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BACKGROUND: Acute non-variceal upper gastrointestinal bleeding (ANVUGIB) represents a significant clinical challenge due to its unpredictability and potentially severe outcomes. The Rockall risk score has emerged as a critical tool for prognostic assessment in patients with ANVUGIB, aiding in the prediction of rebleeding and mortality. However, its applicability and accuracy in the Chinese population remain understudied. AIM: To assess the prognostic value of the Rockall risk score in a Chinese cohort of patients with ANVUGIB. METHODS: A retrospective analysis of 168 ANVUGIB patients' medical records was conducted. The study employed statistical tests, including the t-test, χ 2 test, spearman correlation, and receiver operating characteristic (ROC) analysis, to assess the relationship between the Rockall score and clinical outcomes, specifically focusing on rebleeding events within 3 months post-assessment. RESULTS: Significant associations were found between the Rockall score and various clinical outcomes. High Rockall scores were significantly associated with rebleeding events (r = 0.735, R 2 = 0.541, P < 0.001) and strongly positively correlated with adverse outcomes. Low hemoglobin levels (t = 2.843, P = 0.005), high international normalized ratio (t = 3.710, P < 0.001), active bleeding during endoscopy (χ 2 = 7.950, P = 0.005), large ulcer size (t = 6.348, P < 0.001), and requiring blood transfusion (χ 2 = 6.381, P = 0.012) were all significantly associated with rebleeding events. Furthermore, differences in treatment and management strategies were identified between patients with and without rebleeding events. ROC analysis indicated the excellent discriminative power (sensitivity: 0.914; specificity: 0.816; area under the curve: 0.933; Youden index: 0.730) of the Rockall score in predicting rebleeding events within 3 months. CONCLUSION: This study provides valuable insights into the prognostic value of the Rockall risk score for ANVUGIB in the Chinese population. The results underscore the potential of the Rockall score as an effective tool for risk stratification and prognostication, with implications for guiding risk-appropriate management strategies and optimizing care for patients with ANVUGIB.
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Hyperphosphorylation and aggregation of MAPT (microtubule-associated protein tau) is a pathogenic hallmark of tauopathies and a defining feature of Alzheimer disease (AD). Pathological MAPT/tau is targeted by macroautophagy/autophagy for clearance after being sequestered within autophagosomes, but autophagy dysfunction is indicated in tauopathy. While mitochondrial bioenergetic deficits have been shown to precede MAPT/tau pathology in tauopathy brains, it is unclear whether energy metabolism deficiency is involved in the pathogenesis of autophagy defects. Here, we reveal that stimulation of anaplerotic metabolism restores defective oxidative phosphorylation (OXPHOS) in tauopathy neurons which, strikingly, leads to pronounced MAPT/tau clearance by boosting autophagy functionality through enhancements of mitochondrial biosynthesis and supply of phosphatidylethanolamine for autophagosome biogenesis. Furthermore, early anaplerotic stimulation of OXPHOS elevates autophagy activity and attenuates MAPT/tau pathology, thereby counteracting memory impairment in tauopathy mice. Taken together, our study sheds light on a pivotal role of mitochondrial bioenergetic deficiency in tauopathy-related autophagy defects and suggests a new therapeutic strategy to prevent the buildup of pathological MAPT/tau in AD and other tauopathy diseases.Abbreviation: AA: antimycin A; AD, Alzheimer disease; ATP, adenosine triphosphate; AV, autophagosome/autophagic vacuole; AZ, active zone; Baf-A1: bafilomycin A1; CHX, cycloheximide; COX, cytochrome c oxidase; DIV, days in vitro; DRG, dorsal root ganglion; ETN, ethanolamine; FRET, Förster/fluorescence resonance energy transfer; FTD, frontotemporal dementia; Gln, glutamine; HA: hydroxylamine; HsMAPT/Tau, human MAPT; IMM, inner mitochondrial membrane; LAMP1, lysosomal-associated membrane protein 1; LIs, lysosomal inhibitors; MDAV, mitochondria-derived autophagic vacuole; MmMAPT/Tau, murine MAPT; NFT, neurofibrillary tangle; OCR, oxygen consumption rate; Omy: oligomycin; OXPHOS, oxidative phosphorylation; PPARGC1A/PGC-1alpha: peroxisome proliferative activated receptor, gamma, coactivator 1 alpha; PE, phosphatidylethanolamine; phospho-MAPT/tau, hyperphosphorylated MAPT; PS, phosphatidylserine; PISD, phosphatidylserine decarboxylase;SQSTM1/p62, sequestosome 1; STX1, syntaxin 1; SYP, synaptophysin; Tg, transgenic; TCA, tricarboxylic acid; TEM, transmission electron microscopy.
