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Carcinoma de Células Renales , Neoplasias Renales , Humanos , Carcinoma de Células Renales/patología , Carcinoma de Células Renales/genética , Carcinoma de Células Renales/metabolismo , Neoplasias Renales/patología , Neoplasias Renales/genética , Neoplasias Renales/metabolismo , Masculino , Persona de Mediana Edad , Femenino , Anciano , Estudios Retrospectivos , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/genética , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Factor de Transcripción PAX8/metabolismo , Factor de Transcripción PAX8/genética , Factor de Transcripción PAX2/metabolismo , Factor de Transcripción PAX2/genética , Racemasas y Epimerasas/metabolismo , Racemasas y Epimerasas/genética , Nefrectomía , Estudios de SeguimientoRESUMEN
BACKGROUND: Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by intricate genetic and environmental etiology. The objective of this study was to identify robust non-genetic risk factors for AD through an updated umbrella review. METHODS: We conducted a comprehensive search of meta-analyses and systematic reviews on non-genetic risk factors associated with AD in PubMed, Cochrane, Embase, and Ovid Medline up to June 30, 2023. After collecting data, we estimated the summary effect size and their 95% confidence intervals. The degree of heterogeneity between studies was assessed using I2 statistics and a 95% prediction interval was determined. Additionally, we evaluated potential excess significant bias and small study effects within the selected candidate studies. RESULTS: The umbrella review encompassed a total of 53 eligible papers, which included 84 meta-analyses covering various factors such as lifestyle, diet, environmental exposures, comorbidity or infections, drugs, and biomarkers. Based on the evidence classification criteria employed in this study, two factors as convincing evidence (Class I), including rheumatoid arthritis (RA), potentially reduced the risk of AD, but diabetes significantly increased the risk of AD. Furthermore, three factors as highly suggestive evidence (Class II), namely depression, high homocysteine, and low folic acid level, potentially increased the risk of AD. CONCLUSION: Our findings highlight several risk factors associated with AD that warrant consideration as potential targets for intervention. However, it is crucial to prioritize the identified modifiable risk factors, namely rheumatoid arthritis, diabetes, depression, elevated homocysteine levels, and low folic acid levels to effectively address this complex neurodegenerative disorder.
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Enfermedad de Alzheimer , Enfermedad de Alzheimer/genética , Enfermedad de Alzheimer/epidemiología , Humanos , Factores de Riesgo , Artritis Reumatoide/genética , Biomarcadores/sangre , Estilo de VidaRESUMEN
The article "Imipenem-resistance in Serratia marcescens is mediated by plasmid expression of KPC-2", by W.-Q. Su, Y.-Q. Zhu, N.-M. Deng, L. Li, published in Eur Rev Med Pharmacol Sci 2017; 21 (7): 1690- 1694-PMID: 28429335 has been retracted by the Editor in Chief. Following some concerns raised on PubPeer (link: https://pubpeer.com/publications/F7E91E2863540C7CB030B86E16917F), the Editor in Chief has started an investigation to assess the validity of the results as well as possible figure and data manipulation. The authors were informed about the journal's investigation but have remained unresponsive and have not provided the manuscript's raw data. Therefore, the validity of the overall results could not be verified. The journal's investigation revealed that Figures 2 and 3 have been computer-generated. Additionally, Figure 1 was duplicated from a previously published article. Moreover, several terminology inaccuracies were identified within the manuscript. Consequently, the Editor in Chief mistrusts the results presented and has decided to retract the article. This article has been retracted. The Publisher apologizes for any inconvenience this may cause. https://www.europeanreview.org/article/12540.
RESUMEN
Objective: To compare the accuracy of intraocular lens (IOL) power calculations using total keratometry (TK) versus standard keratometry (K) in post-corneal refractive surgery cataract patients. Methods: This retrospective case series study included 30 patients (36 eyes) with a history of laser corneal refractive surgery who underwent cataract extraction and IOL implantation at Qingdao Eye Hospital, Affiliated to Shandong First Medical University, from September 2022 to December 2023. The cohort comprised 16 males and 14 females, with an average age of (53.6±8.1) years. IOL power was calculated using the K-based Haigis-L and Barrett True-K formulas, as well as the TK-based Haigis and Barrett Universal â ¡ formulas. Postoperative objective refraction was performed to obtain the actual refractive status of the operated eyes. The refractive prediction error (RPE) was defined as the difference between the actual spherical equivalent and the predicted refraction. The absolute value of the RPE was taken as the refractive absolute error (RAE). Differences in errors calculated by the four formulas were compared. Results: TK showed good consistency with K, with TK being on average 0.50 D lower than K. Analysis of variance revealed statistically significant differences in RPE among the four formulas (P<0.001). The RPE for the TK-based Haigis formula was (0.17±0.09) D, and for the Barrett Universal â ¡ formula, it was (0.21±0.11) D, both significantly better than the K-based Haigis-L formula (-0.61±0.12) D and Barrett True-K formula (-0.57±0.11) D (all P<0.001). The percentage of eyes with postoperative RPE<±1.00 D was higher for the TK-based Haigis (92%, 33 eyes) and Barrett Universal â ¡ (86%, 31 eyes) formulas compared to the TK-based Barrett True-K (75%, 27 eyes) and Haigis-L formulas (67%, 24 eyes), with statistically significant differences (P<0.05). Conclusions: Compared with K, TK improves the accuracy of IOL power calculation in post-corneal refractive surgery patients. Both the TK-based Barrett Universal â ¡ and Haigis formulas demonstrate high accuracy.
