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Despite many clinical trials, CAR-T cells are not yet approved for human solid tumor therapy. One popular target is mesothelin (MSLN) which is highly expressed on the surface of about 30% of cancers including mesothelioma and cancers of the ovary, pancreas, and lung. MSLN is shed by proteases that cleave near the C terminus, leaving a short peptide attached to the cell. Most anti-MSLN antibodies bind to shed MSLN, which can prevent their binding to target cells. To overcome this limitation, we developed an antibody (15B6) that binds next to the membrane at the protease-sensitive region, does not bind to shed MSLN, and makes CAR-T cells that have much higher anti-tumor activity than a CAR-T that binds to shed MSLN. We have now humanized the Fv (h15B6), so the CAR-T can be used to treat patients and show that h15B6 CAR-T produces complete regressions in a hard-to-treat pancreatic cancer patient derived xenograft model, whereas CAR-T targeting a shed epitope (SS1) have no anti-tumor activity. In these pancreatic cancers, the h15B6 CAR-T replicates and replaces the cancer cells, whereas there are no CAR-T cells in the tumors receiving SS1 CAR-T. To determine the mechanism accounting for high activity, we used an OVCAR-8 intraperitoneal model to show that poorly active SS1-CAR-T cells are bound to shed MSLN, whereas highly active h15B6 CAR-T do not contain bound MSLN enabling them to bind to and kill cancer cells.
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Neoplasias Pancreáticas , Receptores Quiméricos de Antígenos , Femenino , Humanos , Línea Celular Tumoral , Proteínas Ligadas a GPI/metabolismo , Mesotelina , Neoplasias Pancreáticas/tratamiento farmacológico , Linfocitos T/metabolismoRESUMEN
C-phycocyanin (C-PC) is the main component of water-soluble light-harvesting complexes (phycobilisomes, PBS) of cyanobacteria. PBS are involved in the absorption of quantum energy and the transfer of electronic excitation energy to the photosystems. A specific environment of C-PC chromophoric groups is provided by the protein matrix structure including protein-protein contacts between different subunits. Registration of C-PC spectral characteristics and the fluorescence anisotropy decay have revealed a significant pH influence on the chromophore microenvironment: at pH 5.0, a chromophore is more significantly interacts with the solvent, whereas at pH 9.0 the chromophore microenvironment becomes more viscous. Conformations of chromophores and the C-PC protein matrix have been studied by Raman and infrared spectroscopy. A decrease in the medium pH results in changes in the secondary structure either the C-PC apoproteins and chromophores, the last one adopts a more folded conformation.
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Proteínas Bacterianas , Complejos de Proteína Captadores de Luz , Ficocianina , Spirulina , Ficocianina/química , Concentración de Iones de Hidrógeno , Polarización de Fluorescencia , Espectrometría Raman , Espectrofotometría Infrarroja , Estructura Secundaria de Proteína , Complejos de Proteína Captadores de Luz/química , Pliegue de Proteína , Spirulina/enzimología , Proteínas Bacterianas/químicaRESUMEN
AIM: To compare the proportion of participants with type 2 diabetes (T2D) treated with once-weekly (OW) subcutaneous (SC) semaglutide versus comparators who achieved a composite metabolic endpoint. MATERIALS AND METHODS: SUSTAIN 1-5, 7-10 and SUSTAIN China trial data were pooled. Participants with T2D (aged ≥18 years) and glycated haemoglobin ≥7.0% (≥53 mmol/mol) who had been randomized to OW SC semaglutide (0.5 or 1.0 mg) or comparator in addition to background medication. Using patient-level data pooled by treatment, proportions of participants achieving the metabolic composite endpoint, defined as glycated haemoglobin <7% (<53 mmol/mol), blood pressure <140/90 mmHg and non-high-density lipoprotein cholesterol <130 mg/dl (<3.37 mmol/L), were evaluated following baseline adjustments. Endpoints were analysed per trial using a binomial logistic regression model with treatment, region/country and stratification factor as fixed effects and baseline value as covariate. Pooled analysis used logistic regression with treatment and trial as fixed effects and baseline value as covariate. RESULTS: This post hoc analysis included data from 7633 participants across 10 trials. The proportion of participants who achieved the metabolic composite endpoint was significantly higher with OW SC semaglutide 0.5 and 1.0 mg versus comparators (23.7% and 32.0% vs. 11.5%, respectively; p < .0001). Likewise, when the OW SC semaglutide doses were pooled, significantly higher proportions of patients receiving semaglutide achieved the composite metabolic endpoint versus comparators (29.1% vs. 11.4%, respectively; p < .0001). CONCLUSIONS: Treatment with OW SC semaglutide versus comparators was associated with increased proportions of participants with T2D meeting the composite metabolic endpoint.
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Diabetes Mellitus Tipo 2 , Humanos , Adolescente , Adulto , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Hipoglucemiantes/uso terapéutico , Hemoglobina Glucada , Péptidos Similares al Glucagón/efectos adversos , China/epidemiologíaRESUMEN
AIM: To develop an aggregate model that integrated clinical data, habitat characteristics, and intratumoral and peritumoral features to assess the risk categorization of thymomas. MATERIALS AND METHODS: We retrospectively analyzed 140 thymoma patients (70 low-risk and 70 high-risk), including pathological data. The patients were randomly divided into training cohort (n = 114) and test cohort (n = 26). The k-means clustering was utilized to partition the primary tumor into habitats based on intratumoral radiomic features, 6 distinct habitats were identified. By expanding the region of interest (ROI) mask, 2 peritumoral regions were obtained. Finally, 7 clinical characteristics, 3 habitat values, 20 radiomic features were utilized to develop an aggregated model, to predict the risk of thymoma. Shapley additive explanations (SHAP) interpretation was used for features importance ranking. The accuracy and area under curve (AUC) were used to analyze the performance of the models. RESULTS: The aggregated model, which utilized the XGBoost classifier, demonstrated the best performance with an AUC of 0.811 and an accuracy of 0.769. In comparison, the radiomic model produced an AUC of 0.654 and an accuracy of 0.692. Additionally, the Intratumoral + peritumoral model exhibited an AUC of 0.728 and an accuracy of 0.769. CONCLUSION: Our study establishes a novel tool to predict the risk of thymoma with a good performance. If prospectively validated, the model may refine thymoma patient selection for risk-adaptative therapy and improve prognosis.
