Differences of bioelectrical impedance in the development and healing phase of pressure ulcers and erythema in mouse model.

Pressure ulcers (PUs) are economically burdensome medical conditions. Early changes in pressure ulcers are associated with erythema. In this study, bioelectrical impedance was used to measure the differences between PUs and blanchable erythema. We divided 21 ICR mice into three groups: control, 1000 mmHg-1h, and 1000 mmHg-6h. Healthy skin, blanchable erythema, and PUs were induced on the dorsal skin. The results indicated an immediate increase in impedance, resistance, and reactance values in the pressure group after release, followed by a subsequent decrease until two days after release. Compared with the control group, impedance and reactance significantly increased by 30.9% (p < 0.05) and 30.1% (p < 0.01), respectively, in the 6 h-loading group immediately after release. One and two days after release, the 1 h-loading and 6 h-loading groups exhibited significantly different degrees of decline. One day after release, impedance and resistance decreased by 30.2% (p < 0.05) and 19.8% (p < 0.05), respectively, in the 1 h-loading group; while impedance, resistance, and reactance decreased by 39.2% (p < 0.01), 26.8% (p < 0.01), and 45.7% (p < 0.05), respectively, in the 6 h-loading group. Two days after release, in the 1 h-loading group, impedance and resistance decreased by 28.3% (p < 0.05) and 21.7% (p < 0.05), respectively; while in the 6 h-loading group, impedance, resistance, and reactance decreased by 49.8% (p < 0.001), 34.2% (p < 0.001), and 59.8% (p < 0.01), respectively. One and two days after release the pressure group reductions were significantly greater than those in the control group. Additionally, we monitored changes during wound healing. Distinguishing early PUs from blanchable erythema by noninvasive bioelectrical impedance technology may have applications value in early assessment of PUs.

Clinicopathological characteristics of myelodysplastic syndromes with del(5q) in Taiwan.

BACKGROUND: Myelodysplastic syndromes (MDS) are a group of clonal haematopoietic stem cell disorders characterised by ineffective haematopoiesis and cytopenia. Studies have reported differences in MDS between Asian and Western countries, but data from Taiwan are scarce. MATERIALS AND METHODS: In this study we analysed the clinical and pathological features of 32 Taiwanese MDS patients with del(5q) (ie, del(5q) alone [Group A, n = 11], del(5q) with one additional cytogenetic abnormality other than monosomy 7 or del(7q) [Group B, del(5q)+1; n = 6], and del(5q) with ≥2 additional cytogenetic abnormalities [Group C, n = 15]). RESULTS: Progression-free survival (PFS) and overall survival (OS) were more favourable for Group A than for Groups B (p < 0.05) and C (p ≤ 0.001). Multivariate analysis showed that age >70 years, thrombocytopenia, and karyotype other than del(5q) alone were poor prognostic factors. Among the patients that had World Health Organization (WHO)-defined MDS with isolated del(5q), one patient (9%) had a typical marrow morphology of 5q minus syndrome with erythroid hypoplasia and four patients (36%) had hypolobated megakaryocytes. In addition, PFS and OS were significantly more favorable for the patients with del(5q) alone than for those with del(5q)+1 (p < 0.05). CONCLUSION: The bone marrow morphology, clinical features, and prognosis of Taiwanese MDS patients with del(5q) were different from those associated with MDS with isolated del(5q) as defined in the current WHO classification. Researchers should compare different geographic regions and racial populations to determine whether geographic and racial differences exist with respect to MDS with del(5q).

The Impact of Frailty Status on Pulmonary Function and Mortality in Older Patients with Chronic Obstructive Pulmonary Disease.

