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1.
J Pediatr Urol ; 2024 Aug 29.
Artículo en Inglés | MEDLINE | ID: mdl-39244432

RESUMEN

INTRODUCTION/BACKGROUND: The repeated or lengthy use of general anesthesia (GA) in children under three years old is cautioned against due to potential neurodevelopment effects. Spinal anesthesia (SA) has emerged as a safe and effective alternative for routine pediatric urologic procedures. In this study, we describe the use of SA in the urgent surgical treatment of neonatal testicular torsion. OBJECTIVE: We aim to evaluate the safety and efficacy of SA for urgent scrotal exploration in neonates. STUDY DESIGN: We retrospectively collected data on neonates younger than 30 days old undergoing SA for the indication of testicular torsion from May 2018 to June 2022. We recorded patient demographics, adjuvant medications use, and time points for start/stop of spinal injection, procedure, and operating room utilization. RESULTS: Six neonates, with an average age of 1.9 days of life and average weight of 3.4 kg, underwent scrotal exploration for testicular torsion using SA. Four patients (67%) required orchiectomy of the nonviable torsed testicle, and all patients underwent orchiopexy of the unaffected testicle. Mean total operative time was 45.3 (SD 11.7) minutes, including Gomco circumcision in five patients. One patient received preoperative intranasal dexmedetomidine for sedation. Mean time for SA administration was 6.3 (SD 5.5) minutes, with a mean total time in the operating room of 77.3 (SD 9.8) minutes. There were no perioperative or postoperative complications. DISCUSSION: We describe a single institution experience of surgical management of neonatal torsion under SA. In this case series, SA was safely utilized for all neonates involved without the need for conversion to GA or intravenous (IV) sedation. CONCLUSION: The use of SA is safe and efficacious for urgent scrotal exploration for testicular torsion in neonates, even those under 48 h of age. More widespread utilization requires collaboration between pediatric urologists and experienced pediatric anesthesiologists trained in SA.

2.
J Surg Educ ; 81(11): 1743-1747, 2024 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-39305604

RESUMEN

Video-based educational programs offer a promising avenue to augment surgical preparation, allow for targeted feedback delivery, and facilitate surgical coaching. Recently, developments in surgical intelligence and computer vision have allowed for automated video annotation and organization, drastically decreasing the manual workload required to implement video-based educational programs. In this article, we outline the development of a novel AI-assisted video forum and describe the early use in surgical education at our institution.


Asunto(s)
Inteligencia Artificial , Urología , Grabación en Video , Humanos , Urología/educación , Educación de Postgrado en Medicina/métodos , Internado y Residencia/métodos , Competencia Clínica
4.
Urology ; 2024 Aug 21.
Artículo en Inglés | MEDLINE | ID: mdl-39154839

RESUMEN

OBJECTIVE: To call to attention the often-overlooked aspect of pediatric transgender care: the importance of fertility preservation prior to instituting gender-affirming therapy. The transgender population has long been marginalized by society. Societal stigmata, fear to seek care, and dearth of provider knowledge regarding transgender health issues have caused disparities to widen. Gender-affirming procedures and hormone therapy affect the long-term reproductive potential of transgender individuals. While cost concerns and insurance coverage regarding oncofertility is a prominent area of discussion, the transgender community is often excluded. METHODS: Sixteen genetically XY females, followed by their multidisciplinary transgender care teams, were interested in starting hormone therapy due to impending onset and/or progression of puberty. Their physicians were aware of fertility struggles after undergoing hormone therapy and therefore referred to urology. Sperm cryopreservation via open gonadal biopsy, testicular tissue cryopreservation (TTC), and semen sample (when age/maturity-appropriate) were discussed. Though requiring surgery, biopsy/TTC relieves patients of the psychological impact of semen sample production. RESULTS: Under IRB approval, 15 patients (median age 12 years, range 10-16 years) underwent TTC (Fig. 1). One patient (aged years) opted for semen sample. All patients had success with spermatogonial stem cells cryopreserved for future patient use. CONCLUSION: With more individuals beginning medical and surgical therapy at a younger age, fertility preservation discussions are essential but often overlooked, depriving these individuals the joy of becoming a biological parent. TTC can be safely done in pediatric populations, though research is necessary to expand beyond current experimental stage of tissue development.

