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In the past decade, chimeric antigen receptor (CAR)-T cell therapy has emerged as a promising immunotherapeutic approach for combating cancers, demonstrating remarkable efficacy in relapsed/refractory hematological malignancies in both pediatric and adult patients. CAR-natural killer (CAR-NK) cell complements CAR-T cell therapy by offering several distinct advantages. CAR-NK cells do not require HLA compatibility and exhibit low safety concerns. Moreover, CAR-NK cells are conducive to "off-the-shelf" therapeutics, providing significant logistic advantages over CAR-T cells. Both CAR-T and CAR-NK cells have shown consistent and promising results in hematological malignancies. However, their efficacy against solid tumors remains limited due to various obstacles including limited tumor trafficking and infiltration, as well as an immuno-suppressive tumor microenvironment. In this review, we discuss the recent advances and current challenges of CAR-T and CAR-NK cell immunotherapies, with a specific focus on the obstacles to their application in solid tumors. We also analyze in depth the advantages and drawbacks of CAR-NK cells compared to CAR-T cells and highlight CAR-NK CAR optimization. Finally, we explore future perspectives of these adoptive immunotherapies, highlighting the increasing contribution of cutting-edge biotechnological tools in shaping the next generation of cellular immunotherapy.
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OBJECTIVE: To investigate the feasibility, safety and effectiveness of robot-assisted laparoscopic buccal mucosa graft ureteroplasty in the treatment of complex long proximal ureteral stricture. METHODS: The clinical data of 20 patients with proximal ureteral stricture undergoing robot-assisted laparoscopic buccal mucosa graft ureteroplasty admitted to the Department of Urology, Peking University First Hospital and Beijing Jiangong Hospital from July 2022 to January 2023 were prospectively collected and analyzed. Intraoperative conditions, postoperative complications and follow-up data were also recorded and analyzed. RESULTS: The operations under robot-assisted laparoscopy were performed successfully in all the 20 patients without conversion to traditional laparoscopic surgery or open surgery. The study included 14 males and 6 females with a mean age of (41±11) years (range: 19 to 60 years) and a mean body mass index of (24.3±3.6) kg/m2 (range: 18.2 to 31.8 kg/m2). There were 9 cases on the left side and 11 cases on the right side. The strictures of all the patients were located in the proximal segment of the ureter (including the ureteropelvic junction). The mean preoperative serum creatinine was (92.2±23.3) µmol/L (range: 49.2 to 138.9 µmol/L), and the mean length of ureteral stricture was (2.8±0.9) cm (range: 1.0 to 4.0 cm). Ten patients had previously undergone unsuccessful reconstructive surgery. During the operation, 12 patients received posteriorly augmented anastomosis with ventral onlay. The mean length of the buccal mucosa graft harvested during the operation was (3.1±0.6) cm (range: 2.0 to 4.3 cm), and the median width was 1.5 cm (range: 1.0 to 2.0 cm). The omentum flap was used to wrap the reconstructed ureteral segment in all the 20 cases. The median operative time was 154 min (range: 113 to 300 min), and the median estimated blood loss was 45 mL (range: 0 to 100 mL). The median postoperative hospital stay was 4 d (range: 4 to 14 d). The mean postoperative follow-up time was (15.0±1.7) months (range: 12.5 to 17.9 months), and the surgical success rate was 100.0% in this study. After surgery, 11 patients reported mild discomfort at the oral donor site, 2 patients deve-loped urinary tract infection, and no postoperative complications were reported in the other 7 patients. The mean serum creatinine was (90.9±23.9) µmol/L (range: 60.0 to 153.0 µmol/L) six months after surgery. CONCLUSION: Robot-assisted laparoscopic buccal mucosa graft ureteroplasty for the treatment of complex long proximal ureteral stricture has satisfactory efficacy without severe complications, which has shown good feasibility, safety and effectiveness. However, large sample studies and long-term follow-up are still needed to evaluate its long-term efficacy.
