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The study aimed to predict surgical risks for patients with symptomatic stricturing Crohn's disease (CD) using computed tomography enterography (CTE) and to assess the association between CTE findings and pathological changes.Crohn's disease patients with symptomatic stricture(s) were included. Exclusion criteria were concomitant penetrating disease, intra-abdominal abscess, previous bowel resection, or asymptomatic. Patients from January 2016 to December 2019 were identified as the primary cohort and those from January 2020 to June 2020 were identified as the validation cohort. Two independent experienced radiologists evaluated CTE variables including mucosal enhancement, mural stratification, wall enhancement, comb sign, lymphadenopathy, thick non-enhancing wall, bowel wall thickness, luminal diameter, and upstream lumen. Receiver operating characteristic, logistic regression, and nomogram were performed to identify the independent predictors of surgical-free survival. Histopathological scores of surgical specimens were also evaluated.198 patients (primary cohort, 123 with surgery and 75 under non-surgical intervention, and 41 patients (validation cohort) were analyzed. Bowel wall thickness 5.9 mm, luminal stenosis 3.35 mm, and upstream lumen 27.5 mm were predictors of surgical-free survival for symptomatic stricturing CD patients. Logistic analysis showed the three CTE variables were the independent predictors of surgical-free survival (p 0.001). A nomogram was developed with the concordance indexes of 0.905 and 0.892 in the primary and validation cohorts. Histopathological analysis showed bowel wall muscular hyperplasia/hypertrophy significantly correlated with luminal stenosis (r = - 0.655, p = 0.008) and combined CTE variable (r = - 0.683, p = 0.005).CTE is highly predictive of disease course and surgical-free survival for patients with symptomatic stricturing CD, suggesting the important role of CTE in decision-making of treatment.

The number of internet users has increased substantially in the last decade and these increasing rates of internet use also apply to children. Children usually have poorer self-control and poorer cognition than college-age populations or adults, the impact of Internet addiction on the health of this group has important implications not only for their individual economic and social outcomes but also the future human capital development in China.We use data from the 2016 and 2018 China Family Panel Survey, a survey that collected data from a large and nationally representative sample of the Chinese population, to construct a sample of children from 25 provinces, and then use DID and PSM-DID methods to investigate whether Internet addiction (increased screen time in this article) impacts the physical and mental health of children (ages 10-15) in China.Internet addiction has a significant negative impact on child physical and mental health. The mediating effect model shows that Internet addiction impairs child physical and mental health by reducing their sleep and exercise time. The heterogeneity analysis shows that, Internet addiction has a stronger negative effect on urban children than rural children. Additionally, Internet addiction has a significant correlation with the mental health of left-behind children (LBC), but not children living with both parents (CLP).Our research has several weaknesses. First, this article uses time spent online to measure Internet addiction and this measurement method is not perfect. Also, given that the sample is made up of only Chinese children, conclusions about generalizability remain tentative. Future studies should be conducted in other countries.This study systematically studied the effects of Internet addiction on the physical and mental health of Chinese children. This study can help government leaders make targeted programs to prevent children from Internet addiction in the future, especially to reduce internet dependence among students.

Background Uptake of HIV pre-exposure prophylaxis (PrEP) has been increasing in the United States since its FDA approval in 2012; however, the COVID-19 pandemic may have affected this trend. Our objective was to assess the impact of COVID-19 on PrEP prescriptions in the United States. Methods We analyzed data from a national pharmacy database from January 2017 through March 2021 to fit an interrupted time-series model that predicted PrEP prescriptions and new PrEP users had the pandemic not occurred. Observed PrEP prescriptions and new users were compared with those predicted by the model. Main outcomes were weekly numbers of PrEP prescriptions and new PrEP users based on a previously developed algorithm. The impact of the COVID-19 pandemic was quantified by computing rate ratios and percentage decreases between the observed and predicted counts during 15/3/2020–31/3/2021. Results In the absence of the pandemic, our model predicted that there would have been 1 058 162 PrEP prescriptions during 15/3/2020–31/3/2021. We observed 825 239 PrEP prescriptions, a 22.0% reduction (95% CI: 19.1–24.8%) after the emergency declaration. The model predicted 167 720 new PrEP users during the same period; we observed 125 793 new PrEP users, a 25.0% reduction (95% CI: 20.9–28.9%). The COVID-19 impact was greater among younger persons and those with commercial insurance. The impact of the pandemic varied markedly across states. Conclusions The COVID-19 pandemic disrupted an increasing trend in PrEP prescriptions in the United States, highlighting the need for innovative interventions to maintain access to HIV-prevention services during similar emergencies.

Background The number and characteristics of pre-exposure prophylaxis (PrEP) health care providers in the United States have not been reported. Methods We analyzed a national pharmacy database that included >90% of all prescriptions dispensed by retail pharmacies and 60%-86% dispensed by mail-order outlets. We estimated the number of PrEP providers by year, provider type, physician specialty, and geographic location. We also measured the Gini coefficients for the distribution of PrEP patients among providers. Results The number of PrEP providers increased from 9621 in 2014 to 65,822 in 2019. In 2019, 68.1% of PrEP providers were physicians. The proportion of nurse practitioners or physician assistants increased from 18.0% in 2014 to 29.7% in 2019. Among all the US health care providers, those who prescribed PrEP increased from 0.7% in 2014 to 4.3% in 2019. Among all general practice/family medicine physicians, the percentage of who prescribed PrEP increased from 1.8% in 2014 to 13.6% in 2019 and from 14.2% to 34.2% among infectious disease physicians. The ratio of PrEP providers to 100 persons with PrEP indications was lowest in the South with 4.4. The Gini coefficient for the distribution of PrEP patients among providers was 0.75 in 2019, with 50% of the PrEP patients prescribed PrEP by 2.2% of PrEP providers. Conclusions An increasing number of providers prescribed PrEP during 2014-2019. The South had the largest number of new HIV diagnoses and greatest need for HIV prevention but had less PrEP service capacity compared with other regions. Expanded access to PrEP services is needed in the United States.

OBJECTIVE Ulcerative colitis (UC) is an independent risk factor for thromboembolism, especially during the perioperative period. This study aimed to determine the effects of perioperative parenteral nutrition (PN) supplemented with fish oil (FO) on coagulation function and postoperative outcomes in patients with UC. METHODS This retrospective cohort included 92 consecutive patients who underwent colectomy for UC. Postoperative coagulation indices and outcomes, including thromboelastography (TEG) findings and comprehensive complication index (CCI), were compared. The relative change in serum D-dimer (ΔD-dimer) levels and maximal amplitude (ΔMA) on TEG were also determined. RESULTS Patients receiving PN supplemented with FO (n = 48) had lower D-dimer (P = .036) levels on postoperative day (POD) 5 and a higher MA (P < 0.001) on POD 1 than those who did not receive it (n = 44). A lower ΔD-dimer level (P = .048) and ΔMA (P < 0.001) were also observed in patients receiving FO. The incidence of major postoperative complications (6.3 vs 22.7%; P = .017) and CCI (20.9 vs 23.4%; P = .044) were significantly lower in patients receiving FO. In multivariate analysis, FO (odds ratio, 0.231; 95% confidence interval, 0.055-0.971; P = .046) was a positive protector of major postoperative complications. CONCLUSION Perioperative PN supplemented with FO improved coagulation function and reduced major postoperative complications in patients with UC requiring colectomy. These results may provide cues in formulating management strategies for preventing thromboembolisms and postoperative complications in patients with UC.

Anastomotic recurrence after bowel resection is problematic in patients with Crohn's disease. Antimesenteric functional end-to-end handsewn (Kono-S) anastomosis is associated with a low risk of anastomotic recurrence in patients with Crohn's disease.Kono-S anastomosis is effective but may be time-consuming. This study aimed to describe stapled antimesenteric functional end-to-end anastomosis for patients with Crohn's disease.The mesentery of the affected bowel segment was divided. A 5-cm-wide stapled functional end-to-end anastomosis was performed approximately 6 cm from the affected segment. The bowel was divided transversely exactly 90° to the intestinal lumen and the mesentery, and a supporting column was then constructed.From January 2018 to June 2021, 17 stapled antimesenteric functional end-to-end anastomoses were performed. The mean operative time was 106 (range, 80-135) minutes, and the time to construct the stapled antimesenteric functional end-to-end anastomosis was 21 (range, 18-28) minutes. The mean follow-up time was 8.9 (range, 1-15) months. In total, 10 patients underwent surveillance endoscopy. The average Rutgeerts score was 0.8 (range, 0-4), and the incidence of endoscopic recurrence was 11.8%. No postoperative mortality or anastomotic leakage was observed.Stapled antimesenteric functional end-to-end anastomosis may be a safe and time-saving procedure for patients with Crohn's disease.Further prospective studies with a large sample size are warranted.

