Recovery Dynamics and Prognosis After Dialysis for Acute Kidney Injury.

Importance: The interplay among baseline kidney function, severity of acute kidney disease (AKD), and post-AKD kidney function has significant associations with patient outcomes. However, a comprehensive understanding of how these factors are collectively associated with mortality, major adverse cardiac events (MACEs), and end-stage kidney disease (ESKD) in patients with dialysis-requiring acute kidney injury (AKI-D) is yet to be fully explored. Objective: To investigate the associations of baseline kidney function, AKD severity, and post-AKD kidney function with mortality, MACEs, and ESKD in patients with AKI-D. Design, Setting, and Participants: This nationwide, population-based cohort study of patients with AKI-D was conducted between January 1, 2015, and December 31, 2018, using data from various health care settings included in the Taiwan nationwide population-based cohort database. Data analysis was conducted from April 28, 2022, to June 30, 2023. Exposure: Exposure to severe AKI and baseline and post-AKD kidney function. Main Outcomes and Measures: The primary outcomes were all-cause mortality and incident MACEs, and secondary outcomes were risks of permanent dialysis and readmission. Results: A total of 6703 of 22 232 patients (mean [SD] age, 68.0 [14.7] years; 3846 [57.4%] male) with AKI-D with post-AKD kidney function follow-up and AKD stage data were enrolled. During a mean (SD) 1.2 (0.9) years of follow-up, the all-cause mortality rate was 28.3% (n = 1899), while the incidence rates of MACEs and ESKD were 11.1% (n = 746) and 16.7% (n = 1119), respectively. After adjusting for known covariates, both post-AKD kidney function and baseline kidney function, but not AKD severity, were independently associated with all-cause mortality, MACEs, ESKD, and readmission. Moreover, worse post-AKD kidney function correlated with progressive and significant increases in the risk of adverse outcomes. Conclusions and Relevance: In this cohort study of patients with AKI-D, more than one-quarter of patients died after 1.2 years of follow-up. Baseline and post-AKD kidney functions serve as important factors associated with the long-term prognosis of patients with AKI-D. Therefore, concerted efforts to understand the transition from post-AKD to chronic kidney disease are crucial.

Investigation of the Correlation between Enterovirus Infection and the Climate Factor Complex Including the Ping-Year Factor and El Niño-Southern Oscillation in Taiwan.

Enterovirus infection and enterovirus infection with severe complications (EVSC) are critical issues in several aspects. However, there is no suitable predictive tool for these infections. A climate factor complex (CFC) containing several climate factors could provide more effective predictions. The ping-year factor (PYF) and El Niño-Southern Oscillation (ENSO) are possible CFCs. This study aimed to determine the relationship between these two CFCs and the incidence of enterovirus infection. Children aged 15 years and younger with enterovirus infection and/or EVSC were enrolled between 2007 and 2022. Each year was categorized into a ping-year or non-ping-year according to the PYF. Poisson regression was used to evaluate the associations between the PYF, ENSO, and the incidence of enterovirus infection. Compared to the ping-year group, the incidence rate of enterovirus infection, the incidence rate of EVSC, and the ratio of EVSC in the non-ping-year group were 1.24, 3.38, and 2.73 times higher, respectively (p < 0.001). For every one-unit increase in La Niña, the incidence rate of enterovirus infection decreased to 0.96 times (p < 0.001). Our study indicated that CFCs could be potential predictors for enterovirus infection, and the PYF was more suitable than ENSO. Further research is needed to improve the predictive model.

Sodium-Glucose Cotransport Protein 2 Inhibitors in Patients With Type 2 Diabetes and Acute Kidney Disease.

