tbuckley/cabot-search huggingface dataset:
Delirium in Older Persons
Authors: Esther S. Oh, Tamara G. Fong, Tammy T. Hshieh, Sharon K. Inouye
Journal: JAMA (2017)

<h3>Importance</h3> Delirium is defined as an acute disorder of attention and cognition. It is a common, serious, and often fatal condition among older patients. Although often underrecognized, delirium has serious adverse effects on the individual’s function and quality of life, as well as broad societal effects with substantial health care costs. <h3>Objective</h3> To summarize the current state of the art in diagnosis and treatment of delirium and to highlight critical areas for future research to advance the field. <h3>Evidence Review</h3> Search of Ovid MEDLINE, Embase, and the Cochrane Library for the past 6 years, from January 1, 2011, until March 16, 2017, using a combination of controlled vocabulary and keyword terms. Since delirium is more prevalent in older adults, the focus was on studies in elderly populations; studies based solely in the intensive care unit (ICU) and non–English-language articles were excluded. <h3>Findings</h3> Of 127 articles included, 25 were clinical trials, 42 cohort studies, 5 systematic reviews and meta-analyses, and 55 were other categories. A total of 11 616 patients were represented in the treatment studies. Advances in diagnosis have included the development of brief screening tools with high sensitivity and specificity, such as the 3-Minute Diagnostic Assessment; 4 A’s Test; and proxy-based measures such as the Family Confusion Assessment Method. Measures of severity, such as the Confusion Assessment Method–Severity Score, can aid in monitoring response to treatment, risk stratification, and assessing prognosis. Nonpharmacologic approaches focused on risk factors such as immobility, functional decline, visual or hearing impairment, dehydration, and sleep deprivation are effective for delirium prevention and also are recommended for delirium treatment. Current recommendations for pharmacologic treatment of delirium, based on recent reviews of the evidence, recommend reserving use of antipsychotics and other sedating medications for treatment of severe agitation that poses risk to patient or staff safety or threatens interruption of essential medical therapies. <h3>Conclusions and Relevance</h3> Advances in diagnosis can improve recognition and risk stratification of delirium. Prevention of delirium using nonpharmacologic approaches is documented to be effective, while pharmacologic prevention and treatment of delirium remains controversial.
A Clinical Study of the Comparative Effect of Nitrogen Mustard and DON in Patients With Bronchogenic Carcinoma, Hodgkin's Disease, Lymphosarcoma, and Melanoma2
Authors: Simon Krantz, Shirley Rivers, Richard W. Dwight, Howard F. Corbus, Julius Wolf, Ira Green, Paul W. Spear, Louis T. Imperato, Samuel Lobe, Richard M. Whittington, John M. Rumball, Antonio Marquez, Coral Cables, Amoz I. Chernoff, Dwijenora K. Misra, Robert D. Sullivan, Edward Miller, Frank S. Dietrich, Gerald I. Plitman, Henry P. Close, Stewart McCracken, Arthur S. Glushien, Donald L. Rucknagel, C. C. Li, Dankward Kodlin
Journal: JNCI Journal of the National Cancer Institute (1959)

In a cooperative study involving 11 Veterans Administration Hospitals, the effect of HN2 (nitrogen mustard) and DON (6-diazo-5-oxo-L-norleucine), an “antibiotic” isolated from Streptomyces, was compared in patients with bronchogenic carcinoma, Hodgkin's disease, lymphosarcoma, and melanoma. HN2 was given intravenously in a dose of 0.2 mg. per kg. of body weight for 2 consecutive days. DON was given in a single oral dose of 0.2 mg. per kg. daily for 30 days. The effects were compared by measuring changes in tumor size, by the performance status of the patient, and by the impression of each investigator on the over-all effect. Neither drug was effective in malignant melanoma. HN2 was superior to DON in Hodgkin's disease and lymphosarcoma and slightly better than DON in bronchogenic carcinoma.
Programmed cell death-1 (PD-L1) expression and Fibroblast growth factor receptor 1 (FGFR1) amplification in Chinese stage III/IV lung squamous lung carcinoma (SQC).
Authors: Jie Wang, Qinxiang Guo, Shuhang Wang, Hua Bai, Jianchun Duan
Journal: Journal of Clinical Oncology (2015)