Increasing HIV testing, preexposure prophylaxis (PrEP), and antiretroviral therapy (ART) are pillars of the federal Ending the HIV Epidemic in the U.S. (EHE) initiative, with a goal of decreasing new HIV infections by 90% by 2030.* In response to the COVID-19 pandemic, a national emergency was declared in the United States on March 13, 2020, resulting in the closure of nonessential businesses and most nonemergency health care venues; stay-at-home orders also limited movement within communities (1). As unemployment increased during the pandemic (2), many persons lost employer-sponsored health insurance (3). HIV testing and PrEP prescriptions declined early in the COVID-19 pandemic (4-6); however, the full impact of the pandemic on use of HIV prevention and care services and HIV outcomes is not known. To assess changes in these measures during 2019-2021, quarterly data from two large U.S. commercial laboratories, the IQVIA Real World Data - Longitudinal Prescription Database (IQVIA)

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To assess disruption in healthcare services for HIV treatment by national emergency in response to the coronavirus disease 2019 (COVID-19) pandemic in the United States.Time-series analysis.We analyzed the IQVIA Real World Data-Longitudinal Prescriptions Database and calculated time trends in the weekly number of persons with active antiretroviral prescriptions for HIV treatment, and of persons who obtained antiretroviral prescriptions during January 2017-March 2021. We used interrupted time-series models to estimate the impact of the COVID-19 pandemic on antiretroviral therapy (ART) use between March 2020 and March 2021.We found that the weekly number of persons with active antiretroviral prescriptions decreased by an average 2.5% (95% confidence interval [CI]: -3.8% to -1.1%), compared to predicted use, during March 2020 through March 2021. The weekly number of persons who obtained antiretroviral prescriptions decreased 4.5% (95% CI: -6.0% to -3.0%), compared to the predicted number. Men, persons aged ≤34 years, privately insured persons, and persons in medication assistance programs had greater decreases than other groups.We demonstrated a decrease in the number of persons with active antiretroviral prescriptions during the first year of the COVID-19 pandemic and the number did not return to levels expected in the absence of the pandemic. Disruptions in HIV care and decreased ART may lead to lower levels of viral suppression and immunologic control, and increased HIV transmission in the community.

We analyzed a national pharmacy database to estimate the annual number of persons who abandoned preexposure prophylaxis (PrEP) prescriptions and assessed associated factors. About 9% of persons prescribed PrEP abandoned prescriptions in 2019; abandonment was associated with sex, age, insurance type, black race/ethnicity, and drug copayment amount.

HIV testing is a critical component of effective HIV prevention and care. CDC recommends routine opt-out HIV testing in health care settings for all sexually active persons aged 13-64 years at least once in their lifetime and risk-based testing regardless of age for those who report behaviors associated with HIV acquisition (1). However, recent studies show low HIV testing rates in clinical settings; HIV testing rates at visits to physician offices did not increase during 2009-2016 (2). The objective of the current study is to estimate temporal trends in HIV testing among persons with commercial insurance or Medicaid from 2014 through 2019 and describe their demographic characteristics in 2019. Weighted data from the IBM MarketScan Commercial Claims and Encounters database* (commercial insurance) and from the Centers for Medicare & Medicaid Services (CMS) claims database† (Medicaid) were analyzed to estimate the proportions of persons with commercial insurance or Medicaid who received testing for HIV. Testing rates increased among male and nonpregnant female persons aged ≥13 years with either type of coverage. In 2019, only 4.0% of those with commercial insurance and 5.5% of those with Medicaid received testing for HIV. Testing rates were higher among non-Hispanic Black or African American (Black) persons and Hispanic or Latino (Hispanic) persons. Based on mathematical modeling studies, these annual testing rates would need to increase at least threefold and be sustained over several years (3,4) to achieve the Ending the HIV Epidemic (EHE) in the U.S. initiative goal of ≥95% of persons with HIV being aware of their infection by 2025.§ Interventions need to be implemented to increase routine and risk-based HIV testing in clinical settings to higher levels that can help reduce disparities in HIV diagnoses between Black and Hispanic persons compared with non-Hispanic White (White) persons (5). Increased HIV testing is essential to achieve the goals of the EHE initiative and reduce disparities in HIV diagnoses; public health should partner with health care systems to implement interventions that support increased testing.

Few reports have focused on single-balloon enteroscopy (SBE) for evaluation of small bowel Crohn disease (CD) strictures. The aim of this study was to analyze the relationships between peripheral blood inflammatory markers and small bowel CD strictures observed by SBE.CD patients who underwent SBE between January 2016 and December 2020 were enrolled. The clinical characteristics and peripheral blood inflammatory markers were collected and analyzed to screen for predictive factors significantly associated with small bowel CD strictures.A total of 221 CD patients underwent SBE. The lymphocyte (LC) counts in peripheral blood were significantly lower in the active group (n=178) than in the inactive group (n=43) according to the simple endoscopic score for CD (SES-CD), P =0.011, and was correlated with the SES-CD ( r =-0.134, P =0.047). The LC levels were significantly lower in the stricture group (n=116) than in the nonstricture group (n=105) based on whether small bowel strictures developed, P =0.000, and LC was a risk factor for strictures in the multivariate analysis [hazard ratio (HR), 2.332; 95% CI, 1.102-4.937; P =0.027]. In the subgroup analysis, LC levels notably decreased after stricture aggravation ( P =0.000). Forty-seven patients who underwent small bowel resection underwent SBE at 6 to 12 months after surgery. The LC level was significantly lower in the postoperative patients with strictures ( P =0.025), and LC (HR, 4.444; 95% CI, 1.265-15.617; P =0.020) was a risk of postoperative strictures by univariate analysis, but the age at diagnosis (HR, 6.462; 95% CI, 1.272-22.560; P =0.022) was an independent risk factor by multivariate analysis.Peripheral blood LC levels were correlated with SES-CD and gradually decreased as the intestinal stricture increased in small bowel CD patients. The LC level was also significantly lower in the postoperative CD patients with strictures. The level of LC was a risk factor for small bowel strictures. These results suggest that peripheral blood LC could be a novel marker of small bowel CD strictures to guide CD diagnosis and therapy.

Four new drimane sesquiterpenoids (

Background An excessive postoperative inflammatory response is common after surgery for inflammatory bowel disease (IBD) and may be associated with an increased incidence of postoperative ileus. This study assessed the role of perioperative dexamethasone in postoperative ileus after IBD surgery. Method Patients undergoing elective IBD surgery were randomized to either an intravenous 8-mg dose of dexamethasone (n = 151) or placebo (n = 151) upon induction of anesthesia. The primary outcome was the incidence of prolonged postoperative ileus. Secondary outcomes included incidence of reported nausea or vomiting, time to first passage of flatus and stool, GI-2 recovery, postoperative pain, length of stay, and surgical complications. Results An intention-to-treat analysis revealed that patients who received dexamethasone exhibited a lower incidence of prolonged postoperative ileus (22.5% vs 38.4%; P = 0.003), shorter time to first passage of stool (28 vs 48 h, P Conclusion A single, intravenous 8-mg dose of dexamethasone upon induction of anesthesia reduced the incidence of prolonged postoperative ileus, the intensity of postoperative pain, and shortened the postoperative length of stay for IBD patients undergoing elective surgery. ClinicalTrials.gov: NCT03456752.

Background Use of HIV preexposure prophylaxis (PrEP) has increased nationwide, but the magnitude and distribution of PrEP medication costs across the health care system are unknown. Objective To estimate out-of-pocket (OOP) and third-party payments using a large pharmacy database. Design Retrospective cohort study. Setting Prescriptions for tenofovir disoproxil fumarate with emtricitabine (TDF-FTC) for PrEP in the United States in the IQVIA Longitudinal Prescriptions database, which covers more than 90% of retail pharmacy prescriptions. Measurements Third-party, OOP, and total payments were compared by third-party payer, classified as commercial, Medicaid, Medicare, manufacturer assistance program, or other. Missing payment data were imputed using a generalized linear model to estimate overall PrEP medication payments. Results Annual PrEP prescriptions increased from 73 739 to 1 100 684 during 2014 to 2018. Over that period, the average total payment for 30 TDF-FTC tablets increased from $1350 to $1638 (5.0% compound annual growth rate) and the average OOP payment increased from $54 to $94 (14.9% compound annual growth rate). Of the $1638 in total payments per 30 TDF-FTC tablets in 2018, OOP payments accounted for $94 (5.7%) and third-party payments for $1544 (94.3%). Out-of-pocket payments per 30 tablets were lower among Medicaid recipients ($3) than among those with Medicare ($80) or commercial insurance ($107). Payments for PrEP medication in the IQVIA database in 2018 totaled $2.08 billion; $1.68 billion (80.7%) originated from prescriptions for persons with commercial insurance, $200 million (9.6%) for those with Medicaid, $48 million (2.3%) for those with Medicare, and $127 million (6.1%) for those with manufacturer assistance. Limitation The IQVIA database does not capture every prescription nationwide. Conclusion Third-party and OOP payments per 30 TDF-FTC tablets increased annually. The $2.08 billion in PrEP medication payments in 2018 is an underestimation of national costs. High costs to the health care system may hinder PrEP expansion. Primary funding source Centers for Disease Control and Prevention.

