An Evaluation of the Effectivity of the Green Leaves Biostimulant on Lettuce Growth, Nutritional Quality, and Mineral Element Efficiencies under Optimal Growth Conditions.

The use of biostimulants is becoming a useful tool for increasing crop productivity while enhancing nutritional quality. However, new studies are necessary to confirm that the joint application of different types of biostimulants, together with bioactive compounds, is effective and not harmful to plants. This study examined the impact of applying the biostimulant Green Leaves, comprising Macrocystis algae extract and containing a mixture of amino acids, corn steep liquor extract, calcium, and the bioactive compound glycine betaine. The effect of applying two different doses (3 and 5 mL L-1) of this biostimulant was evaluated on lettuce plants, and growth and quality parameters were analyzed along with photosynthetic efficiency, nutritional status, and nutrient efficiency parameters. The application of Green Leaves improved plant weight (25%) and leaf area and enhanced the photosynthetic rate, the accumulation of soluble sugars and proteins, and the agronomic efficiency of all essential nutrients. The 3 mL L-1 dose improved the nutritional quality of lettuce plants, improving the concentration of phenolic compounds and ascorbate and the antioxidant capacity and reducing NO3- accumulation. The 5 mL L-1 dose improved the absorption of most nutrients, especially N, which reduced the need for fertilizers, thus reducing costs and environmental impact. In short, the Green Leaves product has been identified as a useful product for obtaining higher yield and better quality.

Effect of Irrigation on Sugarcane Morphophysiology in the Brazilian Cerrado.

Since sugarcane is semi-perennial, it has no escape from water stresses in the Brazilian Cerrado, and consequently, drought impacts plant growth and industrial quality. The objective of this study was to evaluate the morphophysiology and quality of the first ratoon of two sugarcane varieties submitted to irrigated and stressed treatments under field conditions. For the biometric characteristics, in general, significant decreases were observed under the stressed treatment for all periods, and only minor differences were detected between the studied cultivars. Physiological parameters decreased under stressed conditions, but to a different extent between the varieties. RB855536 was able to maintain a greater rate of transpiration. Productivity was reduced by 103 t ha-1 for variety RB855536 and 121 t ha-1 for RB867515, compared to plants with full irrigation during the dry period, but cane quality was similar in both genotypes. Measurements of physiological and morphological parameters may prove useful in the rapid identification of genotypes with greater tolerance to abiotic stress.

Phenotypes of MASLD-associated hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) typically develops as consequence of liver cirrhosis, but HCC epidemiology has evolved drastically in recent years. Metabolic dysfunction-associated steatotic liver disease (MASLD), including metabolic dysfunction-associated steatohepatitis (MASH), has emerged as the most common chronic liver disease worldwide and a leading cause of HCC. A substantial proportion of MASLD-associated HCC (MASLD-HCC) can also develop in patients without cirrhosis. The specific pathways that trigger carcinogenesis in this context are not completely elucidated, and recommendations for HCC surveillance in MASLD patients are challenging. In the era of precision medicine, it is critical to understand the processes that define the profiles of patients at increased risk of HCC in the MASLD setting, including cardio-metabolic risk factors, and the molecular targets that could be effectively tackled. Ideally, defining categories that encompass key pathophysiological features, associated with tailored diagnostic and treatment strategies, should facilitate the identification of specific MASLD-HCC phenotypes. In this review, we discuss MASLD-HCC, including its epidemiology and healthcare burden, the mechanistic data promoting MASLD, MASH, and MASLD-HCC. Its natural history, prognosis and treatment are specifically addressed, as the role of metabolic phenotypes of MASLD-HCC as a potential strategy for risk stratification. The challenges in identifying high-risk patients and screening strategies are also discussed, as well as the potential approaches for MASLD-HCC prevention and treatment.

Dynamics of Carbon and Soil Enzyme Activities under Arabica Coffee Intercropped with Brachiaria decumbens in the Brazilian Cerrado.

