tbuckley/cabot-search huggingface dataset:
Are “Allow Natural Death” orders preferable to “Do Not Resuscitate” orders for patients with advanced cancer?
Authors: Dennis Omoding Emuron, Milos Miljkovic, Lori Rhodes, Joseph Abraham, Kenneth David Miller
Journal: Journal of Clinical Oncology (2013)

e20685 Background: Over twenty years after the passage of the Patient Self-Determination Act, patients’ preferences regarding end-of-life (EOL) care are often unknown to physicians. The aim of this study was to assess the knowledge and attitudes of cancer patients regarding EOL care, and to compare “Do Not Resuscitate” (DNR) and “Allow Natural Death” (AND) orders. Methods: Adult patients with advanced cancer were invited to participate. The first 50 consenting patients were surveyed regarding their prognosis and attitudes about critical care and resuscitation. We presented them with hypothetical scenarios in which a decision on their code status had to be made if they had 1 year, 6 months or 1 month left to live. Twenty-five patients were given a choice between being “full code" and DNR, and then 25 patients had a choice between "full code" and AND. Results: Almost half the patients (49%) were not aware that their illness was terminal. Fifty percent reported having a living will. However, only 19% reported that their doctors knew their wishes regarding EOL care. In contrast, greater than 78% reported knowledge of intubation, tracheotomy, feeding tubes, and cardiopulmonary resuscitation (CPR). The proportions of participants choosing full resuscitation compared to the DNR or AND options did not differ significantly from 50% (p-values &gt; 0.54). Their choices did not vary by age, sex, race, type of cancer, education or income level (p-values &gt; 0.05). Patients' attitudes towards CPR, tracheostomy and feeding tubes were not significantly associated with their choice of "DNR" (p-values &gt; 0.17), but those who wanted these interventions were significantly less likely to choose "AND" (p-values &lt; 0.002). As many as 38% of the patients without a living will chose "DNR", while 11% opted for "AND" (p-values &lt; 0.03). Conclusions: In this small sample of patients with advanced cancer many were unaware of their poor prognosis, and few informed their physicians of their EOL preferences. The wording of DNR and AND orders was not associated with patients' EOL preferences. Contrary to our expectation, the "Allow Natural Death" phrasing might be less acceptable to patients who view life-prolonging measures favorably.
Patient-Reported Quality of Life after Allogeneic Hematopoietic Cell Transplantation According to Types and Severity of Chronic Gvhd
Authors: Saiko Kurosawa, Kumi Oshima, Takuhiro Yamaguchi, Atsumi Yanagisawa, Takahiro Fukuda, Heiwa Kanamori, Takehiko Mori, Satoshi Takahashi, Tadakazu Kondo, Akio Kohno, Aika Seto, Yukari Umemoto, Takanori Teshima, Shuichi Taniguchi, Takuya Yamashita, Yoshiko Atsuta
Journal: Blood (2016)
Reply
Authors: Ho Cheol Hong, Kyung Mook Choi
Journal: Hepatology (2015)

Potential conflict of interest: Nothing to report. Author names in bold designate shared co‐first authorship. Aging and other risk factors are often accompanied by simultaneous changes in body composition that lead to decreased muscle mass and increased fat mass. Baumgartner et al. first defined sarcopenia as reduction in appendicular skeletal muscle mass divided by height squared (ASM/height2) of 2 standard deviations (SDs) or more below the normal means for a younger reference group.1 Although this definition have been used widely, Dr. Newman et al. have shown that this definition was highly correlated with body mass index and identified fewer overweight or obese individuals as sarcopenic.2 Janssen et al. proposed a definition of sarcopenia using the skeletal muscle mass index (SMI [%], skeletal muscle mass [kg]/weight [kg] × 100).3 Kim et al. suggested that decreased percent muscle mass in our study should be named by sarcopenic obesity (SO) or increased fat mass, rather than sarcopenia. However, most previous studies defined SO as a combined application of sarcopenia and obesity definition. In the Korean Longitudinal Study on Health and Aging, Lim et al. defined sarcopenia using ASM/height2 or ASM/Wt of <1 SD below the sex‐specific mean for young adults.4 To examine the prevalence of SO, they also defined obesity as a visceral fat area ≥100 cm2. They concluded that subjects with SO defined by ASM/Wt were more insulin resistant and had a higher risk for metabolic syndrome than simply obese subjects.4 The European Working Group on Sarcopenia in Older People recently recommended using the presence of both low muscle mass and low muscle function (strength or performance) for the diagnosis of sarcopenia.5 We agreed with the opinion that muscle strength does not depend solely on muscle mass, and the relationship between muscle mass and strength is not linear. Follow‐up examination, including muscle mass and muscle strength in the Korean Sarcopenic Obesity Study, has been underway, and we hope to explore the reciprocal influence between sarcopenia and nonalcoholic fatty liver disease in future longitudinal studies.
Abstract 17115: Airway Anomalies and Respiratory Factors Significantly Impact Post-operative Intensive Care Management in Patients With Trisomy 13 and 18 Following Cardiac Surgery
Authors: Sara K Swanson, Kurt R Schumacher, Richard G Ohye, Jeff D Zampi
Journal: Circulation (2016)

