Long-term safety of total knee arthroplasty in patients with chronic kidney disease in Taiwan: a retrospective cohort study.

BACKGROUND: Chronic kidney disease (CKD) is a prevalent condition in Taiwan, and the incidence of total knee arthroplasty (TKA) is on the rise. This study aimed to evaluate the postoperative results of patients with different degrees of CKD after TKA, using data from the Taiwan National Health Insurance Research Database. METHODS: The study analyzed 3,078 patients who received TKA from 2012 to 2017, equally divided into three groups: none-CKD, mild CKD (without dialysis), and severe CKD (with dialysis). Propensity score matching was used to minimize selection bias. RESULTS: After TKA, there was no significant difference in the risk of debridement surgery for infection between the three groups (adjusted HR of mild CKD 0.71 95% CI = 0.36 - 1.38, P = 0.3073; adjusted HR of severe CKD: 1.14, 95% CI = 0.63 - 2.06, P = 0.6616). However, CKD patients requiring dialysis had a significantly higher risk of mortality (adjusted HR 1.98, 95% CI = 1.57 - 2.50, P < 0.001) and readmission within 90 days of any causes (adjusted HR 1.83, 95% CI = 1.48 - 2.26, P < 0.001) than non-CKD and mild CKD patients. CONCLUSION: Severe CKD patients needing dialysis after TKA have a higher risk of mortality and readmission rates than that of the non-CKD or mild CKD patients. If the patient is in the early stage of CKD, their prognosis after receiving TKA is expected to be as good as non-CKD patients. LEVEL OF EVIDENCE: IV; well-designed cohort study.

Low-dose imiquimod induces melanogenesis in melanoma cells through an ROS-mediated pathway.

BACKGROUND: Melanogenesis is the process of melanin maturation which not only protects skin from UV radiation but also plays an important role in antigenicity of melanomas. Imiquimod (IMQ) is a toll-like receptor 7 (TLR7) agonist that exhibits antiviral and anticancer activity. OBJECTIVE: To explore whether IMQ could induce melanogenesis in melanoma cells. METHODS: The mouse melanoma cell line B16F10, the mouse immortalized melanocyte Melan-A, and human melanoma cell lines MNT-1, C32 and A375 were utilized in this study. The pigmented level was observed by the centrifuged cell pellet. The intracellular and extracellular melanin levels were examined in the absorbance in NaOH-extracted cell lysate and cell-cultured medium, respectively. The expression of melanogenesis related proteins was examined by immunoblotting. The intracellular cyclic AMP amount was evaluated by the cAMP Glo assay kit. The activity of phosphodiesterase 4B (PDE4B) was investigated by CREB reporter assay with overexpressed PDE4B or not. RESULTS: We demonstrated that a low dose of IMQ could trigger melanogenesis in B16F10 cells. IMQ induced microphthalmia-associated transcription factor (MITF) nuclear translocation, upregulated the expression of melanogenesis-related proteins, increased tyrosinase (TYR) activity, and led to pigmentation in B16F10 cells. Next, we found that IMQ-induced melanogenesis was activated by excessive intracellular cAMP accumulation, which was regulated through IMQ-mediated PDE4B inhibition. Finally, IMQ-induced ROS production was found to be involved in melanogenesis by its control of PDE4B activity. CONCLUSIONS: Low dose of IMQ could activate melanogenesis through the ROS/PDE4B/PKA pathway in melanoma cells.

A Novel Technique for Autograft Preparation Using Patient-Specific Instrumentation (PSI) Assistance in Total Hip Arthroplasty in Developmental Dysplasia of Hip (DDH).

