Unveiling the Anticancer Potential of Pasak Bumi (Eurycoma Longifolia Jack) Root Extract in Prostate Cancer Treatment.

Background: Prostate cancer remains a significant global health concern, necessitating the exploration of novel therapeutic avenues to enhance treatment efficacy and mitigate adverse effects. Objective This study delves into the potential anticancer properties of Pasak Bumi (Eurycoma longifolia Jack) root extract, a traditional Southeast Asian medicinal plant, against prostate cancer. Methods: The research employs a multifaceted approach, encompassing molecular and cellular analyses to unravel the intricate mechanisms underlying Pasak Bumi's effects on prostate cancer cells. Primary focus is given to the PTEN/P13k/Akt pathway, a critical regulator of cell survival and apoptosis. Various concentrations of Pasak Bumi root extract are applied to prostate cancer cell lines, and the impact on apoptosis, cell proliferation, and key molecular targets is assessed. Results: Preliminary findings reveal that Pasak Bumi root extract induces apoptosis in prostate cancer cells, evidenced by downstream molecular events associated with programmed cell death. The extract demonstrates concentration-dependent effects, with higher concentrations exhibiting more pronounced anticancer activity. Moreover, Pasak Bumi root extract appears to modulate the PTEN/P13k/Akt pathway, providing a potential mechanistic link to its anticancer effects. Discussion: The study's significance lies in its contribution to the evolving landscape of natural compounds as anticancer agents, particularly in the context of prostate cancer. Pasak Bumi's traditional use as a medicinal plant, coupled with emerging scientific evidence, underscores its potential translational value. The observed modulation of the PTEN/P13k/Akt pathway aligns with the current understanding of prostate cancer pathogenesis, offering a plausible explanation for Pasak Bumi's anticancer effects. Conclusion: This research sheds light on the promising anticancer potential of Pasak Bumi root extract against prostate cancer. Further exploration of its molecular interactions, synergy with conventional therapies, and efficacy at different stages of cancer progression is warranted. The findings present Pasak Bumi as a nature-inspired candidate for prostate cancer treatment, warranting continued investigation into its therapeutic applications. As the scientific community endeavors to enhance cancer treatment modalities, Pasak Bumi emerges as a captivating subject in the pursuit of effective and minimally invasive prostate cancer therapies.

Evaluation of Cutoff Point Prostate Specific Antigen (PSA) and Prostate Specific Antigen Density (PSAD) in Patients with Suspected Prostate Cancer.

Background: Prostate cancer is the second leading cause of cancer death in men worldwide. There is no national standard for PSA cut-off levels even through the transrectal prostate biopsy procedure causes many serious complications such as bleeding, infection, and sepsis. Therefore, determining cut-off levels for PSA and PSAD is essential to avoid unnecessary biopsies. Objective: This study aims to determine the Prostate Specific Antigen (PSA) and Prostate Specific Antigen Density (PSAD) cut-off points in patients with suspected prostate cancer. Methods: A retrospective study was conducted from January 2018 until March 2021 in Saiful Anwar General Hospital Malang Indonesia. Inclusion criterias were patients with suspected prostate cancer; > 50 years old; underwent PSA, PSAD, and prostate biopsy. Exclusion criterias were patients refuse to participate in the study and incomplete patient medical record data. Medical records from 53 patients who underwent transrectal ultrasonography (TRUS)-guided prostate biopsy were reviewed. Statistical analysis was performed using Mann-Whitney U, Chi-Square, Fisher's Exact, and Receiver Operator Characteristic (ROC) curves. Results and Discussion: Medical records conducted 53 patients who met inclusion criteria and underwent transrectal ultrasonography (TRUS)-guided prostate biopsy were reviewed. PSA cut off level for prostate biopsy was 19.71 ng/ml with a sensitivity of 69.23% and a specificity of 72.5%. The positive predictive value is 45% and the negative predictive value is 87.87%. PSAD cut off level for prostate biopsy was 0.4113 with a sensitivity of 61.54% and a specificity of 63.16%. The positive predictive value is 36.36% and the negative predictive value is 82.76%. Conclusion: Results from this study, the cut off levels of PSA and PSAD in prostate disease patients is higher than the recommended cut off; prostate cancer is the largest malignancy in men worldwide and has a higher incidence in the older age and high serum PSA levels group.

