Cyclophosphamide in refractory autoimmune hepatitis and autoimmune hepatitis coexisting extrahepatic autoimmune disorders: A review.

INTRODUCTION AND OBJECTIVES: Despite tacrolimus (TAC) or mycophenolate mofetil (MMF) for alternate approaches, a proportion of patients still required further exploration of other therapeutic options due to uncontrolled autoimmune hepatitis(AIH). The role of cyclophosphamide (CYC) for AIH has been explored in isolated case reports and small series. We present a review of CYC therapy in AIH patients. MATERIALS AND METHODS: A search for studies with keywords 'autoimmune hepatitis' and 'cyclophosphamide' was performed. Data recorded included gender, age, laboratory parameters and histological findings at the time of AIH diagnosis and before initiation of CYC therapy. RESULTS: We identified 13 patients across 7 studies who met criteria for study inclusion, of whom around 69.2% (9/13) were primary refractory; 30.8% (4/13) patients used CYC as rescue therapy due to their coexisting autoimmune complications. The main findings of the study were that CYC appears to have an acceptable safety profile in difficult-to-treat AIH patients, with an overall remission rate of 88.9% (8/9). The other four patients with AIH accompanied by extrahepatic autoimmune disorders also achieved remission of transaminase levels and stability of liver function after the addition of CYC. A positive response to CYC treatment was seen in 12(92.3%) patients and none of them relapsed during the follow-up. CONCLUSIONS: We cautiously recommend that CYC could be a conditioning alternative to starting second-line therapy after unsuccessful intensification of first-line treatment. Pharmacogenetic methods may play a role in guiding cyclophosphamide therapy. Given our small sample size, results should be considered preliminary.

Nonlinear Relationship Between Low Density Lipoprotein and the Probability of Diabetic Macular Edema.

Purpose: Previous studies simply linearized the relationship between low density lipoprotein (LDL) and diabetic macular edema's (DME) probability, ignoring the possibility of a nonlinear relationship between them. We aimed to investigate the nonlinear relationship between LDL and DME probability in patients with type 2 diabetes mellitus (T2DM). Patients and methods: The study recruited 431 T2DM patients who attended Guangdong Provincial People's Hospital from December 2017 to November 2018. A multivariate logistic regression model was conducted to evaluate the association between LDL and DME probability. The nonlinear relationship was identified by generalized additive model. Subgroup analyses were performed to assess the consistency of the association in different subgroups. Results: LDL was positively associated with DME probability (OR=1.60, 95% CI: 1.10~2.34, P=0.0145) after adjusting for covariates. A nonlinear relationship between LDL and DME probability was discovered, with an inflection point for LDL around 4.85 mmol/L (95% CI: 4.18~4.93, P=0.037). The effect sizes and the confidence intervals on the left and right sides of inflection point were 2.17 (1.31 to 3.58) and 0.26 (0.04 to 1.77), respectively. Subgroup analyses revealed other variables had no effect on the association between them. Conclusion: Our finding suggested LDL was positively correlated with DME probability in T2DM patients. And the relationship between LDL and DME probability was nonlinear. Our findings need to be confirmed by further causal researches.

Getting the Most Out of Your Medical Education Survey: 11 Tips From the Association of Pediatric Program Directors Research and Scholarship Learning Community.

OBJECTIVE: Surveys in medical education are commonplace. However, survey studies often lack scientific rigor. Well-designed surveys can ensure improved response rates and higher likelihood of dissemination. The purpose of this paper is to provide guidance for investigators planning to survey pediatric residency leaders METHODS: We examined the Association of Pediatric Program Directors Research and Scholarship Learning Community (APPD-RSLC) submissions, acceptances, and outcomes between 2015 and 2020. Additionally, we performed a literature review of survey design methods with the help of a research librarian. We established a list of tips and settled on the 11 included here by group discussion and consensus. CONCLUSION: These 11 tips provide specific recommendations for successful design of medical education surveys distributed by the APPD based on experience from current and former leaders of the RSLC and literature review in survey design and implementation.

Taking Our Pulse: Examining 5 Years of Data from the Association of Pediatric Program Directors Research and Scholarship Learning Community.

