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[Clinical Development of Immune Checkpoint Inhibitors in Patients with Small Cell Lung Cancer].

[Clinical Development of Immune Checkpoint Inhibitors in Patients with Small Cell Lung Cancer].

Zhongguo fei ai za zhi = Chinese journal of lung cancer 20(9) 623-628 doi 10.3779/j.issn.1009-3419.2017.09.06 Abstract Small cell lung cancer (SCLC) is a poorly differentiated high-grade neuroendocrine tumor, accounts for approximately 14% of all lung cancers. SCLC is characterized by rapid growth, early metastasis without effective treatments after recurrence. It is urgently need to improve the therapy of patients with SCLC. In recent years Tumor immunotherapy has shown promising efficacy, especially in immune checkpoints including inhibitors programmed cell-death protein 1 (PD-1) and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4). These immune checkpoint inhibitors of the researches are changing the clinical practice of many kinds of solid tumor. SCLC is a potential ideal type of tumor immunotherapy for tobacco exposure and the highest mutational load. In this report, the authors review the current state of the immunotherapy in SCLC, to discussing the problems, challenge and application development...
[Role of Hippo Signaling Pathway in Lung Cancer].

[Role of Hippo Signaling Pathway in Lung Cancer].

Zhongguo fei ai za zhi = Chinese journal of lung cancer 20(9) 629-634 doi 10.3779/j.issn.1009-3419.2017.09.07 Abstract Lung cancer is the leading cause of cancer related mortality in the world, with more than 1 million deaths per year, accounting for about one fifth of all cancer deaths worldwide. Over the past years, lung cancer treatment has been based on surgery, radiation therapy, chemotherapy, targeted therapies, and immunotherapy, but the improvement is not very perfect. Therefore, it has become clear that additional therapeutic strategies are urgently required to provide an improved survival benefit for patients. In recent years, Hippo signaling pathway has become a popular direction in the field of cancer research. When the Hippo pathway is active, the core Hippo kinase, such as MST/MOB and LATS1/2, inhibit the two transcriptional co-activators, YAP/TAZ. And YAP/TAZ are phosphorylated and sequestered in the cytoplasm. Dysregulation of the Hippo pathway drives multiple aspects of lung tumor initiation and progression. Moreover, the potential value of this pathway is getting more and more prevalent in clinical application. In this review, we summarize the molecular mechanism and the core components, upstream or downstream targets of Hippo signaling pathway which contribute the formation of lung cancer and discuss the therapeutic potential of targeted strategies in lung cancer. Additionally, we highlight the prospect of research on Hippo signaling pathway in the...
[Progress of Epigenetic Methylation in Lung Cancer Research].

[Progress of Epigenetic Methylation in Lung Cancer Research].

Zhongguo fei ai za zhi = Chinese journal of lung cancer 20(9) 635-640 doi 10.3779/j.issn.1009-3419.2017.09.08 Abstract Lung cancer is becoming an increasing threat to Chinese residents and its incidence continues to rise while the treatment effect is far from satisfactory. Hence, it is essential to improve the level of early diagnosis, treatment, prognosis in lung cancer. An epigenetic trait is a stably heritable phenotype resulting from changes in a chromosome without alterations in the DNA sequence. The epigenetic studies, such as DNA methylation and histone methylation, are progressing rapidly in oncology research. A comprehensive understanding of its development status and existing problems is of great significance for the future research and the implementation of precision medicine. Herein, we aim to outline the progress of DNA methylation and histone methylation modification in lung cancer and make a prospect for the future...
[Advance in Diagnose and Treatment Strategies of Adenocarcinoma in Situ].

[Advance in Diagnose and Treatment Strategies of Adenocarcinoma in Situ].