Due to the change in the structure of the proximal femur and acetabulum in patients with developmental dysplasia of the hip, total hip arthroplasty (THA) was difficult to perform for surgeons. To elevate the acetabular coverage rate, we developed a technique in the use of a patient-specific instrumentation (PSI) graft in patients with developmental dysplasia of hip (DDH) undergoing surgery. This study aims to evaluate the peri-operative outcomes of THA with PSI graft in patients with DDH. This study recruited 6 patients suffering from Crowe I DDH with secondary Grade IV osteoarthritis. All the patients underwent THA with PSI graft performed by a well-experienced surgeon. Perioperative outcomes included surgical procedures, blood loss during operation, the volume of blood transfusion, length of hospitalization, complications, and the mean difference in hemoglobin levels before and after surgery. All the outcomes analyzed were assessed by mean and standard deviation. The average duration of the surgical procedure was found to be 221.17 min, with an SD of 19.65 min. The mean blood loss during the operation was 733.33 mL, with an SD of 355.90 mL. The mean length of hospital stay was calculated to be 6 days, with an SD of 0.89 days. Furthermore, the mean difference between the pre- and postoperative hemoglobin levels was 2.15, with an SD of 0.99. A total of three patients received 2 units of leukocyte-poor red blood cells (LPR) as an accepted blood transfusion. There were no reported complications observed during the admission and one month after the operation. This study reported the peri-operative outcomes in the patients with DDH who underwent THA with PSI graft. We found that THA with PSI graft would provide a safe procedure without significant complications. We assumed that the PSI graft in THA may increase the coverage rate of the acetabulum, which may increase the graft union rates. Further cohort studies and randomized controlled trials were needed to confirm our findings.

Analgesic efficacy of collagen peptide in knee osteoarthritis: a meta-analysis of randomized controlled trials.

BACKGROUND: The management of knee osteoarthritis involves various treatment strategies. It is important to explore alternative therapies that are both safe and effective. Collagen peptides have emerged as a potential intervention for knee osteoarthritis. This study aims to evaluate the analgesic effects and safety of collagen peptide in patients diagnosed with knee osteoarthritis. METHODS: We conducted a systematic literature search following the guidelines of the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement. Multiple databases including PubMed, Scopus, EMBASE, Web of Science, Cochrane, and ClinicalTrials.gov were searched for randomized controlled trials (RCTs) published up to 27 May 2023 that focused on the analgesic outcomes and adverse events associated with collagen peptides or hydrolyzed collagen in patients with osteoarthritis. We assessed the quality of the included studies and the strength of evidence using the Cochrane ROB 2.0 tool and Grading of Recommendations, Assessment, Development, and Evaluations. RESULTS: Four trials involving 507 patients with knee osteoarthritis were included and analyzed using the random-effects model. All these trials were considered to have a high risk of bias. Our results revealed a significant difference in pain relief between the collagen peptide group and the placebo group in patients with knee osteoarthritis (standardized mean difference: - 0.58; 95% CI - 0.98, - 0.18, p = 0.004; I2: 68%; quality of evidence: moderate). However, there was no significant difference in the risk of adverse events between collagen peptide and placebo (odds ratio: 1.66; 95% CI 0.99, 2.78, p = 0.05; I2: 0%; quality of evidence: very low). CONCLUSIONS: Our findings demonstrate significant pain relief in patients with knee osteoarthritis who received collagen peptides compared to those who received placebo. In addition, the risk of adverse events did not differ significantly between the collagen peptide group and the placebo group. However, due to potential biases and limitations, well-designed randomized controlled trials are needed to validate and confirm these findings.

Impact on carbamazepine usage and cutaneous adverse reactions before and after the reimbursement of HLA-B*1502 genotyping in Taiwan, 2000-2017: A nationwide longitudinal study.