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Background: Cavities have been reported in approximately 20% of lung cancer after anti-angiogenesis treatments. However, the effect of which on treatment outcomes remains unclear. This study sought to investigate the incidence and radiographic patterns of tumor cavitation in patients with non-small cell lung cancer (NSCLC) treated with apatinib, and its associations with patients' clinical characteristics and outcomes. Methods: A total of 300 patients with NSCLC treated with apatinib were retrospectively identified. Baseline and follow-up chest computed tomography scans were reviewed to identify tumor cavitation, and the subsequent filling-in of the cavitation. A multivariate logistic regression analysis was conducted to identify the factors associated with tumor cavitation. Survival curves were constructed using the Kaplan-Meier method and compared using the log-rank test. Results: Of the 300 patients, 51 (17.0%) developed lung cavitation after initiating apatinib therapy. The results of the multivariate analysis showed that apatinib combination therapy (vs. apatinib monotherapy, odds ratio: 0.593, 95% confidence interval: 0.412-0.854, P=0.005) was significantly associated with tumor cavitation. Patients with tumor cavitation had significantly longer progression-free survival (PFS) than those without cavitation (8.2 vs. 5.2 months, P<0.01). Of the patients, 18 had cavity filling after progression, while 13 had persistent cavities after progression. The corresponding median PFS times were 11.9 and 3.2 months in patients with filled and persistent cavities after disease progression, respectively (P<0.001). Conclusions: Tumor cavitation occurred in 17% of the NSCLC patients treated with apatinib and was associated with better PFS. Patients who had cavities filled after progression had a better prognosis than those with persistent cavities.
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BACKGROUND: Accurately assessing 5-year recurrence rates is crucial for managing non-muscle-invasive bladder carcinoma (NMIBC). However, the European Organization for Research and Treatment of Cancer (EORTC) model exhibits poor performance. PURPOSE: To investigate whether integrating multiparametric MRI (mp-MRI) with clinical factors improves NMIBC 5-year recurrence risk assessment. STUDY TYPE: Retrospective. POPULATION: One hundred ninety-one patients (median age, 65 years; age range, 54-73 years; 27 females) underwent mp-MRI between 2011 and 2017, and received ≥5-year follow-ups. They were divided into a training cohort (N = 115) and validation/testing cohorts (N = 38 in each). Recurrence rates were 23.5% (27/115) in the training cohort and 23.7% (9/38) in both validation and testing cohorts. FIELD STRENGTH/SEQUENCE: 3-T, fast spin echo T2-weighted imaging (T2WI), single-shot echo planar diffusion-weighted imaging (DWI), and volumetric spoiled gradient echo dynamic contrast-enhanced (DCE) sequences. ASSESSMENT: Radiomics and deep learning (DL) features were extracted from the combined region of interest (cROI) including intratumoral and peritumoral areas on mp-MRI. Four models were developed, including clinical, cROI-based radiomics, DL, and clinical-radiomics-DL (CRDL) models. STATISTICAL TESTS: Student's t-tests, DeLong's tests with Bonferroni correction, receiver operating characteristics with the area under the curves (AUCs), Cox proportional hazard analyses, Kaplan-Meier plots, SHapley Additive ExPlanations (SHAP) values, and Akaike information criterion for clinical usefulness. A P-value <0.05 was considered statistically significant. RESULTS: The cROI-based CRDL model showed superior performance (AUC 0.909; 95% CI: 0.792-0.985) compared to other models in the testing cohort for assessing 5-year recurrence in NMIBC. It achieved the highest Harrell's concordance index (0.804; 95% CI: 0.749-0.859) for estimating recurrence-free survival. SHAP analysis further highlighted the substantial role (22%) of the radiomics features in NMIBC recurrence assessment. DATA CONCLUSION: Integrating cROI-based radiomics and DL features from preoperative mp-MRI with clinical factors could improve 5-year recurrence risk assessment in NMIBC. EVIDENCE LEVEL: 3 TECHNICAL EFFICACY: Stage 3.
