A high black-hole-to-host mass ratio in a lensed AGN in the early Universe.

Early JWST observations have uncovered a population of red sources that might represent a previously overlooked phase of supermassive black hole growth1-3. One of the most intriguing examples is an extremely red, point-like object that was found to be triply imaged by the strong lensing cluster Abell 2744 (ref. 4). Here we present deep JWST/NIRSpec observations of this object, Abell2744-QSO1. The spectroscopy confirms that the three images are of the same object, and that it is a highly reddened (AV ≃ 3) broad emission line active galactic nucleus at a redshift of zspec = 7.0451 ± 0.0005. From the width of Hß (full width at half-maximum = 2,800 ± 250 km s-1), we derive a black hole mass of M BH = 4 - 1 + 2 × 1 0 7 M ⊙ . We infer a very high ratio of black-hole-to-galaxy mass of at least 3%, an order of magnitude more than that seen in local galaxies5 and possibly as high as 100%. The lack of strong metal lines in the spectrum together with the high bolometric luminosity (Lbol = (1.1 ± 0.3) × 1045 erg s-1) indicate that we are seeing the black hole in a phase of rapid growth, accreting at 30% of the Eddington limit. The rapid growth and high black-hole-to-galaxy mass ratio of Abell2744-QSO1 suggest that it may represent the missing link between black hole seeds6 and one of the first luminous quasars7.

Application of STREAM-URO and APPRAISE-AI reporting standards for artificial intelligence studies in pediatric urology: A case example with pediatric hydronephrosis.

INTRODUCTION: Artificial intelligence (AI) and machine learning (ML) in pediatric urology is gaining increased popularity and credibility. However, the literature lacks standardization in reporting and there are areas for methodological improvement, which incurs difficulty in comparison between studies and may ultimately hurt clinical implementation of these models. The "STandardized REporting of Applications of Machine learning in UROlogy" (STREAM-URO) framework provides methodological instructions to improve transparent reporting in urology and APPRAISE-AI in a critical appraisal tool which provides quantitative measures for the quality of AI studies. The adoption of these will allow urologists and developers to ensure consistency in reporting, improve comparison, develop better models, and hopefully inspire clinical translation. METHODS: In this article, we have applied STREAM-URO framework and APPRAISE-AI tool to the pediatric hydronephrosis literature. By doing this, we aim to describe best practices on ML reporting in urology with STREAM-URO and provide readers with a critical appraisal tool for ML quality with APPRAISE-AI. By applying these to the pediatric hydronephrosis literature, we provide some tutorial for other readers to employ these in developing and appraising ML models. We also present itemized recommendations for adequate reporting, and critically appraise the quality of ML in pediatric hydronephrosis insofar. We provide examples of strong reporting and highlight areas for improvement. RESULTS: There were 8 ML models applied to pediatric hydronephrosis. The 26-item STREAM-URO framework is provided in Appendix A and 24-item APPRAISE-AI tool is provided in Appendix B. Across the 8 studies, the median compliance with STREAM-URO was 67 % and overall study quality was moderate. The highest scoring APPRAISE-AI domains in pediatric hydronephrosis were clinical relevance and reporting quality, while the worst were methodological conduct, robustness of results, and reproducibility. CONCLUSIONS: If properly conducted and reported, ML has the potential to impact the care we provide to patients in pediatric urology. While AI is exciting, the paucity of strong evidence limits our ability to translate models to practice. The first step toward this goal is adequate reporting and ensuring high quality models, and STREAM-URO and APPRAISE-AI can facilitate better reporting and critical appraisal, respectively.

Most of the photons that reionized the Universe came from dwarf galaxies.