OBJECTIVE: The HLA-B*1502 allele is strongly associated with carbamazepine (CBZ)-induced Stevens-Johnson syndrome/toxic epidermal necrolysis (SJS/TEN) in the Han Chinese population. This study investigated the impact of HLA-B*1502 screening on CBZ utilization and rates of severe cutaneous allergic reactions (SCARs) and SJS/TEN over time in Taiwan, where screening for HLA-B*1502 genotyping before prescribing CBZ was reimbursed in June 2010. METHODS: Using the Taiwan National Health Insurance Research Database, we analyzed 13 277 457 episodes of seeking treatment for epilepsy or neuralgia between 2000 and 2017. Episodes were categorized into quarters based on treatment time. Propensity score-based stabilized weighting (PSSW) ensured well-balanced covariates. The difference in 3-month SCAR and SJS/TEN rates between phase 2 (2011-2017) and phase 1 (2000-2009) was examined using a one-sample Z-test. Pearson correlation coefficients assessed the association between screening rate, the number of CBZ users and nonusers, and SCAR and SJS/TEN rates after HLA-B*1502 genotyping. RESULTS: CBZ prescriptions reduced from 7% (2000-2003) to 6% (2004-2010) and 4% (2011-2017). The screening rates of CBZ nonusers and CBZ users increased from 0%, .5% in 2011 to .8%, 16% in 2017, respectively. After PSSW, the mean 3-month SCAR incidence rates (per 10 000 episodes) significantly decreased from phase 1 to phase 2 for CBZ users (6.91 vs. 3.09, p < .0001) and nonusers (1.96 vs. 1.65, p < .0001). SJS/TEN incidence rates (per 10 000 episodes) significantly decreased from phase 1 to phase 2 for CBZ users (2.94 vs. 1.93, p < .0001) but not for nonusers (.71 vs. .74, p = .1492). In phase 2, SCAR incidence rates were significantly and negatively correlated with the screening rate for both CBZ users (r = -.38, p = .0342) and nonusers (r = -.80, p < .001). No significant correlation was found between SJS/TEN incidence rates and screening rates. SIGNIFICANCE: Recognizing HLA-B*1502 allele and avoiding CBZ therapy in HLA-B*1502-positive patients is critical for preventing CBZ-induced severe adverse events.

Respiratory Outcomes of Insulin Use in Patients with COPD: A Nationwide Population-Based Cohort Study.

Acute exacerbations of chronic obstructive pulmonary disease (COPD) with severe hyperglycemia may require insulin to lower glucose levels in people with coexisting type 2 diabetes (T2D) and COPD. We conducted this study to examine the risk of hospitalization for COPD, pneumonia, ventilator use, lung cancer, hypoglycemia, and mortality with and without insulin use in people with T2D and COPD. We adopted propensity-score-matching to identify 2370 paired insulin users and non-users from Taiwan's National Health Insurance Research Database between 1 January 2000 and 31 December 2018. Cox proportional hazards models and the Kaplan-Meier method were utilized to compare the risk of outcomes between study and control groups. The mean follow-up for insulin users and non-users was 6.65 and 6.37 years. Compared with no insulin use, insulin use was associated with a significantly increased risk of hospitalization for COPD (aHR 1.7), bacterial pneumonia (aHR 2.42), non-invasive positive pressure ventilation (aHR 5.05), invasive mechanical ventilation (aHR 2.72), and severe hypoglycemia (aHR 4.71), but with no significant difference in the risk of death. This nationwide cohort study showed that patients with T2D and COPD requiring insulin therapy may have an increased risk of acute COPD exacerbations, pneumonia, ventilator use, and severe hypoglycemia without a significant increase in the risk of death.

Ambient Temperature Effect on Acute Myocardial Infarction by Risk Factors: Daily Data From 2000 to 2017, Taiwan.

Background: A U-shaped relationship between temperature and acute myocardial infarction (AMI) was observed, but the risk factors were rarely included. Objectives: The authors sought to examine AMI's cold and heat exposure after considering their risk groups. Methods: Daily data on ambient temperature, newly diagnosed AMI, and 6 known risk factors of AMI for the Taiwan population from 2000 to 2017 were created by linking 3 Taiwan national databases. Hierarchical clustering analysis was performed. Poisson regression was performed on the AMI rate with the clusters along with the daily minimum temperature in cold months (November-March) and the daily maximum temperature in hot months (April-October). Results: There were 319,737 patients with new-onset AMI over 109.13 billion person-days, corresponding to the incidence rate of 107.02 per 100,000 person-years (95% CI: 106.64-107.39 person-years). Hierarchical clustering analysis identified 3 distinct clusters (1: age <50 years, 2: age ≥50 years without hypertension, and 3: mainly age ≥50 years with hypertension) with AMI incidence rates of 16.04, 105.13, and 388.17 per 100,000 person-years, respectively. Poisson regression revealed that below 15 °C, cluster 3 had the highest risk of AMI per 1°C reduce in temperature (slope = 1.011) compared with clusters 1 (slope = 0.974) and 2 (slope = 1.009). However, above the 32 °C thresholds, cluster 1 had the highest risk of AMI per 1 °C increase in temperature (slope = 1.036) compared with clusters 2 (slope = 1.02) and 3 (slope = 1.025). Cross validation showed a good fit for the model. Conclusions: People ≥50 years of age with hypertension are more susceptible to cold-related AMI. However, heat-related AMI is more prominent in individuals <50 years of age.