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Excitonic devices based on interlayer excitons in van der Waals heterobilayers are a promising platform for advancing photoelectric interconnection telecommunications. However, the absence of exciton emission in the crucial telecom C-band has constrained their practical applications. Here, this limitation is addressed by reporting exciton emission at 0.8 eV (1550 nm) in a chemically vapor-deposited, strictly aligned MoTe2/MoS2 heterobilayer, resulting from the direct bandgap transitions of interlayer excitons as identified by momentum-space imaging of their electrons and holes. The decay mechanisms dominated by direct radiative recombination ensure constant emission quantum yields, a basic demand for efficient excitonic devices. The atomically sharp interface enables the resolution of two narrowly-splitter transitions induced by spin-orbit coupling, further distinguished through the distinct Landé g-factors as the fingerprint of spin configurations. By electrical control, the double transitions coupling into opposite circularly-polarized photon modes, preserve or reverse the helicities of the incident light with a degree of polarization up to 90%. The Stark effect tuning extends the emission energy range by over 150 meV (270 nm), covering the telecom C-band. The findings provide a material platform for studying the excitonic complexes and significantly boost the application prospects of excitonic devices in silicon photonics and all-optical telecommunications.
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BACKGROUND: High healthcare costs could arise from unmet needs. This study used random forest (RF) and regression methods to identify predictors of high costs from a US payer perspective in patients newly diagnosed with generalized myasthenia gravis (gMG). METHODS: Adults with gMG (first diagnosis = index) were selected from the IQVIA PharMetrics® Plus database (2017-2021). Predictors of high healthcare costs were measured 12 months pre-index (main cohort) and during both the 12 months pre- and post-index (subgroup). Top 50 predictors of high costs [≥ $9404 (main cohort) and ≥ $9159 (subgroup) per-patient-per-month] were identified with RF models; the magnitude and direction of association were estimated with multivariable modified Poisson regression models. RESULTS: The main cohort and subgroup included 2739 and 1638 patients, respectively. In RF analysis, the most important predictors of high costs before/on the index date were index MG exacerbation, all-cause inpatient admission, and number of days with corticosteroids. After the index date, these were immunoglobulin and monoclonal antibody use and number of all-cause outpatient visits and MG-related encounters. Adjusting for the top 50 predictors, post-index immunoglobulin use increased the risk of high costs by 261%, monoclonal antibody use by 135%, index MG exacerbation by 78%, and pre-index all-cause inpatient admission by 27% (all p < 0.05). CONCLUSIONS: This analysis links patient characteristics both before the formal MG diagnosis and in the first year to high future healthcare costs. Findings may help inform payers on cost-saving strategies, and providers can potentially shift to targeted treatment approaches to reduce the clinical and economic burden of gMG.
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Costos de la Atención en Salud , Aprendizaje Automático , Miastenia Gravis , Humanos , Miastenia Gravis/economía , Miastenia Gravis/tratamiento farmacológico , Masculino , Femenino , Persona de Mediana Edad , Costos de la Atención en Salud/estadística & datos numéricos , Estados Unidos , Adulto , Anciano , Análisis de RegresiónRESUMEN
Cognitive impairment frequently presents as a prevalent consequence following stroke, imposing significant burdens on patients, families, and society. The objective of this study was to assess the effectiveness and underlying mechanism of nerve growth factor (NGF) in treating post-stroke cognitive dysfunction in rats with cerebral ischemia-reperfusion injury (MCAO/R) through delivery into the brain using specific mode electroacupuncture stimulation (SMES). From the 28th day after modeling, the rats were treated with NGF mediated by SMES, and the cognitive function of the rats was observed after treatment. Learning and memory ability were evaluated using behavioral tests. The impact of SMES on blood-brain barrier (BBB) permeability, the underlying mechanism of cognitive enhancement in rats with MCAO/R, including transmission electron microscopy, enzyme-linked immunosorbent assay, immunohistochemistry, immunofluorescence, and TUNEL staining. We reported that SMES demonstrates a safe and efficient ability to open the BBB during the cerebral ischemia repair phase, facilitating the delivery of NGF to the brain by the p65-VEGFA-TJs pathway.