The identification of sources driving cosmic reionization, a major phase transition from neutral hydrogen to ionized plasma around 600-800 Myr after the Big Bang1-3, has been a matter of debate4. Some models suggest that high ionizing emissivity and escape fractions (fesc) from quasars support their role in driving cosmic reionization5,6. Others propose that the high fesc values from bright galaxies generate sufficient ionizing radiation to drive this process7. Finally, a few studies suggest that the number density of faint galaxies, when combined with a stellar-mass-dependent model of ionizing efficiency and fesc, can effectively dominate cosmic reionization8,9. However, so far, comprehensive spectroscopic studies of low-mass galaxies have not been done because of their extreme faintness. Here we report an analysis of eight ultra-faint galaxies (in a very small field) during the epoch of reionization with absolute magnitudes between MUV ≈ -17 mag and -15 mag (down to 0.005L⋆ (refs. 10,11)). We find that faint galaxies during the first thousand million years of the Universe produce ionizing photons with log[ξion (Hz erg-1)] = 25.80 ± 0.14, a factor of 4 higher than commonly assumed values12. If this field is representative of the large-scale distribution of faint galaxies, the rate of ionizing photons exceeds that needed for reionization, even for escape fractions of the order of 5%.

Predicting obstruction risk using common ultrasonography parameters in paediatric hydronephrosis with machine learning.

OBJECTIVE: To sensitively predict the risk of renal obstruction on diuretic renography using routine reported ultrasonography (US) findings, coupled with machine learning approaches, and determine safe criteria for deferral of diuretic renography. PATIENTS AND METHODS: Patients from two institutions with isolated hydronephrosis who underwent a diuretic renogram within 3 months following renal US were included. Age, sex, and routinely reported US findings (laterality, kidney length, anteroposterior diameter, Society for Fetal Urology [SFU] grade) were abstracted. The drainage half-times were collected from renography and stratified as low risk (<20 min, primary outcome), intermediate risk (20-60 min), and high risk of obstruction (>60 min). A random Forest model was trained to classify obstruction risk, here named the 'Artificial intelligence Evaluation of Renogram Obstruction' (AERO). Model performance was determined by measuring area under the receiver-operating-characteristic curve (AUROC) and decision curve analysis. RESULTS: A total of 304 patients met the inclusion criteria, with a median (interquartile range) age of diuretic renogram at 4 (2-7) months. Of all patients, 48 (16%) were low risk, 102 (33%) were intermediate risk, 156 (51%) were high risk of obstruction based on diuretic renogram. The AERO achieved a binary AUROC of 0.84, multi-class AUROC of 0.74 that was superior to the SFU grade, and external validation (n = 64) binary AUROC of 0.76. The most important features for prediction included age, anteroposterior diameter, and SFU grade. We deployed our application in an easy-to-use application (https://sickkidsurology.shinyapps.io/AERO/). At a threshold probability of 30%, the AERO would allow 66 more patients per 1000 to safely avoid a renogram without missing significant obstruction compared to a strategy in which a renogram is routinely performed for SFU Grade ≥3. CONCLUSIONS: Coupled with machine learning, routine US findings can improve the criteria to determine in which children with isolated hydronephrosis a diuretic renogram can be safely avoided. Further optimisation and validation are required prior to implementation into clinical practice.

Penile keloid formation post-circumcision: A case series and review of literature.

The formation of penile keloid after circumcision is an uncommon complication. Herein, we report two pediatric cases of large circumferential keloids that developed post-circumcision and were successfully treated by surgical excision and intralesional triamcinolone injections. In addition, we provide a comprehensive review of the reported cases of penile keloids that developed after circumcision in the literature to highlight the various presentations, treatment options, and outcomes for this condition.

Posterior urethral valves in patients with trisomy 21: Similar renal outcomes and rates of volitional voiding.