Zhongguo fei ai za zhi = Chinese journal of lung cancer 20(9) 641-644 doi 10.3779/j.issn.1009-3419.2017.09.09 Abstract Adenocarcinoma in situ (AIS) is a new concept which was introduced to the 2011 The International Association for the Study of Cancer (IASLC)/ American Thoracic Society (ATS)/ European Respiratory Society (ERS) International Multidisciplinary Classification of Lung Adenocarcinoma firstly and an important supplement of The 2015 World Health Organization Classification of Lung Tumors. Because AIS is at an early stage of development of lung adenocarcinoma, the deepening understanding of its pathology, differential diagnosis, treatment strategies, has an important significance for the improvement of the prognosis of lung adenocarcinoma. This review will provide a systematic review of the main progress of occurrence and development, pathological characteristics, differential diagnosis and treatment strategy of AIS, in order to provide theoretical basis for the further research of...
[Novel Immuno-oncology Therapy: Current Status of Clinical Research and Prospect of Application].

[Novel Immuno-oncology Therapy: Current Status of Clinical Research and Prospect of Application].

Zhongguo fei ai za zhi = Chinese journal of lung cancer 20(9) 645-651 doi 10.3779/j.issn.1009-3419.2017.09.10 Abstract Recently, immune-oncologic therapy advanced rapidly and has been defined as another option, following surgery, radiotherapy, chemotherapy and molecular targeted therapy, for treatment of malignant diseases. To date, several immune checkpoint inhibitors and compounds have been approved to treat various of malignant diseases with efficiency. Meanwhile, more and more potential therapeutic targets in processes of the cancer immunity have been noticed. We aimed to summarize the research status and clinical prospects of novel immune-oncologic treatment agencies targeted to different steps of the cancer-immunity...
[One Case about Primary Pulmonary Squamous Cell Carcinoma 
with Retinal Metastasis].

[One Case about Primary Pulmonary Squamous Cell Carcinoma 
with Retinal Metastasis].

Zhongguo fei ai za zhi = Chinese journal of lung cancer 20(9) 652-656 doi 10.3779/j.issn.1009-3419.2017.09.11 Abstract Lung cancer is a common malignant tumor in clinic. Morbidity and mortality are the first place in cancer, which seriously threaten the health of human beings. Due to the lack of effective and specific screening methods, most patients were found already at an advanced stage, and often combined with bone, brain, liver, adrenal and other parts of the metastasis. Symptoms of patient resulted from the primary tumor, metastatic spread, or paraneoplastic syndrome commonly cause the medical attention. For the syndrome related to the distant metastatic spread as the first manifestation, diagnosis would be a challenge. Retinal metastasis is very rare as the first symptom of squamous cell carcinoma of the lung. This paper reviewed a case, in which a patient developed the retinal metastasis as the inital presentation. After systemic evaluation, our patient was managed in multidisciplinary treatments, including surgery and chemotherapy. Now, the patient has a good short-term prognosis and is still in fellow-up condition. Later, we summarized the characteristics of the diagnosis and treatment of this case and provided experience for clinicians. At the same time, reviewing the relevant literature on tumor metastasis provides a window for our understanding of the rare manifestations of lung...
[Report of Successful Treatment of A Rectal Cancer Patient with Endobronchial 
Metastasis by Bronchial Stent Implantation Combined with Chemotherapy and Apatinib].

[Report of Successful Treatment of A Rectal Cancer Patient with Endobronchial 
Metastasis by Bronchial Stent Implantation Combined with Chemotherapy and Apatinib].

Zhongguo fei ai za zhi = Chinese journal of lung cancer 20(9) 657-660 doi 10.3779/j.issn.1009-3419.2017.09.12 Abstract The lungs are the most common sites of metastases from non-pulmonary malignancies. On the other hand, endobronchial metastases are rare. Various tumors have been associated with endobronchial metastasis, most commonly renal, breast and colorectal cancer. Advanced rectal cancerwith lung metastasis is common. However, endobronchial metastasis without lung metastasis of rectal cancer is rare, and easily misdiagnosed. We report one case of postoperative rectal cancer with endobronchial, pleuralcavity, pericardial cavitymetastasis, giving the comprehensive treatment of bronchial stentimplantation, chemotherapy, targeted drugs and remission. The process of diagnosis and treatmentis relatively complex, therefore it has a certain clinical reference...
The Adverse Drug Reactions from Patient Reports in Social Media Project: Five Major Challenges to Overcome to Operationalize Analysis and Efficiently Support Pharmacovigilance Process.