BACKGROUND: The Association of Pediatric Program Directors Research and Scholarship Learning Community (RSLC) prioritizes and comprehensively reviews medical education surveys directed to residency program leadership. Each survey is reviewed by two members of RSLC and the Chair and Vice Chair using a standardized scoring rubric and a limited number of surveys are accepted per cycle. METHODS: Internal review data from 2015 to 2020 were analyzed to determine factors associated with survey acceptance, and for surveys accepted for distribution, determine factors associated with response rates or dissemination status. One-Way analysis of variance (ANOVA) assessed differences in evaluation scores by initial determination status. T-tests and Pearson Product Correlation assessed associations between evaluation scores and response rates by dissemination status. RESULTS: The majority (47/81; 58%) of surveys submitted to RSLC are eventually accepted for distribution. Response rates for distributed surveys varied between 14% and 73%. Most (35/47; 74%) surveys distributed through RSLC are presented (62%) and/or published (60%). Higher review scores were associated with acceptance for distribution but not with response rates or dissemination status. CONCLUSION: Most surveys are eventually accepted by RSLC for distribution and those distributed often get published or presented despite variability in response rates.

FOXO1 regulates NLRP3 inflammasome proteins in LPS-induced cardiotoxicity.

OBJECTIVE: Forkhead box protein O1 (FOXO1) has been shown to regulate multiple proteins in various cardiovascular disease processes. However, the effect of FOXO1 on lipopolysaccharide (LPS)-induced cardiotoxicity remains unknown. The aim of this study was to explore the impact of FOXO1 on LPS-induced cardiotoxicity. METHODS: Rat-derived H9c2 cells were subjected to LPS, and the manipulation of FOXO1 was achieved through overexpression and knockdown using the adeno-associated virus system and siRNA, respectively. Western blotting and quantitative real-time polymerase chain reaction were utilized to examine the inhibitory effect of FOXO1. Cell viability was examined utilizing Cell Counting Kit-8 assay. The changes of apoptosis were examined utilizing Annexin V-FITC/PI method. The levels of pro-inflammatory cytokines, including interleukin (IL)-1ß, IL-18, and tumor necrosis factor-α in the H9c2 cells were measured using ELISA kits. Reactive oxygen species (ROS) generation was quantified using the 2'-7'dichlorofluorescin diacetate assay kit. RESULTS: In H9c2 cells treated with LPS, FOXO1 expression was downregulated in a dose-dependent and time-dependent manner. Overexpression of FOXO1 attenuated LPS-induced apoptosis, oxidative stress injury, and cardiomyocyte inflammation, while FOXO1 inhibition aggravated these processes. Additionally, FOXO1 was found to regulate LPS-related myocardial injury by downregulating the expression of NLR family pyrin domain-containing 3 (NLRP3). CONCLUSION: FOXO1 overexpression attenuated apoptosis, ROS generation, and inflammation, whereas FOXO1 inhibition aggravated LPS-induced cardiomyocyte injury via the NLRP3 inflammasome signaling pathway.

A scoping review of social media in child, adolescents and young adults: research findings in depression, anxiety and other clinical challenges.

BACKGROUND: Social media and other technologies are reshaping communication and health. AIMS: This review addresses the relationship between social media use, behavioural health conditions and psychological well-being for youth aged <25 years. METHOD: A scoping review of 11 literature databases from 2000 to 2020 explored research studies in youth in five areas: clinical depression and anxiety, quantitative use, social media mode, engagement and qualitative dimensions and health and well-being. RESULTS: Out of 2820 potential literature references, 140 met the inclusion criteria. The foci were clinical depression and anxiety disorders (n = 78), clinical challenges (e.g. suicidal ideation, cyberbullying) (n = 34) and psychological well-being (n = 28). Most studies focused on Facebook, Twitter, Instagram and YouTube. Few studies are longitudinal in design (n = 26), had comparison groups (n = 27), were randomised controlled trials (n = 3) or used structured assessments (n = 4). Few focused on different youth and sociodemographic populations, particularly for low-income, equity-seeking and deserving populations. Studies examined association (n = 120; 85.7%), mediating (n = 16; 11.4%) and causal (n = 4; 2.9%) relationships. Prospective, longitudinal studies of depression and anxiety appear to indicate that shorter use (≤3 h/day) and purposeful engagement is associated with better mood and psychological well-being. Depression may predict social media use and reduce perception of support. Findings provide families, teachers and providers ways to engage youth. CONCLUSIONS: Research opportunities include clinical outcomes from functional perspective on a health continuum, diverse youth and sociodemographic populations, methodology, intervention and privacy issues. More longitudinal studies, comparison designs and effectiveness approaches are also needed. Health systems face clinical, training and professional development challenges.

