Phospholipase A2 expression in prostate cancer as a biomarker of good prognosis: A comprehensive study in patients with long follow-up.

BACKGROUND: Phospholipase A2 (PLA2) is a large family of enzymes involved in the inflammatory process that catalyzes the hydrolysis of membrane phospholipids, leading to the production of free fatty acids and lysophospholipids, starting the arachidonic acid cascade. Their expression has been related to the behavior of several cancers. Our objective is to search for PLA2 expression in prostate cancer (PCa) tissue that correlates with prognosis and survival. METHODS: Using qRT-PCR, we analyzed the expression levels of PLA2G1B, PLA2G2A, PLA2G2D, PLA2G4A, PLA2G4B, PLA2G4C, PLA2G4D, PLA2G4E, PLA2G4F, PLA2G6, PLA2G7, PLA2G16, PNPLA1, and PNPLA2 in PCa tissue from 108 patients submitted to radical prostatectomy, followed by a mean time of 163 months. RESULTS: All PLA2 was overexpressed in PCa compared to normal tissue. Interestingly, higher expression of some PLA2 was related to favorable prognostic factors: lower levels of PSA (PLA2G2A, PLA2G4D), lower rates of lymph node metastasis (PLA2G16 and PLA2G1B), and organ-confined disease (PLA2G4A). Most importantly, PLAG4B was independently related to longer disease-free survival. CONCLUSION: This is the first study exploring comprehensively the expression levels of PLA2 in PCa, showing that the higher expression of some PLA2 should be used as biomarkers of good prognosis and longer disease-free survival.

MicroRNA-29b attenuates fibrosis in a rat model of Peyronie's disease.

BACKGROUND: Peyronie's disease is characterized by the formation of fibrotic plaques in the penile tunica albuginea. Effective treatments are limited, warranting the investigation of new promising therapies, such as the application of microRNAs that regulate fibrosis-related genes. OBJECTIVE: We aimed to investigate the therapeutic potential of mimicking microRNA-29b in a fibrin-induced rat model of Peyronie's disease. MATERIAL/METHODS: The study was designed in two phases. To establish an optimal Peyronie's disease model, rats received either human fibrin and thrombin or saline solutions into the tunica albuginea on days 0 and 5. The animal model validation was done through expression and histopathological analyses, the latest by an experienced uropathologist. After validation, we performed microRNA-29b treatment on days 14, 21, and 28 of the study. This phase had control (normal saline) and scramble (microRNA scramble) groups. The mid-penile shaft was removed on day 30 for histological examination and molecular analyses in both study stages. RESULTS: The control group displayed typical tunica albuginea histologic architecture in the animal model validation. In Peyronie's disease group, the Hematoxylin and eosin and Masson Trichrome staining methods demonstrated an interstitial inflammatory process with concomitant dense fibrotic plaques as well as disarrangement of collagen fibers. Additionally, we found out that reduced microRNA-29b (p = 0.05) was associated with significantly increased COL1A1 and transforming growth factor ß1 genes and proteins (p > 0.05) in the Peyronie's disease group. After treatment with mimic microRNA-29b stimulation, the Hematoxylin & eosin and Masson Trichrome staining revealed a discrete and less dense fibrotic plaque. This result was associated with significantly decreasing expression of COL1A1, COL3A1, and transforming growth factor ß1 genes and proteins (p < 0.05). DISCUSSION: The fibrin-induced animal model showed significant histopathological and molecular changes compared to the Control group, suggesting that our model was appropriate. Previous findings have shown that increased expression of microRNA-29b was associated with decreased pathological fibrosis. In the present study, treatment with microRNA-29b decreased the gene and protein expression of collagens and transforming growth factor ß1. This study reveals the therapeutic potential for Peyronie's disease involving molecular targets. CONCLUSION: MicroRNA-29b application on the rat's tunica albuginea attenuated fibrosis, arising as a novel potential strategy for Peyronie's disease management.