Staged surgery (SS) and primary anastomosis (PA) are alternatives to emergency surgery in Crohn's disease (CD). This study aimed to compare postoperative patient outcomes and medical cost of SS and PA for CD emergencies.Consecutive patients with CD undergoing emergency surgery between December 1997 and January 2017 in three centers were included. The PA and SS groups were compared regarding patient outcomes including postoperative complications and surgical recurrence, as well as hospitalization costs.Altogether 96 (39.5%) patients underwent an emergency PA, and 147 (60.5%) underwent an emergency SS. The incidence of intra-abdominal septic complications (IASC) in the PA group was 15.6% compared with 7.5% in the SS group (P = 0.04). The length of hospitalization was longer (32.36 ± 1.76 d vs 19.33 ± 2.36 d, P0.01) and the hospitalization cost was higher in the SS group (USD 15 811.1 ± 1697.1 vs USD 8345.3 ± 919.5, P0.01) than the PA group. SS correlated with a lower surgical recurrence rate than PA (log-rank test, P = 0.04). Presence of diffuse peritonitis, perforating or colonic disease, decision of operation choice made by a senior consultant and more than two concurrent surgical indications were related to the need for SS in emergencies. Localized peritonitis, body mass index (18.5 kg/mSS can be performed with limited IASC and low surgical recurrence rates for surgical emergencies in CD, although it increases hospitalization costs and delays discharge.

The Global Leadership Initiative on Malnutrition (GLIM) has recently been proposed as a consensus criterion for identifying malnutrition. However, data on the application of GLIM criteria in patients with inflammatory bowel disease (IBD) are limited. Therefore, this study aimed to explore the validity of this neoteric criterion for identifying malnutrition and investigate the association between malnutrition and quality of life (QoL) in patients with IBD.This multicenter, prospective, observational study assessed hospitalized patients with IBD at four general hospitals. Nutritional status was evaluated using criteria from the World Health Organization (WHO) related body mass index (BMI) cut-off value, Subjective Global Assessment (SGA), European Society for Clinical Nutrition and Metabolism (ESPEN) criteria of malnutrition in 2015, and GLIM criteria. Kappa (K) values were calculated to determine interrater validity and consistency among different prevalence of malnutrition. Patients' QoL was assessed by the Inflammatory Bowel Disease Questionnaire (IBDQ).A total of 238 hospitalized patients with IBD were enrolled, with a mean age of 38.5 ± 14.0 years, 68.5% of them were male, and 177 with Crohn's disease (CD). Among all patients, 39.5% were underweight (BMI18.5 kg/mThe prevalence of malnutrition is high in patients with IBD. The GLIM criteria may be an appropriate and effective tool to identify malnutrition in the IBD populations due to its substantial concordance with ESPEN and a fair concordance with SGA and WHO-related BMI. GLIM-defined malnutrition showed an enormous adverse impact on patients' QoL.

Concomitant lesions in the small intestine are common in Crohn's disease (CD). This study aimed to detect the incidence of small bowel (SB) lesions in patients undergoing surgical resection for symptomatic ileocolic disease and whether concomitant SB lesions are associated with reoperation due to recurrent CD.In this observational, historical cohort study, consecutive patients with CD undergoing primary ileocolic resection (ICR) from 2007 to 2019 were included. Clinical variables and intraoperative findings were extracted from a prospectively maintained database and analyzed by Cox proportional hazards regression models for identifying risk factors of reoperation.Of the 404 patients included, there were 202 (50%) patients having concomitant SB lesions, and 108 of them underwent concurrent surgical intervention for SB lesions whereas 94 did not. The presence of concomitant SB lesions was a risk factor for reoperation (p = 0.041). Subgroup analysis indicated that patients with concomitant uncomplicated SB lesions left in situ had a comparable rate of reoperation (p = 0.605) whereas patients having concomitant complicated SB lesions undergoing simultaneous surgical intervention showed a higher reoperation rate (P = 0.006) when compared with those without concomitant SB lesions. Interestingly, the adverse effects of concomitant SB lesions can be reversed in the setting of postoperative anti-TNF agents [HR 0.2; 95% CI (0.04-0.9); P=0.040].Concomitant SB lesion(s), especially those complicated lesions, could be a risk factor for postoperative surgical recurrence in patients undergoing ICR. Active postoperative management strategies such as anti-TNF agents should be provided for these patients.

Background Although the interaction between gut microbiota and pouchitis after ileal pouch anal anastomosis (IPAA) for ulcerative colitis (UC) has been confirmed, evidence of commensal mycobiota in the etiology of pouchitis is still lacking. This study aimed to investigate the role of fungi in the pathogenesis of pouchitis. Methods Fecal samples were collected from UC patients with or without pouchitis after IPAA. Experimental pouchitis was induced by 5% dextran sulfate sodium for 7 consecutive days in a rat model of IPAA. Fungal dysbiosis was induced by 0.5% fluconazole (Flu), and commensal fungal recognition through dectin-1 was blocked by 5% laminarin. Fecal fungal composition was analyzed using internal transcribed spacer 2 sequencing. Severity of pouchitis and activation of the CARD9-nuclear factor kappa-B pathway was determined among different groups. Results Patients with pouchitis had a lower alpha (α) diversity in mycobiota composition and a higher abundance of Saccharomyces at the genus level compared with those with a normal pouch. In the rat model of pouchitis, Flu treatment decreased fungal burden but induced fungal dysbiosis, characterized by increased α diversity, a decreased relative abundance of Kazachstania, and increased Polythrincium and Saccharomyces. In addition, Flu treatment worsened dextran sulfate sodium pouchitis, as indicated by increased mortality, weight loss, higher histological score, and CD4+ cell infiltration. Laminarin also increased the severity of pouchitis. In the Flu and laminarin groups, the expression of interferon-γ, tumor necrosis factor-α, CARD9, and phosphorylated nuclear factor kappa-B inhibitor alpha was decreased. Conclusions Patients with pouchitis had altered fungal composition. Fungal dysbiosis or recognition deficiency by the host may exacerbate experimental pouchitis. Strategies targeting commensal mycobiota may provide therapeutic potential against pouchitis, especially for antibiotic-refractory patients.

In 2019, the U.S. Department of Health and Human Services launched the Ending the HIV Epidemic: A Plan for America (EHE) initiative to end the U.S. human immunodeficiency virus (HIV) epidemic by 2030. A critical component of the EHE initiative involves early diagnosis of HIV infection, along with prevention of new transmissions, treatment of infections, and response to HIV outbreaks (1). HIV testing is the first step in identifying persons with HIV infection who need to be engaged in treatment and care as well as persons with a negative HIV test result and who are at high risk for infection and can benefit from HIV preexposure prophylaxis (PrEP) and other prevention services. These opportunities are often missed for persons receiving clinical services in ambulatory care settings (2). Data from the 2009-2016 National Ambulatory Medical Care Survey (NAMCS) and 2009-2017 National Hospital Ambulatory Medical Care Survey (NHAMCS) were analyzed to estimate trends in HIV testing at visits by males and nonpregnant females to physician offices, community health centers (CHCs), and emergency departments (EDs) in the United States. HIV tests were performed at 0.63% of 516 million visits to physician offices, 2.65% of 37 million visits to CHCs, and 0.55% of 87 million visits to EDs. The percentage of visits with an HIV test did not increase at visits to physician offices during 2009-2016, increased at visits to CHC physicians during 2009-2014, and increased slightly at visits to EDs during 2009-2017. All adolescents and adults should have at least one HIV test in their lifetime (3). Strategies that reduce clinical barriers to HIV testing (e.g., clinical decision supports that use information in electronic health records [EHRs] to order an HIV test for persons who require one or standing orders for routine opt-out testing) are needed to increase HIV testing at ambulatory care visits.

BACKGROUND Postoperative intra-abdominal septic complications of Crohn's disease substantially increase the healthcare expenditure and prolong hospitalization. OBJECTIVE We aimed to develop and validate a prediction model for intra-abdominal septic complications after bowel resection and primary anastomosis for Crohn's disease. DESIGN This was a retrospective cohort study. SETTINGS This study was conducted in a tertiary center. PATIENTS Data of 949 Crohn's disease-related primary bowel resections and anastomosis from January 2011 to December 2017 were collected. MAIN OUTCOME MEASURES Primary outcomes were prevalence of intra-abdominal septic complications. RESULTS Overall prevalence of intra-abdominal septic complications after Crohn's disease surgery was 11.6%. Predictors included preoperative C-reactive protein level ≥40 mg/L (OR = 3.545), preoperative glucocorticoids (OR = 1.829) and infliximab use (OR = 3.365), upper GI involvement (OR = 2.072), and hypoalbuminemia (albumin level

Objective: Daily tenofovir disoproxil fumarate/emtricitabine (TDF/FTC) use as HIV preexposure prophylaxis (PrEP) is monitored by identifying TDF/FTC prescriptions from pharmacy databases and applying diagnosis codes and antiretroviral data to algorithms that exclude TDF/FTC prescribed for HIV postexposure prophylaxis (PEP), HIV treatment, and hepatitis B virus (HBV) treatment. We evaluated the accuracy of 3 algorithms used by the Centers for Disease Control and Prevention (CDC), Gilead Sciences, and the New York State Department of Health (NYSDOH) using a reference population in Bronx, New York. Methods: We extracted diagnosis codes and data on all antiretroviral prescriptions other than TDF/FTC from an electronic health record database for persons aged ≥16 prescribed TDF/FTC during July 2016–June 2018 at Montefiore Medical Center. We reviewed medical records to classify the true indication of first TDF/FTC use as PrEP, PEP, HIV treatment, or HBV treatment. We applied each algorithm to the reference population and compared the results with the medical record review. Results: Of 2862 patients included in the analysis, 694 used PrEP, 748 used PEP, 1407 received HIV treatment, and 13 received HBV treatment. The algorithms had high specificity (range: 98.4%-99.0%), but the sensitivity of the CDC algorithm using a PEP definition of TDF/FTC prescriptions ≤30 days was lower (80.3%) than the sensitivity of the algorithms developed by Gilead Sciences (94.7%) or NYSDOH (96.1%). Defining PEP as TDF/FTC prescriptions ≤28 days improved CDC algorithm performance (sensitivity, 95.8%; specificity, 98.8%). Conclusions: Adopting the definition of PEP as ≤28 days of TDF/FTC in the CDC algorithm should improve the accuracy of national PrEP surveillance.