The Adverse Drug Reactions from Patient Reports in Social Media Project: Five Major Challenges to Overcome to Operationalize Analysis and Efficiently Support Pharmacovigilance Process.

JMIR research protocols 2017 09 216(9) e179 doi 10.2196/resprot.6463 Abstract BACKGROUND Adverse drug reactions (ADRs) are an important cause of morbidity and mortality. Classical Pharmacovigilance process is limited by underreporting which justifies the current interest in new knowledge sources such as social media. The Adverse Drug Reactions from Patient Reports in Social Media (ADR-PRISM) project aims to extract ADRs reported by patients in these media. We identified 5 major challenges to overcome to operationalize the analysis of patient posts: (1) variable quality of information on social media, (2) guarantee of data privacy, (3) response to pharmacovigilance expert expectations, (4) identification of relevant information within Web pages, and (5) robust and evolutive architecture. OBJECTIVE This article aims to describe the current state of advancement of the ADR-PRISM project by focusing on the solutions we have chosen to address these 5 major challenges. METHODS In this article, we propose methods and describe the advancement of this project on several aspects: (1) a quality driven approach for selecting relevant social media for the extraction of knowledge on potential ADRs, (2) an assessment of ethical issues and French regulation for the analysis of data on social media, (3) an analysis of pharmacovigilance expert requirements when reviewing patient posts on the Internet, (4) an extraction method based on natural language processing, pattern based matching, and selection of relevant medical concepts in reference terminologies, and (5) specifications of a component-based architecture for the monitoring system. RESULTS Considering the 5 major challenges, we (1) selected a set of 21 validated criteria for selecting social media to support the extraction of potential ADRs, (2) proposed solutions to...
Social Communication Coaching Smartglasses: Well Tolerated in a Diverse Sample of Children and Adults With Autism.

Social Communication Coaching Smartglasses: Well Tolerated in a Diverse Sample of Children and Adults With Autism.

JMIR mHealth and uHealth 2017 09 215(9) e140 doi 10.2196/mhealth.8534 Abstract BACKGROUND Augmented reality (AR) smartglasses are an emerging technology that is under investigation as a social communication aid for children and adults with autism spectrum disorder (ASD) and as a research tool to aid with digital phenotyping. Tolerability of this wearable technology in people with ASD is an important area for research, especially as these individuals may experience sensory, cognitive, and attentional challenges. OBJECTIVE The aim of this study was to assess the tolerability and usability of a novel smartglasses system that has been designed as a social communication aid for children and adults with autism (the Brain Power Autism System [BPAS]). BPAS runs on Google Glass Explorer Edition and other smartglasses, uses both AR and affective artificial intelligence, and helps users learn key social and emotional skills. METHODS A total of 21 children and adults with ASD across a spectrum of severity used BPAS for a coaching session. The user’s tolerability to the smartglasses, user being able to wear the smartglasses for 1 minute (initial tolerability threshold), and user being able to wear the smartglasses for the entire duration of the coaching session (whole session tolerability threshold) were determined through caregiver report. RESULTS Of 21 users, 19 (91%) demonstrated tolerability on all 3 measures. Caregivers reported 21 out of 21 users (100%) as tolerating the experience, while study staff found only 19 out of 21 users managed to demonstrate initial tolerability (91%). Of the 19 users who demonstrated initial tolerability, all 19 (100%) were able to use the smartglasses for the entire session (whole session tolerability threshold)....
A Dermatologist’s Ammunition in the War Against Smoking: A Photoaging App.

A Dermatologist’s Ammunition in the War Against Smoking: A Photoaging App.

Journal of medical Internet research 2017 09 2119(9) e326 doi 10.2196/jmir.8743 Abstract This viewpoint reviews the perspectives for dermatology as a specialty to go beyond the substantial impact of smoking on skin disease and leverage the impact of skin changes on a person’s self-concept and behavior in the design of effective interventions for smoking prevention and...
A Lifestyle Intervention via Email in Minority Breast Cancer Survivors: Randomized Parallel-Group Feasibility Study.

A Lifestyle Intervention via Email in Minority Breast Cancer Survivors: Randomized Parallel-Group Feasibility Study.