The change in land use in the Brazilian Cerrado modifies the dynamics of soil organic matter (SOM) and, consequently, carbon (C) stocks and their fractions and soil enzyme activities. This study evaluated the effect of brachiaria (Brachiaria decumbens Stapf.) intercropped with Arabica coffee (Coffea arabica L.) on the stock and fractions of soil carbon and enzyme activities. The experiment was arranged in a completely randomized block design with three replications and treatments in a factorial design. The first factor consisted of coffee with or without intercropped brachiaria, the second of Arabica coffee cultivars ('I.P.R.103' and 'I.P.R.99') and the third factor of the point of soil sampling (under the canopy (UC) and in inter-rows (I)). Soil was sampled in layers of 0-10, 10-20, 20-30, 30-40, 40-60 and 60-80 cm. Soil from the 0-10 cm layer was also used to analyze enzymatic activity. Significant effects of coffee intercropped with brachiaria were confirmed for particulate organic carbon (POC), with highest contents in the 0-10 and 20-30 cm layers (9.62 and 6.48 g kg-1, respectively), and for soil enzymes (280.83 and 180.3 µg p-nitrophenol g-1 for arylsulfatase and ß-glucosidase, respectively).

Prevalence of diagnosed and undiagnosed osteoarthrosis and associated factors in the adult general Spanish population.

OBJECTIVE: To determine the prevalence and related factors of diagnosed osteoarthrosis (DO) and undiagnosed osteoarthrosis (UO) in the general Spanish adult population. SETTING: Cross-sectional study with data from the Spanish National Health Survey 2017. PARTICIPANTS: N=23,089 adults. Three groups of people were defined: DO, UO, and no osteoarthrosis (NO). MAIN MEASUREMENTS: Sociodemographic information, lifestyle (tobacco, alcohol, physical activity, body mass index) and health factors (intensity of pain, pain drug consumption, mental health, self-perceived health status, pain involvement in daily living) were collected. Descriptive and bivariate analyses were performed, and a multinomial logistic regression model for the factors associated with each group. RESULTS: The prevalence of DO was 22.4% (95%CI=21.8;22.9) and 0.9% (95%CI=0.8;1) of UO. With respect to NO, risk factors for DO and UO included higher pain levels and pain drug consumption. Better self-perceived health status was inversely related with both. More pain involvement in daily living was associated with increased risk of DO, but reduced risk of UO. CONCLUSIONS: The prevalence of DO and UO was similar to that reported in Europe, but slightly higher than in low/middle-income countries. It was more prevalent in females, older people, people with worse perceived health status and worse mental health. Higher pain levels and pain drug consumption were risk factors for DO and UO. Better self-perceived health status was protective. Pain involvement in daily living was a risk factor for DO, but protective for UO. Different public health strategies should be considered in view of this.

Lung ultrasound and procalcitonin, improving antibiotic management and avoiding radiation exposure in pediatric critical patients with bacterial pneumonia: a randomized clinical trial.

BACKGROUND: Pneumonia is a major public health problem with an impact on morbidity and mortality. Its management still represents a challenge. The aim was to determine whether a new diagnostic algorithm combining lung ultrasound (LUS) and procalcitonin (PCT) improved pneumonia management regarding antibiotic use, radiation exposure, and associated costs, in critically ill pediatric patients with suspected bacterial pneumonia (BP). METHODS: Randomized, blinded, comparative effectiveness clinical trial. Children < 18y with suspected BP admitted to the PICU from September 2017 to December 2019, were included. PCT was determined at admission. Patients were randomized into the experimental group (EG) and control group (CG) if LUS or chest X-ray (CXR) were done as the first image test, respectively. Patients were classified: 1.LUS/CXR not suggestive of BP and PCT < 1 ng/mL, no antibiotics were recommended; 2.LUS/CXR suggestive of BP, regardless of the PCT value, antibiotics were recommended; 3.LUS/CXR not suggestive of BP and PCT > 1 ng/mL, antibiotics were recommended. RESULTS: 194 children were enrolled, 113 (58.2%) females, median age of 134 (IQR 39-554) days. 96 randomized into EG and 98 into CG. 1. In 75/194 patients the image test was not suggestive of BP with PCT < 1 ng/ml; 29/52 in the EG and 11/23 in the CG did not receive antibiotics. 2. In 101 patients, the image was suggestive of BP; 34/34 in the EG and 57/67 in the CG received antibiotics. Statistically significant differences between groups were observed when PCT resulted < 1 ng/ml (p = 0.01). 3. In 18 patients the image test was not suggestive of BP but PCT resulted > 1 ng/ml, all of them received antibiotics. A total of 0.035 mSv radiation/patient was eluded. A reduction of 77% CXR/patient was observed. LUS did not significantly increase costs. CONCLUSIONS: Combination of LUS and PCT showed no risk of mistreating BP, avoided radiation and did not increase costs. The algorithm could be a reliable tool for improving pneumonia management. CLINICAL TRIAL REGISTRATION: NCT04217980.