Are Final Residency Milestones Correlated With Early Fellowship Performance in Pediatrics?

PURPOSE: Milestones have been used to assess trainees across graduate medical education programs and reflect a developmental continuum from novice to expert. This study examined whether residency milestones are correlated with initial fellowship milestone performance in pediatrics. METHOD: This retrospective cohort study used descriptive statistics to assess milestone scores from pediatric fellows who began fellowship training between July 2017 and July 2020. Milestone scores were obtained at the end of residency (R), middle of the first fellowship year (F1), and end of the first fellowship year (F2). RESULTS: Data represent 3,592 unique trainees. High composite R scores, much lower F1 scores, and slightly higher F2 scores were found over time for all pediatric subspecialities. R scores were positively correlated with F1 scores (Spearman ρ = 0.12, P < .001) and F2 scores (Spearman ρ = 0.15, P < .001). Although scores are negligibly different when trainees graduate from residency, there were differences in F1 and F2 scores among fellows in different specialties. Those who trained at the same institution for residency and fellowship had higher composite milestone F1 and F2 scores compared with those who trained at different institutions ( P < .001). The strongest associations were between R and F2 scores for the professionalism and communication milestones, although associations were still relatively weak overall (r s = 0.13-0.20). CONCLUSIONS: This study found high R scores and low F1 and F2 scores across all shared milestones, with weak association of scores within competencies, indicating that milestones are context dependent. Although professionalism and communication milestones had a higher correlation compared with the other competencies, the association was still weak. Residency milestones may be useful for individualized education in early fellowship, but fellowship programs should be cautious about overreliance on R scores due to the weak correlation with F1 and F2 scores.

Effects of comfort nursing on pain and quality of life in children undergoing tonsillectomy.

OBJECTIVE: To observe the effect of comfort nursing on pain, quality of life, and nutritional status in children undergoing tonsillectomy. METHODS: In this retrospective study, a total of 114 children who underwent tonsillectomy in Chun'an Hospital of Traditional Chinese Medicine were divided into a research group and a control group according to the nursing methods, with 57 cases in each group. The control group received routine nursing care, and the research group received additional comfort nursing. We compared the pain level (assessed by visual analogue scale (VAS) scale), quality of life (assessed by Generic Quality of Life Inventory-74 (GQOLI-74)), relevant clinical indicators (postoperative swallowing recovery time, wake-up time, and hospital stay), nutrition indicators (total blood protein and albumin), sleep quality (assessed by Pittsburgh Sleep Quality Index (PAQI)), nursing satisfaction, and postoperative complications between the two groups. RESULTS: After postoperative nursing, the VAS scores and PSQI scores were significantly decreased (both P<0.05), and the GQOLI-74 scores were significantly increased (P<0.05) in both groups. The postoperative swallowing recovery time, wake-up time, and hospital stay in the research group were significantly shorter than those in the control group (all P<0.05). The levels of total serum protein and albumin in the research group were significantly higher than those in the control group (both P<0.05). The research group showed a significantly higher satisfaction rate and lower incidence of complications as compared with the control group (both P<0.05). The results of the logistic regression analysis showed that postoperative upper respiratory infection and the degree of tonsillar embedment were independent risk factors for hemorrhage after tonsillectomy (P<0.05). CONCLUSION: In children undergoing tonsillectomy, providing comfort nursing can significantly reduce pain and improve their quality of life.

Gynecological prevention and control model based on ward rearrangement and zoning management in pandemic period of COVID-19.

By April 25, 2020, the outbreak of COVID-19 caused 2,719,897 confirmed cases and 18,7705 deaths globally, remarkably more than severe acute respiratory syndrome (SARS) (8273 cases, 775 deaths) and middle east respiratory syndrome (MERS) (1139 cases, 431 deaths) in 2003 and 2013, respectively. Gynecology is a specialty department with many critical and severe patients. Consequently, it is of preeminent importance to formulate the in-patient management process. Rearranging the gynecological wards and managing ward partition, as well as the medical protection measures in specialized areas, are suitable for the current prevention and control for COVID-19 pandemic and the therapeutic requirements of patients. To effectively minimize nosocomial infections during the COVID-19 pandemic period, our department implemented a novel prevention strategy based on the ward redesign and partition management. With this model, our department effectively protected the safety and health of patients and medical care staff from cross and nosocomial infection in the hospital. Now we would like to share the experience and strategies we implemented as following.

