Adjuvant chemotherapy for stage II and III gastric adenocarcinoma: A retrospective analysis with long-term follow-up.

BACKGROUND: Whether adjuvant chemotherapy should be different for patients with stage II and III gastric cancer is unknown. METHODS: We retrospectively analyzed the effects of adjuvant chemotherapy on the outcomes of 140 and 256 patients with stage II and III gastric cancer, respectively, between January 2008 and December 2018. Chemotherapies were stratified as fluoropyrimidine plus platinum versus fluoropyrimidine alone, tegafur/gimeracil/octeracil (S-1)-containing versus non-S-1-containing regimens, and S-1 plus cisplatin versus S-1 alone. RESULTS: The median age of patients was 67.0 (range 24.6-98.8) years. With a median follow-up of 105 months, recurrence occurred in 32 (22.9%) and 130 (50.8%) patients with stage II and III disease, respectively. Adjuvant chemotherapy was administered as fluoropyrimidine monotherapy to 68 (48.6%) and 73 (28.5%) patients, fluoropyrimidine plus platinum to 9 (6.4%) and 104 (40.6%) patients, and none to 63 (45.0%) and 79 (30.9%) patients with stage II and III gastric cancer, respectively. Doublet chemotherapy was associated with longer disease-free survival (DFS) (26.5 vs. 15.2 months, P = 0.001) and overall survival (OS) (41.2 vs. 22.0 months, P < 0.001) than fluoropyrimidine monotherapy for stage IIIB-IIIC disease. Furthermore, S-1-containing regimens prolonged DFS (57.4 vs. 21.9 months, P = 0.044) and OS (81.4 vs. 28.6 months, P = 0.023) compared with non-S-1-containing chemotherapy in stage III disease. CONCLUSION: Although fluoropyrimidine monotherapy is feasible for stage II-IIIA disease, doublet chemotherapy is significantly associated with longer survival than monotherapy for stage IIIB-IIIC disease. S-1-containing regimens might lead to longer survival than non-S-1-containing chemotherapy in stage III gastric cancer.

How Long After Coronary Artery Bypass Surgery Can Patients Have Elective Safer Non-Cardiac Surgery?

Objective: To evaluate the complications and mortality after noncardiac surgeries in patients who underwent previous coronary artery bypass grafting (CABG). Methods: We used insurance data and identified patients aged ≥20 years undergoing noncardiac surgeries between 2010 and 2017 in Taiwan. Based on propensity-score matching, we selected an adequate number of patients with a previous history of CABG (within preoperative 24 months) and those who did not have a CABG history, and both groups had balanced baseline characteristics. The association of CABG with the risk of postoperative complications and mortality was estimated (odds ratio [OR] and 95% confidence interval [CI]) using multiple logistic regression analysis. Results: The matching procedure generated 2327 matched pairs for analyses. CABG significantly increased the risks of 30-day in-hospital mortality (OR 2.28, 95% CI 1.36-3.84), postoperative pneumonia (OR 1.49, 95% CI 1.12-1.98), sepsis (OR 1.49, 95% CI 1.17-1.89), stroke (OR 1.53, 95% CI 1.17-1.99) and admission to the intensive care unit (OR, 1.75, 95% CI 1.50-2.05). The findings were generally consistent across most of the evaluated subgroups. A noncardiac surgery performed within 1 month after CABG was associated with the highest risk for adverse events, which declined over time. Conclusion: Prior history of CABG was associated with postoperative pneumonia, sepsis, stroke, and mortality in patients undergoing noncardiac surgeries. Although we raised the possibility regarding deferral of non-critical elective noncardiac surgeries among patients had recent CABG when considering the risks, critical or emergency surgeries were not in the consideration of delay surgery, especially cancer surgery.

Inhibition of ADAM9 promotes the selective degradation of KRAS and sensitizes pancreatic cancers to chemotherapy.