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Laparoscopía , Mucosa Bucal , Procedimientos Quirúrgicos Robotizados , Uréter , Obstrucción Ureteral , Humanos , Masculino , Femenino , Adulto , Mucosa Bucal/trasplante , Persona de Mediana Edad , Laparoscopía/métodos , Procedimientos Quirúrgicos Robotizados/métodos , Obstrucción Ureteral/cirugía , Uréter/cirugía , Adulto Joven , Constricción Patológica , Procedimientos Quirúrgicos Urológicos/métodos , Tempo Operativo , Complicaciones Posoperatorias/etiología , Procedimientos de Cirugía Plástica/métodosRESUMEN
Data on prevalence of programmed death ligand-1 (PD-L1) expression and its correlation with tumor biomarkers in Chinese patients with muscle-invasive urothelial bladder cancer (MIUBC) are scarce. We investigated the prevalence of PD-L1 expression, PD-L1 expression in tumor cells (TC) and immune cells (IC), and its correlation with tumor biomarkers (CD8+ T cells and tumor mutation burden [TMB]) in Chinese patients with newly diagnosed MIUBC (NCT03433924). Of 248 patients enrolled, 229 with PD-L1 data available were analysed. High PD-L1 expression (≥ 25% of TC or IC with PD-L1 expression) was observed in 120 (52.4%) patients. 59 cases showed positive staining in ≥ 25% of TC, and 82 cases had positive staining in ≥ 25% of IC. High expression of CD8+ T cell and TMB (> 10 mutations/megabase) was observed in 44.5% and 54.1% patients, respectively. A positive correlation was observed between percentage of TC with membrane PD-L1 positivity and CD8+ T cells (0.34; P < 0.001) and between IC with membrane PD-L1 positivity and CD8+ T cells (0.44; P < 0.001). There is high prevalence of PD-L1 expression in Chinese patients with MIUBC, suggesting that a sizable subset of patients could benefit from immunotherapy. The correlation of PD-L1 expression with tumor biomarkers provide clues for mechanisms underlying the effects of biomarkers for predicting efficacy.
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Antígeno B7-H1 , Biomarcadores de Tumor , Linfocitos T CD8-positivos , Neoplasias de la Vejiga Urinaria , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Masculino , Persona de Mediana Edad , Antígeno B7-H1/metabolismo , Antígeno B7-H1/genética , Biomarcadores de Tumor/metabolismo , Biomarcadores de Tumor/genética , Linfocitos T CD8-positivos/metabolismo , Linfocitos T CD8-positivos/inmunología , China/epidemiología , Pueblos del Este de Asia/genética , Mutación , Neoplasias de la Vejiga Urinaria/genética , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patologíaRESUMEN
Background: Ureteral strictures (US) could lead to impaired kidney function, which was alleviated by ureteral reconstruction surgery. However, solitary kidney (SK) patients with US were more complicated to treat. This study aimed to evaluate the impact of reconstruction surgery on renal function based on estimated glomerular filtration rate (eGFR) in patients with SK. Methods: We retrospectively enrolled patients who underwent reconstruction surgery between April 2014 to March 2022. eGFR was measured pre- and postoperatively. The 'static renal function' was defined as a change in eGFR of 20% or less at the last follow-up, and the 'worsening renal function group' was defined as a decrease of greater than 20%. Results: A total of 61 SK patients were involved. The success rate of ureteral reconstruction surgery was 90.16% (55/61). The median follow-up time was 20.8 months (range, 3.7-109.2 months). The median eGFR was 65.5 (range, 15.1-99.9) and 65.3 (range, 3.8-123.4) mL/min/1.73 m2 at the baseline and the last follow-up. No statistically significant difference in eGFR was observed between the preoperative baseline and last follow-up visits (P=0.58). However, in patients with baseline renal dysfunction [chronic kidney disease (CKD) stage 3-5], the eGFR significantly improved at the last follow-up compared to the baseline (P=0.02). Three patients developed a 'worsening renal function' (4.92%). Besides, the systolic blood pressures (SBP) at follow-up significantly reduced compared to the preoperative baseline (P=0.002). Conclusions: Ureteral reconstruction surgery is an effective treatment to preserve renal function, which also achieves a high success rate and is associated with the reduction of SBP for SK patients with US.
