Resveratrol, a phytochemical found in various plants and Chinese herbs, is associated with multiple tumor-suppressing activities, has been tested in clinical trials. However, the molecular mechanisms ...involved in resveratrol-mediated tumor suppressing activities are not yet completely defined. Here, we showed that treatment with resveratrol inhibited cell mobility through induction of the mesenchymal-epithelial transition (MET) in lung cancer cells. We also found that downregulation of FOXC2 (forkhead box C2) is critical for resveratrol-mediated suppression of tumor metastasis in an in vitro and in vivo models. We also identified a signal cascade, namely, resveratrol-∣miRNA-520h-∣PP2A/C-∣Akt → NF-κB → FOXC2, in which resveratrol inhibited the expression of FOXC2 through regulation of miRNA-520h-mediated signal cascade. This study identified a new miRNA-520h-related signal cascade involved in resveratrol-mediated tumor suppression activity and provide the clinical significances of miR-520h, PP2A/C and FOXC2 in lung cancer patients. Our results indicated a functional link between resveratrol-mediated miRNA-520h regulation and tumor suppressing ability, and provide a new insight into the role of resveratrol-induced molecular and epigenetic regulations in tumor suppression.
Summary
Background
Few studies have examined the association between psoriasis and glomerulonephritis (GN) as well as chronic kidney disease (CKD).
Objectives
To determine the risk of CKD in patients ...with psoriasis and evaluate the impact of the severity of psoriasis, comorbidities and concomitant drugs on the risk of GN and CKD in patients with psoriasis.
Methods
We identified 4344 patients with psoriasis for the study cohort and randomly selected 13 032 subjects as a control cohort. Each subject was individually followed for up for 5 years to identify those who subsequently developed GN and CKD.
Results
After adjustment for traditional CKD risk factors, psoriasis was found to be independently associated with an increased risk of CKD during the follow‐up period hazard ratio (HR) 1·28; 95% confidence interval (CI) 1·14–1·44. The increased incidence of GN in patients with psoriasis (HR 1·50, 95% CI 1·24–1·81) may contribute to the positive association between psoriasis and CKD. Patients with mild and severe psoriasis had an increased risk of CKD and GN compared with the control cohort; the risk increased with severity. Patients with psoriasis and arthritis exhibited a higher risk of CKD than patients without arthritis (HR 1·62 vs. 1·26). Among drugs, nonsteroidal anti‐inflammatory drugs (NSAIDs) have the strongest association with CKD in patients with psoriasis (adjusted odds ratio 1·69, 95% CI 1·14–2·49).
Conclusions
Psoriasis was associated with a higher risk of developing CKD and GN. High severity, psoriatic arthritis involvement and concomitant NSAIDs use further increased the risk of CKD in patients with psoriasis.
What's already known about this topic?
There is an increased risk of multiple comorbidities in patients with psoriasis.
What does this study add?
Both mild and severe psoriasis presented an increased risk of chronic kidney disease (CKD) and glomerulonephritis, independent of traditional risk factors for CKD.
The development of CKD in patients with psoriasis was multifaceted. High severity, psoriatic arthritis involvement and concomitant nonsteroidal anti‐inflammatory drug use further increased the risk of CKD in patients with psoriasis.
Aims
To investigate the temporal relationship between non‐steroidal anti‐inflammatory drug use and the development of chronic kidney disease in people with Type 2 diabetes mellitus.
Methods
We ...conducted a retrospective cohort study and followed up a population with Type 2 diabetes who were chronic kidney disease‐free (n = 48 715) using national health insurance claims data in Taiwan. Exposure status to non‐steroidal anti‐inflammatory drugs in 2007 was measured. A total of 6406 subjects with incident chronic kidney disease were identified from the period 2008 to 2011. Multivariable proportional hazards models were applied to determine the temporal relationship between non‐steroidal anti‐inflammatory drug use and the development of chronic kidney disease.
Results
We observed a significant temporal relationship between non‐steroidal anti‐inflammatory drug use and the development of chronic kidney disease in people with Type 2 diabetes. Compared with people not taking any non‐steroidal anti‐inflammatory drug in 2007, those who were taking such drugs for at least 90 days in 2007 had a higher risk of chronic kidney disease development (adjusted hazard ratio 1.37, 95% CI 1.26–1.49). In subgroup analyses, those people (irrespective of age, sex, various comorbidities and use of anti‐hypertensive drugs, aspirin or acetaminophen) who were taking non‐steroidal anti‐inflammatory drugs for at least 90 days were more likely to develop chronic kidney disease than people who were not taking any non‐steroidal anti‐inflammatory drug.