JMIR cancer 2017 09 213(2) e13 doi 10.2196/cancer.7495 Abstract BACKGROUND Our data have indicated that minority breast cancer survivors are receptive to participating in lifestyle interventions delivered via email or the Web, yet few Web-based studies exist in this population. OBJECTIVE The aim of this study was to examine the feasibility and preliminary results of an email-delivered diet and activity intervention program, "A Lifestyle Intervention Via Email (ALIVE)," delivered to a sample of racial and ethnic minority breast cancer survivors. METHODS Survivors (mean age: 52 years, 83% [59/71] African American) were recruited and randomized to receive either the ALIVE program’s 3-month physical activity track or its 3-month dietary track. The fully automated system provided tools for self-monitoring and goal setting, tailored content, and automated phone calls. Descriptive statistics and mixed-effects models were computed to examine the outcomes of the study. RESULTS Upon completion, 44 of 71 survivors completed the study. Our "intention-to-treat" analysis revealed that participants in the physical activity track made greater improvements in moderate to vigorous activity than those in the dietary track (+97 vs. +49 min/week,...
Professional Medical Interpreters Influence the Quality of Acute Ischemic Stroke Care for Patients Who Speak Languages Other than English.

Professional Medical Interpreters Influence the Quality of Acute Ischemic Stroke Care for Patients Who Speak Languages Other than English.

Journal of the American Heart Association 2017 09 216(9) pii e006175 Abstract BACKGROUND The inability to communicate effectively in a common language can jeopardize clinicians’ efforts to provide quality patient care. Professional medical interpreters (PMIs) can help provide linguistically appropriate health care, in particular for the >25 million Americans who identify speaking English less than very well. We aimed to evaluate the relationship between use of PMIs and quality of acute ischemic stroke care received by patients who preferred to have their medical care in languages other than English. METHODS AND RESULTS We analyzed data from 259 non-English-preferring acute ischemic stroke patients who participated in the American Heart Association Get With The Guidelines-Stroke program at our hospital from January 1, 2003, to April 30, 2014. We used descriptive statistics and logistic regression models to examine associations between involvement of PMIs and patients’ receipt of defect-free stroke care. A total of 147 of 259 (57%) non-English-preferring patients received PMI services during their hospital stays. Multivariable analyses adjusting for other socioeconomic factors showed that acute ischemic stroke patients who did not receive PMIs had lower odds of receiving defect-free stroke care (odds ratio: 0.52; P=0.04). CONCLUSIONS Our findings suggest that PMIs may influence the quality of acute ischemic stroke...
Cardiac Events During Competitive, Recreational, and Daily Activities in Children and Adolescents With Long QT Syndrome.

Cardiac Events During Competitive, Recreational, and Daily Activities in Children and Adolescents With Long QT Syndrome.

Journal of the American Heart Association 2017 09 216(9) pii e005445 Abstract BACKGROUND The 2005 Bethesda Conference Guidelines advise patients with long QT syndrome against competitive sports. We assessed cardiac event rates during competitive and recreational sports, and daily activities among treated long QT syndrome patients. METHODS AND RESULTS Long QT syndrome patients aged ≥4 years treated with anti-adrenergic therapy were included. Demographics included mechanism of presentation, corrected QT interval pretreatment, symptom history, medication compliance, and administration of QT-prolonging medications. Corrected QT interval ≥550 ms or prior cardiac arrest defined high risk. Sports were categorized by cardiovascular demand per the 2005 Bethesda Conference Guidelines. Each was classified as recreational or competitive. One hundred seventy-two patients (90; 52% female) with median age 15.2 years (interquartile range 11.4, 19.4) were included. Evaluation was performed for family history (102; 59%), incidental finding (34; 20%), and symptoms (36; 21%). Median corrected QT interval was 474 ms (interquartile range 446, 496) and 14 patients (8%) were deemed high risk. Treatment included β-blockers (171; 99%), implantable cardioverter-defibrillator (27; 16%), left cardiac sympathetic denervation (7; 4%), and pacemaker (3; 2%). Sports participation was recreational (66; 38%) or competitive (106; 62%), with 92 (53%) exercising against the Bethesda Conference Guidelines. There were no cardiac events in competitive athletes and no deaths. There were 13 cardiac events in 9 previously symptomatic patients during either recreational exercise or activities of daily life. CONCLUSIONS In this cohort of appropriately managed children with long QT syndrome, cardiac event rates were low and occurred during recreational but not competitive activities. This study further supports the need for increased assessment of arrhythmia risk during exercise in this...
Sex Differences in the Utilization and Outcomes of Surgical Aortic Valve Replacement for Severe Aortic Stenosis.

