Satisfaction With and Adherence to Off-Label Corticosteroids in Adolescents and Adults With Eosinophilic Esophagitis: Results of a Web-Based Survey in the United States.

GOALS: We assessed satisfaction with and adherence to off-label corticosteroids in patients with eosinophilic esophagitis (EoE) in the United States. BACKGROUND: EoE is a chronic inflammatory disease for which there are currently no US Food and Drug Administration-approved swallowed topical corticosteroids. STUDY: This noninterventional, cross-sectional, web-based survey included caregivers of adolescents (aged 11 to 17 y) and adults (aged 18 years or older) with a self-reported [or caregiver-reported (adolescents)] physician diagnosis of EoE who were receiving corticosteroids. Participants were recruited through 2 nonprofit, patient advocacy groups. The 9-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) was used to assess satisfaction across effectiveness, convenience, and global satisfaction domains (scale: 1 to 100 per domain); higher scores indicated greater satisfaction. The 4-item Morisky Green Levine Medication Adherence Scale (MGL-4) was used to assess adherence; an MGL-4 score of <3 indicated adherence. Participants also reported reasons for nonadherence. RESULTS: Overall, 201 participants (caregivers of adolescents, n=98; adults, n=103) were included in this study. Mean TSQM-9 scores indicated low satisfaction with off-label corticosteroids across all 3 satisfaction domains in adolescents (≤61.1) and adults (≤55.7). Slightly fewer adolescents (37.1%) than adults (40.8%) were considered adherent. Forgetfulness was the most frequently reported reason for nonadherence; some patients chose not to take their medications, owing to poor palatability (adolescents), difficulty taking medications at specific times (adults), or feeling depressed/overwhelmed (adolescents and adults). CONCLUSIONS: Satisfaction with and adherence to off-label corticosteroids were low in this web-based survey of adolescents and adults with EoE in the United States.

Efficacy and Safety of Teduglutide in Infants and Children With Short Bowel Syndrome Dependent on Parenteral Support.

OBJECTIVES: Our objective was to evaluate the short- and long-term safety and efficacy of teduglutide treatment in infants and children with short bowel syndrome with intestinal failure (SBS-IF). METHODS: Two open-label phase 3 studies and 1 extension study investigated the short- and long-term safety and efficacy of teduglutide (0.05 mg/kg/day) in infants and children with SBS-IF: NCT03571516, 24-week study of infants who were randomized to receive teduglutide or standard of care (SoC); NCT02980666, 24-week study of infants and children who all received teduglutide; and NCT03268811, 24-week extension study of patients who completed NCT02980666 (patients could receive up to 48 weeks of total treatment). RESULTS: Twelve infants and 8 children enrolled in the core studies, and 2 infants and 7 children in the extension study. After 24 weeks of treatment, parenteral support (PS) requirements reduced by ≥20% from baseline for 4 infants (57.1%) and 4 children (66.7%) receiving teduglutide and for 2 infants receiving SoC (50.0%). One infant (50.0%) and 4 children (80.0%) receiving teduglutide maintained the ≥20% reduction in PS at 48 weeks of treatment. Two children receiving teduglutide achieved enteral autonomy, after 12 weeks and 28 weeks of treatment, respectively. All adverse events (AEs) were in line with known impacts of SBS-IF and adverse reactions to teduglutide. Only one serious AE (abdominal pain) was considered related to teduglutide. CONCLUSIONS: Short- and long-term treatment with teduglutide resulted in clinically meaningful reductions in PS requirements for infants and children with SBS-IF. Teduglutide was well tolerated, and efficacy improved with longer-term treatment.

Efficacy, safety, and pharmacokinetics of teduglutide in adult Japanese patients with short bowel syndrome and intestinal failure: two phase III studies with an extension.

