The effect of early radiofrequency turbinate reduction, intranasal steroid, and antihistamine H-1 on persistent allergic rhinitis: a randomized clinical trial.

OBJECTIVE: We aimed to evaluate the effect of radiofrequency turbinate reduction as an initial treatment on clinical improvement, inflammatory mediators, and remodeling process. METHODS: Between July 2018-February 2020, 32 patients with moderate-severe persistent AR were randomly divided into 2 groups. Intervention group received radiofrequency turbinate reduction followed by intranasal steroid and Antihistamine H-1 (AH-1), control group received intranasal steroid and AH-1. Both groups were evaluated for clinical improvement (using visual analogue scale based on total nasal symptoms score, peak nasal inspiratory flow, and turbinate size using imageJ) after 4 and 8 weeks of treatment. Inflammatory mediators (ELISA from nasal secretions was performed to measure ECP, IL-5, and HSP-70) and remodeling markers (nasal biopsy followed by immunohistochemistry examination was performed to evaluate MMP-9, TIMP-1, and PAI-1) were evaluated in week 4. RESULTS: Three patients dropped out of the study, resulting in 16 patients in intervention group and 13 patients in control group. At week 4, clinical response improved significantly in the intervention group compared to control group (Chi-Square test, p < 0.05). Compared to control, intervention group experienced a reduction of IL-5 and no significant change in ECP level (Mann Whitney test, p > 0.05). Reduction in the ratio of MMP-9/TIMP-1 were significantly higher in intervention group (unpaired t-test, p < 0,05). Meanwhile, increase in HSP-70 in the intervention group was slightly lower than in control group, but the difference with control group was not significant (Mann Whitney test, p > 0.05). CONCLUSION: Early radiofrequency turbinate reduction followed by pharmacotherapy given to persistent moderate-severe AR patients give more improvement only in early clinical symptoms and reduce MMP-9/TIMP-1 ratio, thus it might be suggested as one of the adjuvant therapies for the management of moderate-severe persistent AR. However, further investigation with a larger sample size and longer follow-up period is needed. LEVEL OF EVIDENCE: 1B.

CD44+/CD24- Expression as predictors of ovarian cancer chemoresistance: immunohistochemistry and flow cytometry study.

BACKGROUND: The conventional standard treatment for ovarian cancer is not very effective, and the disease is fatal for women. Cancer Stem Cells (CSCs) that express CD44+/CD24- can contribute to chemoresistance and a poor prognosis. We seek to investigate the expression of CSCs (CD44+/CD24-) in ovarian cancer and their predictive significance. METHODS: The ambispective cohort was performed on 64 patients (32 patients in each group) at four hospitals (Cipto Mangunkusumo, Tarakan, Fatmawati, and Dharmais Hospital). Debulking surgery was performed on the patients, followed by histopathological analysis. The patients had six rounds of chemotherapy and were under monitoring for six months. The therapeutic responses were evaluated using the RECIST criteria (Response Criteria in Solid Tumors) and categorized as chemoresistant or chemosensitive. Using immunohistochemistry, we directly assess the CSCs from ovarian cancer tissue and using flow cytometry to assess the CSCs from the blood. RESULTS: High CSCs expression and ovarian cancer chemoresistance were significantly related in both trials (p 0.05). A better outcome was obtained using CD44+/CD24- immunohistochemistry. CONCLUSIONS: We conclude that there is a substantial association between high CSCs expression and chemoresistance in ovarian cancer and that CSCs immunohistochemistry has a higher predictive value.

Circadian as a prognostic factor for radiation responses in patients with cervical cancer: A nested case­control study.

