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1.
Front Public Health ; 12: 1396460, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38774054

RESUMEN

Objectives: Suicide is a global health concern, exacerbated by stigma around mental illnesses. Online platforms like Twitter and Sina Weibo have seen a rise in "online broadcast suicide," where individuals share suicidal thoughts and actions. However, there is limited understanding of the epidemiological characteristics, particularly in China. This study aims to analyze the demographics and behaviors of individuals engaging in online broadcast suicide in China to inform targeted prevention strategies. Methods: A total of 525 incidents were identified through systematic retrieval of relevant news reports from online sources. Subsequently, a content analysis was performed on these reports to extract detailed information on the characteristics of each individual incident. Results: Among the incidents analyzed, the male-to-female ratio was 1:1.6, with an average age of 23.1 ± 5.9 years. Approximately 71.9% took place in Southern China. Unemployment was reported in 15.0% of incidents. Relationship breakup (62.3%) was cited as the leading cause of suicide. Wrist cutting (58.2%) emerged as the predominant suicide method, and home (36.2%) was the most common location for these tragic events. Instant messaging apps were the primary platforms (54.7%) for conveying suicidal thoughts and actions. Additionally, among the 525 incidents examined, 12.0% disclosed having a mental disorder, and 7.6% had a history of prior suicide attempts. Significant variations were observed across age, gender, region, and occupation categories. Conclusion: This study emphasizes the importance of developing suicide prevention programs for internet users. Besides, interventions should be customized to meet the specific needs of various populations.


Asunto(s)
Suicidio , Humanos , China/epidemiología , Masculino , Femenino , Adulto , Suicidio/estadística & datos numéricos , Suicidio/psicología , Adulto Joven , Adolescente , Prevención del Suicidio , Ideación Suicida , Medios de Comunicación Sociales/estadística & datos numéricos , Internet , Persona de Mediana Edad
2.
Front Public Health ; 12: 1295975, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38550327

RESUMEN

Objectives: Workplace violence (WPV) against healthcare workers (HCWs) has reached significant levels globally, impeding the quality and accessibility of healthcare systems. However, there is limited available knowledge regarding the determinants linked with WPV among HCWs and the discrepancies observed across various levels of hospitals in China. The objective of the present research was to investigate the factors linked to WPV and job satisfaction among HCWs in China. Methods: A self-developed questionnaire based on WeChat was employed to collect data. The questionnaire consisted of demographic information as well as occupational factors. To measure WPV, the Chinese version of the Workplace Violence Scale was utilized. Career satisfaction was assessed through two questions regarding career choices. The collected data was analyzed using descriptive analyses, chi-square tests, and multivariate logistic regressions. Results: A total of 3,781 valid questionnaires (1,029 doctors and 2,752 nurses) were collected. Among all participants, 2,201 (58.2%) reported experiencing at least one form of WPV in the past year, with emotional abuse being the most frequent occurrence (49.7%), followed by threats (27.9%). The multivariate logistic regression analysis revealed several risk factors associated with WPV, including male gender, shift work, senior professional title, bachelor's degree education, employment in secondary-level hospitals, and working over 50 h per week (p < 0.05). Career satisfaction among HCWs who experienced high levels of WPV was low, with only 11.2% remaining confident in their profession, and a mere 2.0% supporting their children pursuing careers in healthcare. Conclusion: WPV poses a significant challenge within the Chinese healthcare system. Efforts should be made to address the identified risk factors and promote a safe and satisfying working environment for HCWs.


Asunto(s)
Médicos , Violencia Laboral , Niño , Humanos , Masculino , Violencia Laboral/psicología , Estudios Transversales , China/epidemiología , Médicos/psicología , Hospitales
4.
Int J Ophthalmol ; 16(9): 1386-1394, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37724272

RESUMEN

Pterygium is a prevalent ocular disease that can cause discomfort and vision impairment. Early and accurate diagnosis is essential for effective management. Recently, artificial intelligence (AI) has shown promising potential in assisting clinicians with pterygium diagnosis. This paper provides an overview of AI-assisted pterygium diagnosis, including the AI techniques used such as machine learning, deep learning, and computer vision. Furthermore, recent studies that have evaluated the diagnostic performance of AI-based systems for pterygium detection, classification and segmentation were summarized. The advantages and limitations of AI-assisted pterygium diagnosis and discuss potential future developments in this field were also analyzed. The review aims to provide insights into the current state-of-the-art of AI and its potential applications in pterygium diagnosis, which may facilitate the development of more efficient and accurate diagnostic tools for this common ocular disease.