INTRODUCTION: Posterior urethral valves (PUV) occur in patients with Down Syndrome (DS) at a rate of 3-4%; far higher than the general population. Our understanding of the relationship between PUVs and DS is in its infancy, with the majority of the literature consisting of case reports. In this study, we present the largest known series of DS patients with PUVs. AIM: We hypothesized that patients with DS and PUVs would have worse functional bladder outcomes and renal outcomes when compared to PUV patients without DS. STUDY DESIGN: We queried our prospectively managed multi-institutional database of PUV patients from 1990 to 2021. We identified patients with a concomitant diagnosis of DS and PUV. In addition, we performed a systematic review of the literature describing the presentation of children with PUV and DS. Patient demographics, renal outcomes, voiding habits, surgical interventions, and radiologic images were aggregated and analyzed. RESULTS: Out of the 537 patients in our PUV database, we identified 18 patients with a concomitant diagnosis of PUV and DS, as well as 14 patients with a concomitant diagnosis of PUV and DS from the literature. DS and non-DS patients had a similar age at presentation, 31.5 days (2-731) and 17 (4-846), and length of follow up 6.32 years (2-11.2) and 6.98 (1-13). Both groups had similar nadir creatinines DS 0.43 (0.4-0.8), non-DS 0.31 (0.2-0.5) and similar rates of renal failure (DS 11.1% and non-DS 14.5%). With respect to bladder outcomes, a similar percentage of patients were volitionally voiding at last follow up (DS 72.2% and non-DS 72.3%). Our literature review corroborated these findings. CONCLUSIONS: Patients with DS and PUV have similar renal outcomes to other PUV patients in terms of renal function, progression to renal failure, and probability of volitional voiding with continence. Given the increased rate of PUVs in the DS population, physicians should have a high index of suspicion for PUV when patients with DS present with voiding dysfunction.

Automated Society of Fetal Urology (SFU) grading of hydronephrosis on ultrasound imaging using a convolutional neural network.

INTRODUCTION: Grading of hydronephrosis severity on postnatal renal ultrasound guides management decisions in antenatal hydronephrosis (ANH). Multiple systems exist to help standardize hydronephrosis grading, yet poor inter-observer reliability persists. Machine learning methods may provide tools to improve the efficiency and accuracy of hydronephrosis grading. OBJECTIVE: To develop an automated convolutional neural network (CNN) model to classify hydronephrosis on renal ultrasound imaging according to the Society of Fetal Urology (SFU) system as potential clinical adjunct. STUDY DESIGN: A cross-sectional, single-institution cohort of postnatal renal ultrasounds with radiologist SFU grading from pediatric patients with and without hydronephrosis of stable severity was obtained. Imaging labels were used to automatedly select sagittal and transverse grey-scale renal images from all available studies from each patient. A VGG16 pre-trained ImageNet CNN model analyzed these preprocessed images. Three-fold stratified cross-validation was used to build and evaluate the model that was used to classify renal ultrasounds on a per patient basis into five classes based on the SFU system (normal, SFU I, SFU II, SFU III, or SFU IV). These predictions were compared to radiologist grading. Confusion matrices evaluated model performance. Gradient class activation mapping demonstrated imaging features driving model predictions. RESULTS: We identified 710 patients with 4659 postnatal renal ultrasound series. Per radiologist grading, 183 were normal, 157 were SFU I, 132 were SFU II, 100 were SFU III, and 138 were SFU IV. The machine learning model predicted hydronephrosis grade with 82.0% (95% CI: 75-83%) overall accuracy and classified 97.6% (95% CI: 95-98%) of the patients correctly or within one grade of the radiologist grade. The model classified 92.3% (95% CI: 86-95%) normal, 73.2% (95% CI: 69-76%) SFU I, 73.5% (95% CI: 67-75%) SFU II, 79.0% (95% CI: 73-82%) SFU III, and 88.4% (95% CI: 85-92%) SFU IV patients accurately. Gradient class activation mapping demonstrated that the ultrasound appearance of the renal collecting system drove the model's predictions. DISCUSSION: The CNN-based model classified hydronephrosis on renal ultrasounds automatically and accurately based on the expected imaging features in the SFU system. Compared to prior studies, the model functioned more automatically with greater accuracy. Limitations include the retrospective, relatively small cohort, and averaging across multiple imaging studies per patient. CONCLUSIONS: An automated CNN-based system classified hydronephrosis on renal ultrasounds according to the SFU system with promising accuracy based on appropriate imaging features. These findings suggest a possible adjunctive role for machine learning systems in the grading of ANH.