Kirsten rat sarcoma virus (KRAS) signaling drives pancreatic ductal adenocarcinoma (PDAC) malignancy, which is an unmet clinical need. Here, we identify a disintegrin and metalloproteinase domain (ADAM)9 as a modulator of PDAC progression via stabilization of wild-type and mutant KRAS proteins. Mechanistically, ADAM9 loss increases the interaction of KRAS with plasminogen activator inhibitor 1 (PAI-1), which functions as a selective autophagy receptor in conjunction with light chain 3 (LC3), triggering lysosomal degradation of KRAS. Suppression of ADAM9 by a small-molecule inhibitor restricts disease progression in spontaneous models, and combination with gemcitabine elicits dramatic regression of patient-derived tumors. Our findings provide a promising strategy to target the KRAS signaling cascade and demonstrate a potential modality to enhance sensitivity to chemotherapy in PDAC.

Diagnostic rate of germline pathogenic variants in pancreatic ductal adenocarcinoma patients using whole genome sequencing.

Identification of germline pathogenic variants in cancer patients is critical for treatment planning, genetic counseling, and health policymaking. However, previous estimates of the prevalence of germline etiology of pancreatic ductal adenocarcinoma (PDAC) were biased because they were based only on sequencing data of protein-coding regions of known PDAC candidate genes. To determine the percentage of patients with PDAC carrying germline pathogenic variants, we enrolled the inpatients from the digestive health clinics, hematology and oncology clinics, and surgical clinics of a single tertiary medical center in Taiwan for whole genome sequencing (WGS) analysis of genomic DNA. The virtual gene panel of 750 genes comprised PDAC candidate genes and those listed in the COSMIC Cancer Gene Census. The genetic variant types under investigation included single nucleotide substitutions, small indels, structural variants, and mobile element insertions (MEIs). In 8 of 24 (33.3%) patients with PDAC, we identified pathogenic/likely pathogenic variants, including single nucleotide substitutions and small indels in ATM, BRCA1, BRCA2, POLQ, SPINK1 and CASP8, as well as structural variants in CDC25C and USP44. We identified additional patients carrying variants that could potentially affect splicing. This cohort study demonstrates that an extensive analysis of the abundant information yielded by the WGS approach can uncover many pathogenic variants that could be missed by traditional panel-based or whole exome sequencing-based approaches. The percentage of patients with PDAC carrying germline variants might be much higher than previously expected.

Salvage surgeries for splanchnic artery aneurysms after failed endovascular therapy: case series.

INTRODUCTION: Splanchnic arterial aneurysms are a rare but potentially lethal disease with a mortality rate of more than 10% after rupture. Endovascular therapy is the first-line treatment for splanchnic aneurysms. However, appropriate management for splanchnic aneurysms after failed endovascular therapy remained inconclusive. MATERIALS AND METHODS: A retrospective review was performed for consecutive patients (from 2019 to 2022) who underwent salvage surgeries for splanchnic artery aneurysms following failed endovascular therapy. The authors defined failed endovascular therapy as the technical infeasibility to apply endovascular therapy, the incomplete exclusion of the aneurysm, or the incomplete resolution of preoperative aneurysm-associated complications. Salvage operations included aneurysmectomy with vascular reconstruction and partial aneurysmectomy with directly closing of bleeders from the intraluminal space of the aneurysms. RESULTS: Seventy-three patients received endovascular therapies for splanchnic aneurysms, and 13 failed endovascular trials. The authors performed salvage surgeries for five patients and enrolled them in this study, including four false aneurysms of the celiac or superior mesenteric arteries and a true aneurysm of the common hepatic artery. The causes of failed endovascular therapy included coil migration, insufficient space for safely deploying the covered stent, a persistent mass effect from the postembolized aneurysm, or infeasibility for catheter cannulation. The mean hospital stay was nine days (mean±SD, 8.8±1.6 days), with no one suffering 90-day surgical morbidity and mortality, and all patients getting symptoms improvement. During the follow-up period (mean±SD, 24±10 months), one patient suffered a small residual asymptomatic celiac artery aneurysm (8 mm in diameter) and was treated conservatively due to underlying liver cirrhosis. CONCLUSION: Surgical management is a feasible, effective, and safe alternative for splanchnic aneurysms after failed endovascular therapy.