5.
J Leukoc Biol ; 114(6): 604-614, 2023 11 24.
Artículo en Inglés | MEDLINE | ID: mdl-37647586

RESUMEN

Bronchopulmonary dysplasia, a common complication of premature infants, is mainly characterized by blocked alveolarization. Proverbially, the injury of alveolar type II epithelial cells is regarded as the pathologic basis of occurrence and development of bronchopulmonary dysplasia. In the case of alveolar epithelial damage, alveolar type II epithelial cells can also differentiate to alveolar type I epithelial cells as progenitor cells. During bronchopulmonary dysplasia, the differentiation of alveolar type II epithelial cells becomes abnormal. Group 2 innate lymphoid cells can produce type 2 cytokines in response to a variety of stimuli, including the epithelial cytokines IL-25, IL-33, and thymic stromal lymphopoietin. Previous studies have shown that group 2 innate lymphoid cells can inhibit the alveolarization process of bronchopulmonary dysplasia by secreting IL-13. However, whether group 2 innate lymphoid cells can affect the differentiation of alveolar type II epithelial cells in the pathologic process of bronchopulmonary dysplasia remains unclear. In this study, we have shown that IL-13 secreted by group 2 innate lymphoid cells increased during bronchopulmonary dysplasia, which was related to the release of large amounts of IL-33 by impaired alveolar type II epithelial cells. This led to abnormal differentiation of alveolar type II epithelial cells, reduced differentiation to alveolar type I epithelial cells, and increased transdifferentiation to mesenchymal cells through the epithelial-mesenchymal transition. Taken together, our study provides a complementary understanding of the development of bronchopulmonary dysplasia and highlights a novel immune mechanism in the pathogenesis of bronchopulmonary dysplasia.


Asunto(s)
Displasia Broncopulmonar , Recién Nacido , Ratones , Animales , Humanos , Displasia Broncopulmonar/etiología , Displasia Broncopulmonar/patología , Interleucina-33 , Inmunidad Innata , Interleucina-13 , Linfocitos/patología , Células Epiteliales Alveolares/patología , Diferenciación Celular , Citocinas
6.
Int J Ophthalmol ; 16(7): 995-1004, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37465510

RESUMEN

AIM: To conduct a classification study of high myopic maculopathy (HMM) using limited datasets, including tessellated fundus, diffuse chorioretinal atrophy, patchy chorioretinal atrophy, and macular atrophy, and minimize annotation costs, and to optimize the ALFA-Mix active learning algorithm and apply it to HMM classification. METHODS: The optimized ALFA-Mix algorithm (ALFA-Mix+) was compared with five algorithms, including ALFA-Mix. Four models, including ResNet18, were established. Each algorithm was combined with four models for experiments on the HMM dataset. Each experiment consisted of 20 active learning rounds, with 100 images selected per round. The algorithm was evaluated by comparing the number of rounds in which ALFA-Mix+ outperformed other algorithms. Finally, this study employed six models, including EfficientFormer, to classify HMM. The best-performing model among these models was selected as the baseline model and combined with the ALFA-Mix+ algorithm to achieve satisfactory classification results with a small dataset. RESULTS: ALFA-Mix+ outperforms other algorithms with an average superiority of 16.6, 14.75, 16.8, and 16.7 rounds in terms of accuracy, sensitivity, specificity, and Kappa value, respectively. This study conducted experiments on classifying HMM using several advanced deep learning models with a complete training set of 4252 images. The EfficientFormer achieved the best results with an accuracy, sensitivity, specificity, and Kappa value of 0.8821, 0.8334, 0.9693, and 0.8339, respectively. Therefore, by combining ALFA-Mix+ with EfficientFormer, this study achieved results with an accuracy, sensitivity, specificity, and Kappa value of 0.8964, 0.8643, 0.9721, and 0.8537, respectively. CONCLUSION: The ALFA-Mix+ algorithm reduces the required samples without compromising accuracy. Compared to other algorithms, ALFA-Mix+ outperforms in more rounds of experiments. It effectively selects valuable samples compared to other algorithms. In HMM classification, combining ALFA-Mix+ with EfficientFormer enhances model performance, further demonstrating the effectiveness of ALFA-Mix+.