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Background: Kangaroo mother care (KMC) is an evidence-based intervention that can effectively reduce morbidity and mortality in preterm infants, but it has yet to be widely implemented in health systems in China. Most qualitative studies on KMC for preterm infants focused on the experiences and influencing factors from the perspective of preterm infant parents, while neglecting the perspective of healthcare providers, who played a critical role in guiding KMC practice. Therefore, this study aimed to explore the perceptions and experiences of healthcare providers regarding their involvement in KMC implementation for preterm infants to promote the contextualized implementation of KMC. Methods: A descriptive qualitative approach was adopted. A purposive sampling was used to select healthcare providers involved in KMC implementation in the neonatal intensive care units (NICUs) as participants from four tertiary hospitals across four cities in Zhejiang Province, China. Face-to-face semi-structured interviews were conducted to collect information. Thematic analysis was employed to analyze the data. Results: Seventeen healthcare professionals were recruited, including thirteen nurses and four doctors in the NICUs. Four themes and twelve subthemes emerged: different cognitions based on different perspectives (acknowledged effects and benefits, not profitable economically), ambivalent emotions regarding KMC implementation (gaining understanding, gratitude and trust from parents, not used to working under parental presence, and concerning nursing safety issues), barriers to KMC implementation (lack of unified norms and standards, lack of systematic training and communication platform, insufficient human resources, and inadequate parental compliance) and suggestions for KMC implementation (improving equipment and environment, strengthening collaboration between nurses and doctors, and support from hospital managers). Conclusions: Despite acknowledging the clinical benefits of KMC, the lack of economic incentives, concerns about potential risks, and various barriers hindered healthcare providers' intrinsic motivation to implement KMC in NICUs in China. To facilitate the effective implementation of KMC, hospital managers should provide bonuses and training programs for healthcare providers, while giving them recognition and encouragement to enhance their motivation to implement KMC.
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Personal de Salud , Recien Nacido Prematuro , Unidades de Cuidado Intensivo Neonatal , Método Madre-Canguro , Investigación Cualitativa , Humanos , China , Método Madre-Canguro/psicología , Recién Nacido , Femenino , Adulto , Masculino , Personal de Salud/psicología , Actitud del Personal de Salud , Entrevistas como AsuntoRESUMEN
To investigate the renal function and fibrosis indexes of conventional western medicine with Chinese medicine for dredging collaterals in the treatment of renal fibrosis (RF). We searched articles from databases (PubMed, Embase, The Cochrane Library, CNKI, and Wanfang data) and references of included studies. The quality of literature was evaluated and data were extracted in regard to the inclusion and exclusion criteria. RevMan5.3 software was applied for all statistical analyses. Eleven eligible RCTs with a total of 898 patients were included in this meta-analysis. Compared with conventional western medicine alone, conventional western medicine with Chinese medicine for dredging collaterals in the treatment of RF has lower BUN levels and SCr levels (P < 0.05). As for fibrosis indexes, conventional western medicine with Chinese medicine for dredging collaterals has lower HA, laminin (LN), IV-Col, and PC-III levels (P < 0.05). Conventional western medicine with Chinese medicine for dredging collaterals with lower BUN, Scr, HA, LN, PC-III, and IV-Col levels, has an advantage in the treatment of RF. These lower serum levels may not be associated with the presence of RF. Ideally, kidney biopsies should be performed to confirm that these markers reduce RF. This is a major limitation of this study.
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BACKGROUND: kangaroo care (KC), endorsed by the World Health Organization, is an evidence-based intervention that plays a pivotal role in mitigating preterm infant mortality and morbidity. However, this intervention has not been fully integrated into healthcare systems in China. This study aimed to gain insight into parents' perceptions and experiences of KC for preterm infants to contribute to the KC implementation on a larger scale. METHODS: This study employed a descriptive qualitative design, using face-to-face, semi-structured, in-depth interviews. Fifteen parents participating in KC for preterm infants in the neonatal intensive care units (NICUs) were purposively sampled from four hospitals across four cities in Zhejiang Province, China. Thematic analysis was employed to analyze the data. RESULTS: Four themes and twelve subthemes regarding the parents' perceptions and experiences about KC were identified. The four themes included: (1) Low motivation upon initial engagement with KC, (2) Dynamic fluctuations of emotional states during KC, (3) Unexpected gains, and (4) Barriers to participation. CONCLUSIONS: Parents' perceptions and experiences of KC was a staged process, with parents exhibiting distinct cognitive patterns and unique experiences at each stage. Overall, as KC progresses, parents' experiences tended to become increasingly positive, despite potential obstacles encountered along the way. To enhance the implementation of KC, healthcare providers could utilize prenatal and postnatal education programs. These programs aim to enhance the understanding of KC among parents of preterm infants, fostering sustained engagement in KC practices.
