Seizures in Children with Cardiac Disease on Extracorporeal Membrane Oxygenation.

BACKGROUND: Children supported with extracorporeal membrane oxygenation (ECMO) have been shown to be at risk for developing seizures. However, previous studies have consisted of heterogeneous patient populations. We aimed to describe the rate of seizures in pediatric patients receiving ECMO for cardiac indications and to identify risk factors for the occurrence of this complication. METHODS: This is a retrospective cohort study of consecutive pediatric patients on ECMO for congenital or acquired cardiac disease between 2014 and 2018 at a tertiary care pediatric hospital. RESULTS: We reviewed 110 children, of whom 104 (95%) received continuous electroencephalogram for at least 48 h after ECMO initiation. Seizures were observed in 20 (18%) children. Seizures were subclinical only in 13 (65%) patients, and 8 (40%) developed status epilepticus. The median time from ECMO initiation to first seizure was 34 h (25%, 75%: 19, 44). Children with seizures were more likely to have suffered pre-ECMO cardiac arrest (odds ratio 5.7, 95% confidence interval 2.0-16.1, p < 0.001), require extracorporeal cardiopulmonary resuscitation (odds ratio 5.2, 95% confidence interval 1.9-14.7, p < 0.001), and have been cannulated via the cervical vessels (p = 0.029). Children with seizures also had lower pH nadir prior to ECMO (p = 0.015) and had higher peak lactate prior to ECMO (p = 0.002). Patients with seizures had significantly a longer median intensive care unit length of stay, (43 versus 32 days, p = 0.02), had a significantly worse pediatric cerebral performance score (2 versus 1, p = 0.03), and tended to have worse survival to hospital discharge (50% versus 71%, p = 0.069). CONCLUSIONS: Seizures in pediatric patients on ECMO for cardiac indications are common, occurring in nearly one in five patients. Seizures are frequently subclinical only and often progress to status epilepticus. Continuous electroencephalogram is therefore warranted for this patient population, especially in the setting of cardiac arrest, extracorporeal cardiopulmonary resuscitation, or severe metabolic acidosis.

Feasibility and acceptability of an acceptance and commitment therapy intervention for caregivers of adults with Alzheimer's disease and related dementias.

BACKGROUND: Caregivers of patients with Alzheimer's disease or a related dementia (ADRD) report high levels of distress, including symptoms of anxiety and depression, caregiving burden, and existential suffering; however, those with support and healthy coping strategies have less stress and burden. Acceptance and Commitment Therapy (ACT) aims to foster greater acceptance of internal events while promoting actions aligned with personal values to increase psychological flexibility in the face of challenges. The objective of this single-arm pilot, Telephone Acceptance and Commitment Therapy Intervention for Caregivers (TACTICs), was to evaluate the feasibility, acceptability, and preliminary effects of an ACT intervention on ADRD caregiver anxiety, depressive symptoms, burden, caregiver suffering, and psychological flexibility. METHODS: ADRD caregivers ≥21 years of age with a Generalized Anxiety Disorder Scale (GAD-7) score ≥ 10 indicative of moderate or higher symptoms of anxiety were enrolled (N = 15). Participants received a telephone-based ACT intervention delivered by a non-licensed, bachelor's-prepared trained interventionist over 6 weekly 1-h sessions that included engaging experiential exercises and metaphors designed to increase psychological flexibility. The following outcome measures were administered at baseline (T1), immediately post-intervention (T2), 3 months post-intervention (T3), and 6 months post-intervention (T4): anxiety symptoms (GAD-7; primary outcome); secondary outcomes of depressive symptoms (Patient Health Questionnaire-9), burden (Zarit Burden Interview), suffering (The Experience of Suffering measure), psychological flexibility/experiential avoidance (Acceptance and Action Questionnaire-II), and coping skills (Brief COPE). RESULTS: All 15 participants completed the study and 93.3% rated their overall satisfaction with their TACTICs experience as "completely satisfied." At T2, caregivers showed large reduction in anxiety symptoms (SRM 1.42, 95% CI [0.87, 1.97], p < 0.001) that were maintained at T3 and T4. At T4, psychological suffering (SRM 0.99, 95% CI [0.41, 1.56], p = 0.0027) and caregiver burden (SRM 0.79, 95% CI [0.21, 1.37], p = 0.0113) also decreased. CONCLUSIONS: Despite a small sample size, the 6-session manualized TACTICs program was effective in reducing anxiety, suggesting that non-clinically trained staff may be able to provide an effective therapeutic intervention by phone to maximize intervention scalability and reach. TRIAL REGISTRATION: Institutional Review Board (IRB) protocol #1904631305 version 05-14-2019. Recruitment began 06-14-2019 and was concluded on 12-09-2019. Recruitment began 06-14-2019 and was concluded on 12-09-2019.