Methylenetetrahydrofolate Reductase C677T (rs1801133) Polymorphism Is Associated with Bladder Cancer in Asian Population: Epigenetic Meta-Analysis as Precision Medicine Approach.

The etiology of bladder cancer remains unclear. This study investigates the impact of gene polymorphisms, particularly methylenetetrahydrofolate reductase gene (MTHFR), on bladder cancer susceptibility, focusing on the rs1801133 single-nucleotide polymorphism (SNP). A meta-analysis was conducted after systematically reviewing the MTHFR gene literature, adhering to PRISMA guidelines and registering in PROSPERO (CRD42023423064). Seven studies were included, showing a significant association between the MTHFR C677T (rs1801133) polymorphism and bladder cancer susceptibility. Individuals with the T-allele or TT genotype had a higher likelihood of bladder cancer. In the Asian population, the overall analysis revealed an odds ratio (OR) of 1.15 (95% CI 1.03-1.30; p-value = 0.03) for T-allele versus C-allele and an OR of 1.34 (95% CI 1.04-1.72; p-value = 0.02) for TT genotype versus TC+CC genotype. The CC genotype, however, showed no significant association with bladder cancer. Notably, epigenetic findings displayed low sensitivity but high specificity, indicating reliable identified associations while potentially overlooking some epigenetic factors related to bladder cancer. In conclusion, the MTHFR T-allele and TT genotype were associated with increased bladder cancer risk in the Asian population. These insights into genetic factors influencing bladder cancer susceptibility could inform targeted prevention and treatment strategies. Further research is warranted to validate and expand these findings.

The Effect Of Continuously Dutasteride Monotherapy on The Expression Of Protein Kinase C-Alpha Enzyme In BPH Model Of Wistar Strain Rattus Novergicus Rat.

Background: Benign prostate hyperplasia (BPH) is frequently found in the elderly and significantly impacts the quality of life. One of the risk factors that induce BPH is the androgen hormone. One of the effective medications in reducing the severity of Lower Urinary Tract Symptoms caused by BPH is the α-adrenergic receptor 5α-reductase inhibitor. Objective: The study aims to see the effect of long-term dutasteride on the expression of the PKC-α enzyme in prostatic stromal tissue in the BPH Model of Wistar strain Rattus norvegicus rats. Method: This study was an experimental, post-test-only, control group design that used randomization in sample selection. The objective is to measure the expression of PKC-α enzyme from prostate tissue of an adult male Wistar Strain of Rattus Novergicus rat that was given testosterone to induce BPH and given dutasteride in 1,3 and 6 days continuously. Data is shown in mean±SD, and all of the data were analyzed using the software SPSS 21st version with the One Way ANOVA Statistical method after fulfilling the normality test and variant homogeneity test. Data analysis with confidence rate 95% and a=0,05. Results: There was a decrease of PKC-α enzyme and prostate weight in dutasteride monotherapy in 1,3,6 days compared to the positive control, and the lowest value was on the sixth day (SD ± 2876.8). There was a constant decrease of PKC-α enzyme from the first day until the sixth day. Conclusion: In conclusion, long-term dutasteride monotherapy could significantly decrease the level of PKC-α enzyme. There was no upregulation of the PKC-α enzyme in the long term of dutasteride monotherapy.

TGF-ß1 Effects on Total Collagen of the New Zealand Rabbit's Urethral Wall (Oryctolagus cuniculus) in Animal Models of Urethral Stricture.

Background: Currently, animal models of urethral stricture are not standardized. Transforming Growth Factor Beta 1 (TGF-ß1) regulates extracellular matrix deposition in homeostatic and pathological responses. Objective: The aim of this study was to present the potential model to be developed as a urethral stricture. Methods: True experimental laboratory research was conducted by using Male New Zealand rabbits (Oryctolagus cuniculus), which were divided into 5 groups; control, placebo, and 3 treatment groups (TGF-ß1 injection of 1 µg, 2 µg, 4 µg). Urethrography, histopathological analysis, and evaluation of total collagen formation of the urethral wall were performed after 6 weeks. Results: An increase in the dose of TGF-ß1 decreased the mean rabbit's urethral lumen diameter (29.3% in the 2µg group and 34% in the 4µg group) compared to controls. Three rabbits decreased as much as ≤ 50% in urethral lumen diameter. Significant increases in total collagen density in the periluminal and peripheral urethral spongiosum were noted by increasing doses of TGF-ß1. The percentage of urethral lumen diameter has a strong negative correlation with periluminal total collagen density (r = -0,798; p = 0,000) and very strong negative correlation with peripheral spongiosa total collagen density (r = -0,748, p = 0,000). Conclusion: TGF-ß1 plays a role in changing total collagen compositions of the rabbit's urethral wall, decreasing the urethral lumen diameter. Further research with increasing doses of TGF-ß1 is needed to determine the effective dose of TGF-ß1 in inducing urethral stricture.