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Extracción de Catarata , Catarata , Córnea , Implantación de Lentes Intraoculares , Lentes Intraoculares , Refracción Ocular , Humanos , Masculino , Femenino , Estudios Retrospectivos , Persona de Mediana Edad , Córnea/cirugía , Implantación de Lentes Intraoculares/métodos , Procedimientos Quirúrgicos Refractivos/métodosRESUMEN
Objective: To explore the relationship between the onset time of sepsis-associated acute kidney injury (SA-AKI) and adverse clinical outcomes. Methods: Data were derived from Beijing Acute Kidney Injure Trial (BAKIT) which investigated the epidemiology of acute kidney injury (AKI) in critically ill patients at 30 intensive care units (ICU) of 28 tertiary hospitals in Beijing from 1 March to 31 August 2012. Patients who were older than 18 years and diagnosed with sepsis and AKI, and expected to stay in ICU for at least 24 h were included in this study. A total of 653 patients were included in this study, 414 males and 239 females with a mean age of (68.2±17.0) years. According to the onset time of SA-AKI, patients were grouped into early AKI (E-AKI) (AKI occurred within 48 hours after ICU admission) and late AKI (L-AKI) (AKI occurred after 48 hours of ICU admission) group. The primary outcome was major adverse kidney events (MAKE), consisted of all-cause mortality, renal replacement therapy-dependence, and an inability to recover to 1.5 times of the baseline creatinine value up to 30 days. Multivariable logistic regression was used to investigate the association between the onset time of SA-AKI and clinical outcomes. Results: A total of 653 patients with SA-AKI were included, 423 (64.8%) patients developed E-AKI, 230 (35.2%) cases developed L-AKI, MAKE occurred in 405 (62.0%) cases, and 301 (46.1%) patients died in hospital. Compared with E-AKI group, L-AKI patients showed higher AKI 3 level rate [55.7%(128/230) vs 40.2%(170/423), P<0.001], incidence of MAKE [72.6%(167/230) vs 56.3%(238/423,P<0.001)] and hospital mortality [55.2%(127/230) vs 44.1%(174/423), P=0.001]. The risk of MAKE and in-hospital mortality in L-AKI group increased for 2.55-fold times (OR=3.55, 95%CI: 1.94-6.04) and 1.84-fold times (OR=2.84, 95%CI: 1.44-5.60) when compared with those in E-AKI, respectively (both P<0.05). Conclusion: Late timing onset of SA-AKI is associated with poor clinical outcomes.
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Lesión Renal Aguda , Unidades de Cuidados Intensivos , Sepsis , Humanos , Lesión Renal Aguda/etiología , Sepsis/complicaciones , Masculino , Femenino , Persona de Mediana Edad , Anciano , Mortalidad Hospitalaria , Enfermedad Crítica , Factores de Tiempo , Terapia de Reemplazo Renal , Modelos LogísticosRESUMEN
Objective: To investigate the correlation between serum growth differentiation factor 11 (GDF11) level and coronary artery lesions in patients with ST-segment elevation myocardial infarction (STEMI), and the predictive efficacy of nomogram risk prediction model based on GDF11 combined with traditional risk factors on the occurrence of STEMI. Methods: This study was a retrospective cross-sectional study. Patients hospitalized in the Department of Cardiology of the 904th Hospital of Joint Logistic Support Force of People's Liberation Army of China from 2016 to 2018 were selected and divided into control group and STEMI group. The demographic data, blood lipid level, laboratory indicators of blood and GDF11 level were collected. Logistic regression analysis screened out independent correlated factors for the occurrence of STEMI. Spearman correlation analysis clarified the correlation of each indicator with the SYNTAX or Gensini scores. A nomogram risk prediction model for the risk of STEMI occurrence and the receiver operating characteristic curve was used to compare the prediction efficiency of each model. Results: A total of 367 patients were enrolled, divided into control group (n=172) and STEMI group (n=195), age (66.5±11.8), male 222 (60.49%). The serum GDF11 level of STEMI group was significantly lower than that of the control group (36.20 (16.60, 70.75) µg/L vs. 85.00 (53.93, 117.10) µg/L, P<0.001). The results of multivariate logistic regression analysis showed serum GDF11(OR=0.98, 95%CI: 0.97-0.99) and traditional independent risk factors such as smoking, diabetes, C-reactive protein, homocysteine, lipoprotein (a) and apolipoprotein A1/B were independent correlate factors for the occurrence of STEMI (P<0.05). Spearman correlation analysis showed that serum GDF11 was negatively correlated with SYNTAX score and Gensini score (P<0.05). The nomogram model constructed by serum GDF11 combined with traditional independent risk factors (AUC=0.85, 95%CI: 0.81-0.89) had better predictive value for the occurrence of STEMI than the traditional nomogram model constructed by independent risk factors(AUC=0.80, 95%CI:0.75-0.84) or serum GDF11 (AUC=0.76, 95%CI: 0.72-0.81), all P<0.01. Conclusions: Serum GDF11 is an independent correlate factor in the occurrence of STEMI and is negatively correlated with the severity of coronary artery lesions in patients with STEMI. The nomogram model constructed based on GDF11 combined with traditional risk factors can be a good predictor for the occurrence of STEMI.