Retroperitoneal and Pelvic Lymph Nodes in Children: What Is Normal?

OBJECTIVE. The purpose of this study was to evaluate size criteria for retroperitoneal and pelvic lymph nodes in healthy children. MATERIALS AND METHODS. We identified all trauma patients younger than 18 years old without underlying disease and with CT scans without abnormalities in the abdomen and pelvis during 2014-2015. Two pediatric radiologists reviewed the studies independently and recorded the number of retroperitoneal and pelvic lymph nodes with a long diameter 5 mm or greater and the size (two perpendicular diameters) of the largest lymph node in five anatomic locations. Discrepant results were reviewed in consensus. The relationship of short diameter to age and interobserver variability was evaluated. RESULTS. A total of 166 patients (86 boys) with a mean age of 7.2 years old (range, 0.1-18.0 years old) were identified. More than 95% of lymph nodes in the retroperitoneum and pelvis had a short diameter measuring at most 7 and 8 mm, respectively, by consensus. The size of the largest short diameter of lymph nodes did not vary with age. More than four lymph nodes were identified in any anatomic location in only three patients, by only one of the radiologists. Agreement for lymph nodes with largest diameter of 5 mm or greater between radiologists ranged from 70.5% to 97.6% for the five anatomic locations with poor interobserver agreement (κ, 0.2-0.3). CONCLUSION. The size and number of retroperitoneal and pelvic lymph nodes in children are less than in adults. A short diameter threshold of 7 mm (retroperitoneal) and 8 mm (pelvic) and more than four lymph nodes with long diameter of 5 mm or greater in one location may define disease.

A pharmacist-managed cardiovascular risk-reduction clinic for individuals experiencing serious mental illness.

OBJECTIVES: This retrospective analysis sought to: (1) characterize a cardiovascular risk-reduction clinic (CVRRC) patient population with serious mental illness (SMI); (2) analyze clinical outcomes of CVRRC patients over a 2-year period; and (3) compare outcomes for individuals prescribed different antipsychotic treatments in the CVRRC patient population over a 2-year period. EVALUATION METHODS: In 2016, A pharmacist-managed CVRRC was implemented within a primary care clinic for patients with SMI. The CVRRC operates under a collaborative practice agreement allowing the pharmacist to initiate and change medications and order laboratory tests. Baseline data collected included demographic information, referring provider, tobacco use, and 10-year atherosclerotic cardiovascular disease risk. Data collected at subsequent visits included date of visit, A1C, estimated average glucose (eAG), blood pressure, weight, body mass index, low-density lipoprotein cholesterol, non-high-density lipoprotein cholesterol, statin and dose, tobacco use, amount smoked, and current antipsychotic treatment. Number of times that treatment for diabetes was initiated or intensified by the pharmacist or primary care provider was also collected. IMPACT OF INNOVATION: A total of 101 patients were referred to the CVRRC over the 2-year period. Of these, 81 (80.2%) had at least 1 subsequent visit and were included in the A1C analysis. CVRRC patients had a statistically significant improvement in A1C over time. Mean A1C decreased by an increment of 0.06% for each month increase in follow-up time (P < 0.0001). There was no significant difference in A1C values between patients on different antipsychotic treatments (P = 0.74). CONCLUSION: The pharmacist-managed CVRRC demonstrated beneficial outcomes for individuals diagnosed with diabetes and SMI. Results provide promising evidence supporting future larger studies to confirm these findings. Considering the morbidity and mortality disparities for individuals with SMI, health care organizations should consider similar models to improve diabetes outcomes.

Perception of immunizations and vaccine recommendation sources for persons living with HIV compared with persons without HIV.