Importance: Sodium-glucose cotransport protein 2 inhibitors (SGLT-2is) have demonstrated associations with positive kidney-related and cardiovascular outcomes in patients with type 2 diabetes. However, the association of SGLT-2is with outcomes among patients with type 2 diabetes and acute kidney disease (AKD) remains unclear. Objective: To examine the long-term associations of SGLT-2is with mortality, major adverse kidney events (MAKEs), and major adverse cardiovascular events (MACEs) in patients with type 2 diabetes and AKD. Design, Setting, and Participants: This cohort study used global health care data (the TriNetX database) spanning from September 30, 2002, to September 30, 2022. Propensity score matching was used to select a cohort of patients, and follow-up was conducted with a maximum duration of 5 years (completed on September 30, 2022) or until the occurrence of an outcome or death. Intervention: The use of SGLT-2is. Main Outcomes and Measures: The primary outcomes measured were mortality, MAKEs, and MACEs. Adjusted hazard ratios (AHR) with 95% CIs were calculated to compare the risks between SGLT-2i users and nonusers, representing the mean treatment effect among the treated patients. Results: A total of 230 366 patients with AKD (mean [SD] age, 67.1 [16.4] years; 51.8% men and 48.2% women) were enrolled in the study, which had a median follow-up duration of 2.3 (IQR, 1.2-3.5) years. Among these, 5319 individuals (2.3%) were identified as SGLT-2i users. Among nonusers, the incidence of mortality was 18.7%, the incidence of MAKEs was 21.0%, and the incidence of MACEs was 25.8%. After propensity score matching, the absolute differences between SGLT-2i users and nonusers for incidence of mortality, MAKEs, and MACEs were 9.7%, 11.5%, and 12.3%, respectively. Based on the treated population, SGLT-2i use was associated with a significantly lower risk of mortality (AHR, 0.69 [95% CI, 0.62-0.77]), MAKEs (AHR, 0.62 [95% CI, 0.56-0.69]), and MACEs (AHR, 0.75 [95% CI, 0.65-0.88]) compared with nonuse. External validation using a multicenter cohort data set of 1233 patients with AKD patients who were SGLT-2i users confirmed the observed beneficial outcomes. Notably, the risk reduction associated with SGLT-2is remained significant even among patients without hypertension, those with advanced chronic kidney disease, and those not receiving other hypoglycemic agents. Conclusions and Relevance: In this cohort study of patients with type 2 diabetes and AKD, administration of SGLT-2is was associated with a significant reduction in all-cause mortality, MAKEs, and MACEs when compared with nonuse, underscoring the importance of SGLT-2is in care after acute kidney injury. These findings emphasize the potential benefits of SGLT-2is in managing AKD and mitigating the risks of major cardiovascular and kidney diseases.

Development of an EBOV MiniG plus system as an advanced tool for anti-Ebola virus drug screening.

The incidence of zoonotic diseases, such as coronavirus disease 2019 and Ebola virus disease, is increasing worldwide. However, drug and vaccine development for zoonotic diseases has been hampered because the experiments involving live viruses are limited to high-containment laboratories. The Ebola virus minigenome system enables researchers to study the Ebola virus under BSL-2 conditions. Here, we found that the addition of the nucleocapsid protein of human coronaviruses, such as severe acute respiratory syndrome coronavirus 2, can increase the ratio of green fluorescent protein-positive cells by 1.5-2 folds in the Ebola virus minigenome system. Further analysis showed that the nucleocapsid protein acts as an activator of the Ebola virus minigenome system. Here, we developed an EBOV MiniG Plus system based on the Ebola virus minigenome system by adding the SARS-CoV-2 nucleocapsid protein. By evaluating the antiviral effect of remdesivir and rupintrivir, we demonstrated that compared to that of the traditional Ebola virus minigenome system, significant concentration-dependent activity was observed in the EBOV MiniG Plus system. Taken together, these results demonstrate the utility of adding nucleocapsid protein to the Ebola virus minigenome system to create a powerful platform for screening antiviral drugs against the Ebola virus.

Effect of Acupuncture on Recovery of Consciousness in Patients with Acute Traumatic Brain Injury: A Multi-Institutional Cohort Study.