Influence of augmented reality technique on the accuracy of autotransplanted teeth in surgically created sockets.

BACKGROUND: The objective of the present study was to evaluate the reliability of an augmented reality drilling approach and a freehand drilling technique for the autotransplantation of single-rooted teeth. MATERIALS AND METHODS: Forty samples were assigned to the following surgical techniques for drilling guidance of the artificial sockets: A. augmented reality technique (AR) (n = 20) and B. conventional free-hand technique (FT) (n = 20). Then, two models with 10 teeth each were submitted to a preoperative cone-beam computed tomography (CBCT) scan and a digital impression by a 3D intraoral scan. Afterwards, the autotrasplanted teeth were planned in a 3D dental implant planning software and transferred to the augmented reality device. Then, a postoperative CBCT scan was performed. Data sets from postoperative CBCT scans were aligned to the planning in the 3D implant planning software to analize the coronal, apical and angular deviations. Student's t-test and Mann-Whitney non-parametric statistical analysis were used to analyze the results. RESULTS: No statistically significant differences were shown at coronal (p = 0.123) and angular (p = 0.340) level; however, apical deviations between AR and FT study groups (p = 0.008) were statistically significant different. CONCLUSION: The augmented reality appliance provides higher accuracy in the positioning of single-root autotransplanted teeth compared to the conventional free-hand technique.

Concurrent inhibition of ALK and SRC kinases disrupts the ALK lung tumor cell proteome.

Precision oncology has revolutionized the treatment of ALK-positive lung cancer with targeted therapies. However, an unmet clinical need still to address is the treatment of refractory tumors that contain drug-induced resistant mutations in the driver oncogene or exhibit resistance through the activation of diverse mechanisms. In this study, we established mouse tumor-derived cell models representing the two most prevalent EML4-ALK variants in human lung adenocarcinomas and characterized their proteomic profiles to gain insights into the underlying resistance mechanisms. We showed that Eml4-Alk variant 3 confers a worse response to ALK inhibitors, suggesting its role in promoting resistance to targeted therapy. In addition, proteomic analysis of brigatinib-treated cells revealed the upregulation of SRC kinase, a protein frequently activated in cancer. Co-targeting of ALK and SRC showed remarkable inhibitory effects in both ALK-driven murine and ALK-patient-derived lung tumor cells. This combination induced cell death through a multifaceted mechanism characterized by profound perturbation of the (phospho)proteomic landscape and a synergistic suppressive effect on the mTOR pathway. Our study demonstrates that the simultaneous inhibition of ALK and SRC can potentially overcome resistance mechanisms and enhance clinical outcomes in ALK-positive lung cancer patients. ONE SENTENCE SUMMARY: Co-targeting ALK and SRC enhances ALK inhibitor response in lung cancer by affecting the proteomic profile, offering hope for overcoming resistance and improving clinical outcomes.

Bacillus pumilus cellulitis with bacteremia in a person who injects drugs, living with HIV-HCV co-infection: a case report.

Bacillus pumilus (B. pumilus) is a ubiquitous spore-forming bacteria that has rarely been implicated in extraintestinal infections, mostly in immunocompromised hosts. The authors report a case of B. pumilus cellulitis with bacteremia in a person who injects drugs living with human immunodeficiency virus-hepatitis C virus (HIV-HCV) co-infection. Although similar cases have been reported for some species of the genus, namely Bacillus anthracis (B. anthracis) and Bacillus cereus (B. cereus), this case reinforces the importance of considering other Bacillus spp. as potential pathogens in skin and soft tissue infections and bloodstream infections related to intravenous drug use.

Prevalence of neonatal lupus in a small group of antibody-carrying mothers and frequency of complete atrioventricular block.

