SUMO-Activating Enzyme Subunit 1 Is Associated with Poor Prognosis, Tumor Progression, and Radio-Resistance in Colorectal Cancer.

Concurrent chemoradiotherapy is an effective treatment option for patients with low-grade colorectal cancer (CRC) in the local disease stage. At present, the principle of the Taiwan Medical Center is to treat CRC patients with combination radiotherapy and chemotherapy (high-dose 5-FU) for a period of about five weeks prior to surgery. Radical resection of the tumor is performed at least six to eight weeks after concurrent chemoradiotherapy (CCRT). However, this approach fails to produce the desired therapeutic effect in approximately 20% to 30% of patients, and such patients are unnecessarily exposed to the risks of radiation and drug toxicity posed by this therapy. Therefore, it is crucial to explore new biomarkers to predict the prognosis of CRC. SUMO-activating enzyme subunit 1 (SAE1) plays an important role in SUMOylation, a post-translational modification involved in cellular functions, such as cell proliferation, cell cycle, and apoptosis. In our study, to explore the clinical-pathological role of SAE1 protein in CRC, we evaluated the clinical data and paraffin sections from CRC patients. The expression of SAE1 was evaluated using immunohistochemical analysis, and clinical parameters were analyzed using chi-square and Kaplan-Meier survival tests. The results of in vitro proliferation and radiosensitive assays were compared between control groups and SAE1 siRNA groups. Western blotting was also used to detect the expressions of the SAE1, PARP, cyclin D1, p-NF-κB, and NF-κB proteins. Flow cytometry and colony formation assays were used to detect the effect of SAE-1 on radiosensitivity. In vivo, we detected the growth curve in a mouse xenograft model. The results showed that SAE-1 was revealed to be an independent prognostic biomarker of CRC. SAE1 knockdown inhibited CRC proliferation in vitro and in vivo, and led to the cleavage of PARP, downregulation of cyclin D1 protein expression, and downregulation of p-NF-κB/NF-κB. Additionally, SAE1 knockdown promoted radiosensitivity in CRC cells. Therefore, it was inferred that SAE1 may be used as a potential therapeutic target in CRC treatment.

The associations of osteoporosis and possible sarcopenia with disability, nutrition, and cognition in community-dwelling older adults.

BACKGROUND: Osteoporosis and sarcopenia, respectively, have detrimental impact on health, and combination of both conditions, termed osteosarcopenia, is becoming an increasingly important disorder in older adults as populations age. This study aimed to explore the relationship between osteoporosis and possible sarcopenia and their joint effect on physical performance, nutritional status, and cognition in community-dwelling older adults. METHODS: This study was conducted at a medical center in Taiwan, which included the adjacent community care station. The participants were recruited through regular activities at the community care station between January 01, 2015 and February 28, 2022. During the study period, dual-energy X-ray absorptiometry and comprehensive geriatric assessment consisting of comorbidity burden, functional status, cognition, mood, and nutritional status were performed during the study period. Possible sarcopenia was identified utilizing the criteria set by the Asian Working Group on Sarcopenia in 2019 using the criteria of low muscle strength alone, and osteoporosis was defined by the World Health Organization criteria. Accordingly, the study subjects were divided into four groups: normal, only osteoporosis, only possible sarcopenia, and possible osteosarcopenia. RESULTS: There were 337 participants (68.6% female) with a median age of 78.0 years (interquartile range: 71.0-85.0 y/o). According to the clinical definition of osteosarcopenia, 78 participants were normal, 69 participants showed possible sarcopenia, 61 participants had osteoporosis, and 129 had osteoporosis with possible sarcopenia. Among the four groups, the prevalence rates of chronic illness, functional capacity, physical performance, cognitive impairment, and malnutrition revealed statistically significant differences. Using logistic regression analysis after adjusting for the other covariates, osteoporosis with possible sarcopenia was associated with an increased odds ratio of cognitive impairment. CONCLUSIONS: The findings suggest that compared to osteoporosis or possible sarcopenia alone, osteoporosis with possible sarcopenia was more likely to be associated with cognitive impairment. Early identification and targeted interventions for cognitive impairment in older adults with osteosarcopenia may be valuable in maintaining cognitive well-being and overall quality of life.

α7 nicotinic acetylcholine receptor agonist improved brain injury and impaired glucose metabolism in a rat model of ischemic stroke.