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Timoma , Neoplasias del Timo , Humanos , Masculino , Femenino , Neoplasias del Timo/diagnóstico por imagen , Timoma/diagnóstico por imagen , Persona de Mediana Edad , Estudios Retrospectivos , Medición de Riesgo , Adulto , Anciano , Tomografía Computarizada por Rayos X/métodosRESUMEN
AIMS: To detect the acute myocardial injury in fulminant myocarditis (FM) survivors after extracorporeal membrane oxygenation (ECMO) and to demonstrate its significant differences from non-FM patients by cardiac magnetic resonance (CMR). MATERIALS AND METHODS: This retrospective study enrolled 59 patients with acute myocarditis (AM), including 35 non-FM patients, 24 FM patients, and 54 controls. The peak value of cardiac troponin T (cTnT) was recorded. Tissue parameters, including native T1, extracellular volume (ECV), late gadolinium-enhancement (LGE)%, and T2 by CMR were assessed. RESULTS: The mean age was 35 ± 14 years, and 45.8% of the population were males in the AM group. Patients had higher levels of peak cTnT, peak NT-proBNP and peak C-reactive protein in the FM group (all p<0.05). Comparing with non-FM, the values of T1-based imaging parameters were significantly higher in the FM group (all p<0.05). In contrast, no difference was observed among the two groups in terms of T2 value (p=0.707). The septal area was more frequently involved in FM survivors after ECMO treatment, both in T1 and T2-based images. In addition, the cubic relationship was the relative best fit of LGE% against logcTnT and indicated that cTnT value exceeding 300ng/L exhibited a rapid upward trend of LGE%. CONCLUSION: Comparing to non-FM, higher myocardial necrosis and fibrosis but similar edema determined by T1 and T2 based imaging was found in FM survivors after ECMO treatment. Furthermore, the inter-ventricular septal area was more frequently involved by acute myocardial injury in FM survivors after ECMO treatment. In addition, LGE% showed an overall increasing trend with cTnT values elevating with rapidly increasing with cTnT exceeding 300 ng/L.
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Oxigenación por Membrana Extracorpórea , Imagen por Resonancia Magnética , Miocarditis , Humanos , Masculino , Oxigenación por Membrana Extracorpórea/métodos , Miocarditis/diagnóstico por imagen , Miocarditis/terapia , Adulto , Femenino , Estudios Retrospectivos , Imagen por Resonancia Magnética/métodos , Sobrevivientes , Persona de Mediana Edad , Enfermedad Aguda , Medios de Contraste , Miocardio/patologíaRESUMEN
AIM: To explore the predictive value of morphological signs and quantitative parameters from spectral CT for EGFR gene mutations in intermediate and advanced non-small-cell lung cancer (NSCLC). MATERIALS AND METHODS: This retrospective observational study included patients with intermediate or advanced NSCLC at Xinjiang Medical University Affiliated Tumor Hospital between January 2017 and December 2019. The patients were divided into the EGFR gene mutation-positive and -negative groups. RESULTS: Seventy-nine patients aged 60.75 ± 9.66 years old were included: 32 were EGFR mutation-positive, and 47 were negative. There were significant differences in pathological stage (P<0.001), tumor diameter (P=0.019), lobulation sign, intrapulmonary metastasis, mediastinal lymph node metastasis, distant metastasis (P<0.001), bone metastasis (P<0.001), arterial phase normalized iodine concentration (NIC) (P=0.001), venous phase NIC (P=0.001), slope of the energy spectrum curve (λ) (P<0.001), and CT value at 70 keV in arterial phase (P=0.004) and venous phase (P=0.003) between the EGFR mutation-positive and -negative patients. The multivariable logistic regression analysis showed that intrapulmonary metastasis, distant metastasis, venous phase NIC, venous phase λ, and pathological stage were independent factors predicting EGFR gene mutations, with high diagnostic power (AUC = 0.975, 91.5% sensitivity, and 90.6% specificity). CONCLUSION: The pathological stage and the spectral CT parameters of intrapulmonary metastasis, distant metastasis, venous phase NIC, and venous phase λ might pre-operatively predict EGFR gene mutations in intermediate and advanced NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Neoplasias Pulmonares , Mutación , Valor Predictivo de las Pruebas , Tomografía Computarizada por Rayos X , Humanos , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico por imagen , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/diagnóstico por imagen , Neoplasias Pulmonares/patología , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Receptores ErbB/genética , Tomografía Computarizada por Rayos X/métodos , Anciano , Pulmón/diagnóstico por imagen , Pulmón/patologíaRESUMEN
AIM: To evaluate the diagnostic value of adenohypophyseal magnetic resonance imaging (MRI) features for precocious puberty (PP) in female children and also to establish a non-invasive diagnostic approach in clinics. MATERIALS AND METHODS: A total of 126 female children (37, 57, and 32 female children clinically diagnosed with central PP [CPP], incomplete PP [IPP], and controls, respectively) were enrolled in this study. Data were collected and analysed using analysis of variance. Pearson correlation and stepwise multivariate linear regression analysis were used to examine the association and build prediction models. Receiver operating characteristic (ROC) analysis was used to evaluate the diagnostic efficacy. RESULTS: The values of adenohypophysis volume (aPV), adenohypophysis height (aPH), and signal-intensity ratio (SIR), height, weight, and seven laboratory testing characteristics were correlated closely with the activation status of the hypothalamic-pituitary-gonad axis in the different groups (all p<0.05). Model 1 including aPV, weight, and aPH and Model 2 including SIR, aPV, and height were built to obtain predicted luteinising hormone (LH; R2 = 0.271) and LH/follicle stimulating hormone (FSH; R2 = 0.311). ROC analysis showed the predicted LH, predicted LH/FSH, and aPV were the top 3 best predictors in distinguishing CPP from controls (AUC = 0.969, 0.949, and 0.938) while predicted LH/FSH was the best predictor in distinguishing CPP from IPP and controls (AUC = 0.829 and 0.828). CONCLUSION: The adenohypophysis volume itself and the prediction models including main adenohypophyseal MRI features increased diagnostic efficiency for PP and offered a non-invasive and credible diagnostic method.