OBJECTIVES: We aimed to evaluate the effect of frailty on lung function and disease outcomes in older adults with chronic obstructive pulmonary disease (COPD). DESIGN: Retrospective observational cohort. SETTING AND PARTICIPANTS: At baseline, comprehensive geriatric assessment and pulmonary function tests were extracted from the case management care system of the geriatric department of a tertiary medical center. MEASUREMENTS: Frailty was assessed by the modified Rockwood frailty index. Kaplan-Meier survival and Cox proportional hazard analyses were used to analyze the primary outcome. Both the Friedman test and generalized estimating equations were used to evaluate the rate of decline in lung function. RESULTS: Among 151 enrolled older patients, comprising 69 non-COPD and 82 COPD subjects, the mean age was 80.9±8.3 years. After a median follow-up of 2.87 years, the serial forced expiratory volume in 1 s/forced vital capacity (FEV1/FVC), and forced expiratory flow at 25-75% of FVC (FEF25-75%) showed significantly different slope changes between older COPD patients with and without frailty. The mortality hazard ratio (HR) was 2.53 for COPD without frailty and 3.62 for COPD with frailty, versus those without COPD. Among COPD patients, the factors most strongly associated with mortality were timed up-and-go, activities of daily living (ADLs), instrumental ADLs, FEV1/FVC, and serum HCO3-. After adjustment for potential confounders, ADLs and FEV1/FVC remained independent mortality predictors. CONCLUSION: Among older patients with COPD, frailty was common and associated with pulmonary function decline, and mortality risk was higher in frail than in non-frail subjects.

Gestational Serum Retinol Deficiency Is Associated with Enamel Hypoplasia.

Enamel hypoplasia (EH) is a prevalent developmental defect of teeth that can result from various insults, including prenatal nutrient deficiencies. This study aimed to evaluate the association between prenatal serum retinol deficiency and EH in the deciduous teeth of offspring at 2-y of age. A cohort of 1,450 pregnant women was enrolled, and their prenatal nutritional status was assessed between 12 and 14 wk of gestation. Maternal serum retinol, serum 25-hydroxyvitamin D (25OHD), hemoglobin, body mass index, and birth outcomes, infant feeding practices, family socioeconomic status, and demographic information were recorded. Oral health examinations were conducted for the children semiannually, and EH was diagnosed using the Modified DDE index on all the surfaces of erupted teeth. A modified Poisson regression analysis was used to assess the cumulative risk of EH over a period of 2-y. A total of 920 (63.4%) mother-child pairs completed the study, and the cumulative EH prevalence among offspring after 2-y of follow-up was 16.5% (N = 152; 87/1,114 children in the first year and 132/920 in the second year, with 20/920 having EH only in the first year). After adjusting for potential confounders, maternal serum retinol deficiency significantly increased the risk of deciduous EH (risk ratio [RR], 2.0; 95% confidence interval [CI], 1.1-3.7). In addition, deficient serum 25OHD (RR, 6.5; 95% CI, 4.0-10.7), caesarean delivery (RR, 1.6; 95% CI, 1.0-2.4), Muslim (RR, 2.9; 95% CI, 2.0-4.1) and Christian (RR, 2.4; 95% CI, 1.6-3.5) versus Hindu religions, and very preterm birth (RR, 1.7; 95% CI, 1.1-2.9) increased the risk of EH. Children presenting with EH had 2 or more teeth affected, and the maxillary incisors were the most frequently affected, followed by the first primary molars and canines. In conclusion, maternal serum retinol deficiency during the 12 to 14 wk of gestation may increase the risk of deciduous EH, besides the well-established 25OHD deficiency.

Intravenous tissue plasminogen activator for acute ischemic stroke in patients with renal dysfunction.

OBJECTIVE: This study used the Taiwan Stroke Registry data to evaluate the efficacy and safety of intravenous tissue plasminogen activator (tPA) in treating acute ischemic stroke in patients with renal dysfunction. DESIGN: We identified 3525 ischemic stroke patients and classified them into two groups according to the estimated glomerular filtration rate (eGFR) at the emergency department: ≥60, and <60 ml/min/1.73 m2 or on dialysis and by the propensity score from August 2006 to May 2015. The odds ratio of poor functional outcome (modified Rankin Scale ≥2) was calculated for patients with tPA treatment (N = 705), compared to those without tPA treatment (N = 2820), by eGFR levels, at 1, 3 and 6 months after ischemic stroke. We also evaluated the risks of intracerebral hemorrhage, upper gastrointestinal bleeding, mortality, between the two groups by eGFR levels. RESULTS: Among patients with eGFR levels of <60 ml/min/1.73 m2, tPA therapy reduced the odds ratio of poor functional outcome to 0.60 (95% confidence interval = 0.42-0.87) at 6 months after ischemic stroke. The tPA therapy was not associated with increased overall risk of upper gastrointestinal bleeding, but with increased risk of intracerebral hemorrhage. The low eGFR was not a significant risk factor of intracerebral hemorrhage among ischemic stroke patients receiving tPA treatment. CONCLUSIONS: tPA for acute ischemic stroke could improve functional outcomes without increasing the risks of upper gastrointestinal bleeding for patients with or without renal dysfunction. The low eGFR was not a significant risk factor for intracerebral hemorrhage among patients receiving tPA treatment.