5.
bioRxiv ; 2024 Mar 27.
Artículo en Inglés | MEDLINE | ID: mdl-38585884

RESUMEN

Spermatogonial stem cell (SSC) acquisition of meiotogenetic state during puberty to produce genetically diverse gametes is blocked by drugs collectively referred as 'puberty blocker' (PB). Investigating the impact of PB on juvenile SSC state and function is challenging due to limited tissue access and clinical data. Herein, we report largest clinically annotated juvenile testicular biorepository with all children with gender dysphoria on chronic PB treatment highlighting shift in pediatric patient demography in US. At the tissue level, we report mild-to-severe sex gland atrophy in PB treated children. We developed most extensive integrated single-cell RNA dataset to date (>100K single cells; 25 patients), merging both public and novel (52 month PB-treated) datasets, alongside innovative computational approach tailed for germ cells and evaluated the impact of PB and aging on SSC. We report novel constitutional ranges for each testicular cell type across the entire age spectrum, distinct effects of treatments on prepubertal vs adult SSC, presence of spermatogenic epithelial cells exhibiting post-meiotic-state, irrespective of age, puberty status, or PB treatment. Further, we defined distinct effects of PB and aging on testicular cell lineage composition, and SSC meiotogenetic state and function. Using single cell data from prepubertal and young adult, we were able to accurately predict sexual maturity based both on overall cell type proportions, as well as on gene expression patterns within each major cell type. Applying these models to a PB-treated patient that they appeared pre-pubertal across the entire tissue. This combined with the noted gland atrophy and abnormalities from the histology data raise a potential concern regarding the complete 'reversibility' and reproductive fitness of SSC. The biorepository, data, and research approach presented in this study provide unique opportunity to explore the impact of PB on testicular reproductive health.

6.
BJU Int ; 133(5): 579-586, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38378021

RESUMEN

OBJECTIVES: To characterise the prevalence of impostor phenomenon (IP; tendency for high-achieving individuals to perceive themselves as fraudulent in their successes) amongst attending staff in urology, to identify variables that predict more severe impostorism, and to study the association of IP with burnout. SUBJECTS AND METHODS: A survey composed of the Clance Impostor Phenomenon Scale (CIPS), demographic information, practice details, and burnout levels was e-mailed to urologists via urological subspecialty societies. Survey results were analysed to identify associations between IP severity, survey respondent characteristics, and symptoms of professional burnout. This study was conducted in the United States of America. RESULTS: A total of 614 survey responses were received (response rate 11.0%). In all, 40% (n = 213) of responders reported CIPS scores qualifying as either 'frequent' or 'intense' impostorism (i.e., scores of 61-100). On multivariable analysis, female gender, fewer years in practice (i.e., 0-2 years), and lower academic rank were all independently associated with higher CIPS scores (adjusted P < 0.05). Regarding burnout, 46% of responders reported burnout symptoms. On multivariable analysis, increase in CIPS score was independently associated with higher odds of burnout (odds ratio 1.06, 95% confidence interval 1.04-1.07; P < 0.001). CONCLUSION: Impostor phenomenon is prevalent in the urological community and is experienced more severely in younger and female urologists. IP is also independently associated with burnout. Increased female representation may improve IP amongst our female colleagues. More work is needed to determine strategies that are effective in mitigating feelings of IP and professional burnout amongst urologists, particularly those earlier in their careers.


Asunto(s)
Trastornos de Ansiedad , Agotamiento Profesional , Urólogos , Humanos , Agotamiento Profesional/epidemiología , Agotamiento Profesional/psicología , Femenino , Masculino , Urólogos/psicología , Urólogos/estadística & datos numéricos , Prevalencia , Adulto , Persona de Mediana Edad , Estados Unidos/epidemiología , Urología , Encuestas y Cuestionarios , Autoimagen
7.
Urol Pract ; 10(4): 341-342, 2023 07.
Artículo en Inglés | MEDLINE | ID: mdl-37341366
8.
J Pediatr Urol ; 19(5): 513.e1-513.e7, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37150637