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Recien Nacido Prematuro , Unidades de Cuidado Intensivo Neonatal , Método Madre-Canguro , Padres , Investigación Cualitativa , Humanos , Método Madre-Canguro/psicología , China , Recién Nacido , Femenino , Padres/psicología , Masculino , Adulto , Percepción , MotivaciónRESUMEN
OBJECTIVE: Mucinous breast cancer (MBC) is a kind of breast cancer (BC), which is rare in clinic, mainly for women, because of the low incidence rate, so there is no unified standard treatment protocol. Elderly patients have a poor prognosis due to their combined comorbidities. This study aims to investigate the effect of surgery and chemoradiotherapy on the prognosis of elderly female MBC patients and construct nomograms for predicting the OS and CSS in elderly female MBC patients. METHODS: Data for female MBC patients over 65 years are obtained from the Surveillance, Epidemiology and End Results (SEER) database, patients were divided into two groups: the training set and the validation set. External validation data of the prediction model were provided by Kunming Hospital of Traditional Chinese Medicine. We used Cox regression modeling, which was used to identify independent risk factors affecting patient prognosis. After avoiding confounding bias according to the multifactorial Cox regression model, we used these screened statistically significant results to construct column-line plots. The performance of the model was tested using the consistency index (c-index), the calibration curve, and the area under the operating characteristic curve of the receiver (AUC). Subsequently, we used decision curve analysis (DCA) to examine the potential clinical value of our nomograms. RESULTS: A total of 8103 elderly MBC female patients were extracted from the database SEER and were assigned to the training and validation set, randomly. A total of 83 patients from Kunming Hospital of Traditional Chinese Medicine were used in the external verification set. After multifactorial Cox regression analysis, we found that age, race, T-stage, M-stage, surgical approach, radiotherapy, and tumor size were independent risk factors for OS in elderly MBC patients. Similarly, independent risk factors of CSS included age, marital status, N stage, M stage, surgical approach, chemotherapy, and tumor size. The C-index for the OS training, validation, and external verification set were 0.731 (95%CI 0.715-0.747), 0.738 (95%CI 0.724-0.752), and 0.809 (95%CI 0.731-0.8874). The C-index of the training set, the validation set, and external verification set for CSS were 0.786 (95%CI 0.747-0.825), 0.776 (95%CI 0.737-0.815), and 0.84 (95%CI0.754-0.926), respectively. The AUC, calibration curves and DCA also showed good accuracy. CONCLUSIONS: In this study, we construct a new nomogram to predict the prognosis of elderly patients with MBC. The nomograms have undergone internal and external validation and have been confirmed to have good clinical applicability. At the same time, we found that for elderly female MBC patients, surgery and radiotherapy significantly benefit their survival, but chemotherapy is not conducive to patient survival.
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Adenocarcinoma Mucinoso , Neoplasias de la Mama , Nomogramas , Programa de VERF , Humanos , Femenino , Neoplasias de la Mama/terapia , Neoplasias de la Mama/patología , Neoplasias de la Mama/mortalidad , Anciano , Estudios Retrospectivos , Programa de VERF/estadística & datos numéricos , China/epidemiología , Adenocarcinoma Mucinoso/terapia , Adenocarcinoma Mucinoso/patología , Adenocarcinoma Mucinoso/mortalidad , Pronóstico , Anciano de 80 o más Años , Factores de Riesgo , Quimioradioterapia/métodosRESUMEN
The emergence of SARS-CoV-2 variants of concern (VOCs) with increased transmissibility and partial resistance to neutralization by antibodies has been observed globally. There is an urgent need for an effective vaccine to combat these variants. Our study demonstrated that the B.1.351 variant inactivated vaccine candidate (B.1.351V) generated strong binding and neutralizing antibody responses in BALB/c mice against the B.1.351 virus and other SARS-CoV-2 variants after two doses within 28 days. Immunized K18-hACE2 mice also exhibited elevated levels of live virus-neutralizing antibodies against various SARS-CoV-2 viruses. Following infection with these viruses, K18-hACE2 mice displayed a stable body weight, a high survival rate, minimal virus copies in lung tissue, and no lung damage compared to the control group. These findings indicate that B.1.351V offered protection against infection with multiple SARS-CoV-2 variants in mice, providing insights for the development of a vaccine targeting SARS-CoV-2 VOCs for human use.
