tbuckley/cabot-search huggingface dataset:
C-reactive protein (CRP) as a predictive marker for immunotherapy in lung cancer.
Authors: Odd Terje Brustugun, Mette Sprauten, Aslaug Helland
Journal: Journal of Clinical Oncology (2016)

e20623 Background: The PD1-inhibitor nivolumab is approved in second line metastatic squamous cell carcinomas of the lung, and has in clinical trials shown response rates of around 20%. Overexpression of PD-L1 has shown predictive value in non-squamous cell carcinomas, but not in squamous subtype. There is a substantial need to study possible markers, to avoid futile treatment with an expensive drug with potential severe side effects. Markers of an activated immune system as elevated CRP may indicate a reduced likelihood of response to immunotherapy. Methods: Patients with lung squamous cell carcinoma who progressed after first or later line chemotherapy were treated with nivolumab (3 mg/kg every 2 weeks) in a named patient use program until unequivocal progression or intolerable side effects. Time from treatment start until documented progression was recorded. Blood was drawn before the first dosing, and CRP was measured using standard methods. Statistical analyses were performed using GraphPad Prism v 6. Results: From June through August 2015, 24 consecutively nivolumab-treated patients were included, 12 females and 12 males. Median age was 64.7 years (range 48.0 – 77.5). Twelve patients had received only platinum-based doublet chemotherapy, 8 had been treated with two lines, and 4 with three lines before nivolumab. Median observation time was 5.6 months, and median duration of treatment was 4.0 months. Nine patients were still in treatment, 15 had stopped therapy and 11 had died at the time of analysis. None experienced side effects > grade 2, and none were off treatment due to side effects. There were no survival differences related to age or number of previous treatment lines. Females had longer median time to treatment failure than men (6.3 vs 1.9 months, p = 0.035). CRP-levels were available for 22 of the patients, ranging from 3.2 to 239 mg/L (median 64). Patients with CRP below median (4 females, 7 males) had substantially longer median time to treatment failure than when CRP was above median (not reached vs 1.5 months, p = 0.029). Pre-treatment CRP correlated significantly with treatment duration (R2= 0.37, p = 0.0026). Conclusions: CRP should be studied further as a predictive marker for nivolumab in lung cancer.
リアルタイムモニタリング性能を有する高効率腫瘍アブレーションのためのマイクロ波活性化ナノ液滴蒸発【Powered by NICT】
Authors: Xu Jinshun, Chen Yu, Deng Liming, Liu Jianxin, Cao Yang, Li Pan, Ran Haitao, Zheng Yuanyi, Wang Zhigang
Journal: Biomaterials (2016)
Use of Outpatient Cardiac Rehabilitation Among Heart Attack Survivors — 20 States and the District of Columbia, 2013 and Four States, 2015
Authors: Jing Fang, Carma Ayala, Cecily Luncheon, Matthew Ritchey, Fleetwood Loustalot
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

Heart disease is the leading cause of death in the United States (1). Each year, approximately 790,000 adults have a myocardial infarction (heart attack), including 210,000 that are recurrent heart attacks (2). Cardiac rehabilitation (rehab) includes exercise counseling and training, education for heart-healthy living, and counseling to reduce stress. Cardiac rehab provides patients with education regarding the causes of heart attacks and tools to initiate positive behavior change, and extends patients' medical management after a heart attack to prevent future negative sequelae (3). A systematic review has shown that after a heart attack, patients using cardiac rehab were 53% (95% confidence interval [CI] = 41%-62%) less likely to die from any cause and 57% (95% CI = 21%-77%) less likely to experience cardiac-related mortality than were those who did not use cardiac rehab (3). However, even with long-standing national recommendations encouraging use of cardiac rehab (4), the intervention has been underutilized. An analysis of 2005 Behavioral Risk Factor Surveillance System (BRFSS) data found that only 34.7% of adults who reported a history of a heart attack also reported subsequent use of cardiac rehab (5). To update these estimates, CDC used the most recent BRFSS data from 2013 and 2015 to assess the use of cardiac rehab among adults following a heart attack. Overall use of cardiac rehab was 33.7% in 20 states and the District of Columbia (DC) in 2013 and 35.5% in four states in 2015. Cardiac rehab use was underutilized overall and differences were evident by sex, age, race/ethnicity, level of education, cardiovascular risk status, and by state. Increasing use of cardiac rehab after a heart attack should be encouraged by health systems and supported by the public health community.
Age-Dependent Associations Between Sleep-Disordered Breathing and Hypertension
Authors: Donald C. Haas, Gregory L. Foster, F. Javier Nieto, Susan Redline, Helaine E. Resnick, John A. Robbins, Terry Young, Thomas G. Pickering
Journal: Circulation (2005)