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BACKGROUND: The KangDuo Surgical Robot (KD-SR) is a newly developed surgical robot. OBJECTIVE: To compare the safety and efficacy of robot-assisted radical prostatectomy (RARP) using the KD-SR with those of the da Vinci Si Surgical System (DV-SS-Si). DESIGN, SETTING, AND PARTICIPANTS: A prospective double-center noninferiority randomized controlled trial was conducted among 18-75-yr-old patients with suspected T1-2N0M0 prostate cancer (PCa) scheduled for RARP. INTERVENTION: RARP with the KD-SR (KD-RARP) versus RARP with the DV-SS-Si (DV-RARP). OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary outcome was surgical success, defined as follows: surgery can be performed according to the established protocol, without switching to other surgical modalities, and without secondary surgery due to surgical complications after surgery. The secondary outcome was short-term functional and oncological outcomes. The noninferiority threshold was set at 10%. RESULTS AND LIMITATIONS: Eighty patients were enrolled, while the full analysis set finally included 79 patients (40 with KD-RARP and 39 with DV-RARP). The success rate was 100% in both groups. We could not find differences in urinary continence rate at 1, 2, 3, and 4 wk after catheter removal between the groups (p > 0.05). The rate of Clavien-Dindo grade II adverse events was 20% in the KD-RARP group and 17.9% in the DV-RARP group (p = 0.82), and no grade ≥III adverse events occurred. The median operation time was significantly longer in the KD-RARP group than in the DV-RARP group (177.5 vs 145 min, p = 0.012). The main limitations were the short follow-up period and that survival was not considered as the primary outcome. CONCLUSIONS: The KD-SR is a viable option for RARP, with acceptable short-term outcomes compared with the DV-SS-Si for T1-2 PCa. PATIENT SUMMARY: This is the first prospective randomized controlled trial to compare the KangDuo Surgical Robot (KD-SR) versus the da Vinci Si Surgical System (DV-SS-Si) for robot-assisted radical prostatectomy, which determines that the KD-SR is noninferior to the DV-SS-Si regarding safety and efficacy for T1-T2 prostate cancer.
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BACKGROUND: To evaluate the feasibility and safety of dual-console telesurgery with the new KangDuo system in an animal experiment and clinical study. METHODS: Six canine models were performed radical prostatectomy with dual-console KanDuo surgical robot-1500 (KD-SR-1500-RARP). The perioperative outcomes, physical and mental workload of the surgeon were collected. Physical workload was evaluated with surface electromyography. Mental workload was evaluated with NASA-TLX. After conducting animal experiments to verify safety of dual-console KD-SR-1500-RARP, we conducted the clinical trial using 5G and wired networks. RESULTS: In the animal experiment, all surgeries were performed successfully. The operative time was 80.2±32.1 min. The docking time was 2.4±0.5 min. The console time was 49.7±25.3 min. There were no perioperative complications or equipment related adverse events. All dogs can micturate after catheter removal at one week postoperatively. The mental workload was at a low level (a scale ranging from 0 to 60), which scored 15.7±6.9. Among the eight recorded muscles, the fatigue degree of the right radial flexor and left biceps was the highest two (iEMG, resection, 299.8±344 uV, 109.9±16.9 uV; suture, 849.4±1252.5 uV, 423.1±621.3 uV, respectively). In the clinical study, the console time was 136 min. The mean latency time was ≤200 ms. The data pocket loss was <1%. The operation was successfully completed without malfunctions occurring throughout the entire process. CONCLUSIONS: Dual-console telesurgery with the KD-SR-1500 system was shown to be feasible and safe in radical prostatectomy using 5G and wired networks.