Immunogenicity of Oral Rabies Vaccine Strain SPBN GASGAS in Local Dogs in Bali, Indonesia.

Dog-mediated rabies is endemic in much of Indonesia, including Bali. Most dogs in Bali are free-roaming and often inaccessible for parenteral vaccination without special effort. Oral rabies vaccination (ORV) is considered a promising alternative to increase vaccination coverage in these dogs. This study assessed immunogenicity in local dogs in Bali after oral administration of the highly attenuated third-generation rabies virus vaccine strain SPBN GASGAS. Dogs received the oral rabies vaccine either directly or by being offered an egg-flavored bait that contained a vaccine-loaded sachet. The humoral immune response was then compared with two further groups of dogs: a group that received a parenteral inactivated rabies vaccine and an unvaccinated control group. The animals were bled prior to vaccination and between 27 and 32 days after vaccination. The blood samples were tested for the presence of virus-binding antibodies using ELISA. The seroconversion rate in the three groups of vaccinated dogs did not differ significantly: bait: 88.9%; direct-oral: 94.1%; parenteral: 90.9%; control: 0%. There was no significant quantitative difference in the level of antibodies between orally and parenterally vaccinated dogs. This study confirms that SPBN GASGAS is capable of inducing an adequate immune response comparable to a parenteral vaccine under field conditions in Indonesia.

Assessing the Utility of Tamsulosin in Delaying Progression to Clean Intermittent Catheterization and End-stage Renal Disease in Patients With Posterior Urethral Valves: Are We Postponing the Inevitable?

OBJECTIVE: To assess whether tamsulosin may aid emptying of the lower urinary tract in posterior urethral valves patients, mitigating the likelihood of progressing to clean intermittent catheterization (CIC) or need for renal replacement therapy. METHODS: We reviewed a prospective institutional database containing posterior urethral valves patients treated between January 2000 and January 2022. After assessing baseline characteristics, Kaplan-Meier survival curves and log-rank tests were generated to assess differences in clinically significant outcomes (progression to CIC, dialysis, or kidney transplantation) between those prescribed tamsulosin and those who were not. RESULTS: A total of 179 patients were included. Fifty-nine patients received tamsulosin prior to initiation of CIC (group 1), and 120 did not (group 2). The baseline characteristics were similar between the two groups, except for anticholinergic use (tamsulosin group - 35/59 vs no tamsulosin - 32/120, P < .001). The median age at tamsulosin initiation was 26.0 months (IQR 15.5-48.6) and the median time from initiation of tamsulosin to progression to CIC was 52.6 months (IQR 10.1-69.3). Kaplan-Meier survival curves showed that patients on tamsulosin were less likely to progress to CIC (P = .021), however, there was no difference in progression to dialysis or kidney transplantation. A Cox-regression analysis controlling for baseline characteristics, including age, anticholinergic use, vesicoureteral reflux severity, and CKD stage at 1-year of life, showed a consistent effect of tamsulosin in delaying progression to CIC (HR 0.444 95%CI 0.218-0.902, P = .025). CONCLUSION: While tamsulosin may delay CIC, it does not appear to delay progression to end-stage renal disease. Additional studies exploring specific patient factors are required to determine the timing and subset who may benefit the most from tamsulosin.

Does Preoperative Testosterone Administration Decrease Complications in Distal Hypospadias Repair With Urethroplasty?