Vagus nerve stimulation through the action of acetylcholine can modulate inflammatory responses and metabolism. α7 Nicotinic Acetylcholine Receptor (α7nAChR) is a key component in the biological functions of acetylcholine. To further explore the health benefits of vagus nerve stimulation, this study aimed to investigate whether α7nAChR agonists offer beneficial effects against poststroke inflammatory and metabolic changes and to identify the underlying mechanisms in a rat model of stroke established by permanent cerebral ischemia. We found evidence showing that pretreatment with α7nAChR agonist, GTS-21, improved poststroke brain infarction size, impaired motor coordination, brain apoptotic caspase 3 activation, dysregulated glucose metabolism, and glutathione reduction. In ischemic cortical tissues and gastrocnemius muscles with GTS-21 pretreatment, macrophages/microglia M1 polarization-associated Tumor Necrosis Factor-α (TNF-α) mRNA, Cluster of Differentiation 68 (CD68) protein, and Inducible Nitric Oxide Synthase (iNOS) protein expression were reduced, while expression of anti-inflammatory cytokine IL-4 mRNA, and levels of M2 polarization-associated CD163 mRNA and protein were increased. In the gastrocnemius muscles, stroke rats showed a reduction in both glutathione content and Akt Serine 473 phosphorylation, as well as an elevation in Insulin Receptor Substrate-1 Serine 307 phosphorylation and Dynamin-Related Protein 1 Serine 616 phosphorylation. GTS-21 reversed poststroke changes in the gastrocnemius muscles. Overall, our findings, provide further evidence supporting the neuroprotective benefits of α7nAChR agonists, and indicate that they may potentially exert anti-inflammatory and metabolic effects peripherally in the skeletal muscle in an acute ischemic stroke animal model.

Death place and palliative outcome indicators in patients under palliative home care service: an observational study.

BACKGROUND: Dying at home accompanied by loved-ones is regarded favorably and brings good luck in Taiwan. This study aimed to examine the relevant factors affecting whether an individual dies at home or not in a group of terminal patients receiving palliative home care service. METHODS: The patients who were admitted to a palliative home care service at a hospital-affiliated home health care agency were consecutively enrolled between March 1, 2021 and March 31, 2022. During the period of care, the instruments of the palliative care outcomes collaboration was used to assess patients in each home visit twice a week, including symptom assessment scale, palliative care problem severity score, Australia-modified Karnofsky performance status, resource utilization groups-activities of daily living, and palliative care phase. RESULTS: There were 56 participants (53.6% female) with a median age of 73.0 years (interquartile range (IQR) 61.3-80.3 y/o), of whom 51 (91.1%) patients were diagnosed with cancer and 49 (96.1%) had metastasis. The number of home visits was 3.5 (IQR 2.0-5.0) and the average number of days under palliative home care service was 31 (IQR 16.3-51.5) before their death. After the end of the study, there was a significant deterioration of sleeping, appetite, and breathing problems in the home-death group, and appetite problems in the non-home death patients. However, physician-reported psychological/spiritual problems improved in the home-death group, and pain improved in the non-home death patients. Physical performance deteriorated in both groups, and more resource utilization of palliative care was needed. The 44 patients who died at home had greater cancer disease severity, fewer admissions, and the proportion of families desiring a home death for the patient was higher. CONCLUSIONS: Although the differences in palliative outcome indicators were minor between patients who died at home and those who died in the hospital, understanding the determinants and change of indicators after palliative care service at different death places may be helpful for improving the quality of end-of-life care.

Fucoidan enhances the effect of chemotherapeutic drug against drug-resistant lung cancer cells.

Development of adjuvant chemotherapy drugs against drug-resistant lung cancer cells is necessary. The use of non-toxic adjuvant natural product combined with chemotherapy drugs will be an important treatment mode in the future. The purpose of the study investigates that fucoidan enhances chemotherapy drug poisoning drug-resistant lung cancer cell. Drug-resistant lung cancer cells are established in the study. Cell culture, MTT assay, wound healing assay, gelatin zymography assay, DNA fragmentation assay, apoptosis assay, reverse transcription polymerase chain reaction (RT-PCR) western blot analysis was adopted. The results showed that fucoidan synergized with doxorubicin increased efficacy of poisoning drug-resistant lung cancer cells and enhanced the ability of doxorubicin to inhibit the migration of drug-resistant lung cancer cells. It was observed that fucoidan synergized with doxorubicin induced the increase of apoptosis and inhibited expression of MMP-9, LC3, Beclin-1 and ß-catenin in drug-resistant lung cancer cells. Fucoidan synergized with doxorubicin significantly inhibited proliferation, migration and metastasis of drug-resistant lung cancer cells. Fucoidan strengthened doxorubicin to induce apoptosis and autophagy of drug-resistant lung cancer cells. This study confirms that the combined use of fucoidan and chemotherapeutic drugs can effectively poison drug-resistant lung cancer cells.