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Estudios de Factibilidad , Prostatectomía , Procedimientos Quirúrgicos Robotizados , Animales , Perros , Procedimientos Quirúrgicos Robotizados/métodos , Procedimientos Quirúrgicos Robotizados/efectos adversos , Masculino , Prostatectomía/métodos , Prostatectomía/efectos adversos , Humanos , Persona de Mediana Edad , Diseño de Equipo , Tempo Operativo , Anciano , Electromiografía , Telemedicina/métodosRESUMEN
BACKGROUND: Cholesteryl ester (CE) accumulation in intracellular lipid droplets (LDs) is an essential signature of clear cell renal cell carcinoma (ccRCC), but its molecular mechanism and pathological significance remain elusive. METHODS: Enabled by the label-free Raman spectromicroscopy, which integrated stimulated Raman scattering microscopy with confocal Raman spectroscopy on the same platform, we quantitatively analyzed LD distribution and composition at the single cell level in intact ccRCC cell and tissue specimens in situ without any processing or exogenous labeling. Since we found that commonly used ccRCC cell lines actually did not show the CE-rich signature, primary cancer cells were isolated from human tissues to retain the lipid signature of ccRCC with CE level as high as the original tissue, which offers a preferable cell model for the study of cholesterol metabolism in ccRCC. Moreover, we established a patient-derived xenograft (PDX) mouse model that retained the CE-rich phenotype of human ccRCC. FINDINGS: Surprisingly, our results revealed that CE accumulation was induced by tumor suppressor VHL mutation, the most common mutation of ccRCC. Moreover, VHL mutation was found to promote CE accumulation by upregulating HIFα and subsequent PI3K/AKT/mTOR/SREBPs pathway. Inspiringly, inhibition of cholesterol esterification remarkably suppressed ccRCC aggressiveness in vitro and in vivo with negligible toxicity, through the reduced membrane cholesterol-mediated downregulations of integrin and MAPK signaling pathways. INTERPRETATION: Collectively, our study improves current understanding of the role of CE accumulation in ccRCC and opens up new opportunities for treatment. FUNDING: This work was supported by National Natural Science Foundation of China (No. U23B2046 and No. 62027824), National Key R&D Program of China (No. 2023YFC2415500), Fundamental Research Funds for the Central Universities (No. YWF-22-L-547), PKU-Baidu Fund (No. 2020BD033), Peking University First Hospital Scientific and Technological Achievement Transformation Incubation Guidance Fund (No. 2022CX02), and Beijing Municipal Health Commission (No. 2020-2Z-40713).
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Carcinoma de Células Renales , Ésteres del Colesterol , Neoplasias Renales , Mutación , Fosfatidilinositol 3-Quinasas , Proteínas Proto-Oncogénicas c-akt , Transducción de Señal , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau , Animales , Humanos , Ratones , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Ésteres del Colesterol/metabolismo , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Neoplasias Renales/metabolismo , Neoplasias Renales/genética , Neoplasias Renales/patología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/genética , Proteína Supresora de Tumores del Síndrome de Von Hippel-Lindau/metabolismoRESUMEN
Purpose: To investigate the feasibility, safety, and efficacy of the KangDuo-Surgical Robot-01 (KD-SR-01) system for robot-assisted radical nephroureterectomy (RARNU). Materials and Methods: This prospective, single-center, single-arm clinical study of patients with upper tract urothelial carcinoma (UTUC) was conducted from August 2022 to July 2023 using the KD-SR-01 system. The perioperative and follow-up data were prospectively recorded. The National Aeronautics and Space Administration task load index was calculated to present ergonomics. The technique was described in detail. Results: A total of 13 patients underwent RARNU. None of the cases conversed to laparoscopic procedure or open procedure. The median docking time and console time were 524 seconds (range 139-963 seconds) and 102.2 minutes (range 55.3-249.3 minutes), respectively. The median estimated blood loss was 40 mL (range 10-100 mL). None of the patients required intraoperative blood transfusion. The median postoperative hospital stay was 4 days (range 2-7 days). Intraoperative or postoperative complications (Clavien-Dindo grade I) occurred in nine patients. The surgeon task load index global score achieved 1.05 ± 1.86. Three patients received the single-docking technique, demonstrating similar perioperative results compared with patients with redocking. The study is registered at www.chictr.org.cn (ChiCTR2200056672). Conclusions: The KD-SR-01 system was feasible, safe, and effective for RARNU.