BACKGROUND: Neonatal lupus (NL) is extremely rare and is caused by the transplacental passage of maternal IgG autoantibodies against Ro, La, and/or RNP proteins into the fetal circulation, which can cause congenital complete atrioventricular block (CCAB), permanent skin lesions, and liver involvement. OBJECTIVE: To know the prevalence of NL in patients with CCAB and the clinical course in long-term follow-up. METHODS: From January 1992 to December 2017, patients with CCAB were included. The presence of anti-SSA/Ro and anti-SSB/La antinuclear antibodies in maternal serum confirmed NL. RESULTS: Eight patients were included with a follow-up of 10 ± 6 years; NL was concluded in 62.5%; two were male. One of them was diagnosed in utero, two at birth, and a pacemaker was implanted in them, one at 12 years of age and another at 15. The other two cases were diagnosed at 18 and 26 years of age, and permanent pacemakers were implanted 8 and 5 years later, respectively. In one case, a definitive pacemaker was not implanted in a newborn with only 1 year of follow-up. At delivery, 60% of the mothers were free of rheumatic disease, and altogether, they all had 19 children; none of them presented NL manifestations. CONCLUSIONS: CCAB is rare and frequently associated with a maternal autoimmune disease, practically all of them will require a definitive pacemaker at some point in their lives.

ANTECEDENTES: El lupus neonatal (LN) es extremadamente raro y es ocasionado por el paso transplacentario de auto-anticuerpos maternos IgG contra las proteínas Ro, La y/o RNP a la circulación fetal que puede ocasionar bloqueo aurículo-ventricular completo congénito (BAVCC) permanente, lesiones dérmicas y afectación hepática. OBJETIVO: Conocer la prevalencia de LN en paciente con BAVCC y la evolución clínica en un seguimiento a largo plazo. MÉTODOS: De enero de 1992 a diciembre 2017 se incluyeron paciente con BAVCC. La presencia de anticuerpos antinucleares anti-SSA/Ro y anti-SSB/La en suero materno confirmó LN. RESULTADOS: Ocho pacientes fueron incluidos con seguimiento de 10 ± 6 años, el 62.5 % con LN; dos fueron del sexo masculino. Uno diagnosticado in útero, dos al nacimiento, en ellos se implantó marcapaso; uno a los 12 años de edad y otro a los 15. Los otros dos casos fueron diagnosticados a los 18 y 26 años, se implantó marcapaso definitivo en ellos 8 y 5 años después respectivamente. En un caso no se implantó marcapaso definitivo; un recién nacido con solo un año de seguimiento. Al dar a luz, el 60 % de las madres estaban libres de enfermedad reumática y en conjunto todas tuvieron 19 hijos, ninguno de ellos presentó manifestaciones de LN. CONCLUSIONES: El BAVCC es raro y frecuentemente está asociado a una enfermedad autoinmune materna, prácticamente todos requerirán de marcapaso definitivo en alguna época de su vida.

Clinical Experience on the Use of a Single-day, Two-injection Start Initiation Regimen of Aripiprazole Once Monthly in Patients With Schizophrenia in Spain: SaTISfy Study.

OBJECTIVE: The two-injection start (TIS) initiation regimen was recently approved for aripiprazole once monthly 400 mg (AOM400), with potential benefits in adherence. The SaTISfy study described in this article analyzed Spanish psychiatrists' perspectives on hospitalization lengths of stay, schizophrenia management, and the use of AOM400-TIS. METHODS: The authors describe an ecological study of aggregated data collected using a 41-question survey. Fifty psychiatrists were asked to provide their perceptions of their patients with schizophrenia and treatment with AOM400. RESULTS: The psychiatrists reported that lack of treatment adherence was the main reason for hospitalization for 58.3% of their patients diagnosed with schizophrenia. Aripiprazole, in any formulation, was the most commonly prescribed therapeutic option, being prescribed for a mean (SD) of 2.5 (0.9) out of 5 patients, while 98% of psychiatrists chose AOM400-TIS for patients who failed to adhere to previous treatments. Patients with schizophrenia, regardless of their treatment, were hospitalized for an average of 17.7 (3.93) days versus patients with schizophrenia treated with AOM400-TIS, who were hospitalized for an average of 14.2 (4.18) days, a reduction of 3.5 (3.86) days. Patients treated with AOM400-TIS showed a reduction of 5 (4.18) days compared with the mean national duration of hospitalization for acute patients in psychiatry units in Spain (19.18 d). The surveyed psychiatrists reported that AOM400-TIS improved safety and tolerability. Most of the psychiatrists were satisfied with the administration and results of AOM400-TIS. Most of the psychiatrists (90%) also reported that fewer health care resources were consumed with AOM400-TIS, mainly due to a reduction in hospitalization days and in the use of concomitant medications. CONCLUSIONS: AOM400-TIS was considered to have a positive impact on the duration of hospitalization and thus on the use of health care resources. There was a positive perception of adherence, safety, and tolerability with the use of AOM400-TIS in patients with schizophrenia.