7.
J Dig Dis ; 24(3): 181-193, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37210622

RESUMEN

OBJECTIVES: Nonvariceal gastrointestinal bleeding (NVGIB) is a common medical condition with significant mortality and morbidity. Several types of hemostatic modalities are currently available in clinical setting. This systematic review and network meta-analysis aimed to assess the efficacy of these modalities in treating NVGIB. METHODS: PubMed, EMBASE, and the Cochrane Library databases were searched for studies that compared the efficacy of different hemostatic techniques (over-the-scope clip [OTSC], hemostatic powder [HP] and conventional endoscopic treatment [CET]) for NVGIB published up to June 2022. The 30-day rebleeding rate was regarded as the primary outcome. We performed pairwise and network meta-analyses for all treatments. The heterogeneity and transitivity were evaluated. RESULTS: Twenty-two studies were included. Regarding the 30-day rebleeding rate, OTSC and HP plus CET showed superior efficacy in treating NVGIB compared with CET (OTSC vs CET: relative risk [RR] 0.42, 95% confidence interval [CI] 0.28-0.60; HP plus CET vs CET: RR 0.40, 95% CI 0.17-0.87), while OTSC and HP plus CET had comparable efficacy (RR 0.95, 95% CI 0.38-2.31). HP plus CET ranked the highest in the network ranking estimate. The sensitivity analysis showed that it was not robust that OTSC was superior to CET regarding the short-term rebleeding rate and the initial hemostasis rate. While all-cause mortality, bleeding-related mortality and necessity of surgical or angiographic salvage therapy showed no statistically significant difference. CONCLUSION: OTSC and HP plus CET significantly reduced 30-day rebleeding rate compared to CET and had comparable efficacy in the treatment of NVGIB.


Asunto(s)
Hemostasis Endoscópica , Hemostáticos , Humanos , Metaanálisis en Red , Hemorragia Gastrointestinal , Técnicas Hemostáticas , Endoscopía , Hemostáticos/uso terapéutico , Hemostasis Endoscópica/métodos
8.
9.
Cyberpsychol Behav Soc Netw ; 26(3): 188-197, 2023 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-36787470

RESUMEN

Consumption is undergoing a digital revolution brought about by virtual technology, and the emergence of virtual spokespersons has changed the pattern of advertising endorsement sales. Are virtual character spokespersons better than real celebrity spokespersons? This article aims to explore the relationships between different types of advertising spokespersons, different types of advertising scenarios, and consumers' purchase intentions. The results of 2 pilot experiments and 4 formal experiments show that compared with spokespersons by real people, virtual character spokespersons have a greater positive impact on consumers' purchase intentions, which is achieved through the mediating role of psychological need satisfaction. In addition, different advertising scenarios provided by virtual technology have a moderating effect on this process. This empirical study investigates the possible positive effects of virtual character spokesperson compared with real character spokesperson and expands the results of spokesperson category based on self-determination theory.


Asunto(s)
Publicidad , Comportamiento del Consumidor , Humanos , Encuestas y Cuestionarios , Intención , Comercio
12.
Vascular ; 31(6): 1194-1200, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-35799413

RESUMEN

OBJECTIVES: The aim of this study was to evaluate the effect of microbubbles on the efficacy of transcranial doppler (TCD) ultrasound-assisted thrombolytic therapy of recombinant tissue-type plasminogen activator (rt-PA). METHODS: Male New Zealand white rabbits (n = 36) were randomly divided into an rt-PA group (n = 18) and an rt-PA plus microbubble group (n = 18). After the cerebral infarction model was constructed with autologous blood clots, rt-PA and rt-PA plus microbubble intervention were performed, respectively. The hemodynamic changes and infarct size of the two groups were recorded. In addition, the ELISA method was used to detect the level of nitric oxide (NO), superoxide dismutase (SOD), and malondialdehyde (MDA) in the brain tissue of the two-group graph model and high-sensitivity C-reactive protein (hs-CRP) in the serum. RESULTS: In the rt-PA group, the recanalization rate was 38.9% and the average infarct size was 11.8%. In the rt-PA plus microbubble group, the recanalization rate was 66.7% and the average infarct size was 8.2%. In addition, the average values for NO, SOD, MDA, and hs-CRP were 16.48 ± 5.39 µmol/L, 730.2 ± 9.86 U/mg, 0.92 ± 0.43 nmol/mg, and 8.56 ± 1.64 mg/L in the rt-PA group, respectively, and the average values were 9.18 ± 3.37 µmol/L, 426.2 ± 6.39 U/mg, 0.73 ± 0.44 nmol/mg, and 5.23 ± 0.94 mg/L in the rt-PA plus microbubble group, respectively. CONCLUSIONS: The addition of microbubbles enhanced the effects of TCD-assisted rrt-PA thrombolysis.


