ESR Essentials: using the right scoring system in prostate MRI-practice recommendations by ESUR.

MRI has gained prominence in the diagnostic workup of prostate cancer (PCa) patients, with the Prostate Imaging Reporting and Data System (PI-RADS) being widely used for cancer detection. Beyond PI-RADS, other MRI-based scoring tools have emerged to address broader aspects within the PCa domain. However, the multitude of available MRI-based grading systems has led to inconsistencies in their application within clinical workflows. The Prostate Cancer Radiological Estimation of Change in Sequential Evaluation (PRECISE) assesses the likelihood of clinically significant radiological changes of PCa during active surveillance, and the Prostate Imaging for Local Recurrence Reporting (PI-RR) scoring system evaluates the risk of local recurrence after whole-gland therapies with curative intent. Underlying any system is the requirement to assess image quality using the Prostate Imaging Quality Scoring System (PI-QUAL). This article offers practicing radiologists a comprehensive overview of currently available scoring systems with clinical evidence supporting their use for managing PCa patients to enhance consistency in interpretation and facilitate effective communication with referring clinicians. KEY POINTS: Assessing image quality is essential for all prostate MRI interpretations and the PI-QUAL score represents  the standardized tool for this purpose. Current urological clinical guidelines for prostate cancer diagnosis and localization recommend adhering to the PI-RADS recommendations. The PRECISE and PI-RR scoring systems can be used for assessing radiological changes of prostate cancer during active surveillance and the likelihood of local recurrence after radical treatments respectively.

Discovery of Hit Compounds Targeting the P4 Allosteric Site of K-RAS, Identified through Ensemble-Based Virtual Screening.

Mutants of Ras are oncogenic drivers of a large number of human tumors. Despite being recognized as an attractive target for the treatment of cancer, the high affinity for its substrate tagged the protein as undruggable for a few years. The identification of cryptic pockets on the protein surface gave the opportunity to identify molecules capable of acting as allosteric modulators. Several molecules were disclosed in recent years, with sotorasib and adagrasib already approved for clinical use. The present study makes use of computational methods to characterize eight prospective allosteric pockets (P1-P8) in K-Ras, four of which (P1-P4) were previously characterized in the literature. The present study also describes the results of a virtual screening study focused on the discovery of hit compounds, binders of the P4 site that can be considered as peptidomimetics of a fragment of the SOS αI helix, a guanine exchange factor of Ras. After a detailed description of the computational procedure followed, we disclose five hit compounds, prospective binders of the P4 allosteric site that exhibit an inhibitory capability higher than 30% in a cell proliferation assay at 50 µM.

Effect of Trace Metal Ions on the Conformational Stability of the Visual Photoreceptor Rhodopsin.

Trace metals are essential elements that play key roles in a number of biochemical processes governing human visual physiology in health and disease. Several trace metals, such as zinc, have been shown to play important roles in the visual phototransduction process. In spite of this, there has been little research conducted on the direct effect of trace metal elements on the visual photoreceptor rhodopsin. In the current study, we have determined the effect of several metal ions, such as iron, copper, chromium, manganese, and nickel, on the conformational stability of rhodopsin. To this aim, we analyzed, by means of UV-visible and fluorescence spectroscopic methods, the effects of these trace elements on the thermal stability of dark rhodopsin, the stability of its active Metarhodopsin II conformation, and its chromophore regeneration. Our results show that copper prevented rhodopsin regeneration and slowed down the retinal release process after illumination. In turn, Fe3+, but not Fe2+, increased the thermal stability of the dark inactive conformation of rhodopsin, whereas copper ions markedly decreased it. These findings stress the important role of trace metals in retinal physiology at the photoreceptor level and may be useful for the development of novel therapeutic strategies to treat retinal disease.

[Determination of reference values of CTx and NMID-Osteocalcin and their association with osteoporosis in postmenopausal chilean women]. / Determinación de rangos de BCTx y N-MID Osteocalcina y asociación con Osteoporosis en mujeres chilenas posmenopáusicas.