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Enfermedad de la Arteria Coronaria , Infarto del Miocardio , Intervención Coronaria Percutánea , Infarto del Miocardio con Elevación del ST , Humanos , Masculino , Proteínas Morfogenéticas Óseas/sangre , Proteínas Morfogenéticas Óseas/química , Enfermedad de la Arteria Coronaria/diagnóstico , Enfermedad de la Arteria Coronaria/metabolismo , Estudios Transversales , Factores de Diferenciación de Crecimiento/sangre , Factores de Diferenciación de Crecimiento/química , Infarto del Miocardio/sangre , Infarto del Miocardio/metabolismo , Estudios Retrospectivos , Factores de Riesgo , Infarto del Miocardio con Elevación del ST/sangre , Infarto del Miocardio con Elevación del ST/metabolismoRESUMEN
BACKGROUND: Human epidermal growth factor receptor 3 (HER3) is broadly expressed in non-small-cell lung cancer (NSCLC) and is the target of patritumab deruxtecan (HER3-DXd), an antibody-drug conjugate consisting of a HER3 antibody attached to a topoisomerase I inhibitor payload via a tetrapeptide-based cleavable linker. U31402-A-U102 is an ongoing phase I study of HER3-DXd in patients with advanced NSCLC. Patients with epidermal growth factor receptor (EGFR)-mutated NSCLC that progressed after EGFR tyrosine kinase inhibitor (TKI) and platinum-based chemotherapy (PBC) who received HER3-DXd 5.6 mg/kg intravenously once every 3 weeks had a confirmed objective response rate (cORR) of 39%. We present median overall survival (OS) with extended follow-up in a larger population of patients with EGFR-mutated NSCLC and an exploratory analysis in those with acquired genomic alterations potentially associated with resistance to HER3-DXd. PATIENTS AND METHODS: Safety was assessed in patients with EGFR-mutated NSCLC previously treated with EGFR TKI who received HER3-DXd 5.6 mg/kg; efficacy was assessed in those who also had prior PBC. RESULTS: In the safety population (N = 102), median treatment duration was 5.5 (range 0.7-27.5) months. Grade ≥3 adverse events occurred in 76.5% of patients; the overall safety profile was consistent with previous reports. In 78/102 patients who had prior third-generation EGFR TKI and PBC, cORR by blinded independent central review (as per RECIST v1.1) was 41.0% [95% confidence interval (CI) 30.0% to 52.7%], median progression-free survival was 6.4 (95% CI 4.4-10.8) months, and median OS was 16.2 (95% CI 11.2-21.9) months. Patients had diverse mechanisms of EGFR TKI resistance at baseline. At tumor progression, acquired mutations in ERBB3 and TOP1 that might confer resistance to HER3-DXd were identified. CONCLUSIONS: In patients with EGFR-mutated NSCLC after EGFR TKI and PBC, HER3-DXd treatment was associated with a clinically meaningful OS. The tumor biomarker characterization comprised the first description of potential mechanisms of resistance to HER3-DXd therapy.