Traumatic brain injury (TBI) causes cognitive dysfunction and long-term impairments. This study aims to examine the effectiveness of acupuncture on the recovery of consciousness in TBI patients. This is a retrospective, multi-institutional cohort study. We enrolled patients with newly diagnosed TBI from 1 January 2007 to 3 August 2021, aged 20 years and older, from the Chang Gung Research Database (CGRD). The outcome was defined based on the difference between the first and last Glasgow Coma Scale (GCS). A total of 2163 TBI patients were analyzed, and 237 (11%) received acupuncture in the treatment period. Generally, the initial GCS was lower in the acupuncture users (11 vs. 14). For the results of our study, a higher proportion of acupuncture patients achieved significant improvement (GCS differences ≥ 3) compared to non-acupuncture users (46.0% vs. 22.4%, p-value < 0.001). The acupuncture users had a 2.11 times higher chance of achieving a significant improvement when considering all assessable covariates (adjusted odds ratio (aOR) 2, 11, 95% confidence interval [CI]: 1.31-3.40; p-value = 0.002). Using 1:1 propensity score matching (PSM), the acupuncture users still had better outcomes than the non-acupuncture users (45.3% vs. 32.9%, p-value = 0.020). In conclusion, this study suggests that acupuncture treatment may be beneficial for TBI patients.

Incomplete Recovery from the Radiocontrast-Induced Dysregulated Cell Cycle, Adhesion, and Fibrogenesis in Renal Tubular Cells after Radiocontrast (Iohexol) Removal.

Contrast-induced nephropathy (CIN) is one of the most common causes of acute kidney injury (AKI). However, management is still limited, and the cellular response to radiocontrast removal for CIN remains unclear. This study aimed to explore the latent effects of iohexol in cultured renal tubular cells with or without the removal of iohexol by medium replacement. HK2 renal tubular cells were subcultured 24 h before use in CIN experiments. Three treatment groups were established: the control, a radiocontrast (iohexol)-only group at 75 mg I/mL (I-75), and iohexol exposure for 24 h with culture medium replacement (I-75/M). Cell cycle arrest, fibrogenic mediator assays, cell viability, cell function, and cell-cycle-related protein expression were compared between groups. Iohexol induced numerous changes in HK2 renal tubular cells, such as enlarged cell shape, cell cycle arrest, increased apoptosis, and polyploidy. Iohexol inhibited the expression of cyclins, CDKs, ZO-1, and E-cadherin but conversely enhanced the expression of p21 and fibrosis-related genes, including TGF-ß1, CTGF, collagen I, collagen III, and HIF-1α within 60 hr after the exposure. Except for the recovery from cell cycle arrest and cell cycle gene expression, notably, the removal of iohexol by medium replacement could not fully recover the renal tubular cells from the formation of polyploid cells, the adhesion or spreading, or the expression of fibrosis-related genes. The present study demonstrates, for the first time, that iohexol exerts latent cytotoxic effects on cultured renal tubular cells after its removal, suggesting that these irreversible cell changes may cause the insufficiency of radiocontrast reduction in CIN, which is worth investigating further.

Corrigendum: Risk factors and 180-day mortality of acute kidney disease in critically ill patients: a multi-institutional study.

[This corrects the article DOI: 10.3389/fmed.2023.1153670.].

Corrigendum: Chinese herbal medicine is associated with higher body weight reduction than liraglutide among the obese population: a real-world comparative cohort study.

[This corrects the article DOI: 10.3389/fphar.2022.978814.].

Topical Chinese herbal medicine in treating atopic dermatitis (eczema): A systematic review and meta-analysis with core herbs exploration.