Inhibition of CDCP1 by 8-isopentenylnaringenin synergizes with EGFR inhibitors in lung cancer treatment.

CUB domain-containing protein 1 (CDCP1) contributes to epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI) resistance by regulating EGFR signaling pathways and is a potential target in lung cancer treatment. This study aims to identify a CDCP1 reducer that synergistically improves TKI treatment. Utilizing a high-throughput drug screening system, a phytoestrogen 8-isopentenylnaringenin (8PN) was identified. Upon 8PN treatment, CDCP1 protein levels and malignant features were reduced. 8PN exposure caused the accumulation of lung cancer cells in G0/G1 phase and increased the proportion of senescent cells. In EGFR TKI-resistant lung cancer cells, the combination of 8PN and TKI synergistically reduced cell malignance, inhibited downstream EGFR pathway signaling, and exerted additive effects on cell death. Moreover, combination therapy effectively reduced tumor growth and enhanced tumor necrosis in tumor xenograft mice models. Mechanistically, 8PN increased interleukin (IL)6 and IL8 expression, induced neutrophil infiltration, and enhanced neutrophil-mediated cytotoxicity to attenuate lung cancer cell growth. In conclusion, 8PN enhances the anticancer efficacy of EGFR TKI on lung cancer and triggers neutrophil-dependent necrosis, highlighting the potential to overcome TKI resistance in lung cancer patients who have EGFR mutation.

Non-Contrast-Enhanced MR Arteriography of Potential Living-Related Liver Donor: Using Contrast Enhanced CT Arteriography as Standard Reference.

BACKGROUND: Contrast-enhanced computed tomography angiography (CTA) and magnetic resonance angiography (MRA) are the primary modalities to assess donors' vessels before transplant surgery. Radiation and contrast medium are potentially harmful to donors. PURPOSE: To compare the image quality and visualization scores of hepatic arteries on CTA and balanced steady-state free-precession (bSSFP) non-contrast-enhanced MRA (NC-MRA), and to evaluate if bSSFP NC-MRA can potentially be a substitute for CTA. STUDY TYPE: Prospective. POPULATION: Fifty-six consecutive potential living-related liver donors (30.9 ± 8.4 years; 31 men). FIELD STRENGTH/SEQUENCE: 1.5T; four bSSFP NC-MRA sequences: respiratory-triggered (Inhance inflow inversion recovery [IFIR]) and three breath-hold (BH); and CTA. ASSESSMENT: The artery-to-liver contrast (Ca-l) was quantified. Three radiologists independently assigned visualization scores using a four-point scale to potential origins, segments, and branches of the hepatic arteries, determined the anatomical variants based on Hiatt's classification, and assessed the image quality of NC-MRA sequences. STATISTICAL TESTS: Fleiss' kappa to evaluate the readers' agreement. Repeat measured ANOVA or Friedman test to compare Ca-l of each NC-MRA. Friedman test to compare overall image quality and visualization scores; post hoc analysis using Wilcoxon signed-rank test. P-value <0.05 was considered statistically significant. RESULTS: Inhance IFIR Ca-l was significantly higher than all BH bSSFP Ca-l (0.56 [0.45-0.64] vs. 0.37 [0.29-0.47] to 0.41 [0.23-0.51]). Overall image quality score of BH bSSFP TI1200 was significantly higher than other NC-MRA (4 [4-4] vs. 4 [3 to 4-4]). The median visualization scores of almost all arteries on CTA were significantly higher than on NC-MRA (4 [3 to 4-4] vs. 1 [1-2] to 4 [4-4]). The median visualization scores were all 4 [4-4 ] on Inhance IFIR with >92.3% observed scores ≥3, except the segment 4 branch (3 [1-4], 53.6%). The identification rates of arterial variants were 92.9%-97% on Inhance IFIR. DATA CONCLUSIONS: Although CTA is superior to the NC-MRA, all NC-MRA depict the donor arterial anatomy well. Inhance IFIR can potentially be an alternative image modality for CTA to evaluate the arterial variants of living donors. LEVEL OF EVIDENCE: 3 TECHNICAL EFFICACY: Stage 2.