Increased risk of end-stage renal disease in patients with systemic sclerosis.

OBJECTIVE: Systemic sclerosis (SSc) is a systemic autoimmune disease affecting multiple organs, including the kidneys. There is a lack of long-term renal prognosis studies on patients with SSc. The aim of this study was to assess the risk of end-stage renal disease (ESRD) in patients with SSc. METHOD: We designed a prospective cohort study based on the National Health Insurance Research Database of Taiwan. Patients with SSc and a non-SSc control group were selected from 1 January 2000 to 31 December 2013. The SSc cohort and control group were matched on the propensity score in a 1:2 ratio. The primary outcome was development of ESRD. Cox proportional hazard regression was performed to assess the effects of SSc on ESRD. RESULTS: After propensity score matching, we enrolled 2012 patients in the SSc group and 4024 patients in the control group. During a mean follow-up of 6.5 years, 86 individuals [SSc group, n = 41 (2.04%); control group, n = 45 (1.12%)] had developed ESRD. The risk of ESRD in the SSc group was approximately two times higher than that in the control group [hazard ratio (HR) = 2.12, 95% confidence interval (CI) 1.39-3.24]. Subgroup analysis revealed that the higher risk of ESRD was predominantly in males (HR = 4.14, 95% CI 1.97-8.71) and the younger population (HR = 7.09, 95% CI 2.31-21.80). CONCLUSION: There was a significantly higher risk of ESRD among SSc patients than among the general population, with males and younger generations being the most vulnerable groups.

Accurate quantification of phosphorus intergranular segregation in iron by STEM-EDX.

This study describes a method to quantify phosphorus grain boundary segregation by Energy Dispersive X-ray Spectroscopy in Scanning Transmission Electron Microscope (STEM-EDX). A "box-type method" is employed, removing the long-discussed problems of interaction volume and the beam broadening effect. The proposed methodology also introduces a novel way of subtracting the spectrum background to remove the influence of coherent Bremsstrahlung and spurious peaks. A Fe-P model alloy was used to compare the box method to the quantification results previously obtained by atom probe tomography on two high angle grain boundaries. The results are specifically reported in surface concentration (atom/nm2) to avoid additional hypotheses and allow the results between the two techniques to be directly compared. The measurements show that the box-type method can accurately measure phosphorus intergranular segregation in iron.

COVID-19 vaccination and breakthrough infections in patients with cancer.

BACKGROUND: Vaccination is an important preventive health measure to protect against symptomatic and severe COVID-19. Impaired immunity secondary to an underlying malignancy or recent receipt of antineoplastic systemic therapies can result in less robust antibody titers following vaccination and possible risk of breakthrough infection. As clinical trials evaluating COVID-19 vaccines largely excluded patients with a history of cancer and those on active immunosuppression (including chemotherapy), limited evidence is available to inform the clinical efficacy of COVID-19 vaccination across the spectrum of patients with cancer. PATIENTS AND METHODS: We describe the clinical features of patients with cancer who developed symptomatic COVID-19 following vaccination and compare weighted outcomes with those of contemporary unvaccinated patients, after adjustment for confounders, using data from the multi-institutional COVID-19 and Cancer Consortium (CCC19). RESULTS: Patients with cancer who develop COVID-19 following vaccination have substantial comorbidities and can present with severe and even lethal infection. Patients harboring hematologic malignancies are over-represented among vaccinated patients with cancer who develop symptomatic COVID-19. CONCLUSIONS: Vaccination against COVID-19 remains an essential strategy in protecting vulnerable populations, including patients with cancer. Patients with cancer who develop breakthrough infection despite full vaccination, however, remain at risk of severe outcomes. A multilayered public health mitigation approach that includes vaccination of close contacts, boosters, social distancing, and mask-wearing should be continued for the foreseeable future.