OBJECTIVES: To measure and compare the perception of immunizations, immunization status, and recommendation sources in persons living with HIV (PLWHs) and persons without HIV and determine a strategy for improving immunization rates by increasing awareness of pharmacy services. DESIGN: A 19-item survey based on the Health Belief Model assessed patients' perceptions and recommendation sources regarding immunization acceptance for specific vaccines: Tdap, pneumococcal, and hepatitis B (HepB). Survey items used a 5-point Likert-type scale assessing participants' perceptions, with questions identifying participants' most trusted sources of immunization information and patient demographics. Survey questions were designed to identify perceived susceptibility and severity of vaccine-preventable illness, barriers, benefits, and self-efficacy regarding immunization acceptance, and sources of patient-trusted immunization information. SETTING AND PARTICIPANTS: Survey recruitment occurred in Indiana and included any patient 18 years of age or older picking up medications at a specialty pharmacy predominantly serving PLWHs or a traditional community chain pharmacy. MAIN OUTCOME MEASURES: Primary outcomes included perceived barriers to immunization acceptance obtained from Likert-type scale questions, patient-reported immunization rates of selected vaccines (Tdap, pneumococcal pneumonia, and HepB), and trusted immunization recommendation sources. Logistic regression was performed to model association between perceived barriers, HIV status, and immunization recommendation sources. RESULTS: A total of 142 participants (68 PLWHs, 74 persons without HIV) completed the survey. PLWHs were more likely to have immunization barriers, but this was not statistically significant (odds ratio 2.537, 95% confidence interval 0.585-10.996). Both participant groups reported "family doctor" as the most trusted source, with only 5% selecting "pharmacist." Significantly fewer PLWHs reported completing the HepB series (18% vs. 52%; P = 0.0224). CONCLUSION: PLWHs possess barriers to immunization acceptance similar to persons without HIV yet report lower rates of HepB vaccine completion. Although pharmacists were less frequently selected as the most trusted source, additional studies on percptions of pharmacists' role in immunizing PLWHs should be considered.

Hepatocyte-specific deletion of BAP31 promotes SREBP1C activation, promotes hepatic lipid accumulation, and worsens IR in mice.

Conditional knockout mice with targeted disruption of B-cell associated protein (BAP)31 in adult mouse liver were generated and challenged with a high-fat diet (HFD) for 36 or 96 days and markers of obesity, diabetes, and hepatic steatosis were determined. Mutant mice were indistinguishable from WT littermates, but exhibited increased HFD-induced obesity. BAP31-deletion in hepatocytes increased the expression of SREBP1C and the target genes, including acetyl-CoA carboxylase 1 and stearoyl-CoA desaturase-1, and increased hepatic lipid accumulation and HFD-induced liver steatosis. Immunoprecipitation assay showed that BAP31 interacts with SREBP1C and insulin-induced gene 1 (INSIG1), and BAP31-deletion reduces INSIG1 expression, suggesting that BAP31 may regulate SREBP1C activity by modulating INSIG1 protein levels. Additionally, BAP31-deletion induced glucose and insulin intolerance, decreased Akt and glycogen synthase kinase 3ß phosphorylation, and enhanced hepatic glucose production in mice. Expression of endoplasmic reticulum (ER) stress markers was significantly induced in BAP31-mutant mice. HFD-induced inflammation was aggravated in mutant mice, along with increased c-Jun N-terminal kinase and nuclear factor-κB activation. These findings demonstrate that BAP31-deletion induces SREBP activation and promotes hepatic lipid accumulation, reduces insulin signaling, impairs glucose/insulin tolerance, and increases ER stress and hepatic inflammation, explaining the protective roles of BAP31 in the development of liver steatosis and insulin resistance in HFD-induced obesity in animal models.

Prevalence and diagnosis rate of intra-abdominal hypertension in critically ill adult patients: A single-center cross-sectional study.