A Patient with Acute Necrotizing Fasciitis after a Total Knee Replacement: A Case Report.

Necrotizing fasciitis is a relatively rare and serious fatal soft-tissue infection that is characterized by a rapidly spreading bacterial infection located in the subcutaneous tissues. We report a 59-year-old man who was diagnosed with acute necrotizing fasciitis, following a primary total knee replacement. He received primary total knee replacement that was uneventful and smooth intraoperatively. An immediate high fever was reported in the next few days, with several complications, confirming a diagnosis of necrotizing fasciitis. The most effective treatment for this disease is a rapid primary diagnosis and surgical debridement. Gold standard treatment includes intravenous therapy, such as antibiotics, surgical debridement, and intensive care. As a result of possible GI complications that triggered necrotizing fasciitis, the patient underwent flap reconstruction. This report's aim is to review the comprehensive treatment, management, and experience of necrotizing fasciitis, highlighting the roles with a multidisciplinary care team for improving the condition of this patient.

Exploration of COVID-19 Pandemic Prevention Behaviors among Healthcare Workers.

Since the outbreak of COVID-19, the pandemic has become an important topic of global public health. To reduce the rapid spread of the pandemic, compliance with preventive behaviors has become one of the important guidelines from the World Health Organization (WHO). Healthcare workers stand on the frontline for pandemic prevention, and preventive behaviors are essential measures to protect their health and safety. The purpose of this study was to propose an integrative model that explained and predicted COVID-19 preventive behaviors among healthcare workers. The study integrated workplace safety climate and the health belief model (HBM) to verify the impact of workplace safety climate and health belief factors on the safety attitude, safety compliance, and safety satisfaction of healthcare workers performing COVID-19 pandemic prevention behaviors. A cross-sectional study was conducted from March to August 2021 with a self-administered online questionnaire. The sample of the study was drawn from healthcare workers of a famous medical institution in Taipei City as research subjects. After collecting 273 valid questionnaires and verifying them through the analysis of structural equation modeling (SEM), the findings revealed that workplace safety climate had an impact on health belief factors, and then health belief factors had impacts on safety attitudes. In addition, safety attitude affected safety compliance, while safety compliance further affected safety satisfaction. The study showed that workplace safety climate can strengthen healthcare workers' health beliefs and further affect their safety attitudes, safety compliance, and safety satisfaction. The study attempted to propose a model of healthcare workers' pandemic prevention behaviors as a reference for medical facility administrators in real practice.

Is Thrombocytopenia an In-Hospital Mortality Risk Factor among Patients with Acute Ischemic Stroke? A Propensity Score-Matched Analysis from the MIMIC-IV Database.