Conclusions
The results suggest that there is a positive temporal relationship between non‐steroidal anti‐inflammatory drug use and increased risk of chronic kidney disease in people with Type 2 diabetes. The use of non‐steroidal anti‐inflammatory drugs should be based on clinical evaluations of benefits and risks, and should be prescribed with caution for people with Type 2 diabetes.
What's new?
This is the first nationwide longitudinal cohort study to examine the temporal relationship between non‐steroidal anti‐inflammatory drug use and an increased risk of developing chronic kidney disease in people with Type 2 diabetes.
Compared with those not taking any non‐steroidal anti‐inflammatory drugs, people with Type 2 diabetes who used non‐steroidal anti‐inflammatory drugs for at least 90 days were 29% more likely to develop chronic kidney disease, and elderly patients were found to be more vulnerable to the hazardous effects caused by non‐steroidal anti‐inflammatory drugs.
Objectives
This study aims to assess the effectiveness of a multidomain intervention program on the change in functional status of hospitalized older adults.
Design
This single-arm, prospective, ...non-randomized interventional study investigates the efficacy of a multidomain interventional program including cognitive stimulation activity, simple exercises, frailty education, and nutrition counseling.
Setting and Participants
At a tertiary hospital in southern Taiwan, 352 eligible patients were sequentially enrolled. Included patients were aged ≥65 years (mean age, 79.6 ± 9.0 years; 62% male), scored 3–7 on the Clinical Frailty Scale (CFS), and were hospitalized in the geriatric acute ward.
Intervention
Those receiving standard care (physical rehabilitation and nutrition counseling) during January–July 2019 composed the historical control group. Those receiving the multidomain intervention during August–December 2019 composed the intervention group.
Measurements
The primary outcome was the change in activities of daily life (ADL) and frailty status, as assessed by Katz Index and Clinical Frailty Scale, with using the generalized estimating equation model. The length of hospital stay, medical costs, and re-admission rates were secondary outcomes.
Results
Participants undergoing intervention (n = 101; 27.9%) showed greater improvements in the ADL and CFS during hospitalization (ADL adjusted estimate, 0.61; 95% CI, 0.11–1.11; p = 0.02; CFS adjusted estimate, −1.11; 95% CI, −1.42–−0.80; p < 0.01), shorter length of hospital stay (adjusted estimate, -5.00; 95% CI, −7.99–−2.47; p < 0.01), lower medical costs (adjusted estimate, 0.58; 95% CI, 0.49–0.69; p < 0.01), and lower 30- and 90-day readmission rates (30-day adjusted OR aOR, 0.12; 95% CI, 0.27–0.50; p < 0.01; 60-day aOR, 0.04; 95% CI, 0.01–0.33; p < 0.01) than did controls.
Conclusions
Participation in the multidomain intervention program during hospitalization improved the functional status and decreased the hospital stay length, medical costs, and readmission rates of frail older people.
Efficient organic light‐emitting diodes (OLEDs) incorporating IrIII bis(4,6‐difluorophenylpyridinato)‐3‐(trifluoromethyl)‐5‐ (pyridin‐2‐yl)‐1,2,4‐triazolate (FIrtaz) and IrIII ...bis(4,6‐difluorophenylpyridinato)‐5‐(pyridin‐2‐yl)‐1H‐tetrazolate (FIrN4) demonstrate higher‐purity blue‐light emission than the long‐known IrIII bis(4,6‐difluorophenylpyridinato)picolate (FIrpic) phosphorophore. New host materials with higher glass‐transition temperatures were also found to enhance the OLED performance.