e19127 Background: Status of PD-L1 expression and FGFR1 amplification in stage IIIB/IV Chinese SQC is still unknown, neither does the correlation of these molecular parameters with clinicpothological characteristics, efficacy of gemcitabine based chemotherapy and prognosis of SQC patients. Methods: 128 stage IIIB/IV SQC patients were enrolled into this study from May 1st 2009 to May 31st2014, all of which had complete clinical profile. 78 patients received gemcitabine-based chemotherapy. Immunohistochemistry (IHC) was used to detect PD-L1 expression; fluorescence in situ hybridization (FISH) was applied to detect FGFR1 amplification. SPSS17.0 was used for statistical analysis. Results: 80 (62.5%) SQC had IHC positive PD-L1 expression. Among clinical characteristics including gender, age, smoking history, stage, lymph node metastasis and distance metastasis, male patients and smokers had significantly higher expression rates than female and non-smoker (65.5% vs. 22.2%, P = 0.011; 67.0% VS. 44.0%, P = 0.039, respectively). PD-L1 expression had no correlation with response rate (RR) and disease control rate (DCR) for gemcitabine-based chemotherapy. However, the overall survival (OS) of PD-L1 negative SQC was significantly longer than PD-L1 positive group (29.8 vs. 20.1 months, P = 0.001). 32 of 128 (25%) SQC presented FGFR1 FISH positive , and stage III patients present lower rate compared with stage IV SQC (17.1% vs. 36.5%, P = 0.013). FGFR1 amplification had no correlation with RR and DCR in patients treated with gemcitabine-base chemotherapy. No correlation between PD-L1 expression and FGFR1 amplification was found (P = 0.916). Conclusions: PD-L1 expression could act as a prognosis factor in Chinese stage IIIB/IV SQC patients. PD-L1 expression and FGFR1 amplification might be irrelevant.
O-Acetylation of Peptidoglycan Limits Helper T Cell Priming and Permits Staphylococcus aureus Reinfection
Authors: Marisel Sanchez, Stacey L. Kolar, Sabrina Müller, Christopher N. Reyes, Andrea J. Wolf, Chihiro Ogawa, Rajat Singhania, Daniel D. De Carvalho, Moshe Arditi, David M. Underhill, Gislâine A. Martins, George Y. Liu
Journal: Cell Host & Microbe (2017)
Spironolactone-induced degradation of the TFIIH core complex XPB subunit suppresses NF-κB and AP-1 signalling
Authors: Jason M Elinoff, Li-Yuan Chen, Edward J Dougherty, Keytam S Awad, Shuibang Wang, Angelique Biancotto, Afsheen H Siddiqui, Nargues A Weir, Rongman Cai, Junfeng Sun, Ioana R Preston, Michael A Solomon, Robert L Danner
Journal: Cardiovascular Research (2017)

Abstract Aims Spironolactone (SPL) improves endothelial dysfunction and survival in heart failure. Immune modulation, including poorly understood mineralocorticoid receptor (MR)-independent effects of SPL might contribute to these benefits and possibly be useful in other inflammatory cardiovascular diseases such as pulmonary arterial hypertension. Methods and results Using human embryonic kidney cells (HEK 293) expressing specific nuclear receptors, SPL suppressed NF-κB and AP-1 reporter activity independent of MR and other recognized nuclear receptor partners. NF-κB and AP-1 DNA binding were not affected by SPL and protein synthesis blockade did not interfere with SPL-induced suppression of inflammatory signalling. In contrast, proteasome blockade to inhibit degradation of xeroderma pigmentosum group B complementing protein (XPB), a subunit of the general transcription factor TFIIH, or XPB overexpression both prevented SPL-mediated suppression of inflammation. Similar to HEK 293 cells, a proteasome inhibitor blocked XPB loss and SPL suppression of AP-1 induced target genes in human pulmonary artery endothelial cells (PAECs). Unlike SPL, eplerenone (EPL) did not cause XPB degradation and failed to similarly suppress inflammatory signalling. SPL combined with siRNA XPB knockdown further reduced XPB protein levels and had the greatest effect on PAEC inflammatory gene transcription. Using chromatin-immunoprecipitation, PAEC target gene susceptibility to SPL was associated with low basal RNA polymerase II (RNAPII) occupancy and TNFα-induced RNAPII and XPB recruitment. XP patient-derived fibroblasts carrying an N-terminal but not C-terminal XPB mutations were insensitive to both SPL-mediated XPB degradation and TNFα-induced target gene suppression. Importantly, SPL treatment decreased whole lung XPB protein levels in a monocrotaline rat model of pulmonary hypertension and reduced inflammatory markers in an observational cohort of PAH patients. Conclusion SPL has important anti-inflammatory effects independent of aldosterone and MR, not shared with EPL. Drug-induced, proteasome-dependent XPB degradation may be a useful therapeutic approach in cardiovascular diseases driven by inflammation.
Multiplex ALK, RET, and ROS1 fusion mutation detection in FFPE from lung cancer patients by MALDI-TOF mass spectrometry.
Authors: Kang-Yi Su, Bing-Ching Ho, Gee-Chen Chang, Hsuan-Yu Chen, Pan-Chyr Yang, Sung-Liang Yu
Journal: Journal of Clinical Oncology (2017)