Accuracy of simultaneous measurement of serum biomarkers: Carbohydrate antigen 19-9, pancreatic elastase-1, amylase, and lipase for diagnosing pancreatic ductal adenocarcinoma.

BACKGROUND: Pancreatic cancer is difficult to diagnose early since tumor markers have low sensitivity and specificity. We simultaneously measured serum carbohydrate antigen (CA) 19-9, pancreatic elastase-1, lipase, and amylase, and evaluated the accuracy of a single marker or a combination of two, three, or four markers in the diagnosis of pancreatic ductal adenocarcinoma (PDAC). METHODS: Seventy-six patients with PDAC were included, and 75 patients with non-PDAC diseases were enrolled as the control group. Blood specimens were collected and analyzed for pancreatic elatase-1, CA19-9, amylase and lipase. Sensitivity, specificity, and accuracy for each individual marker and in combination were determined. RESULTS: In PDAC subjects, abnormal CA19-9 was seen most frequently at 80.3%, followed by pancreatic elastase-1 at 57.9%, lipase at 53.9%, and amylase at 51.3%. In non-PDAC subjects, the percentage of abnormal serum pancreatic elastase-1, CA19-9, lipase, and amylase were 50.7%, 41.3%, 40.0%, and 28.0%, respectively. The accuracy rate of amylase and CA19-9 results combined was 64.9% and was higher than the combination of other markers in the intersection set. In the union set, the group of amylase and CA19-9 combined and the group of lipase and CA19-9 combined had the highest accuracy at 66.2%. In the intersection and union set, the area under the curve of CA19-9 was the highest at 0.695. CONCLUSION: CA19-9 as a single marker is the most accurate in the clinical diagnosis of PDAC. Combination of lipase, amylase, or pancreatic elastase-1 results does not significantly increase the accuracy of PDAC diagnosis.

Risk factors related to age at diagnosis of pancreatic cancer: a retrospective cohort pilot study.

BACKGROUND: Increased pancreatic cancer incidence has been observed among younger than in older adults. This pilot study aimed to determine the feasibility of a large study that would compare the age at diagnosis of pancreatic cancer among patients with different risk factors. METHODS: We compared the age at diagnosis of pancreatic cancer between groups of pancreatic cancer patients exposed and not exposed to the identified risk factors. We estimated the age at which exposure started, average exposure quantity, and total years of exposure and investigated their relationships with age at diagnosis of pancreatic cancer. RESULTS: Sixteen out of 24 (67%) subjects carried known genetic factors and/or had smoking and/or drinking habits; however, an earlier age of pancreatic cancer diagnosis was not observed. Conversely, we found a significant correlation between the age at which alcohol consumption was started and the age at diagnosis of pancreatic cancer (r = 0.8124, P = 0.0043). CONCLUSIONS: Our pilot study suggested that a large study following this study design is feasible and that the following should be conducted in a large study: mediation analysis for disease-related factors, advanced genomic analysis for new candidate genes, and the correlation between age of first exposure to risk factors and pancreatic cancer onset.

Complications and Mortality after Surgeries in Patients with Prior Stroke Who Received General and Neuraxial Anesthesia: A Propensity-Score Matched Study.