Summary
Pityriasis rubra pilaris (PRP) represents a group of rare chronic inflammatory skin disorders in which around one in 20 affected individuals show autosomal dominant inheritance. In such cases ...there may be gain‐of‐function mutations in CARD14, encoding caspase recruitment domain‐containing protein 14 (CARD14), which activates the noncanonical nuclear factor (NF)‐κB pathway, thereby promoting cutaneous inflammation. Here we report a mother and son with PRP due to a new missense mutation in CARD14 and describe the beneficial clinical effects of ustekinumab, a monoclonal antibody against interleukins 12 and 23, in both patients. A 49‐year‐old woman and her 20‐year‐old son had lifelong, generalized, patchy erythematous scale with a few islands of sparing, as well as minor nail ridging and mild palmoplantar keratoderma, features consistent with generalized PRP. Topical steroids, phototherapy and oral retinoids proved ineffective. Following informed consent, Sanger sequencing of CARD14 in both individuals revealed a new heterozygous single‐nucleotide transversion in exon 4, c.356T>G, resulting in the missense mutation p.Met119Arg. Ustekinumab, at a dose of 45 mg every 12 weeks, brought about a significant physical and emotional improvement in both the mother and son within a few days of the initial dose, which was sustained on maintenance dosing. This report highlights the therapeutic potential of biologics that downregulate NF‐κB signalling in familial PRP with mutations in CARD14.
What's already known about this topic?
Pityriasis rubra pilaris (PRP) represents a group of rare chronic inflammatory skin disorders in which some cases show autosomal dominant inheritance.
Some cases also reveal heterozygous gain‐of‐function mutations in CARD14, encoding caspase recruitment domain‐containing protein 14 (CARD14).
Ustekinumab, an interleukin‐12/23 antagonist, is a licensed biological therapy for psoriasis, although its use has not been widely assessed in PRP, despite anecdotal reports of its potential efficacy.
What does this study add?
We report a mother and son with refractory generalized PRP. DNA sequencing revealed that both carried a new de novo missense mutation in CARD14, p.Met119Arg.
Identification of this CARD14 mutation was used as justification for a trial of ustekinumab, whereupon both patients had a beneficial clinical response, physically and emotionally, with sustained improvements over several months of follow‐up.
Ustekinumab may be considered as a targeted anti‐inflammatory therapy for familial PRP with an underlying mutation in CARD14.
Objectives
To evaluate the negative effect of physical restraint use on the hospital outcomes of older patients.
Design
A retrospective cohort study.
Setting
Internal medicine wards of a tertiary ...medical center in Taiwan.
Participants
Subjects aged 65 years and over who were admitted during April to Dec 2017 were recruited for study.
Measurements
Demographic data, geriatric assessments (polypharmacy, visual impairment, hearing impairment, activities of daily living before and after admission, risk of pressure sores, change in consciousness level, mood condition, history of falls in the previous year, risk of malnutrition and pain) and hospital conditions (admission route, department of admission, length of hospital stay and mortality) were collected for analysis.
Results
Overall, 4,352 participants (mean age 78.7±8.7 years, 60.2% = male) were enrolled and 8.3% had physical restraint. Results of multivariate logistic regression showed that subjects with physical restraints were at greater risk of functional decline (adjusted odds ratio 2.136, 95% confidence interval 1.322–3.451, p=0.002), longer hospital stays (adjusted odds ratio 5.360, 95% confidence interval 3.627–7.923, p<0.001) and mortality (adjusted odds ratio 4.472, 95% confidence interval 2.794–7.160, p<0.001) after adjustment for covariates.
Conclusion
The use of physical restraints during hospitalization increased the risk of adverse hospital outcomes, such as functional decline, longer length of hospital stay and mortality.
Background
Obesity accelerates and exacerbates the age-related changes on muscle function and exercise capacity. In addition, the middle-aged population is often overlooked when talking about the ...prevention of sarcopenia. This study investigated the effects of exercise alone or in combination with a high-protein diet on muscle function and physical fitness in middle-aged obese adults.
Materials and methods
Sixty-nine middle-aged (501–64 years old) obese adults were randomly assigned to one of the following groups: control group (C; n=23), exercise group (E; n=23) or exercise plus high-protein group (EP; n=23). Individuals within the E and EP groups received 12 weeks of exercise training; whereas, the individuals in the EP group also received a highprotein diet intervention (1.6g/kg/day). Individuals within the C group were asked to maintain their lifestyle for 12 weeks. Participants were evaluated before and after the intervention. Outcome measures included maximal exercise capacity, muscle function and functional physical performance. Analysis of covariance was used to determine the effects of the intervention.