Background— Sleep-disordered breathing (SDB) is associated with hypertension in the middle-aged. The association is less clear in older persons. Most middle-aged hypertensives have systolic/diastolic hypertension, whereas isolated systolic hypertension (ISH) is common among persons over 60 years. Mechanistically, only systolic/diastolic hypertension is expected to be associated with SDB, but few studies of SDB and hypertension distinguish systolic/diastolic hypertension from ISH. Prior investigations may have underestimated an association between SDB and systolic/diastolic hypertension in the elderly by categorizing individuals with ISH as simply hypertensive. Methods and Results— We conducted cross-sectional analyses of 6120 participants in the Sleep Heart Health Study, stratified by age: 40 to 59 (n=2477) and ≥60 years. Outcome measures included apnea-hypopnea index (AHI; average number of apneas plus hypopneas per hour of sleep), systolic/diastolic hypertension (≥140 and ≥90 mm Hg), and ISH (≥140 and &lt;90 mm Hg). With adjustment for covariates, ISH was not associated with SDB in either age category. In those aged&lt;60 years, AHI was significantly associated with higher odds of systolic/diastolic hypertension (AHI 15 to 29.9, OR=2.38 [95% CI 1.30 to 4.38]; AHI ≥30, OR=2.24 [95% CI 1.10 to 4.54]). Among those aged ≥60 years, no adjusted association between AHI and systolic/diastolic hypertension was found. Conclusions— SDB is associated with systolic/diastolic hypertension in those aged &lt;60 years. No association was found between SDB and systolic/diastolic hypertension in those aged ≥60 years or between SDB and ISH in either age category. These findings have implications for SDB screening and treatment. Distinguishing between hypertensive subtypes reveals a stronger association between SDB and hypertension for those aged &lt;60 years than previously reported.
A Lead to the Culprit
Authors: Haseeb Rahman, Bhavik Modi, Howard Ellis, Satpal Arri, Divaka Perera
Journal: Circulation (2017)

ECG CHALLENGEA 45-year-old woman presented with persistent chest pain.She had no past medical history and was otherwise fit and well.A 12-lead ECG (Figure 1) recorded by the ambulance team triggered the primary percutaneous intervention pathway.On transit to the primary percutaneous intervention center, the patient suffered a ventricular fibrillation arrest, and sinus rhythm was successfully restored after 3 minutes of resuscitation protocol.What is the likely angiographic finding that would explain the 12-lead ECG pattern?Please turn the page to read the diagnosis.
The Rac GTPase in Cancer: From Old Concepts to New Paradigms
Authors: Marcelo G. Kazanietz, Maria J. Caloca
Journal: Cancer Research (2017)

Rho family GTPases are critical regulators of cellular functions that play important roles in cancer progression. Aberrant activity of Rho small G-proteins, particularly Rac1 and their regulators, is a hallmark of cancer and contributes to the tumorigenic and metastatic phenotypes of cancer cells. This review examines the multiple mechanisms leading to Rac1 hyperactivation, particularly focusing on emerging paradigms that involve gain-of-function mutations in Rac and guanine nucleotide exchange factors, defects in Rac1 degradation, and mislocalization of Rac signaling components. The unexpected pro-oncogenic functions of Rac GTPase-activating proteins also challenged the dogma that these negative Rac regulators solely act as tumor suppressors. The potential contribution of Rac hyperactivation to resistance to anticancer agents, including targeted therapies, as well as to the suppression of antitumor immune response, highlights the critical need to develop therapeutic strategies to target the Rac pathway in a clinical setting. Cancer Res; 77(20); 5445-51. ©2017 AACR.
ヒトES/iPS細胞のスケーラブル拡張のためのナノに対する微線維性細胞外マトリックス【Powered by NICT】
Authors: Liu Li, Kamei Ken-ichiro, Yoshioka Momoko, Nakajima Minako, Li Junjun, Fujimoto Nanae, Terada Shiho, Tokunaga Yumie, Koyama Yoshie, Sato Hideki, Hasegawa Kouichi, Nakatsuji Norio, Chen Yong
Journal: Biomaterials (2017)
Toward Improving Patient Safety
Authors: Paul D. Varosy
Journal: JAMA Internal Medicine (2017)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA Internal Medicine HomeNew OnlineCurrent IssueFor Authors Podcast Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA Internal Medicine journal
Relapsing Polychondritis Diagnosed by Fusion Images of Gallium‐67 Uptake on Computed Tomography and Single‐Photon–Emission Computed Tomography
Authors: Kazuhisa Nakano, Takafumi Aritomi, Naoaki Ohkubo, Yoshiya Tanaka
Journal: Arthritis & Rheumatology (2017)