Patients who previously suffered a stroke have increased risks of mortality and complications after surgeries, but the optimal anesthesia method is not fully understood. We aimed to compare the outcomes after surgeries for stroke patients who received general anesthesia (GA) and neuraxial anesthesia (NA). Using health insurance research data, we identified 36,149 stroke patients who underwent surgeries from 1 January 2008 to 31 December 2013. For balancing baseline covariates, the propensity-score-matching procedure was used to select adequate surgical patients who received GA and NA at a case-control ratio of 1:1. Multiple logistic regressions were applied to calculate adjusted odds ratios (ORs) with 95% confidence intervals (CIs) for postoperative mortality and complications between surgical patients with prior stroke who received GA and NA. Among the 4903 matched pairs with prior stroke, patients with GA had higher risks of pneumonia (OR 2.00, 95% CI 1.62-2.46), pulmonary embolism (OR 3.30, 95% CI 1.07-10.2), acute renal failure (OR 3.51, 95% CI 1.13-2.10), intensive care unit stay (OR 3.74, 95% CI 3.17-4.41), and in-hospital mortality (OR 2.02, 95% CI 1.16-3.51) than those who received NA. Postoperative adverse events were associated with GA in patients aged more than 60 years and those who received digestive surgery (OR 3.11, 95% CI 2.08-4.66). We found that stroke patients undergoing GA had increased postoperative complications and mortality after surgery compared with those who received NA. However, these findings need more validation and evaluation by clinical trials.

TRIM37 Promotes Pancreatic Cancer Progression through Modulation of Cell Growth, Migration, Invasion, and Tumor Immune Microenvironment.

TRIM37 dysregulation has been observed in several cancer types, implicating its possible role in tumorigenesis. However, the role of TRIM37 in pancreatic cancer progression remains unclear. In the present study, we observed that TRIM37 knockdown resulted in reduced proliferation, clonogenicity, migration, and invasion ability of pancreatic cancer cells. Furthermore, an in vivo study using an orthotopic syngeneic animal model further confirmed that reduced expression of TRIM37 in cancer cells suppressed tumor growth in vivo. Moreover, in mice bearing TRIM37 knockdown pancreatic cancer cells, the proportion of CD11b+F4/80+MHCIIlow immunosuppressive macrophages was significantly reduced in tumor milieu, which might be due to the regulatory role of TRIM37 in cytokine production by pancreatic cancer cells. Collectively, these findings suggest a key role of TRIM37 in promoting pancreatic cancer progression.

Endoscopic ultrasound-guided fine-needle biopsy as a tool for studying the intra-tumoral microbiome in pancreatic ductal adenocarcinoma: a pilot study.

A new approach by investigating the intra-tumoral microbiome raised great interest because they may influence the host immune response and natural history of the disease. However, previous studies on the intra-tumoral microbiome of pancreatic ductal adenocarcinoma (PDAC) were mostly based on examining the formalin-fixed paraffin-embedded tumor specimens. This study aims to investigate the feasibility of using endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) as a complementary procedure of surgical biopsy to obtain adequate fresh pancreatic cancer tissue for intra-tumoral microbial research. This was a prospective pilot study performed at a single tertiary referral center. We obtained pancreatic cancer tissue by EUS-FNB and surgical biopsy, respectively. We amplified the V3-V4 hyper-variable region of bacterial 16S ribosomal ribonucleic acid (rRNA) genes, constructed a pair-end library, and performed high-throughput sequencing. From August 2020 to November 2020, nine eligible patients with PDAC were enrolled in this study. The intra-tumoral microbiome profile was successfully generated from the PDAC cancer tissue obtained by EUS-FNB as well as by surgical biopsy. There was no significant difference in intra-tumoral alpha-diversity or bacterial taxonomic composition between tissues obtained by EUS-FNB and by surgical biopsy. EUS-FNB can collect sufficient fresh cancer tissue for microbiome analyses without complication. The intra-tumoral microbiome profile in tissues obtained by EUS-FNB had similar alpha-diversity and taxonomic profiles with those obtained by surgical biopsy. It implicated, except for surgical biopsy, EUS-FNB can be another valid and valuable tool for studying intra-tumoral microbiome in patients with resectable and unresectable PDAC.

Adverse outcomes after noncardiac surgery in patients with aortic stenosis.