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Nefroureterectomía , Procedimientos Quirúrgicos Robotizados , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Masculino , Femenino , Estudios Prospectivos , Nefroureterectomía/métodos , Anciano , Persona de Mediana Edad , Estudios de Factibilidad , Resultado del Tratamiento , Complicaciones Posoperatorias/etiología , Tempo OperativoRESUMEN
INTRODUCTION: The aim of this study was to present the surgical technique and clinical outcomes of modified ileal conduit for pelvic lipomatosis (PL). METHODS: From 2020 to 2022, we prospectively enrolled 9 patients with PL undergoing modified ileal conduit. The patient characteristics, perioperative variables, and follow-up outcomes as well as the description of surgical technique were reported. RESULTS: All 9 patients successfully completed the operation. Two patients had perioperative complications of Clavien-Dindo grade I. The mean operation time and bleeding volumes were 253 ± 51.4 min and 238.9 ± 196.9 mL, with a mean postoperative follow-up time of 13.0 ± 5.6 months. The postoperative 3-month and 1-year creatinine values were significantly decreased versus the preoperative (p = 0.006 and p = 0.024). The postoperative 3-month and 1-year estimated glomerular filtration rate values were significantly increased compared with those before operation (p = 0.0002 and p = 0.018). The separation value of left renal pelvis collection system after operation was significantly reduced compared with preoperative evaluation (p = 0.023 at 3 months and p = 0.042 at 1 year) and so was the right side (p = 0.019 and p = 0.023). CONCLUSION: Modified ileal conduit is safe and feasible for PL. A large sample cohort with long-term follow-up is needed to evaluate the clinical outcomes of PL.
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Lipomatosis , Derivación Urinaria , Humanos , Masculino , Persona de Mediana Edad , Femenino , Resultado del Tratamiento , Estudios Prospectivos , Derivación Urinaria/métodos , Lipomatosis/cirugía , Adulto , Anciano , Enfermedades de la Vejiga UrinariaRESUMEN
OBJECTIVE: Real-word data on long-acting luteinizing hormone-releasing hormone (LHRH) agonists in Chinese patients with prostate cancer are limited. This study aimed to determine the real-world effectiveness and safety of the LHRH agonist, goserelin, particularly the long-acting 10.8-mg depot formulation, and the follow-up patterns among Chinese prostate cancer patients. METHODS: This was a multicenter, prospective, observational study in hormone treatment-naïve patients with localized or locally advanced prostate cancer who were prescribed goserelin 10.8-mg depot every 12 weeks or 3.6-mg depot every 4 weeks with or without an anti-androgen. The patients had follow-up evaluations for 26 weeks. The primary outcome was the effectiveness of goserelin in reducing serum testosterone and prostate-specific antigen (PSA) levels. The secondary outcomes included testosterone and PSA levels, attainment of chemical castration (serum testosterone <50 ng/dL), and goserelin safety. The exploratory outcome was the monitoring pattern for serum testosterone and PSA. All analyses were descriptive. RESULTS: Between September 2017 and December 2019, a total of 294 eligible patients received ≥ 1 dose of goserelin; 287 patients (97.6%) were treated with goserelin 10.8-mg depot. At week 24 ± 2, the changes from baseline [standard deviation (95% confidence interval)] in serum testosterone (n = 99) and PSA (n = 131) were -401.0 ng/dL [308.4 ng/dL (-462.5, -339.5 ng/dL)] and -35.4 ng/mL [104.4 ng/mL (-53.5, -17.4 ng/mL)], respectively. Of 112 evaluable patients, 100 (90.2%) achieved a serum testosterone level < 50 ng/dL. Treatment-emergent adverse events (TEAEs) and severe TEAEs occurred in 37.1% and 10.2% of patients, respectively. The mean testing frequency (standard deviation) was 1.6 (1.5) for testosterone and 2.2 (1.6) for PSA. CONCLUSIONS: Goserelin 10.8-mg depot effectively achieved and maintained castration and was well-tolerated in Chinese patients with localized and locally advanced prostate cancer.