BackgroundWe assessed prevalence of testing for human immunodeficiency virus (HIV) and hepatitis C virus (HCV) infection among persons who inject drugs (PWID).MethodsUsing a nationwide health insurance database for claims paid during 2010–2017, we identified PWID by using codes from the International Classification of Diseases, Current Procedural Terminology, and National Drug Codes directory. We then estimated the percentage of PWIDs tested for HIV or HCV within 1 year of an index encounter, and we used multivariate logistic regression models to assess demographic and clinical factors associated with testing.ResultsOf 844 242 PWIDs, 71 938 (8.5%) were tested for HIV and 65 188 (7.7%) were tested for HCV infections. Missed opportunities were independently associated with being male (odds ratios [ORs]: HIV, 0.50 [95% confidence interval {CI}, 0.49–0.50], P < .001; HCV, 0.66 [95% CI, 0.65–0.72], P < .001), rural residence (ORs: HIV, 0.67 [95% CI, 0.65–0.69], P < .001; HCV, 0.75 [95% CI, 0.73–0.77], P < .001), and receiving services for skin infections or endocarditis (adjusted ORs: HIV, 0.91 [95% CI, 0.87–0.95], P < .001; HCV, 0.90 [95% CI, 0.86–0.95], P < .001).ConclusionsApproximately 90% of presumed PWIDs missed opportunities for HIV or HCV testing, especially male rural residents with claims for skin infections or endocarditis, commonly associated with injection drug use.

Nowadays, pancreatic cancer has been recognized as one of the most fatal malignancies worldwide, the molecular mechanism of which is still not fully understood. In this study, we aimed to uncover the fundamental functions of the eukaryotic translation initiation factor 3H subunit (EIF3H) in the development and progression of pancreatic cancer. Firstly, the results of immunohistochemical (IHC) staining revealed that EIF3H was highly expressed in pancreatic cancer. Moreover, lentiviruses were used to deliver shRNAs into pancreatic cancer cells for silencing EIF3H. Furthermore, the loss-of-function assays demonstrated that knockdown of EIF3H could inhibit the progression of pancreatic cancer cells by reducing proliferation capacity, promoting apoptosis, arresting cell cycle in G2 and suppressing cell migration. In summary, EIF3H may play a critical role in the development and progression of pancreatic cancer, which possesses the potential to act as a therapeutic target for pancreatic cancer treatment.

Five undescribed bis(lauric acid-12-yl)lignanoates, liglaurates A-E, along with the known methyl and glyceryl 12-caffeoyloxylaurates were isolated from the rhizomes of Drynaria roosii Nakaike. Their structures including absolute configurations were determined by HRESIMS, NMR techniques, and ECD calculation. Liglaurates A-D were isolated as the racemates, among which (±)-liglaurate A and (±)-liglaurate B were synthesized by a metal-mediated oxidative coupling reaction and further resolved as the enantiomerically pure compounds. Liglaurates (+)-A, (-)-A, (+)-B, (-)-B, (±)-C and (±)-D exhibited remarkable cytotoxic activities against HeLa cell line, with the IC

Background. Aphasia is a common symptom in stroke patients, presenting with the impairment of spontaneous speech, repetition, naming, auditory comprehension, reading, and writing function. Multiple rehabilitation methods have been suggested for the recovery of poststroke aphasia, including medication treatment, behavioral therapy, and stimulation approach. Acupuncture has been proven to have a beneficial effect on improving speech functions in repetition, oral speech, reading, comprehension, and writing ability. Neuroimaging technology provides a visualized way to explore cerebral neural activity, which helps reveal the therapeutic effect of acupuncture therapy. In this systematic review, we aim to reveal and summarize the neuroimaging mechanism of acupuncture therapy on poststroke aphasia to provide the foundation for further study. Methods. Seven electronic databases were searched including PubMed, Web of Science, Embase, Cochrane Central Register of Controlled Trials, China National Knowledge Infrastructure, the Wanfang databases, and the Chinese Scientific Journal Database. After screening the studies according to the inclusion and exclusion criteria, we summarized the neuroimaging mechanism of acupuncture on poststroke aphasia, as well as the utilization of acupuncture therapy and the methodological characteristics. Result. After searching, 885 articles were retrieved. After removing the literature studies, animal studies, and case reports, 16 studies were included in the final analysis. For the acupuncture type, 10 studies used manual acupuncture and 5 studies used electroacupuncture, while body acupuncture (10 studies), scalp acupuncture (7 studies), and tongue acupuncture (8 studies) were applied for poststroke aphasia patients. Based on blood oxygen level-dependent (BOLD) and diffusion tensor imaging (DTI) technologies, 4 neuroimaging analysis methods were used including amplitude of low-frequency fluctuation (ALFF), regional homogeneity (ReHo), seed-based analysis, and independent component analysis (ICA). Two studies reported the instant acupuncture effect, and 14 studies reported the constant acupuncture’s effect on poststroke aphasia patients. 5 studies analyzed the correlation between the neuroimaging outcomes and the clinical language scales. Conclusion. In this systematic review, we found that the mechanism of acupuncture’s effect might be associated with the activation and functional connectivity of language-related brain areas, such as brain areas around Broca’s area and Wernicke’s area in the left inferior temporal gyrus, supramarginal gyrus, middle frontal gyrus, and inferior frontal gyrus. However, these studies were still in the preliminary stage. Multicenter randomized controlled trials (RCT) with large sample sizes were needed to verify current evidence, as well as to explore deeply the neuroimaging mechanisms of acupuncture’s effects.

Endoscopy remains the gold standard for evaluating postoperative recurrence in Crohn's disease. Timely therapy adjustment according to endoscopic findings can improve long-term outcomes.We aimed to determine the characteristics, clinical values, and safety of the endoscopic evaluation at 1 month after surgery.This was a prospective observational study.This study was conducted in a tertiary referral hospital.Patients with Crohn's disease undergoing ileocolic resection between January 2016 and November 2018 were included.The first postoperative ileocolonoscopy was performed at 4-5 weeks after surgery.The primary outcome was postoperative recurrence within 12 months after surgery. Univariate and multivariate analyses were performed to identify risk factors.Among 84 ileocolonoscopies at 4-5 weeks, no endoscopic complication occurred. The main endoscopic findings at the first evaluation were anastomotic circumferential ulcers (10, 11.9%), anastomotic scattered ulcers (35, 41.7%), ulcers in the neoterminal ileum (16, 19.0%), edema in anastomosis (50, 59.5%), mild narrowing in anastomosis (7, 8.3%), and mild narrowing in neoterminal ileum (3, 3.6%). Anastomotic scattered ulcers were associated with future postoperative recurrence (OR, 2.532 (95% CI, 1.02-6.32), p = 0.046). Fecal calprotectin150 ug/g on postoperative day 14 could predict anastomotic scattered ulcers (OR' 2.91 (95% CI, 1.31-7.47), p = 0.027). The modified Rutgeerts score was used to define endoscopic findings: i0, 37 (44.0%); i1, 4 (4.8%); i2a, 29 (34.5%); i2b, 11 (13.1%); i3, 0; i4, 3 (3.6%). Score ≥i2a were associated with future postoperative recurrence (OR, 3.17 (95% CI, 1.22-8.27), p = 0.018). No factor was associated with a Rutgeerts score of ≥i2a at the first endoscopic evaluation.This was a single-center study with a small cohort of patients.Endoscopic evaluation at 1 month after surgery in CD was safe. Anastomotic scattered ulcers occurred in nearly half of patients and were associated with future postoperative recurrence. See Video Abstract at http://links.lww.com/DCR/B760.LA EVALUACIÓN ENDOSCÓPICA A UN MES DESPUÉS DE LA RESECCIÓN ILEOCÓLICA PARA LA ENFERMEDAD DE CROHN, PREDICE FUTURA RECURRENCIA POSOPERATORIA Y ES SEGURAANTECEDENTES:La endoscopia sigue siendo el estándar de oro para evaluar la recurrencia posoperatoria en la enfermedad de Crohn (EC). El ajuste oportuno en la terapia de acuerdo con los hallazgos endoscópicos, puede mejorar los resultados a largo plazo.OBJETIVO:Determinar las características, valores clínicos y seguridad de la evaluación endoscópica, al mes de la cirugía.DISEÑO:Estudio observacional prospectivo.ENTORNO CLINICO:El estudio se llevó a cabo en un hospital de referencia terciario.PACIENTES:Se incluyeron pacientes con EC sometidos a resección ileocólica entre enero de 2016 y noviembre de 2018.INTERVENCIONES:La primera ileocolonoscopia posoperatoria se realizó a las 4-5 semanas posteriores a la cirugía.PRINCIPALES MEDIDAS DE RESULTADO:El resultado primario fue la recurrencia posoperatoria dentro de los 12 meses posteriores a la cirugía. Se realizaron análisis univariados y multivariados para identificar factores de riesgo.RESULTADOS:Entre 84 ileocolonoscopias a las 4-5 semanas, no ocurrió ninguna complicación endoscópica. Los principales hallazgos endoscópicos en la primera evaluación, fueron úlceras anastomóticas circunferenciales (10, 11,9%), úlceras anastomóticas dispersas (35, 41,7%), úlceras en el íleon neo-terminal (16, 19,0%), edema en la anastomosis (50, 59,5%), estrechamiento leve en la anastomosis (7, 8,3%) y estrechamiento leve en el íleon neo-terminal (3, 3,6%). Las úlceras anastomóticas dispersas se asociaron con recurrencia posoperatoria futura (OR, 2,532 (95% CI, 1,02-6,32), p = 0,046). La calprotectina fecal en el post d 14150 ug / g podría predecir úlceras anastomóticas dispersas (OR' 2,91 (95% CI, 1,31-7,47), p = 0,027). Se utilizó la puntuación de Rutgeerts modificada para definir los hallazgos endoscópicos: i0, 37 (44,0%); i1, 4 (4,8%); i2a, 29 (34,5%); i2b, 11 (13,1%); i3, 0; i4, 3 (3,6%). La puntuación ≥i2a se asoció con recurrencia posoperatoria futura (OR, 3,17 (95% CI, 1,22-8,27), p = 0,018). Ningún factor se asoció con ≥i2a en la primera endoscopia.LIMITACIONES:Estudio de un solo centro con una pequeña cohorte de pacientes.CONCLUSIONES:La evaluación endoscópica al mes de la cirugía en EC, fue segura. Se produjeron úlceras anastomóticas dispersas en casi la mitad de los pacientes y se asociaron con una futura recurrencia posoperatoria. Consulte Video Resumen en http://links.lww.com/DCR/B760. (Traducción - Dr. Fidel Ruiz Healy).