INTRODUCTION: Bone densitometry (BD) has high specificity in the osteoporosis diagnosis but suboptimal sensitivity to estimate fracture risk. It was proposed that bone turnover markers (BTM) could be included in the osteoporosis risk algorithm, although the extent of its association is unknown. One recommended BTM to assess bone resorption is Beta-Cross Laps (B-CTx), while a BTM to assess bone formation is osteocalcin. AIMS: To establish BCTx and N-MID osteocalcin (N-MID) ranges in postmenopausal women (PM) and compare BTM levels in two groups: control and with abnormal BD. METHODS: PM with BD within the last year were recruited. A questionnaire of risk factors for fractures was applied, and BTM was measured. Volunteers with diseases that would affect bone remodeling were excluded. RESULTS: 117 PM (57 control and 60 with abnormal BD) were recruited. 18% had osteoporosis, and the groups were comparable. The ranges for B-CTx and N-MID were 0.41 ± 0.18 [IC95% 0.37-0.45] and 22.76 ± 7.73 [IC95% 21.29-24.24] ng/mL. The mean levels of B-CTx and N-MID were higher in the group with abnormal BD (0.46 ± 0.19 and 24.29 ± 8.04 ng/mL). A moderate correlation between both BTM was found, but it was weak with abnormal BD. CONCLUSIONS: B-CTx and N-MID ranges were assessed for the first time in Chilean PM, similar to values found in other countries. Slightly higher values of BTM were found in the group with abnormal BD, which the presence of omitted secondary causes could explain. These BTM could be a complementary tool to BD and FRAX in bone evaluation.

Effects of solvents on the conformational profile of Balaram's peptide: a computational study.

The present work reports the results of a computational study aimed at characterizing the conformational profile of Balaram's peptide (Ace-Leu-Val-Val-Aib-Gly-Leu-Val-Val-NHMe) in different solvents, including chloroform, dimethyl sulfoxide, methanol and water. For this purpose, 10 µs molecular dynamics trajectories were computed in explicit solvents for each system, starting from an extended conformation. The results of the present study confirm the former NMR and CD findings and provide further insights that permit fine-tuning of the conclusions previously derived. The present results show that the peptide exhibits a helical conformation in chloroform, but a mixture of ß-hairpin and Ω-shape conformations, as the predominant structures in DMSO and MeOH. Finally, the peptide does not exhibit a preferred conformation in water, although significant populations of helical and ß-hairpin conformations are available. The present results underline the role of solvents in the conformational profile of a peptide and it is an example of the complementarity between computational methods and spectroscopy studies.

Discovery of Diverse Natural Products as Inhibitors of SARS-CoV-2 Mpro Protease through Virtual Screening.

SARS-CoV-2 is a type of coronavirus responsible for the international outbreak of respiratory illness termed COVID-19 that forced the World Health Organization to declare a pandemic infectious disease situation of international concern at the beginning of 2020. The need for a swift response against COVID-19 prompted to consider different sources to identify bioactive compounds that can be used as therapeutic agents, including available drugs and natural products. Accordingly, this work reports the results of a virtual screening process aimed at identifying antiviral natural product inhibitors of the SARS-CoV-2 Mpro viral protease. For this purpose, ca. 2000 compounds of the Selleck database of Natural Compounds were the subject of an ensemble docking process targeting the Mpro protease. Molecules that showed binding to most of the protein conformations were retained for a further step that involved the computation of the binding free energy of the ligand-Mpro complex along a molecular dynamics trajectory. The compounds that showed a smooth binding free energy behavior were selected for in vitro testing. From the resulting set of compounds, five compounds exhibited an antiviral profile, and they are disclosed in the present work.

Discovery of a Bradykinin B2 Partial Agonist Profile of Raloxifene in a Drug Repurposing Campaign.