Whether aortic stenosis (AS) increases perioperative risk in noncardiac surgery remains controversial. Limited information is available regarding adequate anesthetic techniques for patients with AS. Using the reimbursement claims data of Taiwan's National Health Insurance, we performed propensity score matching analyses to evaluate the risk of adverse outcomes in patients with or without AS undergoing noncardiac surgery between 2008 and 2013. We also compared the perioperative risk of AS patients undergoing general anesthesia or neuraxial anesthesia. Multivariable logistic regressions were applied to calculate the adjusted odds ratios (aORs) with 95% confidence intervals (CIs) for postoperative mortality and major complications. The matching procedure generated 9741 matched pairs for analyses. AS was significantly associated with 30-day in-hospital mortality (aOR 1.31, 95% CI 1.03-1.67), acute renal failure (aOR 1.42, 95% CI 1.12-1.79), pneumonia (aOR 1.16, 95% CI 1.02-1.33), stroke (aOR 1.14, 95% CI 1.01-1.29), and intensive care unit stay (aOR 1.38, 95% CI 1.27-1.49). Compared with neuraxial anesthesia, general anesthesia was associated with increased risks of acute myocardial infarction (aOR 3.06, 95% CI 1.22-7.67), pneumonia (aOR 1.80, 95% CI 1.32-2.46), acute renal failure (aOR 1.82, 95% CI 1.11-2.98), and intensive care (aOR 4.05, 95% CI 3.23-5.09). The findings were generally consistent across subgroups. AS was an independent risk factor for adverse events after noncardiac surgery. In addition, general anesthesia was associated with greater postoperative complications in AS patients compared to neuraxial anesthesia. This real-world evidence suggests that neuraxial anesthesia should not be contraindicated in patients with AS.

Predicting microvascular invasion in hepatocellular carcinoma: a deep learning model validated across hospitals.

BACKGROUND: The accuracy of estimating microvascular invasion (MVI) preoperatively in hepatocellular carcinoma (HCC) by clinical observers is low. Most recent studies constructed MVI predictive models utilizing radiological and/or radiomics features extracted from computed tomography (CT) images. These methods, however, rely heavily on human experiences and require manual tumor contouring. We developed a deep learning-based framework for preoperative MVI prediction by using CT images of arterial phase (AP) with simple tumor labeling and without the need of manual feature extraction. The model was further validated on CT images that were originally scanned at multiple different hospitals. METHODS: CT images of AP were acquired for 309 patients from China Medical University Hospital (CMUH). Images of 164 patients, who took their CT scanning at 54 different hospitals but were referred to CMUH, were also collected. Deep learning (ResNet-18) and machine learning (support vector machine) models were constructed with AP images and/or patients' clinical factors (CFs), and their performance was compared systematically. All models were independently evaluated on two patient cohorts: validation set (within CMUH) and external set (other hospitals). Subsequently, explainability of the best model was visualized using gradient-weighted class activation map (Grad-CAM). RESULTS: The ResNet-18 model built with AP images and patients' clinical factors was superior than other models achieving a highest AUC of 0.845. When evaluating on the external set, the model produced an AUC of 0.777, approaching its performance on the validation set. Model interpretation with Grad-CAM revealed that MVI relevant imaging features on CT images were captured and learned by the ResNet-18 model. CONCLUSIONS: This framework provide evidence showing the generalizability and robustness of ResNet-18 in predicting MVI using CT images of AP scanned at multiple different hospitals. Attention heatmaps obtained from model explainability further confirmed that ResNet-18 focused on imaging features on CT overlapping with the conditions used by radiologists to estimate MVI clinically.

Adverse Outcomes after Non-Cardiac Surgeries in Patients with Heart Failure: A Propensity-Score Matched Study.