PURPOSE: The short- and long-term efficacy, safety, and pharmacokinetics of teduglutide were analyzed in adult Japanese patients with short bowel syndrome and intestinal failure (SBS-IF). METHODS: Patients received teduglutide 0.05 mg/kg/day in clinical trials (TED-C14-004, SHP633-306, and extension SHP633-307). Data were analyzed at 24 weeks and an interim data cut-off of 4.5 years. RESULTS: The parenteral support (PS) volume decreased by ≥ 20% for 9/18 patients at 24 weeks and in all 11 patients by data cut-off in SHP633-307. The mean (standard deviation) PS volume decreased from baseline at 24 weeks in TED-C14-004 (-30.1 ± 25.9%) and SHP633-306 (-25.6 ± 25.5%), and at data cut-off in SHP633-307 (-57.08 ± 28.49%). Teduglutide was absorbed quickly. The adverse events were consistent with the underlying disease and known adverse drug reactions. Anti-teduglutide antibody titers declined with long-term treatment. CONCLUSIONS: In Japanese adults with SBS-IF, teduglutide treatment was associated with clinically meaningful reductions in PS requirements, similar to findings in prior international studies. No new safety concerns specific to the Japanese SBS-IF patient population were identified with short- or long-term teduglutide treatment. Anti-teduglutide antibody titers disappeared in most Japanese adults with long-term treatment. These results constitute the longest evaluation of teduglutide treatment within clinical trials reported to date.

Validation of a Claims-based Algorithm to Identify Pregestational Diabetes Among Pregnant Women in the United States.

BACKGROUND: Identifying pregestational diabetes in pregnant women using administrative claims databases is important for studies of the safety of antidiabetic treatment in pregnancy, but limited data are available on the validity of case-identifying algorithms. The purpose of this study was to evaluate the validity of an administrative claims-based algorithm to identify pregestational diabetes. METHODS: Using a cohort of pregnant women nested within the Medicaid Analytic Extract (MAX) database, we developed an algorithm to identify pregestational type 1 and type 2 diabetes, distinct from gestational diabetes. Within a single large healthcare system in the Boston area, we identified women who delivered an infant between 2000 and 2010 and were covered by Medicaid, and linked their electronic health records to their Medicaid claims within MAX. Medical records were reviewed by two physicians blinded to the algorithm classification to confirm or rule out pregestational diabetes, with disagreements resolved by discussion. We calculated positive predictive values with 95% confidence intervals using the medical record as the reference standard. RESULTS: We identified 49 pregnancies classified by the claims-based algorithm as pregestational diabetes that were linked to the electronic health records and had records available for review. The PPV for any pregestational diabetes was 92% [95% confidence interval (CI) 82%, 97%], type 2 diabetes 87% (68%, 95%), and type 1 diabetes 57% (37%, 75%). CONCLUSIONS: The claims-based algorithm for pregestational diabetes and type 2 diabetes performed well; however, the PPV was low for type 1 diabetes.

Accuracy and comparison of two rapid multiplex PCR tests for gastroenteritis pathogens: a systematic review and meta-analysis.

OBJECTIVES: The primary aim is to provide a summary of evidence for the diagnostic accuracies of multiplex PCR gastrointestinal (GI) panels-BioFire FilmArray and Luminex xTAG on the detection of gastroenteritis pathogens. The secondary aim is to compare the performance of these GI panels head to head. METHODS: A comprehensive search up to 1 December 2019 was conducted on PubMed, Embase, Ovid Medline and Web of Science for studies that used FilmArray or Luminex xTAG Gastrointestinal Pathogen Panel (GPP) for diagnosis of acute gastroenteritis. A summary of diagnostic accuracies for the 16 pathogens were calculated by comparing the GI panels to the current gold standards (conventional standard microbiology techniques such as culture or PCR for bacteria, PCR or enzyme immunoassay (EIA) for viruses, microscopy or EIA for parasite). Hierarchical summary receiver operating characteristic (HSROC) curve analysis, pretest and post-test probabilities were used for estimating the pathogen detection performance. RESULTS: A total of 11 studies with 7085 stool samples were eligible for analysis. Multiplex PCRs demonstrated high diagnostic accuracy, with specificity ≧0.98 and area under the ROC curve (AUROC) ≧0.97 for all the pathogens except for Yersinia enterocolitica (AUROC 0.91). The FilmArray panel demonstrated a higher sensitivity than xTAG GPP for most of the pathogens with the exception of Rotavirus A (xTAG GPP and FilmArray were both 0.93). CONCLUSIONS: This is the first meta-analysis that is a head-to-head comparison examining the performance of the novel multiplex PCR-based tests Luminex xTAG GPP and FilmArray GI panel in detecting each pathogen. Point estimates calculated from eligible studies showed that both GI panels are highly accurate and may provide important diagnostic information for early identification of gastroenteritis. In addition, although FilmArray has higher sensitivity and post-test probability than xTAG GPP for most of the pathogens, how this will translate to a clinical setting remains unclear.