Covid-19 urges a deeper understanding of the underlying molecular mechanisms involved in illness progression to provide a prompt therapeutical response with an adequate use of available drugs, including drug repurposing. Recently, it was suggested that a dysregulated bradykinin signaling can trigger the cytokine storm observed in patients with severe Covid-19. In the scope of a drug repurposing campaign undertaken to identify bradykinin antagonists, raloxifene was identified as prospective compound in a virtual screening process. The pharmacodynamics profile of raloxifene towards bradykinin receptors is reported in the present work, showing a weak selective partial agonist profile at the B2 receptor. In view of this new profile, its possible use as a therapeutical agent for the treatment of severe Covid-19 is discussed.

[Mucinous cystadenoma of the ileocecal valve. Uncommon intestinal tumor in a oneyear-old boy. Case report]. / Cistoadenoma mucinoso de la vá lvula ileocecal: tumoración intestinal infrecuente en un niñ o de 1 añ o. Reporte de caso.

Mucinous cystadenoma is usually found in the ovary, pancreas and appendix but its presentation in the intestine is extremely rare. In this case report we present an infant with partial intestinal occlusion due to a mucinous cystadenoma of the ileocecal valve. We performed an excision of the terminal ileum, ileocecal valve, cecum and appendix, followed by ileocolic anastomosis. The patient did well after the procedure and recovered uneventfully. To our knowledge, this is the first case report of this tumor in this location.

Structural Study of a New HIV-1 Entry Inhibitor and Interaction with the HIV-1 Fusion Peptide in Dodecylphosphocholine Micelles.

Previous studies support the hypothesis that the envelope GB virus C (GBV-C) E1 protein interferes the HIV-1 entry and that a peptide, derived from the region 139-156 of this protein, has been defined as a novel HIV-1 entry inhibitor. In this work, we firstly focus on the characterization of the structural features of this peptide, which are determinant for its anti-HIV-1 activity and secondly, on the study of its interaction with the proposed viral target (i.e., the HIV-1 fusion peptide). We report the structure of the peptide determined by NMR spectroscopy in dodecylphosphocholine (DPC) micelles solved by using restrained molecular dynamics calculations. The acquisition of different NMR experiments in DPC micelles (i.e., peptide-peptide titration, diffusion NMR spectroscopy, and addition of paramagnetic relaxation agents) allows a proposal of an inhibition mechanism. We conclude that a 18-mer peptide from the non-pathogenic E1 GBV-C protein, with a helix-turn-helix structure inhibits HIV-1 by binding to the HIV-1 fusion peptide at the membrane level, thereby interfering with those domains in the HIV-1, which are critical for stabilizing the six-helix bundle formation in a membranous environment.

Identification of Potential Small Molecule Binding Pockets in p38α MAP Kinase.

Given the essential role played by protein kinases in regulating cellular pathways, their dysregulation can result in the onset and/or progression of various human diseases. Structural analysis of diverse protein kinases suggests that these proteins exhibit a remarkable plasticity that allows them to adopt distinct conformations in response to interactions with other proteins, providing an opportunity for designing allosteric modulators. The present work reports the results of an in silico screening study aimed at identifying novel prospective allosteric binding sites in the paradigmatic p38α MAP kinase. The process was carried out using a protein ensemble generated from a 6 µs accelerated molecular dynamics simulation. The results of this calculation were first used to study the flexibility of the protein using Principal Component Analysis, followed by a Cluster Analysis aimed at producing an ensemble of conformations representative of the sampling process. Representative structures of the diverse clusters were subsequently screened for hot spots using FTMAP. The procedure permitted the identification of diverse allosteric sites of p38α already described in the literature including the DFG pocket, the lipid binding pocket, the DEF site, the docking groove, the CD and ED sites, and the backside site as well as a novel site recently reported: the A-loop regulatory site. Furthermore, the study also permitted the identification of ten novel prospective allosteric sites named NP1 to NP10, involving in most of the cases protein structural elements that control kinase activation including the activation loop, the catalytic loop, the αC helix, the L16 loop, and the glycine-rich loop.