Background Malnutrition is prevalent among patients with inflammatory bowel disease (IBD). Nutritional profiles among Asian patients with IBD have seldom been investigated. We assessed the prevalence of and risk factors for malnutrition, use of nutrition support, and sociopsychological status associated with malnutrition among patients with IBD in China. Methods Patients with ulcerative colitis and Crohn’s disease (CD) recruited from 43 tertiary referral hospitals were screened for malnutrition and nutrient deficiencies in this cross-sectional study. The use of nutrition support was recorded. The sociopsychological status was assessed by subjective questionnaires. Factors associated with malnutrition were analyzed, and multivariate regression was used to determine independent predictors for malnutrition. Results We recruited 1013 patients with a median age of 35.0 years, 58.5% of them had CD, and 61.4% of all patients were male. Overall, 49.5% (n = 501) of patients were diagnosed with malnutrition, including 57.0% of patients with CD, 38.8% of patients with ulcerative colitis, and 44.1% of patients with quiescent or mildly active disease. Nutrient deficiencies were prevalent despite the absence of malnutrition. Malnutrition was associated with adverse sociopsychological status, including decreased social support, higher perceived stress, and impaired quality of life. Moderate to severe disease activity and extensive disease were 2 independent risk factors for malnutrition. In total, 41.6% of patients received nutrition support, and patients with risk factors were more likely to receive nutrition support. Conclusions Malnutrition was highly prevalent and associated with adverse consequences in Chinese patients with IBD. Malnutrition screening and early initiation of nutrition support are essential components in IBD care.

Postoperative intra-abdominal septic complications in patients with Crohn's disease undergoing intestinal resection and anastomosis are frequent and difficult to manage.This study sought to explore the value of preoperative CT enterography to predict intra-abdominal septic complications.This was a retrospective and prospective observational study.This study was conducted in a tertiary referral hospital.Patients with Crohn's disease undergoing primary intestinal resection were enrolled in our study.The CT enterography severity index was calculated and its ability to predict intra-abdominal septic complications evaluated by multivariate analyses. A prospective study was then performed to assess the reliability of this CT enterography index.The incidence of postoperative intra-abdominal septic complications in patients undergoing a 1-stage procedure was significantly higher than those undergoing a 2-stage procedure (3/103 vs 24/241; 2.9% vs 10.0%; p = 0.026). A multivariate analysis identified 5 CT enterography parameters, including mesenteric fibrofatty proliferation, intra-abdominal abscess or phlegmon, intestinal fistula, peritoneal effusion, and intestinal dilatation with stricture to be independent predictors of intra-abdominal septic complications (p0.001). A nomogram model based on these 5 parameters was constructed. A receiver operating characteristic analysis identified a CT enterography nomogram score cutoff of 175 as a predictor of intra-abdominal septic complications with a sensitivity of 83.3% and a specificity of 85.3%. In the prospective study, those patients with a CT enterography nomogram score175 were assigned to the 2-stage group, which resulted in a similar intra-abdominal septic complication incidence in those undergoing intestinal resection with or without anastomosis (2/82 vs 2/34; p = 0.355).This study was limited by its single-center scope.Preoperative CT enterography findings may predict postoperative outcomes and help determine surgical approach in Crohn's disease. Patients with worse intra-abdominal findings confirmed by CT enterography may benefit from stoma creation after intestinal resection. See Video Abstract at http://links.lww.com/DCR/B588.ANTECEDENTES:Las complicaciones sépticas intra-abdominales postoperatorias en pacientes con enfermedad de Crohn sometidos a resección intestinal y anastomosis son frecuentes y difíciles de manejar.OBJETIVO:Este estudio buscó explorar el valor del índice enterográfico por tomografía computada en el pré-operatorio y así poder predecir futuras complicaciones sépticas intra-abdominales.DISEÑO:Estudio observacional retro-prospectivo.AJUSTE:Investigación realizada en un hospital de referencia terciaria.PACIENTES:Se incluyeron en nuestro estudio pacientes con enfermedad de Crohn sometidos a una resección intestinal primaria.PRINCIPALES MEDIDAS DE RESULTADO:Se calculó el índice de gravedad de la enterografía por tomografía axial computada y se evaluó su capacidad para predecir las complicaciones sépticas intra-abdominales mediante un análisis multivariado. Luego se realizó un estudio prospectivo para evaluar la confiabilidad del índice enterográfico por tomografía axial computada.RESULTADOS:La incidencia de complicaciones sépticas intra-abdominales postoperatorias en pacientes sometidos a un procedimiento de un solo tiempo fue significativamente mayor que aquellos sometidos a un procedimiento de dos tiempos (3/103 frente a 24/241; 2,9% frente a 10,0%; p = 0,026). El análisis multivariado identificó cinco parámetros enterográficos por tomografía axial computada, incluidos la proliferación fibrograsa mesentérica, el absceso o flegmón intra-abdominal, la fístula entérica, el derrame peritoneal y la dilatación intestinal debido a estenosis como predictores independientes de complicaciones sépticas intra-abdominales (p0,001). Se construyó un modelo de Nomograma basado en estos cinco parámetros. Un análisis de las características operatorias del receptor identificó una puntuación de cohortes del nomograma de la enterografía por tomografía axial computada de 175 como predictor de complicaciones sépticas intra-abdominales con una sensibilidad del 83,3% y una especificidad del 85,3%. En el estudio prospectivo, los pacientes con puntuación de nomograma enterográfico por tomografía axial computada superior a 175 fueron asignados al grupo en dos tiempos, lo que resultó en una incidencia similar de complicaciones sépticas intra-abdominales en aquellos sometidos a resección intestinal con o sin anastomosis (2/82 vs. 2/34; p = 0,355).LIMITACIONES:Este estudio estuvo limitado por su alcance unicéntrico.CONCLUSIÓN:Los hallazgos enterográficos por tomografía axial computada pré-operatoria pueden predecir ciertos resultados postoperatorios y ayudar a determinar el abordaje quirúrgico en la enfermedad de Crohn. Los pacientes con peores hallazgos intra-abdominales confirmados por enterografía en la tomografía axial computada podrían beneficiarse de la creación de un estoma después de la resección intestinal. Consulte Video Resumen en http://links.lww.com/DCR/B588. (Traducción-Dr Xavier Delgadillo).

Aim Crohn's disease affects the entire gastrointestinal tract and is accompanied by changes in disease location and behaviour. We aimed to analyse changes and the factors in patients with Crohn's disease undergoing intestinal repeated-resection. Methods We included and retrospectively analyzed patients with Crohn's disease who received ≥2 bowel surgeries from a tertiary inflammatory bowel disease centre from January 2008 to December 2019. The Montreal classification was used to describe the disease site and behaviour. Factors were assessed by univariate and multivariate analysis. Results A total of 339 patients were included of whom 94 patients received ≥3 bowel resections. The median patient's age at the second and third surgery was 36.4 and 39.6, respectively. Repeated-resection most commonly occurred in the original surgical site. However, disease behaviour progressed with the number of surgical interventions and disease duration, especially for patients with B1 phenotype. Patients with L1 Crohn's disease at a primary resection that progressed to L2 Crohn's disease at a second surgical resection required a resection earlier than patients whose disease remained in L1 or progressed to L3 Crohn's disease. Multivariate analysis showed that history of appendectomy was a predictor of progression from L1 to L3 Crohn's disease at a second surgical resection, while treatment with azathioprine (AZA) may be a protective factor that abated the risk of progression from L1 to L3 Crohn's disease. Conclusion The original resection site is the most common location for recurrence in patients with Crohn's disease, but disease behaviour progresses with the number of surgeries and disease duration. L1 Crohn's disease patients with a history of appendectomy have a higher risk to progress to L3 Crohn's disease at a second surgical resection, while the AZA may be a protective factor that reduces the risk of progression from L1 to L3.