ETHNOPHARMACOLOGICAL RELEVANCE: Topical Chinese herbal medicine (CHM) is commonly used to relieve atopic dermatitis (AD); however, the up-to-date evidence concerning the effectiveness of topical CHM on treating AD is lacking. Moreover, the CHM prescriptions are often too complicated to realize the overall mechanisms of CHM, especially when compared to western medicines (WM). AIM OF THE STUDY: To evaluate the effectiveness of topical CHM for treating AD by conducting a meta-analysis on randomized clinical trials (RCTs). METHODS: Twenty RCTs comparing topical CHM to active control/placebo were included in the final analysis. The primary outcome was the symptom scores changed from baseline and the effectiveness rate was the secondary outcome. Subgroup analysis on different initial symptom severity and the different interventions in control groups was performed. System pharmacology analysis was performed to explore core CHM and possible pharmacological mechanisms of CHM for AD. RESULTS: Compared with active/blank placebo, topical CHM seemed more effective (SMD: -0.35, 95 %CI: -0.59 to -0.10, p-value = 0.005, I2 = 60%). The effectiveness rate was higher (RR: 1.29, 95 %CI 1.15-1.44, p-value <0.00001, I2 = 71%). In subgroup analysis, mild and moderate AD patients with topical CHM were more effective than placebo (SMD: -0.28, 95 %CI -0.56 to -0.01, p-value = 0.04, I2 = 5%; -0.34, 95%CI -0.64 to -0.03, p-value = 0.03, I2 = 0%, separately). Topical CHM has 1.25 times more effective than the topical glucocorticoid (95 %CI 1.09-1.43, p-value = 0.001, I2 = 64%). Core CHMs, such as Phellodendron chinense C.K. Schneid., Sophora flavescens Ait., Cnidium monnieri (L.) Cusson, and Dictamnus dasycarpus Turcz., had effects on the pathways on immune and metabolism systems different from WM. CONCLUSION: Our results exploit the potential role of CHM on treating AD, especially for mild and moderate AD.

Risk factors and 180-day mortality of acute kidney disease in critically ill patients: A multi-institutional study.

Background: Critically ill patients with acute kidney injury (AKI) have a poor prognosis. Recently, the Acute Disease Quality Initiative (ADQI) proposed to define acute kidney disease (AKD) as acute or subacute damage and/or loss of kidney function post AKI. We aimed to identify the risk factors for the occurrence of AKD and to determine the predictive value of AKD for 180-day mortality in critically ill patients. Methods: We evaluated 11,045 AKI survivors and 5,178 AKD patients without AKI, who were admitted to the intensive care unit between 1 January 2001 and 31 May 2018, from the Chang Gung Research Database in Taiwan. The primary and secondary outcomes were the occurrence of AKD and 180-day mortality. Results: The incidence rate of AKD among AKI patients who did not receive dialysis or died within 90 days was 34.4% (3,797 of 11,045 patients). Multivariable logistic regression analysis indicated that AKI severity, underlying early CKD, chronic liver disease, malignancy, and use of emergency hemodialysis were independent risk factors of AKD, while male gender, higher lactate levels, use of ECMO, and admission to surgical ICU were negatively correlated with AKD. 180-day mortality was highest among AKD patients without AKI during hospitalization (4.4%, 227 of 5,178 patients), followed by AKI with AKD (2.3%, 88 of 3,797 patients) and AKI without AKD (1.6%, 115 of 7,133 patients). AKI with AKD had a borderline significantly increased risk of 180-day mortality (aOR 1.34, 95% CI 1.00-1.78; p = 0.047), while patients with AKD but no preceding AKI episodes had the highest risk (aOR 2.25, 95% CI 1.71-2.97; p < 0.001). Conclusion: The occurrence of AKD adds limited additional prognostic information for risk stratification of survivors among critically ill patients with AKI but could predict prognosis in survivors without prior AKI.

Association of clinical factors to functional outcomes in patients with stroke with large-vessel occlusion after endovascular thrombectomy.

BACKGROUND/PURPOSE: Multiple clinical factors have been reported to be associated with functional outcomes in patients with stroke. However, little is known about prognostic predictors of functional independence in patients with stroke undergoing endovascular thrombectomy (EVT). Our study aimed to investigate the correlation between multiple prognostic variables (including EVT and rehabilitation-related parameters) and functional outcomes in patients post-EVT. METHODS: This retrospective cohort study recruited patients hospitalized between December 2018 and March 2022. Patients with stroke with large-vessel occlusion who underwent EVT were eligible for inclusion in the study. Prognostic factors, including premorbid characteristics, laboratory data, EVT- and rehabilitation-related parameters, functional activity level, balance ability, swallowing, and sphincter function, were collected. Logistic regression and generalized linear models were used to analyze their correlations with functional outcomes. RESULTS: A total of 148 patients were included. In the univariate logistic regression analysis, younger age, premorbid functional independence, higher hemoglobin (Hb) level, lower National Institute of Health Stroke Scale (NIHSS) score, absence of hemorrhagic transformation in 14 days, no nasogastric (NG) tube placement, earlier rehabilitation, frequent daily rehabilitation sessions, more out-of-bed rehabilitation, better ability of sitting up, better initial sitting balance, higher Barthel index (BI), absence of immobility, and neurological complications were associated with favorable outcomes at 3 months. In the stepwise regression model, the predictors of favorable function at 3 months included age, ability to sit up, and frequency of daily rehabilitation sessions; favorable outcomes at 6 months were associated with age, ability to sit up, and swallowing function. CONCLUSION: In patients with stroke post-EVT, better functional outcomes were associated with prognostic variables, including younger age, better ability to sit up, normal swallowing function, and frequent daily rehabilitation sessions.