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Goserelina , Neoplasias de la Próstata , Masculino , Humanos , Goserelina/efectos adversos , Antígeno Prostático Específico/uso terapéutico , Antineoplásicos Hormonales/efectos adversos , Estudios Prospectivos , Neoplasias de la Próstata/tratamiento farmacológico , Testosterona/uso terapéutico , ChinaRESUMEN
OBJECTIVE: To probe the microbiota composition progressing from healthy individuals to those with laryngopharyngeal reflux disease (LPRD) and subsequently undergoing potassium-competitive acid inhibitor (P-CAB) therapy. STUDY DESIGN: Prospective case-control study. SETTING: Academic Medical Center. METHODS: Forty patients with LPRD and 51 patients without LPRD were recruited. An 8-week P-CAB therapy was initiated (post-T-LPRD), and 39 had return visits. In total, 130 laryngopharyngeal saliva samples were collected and sequenced by targeting the V3-V4 region of the 16S ribosomal RNA (rRNA) gene using an Illumina MiSeq. Amplicon sequence variants (ASVs) and clinical indices were analyzed. RESULTS: Alpha and beta diversities were compared among the non-LPRD, LPRD, and post-T-LPRD groups, and the Observed_ASVs were not significantly different. At the same time, the Shannon and Simpson indices, unweighted Unifrac, weighted Unifrac, and binary Jaccard distance were significantly different between non-LPRD and LPRD groups. In addition, significant differences were found in the abundance of Streptococcus, Prevotella, and Prevotellaceae in the LPRD versus non-LPRD groups, and Neisseria, Leptotrichia, and Allprevotella in the LPRD versus post-T-LPRD groups. The genera model was used to distinguish patients with LPRD from those without, and a better receiver operating characteristic curve was formed after combining the clinical indices of reflux symptom index, reflux finding score, and pepsin, with an area under the curve of 0.960. CONCLUSION: Laryngopharyngeal microbial communities changed after laryngopharyngeal reflux and were modified further after P-CAB treatment, which provides a potential diagnostic value for LPRD, especially when combined with clinical indices.
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Reflujo Laringofaríngeo , Humanos , Reflujo Laringofaríngeo/tratamiento farmacológico , Reflujo Laringofaríngeo/microbiología , Reflujo Laringofaríngeo/diagnóstico , Masculino , Femenino , Estudios Prospectivos , Estudios de Casos y Controles , Persona de Mediana Edad , Inhibidores de la Bomba de Protones/uso terapéutico , Adulto , Faringe/microbiología , Microbiota , Saliva/microbiología , AncianoRESUMEN
Laryngopharyngeal reflux disease (LPRD) is a condition characterized by the regurgitation of stomach and duodenal contents into the laryngopharynx, with variable and non-specific symptoms. Therefore, developing an accurate symptom scale for different regions is essential. Notably, the symptoms of "dryness and burning sensation in the laryngopharynx or mouth" are prevalent among the Chinese population but are often omitted from conventional symptom assessment scales, such as the Reflux Symptom Index (RSI) and Reflux Symptom Score-12 (RSS-12) scales. To address this gap, our study incorporated the symptoms into the RSI and RSS-12 scales, developing the RSI-10/RSS-13 scales. Afterward, we assessed the role of the new scale's reliability (Cronbach's α and test-retest reliability), construct validity (confirmatory factor analysis and confirmatory factor analysis), and diagnostic efficiency. Our study encompassed 479 participants (average = 39.5 ± 13.4 years, 242 female) and 91 (average = 34.01 ± 13.50 years, 44 female) completed 24 h MII-pH monitoring. The