PURPOSE: Testosterone administration prior to hypospadias repair is common practice among pediatric urologists; however, its impact on surgical outcomes remains controversial. We hypothesize that testosterone administration prior to distal hypospadias repair with urethroplasty significantly decreases postoperative complications. MATERIALS AND METHODS: We queried our hypospadias database for primary distal hypospadias repairs with urethroplasty from 2015 to 2021. Patients undergoing repair without urethroplasty were excluded. We collected information on patient age, procedure type, testosterone administration status, initial visit and intraoperative glans width, urethroplasty length, and postoperative complications. To determine the role of testosterone administration on incidence of complications, a logistic regression adjusting for initial visit glans width, urethroplasty length, and age was performed. RESULTS: A total of 368 patients underwent distal hypospadias repair with urethroplasty. One hundred thirty-three patients received testosterone and 235 did not. Initial visit glans width was significantly larger in the no-testosterone vs testosterone group (14.5 mm vs 13.1 mm, P = .001). Testosterone patients had significantly larger glans width at the time of surgery (17.1 mm vs 14.6 mm [no-testosterone group], P = .001). On multivariable logistic regression analysis after controlling for age at surgery, preoperative glans width, testosterone status, and urethroplasty length, testosterone administration did show significant association with reduced odds of postoperative complications (OR 0.4, P = .039). CONCLUSIONS: This retrospective review of patients shows that on multivariable analysis there is significant association between testosterone administration and decreased incidence of complications in patients undergoing distal hypospadias repair with urethroplasty. Future studies on testosterone administration should focus on specific cohorts of patients with hypospadias as benefits of testosterone may be more evident in some subgroups than others.

Deep Learning of Videourodynamics to Classify Bladder Dysfunction Severity in Patients With Spina Bifida.

PURPOSE: Urologists rely heavily on videourodynamics to identify patients with neurogenic bladders who are at risk of upper tract injury, but their interpretation has high interobserver variability. Our objective was to develop deep learning models of videourodynamics studies to categorize severity of bladder dysfunction. MATERIALS AND METHODS: We performed a cross-sectional study of patients aged 2 months to 28 years with spina bifida who underwent videourodynamics at a single institution between 2019 and 2021. The outcome was degree of bladder dysfunction, defined as none/mild, moderate, and severe, defined by a panel of 5 expert reviewers. Reviewers considered factors that increase the risk of upper tract injury, such as poor compliance, elevated detrusor leak point pressure, and detrusor sphincter dyssynergia, in determining bladder dysfunction severity. We built 4 models to predict severity of bladder dysfunction: (1) a random forest clinical model using prospectively collected clinical data from videourodynamics studies, (2) a deep learning convolutional neural network of raw data from the volume-pressure recordings, (3) a deep learning imaging model of fluoroscopic images, (4) an ensemble model averaging the risk probabilities of the volume-pressure and fluoroscopic models. RESULTS: Among 306 videourodynamics studies, the accuracy and weighted kappa of the ensemble model classification of bladder dysfunction when at least 75% expected bladder capacity was reached were 70% (95% CI 66%,76%) and 0.54 (moderate agreement), respectively. The performance of the clinical model built from data extracted by pediatric urologists was the poorest with an accuracy of 61% (55%, 66%) and a weighted kappa of 0.37. CONCLUSIONS: Our models built from urodynamic pressure-volume tracings and fluoroscopic images were able to automatically classify bladder dysfunction with moderately high accuracy.

Increased Complications of Emergent Surgical Procedures During the First Wave of COVID-19.