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Anticuerpos Monoclonales Humanizados , Carcinoma de Pulmón de Células no Pequeñas , Receptores ErbB , Neoplasias Pulmonares , Mutación , Receptor ErbB-3 , Humanos , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Carcinoma de Pulmón de Células no Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidad , Neoplasias Pulmonares/patología , Receptores ErbB/genética , Receptores ErbB/antagonistas & inhibidores , Femenino , Receptor ErbB-3/genética , Receptor ErbB-3/antagonistas & inhibidores , Persona de Mediana Edad , Masculino , Anciano , Adulto , Anticuerpos Monoclonales Humanizados/administración & dosificación , Anticuerpos Monoclonales Humanizados/uso terapéutico , Anticuerpos Monoclonales Humanizados/efectos adversos , Anciano de 80 o más Años , Camptotecina/análogos & derivados , Camptotecina/uso terapéutico , Camptotecina/administración & dosificación , Anticuerpos Monoclonales/uso terapéutico , Anticuerpos Monoclonales/administración & dosificación , Anticuerpos Monoclonales/efectos adversos , Anticuerpos ampliamente neutralizantes , Inmunoconjugados/uso terapéutico , Inmunoconjugados/efectos adversos , Inmunoconjugados/administración & dosificaciónRESUMEN
AIMS: Transformed small cell lung cancer (T-SCLC) is a highly aggressive clinical disease with a notably poor prognosis. It most often arises from epidermal growth factor receptor (EGFR)-mutant non-small cell lung cancer (NSCLC) following treatment. To date, no standard treatment has been established for T-SCLC. Platinum-etoposide was the most commonly used regimen, but progression-free survival remains unsatisfactory. Therefore, there is an urgent unmet need to develop novel and effective strategies for this population. Our study, a multicentre, open-label, single-arm phase II clinical trial (NCT05957510), aims to evaluate the efficacy and safety of serplulimab plus chemotherapy in untreated T-SCLC patients after histological transformation. MATERIALS AND METHODS: In total, 36 eligible participants experiencing SCLC transformation from EGFR-mutant NSCLC will be enrolled to receive combination therapy of serplulimab, etoposide and carboplatin for four to six cycles, followed by maintenance therapy with serplulimab for up to 2 years. The primary endpoint is progression-free survival; secondary endpoints include objective response rate, overall survival and safety. RESULTS: Enrolment started in July 2023 and is ongoing, with an estimated completion date of December 2025. CONCLUSIONS: This study aims to provide valuable insights into the efficacy and safety of combining serplulimab with chemotherapy for treating patients with T-SCLC originating from EGFR-mutant NSCLC.
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Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , Carcinoma Pulmonar de Células Pequeñas , Humanos , Carcinoma Pulmonar de Células Pequeñas/tratamiento farmacológico , Carcinoma Pulmonar de Células Pequeñas/patología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/genética , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/genética , Etopósido , Estudios Prospectivos , Carboplatino/efectos adversos , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Receptores ErbB , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversosRESUMEN
Objective: To understand the epidemiological characteristics of mpox epidemic in Guangzhou and provide scientific evidence for the prevention and control of the disease. Methods: Based on the mpox surveillance system in Guangzhou, suspected mpox cases with fever and rash were reported by local hospitals at all levels to centers for disease control and prevention in Guangzhou for sampling, investigation and diagnosis. Descriptive epidemiological analysis was conducted on the clinical characteristics and treatment of the mpox cases and positive detection rate reported in Guangzhou as of 24:00 on June 23. Whole genome sequencing of the virus isolates was performed using Illumina Miniseq high-throughput sequencing platform. Results: The first mpox case in Guangzhou was reported on June 10 in 2023. As of 24:00 on June 23, a total of 25 confirmed mpox cases were reported. All the mpox cases were men with a M(Q1,Q3) of 32 (26, 36) years, the majority of the cases were MSM (96.0%). The main clinical features were rash (100.0%, 25/25), lymphadenectasis (100.0%, 25/25) and fever (52.0%, 13/25). Rash usually occurred near the genitals (88.0%, 22/25). The close contacts, mainly family members (40.4%, 23/57), showed no similar symptoms, such as fever or rash. The positive rate of mpox virus in household environment samples was 30.5%. The analyses on 3 complete gene sequences of mpox virus indicated that the strains belonged to West African type â ¡b clade, B.1.3 lineage. Conclusions: Hidden transmission of mpox virus had occurred in MSM in Guangzhou. However, the size of affected population is relatively limited, and the possibility of wide spread of the virus is low.