The impact of heart failure (HF) on postoperative outcomes is not completely understood. Our purpose is to investigate complications and mortality after noncardiac surgeries in people who had HF. In the analyses of research data of health insurance in, we identified 32,808 surgical patients with preoperative HF and 32,808 patients without HF undergoing noncardiac surgeries. We used a matching procedure with propensity score and considered basic characteristics, coexisting diseases, and information of index surgery between patients with and without HF. Adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for complications and mortality after noncardiac surgeries in patients with HF were analyzed in multivariate logistic regressions. HF increased the risks of postoperative acute myocardial infarction (OR 2.51, 95% CI 1.99-3.18), pulmonary embolism (OR 2.46, 95% CI 1.73-3.50), acute renal failure (OR 1.97, 95% CI 1.76-2.21), intensive care (OR 1.93, 95% CI 1.85-2.01), and 30-day in-hospital mortality (OR 1.80, 95% CI 1.59-2.04). Preoperative emergency care, inpatient care, and injections of diuretics and cardiac stimulants due to heart failure were also associated with mortality after surgery. Patients with HF had increased complications and mortality after noncardiac surgeries compared with those without HF. The surgical care team may consider revising the protocols for perioperative care in patients with HF.

Septicemia and mortality after noncardiac surgery associated with CHA2DS2-VASc score: a retrospective cohort study based on a real-world database.

BACKGROUND: Little was know about the association between the CHA2DS2-VASc score and postoperative outcomes. Our purpose is to evaluate the effects of CHA2DS2-VASc score on the perioperative outcomes in patients with atrial fibrillation (AF). METHODS: We identified 47,402 patients with AF over the age of 20 years who underwent noncardiac surgeries between 2008 and 2013 from claims data of the National Health Insurance in Taiwan. The CHA2DS2-VASc score was used to evaluate postoperative complications, mortality and the consumption of medical resources by calculating adjusted odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Compared with patients with a CHA2DS2-VASc score of 0, patients with scores ≥ 5 had an increased risk of postoperative septicemia (OR 2.76, 95% CI 2.00-3.80), intensive care (OR 2.55, 95% CI 2.12-3.06), and mortality (OR 2.04, 95% CI 1.14-3.64). There was a significant positive correlation between risk of postoperative complication and the CHA2DS2-VASc score (P < 0.0001). CONCLUSION: The CHA2DS2-VASc score was highly associated with postoperative septicemia, intensive care, and 30-day mortality among AF patients. Cardiologists and surgical care teams may consider using the CHA2DS2-VASc score to evaluate perioperative outcome risks in patients with AF.

Adverse outcomes after major surgery in children with intellectual disability.

AIM: To evaluate outcomes after major surgery in children and adolescents with intellectual disability. METHOD: We used 2004 to 2013 claims data from Taiwan's National Health Insurance programme to conduct a nested cohort study, which included 220 292 surgical patients aged 6 to 17 years. A propensity score matching procedure was used to select 2173 children with intellectual disability and 21 730 children without intellectual disability for comparison. Logistic regression was used to calculate the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) of the postoperative complications and 30-day mortality associated with intellectual disability. RESULTS: Children with intellectual disability had a higher risk of postoperative pneumonia (OR 2.16, 95% CI 1.48-3.15; p<0.001), sepsis (OR 1.67, 95% CI 1.28-2.18; p<0.001), and 30-day mortality (OR 2.04, 95% CI 1.05-3.93; p=0.013) compared with children without intellectual disability. Children with intellectual disability also had longer lengths of hospital stay (p<0.001) and higher medical expenditure (p<0.001) when compared with children with no intellectual disability. INTERPRETATION: Children with intellectual disability experienced more complications and higher 30-day mortality after surgery when compared with children without intellectual disability. There is an urgent need to revise the protocols for the perioperative care of this specific population. WHAT THIS PAPER ADDS: Surgical patients with intellectual disability are at increased risk of postoperative pneumonia, sepsis, and 30-day mortality. Intellectual disability is associated with higher medical expenditure and increased length of stay in hospital after surgical procedures. The influence of intellectual disability on postoperative outcomes is consistent in both sexes and those aged 10 to 17 years. Low income and a history of fractures significantly impacts postoperative adverse events for patients with intellectual disability.