Cronbach's α values of 0.80 and 0.82 for the RSI-10 and RSS-13 scales, respectively. RSI-10 and RSS-13 exhibited strong test-retest reliability (ICCs = 0.82-0.96) and diagnostic efficacy (AUC = 0.84-0.85). Furthermore, the factor analysis identified the RSS-13 and its three sub-scales (ear-nose-throat, digestive tract, respiratory tract) exhibited good to excellent structural validity (χ2/df = 1.95, P < 0.01; CFI = 0.95, RMSEA = 0.06, SRMR = 0.05). The AUC optimal thresholds for the RSI-10 and RSS-13 in the Chinese population were 13 and 36, respectively. Besides, the inclusion of the new item significantly improved the diagnostic efficiency of the RSI scale (P = 0.04), suggesting that RSI-10 holds promise as a more effective screening tool for LPRD, and global validation is needed to demonstrate the impact of this new symptom on the diagnosis of LPRD.
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Reflujo Laringofaríngeo , Humanos , Femenino , Reflujo Laringofaríngeo/diagnóstico , Reproducibilidad de los Resultados , Hipofaringe , SensaciónAsunto(s)
Recurrencia , Stents , Uréter , Humanos , Stents/efectos adversos , Uréter/cirugía , Constricción Patológica/etiología , Masculino , Obstrucción Ureteral/etiología , Obstrucción Ureteral/cirugía , Persona de Mediana Edad , Femenino , Anciano , Adulto , Complicaciones Posoperatorias/etiología , Procedimientos de Cirugía Plástica/métodosAsunto(s)
Imagenología Tridimensional , Laparoscopía , Uréter Retrocavo , Procedimientos Quirúrgicos Robotizados , Uréter , Humanos , Procedimientos Quirúrgicos Robotizados/métodos , Laparoscopía/métodos , Uréter/cirugía , Uréter Retrocavo/cirugía , Resultado del Tratamiento , Masculino , Femenino , Procedimientos Quirúrgicos Urológicos/métodos , Persona de Mediana Edad , AdultoRESUMEN
OBJECTIVE: To evaluate objective treatment efficacy and safety, and subjective patient-reported outcomes in patients with complex ureteral strictures (US) undergoing minimally invasive lingual mucosal graft ureteroplasty (LMGU). MATERIALS AND METHODS: We prospectively enrolled patients underwent robotic or laparoscopic LMGU between May 2020 and July 2022. Clinical success was defined as symptom-free and no radiographic evidence of re-obstruction. Patient-reported outcomes, including health-related quality of life (HRQoL), mental health status and oral health-related quality of life (OHRQoL), were longitudinally evaluated before surgery, 6 and 12 months postoperatively. RESULTS: Overall, 41 consecutive patients were included. All procedures were performed successfully with 32 patients in robotic approach and 9 in laparoscopic. Forty (97.56%) patients achieved clinical success during the median follow-up of 29 (range 15-41) months. Although patients with complex US experienced poor baseline HRQoL, there was a remarkable improvement following LMGU. Specifically, the 6-month and 12-month postoperative scores were significantly improved compared to the baseline (p < 0.05) in most domains. Twenty-eight (68.3%) and 31 (75.6%) patients had anxiety and depression symptoms before surgery, respectively. However, no significant decrease in the incidence of these symptoms was observed postoperatively. Moreover, there was no significant deterioration of OHRQoL at 6 months and 12 months postoperatively when compared to the baseline. CONCLUSIONS: LMGU is a safe and efficient procedure for complex ureteral reconstruction that significantly improves patient-reported HRQoL without compromising OHRQoL. Assessing patients' quality of life enables us to monitor postoperative recovery and progress, which should be considered as one of the criteria for surgical success.