Results
After the intervention, the E and EP groups had greater maximal work rate, peak oxygen consumption, and muscle power during muscle contractions at 180°/sec than that in the C group (P<0.05). The EP group, but not the E group, showed significant improvement in the sit-to-stand test and climbing stairs test than the C group after the intervention (P<0.05). Within group comparisons showed that the anaerobic threshold only increased in the EP group (+12% from pre-test).
Conclusions
For middle-aged obese adults, exercise with a high-protein diet not only improved muscle power and exercise capacity but also enhanced their functional physical performance.
Summary
What is known and objective
Patients with rheumatic disease are at risk for infections. Evaluating antitumour necrosis factor (anti‐TNF) drug‐associated risk of infections requires ...justification of baseline risk in the population at high risk of infection. We examined the incidence of active tuberculosis (TB) and its risk factors in patients with rheumatic disease started with anti‐TNF‐α therapy or with existing disease‐modifying antirheumatic drug (DMARD) therapy.
Methods
A retrospective cohort study of anti‐TNF‐α therapy new users (anti‐TNF‐α group) and those starting with a DMARD after the failure of at least one other DMARD or who had added to existing DMARD treatment (DMARD group) for rheumatic disease in the largest medical setting in Taiwan from 1 January 2005 through 31 November 2013 was conducted to determine relative risk of TB between patient groups. Patients in the DMARD group were stratified into “mild” and “severe” disease severity as proxies for low and high background risk of infection.
Results and discussion
A total of 3640 patients were enrolled (anti‐TNF: 955; DMARD: 2685). The incidence of TB was 903.9/100 000 patient‐years for anti‐TNF‐α new users and 391.7/100 000 patient‐years for DMARD switchers. In Cox regression model, adjusted HR for TB in the anti‐TNF‐α group was higher than for the entire DMARD group (aHR, 2.41; 95% confidence interval CI, 1.2‐4.85), subgroup with mild disease (2.91; 1.31‐6.47) and subgroup with severe disease (1.65; 0.68‐4.03). Significant independent risk factors for TB were being male, age ≥60 years, history of respiratory disease, glucocorticoids dose >7.5 mg/d and living in a TB‐prevalent region.
What is new and conclusion
Anti‐TNF‐α therapy was independently associated with increased risk of TB in patients with mild disease, but it was not significantly correlated in patients with severe disease after adjusting for confounders.
A retrospective new user cohort was conducted to evaluate antitumor necrosis factor‐α (anti‐TNF‐α) therapy‐associated risk of tuberculosis in patients with rheumatic disease. Anti‐TNF‐α therapy was independently associated with increased risk of TB in patients with mild disease, but it does not remain significantly correlated in patients with severe disease after adjusting for confounders.
Summary
Background
The Milan criteria are used to select candidates with small hepatocellular carcinoma (HCC) for liver transplantation. Due to severe shortage of donors, majority of patients within ...the Milan criteria need to seek alternative treatments.
Aim
To propose a prognostic model for these patients undergoing non‐transplant therapies.
Methods
A total of 1106 HCC patients, who were within the Milan criteria and received non‐transplant therapies were retrospectively analysed. Patients were randomly assigned to the derivation and validation set according to treatments. A prognostic model was constructed from independent predictors of survival identified in the multivariate Cox model of the derivation set and was confirmed in the validation set.
Results
In the Cox model, serum bilirubin ≥1.5 mg/dL risk ratio (RR): 1.525, P = 0.016, α‐fetoprotein (AFP) ≥100 ng/mL (RR: 1.728, P < 0.001), mild ascites (RR: 1.705, P = 0.025) and moderate/severe ascites (RR: 4.163, P < 0.001) were independent predictors of poor survival in the derivation set (n = 553). A prognostic model with a total of 0–4 points was derived with the sum of three variables: 1 point each for bilirubin ≥1.5 mg/dL, AFP ≥100 ng/mL and mild ascites, and 2 points for moderate/severe ascites. This scoring system accurately predicted the survival in the validation set (n = 553; P < 0.001). The model consistently discriminated the survival in patients stratified by curative and noncurative treatments (both P values <0.001).
Conclusion
The newly proposed prognostic scoring model, based on serum bilirubin and AFP level, and severity of ascites, is informative to predict the survival in non‐transplant HCC patients within the Milan criteria.
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