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BACKGROUND: Ki-67 and human epidermal growth factor receptor 2 (HER2) are known oncogenes involved in bladder cancer (BCa) patient risk stratification. Preoperative assessment of their expression level can assist in clinical treatment decision-making. Recently, amide proton transfer-weighted (APTw) MRI has shown promising potential in the diagnosis of several malignancies. However, few studies reported the value of APTw imaging in evaluating Ki-67 and HER2 status of BCa. PURPOSE: To investigate the feasibility of APTw MRI in assessing the aggressive and proliferative potential regarding the expression levels of Ki-67 and HER2 in BCa. STUDY TYPE: Retrospective. SUBJECTS: 114 patients (mean age, 64.78 ± 11.93 [SD] years; 97 men) were studied. FIELD STRENGTH/SEQUENCE: APTw MRI acquired by a three-dimensional fast-spin-echo sequence at 3.0 T MRI system. ASSESSMENT: Patient pathologic findings, included histologic grade and the expression status of Ki-67 and HER2, were reviewed by one uropathologist. The APTw values of BCa were independently measured by two radiologists and were compared between high-/low-tumor grade group, high-/low-Ki-67 expression group, and high-/low-HER2 expression group. STATISTICAL TESTS: The interclass correlation coefficient, independent sample t-test, Mann-Whitney U test, Spearman's rank correlation, and receiver operating characteristic curve (ROC) analysis were used. P < 0.05 was considered statistically significant. RESULTS: Significantly higher APTw values were found in high-grade BCa patients (7.72% vs. 4.29%, P < 0.001), high-Ki-67 expression BCa patients (8.40% vs. 3.25%, P < 0.001) and HER2 positive BCa patients (8.24% vs. 5.40%, P = 0.001). APTw values were positively correlated with Ki-67 (r = 0.769) and HER2 (r = 0. 356) expression status. The area under the ROC curve of the APTw values for detecting Ki-67 and HER2 expression status were 0.883 (95% CI: 0.790-0.945) and 0.713 (95% CI: 0.592-0.816), respectively. DATA CONCLUSIONS: APTw MRI is a potential method to assess the biological and proliferation potential of BCa. TECHNICAL EFFICACY: Stage 2.
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Objective: Self-management support services can improve patients' self-management ability. This study summarized the best evidence on a self-management support scheme for patients with inflammatory bowel disease based on a mobile health system to accurately describe the current status of the field and provide recommendations for healthcare workers. Methods: Two researchers retrieved studies from computer decision support systems, guideline websites, official association websites, and databases from the establishment of the database until October 2023. The quality of the included studies was independently evaluated by two authors using the Appraisal of Guidelines for Research and Evaluation Instrument II and the 2016 version of the corresponding evaluation standards of the Australian Joanna Briggs Institute Evidence-based Health Care Center. The classification of evidence and recommendation level adopted the 2014 version of the Australian Joanna Briggs Institute evidence pregrading and recommending level system. Results: Fifteen studies were included, comprising one guideline, two expert consensuses, four systematic reviews, four quasi-experimental studies, and four qualitative studies. The overall quality of the included studies was moderate to high. Thirty-six pieces of best evidence were compiled for seven elements, namely, mobile health system type and functional support; mobile health system application preparation; health information recording, uploading, and presentation; zoning management of diseases and early warning of the active period; support related to health education; healthcare support team formation and services; and virtual communities. Conclusions: Our study evaluated the quality of the included studies and summarized a self-management support scheme for patients with inflammatory bowel disease based on a mobile health system. The main scheme was divided into 7 parts and 36 items, which can be used as a reference for healthcare workers so that they can provide more comprehensive and scientific self-management support services for patients with inflammatory bowel disease through mobile health systems.
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A 71-year-old male had disseminated multiple organ dysfunction syndrome (MODS). Following treatment with cefotaxime and piperacillin-tazobactam, his symptoms have worsened instead. Multiple organ failure caused by Japanese Spotted Fever (JSF) was diagnosed based on metagenomic next-generation sequencing (mNGS), we rapidly treated the patient with doxycycline. Thereafter, his symptoms gradually improved. In this report, we emphasized the importance of rapid microbial diagnostic tools and the early use of tetracyclines for the treatment of JSF.