Asunto(s)
Microburbujas , Activador de Tejido Plasminógeno , Masculino , Animales , Conejos , Activador de Tejido Plasminógeno/efectos adversos , Proteína C-Reactiva , Terapia Trombolítica/efectos adversos , Terapia Trombolítica/métodos , Ultrasonografía Doppler Transcraneal/métodos , Infarto , Superóxido Dismutasa
13.
Front Public Health ; 10: 1030035, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36339236

RESUMEN

Objectives: Patient-initiated hospital violence is a global problem which threatens the safety of health professionals and is indicative of doctor-patient tensions, impeding health system quality and access. The current study aimed to improve the understanding of medical workplace violence (WPV) in China, using authoritative and nationally representative judgment records, and to approach violence prevention strategies. Methods: All litigation records relating to violence against health professionals between 2013 and 2021 were extracted from the China Judgment Online System. Basic case information, victim characteristics, perpetrator characteristics and the nature of the violence were collated. The relationship between different treatment outcomes and violence was also explored. Results: Numbers of cases of hospital violence gradually increased from 2013 to a peak in 2016 before gradually decreasing in the following years. The most common perpetrators were patients' relatives (58.2%), followed by patients themselves (38.2%). Only 9 perpetrators had a confirmed history of mental illness and only two were intoxicated with alcohol. More than half of the cases (52.5%) occurred in rural areas and this percentage is even greater for primary health care institutions (71.4%) and secondary hospitals (73.5%). On a departmental level, the highest incidence of medical WPV was found in the emergency (18.9%), pediatrics (13.2%) and obstetrics (11.5%) departments. Violent behaviors, such as stalking, mass occupation of the ward and sharp instrument injury were significantly related to cases not involving patient death (p < 0.05). Disruptive behavior, such as hanging banners, blocking hospital passages, placing flower wreaths and burning paper money were significantly correlated with cases involving patient death (p < 0.01). The interval between a patient's death and the ensuing violence was short, happening on the same day in 54.8% of cases. Conclusions: A comprehensive overview of medical WPV in China is presented and may have utility for the formulation of prevention strategies.


Asunto(s)
Criminales , Violencia Laboral , Humanos , Niño , Violencia Laboral/prevención & control , Juicio , Personal de Salud , China/epidemiología
14.
Zhongguo Shi Yan Xue Ye Xue Za Zhi ; 30(5): 1572-1576, 2022 Oct.
Artículo en Chino | MEDLINE | ID: mdl-36208268

RESUMEN

OBJECTIVE: To investigate the status of transfusion-transmissible infection (TTI) among voluntary blood donors in Nanjing in recent five years, in order to provide data support for the recruitment of blood donors and formulation and updating of blood screening strategies. METHODS: HIV/HBV/HCV/TP serological markers were detected by ELISA in 487 120 blood donors in Nanjing from 2016 to 2020. Confirmatory assay was applied in anti-HIV positive samples by Nanjing Municipal Center for Disease Control and Prevention. The prevalence of TTI was calculated and the trend of disease was analyzed under different demographic groups. RESULTS: The total positive rate of TTI in blood donors was 0.49% (2 411/487 120), in which the overall seroprevalence rate of HBsAg, anti-HCV, anti-HIV and anti-TP was 0.23%, 0.09%, 0.01% and 0.16%, respectively. The overall prevalence of HIV and TP remained relatively steady (P>0.05), whereas HBV and HCV decreased year by year (P<0.05). The prevalence of TTI was higher among people with lower education level, high age group and first-time blood donation. CONCLUSION: The prevalence of TTI among voluntary blood donors in Nanjing is at a low level from 2016 to 2020, but the risk still exists. The recruitment of regular donors and the improvement of blood screening technology can effectively reduce the risk of TTI.