The impact of heavy alcohol consumption on cognitive impairment in young old and middle old persons.

BACKGROUND: Dementia indicates a significant disease burden worldwide with increased population aging. This study aimed to investigate the impact of alcohol consumption on the risk of cognitive impairment in older adults. METHODS: Participants ≥ 60 years were administered the Digit Symbol Substitution Test (DSST) to evaluate cognitive function in National Health and Nutrition Examination Survey (NHANES) cycles from 1999 to 2002 and 2011 to 2014 for enrollment in the present study. Participants were categorized into non-drinker, drinker, and heavy drinker groups. Logistic regression analyses were performed to explore associations between cognitive impairment and alcohol consumption. RESULTS: Multivariate analysis showed that older adults, men, people from minority races, persons with lower education or income levels, social difficulties, hypertension, or chronic kidney disease were significantly associated with a higher risk of cognitive impairment (all p < 0.05). In the young old (60-69 years), heavy amount of alcohol drinking was significantly associated with lower risk of cognitive impairment compared with drinkers [adjusted odds ratio (aOR): 0.280, 95% Confidence interval (CI) 0.095-0.826]. But in the middle old persons (≥ 70 years), heavy alcohol drinking was associated with higher risk of cognitive impairment (aOR: 2.929, 95% CI 0.624-13.74). CONCLUSIONS: Our study demonstrated that light to heavy drinking was associated with lower risk of cognitive impairment in participants aged between 60 and 69 years, but caution is needed in the middle old people with heavy alcohol drinking.

Risks of central nervous system infections and related mortality in patients undergoing dialysis.

INTRODUCTION: This study aimed to investigate the risks of central nervous system (CNS) infections and related mortality in patients with end-stage renal disease (ESRD) undergoing dialysis. METHODS: Incident dialysis patients were identified from 2000 to 2013. The risks of CNS infection and related mortality were analyzed. RESULTS: The adjusted hazard ratio (HR) of CNS infection in the ESRD group compared with the control group was 3.46 (95% confidence interval [CI] 2.75-4.35). The adjusted odds ratio (OR) of 90-day mortality following CNS infections in the ESRD group in comparison with the control group was 5.99 (95% CI 2.78-12.9). The adjusted HR of overall CNS infection for the peritoneal dialysis (PD) group in comparison with the hemodialysis (HD) group was 1.07 (95% CI 0.63-1.82). Influenza vaccination was associated with a lower risks of CNS infection in dialysis patients (adjusted HR: 0.38, 95% CI 0.30-0.48). The adjusted OR of 90-day mortality following CNS infection for the PD group in comparison with the HD group was 1.01 (95% CI 0.55-1.87). CONCLUSIONS: The risks of CNS infections and related mortality were remarkably high in dialysis patients with no significant difference between patients with ESRD under HD and PD treatment.

Improved outcomes and reduced medical costs through multidisciplinary co-management protocol for geriatric proximal femur fractures: a one-year retrospective study.

BACKGROUND: To manage the rapidly growing incidence of, and related medical burden resulting from hip fractures in older adults in an aging society, studies involving orthogeriatric co-management treatment models have reported improved outcomes, including reduced medical costs. The treatment gap for osteoporosis was however seldom emphasized in the published treatment protocols. Aiming to improve the existing orthogeriatric protocol, we have established a patient-centered protocol for elderly patient hip fractures, which simultaneously focuses on fracture care and anti-osteoporosis agent prescription in regarding to healthcare quality and medical expense. METHODS: This was a retrospective study comparing patients who enrolled in the multidisciplinary co-managed protocol for geriatric hip fractures and those who did not. The inclusion criteria for this study were: (a) single-sided hip fractures treated from 1 to 2018 to 30 June 2020, (b) patients who were 60-years or older (c) trauma treated within 3 days from time of injury, and (d) minimal follow-up period of 12 months after surgery. RESULTS: From 1 to 2018 to 30 June 2020, 578 patients were included (267 patients in the protocol group vs. 331 patients in the conventional group). The protocol group was associated with significantly reduced lengths of hospital stay (p = 0.041), medical expenditures (p = 0.006), and mortality (p = 0.029) during their acute in-hospital admission period. Early osteoporosis diagnosis and anti-osteoporosis agent prescription were achieved in the protocol group, with a significantly wider coverage for BMD assessment (p < 0.001) and prescriptions for anti-osteoporosis medication (p < 0.001). Yet, there was no significant decline in the one-year refracture rate in the protocol group. CONCLUSIONS: The implementation of a multidisciplinary co-managed care protocol for geriatric proximal femur fractures successfully improved patient outcomes with significantly reduced lengths of stay, medical expenditures, and mortality during the acute in-hospital admission period. The high prescription rate of anti-osteoporosis medication after hip fractures in the protocol group was not associated with a significantly lower re-fracture rate in the 12-month follow-up. However, the association between early anti-osteoporosis agent prescription and reduced long-term medical expenses in this group of patients has provided a direction for future research.