(1) Background: We aimed to evaluate the aspect of thrombocytopenia in patients with acute ischemic stroke (AIS); (2) Methods: Patients with AIS were recruited in the Medical Information Mart for Intensive Care IV database from 2008 to 2019. The thrombocytopenia was defined as a platelet blood count of less than 150 K/µL. We compared the patient characteristics and clinical outcomes using propensity score matching (PSM); (3) Results: Thrombocytopenia affected 151 out of the 1236 patients (12.2%). Patients with thrombocytopenia were older (70.5 ± 12.8 vs. 68.4 ± 14.4; SMD = 0.154) and had a higher Charlson comorbidity index (7.3 ± 2.5 vs. 6.7 ± 2.7; SMD = 0.228) and acute physiology score III (44.8 ± 21.0 vs. 38.2 ± 19.1; SMD = 0.328) than those without thrombocytopenia. The risk of in-hospital mortality did not increase linearly or nonlinearly with a lower platelet count (overall p value = 0.794; nonlinear p value = 0.646). After PSM, 147 pairs remained. Thrombocytopenia was not linked with in-hospital mortality (HR: 1.06, 95% CIs: 0.60-1.88); (4) Conclusions: We described the clinical characteristics of patients admitted for thrombocytopenia and AIS who did not receive reperfusion therapy; additionally, we found that thrombocytopenia was not an independent short-term risk factor of in-hospital mortality.

The Role of Nondiabetic Hyperglycemia in Critically Ill Patients with Acute Ischemic Stroke.

In this study, we aim to elucidate the association between nondiabetic hyperglycemia and the short-term prognosis of critically ill patients with acute ischemic stroke. We extracted data using the Medical Information Mart for Intensive Care IV from 2008 to 2019. The primary outcomes were set as intensive care units (ICU) and in-hospital mortality. We developed a Cox proportional hazards model to determine the nonlinear association between serum glucose levels and primary outcomes. Of the 1086 patients included, 236 patients had hyperglycemia. Patients with hyperglycemia were associated with higher ages, female gender, higher Charlson Comorbidity Index scores, and higher Acute Physiology Score III scores. After propensity score matching, 222 pairs remained. The hyperglycemia group had a significantly higher ICU mortality (17.6% vs. 10.8%; p = 0.041). Meanwhile, no significant differences in ICU length of stay (5.2 vs. 5.2; p = 0.910), in-hospital mortality (26.6% vs. 18.9%, p = 0.054), and hospital length of stay (10.0 vs. 9.1; p = 0.404) were observed between the two groups. The Kaplan-Meier curves for ICU and in-hospital survival before matching suggested significant differences; however, after matching, they failed to prove any disparity. Non-diabetic patients with acute ischemic stroke have poor clinical characteristic while encountering hyperglycemic events; therefore, careful monitoring in the acute phase is still required.

Imiquimod-induced ROS production causes lysosomal membrane permeabilization and activates caspase-8-mediated apoptosis in skin cancer cells.

BACKGROUND: Lysosomal cell death is induced by lysosomal membrane permeabilization (LMP) and the subsequent release of lysosomal proteolytic enzymes, including cathepsins (CTSs), which results in mitochondrial dysfunction and apoptosis. Imiquimod (IMQ), a synthetic TLR7 ligand, has both antiviral and antitumor activity against various skin malignancies in clinical treatment. Previously, we demonstrated IMQ not only caused lysosomal dysfunction but also triggered lysosome biogenesis to achieve lysosomal adaptation in cancer cells. OBJECTIVE: To determine whether lysosomes are involved in IMQ-induced apoptosis. METHODS: The human skin cancer cell lines BCC, A375 and mouse melanoma cell line B16F10 were used in all experiments. Cell death was determined by the Cell Counting Kit-8 (CCK-8) assay and DNA content assay. Protein expression was determined by immunoblotting. Caspase-8 activity was assessed using a fluorescence caspase-8 kit and determined by flow cytometry and confocal microscopy. RESULTS: IMQ not only induced lysosome damage but also abrogated lysosome function in skin cancer cells. IMQ-induced caspase-8 activation contributed to the processes of lysosomal cell death. Moreover, the use of ROS scavengers significantly abolished caspase-8 activation and inhibited IMQ-induced LMP. Additionally, pharmacological inhibition of CTSD not only abrogated caspase-8 activation but also rescued IMQ-induced cell death. Finally, lysosome-alkalizing agents enhanced the cytotoxicity of IMQ in vitro and in vivo. CONCLUSIONS: IMQ-induced ROS accumulation promotes LMP, releases CTSs into the cytosol, stimulates caspase-8 activation and finally causes lysosomal cell death. Lysosomal cell death and the CTSD/caspase-8 axis may play a crucial role in IMQ-induced cell death.