Effect of acupuncture on atrial fibrillation stratified by CHA2DS2-VASc score-a nationwide cohort investigation.

OBJECTIVE: This research aimed to make statements regarding the reduction in atrial fibrillation (AF) risk due to acupuncture, stratified by CHA2DS2-VASc score. METHODS: The Kaplan-Meier method was performed to calculate cumulative incidence of outcomes for each group, and the log-rank test were performed to compare differences between groups. Incidences and hazard ratios (HRs) were estimated by univariate Cox proportional hazards models, and adjusted HRs (aHRs) were estimated by multivariate Cox proportional hazards models including demographic covariates and comorbid status. RESULTS: In CHA2DS2-VASc scores of 0-1, 2-3, 4-5 and >5, cases with acupuncture were all associated with decreased incidence of AF (aHR 0.46 with 95% CI 0.42-0.51, P < 0.001 in the CHA2DS2-VASc scores of 0-1; aHR 0.53 with 95% CI 0.50-0.57, P < 0.001 in the CHA2DS2-VASc scores of 2-3; aHR 0.56 with 95% CI 0.52-0.61, P < 0.001 in the CHA2DS2-VASc scores of 4-5; and aHR 0.64 with 95% CI 0.55-0.74, P < 0.001 in the CHA2DS2-VASc scores of >5). CONCLUSION: Protective effect of acupuncture on AF was observed in this study, and the effect was more obvious for those with fewer comorbidities.

Association of clinical factors and recent anticancer therapy with COVID-19 severity among patients with cancer: a report from the COVID-19 and Cancer Consortium.

BACKGROUND: Patients with cancer may be at high risk of adverse outcomes from severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. We analyzed a cohort of patients with cancer and coronavirus 2019 (COVID-19) reported to the COVID-19 and Cancer Consortium (CCC19) to identify prognostic clinical factors, including laboratory measurements and anticancer therapies. PATIENTS AND METHODS: Patients with active or historical cancer and a laboratory-confirmed SARS-CoV-2 diagnosis recorded between 17 March and 18 November 2020 were included. The primary outcome was COVID-19 severity measured on an ordinal scale (uncomplicated, hospitalized, admitted to intensive care unit, mechanically ventilated, died within 30 days). Multivariable regression models included demographics, cancer status, anticancer therapy and timing, COVID-19-directed therapies, and laboratory measurements (among hospitalized patients). RESULTS: A total of 4966 patients were included (median age 66 years, 51% female, 50% non-Hispanic white); 2872 (58%) were hospitalized and 695 (14%) died; 61% had cancer that was present, diagnosed, or treated within the year prior to COVID-19 diagnosis. Older age, male sex, obesity, cardiovascular and pulmonary comorbidities, renal disease, diabetes mellitus, non-Hispanic black race, Hispanic ethnicity, worse Eastern Cooperative Oncology Group performance status, recent cytotoxic chemotherapy, and hematologic malignancy were associated with higher COVID-19 severity. Among hospitalized patients, low or high absolute lymphocyte count; high absolute neutrophil count; low platelet count; abnormal creatinine; troponin; lactate dehydrogenase; and C-reactive protein were associated with higher COVID-19 severity. Patients diagnosed early in the COVID-19 pandemic (January-April 2020) had worse outcomes than those diagnosed later. Specific anticancer therapies (e.g. R-CHOP, platinum combined with etoposide, and DNA methyltransferase inhibitors) were associated with high 30-day all-cause mortality. CONCLUSIONS: Clinical factors (e.g. older age, hematological malignancy, recent chemotherapy) and laboratory measurements were associated with poor outcomes among patients with cancer and COVID-19. Although further studies are needed, caution may be required in utilizing particular anticancer therapies. CLINICAL TRIAL IDENTIFIER: NCT04354701.

Non-alcoholic fatty liver disease increases the prevalence of maintenance haemodialysis in patients with chronic kidney disease.