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Adenohipófisis , Pubertad Precoz , Niño , Femenino , Humanos , Pubertad Precoz/diagnóstico por imagen , Hormona Luteinizante , Hormona Folículo Estimulante , Imagen por Resonancia Magnética , Adenohipófisis/diagnóstico por imagenRESUMEN
BACKGROUND: Resection and strictureplasty are the two surgical modalities used in the management of Crohn's disease (CD). The objective of this study was to compare morbidity and clinical recurrence between patients who underwent strictureplasty and patients who underwent resection. METHODS: Patients with CD who underwent strictureplasty between January 2012 and December 2022 were enrolled. The patients were well matched with patients who underwent resection without strictureplasty. Patient- and disease-specific characteristics, postoperative morbidity, and clinical recurrence were also analyzed. RESULTS: A total of 118 patients who underwent a total of 192 strictureplasties were well matched to 118 patients who underwent resection. The strictureplasty group exhibited significantly less blood loss (30 ml versus 50 ml, p < 0.001) and stoma creation (2.5% versus 16.9%, p < 0.001). No significant difference was found regarding postoperative complications or length of postoperative stay. At the end of the follow-up, the overall rate of clinical recurrence was 39.4%, and no difference was observed between the two groups. Postoperative prophylactic use of biologics (odds ratio = 0.2, p < 0.001) was the only protective factor against recurrence. CONCLUSION: Strictureplasty does not increase the risk of complications or recurrence compared with resection. It represents a viable alternative to resection in selected patients, and as such, it should have a broader scope of indications and greater acceptance among surgeons.
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Enfermedad de Crohn , Humanos , Enfermedad de Crohn/cirugía , Enfermedad de Crohn/complicaciones , Recurrencia , Reoperación , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/cirugía , Resultado del TratamientoRESUMEN
Soft tissue sarcoma (STS) is a group of rare malignant tumors originating from mesenchymal tissue, with a high degree of malignancy and a wide range of pathological subtypes. The prognosis varies among different subtypes, and treatment increasingly relies on selecting appropriate treatment methods for different subtypes. Surgical treatment is still the main treatment method at present, and the development of immune and targeted therapy also brings new hope for the treatment of soft tissue sarcoma. Immune checkpoint inhibitors, oncolytic viruses and T cell therapy have shown well safety and efficacy in clinical trials. Targeted drugs such as trabectedin and lenvatinib have changed the treatment pattern of soft tissue sarcoma. Currently, chemotherapy based on doxorubicin and ifosfamide is still the first line treatment for patients with advanced soft tissue sarcoma who have distant metastasis. However, the adverse reactions of doxorubicin limit its application in elderly patients, and trofosfamide has shown good efficacy and safety as an alternative in clinical trials. The efficacy of postoperative radiotherapy has been confirmed, which can reduce the local recurrence rate after surgical resection of soft tissue sarcoma. In summary, multimodal comprehensive treatment has become the main strategy for the treatment of soft tissue sarcoma. The combination of different treatment methods can generate synergistic effects and help patients obtain more clinical benefits, such as the combination of doxorubicin and immune checkpoint inhibitors, and the combination of antiangiogenic drugs and chemotherapy drugs. At the 2023 annual meeting of the American Society of Clinical Oncology (ASCO), oncologists from all over the world reported many researches related to the treatment of soft tissue sarcoma. This article aims to review the new progress in the treatment of soft tissue sarcoma in the 2023 annual meeting of ASCO.