DHA attenuated Japanese Encephalitis virus infection-induced neuroinflammation and neuronal cell death in cultured rat Neuron/glia.

Japanese Encephalitis Virus (JEV) is a neurotropic virus and its Central Nervous System (CNS) infection causes fatal encephalitis with high mortality and morbidity. Microglial activation and consequences of bystander damage appear to be the dominant mechanisms for Japanese Encephalitis and complications. Docosahexaenoic acid (DHA), an essential fatty acid and a major component of brain cell membranes, possesses additional biological activities, including anti-apoptosis, anti-inflammation, and neuroprotection. Through this study, we have provided experimental evidence showing the anti-inflammatory, neuroprotective, and anti-viral effects of DHA against JEV infection in rat Neuron/glia cultures. By Neuron/glia and Neuron cultures, DHA protected against neuronal cell death upon JEV infection and reduced JEV amplification. In Neuron/glia and Microglia cultures, the effects of DHA were accompanied by the downregulation of pro-inflammatory M1 microglia, upregulation of anti-inflammatory M2 microglia, and reduction of neurotoxic cytokine expression, which could be attributed to its interference in the Toll-Like Receptor (TLR), Mitogen-Activated Protein Kinase (MAPK), and Interferon/Janus Kinase/Signal Transducers and Activators of Transcription (Stat), along with the NF-κB, AP-1, and c-AMP Response Element Binding Protein (CREB) controlled transcriptional programs. Parallel anti-inflammatory effects against JEV infection were duplicated by G Protein-Coupled Receptor (GPR120) and GPR40 agonists and a reversal of DHA-mediated anti-inflammation was seen in the presence of GPR120 antagonist, while the GPR40 was less effectiveness. Since increasing evidence indicates its neuroprotection against neurodegenerative diseases, DHA is a proposed anti-inflammatory and neuroprotective candidate for the treatment of neuroinflammation-accompanied viral pathogenesis such as Japanese Encephalitis.

Impact of day care services on physical and cognitive functions in old people with dementia in a medical center in central Taiwan.

BACKGROUND: Day care service (DCS) provides various activities in a professional environment to meet the old people with functional limitations. However, relatively little is known about the effects of DCS on physical and mental functions. METHODS: This was a retrospective study that we used a comprehensive geriatric assessment to evaluate the changes before and after DCS among participants in a hospital-affiliated geriatric day care center in Taiwan. The burden of the participants' families was also assessed. RESULTS: The 18 participants with a median age of 80.9 (interquartile range (IQR) 75.2-86.6 y/o) were enrolled and followed up for 6 months. Based on the clinical dementia rating (CDR), disease stage was very mild in 3 participants, mild in 10, moderate in 3, and severe in 2. The activities of daily living (ADL) scores of the participants improved significantly from 75 (IQR 60.0-80.0) at baseline to 77.5 (IQR 65.0-90.0) at the 6 month (p < 0.001), and mini-mental state examination (MMSE) scores from 15 (IQR 11.5-20.0) to 18 (IQR 15.8-24.0) (p = 0.026). There was a positive correlation of baseline mini-nutritional assessment-short form score and the 3-level version of the European Quality of Life-5 dimensions utility index with both ADL and MMSE scores at the 6-month follow-up. In addition, the family burden scale was reduced from 22 to 15 (p = 0.002). CONCLUSIONS: The physical and cognitive functions in old people with dementia who received DCS were maintained or partially improved, and their families' stress burden was alleviated.