Introduction: Congenital heart disease is common in individuals with trisomy 13 and 18 (T13/18). While excellent survival after cardiac surgery is reported, there are limited data describing the im...
Abstract P242: Adenylate Kinase 2 Deficiency Disrupts Mitochondrial Energetics, AMP Metabolic Signaling, and Metabolomic Response to Myocardial Stress
Authors: Petras Dzeja, Song Zhang, Emirhan Nemutlu, Andre Terzic
Journal: Circulation Research (2011)

Adenylate kinase 2 (AK2) isoform in mitochondrial intermembrane/intracristal space provides a conduit facilitating ATP export and delivery to cellular ATPases. AK2+/- transgenic mice is viable while homozygous AK2-/- deficiency results in midgestation embryonic lethality. AK2-/- mouse embryonic fibroblasts (MEFs) have severely disrupted mitochondrial cristae structure and display low growth and proliferation potential. Protein knockdown using siRNA indicates that AK2 is critical for cardiomyocyte mitochondrial biogenesis and network formation. Transgenic AK2+/- hearts display greater changes in AMP/ATP ratio and AMPK activation during ischemia compared to wild type suggesting deficient tuning of AMP signals. Metabolomic profile of AK2+/- hearts subjected to myocardial ischemia indicate lower ability to maintain adenine and guanine nucleotide pools. AK2+/- mice have abnormal metabolomic response to treadmill exercise compared to wild type. Metabolomic profiling revealed that most significant plasma metabolites critical in the discrimination between wild type and AK2+/- phenotypes were adenosine, tyrosine, tryptophan and hypoxanthine indicating lower energetic potential of AK2+/- mice. AK2+/- hearts have increased mitochondrial creatine kinase CKmit content which could be viewed as a compensatory mechanism. Thus, AK2 is the first phosphotransfer enzyme which deficiency causes embryonic lethality indicating critical significance of catalyzed nucleotide exchange and conductive transfer in the narrow and crowded mitochondrial intermembrane/intracristal space.
Prevention of Early-Onset Neonatal Group B Streptococcal Disease with Selective Intrapartum Chemoprophylaxis
Authors: Kenneth M. Boyer, Samuel P. Gotoff
Journal: New England Journal of Medicine (1986)

Most cases of neonatal group B streptococcal disease with early onset have an intrapartum pathogenesis. Attack rates are increased substantially in infants born to mothers with prenatal group B streptococcal colonization and various perinatal risk factors (premature labor, prolonged membrane rupture, or intrapartum fever). In a randomized controlled trial, we studied the effect of selective intrapartum prophylaxis with ampicillin in 160 such high-risk women. In infants born to mothers who received intravenous ampicillin during labor, as compared with controls who received no treatment, neonatal colonization with group B streptococci was present in 8 of 85 (9 percent) versus 40 of 79 (51 percent; P<0.001), colonization at multiple (≥3) sites was observed in 3 of 85 (4 percent) versus 24 of 79 (30 percent; P<0.001), and bacteremia occurred in none of 85 versus 5 of 79 (6 percent; P = 0.024). The side effects of ampicillin were limited to a single episode of urticaria in a mother who had no history of penicillin allergy. We conclude that intrapartum ampicillin prophylaxis in women with positive prenatal cultures for group B streptococci who have certain perinatal risk factors can prevent early-onset neonatal group B streptococcal disease. (N Engl J Med 1986; 314:1665–9.)
Association of second primary malignancies with past and family history of malignancy in patients with small cell lung cancer.
Authors: Keisuke Kirita, Koichi Goto, Shigeki Umemura, Kiyotaka Yoh, Seiji Niho, Hironobu Ohmatsu, Kanji Nagai, Yuichiro Ohe
Journal: Journal of Clinical Oncology (2012)