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Epidemias , Exantema , Mpox , Minorías Sexuales y de Género , Estados Unidos , Masculino , Humanos , Femenino , Homosexualidad Masculina , FiebreRESUMEN
Objective: To investigate the effect and regulation of umbilical cord-derived mesenchymal stem cells (UC-MSCs) on islets function and NOD-like receptor family, pyrin domain containing 3 (NLRP3) and autophagy in type 2 diabetic mellitus (T2DM) mice. Methods: Experimental study. Twenty, 8-week-old, male C57BL/6J mice were selected and divided into a normal control group (n=5) and a high-fat feeding modeling group (n=15). The model of T2DM was established by high-fat feeding combined with intraperitoneal injection of low-dose streptozotocin. After successful modeling, those mice were divided into a diabetes group (n=7) and a UC-MSCs treatment group (n=7). The UC-MSCs treatment group was given UC-MSCs (1×106/0.2 ml phosphate buffer solution) by tail vein infusion once a week for a total of 4 weeks; the diabetes group was injected with the same amount of normal saline, and the normal control group was not treated. One week after the treatment, mice underwent intraperitoneal glucose tolerance tests and intraperitoneal insulin tolerance tests, and then the mice were sacrificed to obtain pancreatic tissue to detect the expressions of interleukin-1ß (IL-1ß) and pancreatic and duodenal homeobox 1 (PDX-1) by immunofluorescence. The bone marrow-derived macrophages were stimulated with lipopolysaccharide and adenosine triphosphate (experimental group) in vitro, then co-cultured with UC-MSCs for 24 h (treatment group). After the culture, enzyme-linked immunosorbent assay was used to detect the secretion level of IL-1ß in the supernatant, and immunofluorescence staining was used to detect the expression of NLRP3 inflammasome, and related autophagy proteins. Statistical analysis was performed using unpaired one-way analysis of variance, repeated measure analysis of variance. Results: In vivo experiments showed that compared with the diabetes group, the UC-MSCs treatment group partially repaired islet structure, improved glucose tolerance and insulin sensitivity (all P<0.05), and the expression of PDX-1 increased and IL-1ß decreased in islets under confocal microscopy. In vitro experiments showed that compared with the experimental group, the level of IL-1ß secreted by macrophages in the treatment group was decreased [(85.9±74.6) pg/ml vs. (883.4±446.2) pg/ml, P=0.001], the expression of NLRP3 inflammasome and autophagy-related protein P62 was decreased, and the expressions of microtubule-associated protein 1 light chain 3ß (LC3) and autophagy effector Beclin-1 were increased under confocal microscopy. Conclusions: UC-MSCs can reduce the level of pancreatic inflammation in T2DM mice, preserving pancreatic function. This might be associated with the ability of UC-MSCs to inhibit the activity of NLRP3 inflammasomes in macrophages and enhance autophagy levels.
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Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Células Madre Mesenquimatosas , Humanos , Masculino , Animales , Ratones , Ratones Endogámicos C57BL , Inflamasomas , Proteína con Dominio Pirina 3 de la Familia NLRRESUMEN
The well-being of students and staff directly affects their output and efficiency. This study presents the results of two focus groups conducted in 2022 within a two-phase project led by the Applied Biomedical and Signal Processing Intelligent e-Health Lab, School of Engineering at the University of Warwick, and British Telecom within "The Connected Campus: University of Warwick case study" program. The first phase, by involving staff and students at the University of Warwick, aimed at collecting preliminary information for the subsequent second phase, about the feasibility of the use of Artificial Intelligence and Internet of Things for well-being support on Campus. The main findings of this first phase are interesting technological suggestions from real users. The users helped in the design of the scenarios and in the selection of the key enabling technologies which they considered as the most relevant, useful and acceptable to support and improve well-being on Campus. These results will inform future services to design and implement technologies for monitoring and supporting well-being, such as hybrid, minimal and even intrusive (implantable) solutions. The user-driven co-design of such services, leveraging the use of wearable devices and Artificial Intelligence deployment will increase their acceptability by the users.
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Inteligencia Artificial , Ingeniería Biomédica , Humanos , Bioingeniería , Ingeniería , Grupos FocalesRESUMEN
Objectives: To investigate the clinical and genetic features of young Chinese patients with myeloproliferative neoplasms (MPN). Methods: In this cross-sectional study, anonymous questionnaires were distributed to patients with MPN patients nationwide. The respondents were divided into 3 groups based on their age at diagnosis: young (≤40 years) , middle-aged (41-60 years) , and elderly (>60 years) . We compared the clinical and genetic characteristics of three groups of MPN patients. Results: 1727 assessable questionnaires were collected. There were 453 (26.2%) young respondents with MPNs, including 274 with essential thrombocythemia (ET) , 80 with polycythemia vera (PV) , and 99 with myelofibrosis. Among the young group, 178 (39.3%) were male, and the median age was 31 (18-40) years. In comparison to middle-aged and elderly respondents, young respondents with MPN were more likely to present with a higher proportion of unmarried status (all P<0.001) , a higher education level (all P<0.001) , less comorbidity (ies) , fewer medications (all P<0.001) , and low-risk stratification (all P<0.001) . Younger respondents experienced headache (ET, P<0.001; PV, P=0.007; MF, P=0.001) at diagnosis, had splenomegaly at diagnosis (PV, P<0.001) , and survey (ET, P=0.052; PV, P=0.063) . Younger respondents had fewer thrombotic events at diagnosis (ET, P<0.001; PV, P=0.011) and during the survey (ET, P<0.001; PV, P=0.003) . JAK2 mutations were found in fewer young people (ET, P<0.001; PV, P<0.001; MF, P=0.013) ; however, CALR mutations were found in more young people (ET, P<0.001; MF, P=0.015) . Furthermore, mutations in non-driver genes (ET, P=0.042; PV, P=0.043; MF, P=0.004) and high-molecular risk mutations (ET, P=0.024; PV, P=0.023; MF, P=0.001) were found in fewer young respondents. Conclusion: Compared with middle-aged and elderly patients, young patients with MPN had unique clinical and genetic characteristics.