Enhancing Learner Engagement Through Experiential Learning With Learner-Generated Data.

Integrating self-generated learner data into hands-on curricula enhances learner engagement with material and self-assessed learning. Using learner self-generated data to enhance learner engagement can have widespread applicability and benefit for use in design of educational curricula.

COVID-19 Pandemic Impact on Pediatricians Entering the Pediatric Workforce.

OBJECTIVE: Determine extent of impact of coronavirus disease 2019 (COVID-19) pandemic on career choice and employment of pediatricians entering pediatric workforce. METHODS: A national, cross-sectional electronic survey of pediatricians registering for the 2021 American Board of Pediatrics initial general certifying examination on the impact of the COVID-19 pandemic on 3 aspects of career (career choice, employment search, employment offers) was performed. Data were analyzed using descriptive statistics and multivariate logistic regression to determine factors associated with the pandemic's impact on career. Thematic analysis was used to generate themes for open-ended survey questions. RESULTS: Over half (52.3%, 1767 of 3380) of pediatricians responded. Overall, 29.1% reported that the pandemic impacted their career (career choice [10.4%], employment search [15.6%], or employment offers [19.0%]); applicants to general pediatrics (GP) (52.9%) or pediatric hospitalist (PH) positions (49.3%) were most affected. Multivariate logistic regression modeling found those applying to GP (odds ratio [OR]: 3.83, 95% confidence interval [CI]: 2.22-6.60), PH (OR: 9.02, 95% CI: 5.60-14.52), and International Medical Graduates (IMGs) (OR: 1.90; 95% CI: 1.39-2.59) most likely to experience any career impact. CONCLUSIONS: Almost one third of pediatricians registering for the initial general pediatrics certifying examination reported their careers were impacted by the COVID-19 pandemic, with 10% of respondents reporting the pandemic impacted their career choice. Half of new pediatricians seeking employment reported being impacted by the pandemic, particularly IMGs. As the pandemic evolves, career advising will continue to be critical to support trainees in their career choices and employment.

ArfGAP3 regulates vesicle transport and glucose uptake in myoblasts.

Skeletal muscle injuries are common, and damaged myofibers are repaired through proliferation and differentiation of muscle satellite cells. GLUT4 is enriched in GLUT4 storage vesicles (GSVs) and plays a crucial role in the maintenance of muscle function. ArfGAP3 regulates the vesicle transport especially for COPI coat assembly, but its effects on GSVs and the repair process after skeletal muscle injury remains unclear. In this study, datasets related to skeletal muscle injury and myoblast differentiation GSE469, GSE5413, GSE45577 and GSE108040 were retrieved through the GEO database and the expression of heptameric coat protein complex I (COPI) and Golgi vesicle transport-related genes in various datasets, as well as the expression correlation between ArfGAP2, ArfGAP3 and COPI-related genes COPA, COPB1, COPB2, COPE, COPZ1, COPZ2 were analyzed. The results suggested that ArfGAP3 was expressed in the process of repair after skeletal muscle injury and myoblast differentiation and that ArfGAP3 was positively correlated with COPI-related genes. In vitro experimental results showed that ArfGAP3 was colocalized with COPA, COPB, COPG protein, and GLUT4 in C2C12 myoblasts. After the downregulation of ArfGAP3 expression, intracellular vesicle transport, and glucose uptake were blocked, the proliferation of myoblasts under low glucose culture conditions was impaired, the proportion of apoptosis increased, and myotube differentiation was impaired. In summary, ArfGAP3 regulates COPI-associated vesicle and GSVs transport and affects the proliferation and differentiation ability of myoblasts by influencing glucose uptake, thereby modulating the repair process after skeletal muscle injury.

The Early Effects of the Coronavirus Disease-19 Pandemic on Pediatric Resident Education: A National Assessment.