e17526 Background: Based on recent development in the treatment for small cell lung cancer (SCLC) such as chemotherapy and radiotherapy, long-term survivors are frequently observed. Meanwhile, etoposide and radiotherapy, which are key treatments for SCLC, are also known as methods to set up late complication including carcinogenicity. There have been few reports of second primary malignancies (SPM) in patients with SCLC, and risk factor for SPM has not become evident other than smoking continuation. Methods: From July 1992 to December 2009, 900 patients with SCLC were treated in National Cancer Center Hospital East. Medical records of all patients were retrospectively reviewed, and the incidence and risk factor for SPM were investigated. Results: Demographics of all patients with SCLC were as follows: Male/Female, 738/162; median age, 66 years (range 22-87); smoking pack-year (PY) &lt;30/30≤, 155/745; Limited/Extensive, 468/432. Median follow up time was 4.5 years. Three and 5-year overall survival rate were 16.4% and 11.6%, respectively. Twenty-seven patients (3.0%) developed SPM, 15 patients (54%) of whom died due to SPM. Thoracic cancer occupied 52% of them (lung, 11; trachea, 1; esophagus, 4; breast, 1). Three and 5-year cumulative incidence rate (CIR) of SPM were 2.5% and 11.8%. Although there was no significant risk factor for SPM, the groups having past history of malignant disease and heavy smoker (PY ≥30) tended to develop SPM (p=0.11and 0.07). Using etoposide containing regimen and thoracic irradiation were not significant risk factors for the incidence of SPM (p=0.84 and 0.24). Neither serum level of CEA, NSE nor ProGRP were risk factors of incidence of SPM (p=0.51, 0.09 and 0.21). Within over 2-year survivors, there was a significant correlation between family history of cancer within first-degree relatives and CIR of SPM (p&lt;0.01). Conclusions: Five years CIR of SPM was 11.6%, and secondary thoracic cancer accounted for large portion of them. It was concluded that cumulative smoking amount, past history of malignant disease, and positive family history of cancer within first-degree relatives were risk factors for SPM.
Adverse outcome pathways: Application to enhance mechanistic understanding of neurotoxicity
Authors: Anna Bal-Price, M.E. (Bette) Meek
Journal: Pharmacology & Therapeutics (2017)

Recent developments have prompted the transition of empirically based testing of late stage toxicity in animals for a range of different endpoints including neurotoxicity to more efficient and predictive mechanistically based approaches with greater emphasis on measurable key events early in the progression of disease. The adverse outcome pathway (AOP) has been proposed as a simplified organizational construct to contribute to this transition by linking molecular initiating events and earlier (more predictive) key events at lower levels of biological organization to disease outcomes. As such, AOPs are anticipated to facilitate the compilation of information to increase mechanistic understanding of pathophysiological pathways that are responsible for human disease. In this review, the sequence of key events resulting in adverse outcome (AO) defined as parkinsonian motor impairment and learning and memory deficit in children, triggered by exposure to environmental chemicals has been briefly described using the AOP framework. These AOPs follow convention adopted in an Organization for Economic Cooperation and Development (OECD) AOP development program, publically available, to permit tailored application of AOPs for a range of different purposes. Due to the complexity of disease pathways, including neurodegenerative disorders, a specific symptom of the disease (e.g. parkinsonian motor deficit) is considered as the AO in a developed AOP. Though the description is necessarily limited by the extent of current knowledge, additional characterization of involved pathways through description of related AOPs interlinked into networks for the same disease has potential to contribute to more holistic and mechanistic understanding of the pathophysiological pathways involved, possibly leading to the mechanism-based reclassification of diseases, thus facilitating more personalized treatment.
The APPLE Association President's Message
Authors: Terry M. Therneau, Lewis R. Roberts, Hager A. Ahmed Mohammed, Ju Dong Yang, Nasra H. Giama, Jonggi Choi, Hawa M. Ali, Kristin C. Mara, William S. Harmsen, Russell H. Wiesner, Michael D. Leise, Naoshi Nishida, Satoru Hagiwara, Toshiharu Sakurai, Masatoshi Kudo, Tadaaki Arizumi, Hiroshi Ida, Yoshihiro Sakamoto, Norihiro Kokudo, Yoshikuni Kawaguchi, Keiichi Akita, Guido Torzilli, Masatoshi Kudo, Naoki Morimoto, Norio Isoda, Yoshinari Takaoka, Takuya Hirosawa, Shunji Watanabe, Toshiya Otake, Kozue Murayama, Mamiko Tsukui, Takeshi Fujieda, Natsumi Miyata, Kohei Ono, Shota Yamaguchi, Hironori Yamamoto, Masamitsu Kumon, Druckerei Stückle, Druckerei Stückle
Journal: Liver Cancer (2017)
Treatment of Cytomegalovirus Retinitis in Patients with the Acquired Immunodeficiency Syndrome
Authors: M A Jacobson
Journal: New England Journal of Medicine (1997)