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Procedimientos Quirúrgicos Robotizados , Uréter , Obstrucción Ureteral , Humanos , Constricción Patológica/cirugía , Calidad de Vida , Uréter/cirugía , Obstrucción Ureteral/cirugía , Resultado del Tratamiento , Procedimientos Quirúrgicos Robotizados/métodos , Estudios RetrospectivosRESUMEN
Several clinical studies observed a surprising beneficial effect of obesity on enhancing immunotherapy responsiveness in patients with melanoma, highlighting an as-yet insufficiently understood relationship between metabolism and immunogenicity. Here, we demonstrate that the thiazolidinedione (TZD) rosiglitazone, a drug commonly used to treat diabetes by sequestering fatty acids in metabolically inert subcutaneous adipose tissue, improved sensitivity to anti-programmed cell death protein 1 (PD-1) treatment in YUMMER1.7 tumor-bearing mice, an initially immunotherapy-sensitive murine melanoma model. We observed a transition from high to intermediate PD-1 expression in tumor-infiltrating CD8+ T cells. Moreover, TZD inhibited PD-1 expression in mouse and human T cells treated in vitro. In addition to its direct impact on immune cells, TZD also decreased circulating insulin concentrations, while insulin induced T cell exhaustion in culture. In TZD-treated mice, we observed higher fatty acid concentrations in the tumor microenvironment, with fatty acids protecting against exhaustion in culture. Together, these data are consistent with an indirect mechanism of TZD inhibiting T cell exhaustion. Finally, we analyzed imaging data from patients with melanoma before and after anti-PD-1 treatment, confirming the beneficial effect of increased subcutaneous fat on anti-PD-1 responsiveness in patients. We also found that the expression of peroxisome proliferator-activated receptor gamma (PPARγ), the canonical activator of lipid uptake and adipogenesis activated by TZD, correlated with overall survival time. Taken together, these data identify a new adjuvant to enhance immunotherapy efficacy in YUMMER1.7 melanoma mice, and discover a new metabolism-based prognostic marker in human melanoma.NEW & NOTEWORTHY Zhang et al. demonstrate that the diabetes drug rosiglitazone improves the efficacy of immunotherapy in mouse melanoma. This effect is both direct and indirect: TZD directly reduces PD-1 expression in CD8+ T cells (i.e., reduces exhaustion), and indirectly reduces exhaustion by lowering insulin levels and increasing local fat. Finally, they demonstrate that hallmarks of TZD action (such as PPARγ expression and subcutaneous fat content) correlate with improved immunotherapy efficacy in humans with melanoma.
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Diabetes Mellitus , Melanoma , Tiazolidinedionas , Humanos , Animales , Ratones , Melanoma/tratamiento farmacológico , Rosiglitazona , Receptor de Muerte Celular Programada 1 , PPAR gamma , Tiazolidinedionas/farmacología , Tiazolidinedionas/uso terapéutico , Anticuerpos Monoclonales , Insulina , Ácidos Grasos , Microambiente TumoralRESUMEN
The objective of this study is to explore the safety and effectiveness of two new models of KangDuo surgical robots for partial nephrectomy in porcine models, and evaluate the ergonomic characteristics from both subjective and objective perspectives. Twelve porcine models were equally divided for KD-SR-1500 (three-arm) and KD-SR-2000 (four-arm). The perioperative outcomes, and physical and mental workload of the surgeon were compared. Physical workload was evaluated with surface electromyography. Mental workload was evaluated with NASA-TLX. All surgeries were performed successfully. There were no differences in perioperative variables (p > 0.05). There were no perioperative complications. The mental workload in both groups was at a low level. KD-SR-2000 showed advantages in physical workload (p < 0.01). KD-SR-1500 and KD-SR-2000 are technically feasible, valid, and safe for RAPN in porcine models. KD-SR-2000 had ergonomic advantages over KD-SR-1500.