The landscape of biomedical research funding in Brazil: a current overview

ABSTRACT Objective: The objective of this narrative review is to discuss the current state of research funding in Brazil. Materials and Methods: This study is based on the most recent edition of the course Funding for Research and Innovation in the University of Sao Paulo School of Medicine which was a three-day course with 12 hours of instruction. The course brought together leading experts in the field to comprehensively discuss the current state of research funding in Brazil. Each speaker provided a presentation on a specific topic related to research funding. After the workshop, speakers assembled relevant topics in this manuscript. Results: collaborative research is critical for securing research funding. It optimizes proposal competitiveness, amplifies societal impact, and manages risks effectively. As such, fostering and supporting these collaborations is paramount for both researchers and funding agencies. To maintain the highest integrity in research, investigators involved in these collaborations must disclose any relationships that could potentially influence the outcomes or interpretation of their projects. Conclusions: In Brazil, the mainstay of research funding stems from public entities, with agencies such as CNPq, CAPES, and state bodies like FAPESP, FAPERJ, FAPEMIG and others at the forefront. Concurrently, industry funding offers viable pathways, especially through industry-sponsored studies, investigator-led projects, and collaborative initiatives. The Brazilian funding landscape is further enriched by innovative platforms, including crowdfunding and the contributions of institutions like the Serrapilheira Institute. Internationally, esteemed organizations such as the National Institutes of Health (NIH) and the Bill & Melinda Gates Foundation stand out as potential funders.

Evaluation of AR, AR-V7, and p160 family as biomarkers for prostate cancer: insights into the clinical significance and disease progression.

PURPOSE: To assess the role of the p160 family, AR, and AR-V7 in different initial presentations of prostate cancer and their association with clinical endpoints related to tumor progression. METHODS: The study sample comprises 155 patients who underwent radical prostatectomy and 11 healthy peripheral zone biopsies as the control group. Gene expression was quantified by qPCR from the tissue specimens. The statistical analysis investigated correlations between gene expression levels, associations with disease presence, and clinicopathological features. Additionally, ROC curves were applied for distinct PCa presentations, and time-to-event analysis was used for clinical endpoints. RESULTS: The AR-V7 diagnostic performance for any PCa yielded an AUC of 0.77 (p < 0.05). For locally advanced PCa, the AR-V7 AUC was 0.65 (p < 0.05). Moreover, the metastasis group had a higher expression of SRC-1 than the non-metastatic group (p < 0.05), showing a shorter time to metastasis in the over-expressed group (p = 0.005). Patients with disease recurrence had super-expression of AR levels (p < 0.0005), with a shorter time-to-recurrence in the super-expression group (p < 0.0001). CONCLUSION: Upregulation of SRC-1 indicates a higher risk of progression to metastatic disease in a shorter period, which warrants further research to be applied as a clinical tool. Additionally, AR may be used as a predictor for PCa recurrence. Furthermore, AR-V7 may be helpful as a diagnostic tool for PCa and locally advanced cancer, comparable with other investigated tools.

The landscape of biomedical research funding in Brazil: a current overview.

OBJECTIVE: The objective of this narrative review is to discuss the current state of research funding in Brazil. MATERIALS AND METHODS: This study is based on the most recent edition of the course Funding for Research and Innovation in the University of Sao Paulo School of Medicine which was a three-day course with 12 hours of instruction. The course brought together leading experts in the field to comprehensively discuss the current state of research funding in Brazil. Each speaker provided a presentation on a specific topic related to research funding. After the workshop, speakers assembled relevant topics in this manuscript. RESULTS: collaborative research is critical for securing research funding. It optimizes proposal competitiveness, amplifies societal impact, and manages risks effectively. As such, fostering and supporting these collaborations is paramount for both researchers and funding agencies. To maintain the highest integrity in research, investigators involved in these collaborations must disclose any relationships that could potentially influence the outcomes or interpretation of their projects. CONCLUSIONS: In Brazil, the mainstay of research funding stems from public entities, with agencies such as CNPq, CAPES, and state bodies like FAPESP, FAPERJ, FAPEMIG and others at the forefront. Concurrently, industry funding offers viable pathways, especially through industry-sponsored studies, investigator-led projects, and collaborative initiatives. The Brazilian funding landscape is further enriched by innovative platforms, including crowdfunding and the contributions of institutions like the Serrapilheira Institute. Internationally, esteemed organizations such as the National Institutes of Health (NIH) and the Bill & Melinda Gates Foundation stand out as potential funders.

The Effect of Gene Editing by CRISPR-Cas9 of miR-21 and the Indirect Target MMP9 in Metastatic Prostate Cancer.