RESUMEN

INTRODUCTION: The global prevalence of pediatric nephrolithiasis continues to rise amidst increased sodium and animal protein intake. Plant-based meat alternatives (PBMAs) have recently gained popularity due to health benefits, environmental sustainability, and increased retail availability. PBMAs have the potential to reduce the adverse metabolic impact of animal protein on kidney stone formation. We analyzed PBMAs targeted to children to characterize potential lithogenic risk vs animal protein. METHODS: We performed a dietary assessment using a sample of PBMAs marketed to or commonly consumed by children and commercially available at national retailers. Nutrient profiles for PBMAs were compiled from US Department of Agriculture databases and compared to animal protein sources using standardized serving sizes. We also analyzed nutrient profiles for plant-based infant formulas against typical dairy protein-based formulas. Primary protein sources were identified using verified ingredient lists. Oxalate content was extrapolated from dietary data sources. RESULTS: A total of 41 PBMAs were analyzed: chicken (N = 18), hot dogs (N = 3), meatballs (N = 5), fish (N = 10), and infant formula (N = 5). Most products (76%) contained a high-oxalate ingredient as the primary protein source (soy, wheat, or almond). Average oxalate content per serving was substantially higher in these products (soy 11.6 mg, wheat 3.8 mg, almond 10.2 mg) vs animal protein (negligible oxalate). PBMAs containing pea protein (24%) had lower average oxalate (0.11 mg). Most PBMAs averaged up to six times more calcium and three times more sodium per serving compared to their respective animal proteins. Protein content was similar for most categories. CONCLUSIONS: Three-quarters of the examined plant-based meat products for children and infants contain high-oxalate protein sources. Coupled with higher per-serving sodium and calcium amounts, our findings raise questions about possible lithogenic risk in some PBMAs, and further studies are needed to assess the relationship between PBMAs and nephrolithiasis.


Asunto(s)
Calcio , Cálculos Renales , Animales , Humanos , Niño , Lactante , Factores de Riesgo , Cálculos Renales/epidemiología , Calcio de la Dieta , Carne/efectos adversos , Oxalatos , Sodio
9.
J Pediatr Urol ; 19(4): 426.e1-426.e4, 2023 08.
Artículo en Inglés | MEDLINE | ID: mdl-37069042

RESUMEN

BACKGROUND: In the past two decades, technology has advanced to augment an already minimally-invasive approach in laparoscopic surgery. Robotic-assisted laparoscopic platforms have now evolved to its 4th-generation product: a single-port system, first cleared through the FDA for urologic procedures last year. A single, 2.5 cm incision allows for placement of a port that admits a fully-wristed camera as well as three fully-wristed instruments, all controlled by the surgeon at the console. OBJECTIVE: We sought to document the feasibility of the single-port (SP) robotic platform in the first clinical series of pediatric patients, reporting use of this system for dismembered pyeloplasty and Mitrofanoff. Secondary aims were to report intraoperative details and perioperative outcomes. STUDY DESIGN: Seven patients underwent surgery using the da Vinci SP Surgical System (Intuitive Surgical, Sunnyvale, CA). Six patients, two girls and 4 boys, were diagnosed with ureteropelvic junction obstruction and underwent SP robotic-assisted dismembered pyeloplasty while one male patient with neurogenic bladder underwent SP robotic-assisted Mitrofanoff procedure. Patient's ages ranged from 22 months to 14 years. A 2.5-cm incision was made within the Pfannenstiel line in HIdES fashion for the pyeloplasties, while the previous gastrostomy tube site was used for the Mitrofanoff. Through this incision a 25-mm multichannel port was placed. The 12 × 10-mm articulating robotic camera and two 6-mm articulating robotic instruments were utilized. RESULTS: All surgeries were completed successfully through the single port without intraoperative complications, need for separate ports, or conversion. Median operative time was 120 min, and all patients were dismissed in less than 24 h, taking only acetaminophen and ibuprofen for pain control. There was no issue with instrumentation in older patients; however, shorter working distance in the 22-month-old pyeloplasty limited wristing of the instruments. CONCLUSIONS: We report the first cases utilizing the SP robotic platform in children. Despite their smaller size and limited workspace, we had no issues with instrument clashing or triangulation in older patients, completing the procedures in a similar timeframe as multiport robotic platforms. Use of the SP platform is not recommended if working distance will be < 10 cm from the end of the port as instrument movement is prohibitive. The HIdES approach of placing the port in the Pfannenstiel line gave additional working distance and kept the incision below the swimsuit line for excellent cosmesis (Figure 1). Further study with additional cases will compare this approach with standard multiport robotics to analyze and compare operative data and outcomes.