AIM: To investigate the association between non-alcoholic fatty liver disease (NAFLD) and incidence of maintenance haemodialysis in patients with chronic kidney disease (CKD). METHODS: We enrolled patients diagnosed with CKD between 2001 and 2007. The patients were categorized into two groups based on abdominal ultrasound finding, namely those with NAFLD and those without NAFLD. The disease (maintenance haemodialysis)-free survival rate was estimated using the Kaplan-Meier method. Univariate and multivariate Cox regression analyses was used to evaluate the hazard ratios of covariates for the incidence of maintenance haemodialysis. RESULTS: A total of 161 patients (61 with NAFLD and 100 without NAFLD) were enrolled. The mean age was 69.3 years. The mean follow-up was 7.4 years. The patients with NAFLD had an increased incidence of maintenance haemodialysis (39.3 % vs 24.0 %; p=0.0396) and inferior disease-free survival rate (p=0.006). Furthermore, diabetes (p=0.0126) and proteinuria (p=0.0003) were identified as significant predictors of CKD progression. CONCLUSION: NAFLD was associated with an increased incidence of maintenance haemodialysis and inferior disease-free survival rate. NAFLD may impair renal function and patients with renal impairment should be monitored carefully (Tab. 3, Fig. 1, Ref. 25) Keywords: non-alcoholic fatty liver disease, haemodialysis, chronic kidney disease, proteinuria.

Caries Risk Prediction Models in a Medical Health Care Setting.

Despite development of new technologies for caries control, tooth decay in primary teeth remains a major global health problem. Caries risk assessment (CRA) models for toddlers and preschoolers are rare. Among them, almost all models use dental factors (e.g., past caries experience) to predict future caries risk, with limited clinical/community applicability owing to relatively uncommon dental visits compared to frequent medical visits during the first year of life. The objective of this study was to construct and evaluate risk prediction models using information easily accessible to medical practitioners to forecast caries at 2 and 3 y of age. Data were obtained from the Growing Up in Singapore Towards Healthy Outcomes (GUSTO) mother-offspring cohort. Caries was diagnosed using modified International Caries Detection and Assessment System criteria. Risk prediction models were constructed using multivariable logistic regression coupled with receiver operating characteristic analyses. Imputation was performed using multiple imputation by chained equations to assess effect of missing data. Caries rates at ages 2 y (n = 535) and 3 y (n = 721) were 17.8% and 42.9%, respectively. Risk prediction models predicting overall caries risk at 2 and 3 y demonstrated area under the curve (AUC) (95% confidence interval) of 0.81 (0.75-0.87) and 0.79 (0.74-0.84), respectively, while those predicting moderate to extensive lesions showed 0.91 (0.85-0.97) and 0.79 (0.73-0.85), respectively. Postimputation results showed reduced AUC of 0.75 (0.74-0.81) and 0.71 (0.67-0.75) at years 2 and 3, respectively, for overall caries risk, while AUC was 0.84 (0.76-0.92) and 0.75 (0.70-0.80), respectively, for moderate to extensive caries. Addition of anterior caries significantly increased AUC in all year 3 models with or without imputation (all P < 0.05). Significant predictors/protectors were identified, including ethnicity, prenatal tobacco smoke exposure, history of allergies before 12 mo, history of chronic maternal illness, maternal brushing frequency, childbearing age, and so on. Integrating oral-general health care using medical CRA models may be promising in screening caries-susceptible infants/toddlers, especially when medical professionals are trained to "lift the lip" to identify anterior caries lesions.

Association of fine-particulate and acidic-gas air pollution with premenstrual syndrome risk.