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Sarcoma , Neoplasias de los Tejidos Blandos , Anciano , Humanos , Estados Unidos , Inhibidores de Puntos de Control Inmunológico , Sarcoma/tratamiento farmacológico , Neoplasias de los Tejidos Blandos/tratamiento farmacológico , Doxorrubicina/uso terapéutico , Oncología MédicaRESUMEN
Objective: To analyze the prognostic factors and the influence of surgical margin to prognosis. Methods: A retrospective analysis was performed for 208 pelvic tumors who received surgical treatment from January 2000 to December 2017 in our instituition. Survival analysis was performed using the Kaplan-Meier method and Log rank test, and impact factor analysis was performed using Cox regression models. Results: There were 183 initial patients and 25 recurrent cases. According to Enneking staging, 110 cases were stage â B and 98 cases were stage â ¡B. 19 lesions were in zone â , 1 in zone â ¡, 15 in zone â ¢, 29 in zone â +â ¡, 71 in zone â ¡+â ¢, 29 in zone â +â £, 35 in zone â +â ¡+â ¢, 3 in zone â +â ¡+â £, and 6 in zone â +â ¡+â ¢+â £. Surgical margins including Intralesional excision in 7 cases, contaminated margin in 21 cases, marginal resection in 67 cases, and wide resection in 113 cases. Local recurrence occurred in 37 cases (17.8%), 25 cases were performed by reoperation and 12 cases received amputation finally. The 5-year recurrence rate of marginal resection was higher than wide resection (Pï¼0.05), and the recurrence-free survival rate of marginal resection was lower than wide resection (Pï¼0.05). There was significant differences in recurrence rate and recurrence-free survival rate between R0 and R1 resection (Pï¼0.05). 92 cases were not reconstructed and 116 cases were reconstructed after pelvic surgery. At the last follow-up, 63 patients (30.3%) died, and the 5-year, 10-year and 15-year survival rates were 70.4%, 66.8% and 61.3%, respectively. The 5-year survival rate of stage â B and â ¡B tumor was 90.4% and 46.8%, respectively. There were 29 cases had postoperative wound complications (13.8%), 1 case with pelvic organ injury. The final function was evaluated in 132 patients, with an average MSTS score of 25.1±3.6. Cox multivariate analysis showed that surgical staging, R0/R1 margin and metastasis were independent prognostic factors for pelvic tumors. Conclusions: The safe surgical margin is the key factor for recurrence-free of pelvic tumor. The survival rate of stage â ¡B pelvic tumors was significantly lower than that of stage â B tumors. Wound infection is the main postoperative complication. Surgical staging, R0/R1 margin and metastasis were independent prognostic factors of pelvic tumors.
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Neoplasias Óseas , Márgenes de Escisión , Recurrencia Local de Neoplasia , Huesos Pélvicos , Humanos , Estudios Retrospectivos , Huesos Pélvicos/cirugía , Neoplasias Óseas/cirugía , Pronóstico , Tasa de Supervivencia , Estadificación de Neoplasias , Modelos de Riesgos Proporcionales , Femenino , Reoperación , Masculino , Neoplasias Pélvicas/cirugía , Neoplasias Pélvicas/patologíaRESUMEN
Objectives: To assess the prognostic impact of the neoadjuvant rectal (NAR) score following neoadjuvant short-course radiotherapy and consolidation chemotherapy in locally advanced rectal cancer (LARC), as well as its value in guiding decisions for adjuvant chemotherapy. Methods: Between August 2015 and August 2018, patients were eligible from the STELLAR phase III trial (NCT02533271) who received short-course radiotherapy plus consolidation chemotherapy and for whom the NAR score could be calculated. Based on the NAR score, patients were categorized into low (ï¼8), intermediate (8-16), and high (ï¼16) groups. The Kaplan-Meier method, log rank tests, and multivariate Cox proportional hazard regression models were used to evaluate the impact of the NAR score on disease-free survival (DFS). Results: Out of the 232 patients, 24.1%, 48.7%, and 27.2% had low (56 cases), intermediate (113 cases), and high NAR scores (63 cases), respectively. The median follow-up period was 37 months, with 3-year DFS rates of 87.3%, 68.3%, and 53.4% (Pï¼0.001) for the low, intermediate, and high NAR score groups. Multivariate analysis demonstrated that the NAR score (intermediate NAR score: HR, 3.10, 95% CI, 1.30-7.37, P=0.011; high NAR scores: HR=5.44, 95% CI, 2.26-13.09, Pï¼0.001), resection status (HR, 3.00, 95% CI, 1.64-5.52, Pï¼0.001), and adjuvant chemotherapy (HR, 3.25, 95% CI, 2.01-5.27, Pï¼0.001) were independent prognostic factors for DFS. In patients with R0 resection, the 3-year DFS rates were 97.8% and 78.0% for those with low and intermediate NAR scores who received adjuvant chemotherapy, significantly higher than the 43.2% and 50.6% for those who did not (Pï¼0.001, P=0.002). There was no significant difference in the 3-year DFS rate (54.2% vs 53.3%, P=0.214) among high NAR score patients, regardless of adjuvant chemotherapy. Conclusions: The NAR score is a robust prognostic indicator in LARC following neoadjuvant short-course radiotherapy and consolidation chemotherapy, with potential implications for subsequent decisions regarding adjuvant chemotherapy. These findings warrant further validation in studies with larger sample sizes.
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Quimioterapia de Consolidación , Terapia Neoadyuvante , Neoplasias del Recto , Humanos , Neoplasias del Recto/patología , Neoplasias del Recto/terapia , Quimioterapia Adyuvante , Pronóstico , Supervivencia sin Enfermedad , Modelos de Riesgos Proporcionales , Masculino , Femenino , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Persona de Mediana Edad , Tasa de Supervivencia , RectoRESUMEN
The study aims to summarize the clinical characteristics of patients with ectopic gastric mucosa in the small intestine, comparing clinical presentation differences between domestic and foreign patients through literature review. The clinical characteristics of cases diagnosed with ectopic gastric mucosa in the small intestine at Peking Union Medical College Hospital from January 2000 to January 2024 were retrospectively analyzed. By searching databanks, such as PubMed, EMBASE, the Cochrane Library, Wanfang, VIP, CNKI, and etc (the inclusion period was from the establishment of the database to January 1, 2024). The literature review was conducted on ectopic gastric mucosa in the small intestine. A total of 10 cases were included, all male, age [M (Q1, Q3)] was 27 (13-69) years old. Gastrointestinal bleeding was the first manifestation in most cases, with severe cases leading to hemorrhagic shock. Abdominal CT indicated local intestinal wall thickening and luminal narrowing in 3 cases. Four cases lesions were located at the beginning of the jejunum and 6 lesions were located in the end segment of ileum. All cases underwent local lesion resection, with postoperative pathology confirming ectopic gastric mucosa. Symptoms disappeared postoperatively, with a follow-up period of 0.5-3.0 years. Literature review indicates that the main clinical manifestation of gastric mucosa ectopia in the small intestine in China is gastrointestinal bleeding, while foreign patients are often complicated with intestinal duplication and intussusception, with abdominal pain and vomiting as the primary and main symptoms. The occurrence rate of intestinal obstruction in female patients, both domestically and abroad, is higher than that in male patients. The occurrence rate of ileal lesions with intestinal obstruction and small intestinal duplication is higher than that of duodenal lesions in both domestic and foreign patients. Local small intestine resection is an effective treatment method with generally good prognosis. Ectopic small intestinal mucosa is relatively rare, with symptoms of gastrointestinal bleeding and intestinal obstruction being common presentations, which can serve as one of the differential diagnoses for unexplained gastrointestinal bleeding.