The radiation response of cervical cancer is thought to be enhanced by the levels of melatonin due to its roles in the circadian cycle and cancer growth. In the present study, the roles of circadian rhythms and melatonin levels as prognostic factors for predicting the radiation response in patients with cervical cancer were examined. In this nested case­control study, patients with good and poor responses to radiotherapy were assessed in terms of the time­of­day radiation treatment was administered and further influencing factors. The radiation time was determined, as the subjects were either irradiated in the morning (06.00­10.00 am) or afternoon (04.00­06.00 pm). Data on tumour size and other biological parameters were collected and analysed by binary logistic regression. Among the 56 patients examined, most subjects had good radiation responses. Most patients were <50 years old with an initial body weight of >50 kg, no pain prior to radiation, low erythrocyte sedimentation rates, normal intravenous urography results, moderate or good differentiation on pathology and histo­pathologically non­keratinised cells. According to the multivariate analysis, the irradiation time as a surrogate of the circadian cycle (morning vs. afternoon), the initial haemoglobin (Hb) level and the clinical tumour size were significant predictors of the radiation response. The circadian cycle, tumour size and Hb levels may affect the radiation response in patients with cervical cancer. In addition, the morning group had better 5­year overall survival, but it was not significant, possibly due to the small cohort size. Further research is required to identify more relevant prognostic factors using different radiotherapy techniques [National Clinical Trial (NCT) no. NCT05511740, registration date, 08/20/2022].

Effect of primary balloon angioplasty on draining vein diameter and volume flow in patients with arteriovenous fistula: A cohort study.

Background: Chronic kidney disease (CKD) and end-stage kidney disease (ESKD) cause major morbidity and mortality in 10% of the global population with CKD. The most common renal replacement therapy is hemodialysis with arteriovenous fistula (AVF) access. AVF often undergoes maturation failure due to feeding artery and draining vein inadequacy. Mechanical dilatation, such as primary balloon angioplasty (PBA), can overcome AVF maturation failure. The volume flow (VF) and diameter of the draining veins in AVF patients must be known to evaluate the effect of PBA on AVF maturation. This study aims to analyze the impact of PBA on VF and draining vein diameter in ESKD patients undergoing AVF surgery. Methods: A retrospective cohort clinical trial was conducted at our institution. A total of 75 participants had AVF with an arterial diameter >1.5 mm or vein diameter at the AVF creation site of 2-4 mm. The subjects were divided into 2 groups: the intervention group undergoing PBA (n = 36) and the control group, without PBA (n = 39). PBA was performed using a Mustang ballon (3-6 mm, Medtronic). Follow-ups were conducted at 1 week, 2 weeks, and 6 weeks after AVF creation. Results: Based on the data, the diameter and VF of the draining veins were significantly larger in the intervention group than in the control group (p < 0.001). Furthermore, we found significant differences in the mean diameter and VF of the draining veins between the control and intervention groups at all stages of examination, from preoperatively to 6 weeks postoperatively (p < 0.001). The strength of the analysis was more than 80%. Conclusion: PBA can increase the diameter and VF of the draining veins in patients with AVF.

Clopidogrel Resistance Among Ischemic Stroke Patients and Its Risk Factors in Indonesia.

OBJECTIVE: Clopidogrel is a common antiplatelet used as secondary prevention of ischemic stroke, known to have better efficacy than aspirin, with a equivalent safety profile. However, clopidogrel resistance is not uncommon but has not been widely studied in Asia. This study will further assess clopidogrel resistance and its risk factors. MATERIALS AND METHODS: A cross-sectional study was conducted at Rumah Sakit Universitas, Indonesia, and Rumah Sakit Cipto Mangunkusumo, Indonesia in 2020-2021. All patients had had at least one episode of ischemic stroke. Clopidogrel resistance was assessed using a VerifyNow assay. RESULTS: 57 subjects were enrolled in this study. We found 15.8% of subjects were clopidogrel resistant. Gender was significantly associated with clopidogrel resistance, with males having 80% lower clopidogrel resistance (OR 0.2 (95% CI 0.022 - 0.638); P=0.006). Meanwhile, smoking was not associated with clopidogrel responsiveness (P=0.051). We found no association between haemoglobin, blood glucose, HbA1c, cholesterol, liver enzymes, serum urea concentration or creatinine levels and clopidogrel resistance. CONCLUSION: Clopidogrel remains an effective treatment to prevent recurrent ischemic stroke in Indonesia. Further studies are needed to assess gene polymorphism and clopidogrel resistance, which may explain the findings of this study.

Expression of CD44+/CD24-, RAD6 and DDB2 on chemotherapy response in ovarian Cancer: A prospective flow cytometry study.