OBJECTIVE: Air pollution had been reported to be associated with the reproductive health of women. However, the association of particulate matter (PM) and acid gases air pollution with premenstrual syndrome (PMS) warrants investigation. This study investigated the effects of air pollution on PMS risk. POPULATION: We combined data from the Taiwan Air Quality-Monitoring Database and the Longitudinal Health Insurance Database. In total, an observational cohort of 85 078 Taiwanese women not diagnosed as having PMS. METHODS: Air pollutant concentrations were grouped into four levels based on the concentration quartiles of several types of air pollutants. MAIN OUTCOME MEASURES: We then applied univariable and multivariable Cox proportional hazard regression models to assess PMS risk in association with each pollutant type. RESULTS: Women exposed to Q4-level SO2 exhibited a 7.77 times higher PMS risk compared with those to Q1-level SO2 (95% confidence interval [CI] = 6.22-9.71). Women exposed to Q4-level NOx exhibited a 2.86 times higher PMS risk compared with those exposed to Q1-level NOx (95% CI = 2.39-3.43). Women exposed to Q4-level NO exhibited a 3.17 times higher PMS risk compared with women exposed to Q1-level NO (95% CI = 2.68-3.75). Finally, women exposed to Q4-level PM with a ≤2.5-µm diameter (PM2.5) exhibited a 3.41 times higher PMS risk compared with those exposed to Q1-level PM2.5 (95% CI = 2.88-4.04). CONCLUSIONS: High incidences of PMS were noted in women who lived in areas with higher concentrations of SO2, NOx, NO, NO2 and PM2.5.

Insulin enhances and metformin reduces risk of colorectal carcinoma in type-2 diabetes.

BACKGROUND: Identifying colorectal cancer associated risks is important for conducting a program for the survey and prevention of colorectal cancer. AIM: To investigate the association between use of insulin or metformin with colorectal cancer (CRC) in type 2 diabetes (T2DM). DESIGN: Population-based cohort study. METHODS: Through analysis of National Health Insurance (NHI) database between 1998 and 2010 in Taiwan, we identified 66 324 T2DM patients aged ≥ 20 years and selected subjects without diabetes by 1: 1 randomly matching with the study cohort based on age, sex and index date. We followed up the participants until 31 December 2011 or when they withdrew from the NHI program. RESULTS: Compared with non-diabetic subjects, the T2DM patients exhibited an increased risk of CRC [adjusted HR (aHR) = 1.56, 95% confidence interval (CI) = 1.39-1.75], after adjustment for age, sex, urbanization level, comorbidities and examinations of colonoscopy, sigmoidoscopy, or stool occult blood test. Among the T2DM patients, insulin usage increased the risk of CRC (aHR = 1.86, 95% CI = 1.58-0-2.19) after adjustment for age, sex, urbanization level, comorbidities, metformin usage and examinations; nevertheless, metformin decreased the risk of CRC (aHR = 0.65, 95% CI = 0.54-0.77) after adjustment for age, sex, urbanization level, comorbidities, insulin usage and examinations. Compared with the non-insulin cohort, the risk of CRC tended to increase with the incremental dosage of insulin exposure. CONCLUSION: Our population-based cohort study demonstrated an association between T2DM and CRC. Among the T2DM patients, insulin use was associated with an increased risk of CRC and metformin use was associated with a decreased risk of CRC. Inability to obtain information on several potential confounding factors, such as lifestyle and dietary habits, is the major limitation of the study.

Risk of hyperglycaemic crisis episode in diabetic patients with schizophrenia: A nationwide population-based cohort study.

AIM: Under-management of diabetes can lead to a hyperglycaemic episode (HCE), which could be further strengthened in the presence of schizophrenia and the use of antipsychotics. This study aims to investigate the risk of HCE in diabetic patients with schizophrenia. Additionally, the duration of antipsychotic use on the risk of HCE is examined. MATERIALS AND METHODS: A total of 13858 diabetic patients with schizophrenia and 55407 controls (without schizophrenia) matched by gender, age, index year, and Charlson Comorbidity Index score were included between 1999 and 2010 and followed to the end of 2013 using from the Taiwan National Health Insurance Research Database. During the follow-up period, participants who developed HCE were identified. Cox regression analysis was used to calculate the hazard ratio (HR) with 95% confidence interval (95% CI) of the HCE incidence rate between the two groups studied. RESULTS: Diabetic patients with schizophrenia were associated with an increased risk of HCE compared with unaffected controls after adjusted for baseline demographics and duration of antipsychotic use (4.73 versus 2.43 per 1,000 person-years, HR: 2.16, 95% CI: 1.85-2.51). Also, in diabetic patients with schizophrenia, a longer duration of antipsychotic use was associated with a lower risk of HCE after adjustment for the above-mentioned variables, suggesting a protective effect of antipsychotics against HCE during prolonged use. CONCLUSION: This study highlights the need to pay more attention to the risk of HCE in diabetic patients with schizophrenia and the importance of proper use of antipsychotics may reduce the risk of HCE.