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Trastornos Mieloproliferativos , Policitemia Vera , Mielofibrosis Primaria , Trombocitemia Esencial , Anciano , Persona de Mediana Edad , Humanos , Masculino , Adolescente , Adulto , Femenino , Estudios Transversales , Trastornos Mieloproliferativos/genética , Policitemia Vera/genética , Mielofibrosis Primaria/genética , Trombocitemia Esencial/genética , Mutación , Janus Quinasa 2/genéticaRESUMEN
BACKGROUND: We hypothesized that avelumab plus axitinib could improve clinical outcomes in patients with advanced non-small-cell lung cancer (NSCLC) or urothelial carcinoma (UC). PATIENTS AND METHODS: We enrolled previously treated patients with advanced or metastatic NSCLC, or untreated, cisplatin-ineligible patients with advanced or metastatic UC. Patients received avelumab 800 mg every 2 weeks (Q2W) and axitinib 5 mg orally two times daily. The primary endpoint was objective response rate (ORR). Immunohistochemistry was used to assess programmed death-ligand 1 (PD-L1) expression (SP263 assay) and the presence of CD8+ T cells (clone C8/144B). Tumor mutational burden (TMB) was assessed by whole-exome sequencing. RESULTS: A total of 61 patients were enrolled and treated (NSCLC, n = 41; UC, n = 20); 5 remained on treatment at data cut-off (26 February 2021). The confirmed ORR was 31.7% in the NSCLC cohort and 10.0% in the UC cohort (all partial responses). Antitumor activity was observed irrespective of PD-L1 expression. In exploratory subgroups, ORRs were higher in patients with higher (≥median) CD8+ T cells in the tumor. ORRs were higher in patients with lower TMB (Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas
, Carcinoma de Células Transicionales
, Neoplasias Pulmonares
, Neoplasias de la Vejiga Urinaria
, Humanos
, Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico
, Carcinoma de Pulmón de Células no Pequeñas/patología
, Axitinib/farmacología
, Axitinib/uso terapéutico
, Cisplatino/farmacología
, Cisplatino/uso terapéutico
, Neoplasias Pulmonares/tratamiento farmacológico
, Neoplasias Pulmonares/patología
, Anticuerpos Monoclonales/efectos adversos
RESUMEN
Objective: To analyze the clinical presentation and progression risk factors of patients with monoclonal gammopathy of undetermined significance (MGUS) in China. Methods: We retrospectively assessed the clinical features and disease progression of 1 037 patients with monoclonal gammopathy of undetermined significance between January 2004 and January 2022 at Peking Union Medical College Hospital. Results: A total of 1 037 patients were recruited in the study, including 636 males (63.6%) , with a median age of 58 (18-94) years. The median concentration of serum monoclonal protein was 2.7 (0-29.4) g/L. The monoclonal immunoglobulin type was IgG in 380 patients (59.7%) , IgA in 143 patients (22.5%) , IgM in 103 patients (16.2%) , IgD in 4 patients (0.6%) , and light chain in 6 patients (0.9%) . 171 patients (31.9%) had an abnormal serum-free light chain ratio (sFLCr) . According to the Mayo Clinic model for risk of progression, the proportion of patients in the low-risk, medium-low-risk, medium-high risk, and high-risk groups were 254 (59.5%) , 126 (29.5%) , 43 (10.1%) , and 4 (0.9%) , respectively. With a median follow-up of 47 (1-204) months, 34 of 795 patients (4.3%) had disease progression, and 22 (2.8%) died. The overall progression rate was 1.06 (0.99-1.13) /100 person-years. Patients with non-IgM MGUS have a markedly higher disease progression rate per 100 person-years than IgM-MGUS (2.87/100 person-years vs 0.99/100 person-years, P=0.002) . The disease progression rate per 100 person-years in non-IgM-MGUS patients of Mayo classification low-risk, medium-low risk and medium-high risk groups were 0.32 (0.25-0.39) /100 person-years, 1.82 (1.55-2.09) /100 person-years, and2.71 (1.93-3.49) /100 person-years, which had statistically difference (P=0.005) . Conclusion: In comparison to non-IgM-MGUS, IgM-MGUS has a greater risk of disease progression. The Mayo Clinic progression risk model applies to non-IgM-MGUS patients in China.