New insights into the stereochemical requirements of the bradykinin B2 receptor antagonists binding.

Bradykinin (BK) is a member of the kinin family, released in response to inflammation, trauma, burns, shock, allergy and some cardiovascular diseases, provoking vasodilatation and increased vascular permeability among other effects. Their actions are mediated through at least two G-protein coupled receptors, B1 a receptor up-regulated during inflammation episodes or tissue trauma and B2 that is constitutively expressed in a variety of cell types. The goal of the present work is to carry out a structure-activity study of BK B2 antagonism, taking into account the stereochemical features of diverse non-peptide antagonists and the way these features translate into ligand anchoring points to complementary regions of the receptor, through the analysis of the respective ligand-receptor complex. For this purpose an atomistic model of the BK B2 receptor was built by homology modeling and subsequently refined embedded in a lipid bilayer by means of a 600 ns molecular dynamics trajectory. The average structure from the last hundred nanoseconds of the molecular dynamics trajectory was energy minimized and used as model of the receptor for docking studies. For this purpose, a set of compounds with antagonistic profile, covering maximal diversity were selected from the literature. Specifically, the set of compounds include Fasitibant, FR173657, Anatibant, WIN64338, Bradyzide, CHEMBL442294, and JSM10292. Molecules were docked into the BK B2 receptor model and the corresponding complexes analyzed to understand ligand-receptor interactions. The outcome of this study is summarized in a 3D pharmacophore that explains the observed structure-activity results and provides insight into the design of novel molecules with antagonistic profile. To prove the validity of the pharmacophore hypothesized a virtual screening process was also carried out. The pharmacophore was used as query to identify new hits using diverse databases of molecules. The results of this study revealed a set of new hits with structures not connected to the molecules used for pharmacophore development. A few of these structures were purchased and tested. The results of the binding studies show about a 33% success rate with a correlation between the number of pharmacophore points fulfilled and their antagonistic potency. Some of these structures are disclosed in the present work.

Tau hyperphosphorylation and increased BACE1 and RAGE levels in the cortex of PPARß/δ-null mice.

The role of peroxisome proliferator activator receptor (PPAR)ß/δ in the pathogenesis of Alzheimer's disease has only recently been explored through the use of PPARß/δ agonists. Here we evaluated the effects of PPARß/δ deficiency on the amyloidogenic pathway and tau hyperphosphorylation. PPARß/δ-null mice showed cognitive impairment in the object recognition task, accompanied by enhanced DNA-binding activity of NF-κB in the cortex and increased expression of IL-6. In addition, two NF-κB-target genes involved in ß-amyloid (Aß) synthesis and deposition, the ß site APP cleaving enzyme 1 (Bace1) and the receptor for advanced glycation endproducts (Rage), respectively, increased in PPARß/δ-null mice compared to wild type animals. The protein levels of glial fibrillary acidic protein (GFAP) increased in the cortex of PPARß/δ-null mice, which would suggest the presence of astrogliosis. Finally, tau hyperphosphorylation at Ser199 and enhanced levels of PHF-tau were associated with increased levels of the tau kinases CDK5 and phospho-ERK1/2 in the cortex of PPARß/δ(-/-) mice. Collectively, our findings indicate that PPARß/δ deficiency results in cognitive impairment associated with enhanced inflammation, astrogliosis and tau hyperphosphorylation in the cortex.

Consensus on criteria for potential areas for wolf reintroduction in Mexico.