PURPOSE: To investigate the prevalence and diagnosis rate of intra-abdominal hypertension (IAH) in a mixed-population intensive care unit (ICU), and to investigate the knowledge of ICU staff regarding the guidelines published by the World Society of Abdominal Compartment Syndrome (WSACS) in 2013. METHODS: A one-day cross-sectional study based on the WSACS 2013 guidelines was conducted in the general ICU of a tertiary teaching hospital in Chongqing, China. The included patients were divided into intravesical pressure (IVP) measured group and IVP unmeasured group. The epidemiologic data were recorded, and potential IAH risk factors (RFs) were collected based on the guidelines. IVP measurements were conducted by investigators every 4 h and the result was compared to that measured by the ICU staff to evaluate the diagnosis rate. Besides, a questionnaire was used to investigate the understanding of the guidelines among ICU staff. RESULTS: Thirty-two patients were included, 14 in the IVP measured group and 18 in the IVP unmeasured group. The prevalence of IAH during the survey was 15.63% (5/32), 35.71% (5/14) in IVP measured group. Only one case of IAH had been diagnosed by the ICU physician and the diagnosis rate was as low as 20.00%. Logistic regression analysis showed that sequential organ failure assessment (SOFA) score was an independent RF for IAH (OR: 1.532, 95% CI: 1.029-2.282, p=0.036. Fourteen doctors and 5 nurses were investigated and the response rate was 67.86%. The average scores of the doctors and nurses were 27.14±20.16 and 16.00±8.94 respectively. None of them had studied the WSACS 2013 guidelines thoroughly. CONCLUSION: Patients with a higher SOFA score has a higher incidence of IAH. The IAH prevalence in 14 ICU patients with indwelling catheter was 35.71%. Strengthening the wide and rational use of WSACS guideline is important to improve the diagnosis of IAH.

Bayesian order constrained adaptive design for phase II clinical trials evaluating subgroup-specific treatment effect.

The "one-size-fits-all'' paradigm is inappropriate for phase II clinical trials evaluating biotherapies, which are often expected to have substantial heterogeneous treatment effects among different subgroups defined by biomarker. For these biotherapies, the objective of phase II clinical trials is often to evaluate subgroup-specific treatment effects. In this article, we propose a simple yet efficient Bayesian adaptive phase II biomarker-guided design, referred to as the Bayesian-order constrained adaptive design, to detect the subgroup-specific treatment effects of biotherapies. The Bayesian order constrained adaptive design combines the features of the enrichment design and sequential design. It starts with a "all-comers" stage, and subsequently switches to an enrichment stage for either the marker-positive subgroup or marker-negative subgroup, depending on the interim analysis results. The go/no go enrichment criteria are determined by two posterior probabilities utilizing the inherent ordering constraint between two subgroups. We also extend the Bayesian-order constrained adaptive design to handle the missing biomarker situation. We conducted comprehensive computer simulation studies to investigate the operating characteristics of the Bayesian order constrained adaptive design, and compared it with other existing and conventional designs. The results shown that the Bayesian order constrained adaptive design yielded the best overall performance in detecting the subgroup-specific treatment effects by jointly considering the efficiency and cost-effectiveness of the trials. The software for simulation and trial implementation are available for free download.

Patient characteristics and clinical factors affecting lumpectomy cavity volume: implications for partial breast irradiation.

Introduction: Partial breast irradiation (PBI) has increased in utilization, with the postoperative lumpectomy cavity and clips used to guide target volumes. The ideal timing to perform computed tomography (CT)-based treatment planning for this technique is unclear. Prior studies have examined change in volume over time from surgery but not the effect of patient characteristics on lumpectomy cavity volume. We sought to investigate patient and clinical factors that may contribute to larger postsurgical lumpectomy cavities and therefore predict for larger PBI volumes. Methods: A total of 351 consecutive women with invasive or in situ breast cancer underwent planning CT after breast-conserving surgery at a single institution during 2019 and 2020. Lumpectomy cavities were contoured, and volume was retrospectively computed using the treatment planning system. Univariate and multivariate analyses were performed to evaluate the associations between lumpectomy cavity volume and patient and clinical factors. Results: Median age was 61.0 years (range, 30-91), 23.9% of patients were Black people, 52.1% had hypertension, the median body mass index (BMI) was 30.4 kg/m², 11.4% received neoadjuvant chemotherapy, 32.5% were treated prone, mean interval from surgery to CT simulation was 54.1 days ± 45.9, and mean lumpectomy cavity volume was 42.2 cm3 ± 52.0. Longer interval from surgery was significantly associated with smaller lumpectomy cavity volume on univariate analysis, p = 0.048. Race, hypertension, BMI, the receipt of neoadjuvant chemotherapy, and prone position remained significant on multivariate analysis (p < 0.05 for all). Prone position vs. supine, higher BMI, the receipt of neoadjuvant chemotherapy, the presence of hypertension, and race (Black people vs. White people) were associated with larger mean lumpectomy cavity volume. Discussion: These data may be used to select patients for which longer time to simulation may result in smaller lumpectomy cavity volumes and therefore smaller PBI target volumes. Racial disparity in cavity size is not explained by known confounders and may reflect unmeasured systemic determinants of health. Larger datasets and prospective evaluation would be ideal to confirm these hypotheses.