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Gammopatía Monoclonal de Relevancia Indeterminada , Masculino , Humanos , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Estudios Retrospectivos , Factores de Riesgo , Cadenas Ligeras de Inmunoglobulina , Progresión de la EnfermedadRESUMEN
OBJECTIVES: Summarize the existing evidence regarding the prevalence and risk factors of frailty in stroke patients. DESIGN: A meta-analysis and systematic review. PARTICIPANTS: Stroke patients in hospitals or communities. METHODS: We undertook a systematic review and meta-analysis using articles available in 8 databases, including PubMed, The Cochrane Library, Web of Science, Embase, Chinese Biomedical Database (CBM), China National Knowledge Infrastructure Database (CNKI), Wanfang Database, and Weipu Database (VIP) from January 1990 to April 2022. Studies were quality rated using the Newcastle-Ottawa Scale and Agency for Healthcare Research and Quality tool. RESULTS: A total of 24 studies involving 30,423 participants were identified. The prevalence of frailty and pre-frailty in stroke patients was 27% (95%CI: 0.23-0.31) and 47.9% (95%CI: 0.43-0.53). Female gender (OR = 1.76, 95%CI: 1.63-1.91), advanced age (MD = 6.73, 95%CI: 3.55-9.91), diabetes (OR = 1.34, 95%CI: 1.06-1.69), hyperlipidemia (OR = 1.46, 95%CI: 1.04-2.04), atrial fibrillation (OR = 1.36, 95%CI: 1.01-1.82), National Institutes of Stroke Scale (NIHSS) admission scores (MD = 2.27, 95%CI: 1.72-2.81) were risk factors of frailty in stroke patients. CONCLUSIONS: Frailty was more prevalent in stroke patients. Female gender, advanced age, diabetes, hyperlipidemia, atrial fibrillation, and National Institutes of Stroke Scale (NIHSS) admission scores were identified as risk factors for frailty in stroke patients. In the future, medical staff should pay attention to the early screening of frailty in high-risk groups and provide information on its prevention.
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Fibrilación Atrial , Fragilidad , Accidente Cerebrovascular , Humanos , Femenino , Fragilidad/epidemiología , Prevalencia , Factores de RiesgoRESUMEN
Varicella-zoster virus (VZV) causes chickenpox when it first infects humans, and the virus may reactivate in adulthood and cause herpes zoster (HZ). Broad-spectrum antiviral drugs are one of the treatments for varicella and herpes zoster, but the emergence of drug resistance poses many challenges to this treatment and increases the burden of disease on patients. This paper discusses the resistance mechanisms, resistance sites and resistance detection methods of anti-VZV drugs in order to help further research on new anti-VZV targets, new drugs and monitoring of resistance to existing drugs.
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Varicela , Herpes Zóster , Humanos , Herpesvirus Humano 3 , Antivirales/farmacología , Antivirales/uso terapéutico , Resistencia a MedicamentosRESUMEN
Objective: To analyze the clinicopathological features of IgG4-related diseases (RD) of retroperitoneum and the urinary and male reproductive system (IgG4-RUMR). Methods: A total of 11 IgG4-RUMR cases from January 2013 to March 2021 were retrospectively collected at Peking University Third Hospital and Shandong Provincial Hospital affiliated to Shandong First Medical University. The clinicopathologic features, laboratory and imaging findings were analyzed and scored according to the 2019 ACR/EULAR classification criteria for IgG4-RD. Results: The 11 patients (male:female is 9â¶2; mean age 59 years, range from 44 to 83 years) were initially admitted to the Deparment of Urology/Kidney Transplantation (10 cases) and the Department of Oncology (1 case). All patients had urogenital disorders or imaging abnormalities. Three of the 11 patients had a history of IgG4-RD such as lacrimal gland engorgement, salivary gland engorgement and IgG4-associated pancreatitis. Abnormal retroperitoneal soft tissue and hydronephrosis were found in eight cases, while epididymal and spermatic cord masses were found in one case, simple renal mass in one case, and"benign prostatic hyperplasia"in one case. In the 10 patients tested for serum IgG4, the serum IgG4 level was 0.8-14.4 g/L. Histologically, all cases showed significant lymphoplasmacytic infiltration and storiform fibrosis, and some were accompanied by obliterative phlebitis. The number of IgG4 positive plasma cells was 12-155 per high-power field, and the IgG4/IgG ratio was 15%-77%. According to the 2019 ACR/EULAR IgG4-RD classification standard 11 cases scored 20-48 points, all of which met the diagnostic criteria of IgG4-RUMR. Therapeutically, the patient with a simple renal mass underwent partial nephrectomy. The patient with prostate lesion underwent transurethral resection of prostate and was initially diagnosed as nonspecific chronic prostatitis. Later, the patient was admitted again because of salivary gland swelling, and the pathologic diagnosis was amended. The patient with epididymal and spermatic cord masses participated in a clinical trial about retroperitoneal fibrosis. The remaining eight patients received symptomatic treatment such as adhesiolysis and stent placement. All the patients were subsequently treated with glucocorticoid/immunosuppressant and symptoms relieved. Conclusions: IgG4-RUMR is uncommon. In clinical practice, information from clinical, serologic, radiologic and pathologic evaluations must be integrated. IgG4-RUMR should be considered in the differential diagnosis of urinary and male reproductive diseases. The 2019 ACR/EULAR classification criteria for IgG4-RD, while relatively complex, are objective and practical in the diagnosis of IgG4-RUMR.