Physical frailty and long-term mortality in older people with chronic heart failure with preserved and reduced ejection fraction: a retrospective longitudinal study.

BACKGROUND: Frailty, a syndrome characterized by a decline in function reserve, is common in older patients with heart failure (HF) and is associated with prognosis. This study aimed to evaluate the impact of frailty on outcomes in older patients with preserved and reduced cardiac function. METHODS: In total, 811 adults aged ≥65 years were consecutively enrolled from 2009 to 2018. HF was diagnosed according to the ICD9 code and a 2D echocardiogram was categorized by reduced ejection fraction (HFrEF) and preserved ejection fraction (HFpEF). The index date was registered at the time of HF. All patients received a comprehensive geriatric assessment, and clinical outcomes were examined with adjustment of the other prognostic variables. RESULTS: Mean age was 80.5 ± 7.1 years. The prevalence of HF, HFpEF, HFrEF, Fried, and Rockwood frailty indicators was 28.5, 10.4, 9.7, 52.5, and 74.9%, respectively. At baseline, scores in the Timed Up and Go test was closely associated with the severity of HF, either with HFpEF or HFrEF. After a mean follow-up of 3.2 ± 2.0 years, we found that HF patients with low handgrip strength (HGS) had the poorest survival, followed by non-HF patients with decreased HGS, and HF with fair HGS in comparison with non-HF with fair HGS (p = 0.008) if participants were arbitrarily divided into two HGS groups. In all patients, a high Rockwood frailty index was independently associated with increased mortality (adjusted hazard ratio [aHR] = 1.05; 95% confidence interval [CI]: 1.0004 to 1.10). In addition, the adjusted mortality HR was 3.42 with decreased HGS (95% CI: 1.03 to 11.40), 7.65 with use of mineralocorticoid receptor antagonist (95% CI: 2.22 to 26.32), and 1.26 with associated multi-comorbidities assessed by Charlson comorbidity index (95% CI: 1.05 to 1.51). CONCLUSIONS: Our study results indicate that frailty and decreased physical functions were associated with HF. Besides, frailty and HGS predicted prognosis in the patients, and there was a combined effect of HF and low HGS on survival.

Association between Hydroxychloroquine and bacterial pneumonia in rheumatic patients: A population-based propensity score matching cohort study.

BACKGROUND: Whether hydroxychloroquine (HCQ) use could reduce lesser risk of bacterial infections is unknown. We aimed to conduct a retrospective cohort propensity-matching study to investigate the association between HCQ use and the incidence of bacterial pneumonia in rheumatic patients. METHODS: The Longitudinal Health Insurance Database (LHID) from Taiwan National Health Insurance Research Database (NHIRD) of 23 million Taiwanese populations was used. We included patients who were newly diagnosed with rheumatic and immune disease (ICD-9-CM codes 696.0, 710, 714) within 2000-2012. HCQ users and non-users were then matched according to age, sex, urbanisation level, monthly income, comorbidities and medications in the ratio of 1:1 by the propensity score matching. Cox proportional hazard model was used to evaluate the risk of bacterial pneumonia in rheumatic patients who used HCQ and who did not use HCQ. RESULTS: There were total 3285 patients with rheumatic and immune disease enrolled. The cumulative incidence curve of patients with the use of HCQ sulphate had no difference to that of patient without the use of HCQ sulphate in propensity score-matched cohort, (Log-rank test: P = .5). However, patients who used HCQ sulphate for more than 1400 average use days had a lesser risk of bacterial pneumonia (adjusted HR = 0.55, 95% CI = 0.35, 0.89) in the cohort matched, with regarding HCQ non-users as a reference. CONCLUSION: Rheumatic patients taking HCQ had no overall significant differences of bacterial pneumonia incidences compared with rheumatic patients not taking HCQ. HCQ used more than >1400 days or lupus patients using HCQ was associated with lower risk of bacterial pneumonia.

Risk of diabetes mellitus in patients with prostate cancer receiving injection therapy: A nationwide population-based propensity score-matched study.