Use and effectiveness of dapagliflozin in patients with type 2 diabetes mellitus: a multicenter retrospective study in Taiwan.

AIMS/INTRODUCTION: To investigate the clinical outcomes of patients with type 2 diabetes mellitus (T2DM) who initiated dapagliflozin in real-world practice in Taiwan. MATERIALS AND METHODS: In this multicenter retrospective study, adult patients with T2DM who initiated dapagliflozin after May 1st 2016 either as add-on or switch therapy were included. Changes in clinical and laboratory parameters were evaluated at 3 and 6 months. Baseline factors associated with dapagliflozin response in glycated hemoglobin (HbA1c) were analyzed by univariate and multivariate logistic regression. RESULTS: A total of 1,960 patients were eligible. At 6 months, significant changes were observed: HbA1c by -0.73% (95% confidence interval [CI] -0.80, -0.67), body weight was -1.61 kg (95% CI -1.79, -1.42), and systolic/diastolic blood pressure by -3.6/-1.4 mmHg. Add-on dapagliflozin showed significantly greater HbA1c reduction (-0.82%) than switched therapy (-0.66%) (p = 0.002). The proportion of patients achieving HbA1c <7% target increased from 6% at baseline to 19% at Month 6. Almost 80% of patients experienced at least 1% reduction in HbA1c, and 65% of patients showed both weight loss and reduction in HbA1c. Around 37% of patients had at least 3% weight loss. Multivariate logistic regression analysis indicated patients with higher baseline HbA1c and those who initiated dapagliflozin as add-on therapy were associated with a greater reduction in HbA1c. CONCLUSIONS: In this real-world study with the highest patient number of Chinese population to date, the use of dapagliflozin was associated with significant improvement in glycemic control, body weight, and blood pressure in patients with T2DM. Initiating dapagliflozin as add-on therapy showed better glycemic control than as switch therapy.

Trends in Human Papillomavirus Vaccination in Commercially Insured Children in the United States.

OBJECTIVES: The human papillomavirus (HPV) vaccine was recommended in 2006 for girls and in 2011 for boys. The Healthy People 2020 goal for 2-dose HPV vaccination coverage is 80% by age 15 for girls and boys. We used nationwide population-based data to describe trends in HPV vaccination in children. METHODS: We conducted a cohort study nested within the MarketScan health care database between January 2003 and December 2017. Children were followed from the year they turned 9 until HPV vaccination, insurance disenrollment, or the end of the year when they turned 17, whichever came first. We estimated the cumulative incidence of at least 1- and 2-dose HPV vaccination, stratified by birth year, sex, and state. In secondary analyses, we evaluated the association between state-level vaccination policies and HPV vaccination coverage. RESULTS: This study included 7 837 480 children and 19.8 million person-years. The proportion of 15-year-old girls and boys with at least a 1-dose HPV vaccination increased from 38% and 5% in 2011 to 57% and 51% in 2017, respectively; the proportion with at least a 2-dose vaccination went from 30% and 2% in 2011 to 46% and 39% in 2017, respectively. By 2017, 2-dose HPV vaccination coverage varied from 80% in Washington, District of Columbia, among girls to 15% in Mississippi among boys and was positively correlated with legislation for HPV vaccine education and pediatrician availability. CONCLUSIONS: Despite the increasing trends in uptake, HPV vaccine coverage among commercially insured children in the United States remains behind target levels, with substantial disparities by state.

Web-Based Dashboard for the Interactive Visualization and Analysis of National Risk-Standardized Mortality Rates of Sepsis in the US.

Sepsis mortality is heavily influenced by the quality of care in hospitals. Comparing risk-standardized mortality rate (RSMR) of sepsis patients in different states in the United States has potentially important clinical and policy implications. In the current study, we aimed to compare national sepsis RSMR using an interactive web-based dashboard. We analyzed sepsis mortality using the National Inpatient Sample Database of the US. The RSMR was calculated by the hierarchical logistic regression model. We wrote the interactive web-based dashboard using the Shiny framework, an R package that integrates R-based statistics computation and graphics generation. Visual summarizations (e.g., heat map, and time series chart), and interactive tools (e.g., year selection, automatic year play, map zoom, copy or print data, ranking data by name or value, and data search) were implemented to enhance user experience. The web-based dashboard (https://sepsismap.shinyapps.io/index2/) is cross-platform and publicly available to anyone with interest in sepsis outcomes, health inequality, and administration of state/federal healthcare. After extrapolation to the national level, approximately 35 million hospitalizations were analyzed for sepsis mortality each year. Eight years of sepsis mortality data were summarized into four easy to understand dimensions: Sepsis Identification Criteria; Sepsis Mortality Predictors; RSMR Map; RSMR Trend. Substantial variation in RSMR was observed for different states in the US. This web-based dashboard allows anyone to visualize the substantial variation in RSMR across the whole US. Our work has the potential to support healthcare transparency, information diffusion, health decision-making, and the formulation of new public policies.