e13103 Background: Approximately 3-7% of lung tumors harbor anaplastic lymphoma kinase (ALK) fusions in the subgroup of non-small cell lung cancer (NSCLC). In addition to echinoderm microtubule-associated protein-like 4 (EML4)-ALK fusion, TRK-fused gene (TFG)-ALK, kinesin family member 5B (KIF5B)-ALK and kinesin light chain 1 (KLC1)-ALK had been reported in lung cancer. On the other hand, RET proto-oncogene (RET) and ROS proto-oncogene 1 (ROS1) fusion proteins also have prevalence in lung cancer. Food and Drug Administration (FDA)-approved several target drugs are available to treat patients with fusion mutations. Therefore, the diagnosis of ALK, RET or ROS1 fusion genes shows quite important. However, nowadays methods of detecting fusions such as fluorescence in situ hybridization (FISH) and immunohistochemistry (IHC) are limited to technique, low sensitivity, sample quality as well as subtype classification. Methods: We established nucleotide MALDI-TOF mass spectrometry based multiplex detection platform to distinguish major types including 9 types of EML4-ALK, 5 types of ALK, 5 types of RET and 8 types ROS1 fusions. Results: The detection limitation was about less 1% mutant cells among wild-type cells. In the pilot testing, we used 2 patients’ cell cDNA and 4 patients’ lung FFPE samples cDNA, which had been diagnosed as ALK fusion before, to be detected by this panel, and then identified their variant types successfully. Furthermore, one patient harbored CCDC6-RET fusion mutation was identified by our platform and confirmed by Sanger Sequencing. Conclusions: Taken together, this new panel has high sensitivity and allows little and poor quality samples for detecting. The correlation between clinical characteristics and fusion subtypes can be further investigated by utilizing this platform in the future. Also, the detection panel can be revised based on clinical needs by removing/adding probes.
Risk Factors Associated With Reoperation and Disease-Specific Mortality in Patients With Medullary Thyroid Carcinoma
Authors: Eric J. Kuo, Shonan Sho, Ning Li, Kyle A. Zanocco, Michael W. Yeh, Masha J. Livhits
Journal: JAMA Surgery (2017)

The association of initial neck dissection with recurrence in medullary thyroid carcinoma (MTC) has not been evaluated on a population level to date.To elucidate risk factors associated with reoperation in MTC and disease-specific mortality.A retrospective analysis was performed of hospital data obtained from the California Cancer Registry and the Office of Statewide Health Planning and Development from January 1, 1999, through December 31, 2012. The dates of the analysis were January 1, 1999, to December 31, 2012. A population-based sample of 953 patients with MTC was identified. Patients who underwent thyroid surgery and had a minimum postoperative follow-up of 2 years (n = 609) were included in the analysis.Initial neck dissection in MTC.Recurrent MTC leading to reoperation and disease-specific mortality.Of the 609 patients with MTC who underwent thyroid surgery, the mean (SD) patient age at diagnosis was 52.6 (17.5) years, and 60.8% (n = 370) of the patients were female. The mean (SD) tumor size was 2.8 (2.0) cm. Although initial central neck dissection is recommended by published MTC guidelines, only 35.5% (216 of 609) of patients underwent central neck dissection at the time of the initial thyroidectomy. The rate of reoperation was 16.3% (99 of 609), and the median time to reoperation was 6.4 months. The presence of lymph node metastasis increased the risk of reoperation (hazard ratio [HR], 3.43; 95% CI, 2.00-5.90), while central and lateral neck dissection performed at the initial operation was protective (HR, 0.53; 95% CI, 0.30-0.93). In patients who underwent reoperation, 45.5% (45 of 99) were disease free at a median follow-up of 7.7 years. Five-year disease-specific mortality for the entire cohort was 13.5% (82 of 609). Independent risk factors for disease-specific mortality included older age (HR, 1.36 per decade; 95% CI, 1.17-1.59), tumor size greater than 2 cm (HR, 2.83; 95% CI, 1.08-7.44 for >2 to 4 cm and HR, 2.89; 95% CI, 1.09-7.71 for >4 cm), and regional (HR, 4.77; 95% CI, 2.29-9.94) and metastatic (HR, 21.08; 95% CI, 9.90-44.89) disease. Reoperation was not associated with increased mortality.Lymph node dissection may decrease recurrence leading to reoperation for patients with MTC. Reoperation is a viable strategy to achieve long-term disease-free survival in appropriately selected patients. Central neck dissection remains underused.
Abstract 12142: Are Outcomes After Cardiac Arrest Influenced by the Quality of ICU Care?
Authors: Joseph H Pitcher, John T Dziodzio, Joshua A Keller, Richard R Riker, David B Seder
Journal: Circulation (2016)