Serum Cystatin C Levels Could Predict Rapid Kidney Function Decline in A Community-Based Population.

BACKGROUND: Several biomarkers have been correlated with the prevalence and severity of chronic kidney disease (CKD); however, the association between biomarkers and rapid kidney function decline (RKFD) is unknown. This study aimed to evaluate the predictive performance of biomarkers to determine who is likely to develop RKFD in a healthy population. METHODS: A community-based cohort of 2608 people residing in northern Taiwan were enrolled, and their renal function was followed annually from January 2014 to December 2019. The outcomes of interest were RKFD, defined as a 15% decrease in the estimated glomerular filtration rate (eGFR) within the first 4 years, and a decrease in eGFR without improvement in the fifth year. Clinical variables and potential predictors of RKFD, namely adiponectin, leptin, tumor necrosis factor-alpha, and cystatin C, were measured and analyzed. RESULTS: The incidence of RKFD was 17.0% (105/619). After matching for age and sex at a 1:1 ratio, a total of 200 subjects were included for analysis. The levels of cystatin C and total vitamin D were significantly negatively correlated with eGFR. eGFR was negatively correlated with the levels of cystatin C and total vitamin D. Among the biomarkers, cystatin C showed the best predictive performance for RKFD (area under the receiver operating characteristic curve: 0.789). Lower serum cystatin C was associated with a higher rate of RKFD in healthy subjects. A generalized additive model showed that 0.82 mg/L was an adequate cut-off value of cystatin C to predict RKFD. Multivariable logistic regression analysis further indicated that low cystatin C and eGFR were independent predictors of the possibility of RKFD. CONCLUSIONS: Serum cystatin C level could predict the possibility of RKFD. We suggest that a low cystatin C level should be considered as a risk factor for RKFD in healthy subjects.

The Characteristics and Mortality of Chinese Herbal Medicine Users among Newly Diagnosed Inoperable Huge Hepatocellular Carcinoma (≥10 cm) Patients: A Retrospective Cohort Study with Exploration of Core Herbs.

For patients with inoperable huge hepatocellular carcinoma (H-HCC, tumor size ≥10 cm), treatment options are limited. This study aimed to evaluate the characteristics and outcomes of patients with H-HCC who use Chinese herbal medicine (CHM). Multi-institutional cohort data were obtained from the Chang Gung Research Database (CGRD) between 1 January 2002 and 31 December 2018. All patients were followed up for 3 years or until the occurrence of death. Characteristics of CHM users and risk of all-cause mortality were assessed, and core CHMs with potential pharmacologic pathways were explored. Among 1618 patients, clinical features of CHM users (88) and nonusers (1530) were similar except for lower serum α-fetoprotein (AFP) and higher serum albumin levels in CHM users. CHM users had significantly higher 3 year overall survival rates (15.0% vs. 9.7%) and 3 year liver-specific survival rates (13.4% vs. 10.7%), about 3 months longer median survival time, and lower risk of all-cause mortality. Core CHMs were discovered from the prescriptions, including Hedyotis diffusa Willd combined with Scutellaria barbata D.Don, Salvia miltiorrhiza Bunge., Curcuma longa L., Rheum palmatum L., and Astragalus mongholicus Bunge. CHM use appears safe and is possibly beneficial for inoperable H-HCC patients; however, further clinical trials are still required.