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PURPOSE: To investigate the application value of multiparametric MRI in evaluating the expression status of human epithelial growth factor receptor 2 (HER2) in bladder cancer (BCa). METHODS: From April 2021 to July 2023, preoperative imaging manifestations of 90 patients with pathologically confirmed BCa were retrospectively collected and analyzed. All patients underwent multiparametric MRI including synthetic MRI, DWI, from which the T1, T2, proton density (PD) and apparent diffusion coefficient (ADC) values were obtained. The clinical and imaging characteristics as well as quantitative parameters (T1, T2, PD and ADC values) between HER2-positive and -negative BCa were compared using student t test and chi-square test. The diagnostic efficacy of parameters in predicting HER2 expression status was evaluated by calculating the area under ROC curve (AUC). RESULTS: In total, 76 patients (mean age, 63.59 years ± 12.84 [SD]; 55 men) were included: 51 with HER2-negative and 25 with HER2-positive BCa. HER2-positive group demonstrated significantly higher ADC, T1, and T2 values than HER2-negative group (all P < 0.05). The combination of ADC values and tumor grade yielded the best diagnostic performance in evaluating HER2 expression level with an AUC of 0.864. CONCLUSION: The multiparametric MR characterization can accurately evaluate the HER2 expression status in BCa, which may further guide the determination of individualized anti-HER2 targeted therapy strategies.
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Imágenes de Resonancia Magnética Multiparamétrica , Receptor ErbB-2 , Neoplasias de la Vejiga Urinaria , Humanos , Femenino , Masculino , Neoplasias de la Vejiga Urinaria/diagnóstico por imagen , Neoplasias de la Vejiga Urinaria/metabolismo , Neoplasias de la Vejiga Urinaria/patología , Persona de Mediana Edad , Receptor ErbB-2/metabolismo , Estudios Retrospectivos , Imágenes de Resonancia Magnética Multiparamétrica/métodos , Anciano , Biomarcadores de Tumor/metabolismoRESUMEN
Radiofrequency ablation (RFA), an effective local treatment method for early-stage Hepatocellular Carcinoma (HCC), combined with PD-1 blocking and anti-angiogenic therapy is being extensively explored in advanced HCC, however, the definite results and underlying mechanisms still remain to be elucidated. Therefore, whether non-ablative RFA-based combined therapy can play a synergistic anti-tumor effect through improving tumor immune microenvironment was investigated by us in HCC mouse models. Our results showed that non-ablative RFA could regulate multilayered immunity, such as inducing immunogenic death of tumor cells, upregulating the secretion of inflammatory cytokines, mainly IFN-γ, TNF-α, and IL-10, and subsequently promoting the infiltration of CD8 + T cells. As a result, a significant synergistic anti-tumor effect was demonstrated in the combination therapy group. Similarly, in the real-world setting, non-curative RFA combined with PD-1 blocking and Lenvatinib for 12 patients with Barcelona Clinic Liver Cancer (BCLC) stage C achieve promising results, with 6.9 months (95 % CI: 3.23-15.73) median progression-free survival (mPFS) and 12.7 months (95 % CI: 7.40-19.73) median overall survival (mOS). The common treatment-related adverse reactions were pneumonia and thyroiditis with low prevalence, both less than grade 3 and manageable by symptomatic treatment. Summarily, local non-ablative RFA should be a clinically preferred strategy in combination with PD-1 blocking and anti-angiogenic therapy, because this more flexible scheme abandons its historical concept of tumor eradication, but fully utilizes the immune regulatory function by inducing immunogenic tumor death and has higher-level of safety. Therefore, this is a two-pronged and highly balanced approach to achieved favorable treatment outcomes, while conclusive evidence is still pending, it can be attempted in the real world anyway.