Efficacy and safety of high-dose vs low-dose leucovorin in patients with colorectal cancer: systematic review and meta-analysis.

AIM: The clinical benefits of a combination of leucovorin and fluorouracil have been established in the treatment of colorectal cancer. Due to a leucovorin shortage in 2008, many institutions revised their protocols to reduce the dose of leucovorin. After the shortage was resolved, some hospitals still maintained their modified protocols. Thus, we conducted a systematic review to evaluate the efficacy and safety of low- vs high-dose leucovorin in the treatment of colorectal cancer. METHOD: The PubMed, Embase and Cochrane databases were searched for studies published before May 2019. The meta-analysis was performed to estimate the pooled effect sizes by using a random effect model. The primary outcomes were median survival time and tumour response rate. Secondary outcomes were haematological and nonhaematological toxicities. RESULTS: Eight randomized controlled trials and four retrospective studies were reviewed. The pooled median survival time was similar between the two dose levels (standard mean difference -0.06, 95% CI -0.19 to 0.08). The pooled tumour response rate was comparatively higher in the high-dose leucovorin regimen (OR 0.81; 95% CI 0.55-1.18). No statistically significant difference was found between the haematological and nonhaematological toxicities of the two groups. However, there were fewer diarrhoea events in the low-dose leucovorin regimen. CONCLUSION: Low-dose leucovorin regimens seemed feasible approaches for colorectal cancer treatment when the shortage happened, because both regimens manifested comparable outcomes in survival time and tumour response rate.

Mechanisms of ischaemic neural progenitor proliferation: a regulatory role of the HIF-1α-CBX7 pathway.

AIMS: Investigations of the molecular mechanisms of hypoxia- and ischaemia-induced endogenous neural progenitor cell (NPC) proliferation have mainly focused on factors secreted in response to environmental cues. However, little is known about the intrinsic regulatory machinery underlying the self-renewing division of NPCs in the brain after stroke. METHODS AND RESULTS: Polycomb repressor complex 1-chromobox7 (CBX7) has emerged as a key regulator in several cellular processes including stem cell self-renewal and cancer cell proliferation. The hypoxic environment triggering NPC self-renewal after CBX7 activation remains unknown. In this study, we found that the upregulation of CBX7 during hypoxia and ischaemia appeared to be from hypoxia-inducible factor-1α (HIF-1α) activation. During hypoxia, the HIF-1α-CBX7 cascade modulated NPC proliferation in vitro. NPC numbers significantly decreased in CBX7 knockout mice generated using CRISPR/Cas9 genome editing. CONCLUSIONS: We provided the novel insight that CBX7 expression is regulated through HIF-1α activation, which plays an intrinsically modulating role in NPC proliferation.

Antiplatelet agents for the secondary prevention of ischaemic stroke in patients with or without renal dysfunction.

BACKGROUND AND PURPOSE: Studies on using antiplatelet agents for secondary prevention in ischaemic stroke patients with renal dysfunction are limited. The Taiwan Stroke Registry database was used to compare the efficacy of antiplatelet agents. METHODS: From the Taiwan Stroke Registry data, 39 174 acute ischaemic stroke patients were identified and were classified into three groups by antiplatelet agent: aspirin, clopidogrel and dual antiplatelet therapy (DAPT) with a combination of aspirin and clopidogrel. The re-stroke incidence and 1-year mortality were stratified by estimated glomerular filtration rate (eGFR) levels at admission: ≥90, 60-89 and <60 ml/min/1.73 m2 or on dialysis. RESULTS: Compared to the aspirin group, the re-stroke differences were not statistically significant for the clopidogrel group [adjusted subhazard ratio 0.95, 95% confidence interval (CI) 0.84-1.08] and the DAPT group (adjusted subhazard ratio 1.03, 95% CI 0.77-1.39) after controlling for the competing risk of death. The mortality rate increased as the eGFR level declined. In addition, compared to patients taking aspirin, there was no statistically significant difference in overall 1-year mortality for the clopidogrel group (adjusted hazard ratio 1.11, 95% CI 0.95-1.29) and for the DAPT group (adjusted hazard ratio 1.01, 95% CI 0.67-1.54). The results were consistent in different subgroups stratified by eGFR levels. CONCLUSIONS: There was no difference in the risks of recurrent stroke and 1-year mortality amongst ischaemic stroke patients with or without renal dysfunction receiving antiplatelet agents with aspirin, clopidogrel or dual agents with a combination of aspirin and clopidogrel, regardless of their renal dysfunction status.