Residential exposure to petrochemical industrial complexes and the risk of leukemia: A systematic review and exposure-response meta-analysis.

Exposure to chemicals produced by petrochemical industrial complexes (PICs), such as benzene, ionizing radiation, and particulate matters, may contribute to the development of leukemia. However, epidemiological studies showed controversial results. This systematic review and meta-analysis aimed to summarize the association between residential exposure to PICs and the risk of leukemia incidence, focusing on exposure-response effects. We searched PubMed, Embase, Web of Science, and Cochrane Library databases for studies published before September 1st, 2019. Observational studies investigating residential exposure to PICs and the risk of leukemia were included. The outcome of interest was the incidence of leukemia comparing to reference groups. Relative risk (RR) was used as the summary effect measure, synthesized by characteristics of populations, distance to PICs, and calendar time in meta-regression. We identified 7 observational studies, including 2322 leukemia cases and substantial reference groups, in this meta-analysis. Residential exposure to PICs within a maximal 8-km distance had a 36% increased risk of leukemia (pooled RR = 1.36, 95% CI = 1.14-1.62) compared to controls, regardless of sex and age. In terms of leukemia subtypes, residential exposure to PICs was associated with the risks of acute myeloid leukemia (AML, pooled RR = 1.61, 95% CI = 1.12-2.31) and chronic lymphocytic leukemia (CLL, pooled RR = 1.85, 95% CI = 1.11-6.42). In meta-regression, the positive association occurred after 10 years of follow-up with a pooled RRs of 1.21 (95% CI = 1.02-1.44) and then slightly increased to 1.77 (95% CI = 1.35-2.33) at 30 years after follow-up. No effect modification was found by sex, age, and geographic locations.

Clarithromycin use and the risk of mortality and cardiovascular events: A systematic review and meta-analysis.

BACKGROUND: Although studies reported increased cardiovascular (CV) risks in patients treated with macrolides, the risks remain controversial among clarithromycin (CLR) users. We aimed to summarize the association between CLR use and the risks of mortality and CV events. METHODS: We searched PubMed, EMBASE, Web of Science, and the Cochrane Library for randomized controlled trials (RCTs) and observational studies with population exposed to CLR published until December 31st, 2018. These studies reported either all-cause mortality (primary outcome) or CV adverse events (secondary outcomes) based on multivariate models. Effect measures were synthesized by study design and follow-up duration (long-term, ≥ 1 year; short-term, ≤ 3 months; and immediate, ≤ 2 weeks). This study has been registered on PROSPERO (ID: CRD42018089605). RESULTS: This meta-analysis included 13 studies (3 RCTs and 10 observational studies) and 8,351,815 subjects (1,124,672 cases and 7,227,143 controls). Overall, CLR use was not associated with increased long-term all-cause mortality (pooled rate ratio RR = 1.09, 95% CI = 0.91-1.32), either among patients with or without comorbidities of cardiovascular diseases. Comparing CLR users to placebo, there is no additional risks of cardiac mortality (pooled RR = 1.03, 95% CI = 0.53-2.01), acute myocardial infarction (pooled RR = 1.29, 95% CI = 0.98-1.68), and arrhythmia (pooled RR = 0.90, 95% CI = 0.62-1.32). CONCLUSIONS: Our findings suggested no significant association between CLR use and subsequent long-term all-cause mortality, regardless having comorbidity of cardiovascular diseases or not. Further RCTs investigating the short-term CV risks of CLR use compared to alternative antibiotics are warranted, particularly in high-risk populations.

Estimation and application of population attributable fraction in ecological studies.

Estimation of population attributable fraction (PAF) requires unbiased relative risk (RR) by using either Levin's or Miettinen's formula, on which decision depends on the available exposure information in reference group, not the types of studies. For ecological studies and studies with aggregated outcomes, once having unbiased RRs, Levin's and Miettinen's formulae would provide identical PAF estimates. PAF could also be applied to compare relative burdens of disease between countries across time, which is an additional information in consideration of country-level policies.