Asunto(s)
Laparoscopía , Procedimientos de Cirugía Plástica , Procedimientos Quirúrgicos Robotizados , Robótica , Obstrucción Ureteral , Femenino , Humanos , Masculino , Niño , Anciano , Lactante , Laparoscopía/métodos , Obstrucción Ureteral/cirugía , Hospitalización
12.
Urology ; 172: 228-233, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36495948

RESUMEN

OBJECTIVE: To characterize recent trends among practicing female surgeons, surgical trainees, and surgical residency applicants to assess potential progress toward gender parity. METHODS: Workforce statistics on U.S. practicing surgeons, trainees, and applicants among 9 surgical specialties were obtained from the Association of American Medical Colleges and Electronic Residency Application Service public databases. Physician and trainee data during 2007-2019 and residency applicant data during 2016-2020 were analyzed by surgical specialty. We used Cochrane Armitage trend tests to assess changes over time. RESULTS: Female practicing urologists increased 104% during the study period, the third-largest increase among 9 surgical specialties (range 36%-114%, all P < .01), representing continued growth in the prevalence and proportion of women among surgical trainees in all surgical disciplines. In contrast, the overall change for female urology residents (28%) lagged significantly, ranking eighth among the 9 specialties (range 9%-149%, all P < .01), suggesting slowing growth in the training pipeline. Finally, while the proportional change in urology applicants has been significant (33%, P < .01), growth rates have markedly slowed in the past 5 years compared to women in practice and training since 2007. CONCLUSION: While female representation among practicing urologists has improved relative to other surgical disciplines, declining rates of women entering and applying to urology residency suggest a longer trajectory toward gender parity.


Asunto(s)
Internado y Residencia , Cirujanos , Urología , Humanos , Femenino , Estados Unidos , Educación de Postgrado en Medicina , Urología/educación , Cirujanos/educación , Urólogos
13.
Pediatr Blood Cancer ; 70(5): e28601, 2023 05.
Artículo en Inglés | MEDLINE | ID: mdl-32762004

RESUMEN

The International Soft-Tissue Sarcoma Consortium (INSTRuCT) was founded as an international collaboration between different pediatric soft-tissue sarcoma cooperative groups (Children's Oncology Group, European Pediatric Soft-Tissue Sarcoma Group, and Cooperative Weichteilsarkom Studiengruppe). Besides other tasks, a major goal of INSTRuCT is to develop consensus expert opinions for best clinical treatment. This consensus paper for patients with rhabdomyosarcoma of the female genital tract (FGU-RMS) provides treatment recommendations for local treatment, long-term follow-up, and fertility preservation. Therefore, a review of the current literature was combined with recommendations of the treatment protocols of the appropriate clinical trials. Additionally, opinions of international FGU-RMS experts were incorporated into recommendations. Results were that the prognosis of FGU-RMS is favorable with an excellent response to chemotherapy. Initial complete surgical resection is not indicated, but diagnosis should be established properly. In patients with tumors localized at the vagina or cervix demonstrating incomplete response after induction chemotherapy, local radiotherapy (brachytherapy) should be carried out. In patients with persistent tumors at the corpus uteri, hysterectomy should be performed. Fertility preservation should be considered in all patients. In conclusion, for the first time, an international consensus for the treatment of FGU-RMS patients could be achieved, which will help to harmonize the treatment of these patients in different study groups.


Asunto(s)
Rabdomiosarcoma , Sarcoma , Niño , Humanos , Femenino , Consenso , Sarcoma/terapia , Rabdomiosarcoma/patología , Pronóstico , Genitales Femeninos/patología , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico
14.
J Assist Reprod Genet ; 40(3): 455-464, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36542310

RESUMEN

A systematic review and meta-analysis of pertinent literature published from 2006 to January 2022 were conducted to study and compare vitrification and slow freezing, the two prominent methods of ovarian tissue cryopreservation. The primary outcome measures for this study were (1) proportion of intact primordial follicles, (2) proportion of intact stromal cells, (3) proportion of DNA fragmentation in primordial follicles, and (4) mean primordial follicle density. This meta-analysis of 19 studies revealed a significantly greater proportion of intact stromal cells in vitrified tissue versus slow-frozen tissue. No significant differences upon pooled analyses were observed between the two cryopreservation methods with respect to the proportion of intact primordial follicles, proportion of DNA fragmentation, or mean primordial follicle density. Due to differences seen in stromal cell viability, vitrification may be a preferred option to preserve histology of tissue. However, more work should be done to compare the two freezing techniques with less heterogeneity caused by patients, samples, and protocols.