A 64-year-old man has revealed dry cough and severe pain of ear, nose and throat for several weeks. After visiting clinics and hospitals, he was introduced to our hospital and was diagnosed as relapsing polychondritis (RP) based on McAdam's criteria. The involvement in auricular, nasal and tracheal cartilage was clearly shown by fusion images of gallium-67 on single photon emission computed tomography and computed tomography (SPECT/CT) (A, B). High-dose glucocorticoid (GC) therapy markedly improved relevant signs, symptoms and inflammatory reactions as well as gallium uptake in cartilage detected by gallium-SPECT/CT (C).

This article is protected by copyright. All rights reserved.
11q Deletion (del11q) Is Not a Prognostic Factor for Adverse Outcomes for Patients with Chronic Lymphocytic Leukemia/Small Lymphocytic Lymphoma (CLL/SLL) Treated with Ibrutinib: Pooled Data from 3 Randomized Phase 3 Studies
Authors: Thomas J. Kipps, Peter Hillmen, Fatih Demirkan, Sebastian Grosicki, Steven E. Coutre, Jacqueline C. Barrientos, Paul M. Barr, Ann Janssens, John C. Byrd, Susan M. O'Brien, Graeme Fraser, Ulrich Jaeger, Paula Cramer, Stephan Stilgenbauer, Asher A. Chanan-Khan, Mariya Salman, Isabelle Solman, Mei Cheng, Charles Phelps, Joi Ninomoto, Angela Howes, Danelle F. James, Michael Hallek
Journal: Blood (2016)
B‐1a細胞の発生,自己再生及びBCRレパートリーの調節における転写因子Bhlhe41の必須役割
Authors: Kreslavsky Taras, Vilagos Bojan, Tagoh Hiromi, Poliakova Daniela Kostanova, Schwickert Tanja A, Woehner Miriam, Jaritz Markus, Weiss Siegfried, Taneja Reshma, Rossner Moritz J, Busslinger Meinrad
Journal: Nature Immunology (2017)
Gender dysphoria: referral for ear, nose, and throat or facial surgeries
Authors: Thomas Hampton, Catherine James, Gerry O'Sullivan
Journal: BMJ (2017)

Barrett’s enlightening article on gender dysphoria1 provided our department with much food for thought—in particular, highlighting that, as more than one in 200 patients identifies as transgender, we probably serve at least one such patient a day in our local district general hospital. The article touches on management including surgery but states that the NHS does not fund ear, nose, and throat or facial surgeries.

Our understanding is that such procedures—including voice surgery, nasal surgery, and facial …
miRNases:リンパ肉腫細胞における沈黙させるmiR‐21する新規ペプチド‐オリゴヌクレオチドバイオコンジュゲート【Powered by NICT】
Authors: A Patutina Olga, V Bichenkova Elena, K Miroshnichenko Svetlana, L Mironova Nadezhda, T Trivoluzzi Linda, K Burusco Kepa, A Bryce Richard, V Vlassov Valentin, A Zenkova Marina
Journal: Biomaterials (2017)
An administrative stage inference algorithm for use in patients receiving chemotherapy for colorectal cancer.
Authors: Gabriel A. Brooks, Mary Beth Landrum, Nancy Lynn Keating
Journal: Journal of Clinical Oncology (2017)

e18121 Background: Claims data are often used for evaluating cancer care outcomes; however, such data lack information about cancer stage. We developed a claims-based stage inference algorithm to classify chemotherapy-treated patients with localized vs. metastatic colorectal cancer (CRC). Methods: We used the SEER-Medicare linked data (2010-‘11) to develop and validate an algorithm to predict cancer stage (localized vs. metastatic) among patients receiving chemotherapy within 6 months of CRC diagnosis. We used claims to identify treatments received (surgery, radiation, and chemotherapy agents) during the 6 months before and after the first dose of chemotherapy. The sample was split 1:1 into development and validation cohorts. After testing in the development cohort, the final algorithm was evaluated in the validation cohort. SEER data served as the gold standard for cancer stage. Results: We identified 25,258 patients with fee-for-service Medicare and a new diagnosis of CRC. 6,907 patients (27%) received chemotherapy for CRC within 6 months of diagnosis. The median age of chemotherapy-treated patients was 73, 49% were female, and 76% were white; 69% had localized cancer (AJCC stage 1-3) and 31% had metastasis at diagnosis (stage 4). Split-sample validation of the final classification algorithm demonstrated sensitivity and specificity of 87% (95% CI 86-89%) and 76% (73-78%) for localized cancer and 73% (70-75%) and 91% (90-92%) for metastatic cancer. The overall accuracy of classification was 83%. Stratified analyses demonstrated preserved algorithm performance across subgroups of age, sex, race, geography, and comorbidity. Misclassification was most common among patients with metastatic disease who were treated with surgery followed by fluoropyrimidine chemotherapy with or without oxaliplatin. 2-year overall survival was 79.8% (stage 1-3) and 35.4% (stage 4) for SEER stage groups, vs. 79.6% and 35.8% for predicted stage groups. Conclusions: A claims-based algorithm can classify extent of disease in chemotherapy-treated CRC patients with an accuracy of 83%. This algorithm will allow more clinically-relevant patient stratification for claims-based evaluations of cancer care outcomes.
Transglutaminase 2 Is a Direct Target Gene of YAP/TAZ—Letter
Authors: Chen-Ying Liu, Ajaybabu V. Pobbati, Zhenyu Huang, Long Cui, Wanjin Hong
Journal: Cancer Research (2017)