Risk of cardiovascular disease among different fluoropyrimidine-based chemotherapy regimens as adjuvant treatment for resected colorectal cancer.

Background: Patients with colorectal cancer (CRC) are more likely to develop cardiovascular disease (CVD) than those without cancer. Little is known regarding their CV risk after operative chemotherapy. We aimed to compare the risk of CV disease among different fluoropyrimidine derivatives. Methods: We assembled a nationwide cohort of patients with newly diagnosed CRC between 2004 and 2015 who received fluoropyrimidine-based adjuvant chemotherapy for resected CRC by linking the Taiwan Cancer Registry (TCR), National Health Insurance Research Database (NHIRD), and Taiwan Death Registry (TDR). All eligible patients were followed from CRC diagnosis (index date) until a CV event, death, loss to follow-up, or December 31st 2018, whichever came first. CV outcomes included acute myocardial infarction (AMI), life-threatening arrhythmia (LTA), congestive heart failure (CHF), and ischemic stroke (IS). We used stabilized inverse probability of treatment weighting using propensity score (SIPTW) to balance all covariates among the three chemotherapy groups: tegafur-uracil (UFT), non-UFT, and mixed. In addition, survival analysis was conducted to examine the association between study outcomes and chemotherapy groups. Results: From 2004 to 2015, 10,615 (32.8%) patients received UFT alone, 14,511 (44.8%) patients received non-UFT, and 7,224 (22.3%) patients received mixed chemotherapy. After SIPTW, the UFT group had significantly lower all-cause mortality and cancer-related death rates than the other two chemotherapy groups. However, the UFT group had significantly higher rates of cancer death, ischemic stroke, and heart failure than those of the other two chemotherapy groups. The UFT group also had a significantly higher AMI rate than the mixed group. There was no significant difference in LTA among the three groups. Similar findings were observed in the subgroup analysis (stage II and age <70 years, stage II and age ≥70 years, stage III and age <70 years, stage III and age ≥70 years) as the overall population was observed. Conclusion: Higher heart failure and ischemic stroke rates were found in the UFT group than in the other two chemotherapy groups, especially those with stage III CRC and ≥70 years of age. Careful monitoring of this subset of patients when prescribing UFT is warranted.

Comparative safety of Janus kinase inhibitors and tumor necrosis factor inhibitors in patients undergoing treatment for rheumatoid arthritis.

OBJECTIVES: Since 2010, biological disease-modifying antirheumatic drugs (bDMARDs) have been the dominant mode of treatment for rheumatoid arthritis (RA). However, the safety of DMARDs, such as tumor necrosis factor inhibitors (TNFis) and Janus kinase inhibitors (JAKis), in treating patients with RA is a concern. We compared the safety outcomes of JAKis and TNFis in RA patients in clinical settings. METHODS: Patients diagnosed with RA between 2015 and 2017 were identified from the Taiwan National Health Insurance Research Database and followed till 2018. Propensity score stabilized weighting was used to balance the baseline characteristics of the JAKis and TNFis groups. The incidences of safety outcomes, namely cardiovascular (CV) events, tuberculosis (TB), total hip replacement (THR), total knee replacement (TKR), and all-cause mortality, were compared between the 2 study groups. RESULTS: A total of 3179 patients with RA who were administered JAKis (n = 822) and TNFis (n = 2357) were included in this study. The mean follow-up duration was 2.02 years in the JAKis group and 2.10 in the TNFis group. All-cause mortality had the highest incidence rate, followed by TKR, THR, CV events, and TB. A lower incidence rate of the study outcomes was observed in the JAKis group than in the TNFis group but without statistical significance. CONCLUSION: Comparable safety issues and mortality rates were observed for JAKis and TNFis in RA patients treated in real-world settings.

Trends of adverse events and mortality after DMARDs in patients with rheumatoid arthritis: Interrupted time-series analysis.