Summary Background & aims Exclusive enteral nutrition (EEN) as a primary therapy is safe and effective for inducing the clinical remission of active luminal Crohn's disease (CD). Whether isolated colonic involvement affects the efficacy of EEN is controversial. We aimed to identify the influence of isolated colonic CD on the efficacy of EEN and to determine other potential predictors of the response to induction therapy with EEN in adult patients with CD. Methods Data for adult CD patients treated with EEN as an induction therapy at our centre from January 1, 2014, to May 31, 2017, were reviewed. Eligible patients were divided into an isolated colonic Crohn's disease (cCD) group and a non-isolated colonic Crohn's disease (non-cCD) group according to the disease location. The rates of clinical remission and inflammatory and nutritional serum markers were compared between the groups. Possible relationships between isolated colonic involvement or other potential factors and the efficacy of EEN were assessed by univariate and multivariate analyses. The propensity score matching method was used to confirm the results. Results Overall, 241 patients were included in the analysis: 52 patients in the cCD group and 189 patients in the non-cCD group. The rates of clinical remission differed between the two groups (cCD group: 51.9% versus non-cCD group: 68.3%, P = 0.029). Multivariate analyses indicated that isolated colonic involvement was associated with a reduced response to EEN (OR = 2.74; [CI] 95% = [1.2–6.23], P = 0.016). Additionally, the lean body mass index (LBMI) before treatment was associated with the efficacy of EEN (OR = 0.636; [CI] 95% = [0.444–0.912], P = 0.014). These associations were confirmed using the propensity score model. For patients with isolated colonic CD, multivariate analysis showed that pancolitis (OR = 16.7; [CI] 95% = [1.074–260.5], P = 0.044) was another independent factor for the efficacy of EEN. Further analysis showed that even in patients who achieved clinical remission after EEN, inflammatory serum markers declined more slowly in the cCD group than in the non-cCD group, and the time to remission was longer in the cCD group. Conclusions Isolated colonic CD showed a reduced response to induction therapy with EEN compared with ileal or ileocolonic disease in adult patients. Patients with isolated colonic CD required more time to benefit from EEN therapy compared with patients with non-colonic CD. Additionally, LBMI before treatment was associated with the efficacy of EEN.

The rate of postoperative ileus following stoma closure is high in patients with Crohn’s disease and temporary enterostomy. To evaluate the effect of chyme reinfusion on postoperative outcomes including ileus in these patients. Patients were screened from January 2012 to December 2017 and divided into chyme reinfusion group (n = 33) and non-chyme reinfusion group (n = 84). The following 30-day postoperative outcomes were evaluated. Univariate and multivariate analyses and propensity score matching were performed to identify risk factors for these postoperative outcomes. The incidence of postoperative ileus was significantly lower in the chyme reinfusion than in non-chyme reinfusion group, which had been confirmed by the results after matching (3/26 vs 11/26, p = 0.012). The rate of postoperative diarrhea was significantly lower in the chyme reinfusion group compared with non-chyme reinfusion group, whereas the difference was not significant after matching (2/26 vs 6/26, p = 0.191). Additionally, the postoperative length of stay was significantly shorter in the chyme reinfusion than in non-chyme reinfusion group before and after propensity score matching. In the multivariate analysis, chyme reinfusion was an independent protective factor for postoperative ileus (odds ratio 0.218; 95% confidence interval 0.05–0.95; p = 0.042) and for postoperative length of stay (coefficient − 0.191; 95% confidence interval − 0.350 to − 0.032, p = 0.019). Chyme reinfusion was associated with lower rate of postoperative ileus and shorter length of stay following stoma closure in Crohn’s patients with temporary ileostomy. Further randomized clinical trial between patients with or without chyme reinfusion was needed to confirm these conclusions.

Objective In China, patients generally seek health care at high-level hospitals, which is leading to escalating medical costs and overloaded hospitals. Some studies have suggested that the health system is an important factor influencing individuals' health care-seeking behaviour; however, this association has not been studied in much depth. We therefore examined the impact of the health system (in terms of the interaction between health insurance reimbursement and health workforce) on health care-seeking behaviour. Methods Drawing on national survey data from 2008 and 2013, we linked individual-level data on choice of health care providers (our index of health care-seeking behaviour) with county-level data on the health workforce and health insurance. We then constructed a multilevel multinomial logistic model to examine the impacts of health insurance reimbursement (indexed as average reimbursement rate [ARR]) and the health workforce (number of registered physicians per 1000 population) at county hospitals and primary health care institutions (PHCs) on choice of inpatient care providers. Results Increases in ARR at county hospitals were associated with a greater probability of visiting such hospitals (relative risk ratio [RRR] = 1.23), and this positive impact was even greater in county hospitals with higher physician densities (RRR = 2.76). Greater ARR in PHCs was associated with a 73% lower probability of visiting municipal- and higher-level hospitals; increasing ARR was associated with an even lower probability when physician density in PHCs was considered (RRR = 0.09). Conclusion Increases in the health insurance reimbursement and health workforce are necessary to improve health care access and thereby health care-seeking behaviour. Thus, comprehensive health system reform is necessary.

BACKGROUND The perioperative behavior of fecal calprotectin and whether it predicts early postoperative endoscopic recurrence of Crohn's disease are unknown. OBJECTIVE We aimed to compare the perioperative profiles of fecal calprotectin between patients with Crohn's disease and patients without Crohn's disease undergoing intestinal resection and to identify the association between consecutive fecal calprotectin levels and endoscopic recurrence 3 months after surgery in patients with Crohn's disease. DESIGN This was a prospective observational study. SETTINGS This study was conducted in a tertiary referral hospital. PATIENTS One hundred fourteen consecutive patients (90 Crohn's disease, 24 non-Crohn's disease) who underwent resection were recruited. MAIN OUTCOME MEASURES Univariate and multivariate analyses were performed to identify variations and risk factors. The predictive accuracy of the possible predictors was assessed by using receiver operating characteristic curves. RESULTS The fecal calprotectin levels on preoperative day 14 and postoperative days 14, 21, 28, 60, and 90 were higher in the Crohn's disease group than they were in non-Crohn's disease group (p < 0.05). Twenty patients (22.2%) developed endoscopic recurrence 3 months after resection. The trend for fecal calprotectin change (Δfecal calprotectin) from preoperative day 14 to postoperative day 14 was opposite in the recurrence and nonrecurrence groups. Multivariate analysis showed that this change was a predictive factor of early endoscopic recurrence (p < 0.05). ΔFecal calprotectin was more accurate at predicting early endoscopic recurrence than was fecal calprotectin at single time points with a cutoff value of 240 μg/g. LIMITATIONS This is a single-center trial with a limited cohort of patients. CONCLUSIONS The perioperative fecal calprotectin levels were higher in patients with Crohn's disease than they were in the control group. The change in fecal calprotectin levels from preoperative day 14 to postoperative day 14 could serve as a practical predictive index for early postoperative endoscopic recurrence. See Video Abstract at http://links.lww.com/DCR/A796.

Crohn's disease (CD)-associated adherent invasive Escherichia coli (AIEC) has been implicated as a causative or contributory factor in CD pathology. MicroRNA let-7b/Toll-like receptor 4 (TLR-4) signaling pathways may play an important role in microbiota-mucosa interactions. We aimed to investigate whether AIEC influences IECs' function of expressing TLR4, and the potential role of let-7b in regulating AIEC induced gut inflammation. Wild type (WT) and interleukin-10 knockout (IL-10 KO) mice in specific pathogen free (SPF) housing were infected by AIEC LF82, and IL-10 KO mice were treated with pre-let7b or anti-let-7b. Besides, T84 cells were infected by AIEC LF82 or E. coli K-12, and treated with let-7b mimics or inhibitor. let-7b/TLR4 signaling pathway was investigated and the therapeutic effects of let-7b treatment on colitis in IL-10-mice and on cytokines release in T84 were assessed. We found AIEC elicited/exacerbated colitis in WT/IL-10 KO mice, and promoted proinflammatory cytokines release in T84 cells that correlated with increased TLR4 expression and decreased let-7b. Overexpression of let-7b significantly ameliorated the severity of colitis in AIEC infected IL-10 KO mice, and reduced secretion of cytokines in AIEC-infected T84 cells via regulating TLR4 expression. Besides, overexpression of TLR4 caused by inhibition of let-7b led to increased proinflammatory cytokines release in K-12 infected T84 cells. These results suggest AIEC instigates excessive mucosal immune response against gut microbiota via let-7b/TLR4 signaling pathway. Let-7b may be a potential therapeutic target of CD, especially for CD with AIEC infection.