Continuous Glucose Monitoring and Other Wearable Devices to Assess Hypoglycemia among Older Adult Outpatients with Diabetes Mellitus.

BACKGROUND: Hypoglycemia (HG) causes symptoms that can be fatal, and confers risk of dementia. Wearable devices can improve measurement and feedback to patients and clinicians about HG events and risk. OBJECTIVES: The aim of the study is to determine whether vulnerable older adults could use wearables, and explore HG frequency over 2 weeks. METHODS: First, 10 participants with diabetes mellitus piloted a continuous glucometer, physical activity monitor, electronic medication bottles, and smartphones facilitating prompts about medications, behaviors, and symptoms. They reviewed graphs of glucose values, and were asked about the monitoring experience. Next, a larger sample (N = 70) wore glucometers and activity monitors, and used the smartphone and bottles, for 2 weeks. Participants provided feedback about the devices. Descriptive statistics summarized demographics, baseline experiences, behaviors, and HG. RESULTS: In the initial pilot, 10 patients aged 50 to 85 participated. Problems addressed included failure of the glucometer adhesive. Patients sought understanding of graphs, often requiring some assistance with interpretation. Among 70 patients in subsequent testing, 67% were African-American, 59% were women. Nearly one-fourth (23%) indicated that they never check their blood sugars. Previous HG was reported by 67%. In 2 weeks of monitoring, 73% had HG (glucose ≤70 mg/dL), and 42% had serious, clinically significant HG (glucose under 54 mg/dL). Eight patients with HG also had HG by home-based blood glucometry. Nearly a third of daytime prompts were unanswered. In 24% of participants, continuous glucometers became detached. CONCLUSION: Continuous glucometry occurred for 2 weeks in an older vulnerable population, but devices posed wearability challenges. Most patients experienced HG, often serious in magnitude. This suggests important opportunities to improve wearability and decrease HG frequency among this population.

Composition of the Current Academic Radiation Oncology Workforce in Comprehensive Cancer Centers.

PURPOSE: The landscape of the profession of academic radiation oncology is constantly changing. We sought to determine the demographic makeup of the current academic radiation oncology workforce. MATERIALS AND METHODS: Internet web site searches of the 51 National Cancer Institute-designated Comprehensive Cancer Centers (CCCs) were conducted in September 2019. The Scopus database was subsequently searched in December 2019 to ascertain the h-index for each radiation oncologist. Geographic location was economically stratified (New York, California, Massachusetts, Illinois, and Washington DC) as previously reported. Race and binary sex were attributed by authors using publicly available information. Univariate analysis involved the chi-square test; a multivariable model considered several factors including rank and sex. RESULTS: Of 993 radiation oncologists at CCCs, 53.6% are junior faculty, 24.8% associate professors, and 21.7% full professors. The average radiation oncologist at a CCC has been a physician for 19.7 (standard deviation = 11.3) years; 4.7% (47/993) are under-represented minorities. 24.6% of men and 15.5% of women were full professors, a statistically significant difference (P = .001). Of the 51 department chairs, 11.8% are women and 5.6% are under-represented minorities. There are fewer female than male program directors in the most economically stratified locations (P = .02). The mean h-index for all faculty is 17.6 (standard deviation = 16.9), and significantly differs between junior faculty (8.21), associate professors (18.46), and full professors (40.05; P < .0001). It also differs between men (19.35) and women (14.11). On multivariable analysis, sex, academic rank, and a secondary advanced degree were independently significant correlates of h-index. CONCLUSION: Among academic radiation oncologists at CCCs, under 5% are under-represented minorities, men are significantly over-represented among senior faculty, and women have significantly lower h-indices than men.

Transcriptomic Analysis Reveals the Messenger RNAs Responsible for the Progression of Alcoholic Cirrhosis.