OBJECTIVES: We aimed to investigate whether the risk of diabetes mellitus (DM) is heightened in patients with prostate cancer receiving injection therapy. METHODS: Men diagnosed with prostate cancer between 2000 and 2012 were included in the case cohort, and men without prostate cancer were included as controls. Each patient with prostate cancer was matched with a control patient with the same index year, demographic variables and comorbidities, and comparisons were made using propensity score matching. The hazard ratio of DM was estimated using the Cox proportional hazards model. RESULTS: This cohort study consisted of 1213 patients with prostate cancer and 1213 control patients. The risk of DM in patients with prostate cancer was 1.60 times (95% CI = 1.12, 2.27) that of patients without prostate cancer. Compared with the controls, the hazard ratios of DM for patients with prostate cancer not receiving oral hormone therapy, patients with prostate cancer receiving oral hormone therapy, and patients with prostate cancer not receiving injection hormone therapy were 1.65 (95% CI = 1.01, 2.70), 1.57 (95% CI = 1.07, 2.70), and 1.94 (95% CI = 1.34, 2.81), respectively. The risk of DM in patients who received injection hormone therapy was 0.45 times (95% CI = 0.25, 0.82) that of patients who did not receive injection hormone therapy. CONCLUSION: Patients with prostate cancer had an increased risk of DM compared with patients without prostate cancer. Patients with prostate cancer who received injection therapy had a lower risk of DM compared with those who did not.

Risk of idiopathic peripheral neuropathy in end-stage renal disease: A population-based cohort study.

BACKGROUND: Whether patients with end-stage renal disease (ESRD) have a higher risk of idiopathic polyneuropathy (IPN) than those without ESRD remains unclear. We hypothesised that carpal tunnel syndrome (CTS) is a prodrome of IPN in patients with ESRD. METHODS: Data were collected from the Taiwan National Health Insurance research database (NHIRD) for the 2000-2011 period. Two matching strategies, age- and sex-matching and propensity matching, were used, which yielded 2596 age- and sex-matched patients with ESRD and 2210 propensity-matched patients with ESRD. The comparison cohort was chosen in a 1:4 ratio for the age- and sex-matched method and in a 1:1 ratio for the propensity-matching method. The primary outcome was the incidence of IPN. Cox proportional hazards modelling was used. RESULTS: In the age- and sex-matched cohort, the IPN incidence was 7.64 and 2.88 per 1000 person-years for the ESRD and controls cohorts, respectively. After we adjusted for age, sex, comorbidities and medications relative to controls, having ESRD was significantly associated with increased risk of IPN (hazard ratio [HR] = 2.45, 95% confidence interval [CI] = 1.76-3.41). Competing risk of death as sensitivity analysis revealed that having ESRD with CTS was still associated with higher risk of IPN than having CTS without ESRD (HR = 2.85, 95% CI = 1.87-4.34). CONCLUSION: Patients with ESRD with CTS had higher incidences of idiopathic peripheral neuropathy than those without ESRD with CTS.

Association of antihypertensives during hospitalisation with acute respiratory failure in patients with viral pneumonia: A population-based case-control study.

BACKGROUND: We aimed to identify associations between the risk of acute respiratory failure (ARF) and types of antihypertensive agents in patients with viral pneumonia. METHODS: In this case-control study, data extracted from the Taiwan National Health Insurance Research Database were analysed. The base population comprised patients with viral pneumonia treated from 2000 to 2013. The case group comprised patients with ARF and the control group comprised participants without ARF. Adjusted odds ratios (ORs) were calculated using a multivariable logistic regression model. RESULTS: In total, 4427 viral pneumonia patients with ARF and 4427 matched control participants without ARF were recruited. Patients with diabetes, alcohol-related disease, asthma, chronic kidney disease or end-stage renal disease, chronic obstructive pulmonary disease, cancer, congestive heart failure, stroke, acute pulmonary oedema and shock had increased odds of developing ARF, especially shock (adjusted OR = 49.3; 95% CI = 27.4, 88.7), cancer (12.6; 8.67, 18.2) and stroke (7.51; 5.32, 10.6). Increasing odds of developing ARF were noted in patients using potassium-sparing diuretics (2.95; 1.54, 5.64), loop diuretics (68.2; 48.1, 96.6), calcium channel blockers (1.64; 1.26, 2.13) and angiotensin-converting enzyme inhibitors (1.70; 1.15, 2.53). Patients with prescriptions of α-blockers (0.44; 0.26, 0.74), ß-blockers (0.37; 0.26, 0.52), thiazides (0.38; 0.25, 0.59) and angiotensin receptor blockers (0.65; 0.51, 0.83) had lower odds of having ARF. CONCLUSION: Patients with viral pneumonia who received α-blockers, ß-blockers, thiazides or angiotensin receptor blockers during hospitalisation had a lower risk of developing ARF.