Asunto(s)
Ovario , Vitrificación , Femenino , Humanos , Congelación , Ovario/patología , Criopreservación/métodos , Folículo Ovárico
15.
Urology ; 170: 244-245, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-36462839
16.
Pediatr Radiol ; 52(12): 2254-2266, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-36207454

RESUMEN

Although rare, pediatric peritoneal carcinomatosis does occur in primary abdominopelvic tumors. Additionally, peritoneal carcinomatosis has been described to occur as metastatic disease where the primary tumor is outside the abdominopelvic cavity. Where amenable, cytoreductive surgery and hyperthermic intraperitoneal chemotherapy (HIPEC) can be beneficial in disease management. However, favorable outcomes are predicated on specific tumor histology as well as proper patient selection, which significantly relies on preoperative imaging. This review gives a comprehensive, up-to-date summary on pediatric peritoneal carcinomatosis pre-surgical evaluation; where imaging is beneficial and limited; pediatric radiologists' role in helping to quantify disease; and how we, as pediatric radiologists, can help the surgeons and oncologists in the selection of patients for cytoreductive surgery and HIPEC.


Asunto(s)
Hipertermia Inducida , Neoplasias Peritoneales , Humanos , Niño , Procedimientos Quirúrgicos de Citorreducción/métodos , Neoplasias Peritoneales/terapia , Neoplasias Peritoneales/tratamiento farmacológico , Quimioterapia Intraperitoneal Hipertérmica , Hipertermia Inducida/métodos , Terapia Combinada
17.
J Pediatr Urol ; 18(6): 786.e1-786.e7, 2022 12.
Artículo en Inglés | MEDLINE | ID: mdl-35945145

RESUMEN

INTRODUCTION: Spinal anesthesia (SA) has been safely utilized in infants. There are limited data regarding the safety and efficacy of SA in pediatric urologic surgery lasting ≥60 min. We outlined the perioperative course for infants undergoing single-injection 0.5% plain bupivacaine SA-only for urologic procedures lasting ≥60 min. OBJECTIVE: To characterize the safety and efficacy of SA for urologic surgery in infants lasting ≥60 min. METHODS: We reviewed our prospectively maintained database of infants undergoing SA for urologic procedures lasting ≥60 min from May 2018 to March 2021. Patients received preoperative intranasal dexmedetomidine, some received intranasal fentanyl, and all patients received lidocaine cream applied preoperatively over the lumbar spine. Oral sucrose on a pacifier was provided as needed, and the patient's arms were swaddled for the procedure. Success was defined as no conversion to general anesthesia. Time points for start/end of spinal injection, procedure duration, wheels in/out of operating room (OR), and discharge were collected. RESULTS: Of 245 cases conducted with SA during the study period, 76 (31%) infants underwent surgery lasting ≥60 min. Of these, 73 (96%) were successfully completed with SA alone. In the 3 cases converted to general anesthesia, 2 (67%) required mask anesthesia after 96 and 169 min (for the last <10 min of surgery), and one was converted to intubation before start of surgery. Median patient age was 6 (IQR 5-7) months, and median procedure length was 95 (IQR 75-120) minutes. Following initial preoperative intranasal dexmedetomidine ± fentanyl, at least one additional dose of IV sedative was given in 27 (36%) cases at a median time of 90 (IQR 60-120) minutes into surgery. Following closure, patients exited the OR after a median 10 (IQR 8-12) minutes and subsequently discharged after spending a median of 73 (IQR 61-96) minutes in recovery. DISCUSSION: We describe pediatric urologic surgical cases lasting ≥60 min that employed single-injection intrathecal bupivacaine alone without adjunct intrathecal agents. In this report, SA was safely utilized in infants undergoing urologic procedures lasting at least 60 min, with about 40% of patients receiving additional IV dexmedetomidine and fentanyl. Non-medication measures (swaddling, oral sucrose) were important for maximizing patient comfort. Communication between surgeon and anesthesia as cases progress is key to maintaining adequate anesthesia. CONCLUSION: A single-injection bupivacaine-only spinal anesthesia approach for urologic surgery lasting over an hour and up to 3 h is safe and effective in infants. Selecting appropriate candidates for SA should be a joint decision between the surgeon and the anesthesiologist.