Objective: To determine the association of modifiable hemodynamic and biochemical factors with outcome after cardiac arrest. Hypothesis: Optimal control of modifiable post-arrest factors for secondary injury improves outcome after cardiac arrest. Methods: We identified 222 consecutive cardiac arrest patients who received targeted temperature management in the Maine Medical Center registry from 1/2013 to 8/2015. We abstracted demographics, intra-arrest factors, and modifiable post-arrest factors [e.g. the absence of hypotension (MAP&lt;60mm Hg in the first 6 hours), normoglycemia (median glucose 80-180mg/dl), normoxemia (no PaO2&gt;300 or &lt;60mm Hg), and normocapnia (median PCO2 30-50mm Hg)] during the first 24 hours after return of spontaneous circulation. Primary outcome was cerebral performance category (CPC) at discharge. We compared pre-arrest, intra-arrest, and modifiable post-arrest factors in patients with good and poor outcomes using the Wilcoxon or Fischer-exact test, as appropriate. We also constructed logistic regression models to determine the independent effects of these factors on outcome (SAS 9.3, Cary, NC). Results: Thirty percent of patients had a CPC 1-2 at discharge. In univariate analysis, pre-arrest factors associated with poor outcome were history of COPD, cardiovascular disease, hypertension. A shockable rhythm was associated with good outcome. Of the studied modifiable post-arrest factors, normoglycemia was significantly associated with good outcome (p=0.002). In multivariate analysis that included pre-arrest and intra-arrest variables, optimal control of two or more post-arrest factors was associated with improved outcome (OR 7.2, p=0.0007, AUC for model 0.842). Conclusions: Optimal control of blood glucose, oxygen, carbon dioxide and blood pressure in the post-arrest period is associated with improved outcome after cardiac arrest. The combined endpoint of 2 or more post-arrest modifiable targets controlled was the strongest post-arrest predictor of good outcome in our model. While previous studies have reported these factors to be individually associated with poor outcome, further studies evaluating how the combination of these factors contribute to outcome is warranted.
<i>Notes from the Field</i>: Travel-Associated Melioidosis and Resulting Laboratory Exposures — United States, 2016
Authors: Patrick K. Mitchell, Colin Campbell, Martha P. Montgomery, Julie Paoline, Christopher Wilbur, Leah Posivak-Khouly, Kristin Garafalo, Mindy Elrod, Lindy Liu, Andre Weltman
Journal: MMWR Morbidity and Mortality Weekly Report (2017)