PURPOSE: Residency programs must ensure resident competence for independent practice. The coronavirus disease-19 (COVID-19) pandemic disrupted health care delivery, impacting pediatric residencies. This study examines the impact on pediatric resident education. METHODS: The authors conducted a mixed methods national survey of pediatric residency program directors (PDs) from May 2020 to July 2020. Data analysis included descriptive statistics, chi-square, and Wilcoxon rank sum tests. Multivariable modeling identified factors associated with resident preparation for more senior roles. Thematic analysis was performed on open-ended questions about PD COVID-19 pandemic recommendations to peers, Accreditation Council for Graduate Medical Education and American Board of Pediatrics. RESULTS: Response rate was 55% (110/199). PDs reported the COVID-19 pandemic negatively affected inpatient (n = 86, 78.2%), and outpatient education (n = 104, 94.5%), procedural competence (n = 64; 58.2%), and resident preparation for more senior roles (n = 50, 45.5%). In bivariate analyses, increasingly negative impacts on inpatient and outpatient education were associated with an increasingly negative impact on resident preparation for more senior roles (P = .03, P = .008), these relationships held true in multivariable analysis. Qualitative analysis identified 4 themes from PD recommendations: 1) Clear communication from governing bodies and other leaders; 2) Flexibility within programs and from governing bodies; 3) Clinical exposure is key for competency development; 4) Online platforms are important for education, communication, and support. CONCLUSIONS: The COVID-19 pandemic negatively impacted inpatient and outpatient education. When these were more negatively impacted, resident preparation for more senior roles was worse, highlighting the importance of competency based medical education to tailor experiences ensuring each resident is competent for independent practice.

In vitro antibacterial effect of vancomycin hydrogel on methicillin-resistant Staphylococcus aureus.

OBJECTIVE: To evaluate the in vitro antibacterial effect of vancomycin hydrogel on methicillin-resistant Staphylococcus aureus (MRSA). METHODS: We used polylactide glycolide-polyethylene glycol-polylactide glycolide (PLGA-PEG-PLGA) copolymer as a carrier of vancomycin to prepare vancomycin hydrogel. A vancomycin hydrogel group, a PLGA-PEG-PLGA copolymer group, a phosphate-buffered saline (PBS) negative control group and a vancomycin group were set for comparison. Then, we analyzed the in vitro antibacterial effect of each group to determine the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) and to evaluate the effect of vancomycin hydrogel on the cell activity of bacterial biofilms. RESULTS: The temperature of the successfully prepared PLGA-PEG-PLGA vancomycin copolymer was slightly lower than normal body temperature. The copolymer reduced both MIC (1 µg/mL) and MBC (2 µg/mL) for MRSA by 1 time. Compared with phosphate buffered saline negative control group and PLGA-PEG-PLGA copolymer group, the MIC vancomycin and vancomycin hydrogel groups showed a reduction of 3 CFU/mL (P<0.05) on the inhibitory effect of original colony count (106 CFU/mL). Though the antibacterial effect of MIC the vancomycin group was significantly better than the vancomycin hydrogel group in the first 12 h, the antibacterial effects of the two were similar after 12 hours. The effect of 1 MIC vancomycin on the cell activity of MRSA biofilm was higher than that of 1 MIC vancomycin hydrogel (P<0.05). CONCLUSION: Vancomycin hydrogel with a reduced dosage has a similar antibacterial effect to vancomycin. This finding provides a reference for the development of novel sustained-release vancomycin formulations in future treatment of MRSA.

Effect of Pei Yuan Tong Nao capsules on cerebral infarction: A protocol for systematic review and meta-analysis.

BACKGROUND: Pei Yuan Tong Nao (PYTN) capsules has been widely used for the treatment of cerebrovascular disease, including cerebral infarction. However, the mechanisms of action of PYTN capsule on cerebral infarction are ambiguous and unclear. We conducted a protocol for systematic review and meta-analysis to evaluate the efficacy and safety of PYTN capsules for the treatment of cerebral infarction. METHODS: A comprehensive search of several databases from 1966 to February 2022 will be conducted. The databases includes Ovid Medline In-Process & Other NonIndexed Citations, Ovid MEDLINE, Ovid EMBASE, Ovid PsycINFO, Ovid Cochrane Central Register of Controlled Trials, Ovid Cochrane Database of Systematic Reviews, and Scopus. Two authors independently performed the literature searching, data extraction, and quality evaluation. The risk of bias in each included study will be assessed utilizing the Cochrane Collaboration's risk of bias tool. The Review Manager 5.3 (Cochrane Collaboration, Oxford, UK) will be used to analyze the data. RESULT: A synthesis of current evidence of PYTN capsules for cerebral infarction will be provided in this protocol. CONCLUSION: This review will provide more reliable references to help clinicians make decisions when dealing with cerebral infarction.