Alcohol-associated liver disease is the leading cause of chronic liver disease. We hypothesized that the expression of specific coding genes is critical for the progression of alcoholic cirrhosis (AC) from compensated to decompensated states. For the discovery phase, we performed RNA sequencing analysis of 16 peripheral blood RNA samples, 4 healthy controls (HCs) and 12 patients with AC. The DEGs from the discovery cohort were validated by quantitative polymerase chain reaction in a separate cohort of 17 HCs and 48 patients with AC (17 Child-Pugh A, 16 Child-Pugh B, and 15 Child-Pugh C). We observed that the numbers of differentially expressed messenger RNAs (mRNAs) were more pronounced with worsening disease severity. Pathway analysis for differentially expressed genes for patients with Child-Pugh A demonstrated genes involved innate immune responses; those in Child-Pugh B belonged to genes related to oxidation and alternative splicing; those in Child-Pugh C related to methylation, acetylation, and alternative splicing. We found significant differences in the expression of heme oxygenase 1 (HMOX1) and ribonucleoprotein, PTB binding 1 (RAVER1) in peripheral blood of those who died during the follow-up when compared to those who survived. Conclusion: Unique mRNAs that may implicate disease progression in patients with AC were identified by using a transcriptomic approach. Future studies to confirm our results are needed, and comprehensive mechanistic studies on the implications of these genes in AC pathogenesis and progression should be further explored.

Evaluating the effects of a multidisciplinary transition care management program on hospital readmissions.

PURPOSE: To measure the effect of a pharmacist-initiated transitions of care (TOC) program on rates of 30-day all-cause readmissions and primary care follow-up. METHODS: A retrospective cohort study was conducted to evaluate a pharmacist-initiated TOC program for patients discharged from hospitals of a large health system from September 2015 through July 2016. Discharged patients of 13 primary care physicians (the intervention cohort) received TOC program services, and discharged patients seen by 12 other primary care physicians (the control cohort) received usual care. Patients in both cohorts were followed for 90 days. The primary outcome was 30-day all-cause readmissions, and secondary outcomes were 14-day primary care visits, TOC pharmacist identification and resolution of medication therapy problems (MTPs), and transition care management (TCM) billing. Multivariable modeling was performed to test the associations of patient receipt of TOC services with 30-day readmissions and 14-day primary care visits, with controlling for patient demographics and baseline healthcare utilization. RESULTS: A total of 492 patients received the TOC intervention, and 379 were followed in the usual care cohort. Among intervention patients, 960 MTPs were identified, and 85.7% of identified MTPs were resolved. Moreover, 9% of intervention cohort patients were readmitted within 30 days, compared to 15% of control cohort patients, and this effect was significant in the multivariable model (odds ratio, 1.82; 95% confidence interval, 1.15-2.89; P = 0.0108). Rates of primary care visits did not differ significantly between the groups; 65% of intervention group visits were billed using TCM codes. CONCLUSION: A pharmacist-initiated TOC program was effective in reducing 30-day all-cause readmissions.

[Fractional vegetation cover change based on vegetation seasonal variation correction: A case in Lianjiang County, Fujian Province, China]. / 基于植被信息季节变换的植被覆盖度变化——以福建省连江县为例.

Remote sensing change detection based on fractional vegetation cover (FVC) has become an important way in the research of vegetation and related ecosystems. It is difficult to meet the requirement for optical remote sensing in subtropical areas because of cloudy/rainy weather conditions. Using images from different seasons in the vegetation change detection will inevitably lead to errors in the change detection results due to the seasonal difference. To overcome this problem, we proposed a method for correcting vegetation seasonal variations by taking advantage of high temporal resolution advantage of MODIS remote sensing data and the high spatial resolution of remote sensing data. Based on the relationship between MODIS vegetation data in different seasons via regression analysis, we transformed the vegetation information of the high resolution images of corresponding years to the required season of the years. The method was applied in the Aojiang basin area of Lianjiang County in Fujian Province, China, with good results of vegetation information transformation. The results showed that after transforming vegetation information of the 2007 winter scene and 2013 spring scene of high resolution images to those of summer season, the FVC was enhanced from 66.5% to 79.7% for 2007, and from 58.6% to 77.9% for 2013. Our method effectively removed the seasonal difference of FVC and improved the accuracy of the FVC-based change detection results.

Worldwide Frequency of Commonly Detected EGFR Mutations.