Sex Differences in the Utilization and Outcomes of Surgical Aortic Valve Replacement for Severe Aortic Stenosis.

Journal of the American Heart Association 2017 09 216(9) pii e006370 Abstract BACKGROUND Studies assessing the differential impact of sex on outcomes of aortic valve replacement (AVR) yielded conflicting results. We sought to investigate sex-related differences in AVR utilization, patient risk profile, and in-hospital outcomes using the Nationwide Inpatient Sample. METHODS AND RESULTS In total, 166 809 patients (63% male and 37% female) who underwent AVR between 2003 and 2014 were identified, and 48.5% had a concomitant cardiac surgery procedure. Compared with men, women were older and had more nonatherosclerotic comorbid conditions including hypertension, diabetes mellitus, obstructive pulmonary disease, atrial fibrillation/flutter, and anemia but fewer incidences of coronary and peripheral arterial disease and prior sternotomies. In-hospital mortality was significantly higher in women (5.6% versus 4%,...
Unraveling transcriptome dynamics in human spermatogenesis.

Unraveling transcriptome dynamics in human spermatogenesis.

Development (Cambridge, England) 2017 09 21() pii dev.152413 Abstract Spermatogenesis is a dynamic developmental process that includes stem cell proliferation and differentiation, meiotic cell divisions and extreme chromatin condensation. Although studied in mice, the molecular control of human spermatogenesis is largely unknown. Here, we developed a protocol that enables next generation sequencing of RNA obtained from pools of 500 individually laser capture microdissected cells of specific germ cell-subtypes from fixed human testis samples. Transcriptomic analyses of these successive germ cell subtypes reveals dynamic transcription of over 4000 genes during human spermatogenesis. At the same time, many of the genes encoding for well- established meiotic and post-meiotic proteins are already present in the pre-meiotic phase. Furthermore, we found significant cell type-specific expression of post-transcriptional regulators, including expression of 110 RNA-binding proteins and 137 long non-coding RNAs, most of them previously not linked to spermatogenesis. Together this suggests that the transcriptome of precursor cells already contains genes necessary for cellular differentiation and that timely translation controlled by post-transcriptional regulators seems crucial for normal development. These established transcriptomes provide a reference catalog for further detailed studies on human spermatogenesis and spermatogenic...
Complete Genome Sequence of Clostridioides difficile Epidemic Strain DH/NAP11/106/ST-42, Isolated from Stool from a Pediatric Patient with Diarrhea.

Complete Genome Sequence of Clostridioides difficile Epidemic Strain DH/NAP11/106/ST-42, Isolated from Stool from a Pediatric Patient with Diarrhea.

Genome announcements 2017 09 215(38) pii e00923-17 Abstract We report here the complete genome sequence of Clostridioides difficile strain DH/NAP11/106/ST-42, which is now the most common strain causing C. difficile infection among U.S. adults. This strain was isolated from the stool from a hospitalized pediatric patient with frequent relapses of C. difficile...
Genome Sequence for Shiga Toxin-Producing Escherichia coli O26:H11, Associated with a Cluster of Hemolytic-Uremic Syndrome Cases in South Africa, 2017.

Genome Sequence for Shiga Toxin-Producing Escherichia coli O26:H11, Associated with a Cluster of Hemolytic-Uremic Syndrome Cases in South Africa, 2017.

Genome announcements 2017 09 215(38) pii e00989-17 Abstract Shiga toxin-producing Escherichia coli (STEC) strains are primarily foodborne pathogens that may cause diarrheal outbreaks and are associated with severe complications, specifically hemolytic-uremic syndrome (HUS). We report here genome sequence data for STEC O26:H11, which is associated with a cluster of cases of HUS, a rarely described syndrome in South...
An electronic trigger based on care escalation to identify preventable adverse events in hospitalised patients.