Asunto(s)
Infecciones por VIH , Sífilis , Donantes de Sangre , Infecciones por VIH/epidemiología , Antígenos de Superficie de la Hepatitis B , Humanos , Prevalencia , Estudios Seroepidemiológicos , Voluntarios
15.
Front Public Health ; 10: 978322, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36111194

RESUMEN

Background: Violence against health professionals is a global public health problem. In 2019, a doctor was killed in Civil Aviation General Hospital (CAGH), which triggered national discussion about hospital violence. Sina Weibo, the Chinese version of Twitter, played an important role in this public discussion. The CAGH incident provides us with an opportunity to explore how social media was used in the discussion on violence against doctors. Methods: Using the built-in search engine of Sina Weibo, a data set containing 542 Chinese micro-blogs was established. Three keywords: Civil Aviation General Hospital, doctor, and knife were used to search for related posts between December 24th, 2019 and January 19th, 2020. We made a content analysis of the posts to investigate: Weibo users' demographics, views about the incident of CAGH, and measures to prevent hospital violence. Results: Overall, 89.3% of the posts were sent by individual Weibo users, and 10.7% by organizations. Among the individual users, doctors accounted for 27.4%, but only 1.0% came from the legal profession. In addition, 86.7% of the micro-blogs expressed sympathy for the attacked doctor, and 23.1% of the micro-blogs thought that the imperfect medical system was the main cause of the accident. Nearly half of the posts described their disappointment with the government and the society, and 58.6% of medical staff users expressed regret for engaging in medical work. Only 14.2% of micro-blogs put forward some constructive strategies to prevent hospital violence. Conclusion: Weibo users played an important role in spreading and discussing the CAGH incident. However, constructive measures to protect doctors were rarely mentioned, and legal opinions were not reflected in time. Hospital violence has caused public dissatisfaction with the government and weakened the professional confidence of medical staff. Occupational health and public health stakeholders must take effective measures to solve workplace violence against doctors.


Asunto(s)
Aviación , Médicos , Violencia Laboral , China , Hospitales Generales , Humanos
16.
Eur J Med Res ; 27(1): 176, 2022 Sep 10.
Artículo en Inglés | MEDLINE | ID: mdl-36088368

RESUMEN

Hyperuricemia can induce acute and chronic kidney damage, but the pathological mechanism remains unclear. The potential role of AMP-activated protein kinase (AMPK) α2 in hyperuricemia-induced renal injury was investigated in this study. Acute and chronic hyperuricemic nephropathy was induced by administering intraperitoneal injections of uric acid and oxonic acid to AMPK α2 knockout and wild-type mice. Changes in renal function, histopathology, inflammatory cell infiltration, renal interstitial fibrosis, and urate deposition were analyzed. In both acute and chronic hyperuricemic nephropathy mouse models, knockout of AMPK α2 significantly reduced serum creatinine levels and renal pathological changes. The tubular expression of kidney injury molecule-1 was also reduced in hyperuricemic nephropathy mice deficient in AMPK α2. In addition, knockout of AMPK α2 significantly suppressed the infiltration of renal macrophages and progression of renal interstitial fibrosis in mice with chronic hyperuricemic nephropathy. Knockout of AMPK α2 reduced renal urate crystal deposition, probably through increasing the expression of the uric acid transporter, multidrug resistance protein 4. In summary, AMPK α2 is involved in acute and chronic hyperuricemia-induced kidney injury and may be associated with increased urate crystal deposition in the kidney.


Asunto(s)
Proteínas Quinasas Activadas por AMP/metabolismo , Hiperuricemia , Enfermedades Renales , Fallo Renal Crónico , Proteínas Quinasas Activadas por AMP/genética , Animales , Modelos Animales de Enfermedad , Fibrosis , Hiperuricemia/inducido químicamente , Hiperuricemia/genética , Riñón/patología , Enfermedades Renales/genética , Enfermedades Renales/metabolismo , Ratones , Ratones Noqueados , Ácido Úrico/efectos adversos , Ácido Úrico/metabolismo
17.
Front Immunol ; 13: 863317, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35936008