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Coristoma , Mucosa Gástrica , Hemorragia Gastrointestinal , Intestino Delgado , Humanos , Mucosa Gástrica/patología , Masculino , Adulto , Persona de Mediana Edad , Adolescente , Anciano , Hemorragia Gastrointestinal/etiología , Adulto Joven , Estudios Retrospectivos , Femenino , ChinaRESUMEN
Objective: To evaluate the prevalence, intervention methods and effect of arteriovenous graft (AVG) stenosis. Methods: The clinical data of patients who received AVG in the Blood Purification Center, the First Affiliated Hospital of Zhengzhou University from January 2018 to December 2022 were retrospectively analyzed. The patency rate, prevalence and intervention effect of AVG stenosis were analyzed. Results: A total of 475 patients aged (55.5±11.8) years were included, and there were 193 male cases (40.6%) and 282 female cases (59.4%). The patients were followed up for [M (Q1, Q3)] 19 (12, 30) months, and the primary, assisted primary and secondary patency were 14 (5, 27), 27 (13, 55), and 59 (33, 65) months, respectively. There were 799 access events which needed intervention, with a total standardized intervention rate of 0.90 per patient-year. Totally, 431(53.9%, 431/799) stenosis events occurred in 207 AVG. Among 422 AVG stenosis events with complete clinical data, 57.8% (244/422) were multi-site stenosis and 42.2% (178/422) were single-site stenosis. The most common sites of stenosis were graft-vein anastomosis (47.6%, 340/715), venous outflows (22.7%, 162/715), and puncture zone (20.0%, 143/715). In the 414 stenosis with intact follow-up data, 90.8% (376/414) were treated by balloon angioplasty, 8.5% (35/414) received covered stent insertion, and 0.7% (3/414) were intervened by open surgery. Clinical success rate was 98.1% (406/414). The primary patency time after endovascular treatment was 6 (4, 12) months. Covered stent significantly increased post-intervention primary patency time compared withballoon angioplasty [6 (3, 7) months vs 3 (1, 4) months, P=0.020]. Conclusions: Stenosis is the most common complication of AVG, and the most common sites are graft-vein anastomosis, venous outflows, and puncture zone. Intervention of AVG stenosis has a high clinical success rate, and a relatively low post-intervention patency. Covered stent insertion improves the post-intervention patency of AVG, which has a poor effect using balloon expansion.
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Derivación Arteriovenosa Quirúrgica , Oclusión de Injerto Vascular , Diálisis Renal , Humanos , Masculino , Femenino , Persona de Mediana Edad , Estudios Retrospectivos , Prevalencia , Constricción Patológica , Grado de Desobstrucción Vascular , Stents , AncianoRESUMEN
Objective: To analyze the mid-term efficacy of the China Net Childhood Lymphoma mature B-cell lymphoma 2017 (CNCL-B-NHL-2017) regimen in treating children with high-grade B-cell lymphoma (HGBL). Methods: Clinical and pathological data of HGBL children aged≤18 years admitted to 16 hospitals of the Chinese Children's Lymphoma Collaborative Group (CNCL) from May 2017 to April 2021 were collected retrospectively. They were divided in to high-grade B-cell lymphoma with double hit/triple hit (HGBL-DH/TH) group and high-grade B-cell lymphoma non-specified (HGBL-NOS) group, according to the 2016 version of the World Health Organization (WHO) Hematopoietic and Lymphoid Tissues Cancer Classification. Both groups of patients were treated with stratified chemotherapy by risk according to the CNCL-B-NHL-2017 scheme. The deadline for follow-up was December 31, 2023. All the patients were examined by chromosome fluorescence in situ hybridization (FISH), and the rearrangement of genes MYC, BCL-2 and BCL-6 was confirmed. The clinical and pathological characteristics of patients at disease onset were analyzed, and the therapeutic effects of patients in different clinical stages and risk groups were compared. Survival analysis was drawn by Kaplan Meier method, the log-rank test was used to compare the differences in the cumulative survival rate between different groups, and multivariate Cox regression model was used to identify the prognostic factors. Results: A total of 62 patients were included, with an onset age [M(Q1, Q3)] of 7 (4, 11) years, including 48 males and 14 females. There were 11 (17.7%) patients in stageâ ¡, 33(53.2%)patients in stage â ¢ and 18(29.1%)patients in stage â £. FISH testing showed that 4 cases (6.5%) were HGBL-DH and 3 (4.8%) were HGBL-TH. The remaining 55 cases (88.7%) were HGBL-NOS, with 18 cases accompanied by MYC rearrangement. There were 7 cases in the HGBL-DH/TH group and 55 cases in the HGBL-NOS group. Thirteen cases (20.9%) were treated with the B1 regimen, 3 cases (4.8%) with B2 regimen, 37 cases (59.6%) with C1 regimen, and 9 cases (14.7%) with the C2 regimen. Forty-eight cases (77.4%) received rituximab therapy at the same time. Five cases (8.0%) progressed during treatment. The follow-up time [M(Q1, Q3)] was 43.5 (36.1, 53.7) months. The complete remission rate was 91.9% (57/62). The 3 year overall survival rate was 93.5% and event-free survival (EFS) rate was 91.9%. The 3-year overall survival rate in the HGBL-NOS group was higher than that in the HGBL-DH/TH group (96.3% vs 71.4%, P=0.011). The 3-year EFS rate of the HGBL-NOS group was higher than that of the HGBL-DH/TH group (94.5% vs 71.4%, P=0.037). In the HGBL-NOS subgroup, the overall survival rate of children with MYC rearrangement was lower (100% vs 88.9%,P=0.039). Multivariate Cox regression analysis showed that central invasion (HR=6.05, 95%CI: 1.96-38.13, P=0.046) was a risk factor for overall survival. Conclusion: CNCL-B-NHL-2017 regimen shows significant effects in the treatment of pediatric HGBL, with a good prognosis.