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Enfermedades Autoinmunes , Enfermedad Relacionada con Inmunoglobulina G4 , Resección Transuretral de la Próstata , Adulto , Anciano , Anciano de 80 o más Años , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/patología , Femenino , Glucocorticoides , Humanos , Inmunoglobulina G , Enfermedad Relacionada con Inmunoglobulina G4/patología , Inmunosupresores , Masculino , Persona de Mediana Edad , Próstata/patología , Estudios RetrospectivosRESUMEN
We studied the enhancement effects of ultraviolet (UV) emission from rare earth ytterbium (Yb) doped ZnO films, by using capping layers of Al and SiO2 micro-spheres. The films were deposited on Si substrates with magnetron sputtering followed by high temperature (â¼1000°C) heat treatment, and then capped with a nanoscale ultrathin aluminum (Al) layer and/or SiO2 micro-spheres on the surface of the films. The photoluminescence (PL) results indicate that compared to the case without any capping, the UV emission is enhanced by a factor ranging from several to dozens times, the films capped with 2.0 nm Al layer and 5.0 µm SiO2 microspheres have the longest highest PL intensity among the samples. The PL enhancements are discussed in terms of increased optical (or electrical) fields around the surface of the films combined with defect passivation after the capping. Our work has proposed a strategy to enhance the UV emissions of ZnO, which will broaden the application potential of ZnO in UV photonics.
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Objective: To investigate the prognostic value of translocation t(11;14) in newly-diagnosed primary light-chain (AL) amyloidosis patients treated with bortezomib-based regimen. Method: Clinical information of newly-diagnosed AL amyloidosis patients in Peking Union Medical College Hospital who had baseline t(11;14) data and accepted bortezomib-combined therapies from September, 2015 to September, 2021 was collected. The relationships between t(11;14) status and baseline characteristics, hematological response, organ response and prognosis were analyzed. Results: A total of 152 patients were included, aged (59.5±9.1) years and 93 cases were male (61.2%). Forty-six patients carried t(11;14) (30.3%). There was no statistical difference in the proportion of organ involved, distribution of Mayo 2004 and 2012 stages and laboratory indexes between patients with and without t(11;14) (all P>0.05). For hematological response, the difference in the rates of ≥very good partial response (VGPR) between those with t(11;14) and without after the first cycle [28.2%(11/39) vs 37.4%(34/91), P>0.05] was not statistically significant. After 3 cycles, the difference in the rates of ≥VGPR between two groups was not statistically significant [35.9%(14/39) vs 51.1%(46/90), P>0.05]. The difference in the ratio of the best hematological response reaching ≥VGPR between two groups during the first-line treatment was not statistically significant [52.2%(24/46) vs 64.2%(68/106), P>0.05]. But patients with t(11;14) had lower cardiac response rate at 3 months [15.2%(5/33) vs 34.6%(28/81), P=0.038] and 6 months [19.4%(6/31) vs 50.6%(42/83),P=0.003] than those without, but the difference in cardiac response rates at 12 months was not statistically significant [41.7%(10/24) vs 53.5%(38/71),P>0.05]. For survival, the differences in overall survival (not reached vs 50.1 months, P>0.05) and hematological event-free survival (36.2 months vs 39.9 months, P>0.05) between patients carrying t(11;14) and those without were not statistically significant. Conclusion: Patients with t(11;14) had lower cardiac response rate than those without, but their hematological response and survival are not significantly different from those free from t(11;14).