An electronic trigger based on care escalation to identify preventable adverse events in hospitalised patients.

BMJ quality & safety 2017 09 21() pii bmjqs-2017-006975 Abstract BACKGROUND Methods to identify preventable adverse events typically have low yield and efficiency. We refined the methods of Institute of Healthcare Improvement’s Global Trigger Tool (GTT) application and leveraged electronic health record (EHR) data to improve detection of preventable adverse events, including diagnostic errors. METHODS We queried the EHR data repository of a large health system to identify an ‘index hospitalization’ associated with care escalation (defined as transfer to the intensive care unit (ICU) or initiation of rapid response team (RRT) within 15 days of admission) between March 2010 and August 2015. To enrich the record review sample with unexpected events, we used EHR clinical data to modify the GTT algorithm and limited eligible patients to those at lower risk for care escalation based on younger age and presence of minimal comorbid conditions. We modified the GTT review methodology; two physicians independently reviewed eligible ‘e-trigger’ positive records to identify preventable diagnostic and care management events. RESULTS Of 88 428 hospitalisations, 887 were associated with care escalation (712 ICU transfers and 175 RRTs), of which 92 were flagged as trigger-positive and reviewed. Preventable adverse events were detected in 41 cases, yielding a trigger positive predictive value of 44.6% (reviewer agreement 79.35%; Cohen’s kappa 0.573). We identified 7 (7.6%) diagnostic errors and 34 (37.0%) care management-related events: 24 (26.1%) adverse drug events, 4 (4.3%) patient falls, 4 (4.3%) procedure-related complications and 2 (2.2%) hospital-associated infections. In most events (73.1%), there was potential for temporary harm. CONCLUSION We developed an approach using an EHR data-based trigger and modified review process to efficiently identify...
Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study.

Efficacy and safety of subcutaneous and intravenous rituximab plus cyclophosphamide, doxorubicin, vincristine, and prednisone in first-line diffuse large B-cell lymphoma: the randomized MabEase study.

Haematologica 2017 09 21() pii haematol.2017.173583 Abstract Intravenous rituximab plus chemotherapy is standard treatment for diffuse large B-cell lymphoma. A subcutaneous formulation of rituximab is expected to simplify and shorten drug preparation and administration, and to reduce treatment burden. MabEase (NCT01649856) examined efficacy, safety and patient satisfaction with subcutaneous rituximab plus chemotherapy in treatment-naïve patients with diffuse large B-cell lymphoma. Patients were randomized 2:1 to subcutaneous rituximab (intravenous 375 mg/m(2) cycle 1; subcutaneous 1,400 mg cycles 2-8) or intravenous rituximab (375 mg/m(2) cycles 1-8) plus cyclophosphamide, doxorubicin, vincristine, and prednisone every 14 or 21 days. The primary endpoint was investigator-assessed complete response/unconfirmed complete response. Secondary endpoints included safety, treatment satisfaction (Cancer Treatment Satisfaction Questionnaire and Rituximab Administration Satisfaction Questionnaire), time savings, and survival. Of 576 randomized patients, 572 (378 subcutaneous; 194 intravenous) received treatment. End-of-induction complete response/unconfirmed complete response rates were 50.6% (subcutaneous) and 42.4% (intravenous). After a median 35 months, median overall, event-free and progression-free survivals were not reached. Grade ≥3 adverse events (subcutaneous 58.3%; intravenous 54.3%) and administration-related adverse events (both groups 21%) were similar between arms. Injection-site reactions were more common with subcutaneous (5.7% versus 0%). Rituximab Administration Satisfaction Questionnaire scores for ‘impact on activities of daily living, convenience, and satisfaction were improved with subcutaneous versus intravenous; Cancer Treatment Satisfaction Questionnaire scores were similar between arms. Median administration time (6 minutes vs 2.6-3.0 hours), chair/bed and overall hospital times were shorter with subcutaneous versus intravenous rituximab. Overall, subcutaneous and intravenous rituximab had similar efficacy and safety, with improved patient satisfaction and time...
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