Comparison of type B dissection by open, endovascular, and medical treatments.

OBJECTIVE: This study aimed to address the shortcomings of previous clinical trials that were inadequate to prove the superiority of thoracic endovascular aortic repair (TEVAR) in managing type B aortic dissection (TBAD) over open surgery (OS) or best medical treatment (BMT). The comparative effectiveness of these three treatments was analyzed using data of the National Inpatient Sample, a large U.S. database including patients from 4378 hospitals. METHODS: Adult patients diagnosed with a primary or secondary TBAD in the years 2005 to 2012 were included for analysis. Patients who had aortic aneurysm or received cardioplegia, valve repair, or operations on vessels of the heart were excluded. A three-category propensity score was created by using a multinomial logistic regression model, a three-way matching algorithm for 1:1:1 matching was applied, and a parallel outcome comparison between the three matched treatment groups was performed. RESULTS: Of a total of 54,971 patients included in the study, we matched 17,211 into three equal-size treatment groups (OS, 5755; TEVAR, 5695; BMT, 5761). No significant difference in the 22 baseline covariates was found in the matched cohort. We found TEVAR to have a much lower mortality rate than OS (odds ratio [OR], 0.60; 95% confidence interval [CI], 0.46-0.79) or BMT (OR, 0.62; 95% CI, 0.47-0.83). Mortality rates between OS and BMT were similar (OR, 0.97; 95% CI, 0.74-1.27). We also found TEVAR to have a lower complication rate, shorter hospitalization, and lower medical cost compared with OS. CONCLUSIONS: TEVAR is superior to BMT or OS for treatment of TBAD in terms of mortality, complications, and cost.

Hepcidin correlates with interleukin-1ß and interleukin-6 but not iron deficiency in children with Helicobacter pylori infection.

BACKGROUND: Helicobacter pylori infection is associated with iron deficiency (ID) in children. Inflammatory cytokine reactions could influence the consequences of H. pylori infection. Hepcidin is an important regulator in iron homeostasis and could be induced by chronic inflammation. The relationship between hepcidin and cytokine levels in children infected with H. pylori remains controversial. METHODS: Based on serology testing for anti-H. pylori IgG, participants (43 seropositive and 43 seronegative) aged 10-18 years were enrolled. Serum hepcidin levels and iron profiles, including iron, ferritin, and total iron-binding capacity, were measured. ID is defined as iron saturation less than 15%. Seropositive children were divided into low hepcidin (n = 22) and high hepcidin (n = 21) groups. IL-1ß, IL-6, and IL-8 serum levels were compared. RESULTS: Serum IL-1ß and IL-6 levels were comparable between H. pylori seropositive and seronegative children, as were the median serum hepcidin levels (6.5 ng/mL versus 8.6 ng/mL; P = 0.1318). Median levels of serum iron, ferritin, and iron saturation were significantly lower in seropositive children with low hepcidin than in those with high hepcidin (P = 0.0123, P = 0.0001, and P = 0.0004, respectively). The prevalence of ID was significantly higher in those with low serum hepcidin levels (33.3% versus 4.5%; P = 0.015). Compared to the high hepcidin seropositive group, the low hepcidin group had significantly lower median serum levels of cytokines IL-1ß and IL-6, but not IL-8 (P = 0.0151 and P = 0.0015, respectively). CONCLUSIONS: Inflammatory cytokines IL-1ß and IL-6, but not IL-8, might be associated with increased hepcidin levels among H. pylori-seropositive children. Further studies are needed to clarify the role of hepcidin.

Trend and outcome of sepsis in children: A nationwide cohort study.