OBJECTIVES: Patients with rheumatoid arthritis (RA) experience adverse events because of the characteristics of the disease and the side effects of medications. We investigated the trends of adverse events and mortality associated with disease-modifying antirheumatic drugs (DMARDs). METHODS: We used the Taiwan National Health Insurance Database to enroll patients with incident RA between 2000 and 2017. The 1-year incident rate of gastrointestinal (GI) bleeding and 3-year incident rates of other adverse events and mortality for each calendar-quarter cohort were computed and adjusted using propensity score-based stabilized weights for fair comparisons. Levels and trends of the conventional DMARD era (2000-2002, Phase 1) were compared with those of the TNFi era (2003-2012, Phase 2) and OMA era (2013-2017, Phase 3) by using interrupted time series (ITS) analysis. RESULTS: All patients with RA were prescribed cDMARDs in Phase 1 (2000-2002), and 1%-3% were prescribed either TNFi in phase 2 (2003-2012) or OMAs in phase 3 (2013-2017). The cancer incidence rate was 1.90%, and its mortality rate was 4.19%. After the introduction of TNFi from 2003 to 2012, the main outcomes, except TKA, exhibited a steady or mild decrease in trends. ITS analysis revealed that the slope mildly increased in 2003-2012 compared with that in 2000-2003 by 0.13% for total knee replacement (p = .0322). In 2012-2017 (the OMA era), the events became steady. CONCLUSION: In patients with RA, the introduction of DMARDs was associated with stable adverse events and mortality rates. Moreover, the introduced new treatment for RA exhibited a good safety profile.

Plasma Anion Gap and Risk of In-Hospital Mortality in Patients with Acute Ischemic Stroke: Analysis from the MIMIC-IV Database.

We aimed to investigate the association between the plasma anion gap (AG) and in-hospital mortality among patients with acute ischemic stroke (AIS). In total, 1236 AIS patients were enrolled using the Medical Information Mart for Intensive Care Database IV. Primary outcome was in-hospital mortality. The patients were divided into four groups according to AG category. The mean age and Charlson comorbidity index increased as the AG category increased. The fourth AG category was most related to the in-hospital mortality (hazards ratio (HR), 95% confidence interval (CI): 2.77, 1.60-4.71), even after adjusting for possible confounding variables (Model 1: HR, 95% CI: 3.37, 1.81-6.09; Model 2: HR, 95% CI: 3.57, 1.91-6.69). Moreover, intensive care unit mortality (p = 0.008) was higher in the highest AG category, but the intracranial hemorrhage (p = 0.071) did not associate with the plasma AG. The plasma AG had a satisfactory predictive ability for in-hospital mortality among AIS patients (areas under the receiver operating characteristic curve: 0.631). The plasma AG is an independent risk factor that can satisfactorily predict the in-hospital mortality among AIS patients.

Outcomes after ticagrelor versus clopidogrel treatment in end-stage renal disease patients with acute myocardial infarction: a nationwide cohort study.

Clinical outcomes are unknown after ticagrelor treatment in patients with end-stage renal disease (ESRD) who are diagnosed with acute myocardial infarction (AMI). ESRD patients who were on hemodialysis and received dual antiplatelet therapy (DAPT) for AMI between July 2013 and December 2016 were identified in Taiwan's National Health Insurance Research Database. Using stabilized inverse probability of treatment weighting, patients receiving aspirin plus ticagrelor (n = 530) were compared with those receiving aspirin plus clopidogrel (n = 2462) for the primary efficacy endpoint, a composite of all-cause death, nonfatal myocardial infarction, or nonfatal stroke, and bleeding, defined according to the Bleeding Academic Research Consortium. Study outcomes were compared between the two groups using Cox proportional hazards model or competing risk model for the hazard ratio or subdistribution hazard ratio (SHR). During 9 months of follow-up, ticagrelor was comparable to clopidogrel with respect to the risks of primary efficacy endpoint [11.69 vs. 9.28/100 patient-months; SHR, 1.16; 95% confidence interval (CI) 0.97-1.4] and bleeding (5.55 vs. 4.36/100 patient-months; SHR 1.14; 95% CI 0.88-1.47). In conclusion, among hemodialysis patients receiving DAPT for AMI, ticagrelor was comparable to clopidogrel with regard to the composite efficacy endpoint and bleeding.