Association of Retinal Microangiopathy with Albuminuria in Patient with Chronic Kidney Disease: a Meta-analysis Study.

Background: Chronic kidney disease (CKD) patients suffer renal and cardiovascular problems and early death. In 2016, 13.4% of all ages globally had CKD. Kidney disease, diabetes, and hypertension have a microvascular component. Diabetic retinopathy (DR) and diabetic nephropathy (DN) commonly occur concurrently, indicating that the same mechanisms may be at action in the eyes and kidneys. Chronic kidney disease (CKD) has been a tough medical problem because of late signs and late treatment. Retinal vessels are a non-invasive technique to examine systemic microvasculature. Novel predictors may enhance microvascular disease risk categorization, leading to better therapy. Retinal vascular diameter and retinopathy are reported most often. Numerous investigations have linked this condition to kidney or other systemic disorders. The retinal microvasculature was linked with both the incidence and prevalence of renal illness in this investigation. We wanted to determine whether retinal microvasculature might be utilized to diagnose renal disease. Methods: Initial searching found 625 papers, of which 542 articles were rejected due to primary screening unrelated titles and/or abstracts. There were a total of 81 papers selected for full-text evaluation and due to insufficient data provided and duplication, we got 5 papers to enter the next step. Results: In five investigations, retinal microvascular symptoms correlated with albuminuria. All studies connected retinal vascular diameter with albuminuria. As a categorical variable, CRAE narrowed. There was a U-shaped relationship between CRAE and albuminuria in quintiles 1 and 5. There were relationship between albuminuria to a larger CRVE and a narrower CRAE. Studies relate AVR to albuminuria were associated as well. Conclusion: Our investigation demonstrated retinal vascular symptoms are linked to renal illness. Retinopathy correlates with CKD and ESRD in diabetic and nondiabetic individuals. Evidence linking retinal vascular width to early renal disease implies fundus photography might be a useful screening technique for CKD patients. Insufficient evidence links retinal vascular diameter to kidney-related morbidity and death. Future studies should stratify by age, gender, obesity, hypertension, ethnicity, and others.

Complex Complicated Posterior Urethral Stricture with Contracted Bladder and Prostatorectal Fistula: How Do We Manage It?

Background: Posterior traumatic urethral strictures due to PFUI have a wide variety of complication, such as erectile dysfunction, incontinence, bulbar urethral necrosis, and fistula. Bulbar urethral necrosis caused by inadequate blood supply for bulbar urethra, fistula developed by many surgical attempts done by inexperience surgeon worsen the patient's condition, low vascular capability manifested as erectile dysfunction as well, and long term catheterization causes contracted bladder. This condition deteriorates the function and quality of life. Therefore this is very challenging condition to treat. Case Presentation: Thirty-years-old man presented with the chief complaint of urine leakage from rectum and cutaneous fistula since 9 years ago. Patient also come with complex PFUI, iatrogenic bulbar urethral necrosis, erectile dysfunction with EHS score of 1, contracted bladder, and prostatorectal fistula. Patient underwent eight various surgical procedures including open surgery and internal urethrotomy previously. We performed cystoprostatectomy and fistula repair transabdominally. Continent cutaneous stoma ileal neobladder with Mansoura approach was performed afterwards. Patient was counselled and educated on how to do clean intermittent self-catheterization, patient was fully satisfied with his bladder function which increase quality of life. Conclusion: In this case of BUN with contracted bladder and prostatorectal fistula, continent cutaneous stoma is an option to improve patient's quality of life. PFUI could be treated with high success rate if treated properly from the beginning, more intervention by inexperience surgeon could deteriorate success rate and also quality of life.