Highly Concentrated Linear Guanidine Amides from the Marine Sipunculid Phascolosoma granulatum.

The chemical diversity of annelids, particularly those belonging to the class Sipuncula, remains largely unexplored. However, as part of a Marine Biodiscovery program in Ireland, the peanut worm Phascolosoma granulatum emerged as a promising source of unique metabolites. The purification of the MeOH/CH2Cl2 extract of this species led to the isolation of six new linear guanidine amides, named phascolosomines A-F (1-6). NMR analysis allowed for the elucidation of their structures, all of which feature a terminal guanidine, central amide linkage, and a terminal isobutyl group. Notably, these guanidine amides were present in unusually high concentrations, comprising ∼3% of the dry mass of the organism. The primary concentration of the phascolosomines in the viscera is similar to that previously identified in linear amides from sipunculid worms and marine fireworms. The compounds from sipunculid worms have been hypothesized to be toxins, while those from fireworms are reported to be defensive irritants. However, screening of the newly isolated compounds for inhibitory bioactivity showed no significant inhibition in any of the assays conducted.

Tunable, multifunctional opto-electrical response in multilayer FePS3/single-layer MoS2 van der Waals p-n heterojunctions.

The combination of specific van der Waals semiconductors in vertical stacks leads to atomically sharp heterointerfaces with unique properties, offering versatility and additional functionality for thin, flexible, optoelectronic devices. In this work, we demonstrate heterostructures built from single-layer MoS2 (n-type) and multilayer FePS3 (p-type) as multifunctional p-n junctions where robust photoluminescent light emission and broadband electrical photo-response coexist. This is made possible by the inherent properties of the materials involved and the precise energy band alignment at their interface, which preserves the photoluminescent emission provided by the single-layer MoS2 and confers exceptional tunability to the system. Indeed, through small changes in the applied voltage across the junction, the interplay between photoluminescence and photocurrent generation can be tuned, allowing for a precise control of the light emission of single-layer MoS2 - from severely quenched to an order of magnitude enhancement. Additionally, the broadband photo-response of the system presents an enhanced performance under ultraviolet illumination, in contrast to other van der Waals heterostacks containing single-layer semiconductors. Furthermore, this photo-response can be adjusted by the application of an external electric field, enabling photocurrent generation under both reverse and forward bias, thereby contributing to the overall functionality and versatility of the system.

Duplicación del colédoco asociado a unión biliopancreática anómala: Reporte de caso / Common bile duct duplication associated with anomalous biliopancreatic junction: A case report

Introducción. La duplicación del colédoco es una anomalía congénita poco frecuente. En la mayoría de los casos este defecto se asocia a cálculos en la vía biliar, unión pancreatobiliar anómala, pancreatitis, cáncer gástrico o colangiocarcinoma. Por esta razón, el diagnóstico y el tratamiento temprano son importantes para evitar las complicaciones descritas a futuro. Métodos. Se presenta el caso de una paciente de 30 años, con antecedente de pancreatitis aguda, con cuadro de dolor abdominal crónico, a quien se le realizaron varios estudios imagenológicos sin claro diagnóstico. Fue llevada a manejo quirúrgico en donde se documentó duplicación del colédoco tipo II con unión pancreatobiliar anómala. Resultados. Se hizo reconstrucción de las vías biliares y hepatico-yeyunostomía, con adecuada evolución postoperatoria y reporte final de patología sin evidencia de tumor. Conclusión. El diagnóstico se hace mediante ecografía endoscópica biliopancreática, colangiorresonancia o colangiopancreatografía retrógrada endoscópica. El tratamiento depende de si está asociado o no a la presencia de unión biliopancreática anómala o cáncer. Si el paciente no presenta patología neoplásica, el tratamiento quirúrgico recomendado es la resección del conducto con reconstrucción de las vías biliares.

Introduction. Double common bile duct is an extremely rare congenital anomaly. This anomaly may be associated with bile duct stones, anomalous biliopancreatic junction, pancreatitis, bile duct cancer, or gastric cancers. Thus, early diagnosis and treatment is important to avoid complications. Clinical case. We report a rare case of double common bile duct associated with an anomalous biliopancreatic junction in a 30-year-old female, with prior history of acute pancreatitis, who presented with chronic abdominal pain. She underwent several imaging studies, without clear diagnosis. She was taken to surgical management where duplication of the type II common bile duct was documented with anomalous pancreatobiliary junction. Results. Reconstruction of the bile ducts and hepatico-jejunostomy were performed, with adequate postoperative evolution and final pathology report without evidence of tumor. Conclusion. Diagnosis is usually performed by an endoscopic ultrasound, magnetic resonance cholangiopancrea-tography, or endoscopic retrograde cholangiopancreatography. Treatment depends on the presence of anomalus biliopancreatic junction or concomitant cancer. In cases without associated malignancy, resection of bile duct and biliary reconstruction is the recommended surgical treatment.