CONTEXT: - Recurrent epidermal growth factor receptor ( EGFR) mutations are seen in a subset of pulmonary adenocarcinomas. These mutations are targeted by EGFR inhibitors and are a biomarker for response to EGFR inhibitor therapies. Initial data have indicated an increased frequency of activating EGFR mutations in nonsmoking Asian females. However, there are very few studies of global scope that address the question of mutation distribution across the population of lung cancer. OBJECTIVE: - To determine the frequency of EGFR mutations in exons 18 through 21 detected in clinical laboratories participating in the College of American Pathologists proficiency testing program for EGFR in calendar year 2013. DESIGN: - We reviewed the surveys from 170 clinical laboratories from 20 countries that participated in the College of American Pathologists EGFR proficiency testing program. The proficiency testing includes questions regarding the total numbers of tests performed at each common mutation site, including both activating and resistance mutations, and their frequency. Countries were grouped into regional groups in order to assess frequency of mutation by type, and to indirectly assess ethnic differences in mutation frequencies. RESULTS: - Among the treatment-sensitive activating mutations, the most common are exon 19 mutations (n = 10 802 of 136 533 cases; 7.9% of total cases tested) and the exon 21 L858R mutation (n = 10 351 of 136 533 cases; 7.6% of total cases tested) and the least common are exon 20 mutations (n = 466 of 136 533 cases; 0.3% of total cases tested). The T790M mutation in exon 20 is the more common resistance mutation (n = 1010 of 136 533 cases; 0.7% of all cases tested). The highest activating mutation frequency is seen in southern Asia (n = 4260 of 9337 cases; 46%) and the lowest activating mutation frequencies are in South and North America (n = 113 of 1439 cases and 7926 of 86 654 cases; 8% and 9%, respectively). CONCLUSIONS: - Our data confirm that activating EGFR mutations are more common in southern Asia and that the distribution of activating EGFR mutations varies significantly across the regions. Similarly, the frequency and distribution of resistance mutations also show significant variation when comparing southern Asia with other regions.

BAP31 is involved in T cell activation through TCR signal pathways.

BAP31 is a ubiquitously expressed endoplasmic reticulum (ER) membrane protein. The functions of BAP31 in the immune system have not been investigated due to the lack of animal models. Therefore we created a BAP31 conditional knockdown mouse by performing a knockdown of BAP31 in the thymus. In doing so, we demonstrate that the maturation of T cells is normal but the number of T cells is less in the thymus of the knockout mouse. In addition, the spleen and lymph nodes of peripheral immune organs contained a lesser proportion of the mature T cells in the thymus specific BAP31 knockout mice. The BAP31 knockout T cells decreased the proliferation activated by TCR signal pathways. Further studies clarified that BAP31 affects the phosphorylation levels of both Zap70/Lck/Lat of the upstream members and Akt/GSK/Jnk/Erk of the downstream members of TCR signal pathways. Furthermore, BAP31 can regulate the expression of some markers such as CD3/TCRα/TCRß and some cytokines like IL-2/IFN-γ/IL-6/TNF-α which are important for T cell activation. Taken together, these results demonstrate that BAP31 may play an important role in T cell activation by regulating TCR signaling.

The effect of different types of abdominal binders on intra-abdominal pressure.

OBJECTIVES: To investigate the effect of non-elastic/elastic abdominal binders on intra-vesical pressure (IVP), physiological functions, and clinical outcomes in laparotomy patients at the perioperative stage.  METHODS: This prospective study was conducted from May to October 2014 at the Trauma Surgery Department, Daping Hospital, Chongqing, China. Laparotomy patients were randomly divided into non-elastic abdominal binder group (28 patients), and elastic abdominal binder group (29 patients). Binders were applied for 14 days following the operation, or until discharge. Demographic information, Sequential Organ Failure Assessment (SOFA) and Acute Physiology and Chronic Health Evaluation  II (APACHE-II) scores (prior to the operation, on the first day after operation, the day IVP measurement was stopped, and one day before discharge), and outcomes were recorded. The IVP was measured before the operation to postoperative day 7. RESULTS: There were no significant differences in the demographic information, outcomes, SOFA or APACHE-II scores between the 2 groups. Initial out-of-bed mobilization occurred earlier in the elastic binder group (3.2 ± 2.0 versus 5.0 ± 3.7 days, p=0.028). A greater increase in IVP was observed in the non-elastic binder group than in the elastic binder group (2.9 ± 1.1 versus 1.1 ± 0.7 mm Hg, p=0.000). CONCLUSION: Elastic binders have relatively little effect on IVP and are more helpful at promoting postoperative recovery than non-elastic binders. Therefore, elastic binders are more suitable for clinical use.