The association between mortality and use of Chinese herbal medicine among incident stage IV esophageal cancer patients: A retrospective cohort study with core herbs exploration.

Esophageal cancer (EC) remains a leading cause of death worldwide and in Taiwan. The prognosis of advanced-stage EC is notably poor, and the treatment options are limited. Chinese herbal medicine (CHM) has been widely used as a complementary treatment for cancer, yet the long-term effect of CHM in stage IV EC remains unclear. The multi-institutional cohort obtained from the Chang Gung research database (CGRD) was used to study the long-term outcome of CHM use among incident stage IV EC patients from 1 January 2002, to 31 December 2018. All patients were followed up to 5 years or the occurrence of death. The overall survival (OS) and disease-specific survival rates were conducted using Kaplan-Meier estimation. Overlap weighing and landmark analysis were used to eliminate confounding and immortal time biases. Furthermore, we demonstrated the core CHMs for stage IV EC by using the Chinese herbal medicine network (CMN) analysis on prescriptions. Nine hundred eighty-five stage IV EC patients were analyzed, including 74 CHM users and 911 non-CHM users. We found the use of CHM was associated with a higher 5-year overall survival rate than CHM nonusers (the cumulative probability: 19.52% versus 6.04%, log-rank test: p < 0.001, and the p < 0.001 with overlap weighting). In addition, the overall median survival time was about 7 months longer among CHM users. Moreover, the lower 1-, 3-, 5-year disease-specific survival rates were higher among CHM users. Additionally, the risk of all-cause mortality was lower among CHM users when considering accessible demographic covariates (adjusted hazard ratio: 0.59, 95%CI: 0.39, 0.89, p = 0.011). Furthermore, the CMN analysis revealed that CHMs improved health while relieving tumor burden. For example, Hedyotis diffusa Willd . was the core CHM with an anti-cancer effect, while Fritillaria thunbergii Miq and Sevilla maindronide Rochebrune were used together to relieve cancer-related gastrointestinal discomfort. The use of CHM seems safe and possibly beneficial among stage IV EC patients with a higher 5-year OS. Further clinical trials on CHM were guaranteed to explore the role of CHM in managing stage IV EC patients.

The combination of sarcopenia and biochemical factors can predict the survival of hepatocellular carcinoma patients receiving transarterial chemoembolization.

Background: Transarterial chemoembolization(TACE) is the suggested treatment for hepatocellular carcinoma (HCC) not amenable to curative treatments. We investigated the role of sarcopenia on overall survival in HCC patients receiving TACE and proposed a new prognostic scoring system incorporating sarcopenia. Materials and methods: We retrospectively analyzed 260 HCC patients who received TACE between 2010 and 2015. Total psoas muscle was measured on a cross-sectional CT image before the first TACE session. Sarcopenia was defined by the pre-determined sex-specific cutoff value. We assessed the impact of sarcopenia and other biochemical factors on the overall survival and compared the new scoring system with other prognostic scoring systems. Results: One hundred and thirty patients (50%) were classified as sarcopenia before the first TACE. They were older with a higher male tendency and a significantly lower body mass index (BMI). Cox regression multivariate analysis demonstrated that sarcopenia, multiple tumors, maximal tumor diameter≥ 5cm, major venous thrombosis, sarcopenia, AFP ≥ 200 ng/ml, and albumin<3.5mg/dL were independent poor prognostic factors for overall survival in HCC patients receiving TACE. Our scoring system comprising these factors outperformed other major scoring systems in terms of predicting survival after TACE. Conclusion: The current study demonstrated that sarcopenia was an independent prognostic factor for HCC undergoing TACE therapy. Our newly developed scoring system could effectively predict patient survival after TACE. Physicians could, based on the current score model, carefully select candidate patients for TACE treatment in order to optimize their survival. Further studies are warranted to validate our findings.

A proposal for T1 subclassification in hepatocellular carcinoma: reappraisal of the AJCC 8th edition.