We read with great interest the recent article by Fisher and colleagues showing that transglutaminase 2 (TG2) activates YAP in the ECS cells (1). We noticed that, in Fig. 4A in ref. 1, overexpression of the constitutive active YAP (YAPS127A) did not increase TG2 expression in the SCC13 cells. However, this could be due to high basal expression level of YAP or due to relatively low transfection efficiency. We observed that the Western blot analysis of YAP (in Fig. 4A in ref. 1) only showed a weak increase in YAP protein level after transfection, although a clear FLAG signal was observed, indicating that YAP was not significantly overexpressed.Our data indicate that TG2 levels are significantly increased upon YAPS127A and TAZ4SA overexpression (Fig. 1A–C). The expression of TG2 was inhibited by high cell density (Fig. 1D). Knockdown of YAP/TAZ dramatically decreased TG2 expression in multiple cell lines, including pharynx squamous cell carcinoma cell line FaDu (Fig. 1E). Our analysis of the published chromatin immunoprecipitation (ChIP) sequencing datasets of YAP and TEAD further demonstrated that YAP and TEAD directly bind to the promoter region of TG2 gene in multiple cell lines (Fig. 1F), which was confirmed by ChIP-qPCR (Fig. 1G). Furthermore, the gene coexpression analysis of CCLE dataset showed that the mRNA levels of TG2 positively correlated with multiple known downstream target genes of YAP/TAZ, such as CTGF, CYR61, AXL, ANKRD1, LATS2, and AMOTL2, as well as with the expression levels of YAP/TAZ (Fig. 1H). Treatment with TG2 inhibitor significantly inhibited the growth of the MCF10A cells expressing YAPS127A in the 3D culture (Fig. 1I). Taken together, these data indicate that TG2 is a direct target gene of YAP/TAZ and plays a vital role in the malignant transformation induced by YAP/TAZ.TG2 is a multifunctional protein that is overexpressed in multiple cancers and its expression levels positively correlate with metastasis and poor prognosis (2). Interestingly, TG2 is an activator of NF-κB and is also a direct target gene of NF-κB (3). It has been shown that knockdown of TG2 inhibits YAP activity (1, 4). Here, in various cell lines, we show that TG2 is a direct target gene of YAP/TAZ; by upregulating TG2 expression, YAP/TAZ probably also forms a positive feedback loop and amplifies oncogenic programs. TG2 has been a promising therapeutic target for many diseases, including cancer (5). Our results suggest that inhibition of TG2 could be a potent therapeutic strategy for the YAP/TAZ–active cancers.See the Response, p. 4736No potential conflicts of interest were disclosed.This work was supported by National Natural Science Foundation of China (grant 81672517 to C.Y. Liu and 81372636 to L. Cui), the Medical Engineering Interdisciplinary Grant of Shanghai Jiao Tong University (grant YG2014MS71 to C.Y. Liu). This study was also supported by the Agency for Science, Technology and Research (A*STAR) funds to W. Hong.
<i>CYP2A6</i> Polymorphisms Associate with Outcomes of S-1 Plus Oxaliplatin Chemotherapy in Chinese Gastric Cancer Patients
Authors: Lin Yang, Shanshan Zou, Chang Shu, Yan Song, Yong-Kun Sun, Wen Zhang, Aiping Zhou, Xinghua Yuan, Yi Yang, Songnian Hu
Journal: Genomics Proteomics & Bioinformatics (2017)