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Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Células B , Humanos , Estudios Retrospectivos , Niño , Linfoma de Células B/tratamiento farmacológico , China , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Adolescente , Femenino , Masculino , Proteínas Proto-Oncogénicas c-bcl-6/genética , Estudios de Cohortes , Proteínas Proto-Oncogénicas c-bcl-2/genética , Preescolar , Hibridación Fluorescente in Situ , Resultado del Tratamiento , Proteínas Proto-Oncogénicas c-myc/genéticaRESUMEN
Objective: To explore the age of onset and consultation, the main clinical manifestations, common types of combined malformations, the relationship of endometriosis, surgical prognosis and different types of proportion of adolescent female reproductive system dysplasia. Methods: The medical records of 356 patients (aged 10-19) with female reproductive system dysplasia in Women's Hospital, School of Medicine, Zhejiang University from January 2003 to August 2018 were collected and retrospectively analyzed. Results: (1) Among the 356 adolescent dysplasia patients, uterine dysplasia (23.6%, 84/356), oblique vaginal septum syndrome (OVSS; 22.5%, 80/356) and vaginal dysplasia (21.6%, 77/356) were the most frequent ones, followed by multi-sectional dysplasia (16.0%, 57/356), other types of developmental abnormalities like external genitaliaand urogenital fistula (13.5%, 48/356) and Mayer-Rokitansky-Küster-Hauser syndrome (MRKH syndrome; 2.8%, 10/356). (2) There were significant differences between the median age of onset and the age of consultation of patients with OVSS and other types of abnormalities except hymen atresia (both P<0.05). In contrast, there were no significant differences between the age of onset and the age of consultation of the patients of uterine dysplasia, vaginal dysplasia, hymen atresia, MRKH syndrome and multi-sectional dysplasia (all P>0.05). (3) The clinical manifestations were lack of specificity, and mainly abnormal finding was lower abdominal pain. (4) After admission, the majority of patients underwent comprehensive cardiopulmonary examination (71.3%, 254/356) and urinary system examination (63.5%, 226/356). Only 18.3% (65/356) of patients had completed abdominal organ examination, and 5.9% (21/356) skeletal system examination. About other systemic malformations, urological malformations were the most common (27.5%, 98/356), followed by anorectal malformation (0.6%, 2/356), heart malformations (0.3%, 1/356), and spinal malformations (0.3%, 1/356). 46.4% (84/181) of the surgical patients were diagnosed with combined endometriosis. Patients with obstructive genital tract malformations were more likely to combine with endometriosis than non-obstructive ones [50.3% (74/147) vs 29.4% (10/34); P<0.05]. However, there was no significant difference between the severity of endometriosis of those two kinds (P>0.05). (5) Totally 308 patients were followed up successfully with a median of 25.0 years old, and 20 cases were treated again; 12.0% (37/308) of them were suffering from menstrual disorder and 33.1% (102/308) of them with dysmenorrhea. Totally 130 patients had sexually active reported no sexual problems. Conclusions: Uterine dysplasia, OVSS and vaginal dysplasia are the most common syndromes in adolescent female reproductive system dysplasia along with frequent cases of coexisting urinary malformations and increasing risks of endometriosis. Meanwhile, the lack of specificity of clinical manifestations might delay the timely diagnosis and treatment after the onset of symptoms. Nonetheless, most patients could achieve good surgical outcomes.