Deciphering the Role of TGF-ß1 in Altering Collagen I and Collagen III in the New Zealand Rabbit's (Oryctolagus cuniculus) Urethral Wall in Urethral Stricture Development.

Background: Presently, there's a lack of standardization in animal models used for studying urethral stricture. Transforming Growth Factor Beta 1 (TGF-ß1) is known to regulate the deposition of extracellular matrix in both normal and pathological conditions. This factor holds promise as a potential model for simulating urethral stricture. Objective: This study aims to investigate the impact of Transforming Growth Factor Beta 1 (TGF-ß1) on Collagen I and Collagen III within the urethral wall of New Zealand Rabbits (Oryctolagus cuniculus) in the context of developing urethral stricture in animal models. Methods: We conducted genuine laboratory experiments using Male New Zealand rabbits (Oryctolagus cuniculus), which were categorized into five groups: control, placebo, and three treatment groups (TGF-ß1 injections of 1 µg, 2 µg, 4 µg). After a duration of 6 weeks, we conducted urethrography, histopathological analysis, and assessed the formation of collagen I and collagen III within the urethral wall. Results: Elevating the dosage of TGF-ß1 led to a reduction in the average urethral lumen diameter of rabbits (29.3% in the 2µg group and 34% in the 4µg group) compared to the control group. In fact, three rabbits experienced a decrease of ≤ 50% in their urethral lumen diameter. As the doses of TGF-ß1 increased, we observed significant increases in the density of collagen I, and collagen III in both the periluminal and peripheral regions of the urethral spongiosum. Additionally, there was a tendency for the collagen I/collagen III ratio to decrease in the periluminal region, with collagen III density surpassing that of collagen I. In the peripheral spongiosa area, notable mean differences were observed between the control group, 1T, and 2T groups, with collagen I density tending to be higher than that of collagen III. Furthermore, the percentage of urethral lumen diameter exhibited a robust negative correlation with periluminal collagen I density (r = -0.672, p = 0.001), peripheral spongiosa collagen I density (r = -0.603, p = 0.005), periluminal collagen III density (r = -0.717, p = 0.001), and an exceptionally strong negative correlation with collagen III density of peripheral spongiosa (r = -0.804, p = 0.000). Conclusion: TGF-ß1 exerts an influence on altering the composition of collagen I and collagen III within the urethral wall of rabbits, leading to a reduction in the diameter of the urethral lumen. Further research is warranted to determine the optimal dose of TGF-ß1 required to induce urethral stricture effectively.

The Effect of Long-Term Tamsulosin Monotherapy and Tamsulosin - Dutasteride Combination Therapy on PKC-α Enzyme Expression in Prostate Stromal Tissue.

Background: The α-adrenergic receptor antagonist is the most effective medical therapy to reduce the dynamic component in patients with BPH. However, long-term administration of receptor antagonists can cause upregulation of mRNA receptor expression, resulting in tolerance of drug effectiveness. PKC-α is involved in the process of prostate smooth muscle contraction through activation of the voltage-gated Ca2+ conducted canal, influenced by androgen hormones, especially testosterone, and has an isoform with Twist1, a transcription factor that plays a role in up-regulation of androgen receptors. Objective: The aim of the study was to compare the effect of long-term tamsulosin monotherapy and tamsulosin - dutasteride combination therapy in PKC-α enzyme expression in prostate stromal tissue of Rattus norvegicus rats of Wistar strain. Methods: Out of 80 samples of Rattus norvegicus rats were divided into 8 groups with different interventions: negative control group, positive control group, tamsulosin monotherapy administration for 1 day, 3 day, and 6 day groups, and tamsulosin - dutasteride combination therapy for 1 day, 3 day, and 6 day groups. BPH was induced with 3 mg/kg of testosterone proprionate for 3 weeks, continued with drugs administration according to intervention grouping. Prostate stromal tissue was taken and prepared for PKC-α enzyme measurement with ELISA method. Results: There was a significant difference (p<0.05) in the effect of tamsulosin monotherapy and tamsulosin-dutasteride combination therapy on the PKC-α expression. There was a strong positive relationship between the duration of tamsulosin-dutasteride combination therapy on the PKC-α expression, which means the longer the duration of the combination of tamsulosin-dutasteride combination the higher the PKC-α expression. Conclusion: Administration of long-term tamsulosin - dutasteride combination therapy causes upregulation PKC-α expression more than tamsulosin only.