Given the conflict with human interests that in many cases results in the extirpation of large carnivores, acceptance of their reintroduction is a considerable challenge. By the 1980s Mexican wolves (Canis lupus) were extinct in the wild. In 1998 a population was reintroduced in the Blue Range Mountains of New Mexico (U.S.A.). Efforts to reintroduce the species in Mexico have been ongoing since the late 1980s. Four teams working independently identified 6 areas in northern Mexico in the historic range of Mexican wolves, where reintroductions could potentially be successful. Each team used different methods and criteria to identify the areas, which makes it difficult to prioritize among these areas. Therefore, members of the different teams worked together to devise criteria for use in identifying priority areas. They identified areas with high, intermediate, and low potential levels of conflict between wolves and humans. Areas with low potential conflict had larger buffers (i.e., distance from human settlement to areas suitable for wolves) around human settlements than high- and intermediate-conflict areas and thus were thought most appropriate for the first reintroduction. High-conflict areas contained habitat associated with wolf presence, but were closer to human activity. The first reintroduction of Mexican wolves to Mexico occurred in October 2011 in one of the identified low-conflict areas. The identification of suitable areas for reintroduction represents a crucial step in the process toward the restoration of large carnivores. Choice of the first reintroduction area can determine whether the reintroduction is successful or fails. A failure may preclude future reintroduction efforts in a region or country.

[Magnetic resonance imaging accuracy and utility for testicular cancer diagnosis]. / Precisión y utilidad de la resonancia magnética para el diagnóstico de cáncer de testículo.

PURPOSE: The purpose of our study is to analyze the imaging findings described in MRI and the histopathologic type of testicular lesions to determine which findings are the best predictors of malignancy. MATERIALS AND METHODS: Forty six (46) patients with testicular lesions were initially studied with ultrasound (US) and with testicular MRI (tMRI) on a 1.5-T magnet. MRIs were reviewed by a radiologist with 8 years of experience and imaging findings such as the size of the lesion, the signal intensity in T1, T2 weighted sequences, and the enhancement after endovenous contrast administration, were correlated with the histopathologic diagnosis. Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were analyzed. RESULTS: The enhancement after administration of contrast was the finding of better performance with a sensitivity, specificity, PPV and NPV of 90 (71-97), 47 (24-71), 74 (56-87) and 73 (40-92), respectively. Meanwhile, the results for hypointense/heterogeneous lesions in T2 weighted sequences and with enhancement with intravenous contrast were 87 (49-84), 47 (44-89), 74 (55-86) y 67 (35-89), respectively. CONCLUSION: The finding of a testicular lesion of low signal intensity and heterogeneous in T2 weighted sequences, with IV contrast enhancement represents a valuable predictor of malignancy. The latter being the most sensitive as a predictor of malignancy.

Treatment of Bolivian Leishmania braziliensis Cutaneous and Mucosal Leishmaniasis.

Although infection with Leishmania braziliensis is perhaps the key reason to treat New World cutaneous leishmaniasis (CL) and mucosal leishmaniasis (ML), the total literature contains relatively few reported cases. With the aim of supplementing the meager clinical information available, we searched the records of Jorochito (Dermatology) Hospital, Bolivia, for the years 1999-2020 and identified treatment records for 1,696 naive CL patients and 355 naive ML patients. Because follow-up was poor for this real-world treatment experience in the developing world, only 255 CL patients (15%) and 114 ML patients (32%) attended follow-up at Hospital. We therefore engaged in an Active Search for "lost" patients, located a further 542 CL patients (32%) and 142 ML patients (44%), thus eventually accomplished follow up on 697 CL patients (41%) and 256 ML patients (72%). Granular adverse event data derived from hospital records is listed for the 902 CL and 86 ML patients administered Glucantime intramuscularly, the 401 CL and 202 ML patients administered Glucantime intravenously, and the 163 CL and 89 ML patients administered miltefosine orally. Efficacy was obtained from hospital records for patients seen at hospital and from patient recall communicated by telephone for the patients found in the Active Search. The overall CL cure rate was 508 of 697 CL patients (73%) with follow-up: intramuscular Glucantime-196/293 (67%); intravenous Glucantime-90/126 (71%); intralesional Glucantime-34/54 (63%); oral miltefosine-52/69 (75%). The overall ML cure rate was 161 of 256 ML patients (63%) with follow-up: intramuscular Glucantime-26/48 (54%); intravenous Glucantime-66/104 (63%); intravenous amphotericin B deoxycholate-19/35 (54%); oral miltefosine-50/71 (70%). We offer this extensive adverse event and efficacy experience as useful guides for clinicians presented with a L. braziliensis infection. The cure rates also illustrate the quandary of New World CL and ML chemotherapy: sufficiently high to be useful but nevertheless needing augmentation with new agents.