AIM: The aim of this study was to investigate the trend of incidence and outcome of paediatric sepsis in a population-based database. METHODS: Children with sepsis were identified from the 23 million nationwide health insurance claims database of Taiwan. Sepsis was defined by the presence of single ICD-9 code for severe sepsis or septic shock or a combination of ICD-9 codes for infection and organ dysfunction. We analysed the trend of incidence, mortality and source of infection in three age groups: infant (28 days to 1 year), child (1-9 years) and adolescent (10-18 years). RESULTS: From 2002 to 2012, we identified 38 582 paediatric patients with sepsis, of which 21.3% were infants, 52.8% were children and 25.8% were adolescents. The incidence of sepsis was 336.4 cases per 100 000 population in infants, 3.3 times higher than in children (101.5/100 000 cases) and 7.3 times higher than in adolescents (46.2/100 000 cases). While sepsis incidence decreased from 598.0 to 336.4 cases per 100 000 people in the infant population, it remained relatively unchanged in children and adolescents. For 90-day mortality, there were significant decreases in all three age groups (absolute decrease of 5.0% for infants, 3.7% for children and 14.4% for the adolescents). In the infant population, we observed a decrease in the incidence of lower respiratory tract infections, while the incidence of urinary tract infections remained unchanged. CONCLUSIONS: The incidence and mortality of sepsis among paediatric patients have decreased substantially between 2002 and 2012, especially among infants. The widespread use of Haemophilus influenzae and pneumococcal vaccines in infants could be a possible explanation.

Potential Association of IL1B Polymorphism With Iron Deficiency Risk in Childhood Helicobacter pylori Infection.

OBJECTIVE: Helicobacter pylori infection occurs predominantly in childhood. Host immune response gene polymorphism is reported to affect the susceptibility to H pylori infection and the outcome of H pylori-related gastric cancer. Not all H pylori-infected patients, however, exhibit iron deficiency (ID). The relationship between host genetic polymorphisms and ID mediated by H pylori infection is not well understood. METHODS: Subjects (n = 644) from the general population of age 10 to 18 years were divided into 2 groups based on serology testing for anti-H pylori IgG: seropositive study group; and seronegative control group. Five single nucleotide polymorphisms (SNPs) in IL1B (rs1143627 and rs16944), IL8 (rs4073), IL10 (rs1800896), and ABO (rs505922), were genotyped and the iron status of the 2 groups was compared. RESULTS: The seroprevalence rate for H pylori was 10.7% in this study. Infected subjects were significantly older and had lower serum iron levels than uninfected subjects (P = 0.0195 and 0.0059, respectively). Multivariate analysis revealed a significantly higher frequency of the T allele of rs505922 (odds ratio [OR] = 6.128; P < 0.001) and lower frequency of the T allele of rs1143627 (OR = 0.846; P = 0.014) in seropositive subjects. Among 59 seropositive subjects, the T allele frequency of rs1143627 was significantly higher in those with ID (OR = 3.156; P = 0.043), compared with those without ID. CONCLUSIONS: ABO (rs505922) and IL1B (rs1143627) may affect H pylori infection susceptibility, and IL1B (rs1143627) may also influence ID risk in infected children.

Comparison of outcome and cost among open, laparoscopic, and robotic surgical treatments for rectal cancer: A propensity score matched analysis of nationwide inpatient sample data.

BACKGROUND: Population-based studies evaluating outcomes of different approaches for rectal cancer are scarce. METHODS: We conducted a retrospective cohort study using the Nationwide Inpatient Sample database between 2008 and 2012. We compared the outcomes and costs among rectal cancer patients undergoing robotic, laparoscopic, or open surgeries using propensity scores for adjusted and matched analysis. RESULTS: We identified 194 957 rectal cancer patients. Over the 5-year period, the annual admission number decreased by 13.9%, the in-hospital mortality rate decreased by 32.2%, while the total hospitalization cost increased by 13.6%. Compared with laparoscopic surgery, robotic surgery had significantly lower length of stay (LOS) (OR 0.69, 95%CI 0.57-0.84), comparable wound complications (OR 1.08, 95%CI 0.70-1.65) and higher cost (OR 1.42, 95%CI 1.13-1.79), while open surgery had significantly longer LOS (OR 1.38, 95%CI 1.19-1.59), more wound complications (OR 1.49, 95%CI 1.08-1.79), and comparable cost (OR 0.92, 95%CI 0.79-1.07). There were no difference in in-hospital mortality among three approaches. CONCLUSIONS: Laparoscopic surgery was associated with better outcomes than open surgery. Robotic surgery was associated with higher cost, but no advantage over laparoscopic surgery in terms of mortality and complications. Studies on cost-effectiveness of robotic surgery may be warranted.

Risk of gastrointestinal perforation in patients taking oral fluoroquinolone therapy: An analysis of nationally representative cohort.