Skilled lactation support using telemedicine in the neonatal intensive care unit.

BACKGROUND: NICU mothers face unique challenges in initiating and sustaining breastfeeding, but previous studies have focused on outpatient breastfeeding support. We conducted a retrospective study of NICU breastfeeding outcomes before and after implementing telelactation. METHODS: Pre-Telemedicine mothers received in-person support by NICU lactation consultants, while Telemedicine mothers received solely telemedicine consults after maternal discharge. RESULTS: Exclusive breastmilk feeding at discharge increased in the Telemedicine group. Notably, babies in the Telemedicine cohort who were fed any formula on admission experienced significant improvement in exclusive breastmilk feeding at discharge, and those whose mothers received at least one NICU lactation consult had the greatest improvement in exclusive breastfeeding rates at discharge. CONCLUSIONS: This study is the first to validate the use of telemedicine as a means of maintaining access to skilled lactation support in the NICU when in-person consults are not feasible. Incorporating telemedicine can ensure access and continuity of skilled lactation support, and sustain breastfeeding rates.

Beta-Adrenergic Blockade in Advanced Non-Small Cell Lung Cancer Patients Receiving Immunotherapy: A Multicentric Study.

Introduction The standard treatment of cancer has dramatically improved with immune checkpoint inhibitors (ICIs). Despite their proven advantage, many patients fail to exhibit a meaningful and lasting response. The beta-adrenergic signalling pathway may hold significant promise due to its role in promoting an immunosuppressive milieu within the tumour microenvironment. Inhibiting ß-adrenergic signalling could enhance ICI activity; however, blocking this pathway for this purpose has yielded conflicting results. The primary objective of this study was to evaluate the effect of beta-blocker use on overall survival and progression-free survival during ICI therapy. Methods A multicentric, retrospective, observational study was conducted in four Portuguese institutions. Patients with advanced non-small cell lung cancer treated with ICIs between January 2018 and December 2019 were included. Those using beta blockers for non-oncological reasons were compared with non-users. Results Among the 171 patients included, 36 concomitantly received beta blockers and ICIs. No significant increase was found in progression-free survival among patients who took ß-blockers (HR 0.74, 95% confidence interval (CI) 0.48-1.12, p = 0.151), and no statistically significant difference was found in overall survival. An apparent trend was observed towards better outcomes in the beta-blocker group, with a median overall survival of 9.93 months in the group not taking ß-blockers versus 14.90 months in the ß-blocker group (p = 0.291) and a median progression-free survival of 5.37 in the group not taking ß-blockers versus 10.87 months in the ß-blocker group (p = 0.151). Nine (25%) patients in the beta-blocker group and 16 (12%) in the non-beta-blocker group were progressive disease-free at the end of follow-up. This difference between the two groups is statistically significant (p = 0.047). Conclusion Our study found no statistically significant evidence that beta blockers enhance the effectiveness of immunotherapy. Using adrenergic blockade to modulate the immune system shows promise, warranting the need to develop prospective clinical studies.

What's new about the tumor microenvironment of urothelial carcinoma?

Urothelial carcinoma is a significant global health concern that accounts for a substantial part of cancer diagnoses and deaths worldwide. The tumor microenvironment is a complex ecosystem composed of stromal cells, soluble factors, and altered extracellular matrix, that mutually interact in a highly immunomodulated environment, with a prominent role in tumor development, progression, and treatment resistance. This article reviews the current state of knowledge of the different cell populations that compose the tumor microenvironment of urothelial carcinoma, its main functions, and distinct interactions with other cellular and non-cellular components, molecular alterations and aberrant signaling pathways already identified. It also focuses on the clinical implications of these findings, and its potential to translate into improved quality of life and overall survival. Determining new targets or defining prognostic signatures for urothelial carcinoma is an ongoing challenge that could be accelerated through a deeper understanding of the tumor microenvironment.