Asunto(s)
Anestesia Raquidea , Dexmedetomidina , Humanos , Lactante , Niño , Anestesia Raquidea/métodos , Bupivacaína , Fentanilo , Sacarosa , Anestésicos Locales
18.
Urology ; 169: 211-213, 2022 11.
Artículo en Inglés | MEDLINE | ID: mdl-35623501

RESUMEN

Fetal interventions are often key to fetal survival and growth; however, they can often have complications causing significant morbidity and mortality. This case highlights not only a complication of fetal surgery, but also a very unusual diagnosis. We present the case of a male fetus who was diagnosed with urethral atresia and subsequently underwent 2 vesicoamniotic shunt placements. At birth, he was diagnosed with Megacystis Microcolon Intestinal Hypoperistalsis Syndrome and was noted to have rectovesical and vesicocutaneous fistulae likely iatrogenically created from shunt placement. While fetal interventions are often required, a multidisciplinary team approach is often necessary as complications occur.


Asunto(s)
Anomalías Múltiples , Seudoobstrucción Intestinal , Embarazo , Recién Nacido , Femenino , Humanos , Masculino , Ultrasonografía Prenatal , Seudoobstrucción Intestinal/cirugía , Feto/cirugía , Vejiga Urinaria/diagnóstico por imagen , Anomalías Múltiples/cirugía , Colon/diagnóstico por imagen
19.
Am J Kidney Dis ; 79(1): 125-128, 2022 01.
Artículo en Inglés | MEDLINE | ID: mdl-34245816

RESUMEN

Primary hyperoxaluria (PH) is a group of genetic disorders that result in an increased hepatic production of oxalate. PH type 3 (PH3) is the most recently identified subtype and results from mutations in the mitochondrial 4-hydroxy-2-oxoglutarate aldolase gene (HOGA1). To date, there have been 2 cases of kidney failure reported in PH3 patients. We present a case of a young man with a history of recurrent urinary tract infections and voiding dysfunction who developed kidney failure at 33 years of age. He developed a bladder stone and bilateral staghorn calculi at 12 years of age. Initial metabolic evaluation revealed hyperoxaluria with very low urinary citrate excretion on multiple measurements for which he was placed on oral citrate supplements. Further investigation of the hyperoxaluria was not completed as the patient was lost to follow-up observation until he presented at 29 years of age with chronic kidney disease stage 4 (estimated glomerular filtration rate 24mL/min/1.73m2). Hemodialysis 3 times a week was started at 33 years of age, and subsequent genetic testing revealed a homozygous HOGA1 mutation (C.973G>A p.Gly325Ser) diagnostic of PH3. The patient is currently being evaluated for all treatment options including possible liver/kidney transplantation. All cases of a childhood history of recurrent urinary stone disease with marked hyperoxaluria should prompt genetic testing for the 3 known PH types. Hyperhydration and crystallization inhibitors (citrate) are standard of care, but the role of RNA interference agents for all 3 forms of PH is also under active study.


Asunto(s)
Hiperoxaluria Primaria , Hiperoxaluria , Oxo-Ácido-Liasas , Insuficiencia Renal , Humanos , Hiperoxaluria/complicaciones , Hiperoxaluria/diagnóstico , Hiperoxaluria/genética , Hiperoxaluria Primaria/complicaciones , Hiperoxaluria Primaria/diagnóstico , Hiperoxaluria Primaria/genética , Masculino , Oxalatos
20.
Cancers (Basel) ; 13(18)2021 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-34572755

RESUMEN

Novel therapeutic strategies are needed for the treatment of rhabdomyosarcoma (RMS), the most common soft-tissue sarcoma in children. By using a combination of cell surface proteomics and transcriptomic profiling of RMS and normal muscle, we generated a catalog of targetable cell surface proteins enriched in RMS tumors. Among the top candidates, we identified B7-H3 as the major immunoregulatory molecule expressed by RMS tumors. By using a large cohort of tissue specimens, we demonstrated that B7-H3 is expressed in a majority of RMS tumors while not detected in normal human tissues. Through a deconvolution analysis of the RMS tumor RNA-seq data, we showed that B7-H3-rich tumors are enriched in macrophages M1, NK cells, and depleted in CD8+-T cells. Furthermore, in vitro functional assays showed that B7-H3 knockout in RMS tumor cells increases T-cell mediated cytotoxicity. Altogether, our study uncovers new potential targets for the treatment of RMS and provides the first biological insights into the role of B7-H3 in RMS biology, paving the way for the development of next-generation immunotherapies.

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