Comparison Between Intravesical Chemotherapy Epirubicin and Mitomycin-C after TURB vs TURB Alone With Recurrence Rate of Non-Muscle Invasive Bladder Cancer: Meta-Analysis.

Background: Bladder cancer is still a burden on the world of oncology medicine, which every year affects about 3.4 million people globally with 430,000 new cases per year. It is the fourth most common cancer in men and eighth most common women malignancy in the world. This makes bladder cancer a "silent killer" and it needs appropriate treatment planning. Single immediate instillation of chemotherapy after transurethral resection of the bladder (TURB) is recommended by EAU guideline, but its use remains a controversy. Objective: Study aimed to analyze benefit of intravesical chemotherapy following TURB in terms of recurrency of non-muscle invasive bladder cancer (NMIBC). Methods: Systematic review and meta-analysis of randomized controlled trials comparing the efficacy of a single instillation after TURB with TURB alone in NMIBC (pTa-pT1) patients was conducted. Studies searched throughout Medline, PubMed, Embase, and Cochrane in December 2018. Keywords were intravesical chemotherapy, combination, transurethral resection, bladder cancer. Inclusion criteria were RCT studies, subjects in study were treated single immediate chemotherapy instillation after TURB compared to TURB alone in patient with pTa-pT1 urothelial carcinoma of the bladder. Trials with additional treatment prior to first reccurence were not eligible. Studies using recurrence rate as dependent variable. From 361 studies, in total 11 studies were eligible for this meta-analysis. Results: From those 11 studies, it is shown that intravesical chemotherapy using Epirubicin and Mitomycin-C following TURB showed significant decrease of recurrence rate of bladder cancer even to progression of the disease compared to TURB alone (p<0.05) with pooled Risk Ratio were 0.69 and pooled heterogeneity (I2) were 26.6%. Conclusion: This meta-analysis study showed that combination therapy of intravesical chemotherapy after TURB is superior to TURB alone in showing the recurrence rate of NMIBC.

The Effect of Covid-19 Severity on Lower Urinary Tract Symptoms Manifestations.

Background: The dominant symptoms in the patient with COVID-19 are symptoms of the respiratory organ system such as cough, rhinorrhea, dan shortness of breathing. Nonetheless, some reports found involvement of another organ system, including the gastrointestinal system, cardiovascular system, central nervous system, urinary system, such as lower urinary tract symptoms. Hematuria related to infection of COVID-19 virus on adult and kids were reported. Urinary frequency related to infection of the covid-19 virus was also reported. However, the association between covid-19 infection and lower urinary symptoms was still unknown. Objective: This study aims to identify the effect of covid-19 infection on lower urinary tract symptoms manifestation on the patient with COVID-19 treated in Field Hospital. Methods: The design of this study is cross-sectional. After inclusion and exclusion criteria, the male and female patients were then asked based on question points from the International Prostate Score and latest condition related covid-19. In addition, we statistically analyzed the association and the effect between these two variables. Results: Six hundred and six COVID-19 confirmed patients were included in this study. The most frequent complaints of lower urinary tract symptoms were frequency. The severity of the covid-19 correlates with the lower urinary tracts symptoms score. Conclusion: The most common lower urinary tract symptoms are frequency, urgency, and nocturia. These lower urinary tract symptoms may increase in severity with the severity of the infection from COVID-19. The severity of COVID-19 has a significant effect on the increase in lower urinary tract symptoms.

Modulation of T-cell Regulators Associated with Advanced Stage of Prostate Cancer.