INTRODUCTION: Based on recommendations by CMS elective surgery was stopped during the first wave of COVID-19. Despite hospitals being open for emergent surgery, there were some studies that showed a decrease in surgical volume. METHODS: A retrospective analysis for all surgeries from 185 affiliated hospitals from the first wave of the COVID-19 pandemic (March 2020 to May 2020) and as a comparison the previous year, March 2019 to May 2019 were obtained. Five surgeries were further analyzed: appendectomies, cholecystectomies, craniotomies, exploratory laparotomies, and endoscopic retrograde cholangiopancreatographies (ERCPs). RESULTS: Between March 2019 and May 2019, 326,726 surgeries were performed, and between March 2020 and May 2020, 237,809 surgeries were performed. The highest specialty for both years was gastroenterology. In 2020, 15.7% of the patients were admitted to the ICU versus 13.7% in 2019. For appendectomies, cholecystectomies, craniotomies, exploratory laparotomies and ERCPs, there was an increase from 2019 to 2020 in acute kidney injuries rate, infection, systemic inflammatory response syndrome (SIRS), and sepsis. All the changes in surgical volumes for the five surgeries from 2019 to 2020 were significant. For appendectomy, the statistically significant complications were infection and SIRS and sepsis. CONCLUSIONS: Across the board, there was a decrease in surgical volume during the COVID-19 pandemic first wave. There was a statistically significant decrease in appendectomy, cholecystectomy, exploratory laparotomy, craniotomy, and ERCP. For all five surgeries, we did see an increase in mortality rates and several complications. The only statistically significant complications were infection and SIRS and sepsis, for appendectomy.

Deferring gonadectomy in patients with turner syndrome with a genetic Y component is not a safe practice.

INTRODUCTION: Patients with Turner syndrome who harbor Y chromosome material are known to be at increased risk of developing germ cell neoplasms. The optimal timing to perform gonadectomy to reduce the risk of cancer development in these patients is not well defined. We present outcomes of Turner with a Y component (TSY) patients who underwent gonadectomy at our institution. HYPOTHESIS/OBJECTIVE: We hypothesized that tumors could occur in a significant portion of TSY patients at any age and gonadectomy can be safely performed at diagnosis rather than deferred. STUDY DESIGN: We performed an IRB-approved retrospective single center study in which we queried our institutions electronic health record to identify all patients with TSY who underwent gonadectomy at our institution from 2012 to 2021. RESULTS: In our series of 18 consecutive TSY patients, a tumor was identified in 6 patients (33.3%): 4 (22.2%) with dysgerminoma (DG) [Fig. 1] and 2 (11.1%) with gonadoblastoma (GB). DISCUSSION: Our cohort of 18 consecutive TSY who underwent gonadectomy over a 9-year period is the largest published single site cohort to date. Additionally, our patient who was found to have GB at 40 days is to our knowledge the youngest TSY patient to be diagnosed with GB in the literature. This patient's remarkably early incidence of tumor occurrence illustrates the urgency of protective gonadectomy. Given the high incidence of tumor formation in this population and the minimal morbidity associated with gonadectomy, we do not recommend delaying gonadectomy in this population for any reason. Our study is vulnerable to selection bias and confounding innate to any retrospective study. There was variation with respect to the frequency and timing of pre-operative imaging as a strict preoperative imaging protocol with sequential studies was not in place at our institution. Additionally, we do not have a comparison cohort of patients who are being followed without operative intervention as all TSY patients at our institution have undergone gonadectomy. CONCLUSION: TSY patients cannot be safely observed for tumor formation based on clinical factors such as imaging or age. Gonadectomy is safe with a low complication rate and without tumor recurrence during three-year follow-up. We continue to recommend bilateral gonadectomy in this patient population at the time of diagnosis.

Deep learning imaging features derived from kidney ultrasounds predict chronic kidney disease progression in children with posterior urethral valves.