Sex differences in long-term cardiovascular outcomes among patients with acute myocardial infarction: A population-based retrospective cohort study.

BACKGROUND: Whether a sex difference exists in long-term cardiovascular (CV) outcomes after acute myocardial infarction (AMI) is worth exploration. This study is sought to investigate the relationships among sex, age, and the long-term prognosis after AMI. METHODS: This population-based retrospective cohort study used Taiwan's National Health Insurance Research Database to investigate the sex differences in in-hospital and long-term CV outcomes in patients with AMI. We enrolled patients who were first diagnosed with AMI from January 1, 2000 to December 31, 2013. The outcomes of interest included all-cause mortality, CV death, non-fatal stroke, non-fatal heart failure, and AMI recurrence during hospitalization and 5-year follow up. The CV outcomes were also analyzed by age stratification. RESULTS: Overall, 201 921 patients with AMI were analyzed; 68.72% were men and 31.28% were women, with mean ages of 65.34 ± 14.12 and 73.05 ± 12.22 years, respectively. Major adverse cardiac events during hospitalization and up to 5 years were consistently greater in women than in men. Multivariable regression analysis revealed no sex difference existed in long-term all-cause and CV mortality. Men of all age groups consistently showed higher risk of both short- and long-term recurrence of AMI. Nonetheless, the female sex still independently predicted increased risk of non-fatal stroke and heart failure from hospitalization until 3-year follow up. CONCLUSION: Women with AMI had poorer short-term and long-term outcomes. The sex differences in long-term all-cause and CV death disappear after multivariate analysis. Nonetheless, female AMI patients independently predicted higher risk of stroke and heart failure from hospitalization until a 3-year follow-up. To better understand the pathophysiology of female patients with AMI and develop more effective management, more studies in this field are necessary in the future.

Association between angiotensin-converting enzyme inhibitors or angiotensin receptor blockers and community-acquired pneumonia: A nationwide population propensity-score matching study.

BACKGROUND: Few large-scale cohort studies have investigated the association between community-acquired pneumonia and the use of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs). We aimed to study whether using ACEIs or ARBs had protective effects for community-acquired pneumonia. METHODS: This database cohort study was conducted retrospectively in Taiwan. The hypertensive patients were the target population of this study. Patients with ARB use were defined as our first study cohort. The second study cohort comprised patients who used ACEI. Propensity-score matching at 1:1 was used between ARB users and non-ARB users. We recruited 67 944 participants for the ARB study and 58 062 participants for the ACEI study. The same matching was also performed between ACEI users and non-ACEI users. Cox proportional hazard regression was used to analyse the risk of the outcome of viral pneumonia. RESULTS: The hazard ratio of community-acquired pneumonia for ARB users relative to non-ARB users was 0.33. The hazard ratio of community-acquired pneumonia was 0.71 times in ACEI users compared with ACEI nonusers. In stratification analysis, both ARB and ACEI both exhibited a protective effect for community-acquired pneumonia in each age and sex group. In the analysis of the effects of therapy duration, patients using ARB for fewer than 100 days exhibited a greater reduction in the risk of community-acquired pneumonia (adjusted HR = 0.58) compared with the non-ARB cohort. For the ACEI study, patients who used ACEI for 121-450 days were more likely to exhibit reduced risks of community-acquired pneumonia (adjusted HR = 0.5). CONCLUSION: Both ACEI and ARB uses were associated with decreased risk of community-acquired pneumonia infection.

Risk of Viral Infection in Patients Using Either Angiotensin-converting Enzyme Inhibitors or Angiotensin Receptor Blockers: A Nationwide Population-based Propensity Score Matching Study.

BACKGROUND: We hypothesized that renin-angiotensin system (RAS) blockers have systemic protective effects beyond the respiratory tract and could reduce the risk of viral infections. METHODS: We used the National Health Insurance Research Database and identified 2 study cohorts: the angiotensin receptor blocker (ARB) cohort and angiotensin-converting enzyme inhibitor (ACEI) cohort. Propensity score matching was applied at a 1:1 ratio by all associated variables to select 2 independent control cohorts for the ARB and ACEI cohorts. A Cox proportional hazards model was applied to assess the end outcome of viral infection. RESULTS: The number of ARB and ACEI users was 20 207 and 18 029, respectively. The median age of ARB users and nonusers was 53.7 and 53.8 years, respectively. The median follow-up duration of ARB users and nonusers was 7.96 and 7.08 years; the median follow-up duration of ACEI users and nonusers was 8.70 and 8.98 years, respectively. The incidence rates of viral infections in ARB users and nonusers were 4.95 and 8.59 per 1000 person-years, respectively, and ARB users had a lower risk of viral infection than nonusers (adjusted hazard ratio [aHR], 0.53 [95% confidence interval {CI}, .48-.58]). The incidence rates of viral infections in ACEI users and nonusers were 6.10 per 1000 person-years and 7.72 per 1000 person-years, respectively, and ACEI users had a lower risk of viral infection than nonusers (aHR, 0.81 [95% CI, .74-.88]). CONCLUSIONS: Hypertensive patients using either ARBs or ACEIs exhibit a lower risk of viral infection than nonusers.