BACKGROUND: Benign prostatic hyperplasia (BPH) and prostate cancer are the most common prostate diseases. The possible role of the immune system in the pathogenesis of BPH and prostate cancer in recent years has begun to be widely studied. Although many studies have focused on T lymphocytes on the development of BPH and prostate cancer, the role of regulatory T-cells in the pathogenesis of BPH and prostate cancer is still not well known. OBJECTIVE: To determine the amount of regulatory T-cells in prostate cancer and BPH so that it can contribute to the concept of understanding the pathogenesis of prostate cancer and BPH. METHODS: This study used cross-sectional design study. Total samples were 24 patients, with 13 subjects prostate cancer group, and 11 subjects BPH group. Furthermore, peripheral blood samples are taken and then the amount of regulatory T-cells is calculated. After obtaining data on the amount of CD4+ CD25+ Foxp3+ regulatory T-cells in the blood, data analysis was performed between groups of patients diagnosed with prostate cancer and benign prostatic hyperplasia. RESULTS: The average amount of regulatory T-cells in the CRPC group was 53.44±29.43, prostate cancer group was 57.02±22.49 and the BPH group 89.71±9.31. One Way ANOVA test results showed that the average amount of regulatory T-cells between treatment groups gave a significant difference in regulatory T-cells with a p-value (0,003) <0.05. It can be concluded that there are differences in the average amount of regulatory T-cells, so we continued the testing with Tukey test. We continue to Pearson correlation study and resulted in significantly correlated with p value = 0.011 (P<0.05) and r = 0.414. CONCLUSIONS: It can be concluded there was significant difference between the average number of regulator T-cells in the BPH group compared with prostate cancer and CRPC patient. Further research is needed regarding the number of regulator T-cells CD4 + CD25 + FOXP3 + in prostate cancer patients (grouped according to Gleason score) and benign prostatic hyperplasia before and after therapy with bigger samples.

miRNA-21 Serum Evaluation in BPH, Hormone Sensitive Prostate Cancer, and Castrate Resistant Prostate Cancer: Attempt for Diagnostic Biomarker Evaluation.

BACKGROUND: Some of prostate cancer cases could progress to be Castrate Resistant Prostate Cancer (CRPC). However it is still a challenge to early diagnose it since no reliable examination could be done except PSA, which has high variability. It is now known that miRNAs are involved in nearly all inflammatory responses. Several malignancies in humans that specifically express miRNA have been detected and identified. The expression values of miRNA-21 also correlates with the occurrence of resistant castration of prostate cancer and metastases, therefore miRNA-21 is expected to be a biomarker to estimate the progression of cancer. OBJECTIVE: The purpose of this study was to analyze the expression values and cut-off markers of miRNA-21 as markers of CRPC progression. METHODS: This study used a retrospective cohort design with observational analysis. The forty-eight total sample was obtained from serum, then the RT-PCR was performed to obtain expression values of miRNA-21. Data were analyzed using One Way ANOVA to see the difference in the expression values of miRNA-21. Furthermore, to determine the cut-off analysis was carried out using the ROC curve. RESULTS: In the BPH group, an average expression value of miRNA-21 was 33,785±1.80 ng/dL, in the Prostate cancer group the average miRNA-21 was 34.51±1.32 ng/dL, while in the CRPC group, an average miRNA-21 was obtained, reaching to 34.51±1.32 ng/dL. The cut-off value of miRNA-21 from the BPH category was <33,595, PPV = 50%, NPV = 80% with a value of p = 0.081, the prostate Ca category was 33.595-35.21, PPV = 87.5%, NPV = 66.7% with p value = 0.003, while the value of miRNA-21 in the CRPC category was> 35.21, PPV = 80%, NPV = 58.3 with a value of p = 0.04. CONCLUSION: There is a significant difference in the expression values of miRNA-21 between BPH with CRPC and Prostate cancer and CRPC, therefore, miRNA-21 cut-off point is potential to differentiate the diagnosis.

Acute Kidney Injury Following Mannitol Administration in Traumatic Brain Injury: a Meta-analysis.