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Trastornos del Desarrollo Sexual 46, XX , Anomalías Congénitas , Endometriosis , Conductos Paramesonéfricos , Útero , Vagina , Humanos , Femenino , Adolescente , Estudios Retrospectivos , Vagina/anomalías , Vagina/cirugía , Conductos Paramesonéfricos/anomalías , Endometriosis/cirugía , Endometriosis/diagnóstico , Endometriosis/patología , Trastornos del Desarrollo Sexual 46, XX/cirugía , Anomalías Congénitas/epidemiología , Útero/anomalías , Útero/cirugía , Útero/patología , Adulto Joven , Anomalías Urogenitales/cirugía , Anomalías Múltiples/epidemiología , Niño , Pronóstico , Genitales Femeninos/anomalías , Genitales Femeninos/cirugía , Genitales Femeninos/patologíaRESUMEN
Objective: To explore the correlation between blastomere count variations "skip value" which extracted from by time-lapse technology (TLT) combined with artificial intelligence (AI) and morphological features of in vitro fertilization (IVF) embryo, and to test its feasibility in clinical applications. Methods: This study was a diagnostic experiment (AI reassessment of embryo transferred patients), a total of 6 545 embryos from 1 226 patients who underwent IVF at the Women and Children's Hospital of Chongqing Medical University from December 2020 to December 2021 were retrospectively analyzed, of which 2 869 embryos were attempted to cultured to blastocyst stage by TLT. The embryo dynamic map (EDM) was drawn by Embryo Viewer, a TLT recording software, based on embryo developmental kinetics. The self-developed AI embryo evaluation software identified and recorded the number of cleavages in real time during embryonic development, and compared with the EDM, the correlation between the skip value formed by the change of cleavage sphere counts and the outcomes of the embryos was analyzed. The correlation among skip value, morphological score of embryo, implantation rate and live birth rate were performed by Spearman and step-up logistic regression. The receiver operating characteristic (ROC) curve was selected for reporting there relationship of skip value and morphology. Finally, predicting power of skip value for implantation and live birth rate were performed by ROC analysis. Results: The total skip values extracted from the blastomere count of embryos (72 hours post-fertilization) were negatively correlated with abnormal cleavage, blastocyst formation rate, day 3 (D3)-cell score, uneven size and fragmentation (the ß values were -0.268, -0.116, -0.213, -0.159 and -0.222, respectively; all P<0.001); positively correlated with D3-cell number (ß=0.034; P<0.001); negatively correlated with blastocyst formation rate and implantation rate (OR=0.97, 95%CI: 0.93-0.99, P=0.034; OR=0.96, 95%CI: 0.93-0.98, P=0.044). The power of predicting implantation were similar between the order selection of skip values and traditional morphology criteria [area under curve (AUC): 0.679 vs 0.620]. Live birth rate were negatively correlated with female age (OR=0.91, 95%CI: 0.88-0.93; P<0.001), D3 general score (OR=0.77, 95%CI: 0.59-0.99; P=0.045) and order selection of skip values (OR=0.98, 95%CI: 0.96-0.99; P=0.038), while positively correlated with retrieved oocyte number and endometrial thickness in embryo transferred (OR=1.08, 95%CI:1.05-1.11, P<0.001; OR=1.09, 95%CI:1.06-0.12, P<0.001, respectively) from multivariate regression analysis, and the power of predicting live birth was 0.666 for AUC. Conclusions: The skip value and its order form is a systematic quantification of embryo development, correlated with embryo developmental quality and clinical outcome. It could be an addition parameter for embryo culture and selection.
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Inteligencia Artificial , Blastocisto , Blastómeros , Técnicas de Cultivo de Embriones , Desarrollo Embrionario , Fertilización In Vitro , Humanos , Fertilización In Vitro/métodos , Estudios Retrospectivos , Femenino , Blastómeros/citología , Embarazo , Técnicas de Cultivo de Embriones/métodos , Blastocisto/citología , Transferencia de Embrión/métodos , Índice de Embarazo , Implantación del Embrión , Adulto , Programas Informáticos , Embrión de Mamíferos/citologíaRESUMEN
To analyze the infection and drug-resistant gene 23S rRNA mutations of mycoplasma pneumoniae (Mp) in hospitalized children aged 0-17 in Ningbo City from 2019 to 2023. Throat swabs were collected from hospitalized children with respiratory tract infections in Ningbo University Affiliated Women and Children's Hospital from 2019 to 2023. They were subjected to real-time fluorescence quantitative polymerase chain reaction detection to analyze Mp infection and drug-resistant gene (23S rRNA) mutations. Intergroup comparisons were made by the Chi-square test or Fisher's exact probability method. A total of 18 968 hospitalized children were included, with a total positive rate of 30.37% (5 760/18 968). The total positive rate of drug-resistant gene mutations was 82.45% (4 749/5 760). The positive rate of Mp in male children was 29.26%, which was lower than that in female children (31.67%, χ2=12.948, P<0.001). The positive rate of Mp drug-resistant gene mutations in male children was 82.52%, which was higher than that in female children(82.37%, χ2=0.021, P=0.885). The positive rates of Mp increased with age (χ2=1 722.21, P<0.001). The positive rates of Mp drug-resistant gene mutations also increased with age (χ2=13.152, P<0.001). In the four seasons, the total positive rate of Mp in summer and autumn was significantly higher than that in winter and spring (χ2=1 085.149, P<0.001). Among them, the Mp positive rates in the summer and autumn of 2019 were as high as 38.26% and 34.49%, while in the summer and autumn of 2020, the Mp positive rates were 2.55% and 1.65%, respectively, which were the lowest in previous years. In the summer and autumn of 2023, the Mp positive rates increased to 47.22% and 51.06%. There was no statistically significant difference in the detection rate of Mp drug-resistant gene mutations among the four seasons. In Conclusion, Mp infection was more prevalent in the summer and autumn in Ningbo city and females and children aged 7-17 were more susceptible. The epidemic of Mp infection in Ningbo occurred in the summer of 2019. After the COVID-19 pandemic in 2020, the positive rate of Mp rapidly decreased and later remained in a low incidence state. After the lifting of restrictive prevention and control measures in 2023, the Mp positive rate returned to an epidemic state. The positive rate of Mp drug-resistant gene (23S rRNA) mutations was relatively high.