Structure-Activity Studies of Novel Di-substituted [1,2,5]oxadiazolo [3,4-b]pyrazine Analogs Targeting the A-loop Regulatory Site of p38 MAP Kinase.

INTRODUCTION: In the quest for novel allosteric inhibitors of the p38 MAP kinase, we recently described the A-loop regulatory site, identified by means of molecular modeling studies together with the disclosure of a small molecule hit with a moderate inhibitory profile. Starting from this structure, we subsequently identified two additional hits with simpler molecular structures from an in silico screening study, using a substructure search in the SciFinder database. After corroboration of their inhibitory profile, analysis of their structures permitted to conclude about the suitability of the [1,2,5]oxadiazolo[3,4-b]pyrazine (furazano[ 3,4-b]pyrazine) scaffold for the development of potent A-loop regulatory site p38 MAP kinase inhibitors. Accordingly, we report the synthesis and pharmacological evaluation of a series of di-substituted analogs with a potent inhibitory profile of p38 MAP kinase, as shown by in vitro assays of their capability to inhibit IL-1ß secretion in human monocyte-derived macrophages. OBJECTIVE: To find small molecule potent inhibitors of the p38 MAP kinase A-loop regulatory site. METHODS: Starting from this structure, we subsequently identified two additional hits with simpler molecular structures from an in silico screening study, using a substructure search in the SciFinder database. After corroboration of their inhibitory profile, we carried out a hit-tolead optimization process guided by molecular modeling using a [1,2,5]oxadiazolo[3,4- b]pyrazine (furazano[3,4-b]pyrazine) scaffold. RESULTS: We report the synthesis and pharmacological evaluation of a series of di-substituted analogs with a potent inhibitory profile of p38 MAP kinase, as shown by in vitro assays of their capability to inhibit IL-1ß secretion in human monocyte-derived macrophages. CONCLUSION: We describe in the present work a series of [1,2,5]oxadiazolo[3,4-b]pyrazine (furazano[3,4-b]pyrazine), which are potent inhibitors of IL-1ß secretion in human monocytederived macrophages allosteric modulators of the p38 MAP kinase A-loop regulatory site.

Venous Thromboembolism in Patients with Cancer Receiving Specialist Palliative Care.

CONTEXT: The prevalence of venous thromboembolism (VTE) in patients with cancer is particularly high at disease progression and during relapse. Patients cared for in specialized palliative care units (SPCU) are rarely included in VTE studies. Objective: We sought to study the prevalence, clinical characteristics, and survival of individuals with VTE in an SPCU setting. METHODS: We retrospectively included 2707 consecutive individuals with active cancer managed at a SPCU. Data were summarized using descriptive statistics and frequency for categorical variables. Overall survival was estimated by Kaplan-Meier and comparisons by log-rank test. Thrombotic events were confirmed by imaging. RESULTS: We studied 1984(73.3%) women and 723 (26.7%) men. The overall prevalence of thrombosis was 22.2% with only 6.2% occurring after initiating SPCU care, and was higher in women (24.6% vs 15.8%), particularly with gynecological tumors (cervical: 30.5%, ovarian: 29.2%). Median survival was slightly longer for patients without VTE (80 days [IQR21-334] and 69 days [IQR 25-235]; p = 0.03). CONCLUSIONS: Prevalence of VTE was high and varied by tumor origin. VTE may impact survival. Though median survival is short, some patients are followed over months, suggesting that in the absence of high bleeding risk, treatment for thrombosis in an attempt to decrease the morbidity of re-thrombosis should be considered. On the other hand, few patients developed symptomatic VTE during SPCU care, making generalized primary prophylaxis probably unwarranted. Customizing anticoagulation for the risk of hemorrhage and physical performance is essential.