BACKGROUND: Acute kidney injury (AKI) is one of the most frequent but anticipated potential complications. The objective of this meta-analysis was to evaluate the AKI incidence following mannitol administration in traumatic brain injury (TBI) patients worldwide. OBJECTIVE: So in this study, authors will discuss the incidence of AKI related to the provision of mannitol in TBI cases so it is expected to provide a better prevention of complications. METHODS: We were using meta-analysis. Studies were searched throughout Pubmed, Cochrane, JNS in December 2017. Studies that were included ranged from 2009-2018. Keywords were "renal" or "kidney" and "traumatic brain injury". Inclusion criteria were full-text observational study or randomized control trial, subjects in study were newly diagnosed AKI after TBI, GCS < 13, with age range 15-100 years old, survived and followed at least for 30 days after discharge, and given mannitol at least 1g/kg BW/day for at least 3 days. From 648 studies, total 4 studies were eligible for this study. Statistical analysis was done by using Review Manager 5. RESULTS: From those 4 studies, it is shown than the pooled risk ratio AKI incidence following mannitol administration in traumatic brain injury (TBI) was 1.57. The pooled risk ratio had wide heterogeneity (I2 = 0.95 and 1, p< 0.05) so random effect model was used. CONCLUSION: AKI appeared more frequent in patient with TBI with mannitol administration. It still needs more multicentre and long term period researches in the future to get better understanding AKI in TBI following mannitol administration.

miRNA-21 as Reliable Serum Diagnostic Biomarker Candidate for Metastatic Progressive Prostate Cancer: Meta-analysis Approach.

BACKGROUND: Prostate cancer is the second leading cause of cancer death in men, moreover when it develops metastasis. However, PSA detection in serum as current gold standard to measure disease progressivity had wide variability leading to confounding outcomes. MicroRNA-21 has diagnostic values for cancer over period of time researched, yet results are still inconclusive. OBJECTIVE: The aim of the study was to conduct recent meta-analysis to assess reliability of miRNA-21 as diagnostic biomarker especially in progressivity of prostate cancer. METHODS: Published papers from PubMed, Science Direct, and Embase" as of 1 July 2021 assessing circulating miRNA-21 in progressivity of prostate cancer patients were analyzed using Comprehensive Meta-Analysis tool. Pooled sensitivity, specificity, positive and negative likelihood ratio (LR) and SROC assessed with 95 % confidence intervals were estimated using fixed-effects or random-effects models. RESULTS: In total, we included 6 papers total of 651 samples reporting miRNA-21 capability of detecting progressive prostate cancer. The pooled sensitivity and specificity showed 0.91 (95% CI 0.88-0.94, I2=0%) and 0.89 (95% CI 0.85-0.92, I2=44.8%), respectively. Positive and negative likelihood ratio showed 7.18 (95% CI 4.31-11.96, I2=56%) and 0.11 (95% CI 0.07-0.16, I2=11.8%). SROC were assessed and got Area Under Curve around 97.4%. CONCLUSION: miRNA-21 could serve as biomarkers of prostate cancer progressivity since remarkable diagnostic value of circulating miRNA-21 in prostate cancer metastasis process.

Monosymptomatic Nocturnal Enuresis Treatment Using Alarm-Therapy and Desmopressin: A Meta-analysis Approach.

BACKGROUND: One of the common pediatric issues is monosymptomatic nocturnal enuresis (MNE). MNE is involuntarily urine-voiding in night sleep without lower urinary tract symptoms, such as daytime frequency, incontinence, or urgency. Alarm therapy and desmopressin have been used for treating MNE, but there is no clear comparison of the effectiveness of the two modalities. OBJECTIVE: This study aimed to compare the efficacy of alarm therapy and desmopressin and strategies to improve the therapy. METHODS: Study searches were conducted on PubMed, Embase, and Cochrane with a time span of 2010 to 2021. The keywords used were desmopressin, alarm therapy, pediatrics, and monosymptomatic enuresis. The study included an RCT in English, and no subjects were dropped out. Studies without a definite number of subjects were excluded. RESULTS: As many as 12 studies were included in the meta-analysis, 9 of which looked for response rates, and 3 were for desmopressin-withdrawal optimization strategy. Alarm therapy was superior to desmopressin in well-motivated parents and patients (p=0.02), with a combined risk ratio of 1.10 in the low heterogeneity population (Z-score = 2.31; I2 = 32%). A strategy that could reduce the risk of desmopressin-withdrawal was a structured dose reduction rather than a sudden dose reduction (p=0.001; I2=0%; Z-score = 3.26). However, therapy discontinuation based on time did not differ the risk (p=0.24; I2=0%; Z-score = 1.17). CONCLUSION: The meta-analysis shows that alarm therapy has a better response rate than desmopressin in proactive parents. However, desmopressin may be an option in the opposite subjects, and it is necessary to use structured strategies to optimize the treatment.