Until recently, long-term regimens consisting of daily intravenous infusions of ganciclovir or foscarnet were the only available treatments for patients with cytomegalovirus (CMV) retinitis, a sight-threatening complication that affects approximately one third of patients in the United States with the acquired immunodeficiency syndrome (AIDS).1,2 In the past three years, the results of 11 randomized clinical trials of four new treatments for AIDS-related CMV retinitis have been reported.313 Thus, there are now new therapies from which clinicians can choose.Incidence and Natural History of CMV RetinitisCMV end-organ disease has emerged as one of the most common serious complications . . .
A comparative evaluation of genome assembly reconciliation tools
Authors: Hind Alhakami, Hamid Mirebrahim, Stefano Lonardi
Journal: Genome biology (2017)

The majority of eukaryotic genomes are unfinished due to the algorithmic challenges of assembling them. A variety of assembly and scaffolding tools are available, but it is not always obvious which tool or parameters to use for a specific genome size and complexity. It is, therefore, common practice to produce multiple assemblies using different assemblers and parameters, then select the best one for public release. A more compelling approach would allow one to merge multiple assemblies with the intent of producing a higher quality consensus assembly, which is the objective of assembly reconciliation. Several assembly reconciliation tools have been proposed in the literature, but their strengths and weaknesses have never been compared on a common dataset. We fill this need with this work, in which we report on an extensive comparative evaluation of several tools. Specifically, we evaluate contiguity, correctness, coverage, and the duplication ratio of the merged assembly compared to the individual assemblies provided as input. None of the tools we tested consistently improved the quality of the input GAGE and synthetic assemblies. Our experiments show an increase in contiguity in the consensus assembly when the original assemblies already have high quality. In terms of correctness, the quality of the results depends on the specific tool, as well as on the quality and the ranking of the input assemblies. In general, the number of misassemblies ranges from being comparable to the best of the input assembly to being comparable to the worst of the input assembly.
A Pragmatic View of the New Cholesterol Treatment Guidelines
Authors: John F. Keaney, Gregory D. Curfman, John A. Jarcho
Journal: New England Journal of Medicine (2013)

New ACC–AHA guidelines represent a substantial departure from previous recommendations for lipid management and may have a major effect on clinical practice. Overall, they will move treatment toward statins and deemphasize other agents for a broader range of patients.
Haemopneumothorax after fine needle aspiration of the breast
Authors: R Hoey, H Russell
Journal: Journal of the Royal Society of Medicine (2003)

We must congratulate Dr Whitaker and his team for correctly diagnosing a tension pneumothorax and saving the patient’s life with subsequent needle thoracocentesis (November 2003 JRSM1). The tension had arisen 32 hours after a diagnostic fine needle aspiration (FNA) of the left upper outer quadrant of the breast. However, we disagree that the ensuing haemothorax was caused by the FNA and feel it was far more likely to be caused by the needle thoracocentesis. At operation the lesion was found to be at the apex of the lung which in the normal lung lies above the clavicle, higher than where the FNA was performed. Needle thoracocentesis for a tension pneumothorax at the 2nd intercostal space midclavicular line is much more likely to hit the apex of the lung and cause haemothorax.
Monsters and angels
Authors: Richard Hurley
Journal: BMJ (2017)

The closeted gay lawyer Roy Cohn, who has AIDS and is dying from cancer, is nursed by Belize, a former drag performer, in a sell-out new stage production of Tony Kushner’s 1991 play Angels in America.