Prostate cancer (PCa) has a high prevalence and represents an important health problem, with an increased risk of metastasis. With the advance of CRISPR-Cas9 genome editing, new possibilities have been created for investigating PCa. The technique is effective in knockout oncogenes, reducing tumor resistance. MMP9 and miR-21 target genes are associated with PCa progression; therefore, we evaluated the MMP-9 and miR-21 targets in PCa using the CRISPR-Cas9 system. Single guide RNAs (sgRNAs) of MMP9 and miR-21 sequences were inserted into a PX-330 plasmid, and transfected in DU145 and PC-3 PCa cell lines. MMP9 and RECK expression was assessed by qPCR, WB, and IF. The miR-21 targets, integrins, BAX and mTOR, were evaluated by qPCR. Flow cytometry was performed with Annexin5, 7-AAD and Ki67 markers. Invasion assays were performed with Matrigel. The miR-21 CRISPR-Cas9-edited cells upregulated RECK, MARCKS, BTG2, and PDCD4. CDH1, ITGB3 and ITGB1 were increased in MMP9 and miR-21 CRISPR-Cas9-edited cells. Increased BAX and decreased mTOR were observed in MMP9 and miR-21 CRISPR-Cas9-edited cells. Reduced cell proliferation, increased apoptosis and low invasion in MMP9 and miR-21 edited cells was observed, compared to Scramble. CRISPR-Cas9-edited cells of miR-21 and MMP9 attenuate cell proliferation, invasion and stimulate apoptosis, impeding PCa evolution.

Intratumoral Restoration of miR-137 Plus Cholesterol Favors Homeostasis of the miR-137/Coactivator p160/AR Axis and Negatively Modulates Tumor Progression in Advanced Prostate Cancer.

MicroRNAs (miRNAs) have gained a prominent role as biomarkers in prostate cancer (PCa). Our study aimed to evaluate the potential suppressive effect of miR-137 in a model of advanced PCa with and without diet-induced hypercholesterolemia. In vitro, PC-3 cells were treated with 50 pmol of mimic miR-137 for 24 h, and gene and protein expression levels of SRC-1, SRC-2, SRC-3, and AR were evaluated by qPCR and immunofluorescence. We also assessed migration rate, invasion, colony-forming ability, and flow cytometry assays (apoptosis and cell cycle) after 24 h of miRNA treatment. For in vivo experiments, 16 male NOD/SCID mice were used to evaluate the effect of restoring miR-137 expression together with cholesterol. The animals were fed a standard (SD) or hypercholesterolemic (HCOL) diet for 21 days. After this, we xenografted PC-3 LUC-MC6 cells into their subcutaneous tissue. Tumor volume and bioluminescence intensity were measured weekly. After the tumors reached 50 mm3, we started intratumor treatments with a miR-137 mimic, at a dose of 6 µg weekly for four weeks. Ultimately, the animals were killed, and the xenografts were resected and analyzed for gene and protein expression. The animals' serum was collected to evaluate the lipid profile. The in vitro results showed that miR-137 could inhibit the transcription and translation of the p160 family, SRC-1, SRC-2, and SRC-3, and indirectly reduce the expression of AR. After these analyses, it was determined that increased miR-137 inhibits cell migration and invasion and impacts reduced proliferation and increased apoptosis rates. The in vivo results demonstrated that tumor growth was arrested after the intratumoral restoration of miR-137, and proliferation levels were reduced in the SD and HCOL groups. Interestingly, the tumor growth retention response was more significant in the HCOL group. We conclude that miR-137 is a potential therapeutic miRNA that, in association with androgen precursors, can restore and reinstate the AR-mediated axis of transcription and transactivation of androgenic pathway homeostasis. Further studies involving the miR-137/coregulator/AR/cholesterol axis should be conducted to evaluate this miR in a clinical context.

The influence of interstitial cells of Cajal density in the outcomes of pyeloplasty in adults: A prospective analysis.