BACKGROUND: In the 8th edition of American Joint Committee on Cancer (AJCC) staging system for hepatocellular carcinoma (HCC), tumor size is not considered in T1 stage. The present study aimed to find out the optimal cutoff for tumor size to further stratify patients with T1 HCC. METHODS: Operated HCC patients were identified from the Chang Gung Research Database (CGRD), and the patients with T1bN0M0 tumors were further divided into two groups based on the tumor size. The resulting subgroups were denoted as T1b (≤ cutoff) and T1c (> cutoff). The survivals were compared between T1a/b and T1c as well as T1c and T2. RESULTS: From 2002 to 2018, a total of 2893 patients who underwent surgery for T1N0M0 HCC were identified from the CGRD. After excluding cases who died within 30 days of surgery, Kaplan-Meier survival analysis discovered that T1 tumors > 65 mm (T1c) had survivals similar to those of T2N0M0 tumors. Cox regression multivariate analysis further demonstrated that tumor size > 6.5 cm was an independent poor prognostic indicator for T1 HCC. Sensitivity tests also confirmed that tumors lager than 6.5 cm were significantly more likely to develop both tumor recurrence and liver-specific death after surgery. CONCLUSIONS: Our study demonstrated that tumor size would significantly impact the survival outcome of T1 HCC after surgery. Due to significantly worse survival, we proposed a subclassification within T1 HCC, T1c: solitary tumor > 6.5 cm without vascular invasion, to further stratify those patients at risk. Further studies are mandatory to validate our findings.

Chinese herbal medicine is associated with higher body weight reduction than liraglutide among the obese population: A real-world comparative cohort study.

Introduction: In Taiwan, many people receive Chinese herbal medicine (CHM) as an alternative choice to help control body weight. However, the clinical effectiveness of CHM on weight control has not been well studied, while potential risks and adverse effects are still unknown. The aim of our study is to find out a safe and efficient treatment model of CHM for weight control compared to liraglutide in a real-world setting. Methods: we retrospectively analyzed obese subjects [body mass index (BMI)≧25 kg/m2] from Chang Gung Research Database (2013-2018). We evaluated the effect on body weight and BMI changes in obese groups receiving CHM or western medicine (WM, represented liraglutide) within 180 days. The proportion of subjects who achieved 5 and 10% weight reduction was calculated as well. Furthermore, the potential adverse events were analyzed during the study period. Overlap weighting was used to balance the baseline differences between CHM and WM groups. Results: The full cohort comprised 1,360 participants: 701 in the CHM group and 659 in the WM group. At baseline, the CHM group was younger (42.75 ± 12.12 years old in CHM vs. 52.31 ± 11.7 years old in WM, p-value <0.001) and has more female subjects (77.6% in CHM vs. 53.0% in WM, p-value <0.001). On the other hand, CHM users had lower body weight (79.83 ± 15.66 kg vs. 84.68 ± 17.14 kg, p-value <0.001) and BMI (30.58 ± 5.20 vs. 32.84 ± 6.95, p-value <0.001). At day 180, CHM users lost more body weight (-4.5 ± 4.07 kg vs. -2.15 ± 4.05 kg, p-value <0.001) and higher reduction in BMI (-1.77 ± 1.73 vs. -0.9 ± 2.14, p-value <0.001). A total of 53.21% (n = 373) CHM users lost at least 5% of body weight (22.46% for WM users, p-value <0.001), and 18.97% (n = 132) lost at least 10% of body weight (4.55% for WM users, p-value <0.001). The benefit remained consistent with and without overlap weighting. For adverse events, 18 cases of hypertension occurred in 659 subjects in the WM group (2.7%) in comparison to 1 of 701 subjects in the CHM group (0.1%). Conclusion: CHM led to clinically meaningful weight loss without serious adverse events in a real-world setting. Further clinical trials are warranted to validate this result.