Real-World Effectiveness of Adjuvant Oxaliplatin Chemotherapy in Stage III Colon Cancer: A Controlled Interrupted Time Series Analysis.

Background: The real-world effectiveness of oxaliplatin in stage III colon cancer has not been determined in a large-scale population. We aimed to assess the real-world impact of adjuvant oxaliplatin treatment on the survival of these patients. Methods: Based on Taiwan cancer registry, we evaluated 17,801 patients with resected stage III colon cancer, including 14,168 patients receiving adjuvant chemotherapy and 3,633 not receiving adjuvant chemotherapy as the control group between 2004 and 2014. We used the controlled interrupted time-series analysis to assess the three-year disease-free survival and five-year overall survival rates before (2004-2008) and after (2009-2014) the addition of oxaliplatin. Results: The introduction of oxaliplatin was associated with no significant improvement in the slopes (per half-year) of the three-year disease-free survival rate (0.2%, 95% CI: -1.7∼2.2%) and five-year overall survival rate (0.6%, 95% CI: -1.8∼3%). The patients receiving oxaliplatin-based chemotherapy also showed no significant increase in the slopes (per half-year) of the three-year disease-free survival rate (0.6%, 95% CI: -1.4∼2.6%) and five-year overall survival rate (1%, 95% CI: -1.5∼3.5%). The nonsignificant results were consistent across subgroup analyses of age (<70 vs. ≥70 years), recurrence risk (T1-3 or N1 vs. T4 or N2), and cycle of oxaliplatin use (≤6 vs. >6). However, oxaliplatin-based chemotherapy significantly increased the slope (per half-year) of the five-year OS (2%, 95% CI: 0.2∼3.8%) for patients in the high-risk group (T4 or N2). The present results were robust in several sensitivity analyses. Conclusion: Among real-world patients with stage III colon cancer, the introduction of oxaliplatin does not yield a significant improvement in survival. Future work should identify the subpopulation(s) of patients who benefit significantly from the addition of oxaliplatin.

Emissions of PAHs, PCDD/Fs, dl-PCBs, chlorophenols and chlorobenzenes from municipal waste incinerator cofiring industrial waste.

Concentrations and distributions of PAHs and chlorinated aromatic compounds including PCDD/Fs, dl-PCBs, chlorophenols (CPs), and chlorobenzenes (CBz) in the municipal waste incinerator are investigated to characterize their formation and emission via intensive stack sampling. In addition, the toxicity of fly ash contribution by PCDD/Fs and dl-PCBs is evaluated in this study. The results reveal that concentrations of PCDD/Fs and dl-PCBs in flue gas are significantly lower than those of CPs, CBz, and PAHs. Additionally, the removal efficiencies of PAHs and chlorinated aromatic compounds achieved with existing air pollution control devices are evaluated, indicating that the removal efficiencies achieved with activated carbon injection + baghouse (95-99%) are higher than those with semi-dry scrubber (SDS). Besides, PCDD/Fs and PCBs TEQ concentrations in SDS and BH ashes are within 1.61-2.66 WHO-TEQ/g and 0.09-0.19 WHO-TEQ/g, respectively. Furthermore, the calculated mass flow rates suggest that the input rate of PCDD/Fs and dl-PCBs of SDS are 60.24 mg/h and 59.74 mg/h, respectively. The mass flow rates of PCDD/Fs and dl-PCBs after SDS in flue gas are 32.47 mg/h and 49.73 mg/h, respectively. However, the discharge rates of PCDD/Fs and dl-PCBs from SDS are 120.60 mg/h and 27.05 mg/h, respectively, indicating that PCDD/Fs are significantly formed within the SDS. PCDD/Fs formation is attributed to the operating temperature of SDS (240 ± 11.5 °C), which is within the temperature window for de novo synthesis. Thus, operating parameters of the APCDs should be optimized to reduce the formation of PAHs and chlorinated aromatic pollutants from MWI.