PURPOSE: To evaluate if the density of interstitial cells of Cajal (ICC) in the ureteropelvic junction (UPJ) influences the outcomes of pyeloplasty in adults. METHODS: Twenty-three patients with the diagnosis of ureteropelvic junction obstruction (UPJO) that underwent laparoscopic dismembered pyeloplasty were included. ICC density was measured using immunohistochemistry reaction for c-KIT expression in the resected UPJ segment. Pyeloplasty outcome was evaluated by patient self-report pain, urinary outflow using DTPA renogram and hydronephrosis assessment using ultrasound (US) at 12 months of follow-up. A logistic regression analysis was performed to assess the association of pyeloplasty outcomes and ICC density. RESULTS: Low, moderate, and high ICC density were present in 17.4%, 30.4%, and 52.2% of the patients, respectively. Complete pain resolution was observed in 100%, 85.7%, and 75% of patients with low, moderate and high ICC density, respectively (p = 0.791). DTPA renogram improved in 75%, 85.7%, and 91.7% of patients with low, moderate and high ICC density, respectively (p = 0.739). Hydronephrosis improved in 25%, 85.7%, and 91.7% of patients with low, moderate and high ICC density, respectively (p = 0.032). CONCLUSIONS: Patients with high ICC density have a significant amelioration of hydronephrosis after pyeloplasty. However, ICC density is not associated with functional outcomes.

Can we use Ki67 expression to predict prostate cancer aggressiveness?

INTRODUCTION: specialists have an urge for biomarkers that can discriminate indolent prostate cancer from aggressive tumors. Ki67 is a proliferation marker, and its expression is associated with the aggressiveness of several cancers. OBJECTIVE: analyze the expression of Ki67 in prostate cancer samples correlating with the aggressiveness of the disease. METHODS: Ki67 mRNA levels were determined utilizing data from a TCGA cohort (Tumor(n)=492 and control(n)=52). The protein expression was determined on 94 biopsies from patients by immunohistochemical assay. RESULTS: in mRNA, the Ki67 upregulation is associated with cancer tissue (p<0.0001) and worst disease-free survival (p=0.035). The protein upregulation is associated with increase of the ISUP score (p<0.0001), cancer stage (p=0.05), biochemical recurrence (p=0.0006) and metastasis (p<0.0001). We also show a positive correlation between Ki67 expression and ISUP score (r=0.5112, p<0.0001) and disease risk stratification (r=0.3388, p=0.0009). Ki67 expression is a factor independently associated with biochemical recurrence (p=0.002) and metastasis (p<0.0001). Finally, the patients with high Ki67expression shows better survival regarding biochemical recurrence (p=0.008) and metastasis (p=0.056). Patients with high Ki67 expression are 2.62 times more likely to develop biochemical recurrence (p=0.036). CONCLUSION: Ki67 upregulation is associated with prostate cancer aggressiveness.

Single-use flexible ureteroscopes: update and perspective in developing countries. A narrative review

ABSTRACT Flexible ureteroscopy is a well-established method for treatment of urinary stones but flexible ureteroscopes are expensive and fragile devices with a very limited lifetime. Since 2006 with the advent of digital flexible ureteroscopes a great evolution has occurred. The first single-use flexible ureteroscope was launched in 2011 and new models are coming to the market. The aim of this article is to review the characteristics of these devices, compare their results with the reusable devices and evaluate the cost-benefits of adopting single-use flexible ureteroscopes in developing countries. Materials and Methods: an extensive review of articles listed at PubMed and published between 2000 and 2021 was performed. Results: Single-use flexible ureteroscopes have a shaft with 65 to 68cm length and weight between 119 and 277g. Their deflection goes up to 300 degrees. Their stone-free rates vary between 60 and 95% which is comparable to reusable scopes and operative times ranges from 54 to 86 minutes which are lower when compared to reusable flexible scopes. Their costs vary between 800 and 3180 US dollars. Conclusion: single-use flexible ureteroscopes are lighter and have superior quality of image when compared to fiberoptic ones. There are no definite data showing a higher stone-free rate or less complications with the use of single-use flexible ureteroscopes. Each institution must perform a cost-benefit analysis before making the decision of adopting or not such devices depending on the local circumstances.

Combined spinal and general anesthesia attenuate tumor promoting effects of surgery. An experimental animal study.

Background: Radical prostatectomy, a standard management approach for localized Prostate Cancer (PC), may cause a stress response associated with immune modulating effects. Regional anesthesia was hypothesized to reduce the immune effects of surgery by minimizing the neuroendocrine surgical stress response, thus mitigating tumor cells dissemination. Our primary objective was to investigate whether the use of spinal blocks attenuates PC tumor cells dissemination on an animal model. We also assessed the number of circulating NK cells and the amount of inflammatory and anti-inflammatory cytokines. Materials and methods: A subcutaneous tumor model, with PC-3M cell line transfected with a luciferase-producing gene (PC-3M-luc-C6) was used. After proper tumor establishment and before tumors became metastatic, animals were submitted to tumor excision surgeries under general or combined (general and spinal) anesthesia. A control group was only anesthetized with general anesthesia. Results: The subcutaneous tumor model with PC-3M-luc-C6 cells was effective in causing distant metastasis after 35 days. The number of circulating tumor cells increased in animals that underwent surgery under general anesthesia alone compared to the group submitted to combined anesthesia. Interleukin 6 levels were different in all groups, with increase in the general anesthesia group. Conclusion: Our results suggest that combination of spinal and general anesthesia may attenuate the suppression of innate tumor immunity and it might be related to a reduction in the neuroendocrine response to surgery. Institutional protocol number: Animal Ethics Committee 1332/2019.