BACKGROUND: Fluoroquinolone is a commonly prescribed antimicrobial agent, and up to 20% of its users registers adverse gastroenterological symptoms. We aimed to evaluate the association between use of fluoroquinolone and gastrointestinal tract perforation. METHODS: We conducted a nested case-control study on a national health insurance claims database between 1998 and 2011. The use of fluoroquinolones was classified into current (< 60 days), past (61-365 days prior to the index date) and any prior year use of fluoroquinolones. We used the conditional logistic regression model to estimate rate ratios (RRs), adjusting or matching by a disease risk score (DRS). RESULTS: We identified a cohort of 17,510 individuals diagnosed with gastrointestinal perforation and matched them to 1,751,000 controls. Current use of fluoroquinolone was associated with the greatest increase in risk of gastrointestinal perforations after DRS score adjustment (RR, 1.90; 95% CI, 1.62-2.22). The risk of gastrointestinal perforation was attenuated for past (RR, 1.33; 95% CI, 1.20-1.47) and any prior year use (RR, 1.46; 95% CI, 1.34-1.59). To gain insights into whether the observed association can be explained by unmeasured confounder, we compared the risk of gastrointestinal perforation between fluoroquinolone and macrolide. Use of macrolide, an active comparator, was not associated with a significant increased risk of gastrointestinal perforation (RR, 1.11, 95%CI, 0.15-7.99). Sensitivity analysis focusing on perforation requiring in-hospital procedures also demonstrated an increased risk associated with current use. To mitigate selection bias, we have also excluded people who have never used fluoroquinolone before or people with infectious colitis, enteritis or gastroenteritis. In both of the analysis, a higher risk of gastrointestinal perforation was still associated with the use of fluoroquinolone. CONCLUSIONS: We found that use of fluoroquinolones was associated with a non-negligible increased risk of gastrointestinal perforation, and physicians should be aware of this possible association.

HMGCS2 enhances invasion and metastasis via direct interaction with PPARα to activate Src signaling in colorectal cancer and oral cancer.

Mitochondrial 3-hydroxy-3-methylglutaryl-CoA synthase (HMGCS2) is the rate-limiting enzyme of ketogenesis. Growing evidence indicates that HMGCS2 may be involved in cancer progression, but its exact role is largely unknown. In this study, we demonstrate that HMGCS2 mRNA expression is associated with poor clinical prognosis and outcomes in patients with colorectal cancer (CRC) and oral squamous cell carcinoma (OSCC). In vitro, ectopic expression of HMGCS2 enhanced cancer cell motility in a ketogenesis-independent manner. Moreover, HMGCS2 promoted Src activity by directly binding to peroxisome proliferator-activated receptor alpha (PPARα), a transcriptional activator of Src. Taken together, these results suggest that HMGCS2 may serve as a useful prognostic marker and vital target for future therapeutic strategies against advanced cancer.

Ataxia-telangiectasia mutated interactor regulates head and neck cancer metastasis via KRas expression.

OBJECTIVES: Relapse is the most serious problem affecting the morbidity and mortality rates of patients with head and neck squamous cell carcinoma (HNSCC). Although HNSCC has been studied for several decades, the exact mechanism of cancer recurrence remains unclear. MATERIALS AND METHODS: ataxia-telangiectasia mutated interactor (ATMIN) messenger RNA(mRNA) expression was detected in HNSCC samples by quantitative RT-PCR, and was analyzed with patients' clinical outcomes by Kaplan-Meier analyses. The ectopic ATMIN expression or ATMIN silencing on invasion ability was evaluated in HNSCC cell lines. Lymph node metastasis ability was investigated by buccal orthotopic implantation in vivo. All statistical tests were two-sided. RESULTS: ATMIN mRNA expression was positively correlated with patients' clinical outcomes. ATMIN blockage reduced invasion, migration, and metastasis abilities both in vitro and in vivo. Evidence from a buccal orthotopic implantation mice model showed that silenced ATMIN expression prolongs mice survival and reduced lymph node metastasis. In high-throughput microarray and bioinformative analyses, KRas was identified as a crucial downstream effector in ATMIN-mediated HNSCC metastasis and was positively associated with patients' clinical stages and ATMIN mRNA expression. CONCLUSIONS: The role of ATMIN and its regulatory mechanisms in HNSCC progression are reported for the first time. The study results improve our understanding of the ATMIN-KRas axis leading to HNSCC migration or invasion and metastasis and facilitates the identification of possible therapy targets of downstream genes for designing effective therapeutic strategies in personalized medicine.