This two part Pulitzer and Tony prize winning epic documents the emergence of the HIV epidemic and its effect on gay and bisexual men in the 1980s. Frank, funny, and tender, this elaborate show is …
Adiposity post prophylactic oophorectomy in young women at high risk for breast and ovarian cancer.
Authors: Kala Visvanathan, Minh-Huy Huynh, Rawan Al-Lozi, Jessica Oidtman, Betty J May, Pamela Ouyang
Journal: Journal of Clinical Oncology (2013)

1572 Background: Bilateral prophylactic salpingo-oophorectomy (BPSO) is the current standard of care for BRCA1/2 mutation carriers and women with a strong family history of ovarian cancer. We have previously demonstrated an association between early oophorectomy, adiposity and mortality in the general population. Methods: A cross sectional study was conducted between November 2009 and January 2013 in 87 women with a family history of breast and ovarian cancer and/or BRCA1/2 mutation to identify the effect of early BPSO on multiple health outcomes. Twenty-two women who underwent BPSO within 1 to 5 years of enrollment while premenopausal and not on hormone therapy were compared to 44 premenopausal women with intact ovaries and the same age distribution and 21 postmenopausal women with intact ovaries and not on hormone therapy. Multiple anthropometric measures were taken and % body fat assessed by DEXA scan. Linear regression was used to estimate differences in these measures between the three groups. Results: The mean ages were 47, 47, and 54 years in the BPSO, premenopausal and postmenopausal groups respectively. Parity, alcohol intake, smoking and race did not significantly differ between groups. Fewer BPSO women had ever used oral contraceptives (OCP) compared to the premenopausal group (p =0.05). The BPSO group had lower mean physical activity (p = 0.05) compared to the two other groups. BMI was increased in the BPSO group but was not statistically different across groups. However, mean waist and abdominal circumference and trunk % body fat were significantly higher among women who underwent BPSO compared to both groups. In multivariate analyses adjusting for age, physical activity, and OCP use, the average waist circumference was 7.92 cm (95% CI 1.46, 14.37) higher and 8.98 cm (95% CI 0.40, 17.46) higher in the BPSO group compared to the postmenopausal and premenopausal groups, respectively. A similar pattern was seen for abdominal circumference. Association with % body fat were not statistically significant. Conclusions: This pilot study suggests that increased central adiposity, is a sequelae of BPSO in young women. Longitudinal studies are needed to confirm results and evaluate the efficacy of interventions.
Rac1 inhibition to sensitize triple negative breast cancer to EGFR inhibition.
Authors: Georges Azzi, Erik Goka, Dana Senderoff, Marc E. Lippman
Journal: Journal of Clinical Oncology (2015)

1084 Background: Triple Negative Breast Cancer (TNBC) a subtype of breast cancer with the poorest prognosis lacks expression of estrogen progesterone receptors and does not overexpress HER2. Currently, there are no effective targeted therapies. TNBC frequently overexpresses EGFR, a member of the ErbB family of transmembrane receptor tyrosine kinases. Although EGFR targeted therapies are approved and used widely in lung cancer and head and neck cancer, their use in breast cancer has not revealed significant activity. Previous studies in lung cancer have shown that Rac1 overexpression results in resistance to EGFR inhibition. Rac1, a Rho GTPase, is frequently overexpressed in breast cancer. We have previously reported that Rac inhibition may be an effective therapeutic strategy in breast cancer. Furthermore, we have previously shown that EGFR over-expression results in resistance to Rac inhibition in breast cancer. The aim of the current study was to assess the activity of gefitinib (an EGFR tyrosine kinase inhibitor) and a Rac inhibitor (EHT1864) alone or in combination in TNBC. Methods: Using proliferation and clonogenic assays we assessed the activity of gefitinib (2.5 μM) and EHT1864 (25 μM), and their use in combination on the growth of TNBC breast cancer cell lines (MDA 231, MDA 468, MDA 436, HS578T). We also confirmed the pharmacological effect of gefinitib on EGFR with molecular knockdown of EGFR in HS578T cells. Results: All 4 cell lines tested did not show any significant growth reduction or difference in colony formation with either agent alone but the combination was effective in significantly reducing both growth and colony formation potential in 2 of the TNBC cell lines ( HS578T and MDA468). The combination of shEGFR knockdown and Rac inhibition phenocopied the results of pharmacological inhibition with gefitinib plus EHT1864. Conclusions: Our results suggest that Rac inhibition sensitizes a subset of TNBC to EGFR inhibition and the combination of Rac and EGFR inhibition is a promising therapeutic strategy for a subset of TNBC that warrants further studies.