Backgrounds: Ovarian cancer is the 8th deadliest common cancer in women around the world. Almost all ovarian cancer patients would experience chemoresistance, recurrence, and poor prognosis after cytoreductive surgery and platinum-based chemotherapy. Chemoresistant cancer cells have characteristic expressions of cancer stem cell proteins (CSCs) CD44+/CD24-, RAD6 and DDB2. The increased expression of CD44+/CD24-, RAD6, and decreased DDB2 are believed to be associated with chemoresistance, recurrence, and poor prognosis of the disease. Thus, this study's objective is to analyze the correlation between the expression of CD44+/CD24-, RAD6 and DDB2 with ovarian cancer chemoresistance. Materials and methods: This study was conducted with a prospective cohort of 64 patients who is divided into two groups (32 patients in each group) at the Obstetrics-gynecology and pathology department of Cipto Mangunkusumo, Tarakan, Dharmais, and Fatmawati Hospital. All suspected ovarian cancer patients underwent cytoreductive debulking and histopathological examination. Chemotherapy was given for six series followed by six months of observation. After the observation, we determined the therapy's response with the RECIST Criteria (Response Criteria in Solid Tumors) and then classified the results into chemoresistant or chemosensitive groups. Flow cytometry blood tests were then performed to examine the expression of CD44+/CD24-, RAD6 and DDB2. Results: There was a significant relationship between increased levels of CD44+/CD24-, and RAD6 (p < 0.05) levels with the chemoresistance of ovarian cancer. The logistic regression test showed that the CD44+/CD24- was better marker. Conclusions: These results indicate that CD44+/CD24 and RAD6 expressions are significantly associated with ovarian cancer chemoresistance, and CD44+/CD24- is the better marker to predict ovarian cancer chemoresistance.

Risk of developing cognitive impairment on patients with chronic obstructive pulmonary disease: A systematic review.

BACKGROUND: The increasing number of chronic obstructive pulmonary disease (COPD) incidence has led to a great negative impact on older people's lives. This chronic disease was a critical and independent risk factor for cognitive function impairment in the elderly with mild cognitive impairment as a frequent feature. This systematic review aimed to examine the risk of developing cognitive impairment in COPD. METHODS: A structured search of the literature was conducted using the Preferred Reporting Items for Systematic Reviews and Meta-analyses statement guideline, with a pre-determined search strategy starting from study identification, title and abstract screening, eligibility assessment, and inclusion of relevant study. The search was conducted in PubMed and MEDLINE via EBSCOhost, with restriction to human studies. The studies from inception until January 12, 2021. RESULTS: Five original articles were included. Most studies found that patients with COPD had a higher chance of developing cognitive impairment, especially when patients were followed up for more than 5 years. We discovered that the risk of cognitive impairment seemed to be correlated with the length of time spent following the participants, with the highest risk of cognitive impairment being identified in those who had the longest observation period. It is critical to conduct cognitive screening from the time a diagnosis of COPD is obtained and on a continuing basis in order to recognize and treat these individuals appropriately. CONCLUSION: There is a potential association between COPD and mild cognitive impairment. We encourage more studies to be done with higher sensitivity and specificity cognitive screening tools in the future to build better evidence and qualify to be analyzed quantitatively with meta-analysis.

Role of three-dimensional Doppler ultrasonography and leukemia inhibitory factor from endometrial secretion in predicting endometrial receptivity in IVF treatment: a pilot study.