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Inhibidores de la Angiogénesis , Carcinoma Hepatocelular , Inhibidores de Puntos de Control Inmunológico , Neoplasias Hepáticas , Receptor de Muerte Celular Programada 1 , Ablación por Radiofrecuencia , Microambiente Tumoral , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/inmunología , Carcinoma Hepatocelular/mortalidad , Animales , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/inmunología , Humanos , Receptor de Muerte Celular Programada 1/antagonistas & inhibidores , Masculino , Ablación por Radiofrecuencia/métodos , Femenino , Terapia Combinada , Ratones , Persona de Mediana Edad , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Inhibidores de Puntos de Control Inmunológico/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Inhibidores de la Angiogénesis/farmacología , Anciano , Compuestos de Fenilurea/uso terapéutico , Compuestos de Fenilurea/farmacología , Línea Celular Tumoral , Citocinas/metabolismo , Angiogénesis , QuinolinasRESUMEN
BACKGROUND: This study assessed the incremental healthcare costs and resource utilization (HRU) associated with generalized myasthenia gravis (gMG), as well as variability in these outcomes among patients with gMG and common comorbidities and acute MG-related events. METHODS: Adults with gMG and without MG were identified from a large US database (2017-2021). The index date was the first MG diagnosis (gMG cohort) or random date (non-MG cohort). Cohorts were propensity score matched 1:1. The gMG cohort included subgroups of patients with a 12-month pre-index (baseline) cardiometabolic or psychiatric comorbidity, or a post-index MG exacerbation/crisis. Monthly healthcare costs (2021 USD) and HRU were compared post-index between gMG and non-MG cohorts. RESULTS: The gMG and matched non-MG cohorts each contained 2,739 patients. Mean incremental healthcare costs associated with MG were $4,155 (gMG: $5,567; non-MG: $1,411), with differences driven by incremental inpatient costs of $2,166 (gMG: $2,617; non-MG: $452); all p < 0.001. The gMG versus non-MG cohort had 4.36 times more inpatient admissions and 2.26 times more outpatient visits; all p < 0.001. Among patients with gMG in cardiometabolic (n = 1,859), psychiatric (n = 1,308), and exacerbation/crisis (n = 419) subgroups, mean monthly healthcare costs were $6,660, $7,443, and $17,330, respectively. CONCLUSIONS: gMG is associated with substantial incremental costs and HRU, with inpatient costs driving the total incremental costs. Costs increased by 20% and 34% among patients with cardiometabolic and psychiatric conditions, respectively, and over three times among those with acute MG-related events. gMG is a complex disease requiring management of comorbidities and treatment options that can prevent acute symptomatic events.
Generalized myasthenia gravis (gMG) is a rare long-standing condition that affects the junctions between nerves and muscles, causing them to be weak. In a serious case, the diaphragm a muscle that helps with breathing becomes so weak that a patient will need a machine to breathe for them. This is called MG exacerbation or crisis. In this study, we used a large insurance database in the United States to look at how much money healthcare payers paid for gMG patients on average and what healthcare resources patients with gMG used. We compared these findings with patients without gMG. Also, among patients with gMG, we reported these findings specifically for patients who also had heart, blood, or blood vessel disease; patients who had a mental illness; and patients who had MG exacerbation or crisis later on. We found that patients with gMG used $5,567 per month on average ($4,155 more than patients without gMG), mostly from overnight hospital stays. Patients with gMG also had four times more overnight hospital stays and two times more hospital day visits when we compared them to patients without gMG. Patients with gMG and other health conditions used even more money and resources per month. Patients with MG exacerbation or crisis used $17,330 per month on average. Our results showed that gMG led to higher healthcare cost and resource use. In order to reduce cost and resources, doctors also need to control for other health conditions as they treat patients with gMG, and to prevent patients from having MG exacerbation or crisis later on.
Asunto(s)
Comorbilidad , Costo de Enfermedad , Costos de la Atención en Salud , Miastenia Gravis , Humanos , Miastenia Gravis/economía , Miastenia Gravis/epidemiología , Femenino , Masculino , Estados Unidos/epidemiología , Persona de Mediana Edad , Costos de la Atención en Salud/estadística & datos numéricos , Adulto , Anciano , Hospitalización/economía , Hospitalización/estadística & datos numéricosRESUMEN
INTRODUCTION: Paclitaxel (PTX) cannot effectively treat glioma because it cannot cross the bloodbrain barrier (BBB). A specific mode electroacupuncture stimulation (SMES) can temporarily open the BBB, thereby improving drug delivery to the brain. This study aimed to observe SMES-mediated accumulation of PTX in the brain and its anti-glioma effect and explore the role of the Hedgehog pathway. METHODS: The acupoint selectivity of SMES in opening the BBB was examined in normal rats. The penetration and anti-glioma activity were determined in a C6-Luc glioma rat model. SMES was performed using 2/100â¯Hz, 3â¯mA, 6-6â¯s, and 40â¯min The survival curve was analysed by the KaplanMeier method, brain tumour pathology and size was observed by HE staining, and in vivo imaging system respectively. RESULTS: SMES-induced BBB opening had acupoint selectivity. SMES could improve PTX accumulation in brain and SMES-mediated PTX delivery showed enhanced anti-glioma activity due to better brain penetration. Hedgehog pathway was involved in SMES-mediated PTX delivery by regulating Occludin expression. CONCLUSION: SMES at the head acupoints to deliver PTX is a feasible and effective method for treating glioma. The Hedgehog pathway may play a key role in SMES-mediated PTX delivery across the BBB.