Study of intra-abdominal hypertension prevalence and awareness level among experienced ICU medical staff.

BACKGROUND: Intra-abdominal hypertension (IAH) is a disease with high morbidity and mortality among critically ill patients. The study's objectives were to explore the prevalence of IAH and physicians' awareness of the 2013 World Society of Abdominal Compartment Syndrome (WSACS) guidelines in Chinese intensive care units (ICUs). METHODS: A cross-sectional study of four ICUs in Southwestern China was conducted from June 17 to August 2, 2014. Adult patients admitted to the ICU for more than 24 h, with bladder catheter but without obvious intravesical pressure (IVP) measurement contraindications, were recruited. Intensivists with more than 5 years of ICU working experience were also recruited. Epidemiological information, potential IAH risk factors, IVP measurements and questionnaire results were recorded. RESULTS: Forty-one patients were selected. Fifteen (36.59 %) had IVP ≥ 12 mmHg. SOFA (Sequential Organ Failure Assessment) hepatic and neurological sub-scores were utilized as independent predictors for IAH via logistic backward analysis. Thirty-seven intensivists participated in the survey (response rate: 80.43 %). The average score of each center was less than 35 points. All physicians believed the IAH prevalence in their departments was no more than 20.00 %. A significant negative correlation was observed between the intensivists' awareness of the 2013 WSACS guidelines and the IAH prevalence in each center (r = -0.975, P = 0.025). CONCLUSIONS: The prevalence and independent predictors of IAH among the surveyed population are similar to the reports in the literature. Intensivists generally have a low awareness of the 2013 WSACS guidelines. A systematic guideline training program is vital for improving the efficiency of the diagnosis and treatment of IAH.

Neuropharmacological properties of neurons derived from human stem cells.

Human pluripotent stem cells have enormous potential value in neuropharmacology and drug discovery yet there is little data on the major classes and properties of receptors and ion channels expressed by neurons derived from these stem cells. Recent studies in this lab have therefore used conventional patch-clamp electrophysiology to investigate the pharmacological properties of the ligand and voltage-gated ion channels in neurons derived and maintained in vitro from the human stem cell (hSC) line, TERA2.cl.SP12. TERA2.cl.SP12 stem cells were differentiated with retinoic acid and used in electrophysiological experiments 28-50 days after beginning differentiation. HSC-derived neurons generated large whole cell currents with depolarizing voltage steps (-80 to 30 mV) comprised of an inward, rapidly inactivating component and a delayed, slowly deactivating outward component. The fast inward current was blocked by the sodium channel blocker tetrodotoxin (0.1 µM) and the outward currents were significantly reduced by tetraethylammonium ions (TEA, 5 mM) consistent with the presence of functional Na and K ion channels. Application of the inhibitory neurotransmitters, GABA (0.1-1000 µM) or glycine (0.1-1000 µM) evoked concentration dependent currents. The GABA currents were inhibited by the convulsants, picrotoxin (10 µM) and bicuculline (3 µM), potentiated by the NSAID mefenamic acid (10-100 µM), the general anaesthetic pentobarbital (100 µM), the neurosteroid allopregnanolone and the anxiolytics chlordiazepoxide (10 µM) and diazepam (10 µM) all consistent with the expression of GABA(A) receptors. Responses to glycine were reversibly blocked by strychnine (10 µM) consistent with glycine-gated chloride channels. The excitatory agonists, glutamate (1-1000 µM) and NMDA (1-1000 µM) activated concentration-dependent responses from hSC-derived neurons. Glutamate currents were inhibited by kynurenic acid (1 mM) and NMDA responses were blocked by MgCl(2) (2 mM) in a highly voltage-dependent manner. Together, these findings show that neurons derived from human stem cells develop an array of functional receptors and ion channels with a pharmacological profile in keeping with that described for native neurons. This study therefore provides support for the hypothesis that stem cells may provide a powerful source of human neurons for future neuropharmacological studies.