RESUMEN

IgGFc-binding protein (FCGBP) is a mucin first detected in the intestinal epithelium. It plays an important role in innate mucosal epithelial defense, tumor metastasis, and tumor immunity. FCGBP forms disulfide-linked heterodimers with mucin-2 and members of the trefoil factor family. These formed complexes inhibit bacterial attachment to mucosal surfaces, affect the motility of pathogens, and support their clearance. Altered FCGBP expression levels may be important in the pathologic processes of Crohn's disease and ulcerative colitis. FCGBP is also involved in regulating the infiltration of immune cells into tumor microenvironments. Thus, the molecule is a valuable marker of tumor prognosis. This review summarizes the functional relevance and role of FCGBP in immune responses and disease development, and highlights the potential role in diagnosis and predicting tumor prognosis.


Asunto(s)
Mucinas , Neoplasias , Moléculas de Adhesión Celular/metabolismo , Humanos , Inmunidad Mucosa , Mucosa Intestinal , Mucinas/metabolismo , Neoplasias/metabolismo , Proteínas/metabolismo , Microambiente Tumoral
18.
Front Chem ; 10: 915468, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35755244

RESUMEN

Low or excessively high concentration of S-vacancy (C S-vacancy) is disadvantageous for the hydrogen evolution reaction (HER) activity of MoS2-based materials. Additionally, alkaline water electrolysis is most likely to be utilized in the industry. Consequently, it is of great importance for fine-tuning C S-vacancy to significantly improve alkaline hydrogen evolution. Herein, we have developed a one-step Ru doping coupled to compositing with CoS2 strategy to precisely regulate C S-vacancy of MoS2-based materials for highly efficient HER. In our strategy, Ru doping favors the heterogeneous nucleation and growth of CoS2, which leads to a high crystallinity of Ru-doped CoS2 (Ru-CoS2) and rich heterogeneous interfaces between Ru-CoS2 and Ru-doped MoS2-x (Ru-MoS2-x). This facilitates the electron transfer from Ru-CoS2 to Ru-MoS2-x, thereby increasing C S-vacancy of MoS2-based materials. Additionally, the electron injection effect increases gradually with an increase in the mass of Co precursor (m Co), which implies more S2- leaching from MoS2 at higher m Co. Subsequently, C S-vacancy of the as-synthesized samples is precisely regulated by the synergistic engineering of Ru doping and compositing with CoS2. At C S-vacancy = 17.1%, a balance between the intrinsic activity and the number of exposed Mo atoms (EMAs) to boost highly active EMAs should be realized. Therefore, the typical samples demonstrate excellent alkaline HER activity, such as a low overpotential of 170 mV at 100 mA cm-2 and a TOF of 4.29 s-1 at -0.2 V. Our results show promise for important applications in the fields of electrocatalysis or energy conversion.

19.
Cureus ; 14(4): e24053, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-35573501

RESUMEN

Introduction The elevation of aminotransferase levels is regarded as an indicator of hepatocellular injury. The objective of this study was to describe real-world incidence of elevated aminotransferase levels with or without bilirubin elevation among patients treated with immune checkpoint inhibitors (ICIs) for solid tumors. Methods This retrospective cohort study used an electronic health record database representing > 1.5 million active United States (US) cancer patients and included patients diagnosed with any cancer between January 1, 2014 and March 31, 2019, and treated with one or more ICIs such as ipilimumab, tremelimumab, nivolumab, pembrolizumab, atezolizumab, durvalumab, and avelumab. The frequency, onset, duration, management of grade ≥ 3 elevation of aminotransferase levels with or without bilirubin elevation events, progression rate from isolated elevation of aminotransferase levels (IAT) to elevated aminotransferase levels with elevated bilirubin (ATWB), and mortality were described. Results Overall, 69,140 patients received 85,433 treatment courses. A total of 1,799 (2.11%) IAT and 441 (0.52%) ATWB events were observed during treatment courses. The median onset was 51 and 42 days for IAT and ATWB, respectively, across treatment courses, and the median duration of both was approximately seven days. Approximately 5% (n=96) of IAT events progressed to ATWB in a median time of 11 days. The proportion of patients who received corticosteroids after elevated aminotransferase levels with or without bilirubin was ~37% (n=671/1,799 of IAT and n=147/441 of ATWB) and ~8% discontinued ICI treatment (n=118/1,799 of IAT and n=43/441 of ATWB). About 46% (n=68/147) of ATWB and and 25% (n=172/671) of IAT events treated with steroids led to death within 45 days. Similarly, 49% (n=21/43) of ATWB and 35% (n=42/118) of IAT events leading to treatment discontinuation led to death within 45 days. Conclusions Real-world data from oncology clinics in US suggest low incidence of grade ≥ 3 elevated aminotransferase levels with or without bilirubin elevation following treatment with ICIs. In most cases, ICI treatment was not discontinued and management of elevated aminotransferases consisted of corticosteroid treatment in one-third of cases.