Leptin protects brain from ischemia/reperfusion-induced infarction by stabilizing the blood-brain barrier to block brain infiltration by the blood-borne neutrophils.

The cellular and molecular mechanisms underlying leptin-mediated brain protection against cerebral ischemia were investigated at the blood-brain barrier (BBB) and neutrophil level. Through the ischemia/reperfusion (I/R) animal model, we found that leptin expression level was significantly decreased in ischemic hemisphere. Brain injection with leptin (15 µg/kg, intracisternally) could block the I/R-increased BBB permeability, activation of matrix metallopeptidase 9 (MMP-9) and brain infiltration of blood-borne neutrophils to reduce the infarct volume of ischemic brain. The brain expression level of tight junction protein ZO-1 as well as number and motility of neutrophils in blood was all increased by the same injection, indicating BBB stability (rather than reduction in neutrophils) played a major role in the leptin-inhibited brain infiltration of neutrophils. Leptin-mediated protection of BBB was further confirmed in vitro, through a BBB cellular model under the in vitro ischemic condition (G/R: glucose-oxygen-serum deprivation followed by GOS restoration). The results showed that leptin again could block the G/R-increased neutrophil adherence to EC layer as well as BBB permeability, likely by stimulating the endothelial expression of ZO-1 and VE-Cadherin. The study has demonstrated that leptin could protect ischemic brain via multiple ways (other than neuronal protection), by inhibiting the BBB permeability, brain infiltration of the blood-borne neutrophils and neutrophil adherence to vascular ECs. The role of leptin in vascular biology of stroke could further support its therapeutic potential in other neurodegenerative diseases, associated with BBB disorder.

IMPLEMENTATION OF AN ELECTRONIC DASHBOARD WITH A REMOTE MANAGEMENT SYSTEM TO IMPROVE GLYCEMIC MANAGEMENT AMONG HOSPITALIZED ADULTS.

Objective: Better glycemic control for hospitalized diabetic patients significantly reduces health expenditures and improves disease outcomes. We developed a dynamic dashboard with a remote management system and evaluated its impact on inpatient glycemic control. Methods: This was an observational institution-wide study; study participants were enrolled from a 1,500-bed public medical center from 2016 to 2018. We evaluated the impact of a dynamic dashboard system, which analyzed and monitored all glucose data with virtual glycemic management recommendation by a team of endocrinologists, over 3 × 1-year periods: 2016 (pre-implementation), 2017 (development), and 2018 (implementation). Results: A total of 51,641 discharges with 878,159 blood glucose measurements were obtained during the 3-year period. After implementation of the dashboard system, the proportion of patients with poor glycemic control (hyperglycemia or hypoglycemia) was reduced by 31% (from 10.2 to 7.0 per day per 100 patients with glucose monitoring; P<.001); hyperglycemia decreased by 25% (from 6.1 to 4.6 per day per 100 patients with glucose monitoring; P<.001), and hypoglycemia decreased by 45% (from 4.2 to 2.3 per day per 100 patients with glucose monitoring; P<.001). Furthermore, the trend in the proportion of patients within the treat-to-target range showed significant improvement (P<.001) during the development period, with effectiveness maintained throughout the implementation period. Conclusion: We successfully installed a dynamic, electronic medical records-based dashboard monitoring system to improve inpatient glycemic control. The system, supported by a team of endocrinologists via remote recommendations, could efficiently fill an important need for improved glycemic management among hospitalized adults. Abbreviations: CDE = certified diabetes educator; DM = diabetes mellitus; EMR = electronic medical record; POC = point-of-care; TCVGH = Taichung Veterans General Hospital; UCSF = University of California, San Francisco; U.S. = United States; vGMS = virtual glucose management service.