Objective The Targeted Highly Effective Interventions to Reverse the HIV Epidemic (THRIVE) demonstration project created collaboratives of health departments, community-based organizations, and clinical partners to improve HIV prevention services for men who have sex with men (MSM) and transgender women (TGW) of color. We administered an online survey from September 2018 through February 2019 to assess the collaboratives. Methods We used a Likert scale to measure agreement on collaborative characteristics. We used Fisher exact tests to compare success ratings by health department employment and funding status. We created a radar chart to compare the percentage agreement on key characteristics of the most and least successful collaboratives. We used a general inductive approach in the qualitative analysis of open-ended question responses. Results Of 262 survey recipients, 133 responded (51%); 49 (37%) respondents were from health departments. Most respondents (≥70%) agreed that their collaborative is diverse, cooperates, meets regularly, has realistic goals, has effective leadership, and has effective communication. Most respondents (87%) rated their collaborative as successful in implementing HIV prevention services for MSM and TGW of color. Comparison of the most and least successful collaborative found the greatest difference in respondent agreement in the presence of effective leadership, communication, and adequate resources. The most commonly cited challenge in the open-ended questions was inadequate resources. The most commonly cited success was increased provision of services, particularly preexposure prophylaxis. Conclusions Community collaboratives were considered successful by most collaborative members and may be an effective part of HIV prevention strategies.

Four polyene macrolactams including the previously reported niizalactam C (4), and three new ones, streptolactams A–C (1–3) with a 26-membered monocyclic, [4,6,20]-fused tricyclic and 11,23-oxygen bridged [14,16]-bicyclic skeletons, respectively, were isolated from the fermentation broth of the deep-sea sediment-derived Streptomyces sp. OUCMDZ-3159. Their structures were determined based on spectroscopic analysis, X-ray diffraction analysis, and chemical methods. The abiotic formation of compounds 2 and 4 from compound 1 were confirmed by a series of chemical reactions under heat and light conditions. Compounds 1 and 3 showed a selective antifungal activity against Candida albicans ATCC 10231.

Background Crohn’s disease [CD] is a chronic, relapsing and incurable inflammatory disorder. Micro RNAs [miRNAs], which modulate gene expression by binding to mRNAs, may make significant contributions to understanding the complex pathobiology and aetiology of CD. This study aimed to investigate the therapeutic role and mechanism of miR-130a-3p in CD. Methods Differentially expressed miRNAs in colon tissues of CD patients and normal controls [NCs] were screened using an miRNA microarray and then validated by quantitative reverse transcriptase-PCR [qRT-PCR]. The functional role of miR-130a-3p in the pathogenesis of CD was then demonstrated by in vitro and in vivo studies. The target genes of miR-130a-3p and the associated signalling pathways were identified using bioinformatics analysis and experimental verification of the interactions between the target predicted by the algorithms and dysregulated mRNAs. The therapeutic role of miR-130a-3p in trinitro-benzene-sulfonic acid [TNBS]-induced colitis models was further investigated. Results Our data demonstrated that miR-130a-3p is the most significantly upregulated miRNA and that miR-130a knockout significantly protects mice against TNBS-induced colitis. Gain- and loss-of-function studies indicated that miR-130a-3p promotes CD development by targeting ATG16L1 via the NF-κB pathway. Furthermore, an miR-130a-3p inhibitor significantly suppressed NLRP3 inflammasome activity by inducing autophagy in a mouse macrophage cell line [RAW264.7]. Therapeutically, an miR-130a-3p inhibitor effectively ameliorated the severity of TNBS-induced colitis. Conclusion Our study reveals that miR-130a-3p promotes CD progression via the ATG16L1/NF-κB pathway and serves as a potential preclinical therapeutic target in CD.

Background People bypass primary healthcare (PHC) institutions to seek expensive healthcare at high-level hospitals, leading to escalating medical costs and inefficient use of resources. In 2009, China launched nationwide synergic policies on primary care strengthening, to tackle access to healthcare and financial protection. This study aimed to assess the impact of the two policy areas, health insurance and health workforce, on healthcare seeking behavior. Methods Drawing on national survey data before (2008) and after (2013) the policies, we linked individual-level data on healthcare-seeking behavior with county-level data on health workforce and health insurance. We constructed a multilevel zero-inflated negative binomial regression to examine the impacts of average reimbursement rate (ARR) of health insurance and the density of registered physicians on outpatient/inpatient visits, and multilevel multinomial logistic regression for the impacts on choice of outpatient/inpatient care providers. Results Although the increase in health insurance ARR and physician density have positive impacts on individuals’ healthcare use, their impacts might be weakened during 2008 and 2013, and the negative impacts of investment of those in PHC institutions on likelihood of visiting hospitals was larger. The negative impacts of ARR at PHC institutions on likelihood of visiting county-, municipal- and higher-level hospitals in 2013 was 28 percentage points, 66 percentage points and 33 percentage points larger than these in 2008. Conclusions Primary care strengthening requires synergic policies. Effective mechanisms for coordination across multisectoral actions are necessities for deepening those policies to ensure efficient delivery of healthcare without experiencing financial risks.

Inflammatory bowel disease (IBD) is a chronic relapsing autoimmune disease that is characterized by segmental intestinal inflammation. There is an urgent need for more efficient inflammation-targeting strategies to improve therapeutic effect and reduce systemic drug exposure. Herein, an oxidation-responsive metal-organic framework material (Ce-MOF@PSS) is reported that preferentially adheres to inflamed intestine via enema. The overproduced reactive oxygen species (ROS) at inflammatory sites induces transformation of Ce-MOF@PSS from mesopore to macropore with local drug release. In experimental colitis, the Ce-MOF@PSS delivery system exhibits excellent inflammation-targeting efficacy and superior therapeutic effect over free drug on suppressing inflammation and repairing intestinal barrier function. Accordingly, by targeting intestinal inflammation, increasing local drug concentrations, scavenging ROS, reducing systemic exposure, and exhibiting excellent safety profiles, it is considered that the Ce-MOF drug delivery platform can be intensively developed as a translational nanomedicine for the management of IBD and other inflammatory diseases.

The link between differences in molecular expression and survival among advanced laryngeal (LSCC) and hypopharyngeal squamous carcinoma (HPSCC) remains unclear. Here, we applied the Surveillance, Epidemiology, and End Results (SEER) program, Isobaric tag for relative and absolute quantitation (iTRAQ) with Liquid chromatography-mass spectrometry (LC–MS/MS) proteomics data and The Cancer Genome Atlas (TCGA) related data to discover the possible disparities between HPSCC and LSCC. Our results showed a significantly worse 5-year overall-survival in HPSCC compared with LSCC before and after adjusting for clinical parameters. 240 differentially expressed proteins were enriched in molecular networks of cytoskeleton remodeling and antigen presentation. Moreover, HPSCC consisted of less T-central-memory cells, T-follicular-helper cells, TGF-β response, and CD4 + T memory resting cells, but more wound healing than LSCC. Furthermore, 9 mRNAs expression were significantly and independently correlated to overall survival in 126 HPSCC and LSCC patients, which was further validated in another cohort of head and neck cancers. These findings support that Immunity signatures as well as pathway networks that include cytoskeleton remodeling and antigen presentation may contribute to the observed differences in survival between HPSCC and LSCC.

Background and AimsThe aim of this study was to investigate the metabolic profile of mesenteric adipocytes and the correlations between key metabolic changes and local inflammation in the context of Crohn’s disease [CD].MethodsMetabolic dysfunction was shown to be regulated by fatty acid desaturase-2 [FADS2], through metabolomics and functional analyses of mesenteric adipose tissue biopsies and primary mesenteric adipocytes isolated from surgical specimens collected from CD patients and control subjects. FADS2 was overexpressed in vitro and in vivo using a lentiviral vector and an adeno-associated virus [AAV], respectively. The interaction between mesenteric adipocytes and inflammation responses was evaluated by establishing a cell coculture system and a FADS2-AAV treated animal model; 3T3-L1 cells were used to elucidate the mechanism underlying FADS2 deregulation.ResultsWe observed significant changes in the levels of metabolites involved in the multi-step synthesis of long-chain polyunsaturated fatty acids [PUFAs]. Gas chromatography analysis revealed impaired desaturation fluxes towards the n-6 and n-3 pathways, which are associated with reduced FADS2 activity in human mesentery tissue. Decreased FADS2 expression at both mRNA and protein levels was confirmed in surgical specimens. The restoration of FADS2 expression, which allows for the endogenous conversion of n-3 fatty acids into proresolving lipid mediators, resulted in a significant reduction in pro-inflammatory macrophage infiltration and attenuated expression of inflammatory cytokines or adipokines.ConclusionsThese findings indicate that impaired fatty acid desaturation and lipid mediator imbalance within mesenteric adipose tissue contributes to chronic inflammation in CD. The therapeutic role of FADS2 may lead to improved CD treatment.