A Prospective, Randomized Trial Comparing the Outcomes of Open vs Laparoscopic Partial Nephrectomy.

PURPOSE: Partial nephrectomy is the standard treatment for renal tumors <7 cm, and the trend toward minimally invasive surgery has increased. However, data that could support its use and benefits are still lacking. MATERIALS AND METHODS: We conducted a prospective, randomized controlled trial comparing surgical, functional and oncologic outcomes in patients undergoing open partial nephrectomy (OPN) or laparoscopic partial nephrectomy (LPN). Randomization was 1:1 to OPN or LPN for the treatment of renal tumors <7 cm. The primary endpoint was surgical complications up to 90 days after surgery. Secondary outcomes were comparison of surgical, oncologic and functional results. RESULTS: We randomized 208 patients between 2012 and 2020 (110 with OPN vs 98 with LPN). Operative data showed no differences in operative time, warm ischemia time, estimated blood loss, transfusions or length of hospital stay. Zero ischemia was more frequent in the OPN (35.4% vs 15.5%, p=0.02). OPN was associated with more abdominal wall complications (31.2% vs 13.1%, p=0.004). Regarding oncologic outcomes, no differences were noted. The LPN group had less kidney function reduction at 3 (-5.2% vs -10%, p=0.04; CI 0.09 to 9.46) and 12 months after surgery (-0.8% vs -6.3%, p=0.02; CI 1.18 to 12.95), and a lower rate of downstaging on the chronic kidney disease classification at 12 months (14.1% vs 32.6%, p=0.006). CONCLUSIONS: Surgical and oncologic outcomes of LPN were similar to OPN. Minimally invasive surgery may provide better preservation of kidney function. More studies, especially those involving robotic surgery, are necessary to confirm our findings.

Downregulation of miR-29b is associated with Peyronie's disease.

BACKGROUND: Peyronie's disease (PD) is characterized by the formation of fibrous plaque in tunica albuginea, causing several problems in patients. The etiology of this disease is not fully understood, and there are few effective treatments. To better understand the molecular pathways of PD, we studied miR-29b, a microRNA that could be involved with this illness. MicroRNAs are endogenous molecules that act by inhibiting messenger RNA. MiR-29b regulates 11 of 20 collagen genes and the TGF-ß1 gene, which are related to PD progression. METHODS: We compared miR-29b expression in 11 patients with PD and 14 patients without PD (control group). For the patients with PD, we utilized samples from the fibrous plaque (n = 9), from the tunica albuginea (n = 11), and from the corpus cavernosum (n = 8). For the control group, we utilized samples from the tunica albuginea (n = 14) and from the corpus cavernosum (n = 10). MiR-29b expression was determined by q-PCR. RESULTS: We found a downregulation of miR-29b in the fibrous plaque, tunica albuginea and corpus cavernosum of patients with PD in comparison with the control group (p = 0.0484, p = 0.0025, and p = 0.0016, respectively). CONCLUSION: Although our study has a small sample, we showed for the first time an evidence that the downregulation of miR-29b is associated with PD.

Single-use flexible ureteroscopes: update and perspective in developing countries. A narrative review.

Flexible ureteroscopy is a well-established method for treatment of urinary stones but flexible ureteroscopes are expensive and fragile devices with a very limited lifetime. Since 2006 with the advent of digital flexible ureteroscopes a great evolution has occurred. The first single-use flexible ureteroscope was launched in 2011 and new models are coming to the market. The aim of this article is to review the characteristics of these devices, compare their results with the reusable devices and evaluate the cost-benefits of adopting single-use flexible ureteroscopes in developing countries. MATERIALS AND METHODS: an extensive review of articles listed at PubMed and published between 2000 and 2021 was performed. RESULTS: Single-use flexible ureteroscopes have a shaft with 65 to 68cm length and weight between 119 and 277g. Their deflection goes up to 300 degrees. Their stone-free rates vary between 60 and 95% which is comparable to reusable scopes and operative times ranges from 54 to 86 minutes which are lower when compared to reusable flexible scopes. Their costs vary between 800 and 3180 US dollars. CONCLUSION: single-use flexible ureteroscopes are lighter and have superior quality of image when compared to fiberoptic ones. There are no definite data showing a higher stone-free rate or less complications with the use of single-use flexible ureteroscopes. Each institution must perform a cost-benefit analysis before making the decision of adopting or not such devices depending on the local circumstances.