Ten-year fracture risk by FRAX and osteoporotic fractures in patients with systemic autoimmune diseases.

The Fracture Risk Assessment Tool (FRAX) has been used universally for the purpose of fracture risk assessment. However, the predictive capacity of FRAX for autoimmune diseases remains inconclusive. This study aimed to compare the applicability of FRAX for autoimmune disease patients. This retrospective study recruited rheumatoid arthritis (RA), systemic lupus erythematosus (SLE) and primary Sjögren syndrome (pSS) patients with bone mineral density (BMD) tests. Patients with any osteoporotic fractures were identified. Taiwan-specific FRAX with and without BMD were then calculated. In total, 802 patients (451 RA, 233 SLE and 118 pSS) were enrolled in this study. The cumulative incidences of osteoporotic fractures in the RA, SLE and pSS patients were 43.0%, 29.2% and 33.1%, respectively. For those with a previous osteoporotic fracture, T-scores were classified as low bone mass. Overall, the patients' 10-year probability of major fracture risk by FRAX without BMD was 15.8%, which then increased to 20.3% after incorporation of BMD measurement. When analyzed by disease group, the fracture risk in RA patients was accurately predicted by FRAX. In contrast, current FRAX, either with or without BMD measurement, underestimated the fracture risk both in SLE and pSS patients, even after stratification by age and glucocorticoid treatment. For pSS patients with major osteoporotic fractures, FRAX risks imputed by RA were comparable to major osteoporotic fracture risks of RA patients. Current FRAX accurately predicted fracture probability in RA patients, but not in SLE and pSS patients. RA-imputed FRAX risk scores could be used as a temporary substitute for SLE and pSS patients.

Combination immunosuppressant therapy and lupus nephritis outcome: a hospital-based study.

Lupus nephritis (LN) is the leading cause of mortality in lupus patients. This study aimed to investigate the treatment outcome and renal histological risk factors of LN in a tertiary referral center. Between 2006 and 2017, a retrospective observational study enrolled 148 biopsy-proven LN patients. After propensity score matching, 75 cases were included for further analysis. The classification and scoring of LN were assessed according to the International Society of Nephrology/Renal Pathology Society. Treatment response was evaluated by daily urine protein and urinalysis at two years after commencing induction treatment and the development of end-stage renal disease (ESRD). In total, 50.7% patients achieved complete remission (CR) or partial remission (PR), while 49.3% patients were categorized as nonresponders. Therapeutic responses in terms of CR/PR rates were associated with Systemic Lupus Erythematosus Disease Activity Index scores (odds ratio (OR): 1.34, 95% confidence interval (CI): 1.12-1.60, p = 0.001). Moreover, higher baseline creatinine levels (hazard ratio (HR): 2.10, 95% CI: 1.29-3.40, p = 0.003), higher renal activity index (HR: 1.30, 95% CI: 1.07-1.58, p = 0.008) and chronicity index (HR: 1.40, 95% CI: 1.06-1.85, p = 0.017) predicted ESRD. Among pathological scores, cellular crescents (HR: 4.42, 95% CI: 1.01-19.38, p = 0.049) and fibrous crescents (HR: 5.93, 95% CI: 1.41-24.92, p = 0.015) were independent risk factors for ESRD. In conclusion, higher lupus activity was a good prognostic marker for renal remission. Renal histology was predictive of ESRD. Large-scale prospective studies are required to verify the efficacy of mycophenolate in combination with azathioprine or cyclosporine in LN patients.