PURPOSE: This pilot study aimed to evaluate the potential synergistic role of three-dimensional power Doppler angiography ultrasound and the expression of Leukemia Inhibitory Factor (LIF) protein in predicting the endometrial receptivity of fresh In-Vitro Fertilization (IVF) cycles. MATERIALS AND METHODS: This prognostic cohort study involved 29 good prognosis women who underwent fresh IVF cycles with fresh blastocysts transfer. Serial measurements of sub-endometrial parameters including vascularity index (VI), flow index (FI), and vascularization flow index (VFI) were conducted consecutively via power Doppler angiography on the day of oocyte maturation trigger, oocyte retrieval, and blastocyst transfer. Aspiration of endometrial secretion was performed on the day of embryo transfer. RESULTS: The mean index of VI and VFI on the trigger and oocyte retrieval day and also LIF protein concentration at the window of implantation were significantly higher in clinically pregnant women than that of the non-pregnant women (p < 0.05). The area under the curve (AUC) of VI and VFI was shown to have a powerful predictive value to forecast receptive endometrium on either trigger day (0.788 and 0.813, respectively) or oocyte retrieval day (0.813 and 0.818). Likewise, LIF concentration on the day of embryo transfer was adequate to become a predictor for endometrial receptivity (AUC 0.874). A combination of the VI and VFI on the trigger day and LIF concentration at specific cut-off values (VI > 5.381, VFI > 1.483, LIF 703.5 pg/mL) produced an algorithm with high AUC (0.881) and high specificity (94.4%) for an adequate prediction of non-receptive endometrium. CONCLUSION: VI and VFI index assessed on maturation trigger day and the expression of LIF protein concentration at the window of implantation provided sufficient information to predict endometrial receptivity. A large randomized control trial is needed to validate these findings.

The role of clopidogrel resistance-related genetic and epigenetic factors in major adverse cardiovascular events among patients with acute coronary syndrome after percutaneous coronary intervention.

Despite patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) and receiving clopidogrel therapy, some patients still experience major adverse cardiovascular events (MACEs). Clopidogrel resistance, which may be regulated by genetic and epigenetic factors, may play a role in MACEs. This study aimed to determine the association between genetic (CYP2C19 and P2Y12 polymorphisms) and epigenetic (DNA methylation of CYP2C19 and P2Y12 and miRNA-26a expression) factors and their effects on MACEs among post-PCI patients. Post-PCI patients who received a standard dosage of clopidogrel at Harapan Kita Hospital between September 2018 and June 2020 were included in this study. MACEs were observed in patients within 1 year after PCI. Platelet aggregation was assessed using light transmission aggregometry (LTA). DNA methylation of CYP2C19 and P2Y12 was assessed using the bisulfite conversion method. CYP2C19 and P2Y12 polymorphisms and miRNA-26a expression were evaluated using quantitative real-time polymerase chain reaction (qRT-PCR). Among a total of 201 subjects, 49.8% were clopidogrel-resistant, and 14.9% experienced MACEs within 1 year after PCI (death was 7.5%). Hypomethylation of CYP2C19 (p = 0.037) and miRNA-26a upregulation (p = 0.020) were associated with clopidogrel resistance. CYP2C19*2/*3 polymorphisms (p = 0.047) were associated with MACEs in 1 year. This study demonstrated that hypomethylation of CYP2C19 and miRNA-26a upregulation increased the risk of clopidogrel resistance in post-PCI patients, but there was no correlation between clopidogrel resistance and MACEs. However, CYP2C19*2/*3 polymorphisms were the factors that predicted MACEs within 1 year.

A Modified Preparation Method of Ideal Platelet-Rich Fibrin Matrix From Whole Blood.

One bioproduct that is widely used in the wound healing process is platelet-rich plasma (PRP). PRP is a liquid solution with high autologous platelet concentration, making it a good source of growth factors to accelerate wound healing. Recent development in PRP had created a new product called platelet-rich fibrin matrix (PRFM), which has a denser and more flexible structure. PRFM is the newest generation of platelet concentrate with a fibrin matrix that holds platelet in it. The key concept in creating PRFM from PRP is the addition of CaCl2 followed by centrifugation, which converts fibrinogen to fibrin, and the fibrin cross-links to form a matrix that contains viable platelets. There are many commercially available kits to create PRFM, but they are often expensive and uneconomical. This research will test a modified method of making ideal PRFM from PRP without any commercial kits. The modified method will include determining the minimum level of CaCl2 used, the type of centrifuge, and the speed and duration of centrifugation. By performing a modified preparation method on five samples of whole blood, it was found that the ideal PRFM could be made by mixing PRP with 25 mM CaCl2 and centrifuging it at a speed of 2,264 × g for 25 min at room temperature. The PRP and PRFM platelet counts of this method tend to be lower than the platelet counts found in other studies. Although visually comparable, further study is needed to compare the performance of PRFMs made with this method and PRFMs made with commercial kits.