BACKGROUND: We sought to use deep learning to extract anatomic features from postnatal kidney ultrasounds and evaluate their performance in predicting the risk and timing of chronic kidney disease (CKD) progression for boys with posterior urethral valves (PUV). We hypothesized that these features would predict CKD progression better than clinical characteristics such as nadir creatinine alone. METHODS: We performed a retrospective cohort study of boys with PUV treated at two pediatric health systems from 1990 to 2021. Features of kidneys were extracted from initial postnatal kidney ultrasound images using a deep learning model. Three time-to-event prediction models were built using random survival forests. The Imaging Model included deep learning imaging features, the Clinical Model included clinical data, and the Ensemble Model combined imaging features and clinical data. Separate models were built to include time-dependent clinical data that were available at 6 months, 1 year, 3 years, and 5 years. RESULTS: Two-hundred and twenty-five patients were included in the analysis. All models performed well with C-indices of 0.7 or greater. The Clinical Model outperformed the Imaging Model at all time points with nadir creatinine driving the performance of the Clinical Model. Combining the 6-month Imaging Model (C-index 0.7; 95% confidence interval [CI] 0.6, 0.79) with the 6-month Clinical Model (C-index 0.79; 95% CI 0.71, 0.86) resulted in a 6-month Ensemble Model that performed better (C-index 0.82; 95% CI 0.77, 0.88) than either model alone. CONCLUSIONS: Deep learning imaging features extracted from initial postnatal kidney ultrasounds may improve early prediction of CKD progression among children with PUV. A higher resolution version of the Graphical abstract is available as Supplementary information.

Synchronous Testicular Sperm Extraction in the Setting of Bladder Exstrophy.

Bladder exstrophy (BE) is a devastating congenital abnormality of the urinary tract in which infants are born with the urinary bladder extruded through their abdominal wall, a urethra that is open dorsally, and significant secondary abnormalities of the genitalia. We present a male patient with BE who suffered from infertility and after a long course of failed attempts with assisted reproductive technology ultimately benefitted from a synchronous testicular sperm extraction. We review the literature surrounding assisted reproductive techniques in the setting of bladder exstrophy and comment on innovative technologies that may benefit this population.

Reconstruction After Grizzly Bear Attack in Wyoming.

Bear attacks are rare, although global incidents have been increasing. Injury patterns of bear attacks against humans consistently include injuries to the face, head, neck, chest, and upper extremities. Here, we have a brief report of a 59-year-old male hunter who was attacked by a grizzly bear in Wyoming. He sustained multiple lacerations to his face which included an avulsion of his nose and upper lip, as well as extensive associated facial fractures. Additional injuries included soft tissue and bony injuries to the upper extremities. He underwent 53 operations during his first hospitalization, primarily of facial reconstruction, which required nose and upper lip replant to his arm. His course was complicated by pressure ulcers, bacteria, acute kidney injury, and a urinary tract infection. After successful coordinated multidisciplinary care and a prolonged hospitalization, he was ultimately discharged to his home.

The application of exosomes in the treatment of triple-negative breast cancer.

Triple-negative breast cancer (TNBC) is a heterogeneous and invasive breast cancer (BC) subtype that is estrogen receptor-negative, progesterone receptor-negative, and human epidermal growth factor receptor 2 (Her2)-negative. So far, the treatment of TNBC is still ineffective due to the lack of well-defined molecular targets. Exosomes are nanosized extracellular vesicles composed of lipid bilayers. They originate from various types of donor cells and release a complex mixture of contents including diverse nucleic acid types (miRNA, LnRNA, siRNA, and DNA) and proteins; after binding to recipient cells the exosomes release their contents that execute their biological functions. Exosomes have been reported to play an important role in the tumorigenesis of TNBC, including tumor initiation, metastasis, angiogenesis, cell proliferation, immune escape, and drug resistance. On the other hand, exosomes can be valuable biomarkers for diagnosis, monitoring, and treatment of TNBC. More interestingly, exosomes can be harnessed as a nanosized drug-delivery system specifically targeting TNBC. In this review, we present the most recent mechanistic findings and clinical applications of exosomes in TNBC therapy, focusing on their use as diagnostic and prognostic biomarkers, nanoscale drug delivery platforms, and immunotherapeutic agents. In addition, the associated challenges and future directions of using exosomes for TNBC treatment will be discussed.