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Farmacorresistencia Bacteriana , Mutación , Mycoplasma pneumoniae , Neumonía por Mycoplasma , Humanos , Niño , Lactante , Preescolar , Femenino , Masculino , Mycoplasma pneumoniae/genética , Adolescente , Neumonía por Mycoplasma/epidemiología , Neumonía por Mycoplasma/microbiología , Farmacorresistencia Bacteriana/genética , ARN Ribosómico 23S/genética , Infecciones del Sistema Respiratorio/microbiología , Infecciones del Sistema Respiratorio/epidemiología , Recién Nacido , China/epidemiología , Antibacterianos/farmacología , Antibacterianos/uso terapéuticoRESUMEN
The 5th edition of the World Health Organization (WHO) classification of haematolymphoid tumours used the hierarchical system to classify T-cell and NK-cell lymphoid proliferations and lymphomas (T/NK-LPD/LYM) based on research advances and clinicopathological characteristics of the diseases. In this edition of classification, tumour-like lesions were included, some tumors were added/deleted, the names or terms of certain diseases were refined, and the diagnostic criteria or subtypes of some diseases were revised. This group of diseases was reintegrated from non-clonal hyperplasia to highly aggressive lymphoma, which would further reflect the nature of T/NK-LPD/LYM and benefit to clinical application.
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Células Asesinas Naturales , Linfoma , Linfocitos T , Organización Mundial de la Salud , Humanos , Células Asesinas Naturales/patología , Células Asesinas Naturales/inmunología , Linfocitos T/patología , Linfocitos T/inmunología , Linfoma/patología , Linfoma/clasificación , Linfoma/inmunología , Linfoma de Células T/patología , Linfoma de Células T/clasificación , Linfoma de Células T/inmunología , Trastornos Linfoproliferativos/patología , Trastornos Linfoproliferativos/clasificación , Trastornos Linfoproliferativos/inmunologíaRESUMEN
Objective: To explore the correlation between MYB/NFIB gene fusion and clinicopathological features such as tumor grade and prognosis of head and neck adenoid cystic carcinoma (ACC), and to assess the concordant rate of fluorescent in situ hybridization (FISH) with MYB and NFIB immunohistochemistry. Methods: FISH detection of MYB/NFIB gene fusion was performed on 48 head and neck ACC cases and 15 non-ACC salivary gland tumors at National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China during April 2014 and January 2020. ACC cases were divided into grade â -â ¡, grade â ¢ and high-grade transformation, according to pathological grading criteria. Prognosis, FISH results and other clinicopathological characteristics were analyzed. MYB and NFIB immunohistochemistry was performed on the 48 ACC and 15 non-ACC cases. The diagnostic accuracy of FISH and immunohistochemistry was compared. Results: FISH detected MYB/NFIB gene fusion in 41.7% (20/48) of the ACC. Its positive rate was inversely correlated with higher pathological grades (P=0.036). The higher histological grade was linked to worse progression-free survival (P=0.024), whereas there was no correlation between the status of gene fusion detected by FISH and progression-free survival (P=0.536). FISH didnot detect MYB/NFIB gene fusion in 15 non-ACC salivary gland tumors The specificity of diagnosing ACC is 100% for both FISH detection of gene fusion and immunohistochemical detection of MYB expression. However, the sensitivity for both methods was only about 41.7%, respectively. By combining FISH and MYB immunohistochemistry, the sensitivity for diagnosing ACC was increased to 66.7%. Conclusions: MYB/NFIB gene fusion has a lower detection rate in grade â ¢ ACC and high-grade transformation ACC. Meanwhile gene fusion status is not correlated with prognosis. The sensitivity for diagnosing ACC can be improved by combining FISH and MYB immunohistochemistry.
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Carcinoma Adenoide Quístico , Neoplasias de las Glándulas Salivales , Humanos , Carcinoma Adenoide Quístico/diagnóstico , Carcinoma Adenoide Quístico/genética , Hibridación Fluorescente in Situ , Proteínas de Fusión Oncogénica/genética , Neoplasias de las Glándulas Salivales/diagnóstico , Neoplasias de las Glándulas Salivales/genética , Fusión Génica , Pronóstico , Factores de Transcripción NFI/genéticaRESUMEN
Objective: To investigate the safety and therapeutic effect of split liver transplantation (SLT) in clinical application. Methods: This is a retrospective case-series study. The clinical data of 203 consecutive SLT, 79 living donor liver transplantation (LDLT) and 1 298 whole liver transplantation (WLT) performed at the Third Affiliated Hospital of Sun Yat-sen University from July 2014 to July 2023 were retrospectively analyzed. Two hundred and three SLT liver grafts were obtained from 109 donors. One hundred and twenty-seven grafts were generated by in vitro splitting and 76 grafts were generated by in vivo splitting. There were 90 adult recipients and 113 pediatric recipients. According to time, SLT patients were divided into two groups: the early SLT group (40 cases, from July 2014 to December 2017) and the mature SLT technology group (163 cases, from January 2018 to July 2023). The survival of each group was analyzed and the main factors affecting the survival rate of SLT were analyzed. The Kaplan-Meier method and Log-rank test were used for survival analysis. Results: The cumulative survival rates at 1-, 3-, and 5-year were 74.58%, 71.47%, and 71.47% in the early SLT group, and 88.03%, 87.23%, and 87.23% in the mature SLT group, respectively. Survival rates in the mature SLT group were significantly higher than those in the early SLT group (χ2=5.560,P=0.018). The cumulative survival rates at 1-, 3- and 5-year were 93.41%, 93.41%, 89.95% in the LDLT group and 87.38%, 81.98%, 77.04% in the WLT group, respectively. There was no significant difference among the mature SLT group, the LDLT group and the WLT group (χ2=4.016, P=0.134). Abdominal hemorrhage, infection, primary liver graft nonfunction,and portal vein thrombosis were the main causes of early postoperative death. Conclusion: SLT can achieve results comparable to those of WLT and LDLT in mature technology liver transplant centers, but it needs to go through a certain time learning curve.