20.
Lupus Sci Med ; 9(1)2022 04.
Artículo en Inglés | MEDLINE | ID: mdl-35414608

RESUMEN

OBJECTIVE: Lupus nephritis (LN) is a major complication and cause of death among patients with SLE. This research used in vivo and in vitro experiments to explore the therapeutic potential of metformin in kidney injury from LN-induced inflammation. METHODS: In vivo study, 8-week-old MRL/MpJ-Faslpr/J (MRL/lpr) mice were randomly divided into two groups (n=12 each): daily administration of 0.3 mg/mL metformin in drinking water and control (water only). Body weight and urinary samples were measured biweekly. Mice were sacrificed after 8-week treatment to harvest serum, lymph nodes, spleen and kidneys. In vitro study, human kidney-2 (HK-2) cells were pretreated with 1 mM metformin for 1 hour and then stimulated with 20 µg/mL lipopolysaccharides (LPS) or 10 ng/mL tumour necrosis factor-α (TNF-α) for another 48 hours. Protein was collected for subsequent analysis. RESULTS: We found that metformin administration improved renal function in MRL/lpr lupus-prone mice, measured by decreased urea nitrogen and urinary proteins. Metformin reduced immunoglobulin G and complement C3 deposition in glomeruli. The treatment also downregulated systemic and renal inflammation, as seen in decreased renal infiltration of F4/80-positive macrophages and reduced splenic and renal MCP-1 (monocyte chemoattractant protein-1) and TNF-α, and renal IL-1ß (interleukin 1ß) expression. Metformin administration decreased renal expression of necroptosis markers p-RIPK1 (phosphorylated receptor-interacting protein kinase 1) and p-MLKL, along with tubular injury marker KIM-1 (kidney injury molecule-1) in lupus mice. In addition, metformin alleviated the necroptosis of HK-2 cells stimulated by LPS and TNF-α, evidencing by a decrease in the expression of necroptosis markers p-RIPK1, p-RIPK3 and p-MLKL, and the inflammasome-related markers NLRP3 (NLR family pyrin domain containing 3), ASC (apoptosis-associated speck-like protein containing a CARD), caspase-1. Mechanistically, metformin treatment upregulated p-AMPK (phosphorylated AMP-activated protein kinase) and downregulated p-STAT3 (phosphorylated signal transducer and activator of transcription 3) expression in the kidneys. Moreover, AMPKα2 knockdown abolished the protective effects of metformin in vitro. CONCLUSIONS: Metformin alleviated kidney injury in LN though suppressing renal necroptosis and inflammation via the AMPK/STAT3 pathway.


Asunto(s)
Lupus Eritematoso Sistémico , Nefritis Lúpica , Metformina , Proteínas Quinasas Activadas por AMP/metabolismo , Proteínas Quinasas Activadas por AMP/farmacología , Animales , Humanos , Inflamación , Riñón/metabolismo , Lipopolisacáridos/metabolismo , Lipopolisacáridos/farmacología , Lipopolisacáridos/uso terapéutico , Lupus Eritematoso Sistémico/complicaciones , Lupus Eritematoso Sistémico/tratamiento farmacológico , Nefritis Lúpica/complicaciones , Nefritis Lúpica/tratamiento farmacológico , Metformina/farmacología , Metformina/uso terapéutico , Ratones , Ratones Endogámicos MRL lpr , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Factor de Transcripción STAT3/metabolismo , Factor de Transcripción STAT3/farmacología , Factor de Transcripción STAT3/uso terapéutico , Transducción de Señal/fisiología , Factor de Necrosis Tumoral alfa/metabolismo , Factor de Necrosis Tumoral alfa/farmacología , Factor de Necrosis Tumoral alfa/uso terapéutico
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