Background The structures of the mesentery including adipose tissue, nerves, and lymphatics play an important role in the pathogenesis and disease progression of Crohn’s disease (CD). Conventional surgical resection for CD usually does not involve resecting the mesentery en bloc with the specimen. This contrasts with complete mesocolic excision (CME) in colorectal cancer, which involves radical resection of the mesentery. Preliminary evidence from smaller studies suggests that applying the principle of mesocolic excision to CD surgery may reduce the risk of postoperative recurrence. This randomized controlled trial is designed to test whether applying the principles of mesocolic excision to CD results in reduced postoperative recurrence. It also aims to evaluate intra- and postoperative morbidity between the two approaches. Methods This international, multicenter, randomized controlled trial will randomize patients (n = 116) scheduled to undergo primary ileocolic resection to either receive extensive mesenteric excision (EME) or conventional ileocolic resection with limited mesenteric excision (LME). Five sites will recruit patients in three countries. In the EME group, the mesentery is resected following CME, while avoiding the root region, i.e., 1 cm from the root of the ileocolic artery and vein. In the LME group, the mesentery is retained, i.e., “close shave” or Discussion If mesocolic excision in CD reduces postoperative disease recurrence and does not increase morbidity, this trial has the potential to change practice and reduce recurrence of CD after surgical resection. Trial registration Clinical Trials.gov, ID: NCT03769922. Registered on February 27, 2019.

The aims of the present study were to examine the density of lymphatic vessels in the mesentery and to assess the predictive value of the mesenteric lymphatic vessel density for postoperative clinical recurrence. Ileocolonic resection specimens were obtained from 53 patients with Crohn’s disease and 10 non-inflammatory bowel disease control subjects. Mesentery adipose tissues adjacent to the bowel wall were used for the histological quantification of lymphatic vessels using immunohistochemistry with the D2-40 antibody. The relationships between lymphatic vessel density and disease behavior, the presence of granulomas, the presence of creeping fat, and postoperative clinical recurrence were assessed. Median lymphatic vessel density in the mesentery adjacent to inflamed or non-inflamed intestine was lower in control subjects than in Crohn’s disease patients (2.13‰; interquartile range [IQR], 1.83–2.61; 8.34‰; IQR, 6.39–10.22; 4.43‰; IQR, 3.32–5.78; P ˂ 0.001). Increased mesenteric lymphatic vessel density was significantly associated with stricturing behavior, the presence of intestinal granulomas, the presence of creeping fat, and bowel thickness. Interestingly, patients with disease recurrence had an increased mesenteric lymphatic vessel density of the proximal mesenteric margin at the time of resection compared with those who did not have disease recurrence (6.23‰; IQR, 5.43–6.75 vs. 3.28‰; IQR, 2.93–4.29; P ˂ 0.001). In addition to its correlation with disease behavior, bowel thickness, and the presence of intestinal granulomas and creeping fat, increased mesenteric lymphatic vessel density in the proximal margin is predictive of early clinical recurrence after surgery in patients with Crohn’s disease.

Background Infective endocarditis (IE) is a life-threatening bacterial infection of the heart valves, most often diagnosed in older persons and persons with prior cardiac surgery. It is also associated with injection drug use, a behavior that has increased in recent years along with the US opioid crisis. Methods We conducted a retrospective cohort analysis of commercial and Medicaid health insurance databases to estimate incident cases of IE in the United States in 2017, stratified by persons living with human immunodeficiency virus (HIV), hepatitis C virus (HCV), and opioid use disorder (OUD). We also estimated annual percentage changes (EAPCs) in IE from 2007–2017 among persons with commercial insurance. Results The weighted incidence rate of IE was 13.8 cases per 100 000 persons among persons with commercial insurance, and 78.7 among those with Medicaid. The incidence rate of IE among commercially insured persons increased slightly from 2007–2017 (EAPC, 1.0%). It decreased among commercially insured persons living with HIV, from 148.0 in 2007 to 112.1 in 2017 (EAPC, −4.3%), and increased among those with HCV infection, from 172.4 in 2007 to 238.6 in 2017 (EAPC, 3.2%). Among persons aged 18–29 years with HCV infection, IE increased from 322.3 in 2007 to 1007.1 in 2017 (EAPC, 16.3%), and among those with OUD it increased from 156.4 in 2007 to 642.9 in 2017 (EAPC, 14.8%). Conclusions The incidence rate of IE increased markedly among young persons with HCV infections or OUD. This increase appears to parallel the ongoing national opioid crisis. Harm reduction with syringe services programs, medications for opioid use disorder, and safe injection practices can prevent the spread of HIV, HCV, and IE.

Background Prox1 is a transcription factor necessary for lymphangiogenesis and lymphatic function. The aim of the study was to assess the correlation between the expression of Prox1 and postoperative recurrence in Crohn's disease [CD]. Methods Forty CD patients who underwent ileo-colonic resection were included. Expression levels of Prox1 and D2-40 were detected using immunohistochemistry. Expression levels of Prox1, VEGFR3, and VEGFC protein were also detected in fresh CD specimens using western blotting and quantitative polymerase chain reaction [Q-PCR]. Endoscopic recurrence was used as the endpoint. Patients comprised two groups: endoscopic recurrence [Group R+] and no endoscopic recurrence [Group R-]. Results Prox1 protein expression was significantly higher in CD than in normal tissues [p

BACKGROUND The role of interleukin-6 (IL-6) in the prediction of intra-abdominal septic complications (IASCs) in patients with Crohn's disease (CD) remains unclear. We assessed the serum IL-6 time course and its association with postoperative IASCs in patients undergoing elective intestinal operations for CD. METHODS In total, 118 patients who underwent intestinal operations for CD were prospectively evaluated. They were divided into an IASC group and non-IASC group. Multivariate analyses were used to identify risk factors, and receiver operating characteristic curve analysis was performed. RESULTS Multivariate analysis showed that a high IL-6 concentration of >137.25 pg/mL on postoperative day (POD) 1 was independently associated with IASCs (odds ratio, 5.74; 95% confidence interval [CI], 1.46-22.67; P = 0.012) and a longer postoperative length of hospitalization (6 vs 9 days, P < 0.001). The median interval between surgery and IASCs (interquartile range) was 6 (4-22) days, and the IL-6 concentration was significantly different between patients with and without IASCs on PODs 1, 3, and 5. The ideal IL-6 cutoff value on POD 1 for the prediction of postoperative IASCs was 137.25 pg/mL, yielding a sensitivity of 81%, specificity of 58%, and area under the curve of 0.71 (95% CI, 0.59-0.83), with a negative predictive value of 0.93. CONCLUSIONS A high IL-6 concentration on POD 1 is independently associated with the occurrence of postoperative IASCs in patients undergoing elective surgery for CD and could allow for earlier diagnosis and earlier intervention for IASCs compared with C-reactive protein.

The comprehensive complication index (CCI) is a novel approach to evaluate complications. However, application of the CCI in inflammatory bowel disease (IBD) population is scarce and the difference between the CCI and the Clavien-Dindo classification (CDC) remains unknown. The aim of this study was to compare the CCI to the conventional CDC by applying the CCI among the IBD patients. The data of 426 IBD patients who underwent surgery between September 1, 2015 and August 31, 2017 were collected. Univariate and multivariate analyses were conducted to identify risk factors for postoperative complications. The efficacy of CCI and CDC was compared using correlation analysis and logistic regression. Cumulative sum control (CUSUM) models were applied to monitor the CCI continuously. Totally, 297 complications occurred in 144 (33.8%) patients. The rate of severe complications (CDC grade ≥ III) was 12.9% and the mean CCI was 9.8 ± 15.5. Preoperative glucocorticoids usage and previous abdominal surgery were related to higher CCI value (p = 0.002, p = 0.006, respectively) but not related to higher incidence of severe complications (CDC grade ≥ III) (p = 0.117, p = 0.177, respectively). In patients with multiple complications, the CCI demonstrated a stronger correlation with hospital stay (ρ = 0.604, p

Hyperactivation of Wnt/β-catenin signaling implicated in oncogenesis of colorectal cancer (CRC) is a potential molecular target for chemotherapy. An andrographolide analogue, 3A.1 (19-tert-butyldiphenylsilyl-8, 17-epoxy andrographolide) has previously been reported to be potently cytotoxic toward cancer cells by unknown molecular mechanisms. The present study explored the anti-cancer activity of analogue 3A.1 on Wnt/β-catenin signaling in colon cancer cells (HT29 cells) which were more sensitive to the others (HCT116 and SW480 cells). Analogue 3A.1 inhibited viability of HT29 cells with IC50 value of 11.1 ± 1.4 μM at 24 h, which was more potent than that of the parent andrographolide. Analogue 3A.1 also suppressed the proliferation of HT29 cells and induced cell apoptosis in a dose-dependent manner. Its apoptotic activity was accompanied with increased expressions of proteins related to DNA damages; PARP-1 and γ-H2AX. In addition, analogue 3A.1 significantly inhibited T-cell factor and lymphoid enhancer factor (TCF/LEF) promoter activity of Wnt/β-catenin signaling. Accordingly, the expressions of Wnt target genes and β-catenin protein were suppressed. Moreover, analogue 3A.1 increased the activity of GSK-3β kinase, which is a negative regulator responsible for degradation of intracellular β-catenin. This mode of action was further supported by the absence of the effects after treatment with a GSK-3β inhibitor, and over-expression of a mutant β-catenin (S33Y). Our findings reveal, for the first time, an insight into the molecular mechanism of the anti-cancer activity of analogue 3A.1 through the inhibition of Wnt/β-catenin/GSK-3β pathway and provide a therapeutic potential of the andrographolide analogue 3A.1 in CRC treatment.