Associations between household air pollution and early child development among children aged 36-59 months in Bangladesh.

BACKGROUND: Household air pollution (HAP) from solid fuel use (SFU) for cooking may impact child health in low-resources countries. This study examined the associations between HAP and early childhood development (ECD) outcomes among children under 5 years of age in Bangladesh and explored potential effect modification by sex and urbanicity. METHODS: The study sample consisted of 9395 children aged 36-59 months in the households from the Bangladesh Multiple Indicator Cluster Survey 2019. SFU and levels of exposure to SFU (unexposed, moderately exposed and highly exposed) were used as proxies of HAP exposure. We estimated the covariate-adjusted prevalence ratios (aPRs) and 95% CIs for the associations between HAP and ECD outcomes using multilevel mixed-effects Poisson regression models with a robust variance estimator. RESULTS: 81.4% of children were exposed to SFU, and the prevalence of developmental delay (in Early Childhood Development Index) was 25.3%. Children exposed to SFU were 1.47 times more likely to have developmental delays (95% CI: 1.25, 1.73; p<0.001) compared with children with no SFU exposure. SFU was significantly associated with developmental delay in socioemotional (aPR: 1.17; 95% CI: 1.01, 1.36; p=0.035) and learning-cognitive (aPR: 1.90; 95% CI: 1.39, 2.60; p<0.001) domains. Similarly, children moderately exposed and highly exposed to HAP had higher prevalence of developmental delays than unexposed children. We did not observe effect modification by sex or urbanicity. CONCLUSION: Public health policies should promote the use of clean cooking fuels and cookstoves to reduce the high burden of HAP exposure in low-resource countries for helping younger children to meet their developmental milestones.

Case Report: Mini-endoscopic combined intrarenal surgery in an en-bloc kidney transplant.

BACKGROUND: Overall incidence of stones in kidney transplant recipients is 1%. En-bloc kidney transplant is a rare anatomical condition in which kidney stones treatment can be extremely difficult to treat. As far as we know, no cases of staghorn calculi in en-bloc kidney transplant have been published so far. CASE PRESENTATION: A 27-year-old woman presented to the Emergency Department because of asthenia, adynamia and weight loss associated with lower urinary tract symptoms and subfebrile temperature. Ten years before, she had undergone an en-bloc kidney transplant because of end-stage renal disease secondary to perinatal asphyxia syndrome. One kidney was implanted capo-volta in the right iliac fossa and the other one in the right flank. NCCT scan showed incomplete staghorn calculi in the iliac fossa transplanted kidney. Besides, severe dilation of the native and the right flank transplanted kidney, due to two ureteral stones of 6 and 7 mm impacted in the uretero-ureteral anastomosis, was found. After hospital admission and under ceftriaxone prophylaxis, an attempt to perform primary RIRS following our COVID protocol was carried out. Nevertheless, we ended up placing a JJ stent because once the guidewire passed through the ureteral stones, purulent material came out from the ureteral orifice. She stayed 9 days in-hospital for management of postobstructive polyuria and was discharged with oral antibiotics. Three weeks afterward, we removed the stent and performed flexible ureteroscopy and holmium laser lithotripsy of the ureteral stones. In the same procedure, we performed Mini-ECIRS (21 French) previous ultrasound-guided upper pole puncture. Postoperative NCCT scan showed neither residual fragments nor operative complications. CONCLUSION: This is the first clinical case reporting Mini-ECIRS in a patient with an en-bloc kidney transplant. This endourological approach seems to be a feasible, safe and effective approach to treat stones in this anatomically challenging condition.