In mid-July 2016, a Pennsylvania resident aged 15 years who had recently returned from Thailand was treated by a pediatrician for sore throat, fever, and bilateral thigh abscesses at the sites of mosquito bites (Figure). She had traveled to northeast Thailand with nine other teens as part of an 18-day service-oriented trip run by an Ohio-based youth tour company that arranges travel to Thailand for approximately 500 persons annually. This trip included construction and agricultural activities and recreational mud exposures. The patient subsequently developed right inguinal lymphadenopathy and worsening abscesses, which prompted specimen collection for culture on August 25. This specimen was sent to a commercial laboratory in New Jersey, which identified Burkholderia pseudomallei, the causative organism of melioidosis, on August 30. The patient did not experience pneumonia or bacteremia, and recovered fully after 2 weeks of intensive therapy with parenteral ceftazidime and a 6-month outpatient course of eradication therapy with doxycycline.
Transcription factor MafB may play an important role in secondary hyperparathyroidism
Authors: Naoki Morito, Keigyou Yoh, Toshiaki Usui, Hisashi Oishi, Masami Ojima, Akiko Fujita, Ryusuke Koshida, Hossam H. Shawki, Michito Hamada, Masafumi Muratani, Kunihiro Yamagata, Satoru Takahashi
Journal: Kidney International (2017)
Addressing Variability in Opioid Prescribing
Authors: Selwyn O. Rogers
Journal: JAMA Surgery (2017)

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Serially measured circulating microRNAs and adverse clinical outcomes in patients with acute heart failure
Authors: Nick van Boven, Isabella Kardys, Laura C. van Vark, K. Martijn Akkerhuis, Maurice W.J. de Ronde, Mohsin A.F. Khan, Daphne Merkus, Zhen Liu, Adriaan A. Voors, Folkert W. Asselbergs, Ewout‐Jan van den Bos, Eric Boersma, Hans Hillege, Dirk J. Duncker, Yigal M. Pinto, Douwe Postmus
Journal: European Journal of Heart Failure (2017)
The relationship of increasing age, obesity, and comorbidities in uterine cancer survivors.
Authors: Emily Meichun Ko, Justin C. Brown, Nawar A. Latif, Ashley Haggerty, Kathryn Schmitz
Journal: Journal of Clinical Oncology (2014)

e16551 Background: Age and obesity are both associated with mortality after a diagnosis of uterine cancer. Women with uterine cancer are likely to have multiple comorbidities and are as likely to die of these conditions as of their cancer. These comorbidities may influence associations of age and obesity with mortality; therefore we sought to determine the association of age and obesity with comorbidities among a cohort of uterine cancer survivors. Methods: We conducted a single-institution survey-based study of uterine cancer patients undergoing surveillance who were diagnosed between 2006 and 2010, using the Charlson Comorbidity Index, in addition to collecting clinical-pathologic information. Descriptive analyses were performed followed by crude and adjusted generalized linear models, and multivariate logistic regression using STATA v13.1. Results: We obtained a 43% response rate (n=213). The mean age was 63.6 (SD 10.6). Racial distribution included 83% Caucasian, 13% African-American, and 3% other. Histology included 97% endometrial (75% Type I, 17% type II, 4% carcinosarcoma), and 4% sarcoma. 14% consisted of advanced stage. 96% underwent surgery and 49% received adjuvant treatment. 14% had diabetes and 49% had cardiovascular disease. Increasing age was associated with more frequent comorbidities. 40% of women age≥ 70 had ≥1 comorbidities compared to only 13% in those age<60. This relationship persisted even after adjusting for BMI only (OR 6.27, 95%CI 2.30-17.08); and after adjusting for BMI, race, stage, histology, and length of follow-up (OR 4.81, 95%CI 4.81-15.93). BMI was also independently associated with increased comorbidities. Patients with BMI≥35 had 6.1 times the odds of ≥1 comorbidities (95%CI 1.80-20.70) compared to patients with normal BMI. Conclusions: Both increasing age and BMI were independently associated with increased comorbidities in uterine cancer survivors. Most of the comorbidities in this population are controllable with appropriate medical intervention. Further research into developing interventions to diminish the prevalence and impact of these comorbidities may improve the overall survival of uterine cancer patients.
A Multicenter, Open Label Phase I/II Study of Carfilzomib, Pomalidomide and Dexamethasone in Relapsed and/or Refractory Multiple Myeloma (MM) Patients
Authors: Sara Bringhen, Valeria Magarotto, Anna Marina Liberati, Angelo Belotti, Alessandra Larocca, Milena Gilestro, Francesca Bonello, Gianluca Gaidano, Paola Bertazzoni, Raffaella Stocchi, Rossella Ribolla, Chiara Di Sano, Francesca Patriarca, Roberto Passera, Lorenzo De Paoli, Stefania Oliva, Anna Maria Cafro, Pieter Sonneveld, Antonio Palumbo, Mario Boccadoro
Journal: Blood (2016)