Supine versus Prone Percutaneous Nephrolithotomy for Complex Stones: A Multicenter Randomized Controlled Trial.

PURPOSE: High-quality evidence comparing supine to prone percutaneous nephrolithotomy (PCNL) for the treatment of complex stones is lacking. This study aimed to compare the outcomes of supine position (SUP) and prone position (PRO) PCNL. MATERIALS AND METHODS: A noninferior randomized controlled trial was performed according to the CONSORT (Consolidated Standards for Reporting Trials) criteria. The inclusion criteria were patients over 18 years of age with complex stones. SUP was performed in the Barts flank-free modified position. Except for positioning, all the surgical parameters were identical. The primary outcome was the difference in the success rate on the first postoperative day (POD1) between groups. The secondary outcome was the difference in the stone-free rate (SFR) on the 90th postoperative day (final SFR). A noninferiority margin of 15% was used. Demographic, operative, and safety variables were compared between the groups. Statistical significance was set at p <0.05. RESULTS: Overall, 112 patients were randomized and their demographic characteristics were comparable. The success rates on POD1 were similar (SUP: 62.5% vs PRO: 57.1%, p=0.563). The difference observed (-5.4%) was lower than the predefined limit. The final SFRs were also similar (SUP: 55.4% vs PRO: 50.0%, p=0.571). SUP had a shorter operative time (mean±SD 117.9±39.1 minutes vs 147.6±38.8 minutes, p <0.001) and PRO had a higher rate of Clavien ≥3 complications (14.3% vs 3.6%, p=0.045). CONCLUSIONS: Positioning during PCNL for complex kidney stones did not impact the success rates; consequently, both positions may be suitable. However, SUP might be associated with a lower high-grade complication rate.

Tranexamic acid in patients with complex stones undergoing percutaneous nephrolithotomy: a randomised, double-blinded, placebo-controlled trial.

OBJECTIVES: To assess the efficacy and safety of single-dose tranexamic acid on the blood transfusion rate and outcomes of patients with complex kidney stones undergoing percutaneous nephrolithotomy (PCNL). PATIENTS AND METHODS: In a randomised, double-blinded, placebo-controlled trial, 192 patients with complex kidney stone (Guy's Stone Scores III-IV) were prospectively enrolled and randomised (1:1 ratio) to receive either one dose of tranexamic acid (1 g) or a placebo at the time of anaesthetic induction for PCNL. The primary outcome measure was the occurrence rate of perioperative blood transfusion. The secondary outcome measures included blood loss, operative time, stone-free rate (SFR), and complications. ClinicalTrials.gov identifier: NCT02966236. RESULTS: The overall risk of receiving a blood transfusion was reduced in the tranexamic acid group (2.2% vs 10.4%; relative risk, 0.21, 95% confidence interval [CI] 0.03-0.76, P = 0.033; number-needed-to-treat: 12). Patients randomised to the tranexamic acid group had a higher immediate and 3-month SFR compared with those in the placebo group (29% vs 14.7%, odds ratio [OR] 2.37, 95% CI 1.15-4.87, P = 0.019, and 46.2% vs 28.1%, OR 2.20, 95% CI 1.20-4.02, P = 0.011, respectively). Faster haemoglobin recovery occurred in patients in the tranexamic acid group (mean, 21.3 days; P = 0.001). No statistical differences were found in operative time and complications between groups. CONCLUSIONS: Tranexamic acid administration is safe and reduces the need for blood transfusion by five-times in patients with complex kidney stones undergoing PCNL. Moreover, tranexamic acid may contribute to better stone clearance rate and faster haemoglobin recovery without increasing complications. A single dose of tranexamic acid at the time of anaesthetic induction could be considered standard clinical practice for patients with complex kidney stones undergoing PCNL.