The Potential Complementary Role of Using Chinese Herbal Medicine with Western Medicine in Treating COVID-19 Patients: Pharmacology Network Analysis.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic in 2019-coronavirus disease (COVID-19). More and more Western medicine (WM) and Chinese herbal medicine (CHM) treatments have been used to treat COVID-19 patients, especially among Asian populations. However, the interactions between WM and CHM have not been studied. This study aims at using the network pharmacology approach to explore the potential complementary effects among commonly used CHM and WM in a clinical setting from a biomolecular perspective. Three well-published and widely used CHM formulas (National Research Institute of Chinese Medicine 101 (NRICM101), Qing-Fei-Pai-Du-Tang (QFPDT), Hua-Shi-Bai-Du-Formula (HSBDF)) and six categories of WM (Dexamethasone, Janus kinase inhibitors (JAKi), Anti-Interleukin-6 (Anti-IL6), anticoagulants, non-vitamin K antagonist oral anticoagulants (NOAC), and Aspirin) were included in the network pharmacology analysis. The target proteins on which these CHM and WM had direct effects were acquired from the STITCH database, and the potential molecular pathways were found in the REACTOME database. The COVID-19-related target proteins were obtained from the TTD database. For the three CHM formulas, QFPDT covered the most proteins (714), and 27 of them were COVID-19-related, while HSBDF and NRICM101 covered 624 (24 COVID-19-related) and 568 (25 COVID-19-related) proteins, respectively. On the other hand, WM covered COVID-19-related proteins more precisely and seemed different from CHM. The network pharmacology showed CHM formulas affected several inflammation-related proteins for COVID-19, including IL-10, TNF-α, IL-6, TLR3, and IL-8, in which Dexamethasone and Aspirin covered only IL-10 and TNF-α. JAK and IL-6 receptors were only inhibited by WM. The molecular pathways covered by CHM and WM also seemed mutually exclusive. WM had advantages in cytokine signaling, while CHM had an add-on effect on innate and adaptive immunity, including neutrophil regulation. WM and CHM could be used together to strengthen the anti-inflammation effects for COVID-19 from different pathways, and the combination of WM and CHM may achieve more promising results. These findings warrant further clinical studies about CHM and WM use for COVID-19 and other diseases.

Carboplatin-Induced Thrombocytopenia through JAK2 Downregulation, S-Phase Cell Cycle Arrest and Apoptosis in Megakaryocytes.

Chemotherapy-induced thrombocytopenia (CIT) is a common complication when treating malignancies with cytotoxic agents wherein carboplatin is one of the most typical agents causing CIT. Janus kinase 2 (JAK2) is one of the critical enzymes to megakaryocyte proliferation and differentiation. However, the role of the JAK2 in CIT remains unclear. In this study, we used both carboplatin-induced CIT mice and MEG-01 cell line to examine the expression of JAK2 and signal transducer and activator of transcription 3 (STAT3) pathway. Under CIT, the expression of JAK2 was significantly reduced in vivo and in vitro. More surprisingly, the JAK2/STAT3 pathway remained inactivated even when thrombopoietin (TPO) was administered. On the other hand, carboplatin could cause prominent S phase cell cycle arrest and markedly increased apoptosis in MEG-01 cells. These results showed that the thrombopoiesis might be interfered through the downregulation of JAK2/STAT3 pathway by carboplatin in CIT, and the fact that exogenous TPO supplement cannot reactivate this pathway.

Patient Safety and Staff Well-Being: Organizational Culture as a Resource.

The present study examines the relationship between patient safety culture and health workers' well-being. Applying the conservation of resources mechanism, we tested theory-based hypotheses in a large cross-disciplinary sample (N = 3232) from a Taiwanese metropolitan healthcare system. Using the structural equation modeling technique, we found that patient safety culture was negatively related to staff burnout (ß = -0.74) and could explain 55% of the total variance. We also found that patient safety culture was positively related to staff work-life balance (ß = 0.44) and could explain 19% of the total variance. Furthermore, the above relationships were invariant across groups of diverse staff demography (gender, age, managerial position, and incident reporting) and job characteristics (job role, tenure, and patient contact). Our findings suggest that investing in patient safety culture can be viewed as building an organizational resource, which is beneficial for both improving the care quality and protecting staff well-being. More importantly, the benefits are the same for everyone in the healthcare services.