Outcomes after surgery in patients with diabetes who used metformin: a retrospective cohort study based on a real-world database.

INTRODUCTION: Limited information was available regarding the perioperative outcomes in patients with and without use of metformin. This study aims to evaluate the complications and mortality after major surgery in patients with diabetes who use metformin. RESEARCH DESIGN AND METHODS: Using a real-world database of Taiwan's National Health Insurance from 2008 to 2013, we conducted a matched cohort study of 91 356 patients with diabetes aged >20 years who used metformin and later underwent major surgery. Using a propensity score-matching technique adjusted for sociodemographic characteristics, medical condition, surgery type, and anesthesia type, 91 356 controls who underwent surgery but did not use metformin were selected. Logistic regression was used to calculate the ORs with 95% CIs for postoperative complications and 30-day mortality associated with metformin use. RESULTS: Patients who used metformin had a lower risk of postoperative septicemia (OR 0.94, 95% CI 0.90 to 0.98), acute renal failure (OR 0.87, 95% CI 0.79 to 0.96), and 30-day mortality (OR 0.79, 95% CI 0.71 to 0.88) compared with patients who did not use metformin, in both sexes and in every age group. Metformin users who underwent surgery also had a decreased risk of postoperative intensive care unit admission (OR 0.60, 95% CI 0.59 to 0.62) and lower medical expenditures (p<0.0001) than non-use controls. CONCLUSIONS: Among patients with diabetes, those who used metformin and underwent major surgery had a lower risk of complications and mortality compared with non-users. Further randomized clinical trials are needed to show direct evidence of how metformin improves perioperative outcomes.

Metronomic Celecoxib Therapy in Clinically Available Dosage Ablates Hepatocellular Carcinoma via Suppressing Cell Invasion, Growth, and Stemness in Pre-Clinical Models.

OBJECTIVE: To investigate the anti-carcinogenic effect of metronomic Celecoxib (i.e., frequent administration in clinically available doses) against hepatocellular carcinoma (HCC) in the perspective of metastasis, spontaneous hepatocarcinogenesis, cancer invasion, proliferation, and stemness in vivo and in vitro. BACKGROUND: Celecoxib, a selective cyclooxygenase-2 (COX-2) inhibitor, is known to cause anti-carcinogenic effects for HCC in suprapharmacological doses. However, the effects of metronomic Celecoxib treatment on HCC cells remain unclear. METHODS: The in vivo chemopreventive effect of metronomic Celecoxib (10mg/kg/d) was investigated by the syngeneic HCC implantation model and spontaneous hepatocarcinogenesis in HBV-transgenic(HBVtg) mice individually. HCC cell lines were treated by either suprapharmacological (100 µM) or metronomic (4 µM) Celecoxib therapy. Anti-carcinogenic effects were evaluated using cell invasion, cancer proliferation, angiogenesis, and phenotype of cancer stem/progenitor cells (CSPC). The molecular mechanism of metronomic Celecoxib on HCC was dissected using Luciferase assay. RESULTS: In vivo metronomic Celecoxib exerted its chemopreventive effect by significantly reducing tumor growth of implanted syngeneic HCC and spontaneous hepatocarcinogenesis in HBVtg mice. Unlike suprapharmacological dose, metronomic Celecoxib can only inhibit HCC cell invasion after a 7-day course of treatment via NF-κB/MMP9 dependent, COX2/PGE2 independent pathway. Metronomic Celecoxib also significantly suppressed HCC cell proliferation after a 7-day or 30-day culture. Besides, metronomic Celecoxib reduced CSPC phenotype by diminishing sphere formation, percentage of CD90+ population in sphere cells, and expression of CSPC markers. CONCLUSIONS: Metronomic Celecoxib should be investigated clinically as a chemopreventive agent for selected high-risk HCC patients (e.g., HCC patients after curative treatments).