Gastric carcinoma is a heterogeneous malignant disease involving genetic factors. To identify predictive markers for gastric cancer treatment in Chinese patients, we evaluated the association between polymorphisms of the gene encoding cytochrome P450 2A6 (CYP2A6) and outcomes of S-1 plus oxaliplatin (SOX) chemotherapy treatment. Clinical data on 60 consecutive gastric cancer patients receiving SOX regimen were collected prospectively. We sequenced all exons of CYP2A6 and a total of 22 different polymorphisms were detected in the present study. Comprehensive analyses of these genetic polymorphisms were performed to determine their association with both safety and efficacy of SOX regimen. Our results showed that polymorphisms of CYP2A6 were associated with the safety and efficacy of SOX treatment. Among them, missense mutations CYP2A6 rs60823196 and rs138978736 could be possible risk factors (P<0.05) for severe diarrhea induced by SOX, whereas CYP2A6 rs138978736 could be a conceivable predictor for overall survival of patients treated with SOX adjuvant chemotherapy. Further large-scale randomized prospective studies are warranted to confirm these findings.
David Oliver: In support of acute internal medicine
Authors: David Oliver
Journal: BMJ (2017)

The diabetologist Partha Kar recently wrote a provocative blog post questioning the rationale for acute internal medicine (AIM) existing as a specialty.1 Kar said that he meant to raise debate and ask questions, not to cast doubt, saying that acute physicians shouldn’t take it personally. Meanwhile, a nephrologist, Dr Ross, wrote a journal letter that appeared to disparage AIM specialists and their close cousins, acute geriatricians.2

As a geriatrician, like most other UK hospital physicians working in big “ologies” including nephrology and diabetes, I trained, dually accredited, and gained extensive experience in general internal medicine, including years of unselected general take responsibilities.3

As a consultant, combining this …
Comment on Gagnum et al. Long-term Mortality and End-Stage Renal Disease in a Type 1 Diabetes Population Diagnosed at Age 15–29 Years in Norway. Diabetes Care 2017;40:38–45
Authors: Xue Sun, Peng-Fei Shan, Yue Ding, Hualiang Yu, Zhen-Ya Song
Journal: Diabetes Care (2017)

We read with interest the paper by Gagnum et al. (1) reporting on a well-organized prospective cohort study that assessed long-term mortality and end-stage renal disease in a type 1 diabetes (T1D) population diagnosed at age 15–29 years in Norway. The authors concluded that mortality in the cohort with T1D “was 4.4 times that of the general population, and more than 50% of all deaths were caused by acute or chronic complications. A relatively high proportion of deaths were related to alcohol” (1). We would like to offer further explanation and understanding of the impact of psychological disorders on mortality in patients with T1D.

In this study, high mortality related to alcohol abuse, violence, and …
A Favorable BCL-2 Family Expression Profile May Explain the Increased Susceptibility of the t(11;14) Multiple Myeloma Subgroup to Single Agent Venetoclax
Authors: Jenny Wu, Jeremy Ross, Franklin V. Peale, John D Shaughnessy, Ryan K Van Laar, Gareth J Morgan, Jeffrey M Venstrom, Elizabeth A. Punnoose
Journal: Blood (2016)
Case 26-2017
Authors: Alyssa R. Letourneau, Melissa C. Price, Marwan M. Azar
Journal: New England Journal of Medicine (2017)

A 63-year-old woman with dermatomyositis presented with fever, hypotension, hypoxemia, and pancytopenia. Chest imaging revealed consolidations in the dependent portion of the bilateral lower lobes and bilateral ground-glass opacities. Diagnostic tests were performed.
Role of BACE1 in Alzheimer’s synaptic function
Authors: Brati Das, Riqiang Yan
Journal: Translational Neurodegeneration (2017)

Alzheimer's disease (AD) is the most common age-dependent disease of dementia, and there is currently no cure available. This hallmark pathologies of AD are the presence of amyloid plaques and neurofibrillary tangles. Although the exact etiology of AD remains a mystery, studies over the past 30 have shown that abnormal generation or accumulation of β-amyloid peptides (Aβ) is likely to be a predominant early event in AD pathological development. Aβ is generated from amyloid precursor protein (APP) via proteolytic cleavage by β-site APP cleaving enzyme 1 (BACE1). Chemical inhibition of BACE1 has been shown to reduce Aβ in animal studies and in human trials. While BACE1 inhibitors are currently being tested in clinical trials to treat AD patients, it is highly important to understand whether BACE1 inhibition will significantly impact cognitive functions in AD patients. This review summarizes the recent studies on BACE1 synaptic functions. This knowledge will help to guide the proper use of BACE1 inhibitors in AD therapy.