tbuckley/cabot-search huggingface dataset:
Assessment of the effectiveness of a chemotherapy education program: A Brown University Oncology Research Group study.
Authors: Nathan Theodore Connell, William M. Sikov, Katherine E. Faricy-Anderson, Susan Korber, Anthony George Thomas, Kayla Rosati, Howard Safran, Anthony E. Mega
Journal: Journal of Clinical Oncology (2013)

6574 Background: Patients about to begin chemotherapy often have questions about their treatment along with significant anxiety. This study evaluated whether pre-chemotherapy teaching sessions improved patient knowledge and anxiety. Methods: After meeting with their oncologist to discuss planned chemotherapy treatment, subjects completed a 10-question survey which assessed their knowledge of anticipated side effects and treatment schedule on a 1-4 rating scale (1=no knowledge, 2=minimally informed, 3=reasonably informed, 4=well informed) as well as anxiety about initiating chemotherapy (1=no anxiety, 2=minimal anxiety, 3=moderate anxiety, 4=severe anxiety). Subjects then completed a structured nurse-led chemotherapy education session. The survey was repeated on the first day of cycle 1. Mantel-Haentzel Chi-square tests were used to evaluate for changes across the surveys. Subgroup analysis by Wilcoxon signed-rank test was performed to assess differences in anxiety based on age. Results: At the time of analysis, 142 subjects had completed the education session. Improvement was seen in knowledge of treatment schedule (mean score increase from 2.5 to 3.4, p&lt;0.001), side effects (mean score increase from 2.3 to 3.4, p&lt;0.001), and how to use medications designed to prevent and treat nausea (mean score increase from 1.8 to 3.2, p&lt;0.001). There was significant reduction in patient anxiety about starting treatment (mean score decrease from 2.3 to 2, p&lt;0.001) and anxiety related to treatment side effects (mean score decrease from 2.3 to 2, p&lt;0.001). Analysis of anxiety by age showed that those age &lt;65 had higher baseline anxiety scores with a reduction in anxiety after the education session while those age ≥65 had lower baseline anxiety scores with a rise in anxiety after the education session (Table). Conclusions: A pre-chemotherapy teaching session improves patient knowledge about the planned treatment along with reduction in anxiety. Change in anxiety differs between patients 65 years of age and older as compared to those less than 65. [Table: see text]
Risk of interstitial lung disease and other pulmonary related adverse events among patients taking EGFR inhibitors: A meta-analysis of randomized controlled trials.
Authors: Salvador Ricardo Garcia, Elie Donath, Camilo A. Ortega-Parra, Robert J. Jacobson
Journal: Journal of Clinical Oncology (2013)

e19155 Background: Epidermal growth factor receptor (EGFR) inhibitors are suspected of being a potential cause of interstitial lung disease (ILD). This speculation is based largely on case reports and series in which it is difficult to establish causality. In this meta-analysis we evaluated randomized controlled trials (RCTs) involving EGFR inhibitors to verify if a relationship exists between exposure to EGFR inhibitors and development of ILD and other pulmonary-related events. Methods: EMBASE and Medline were searched for all RCTs evaluating cetuximab, gefitinib or erlotinib in non-small cell lung cancer (NSCLC). Studies were disqualified if the control contained any EGFR inhibitor or drug known to cause ILD. Thirty-one RCTs with 15,736 patients were identified. The primary outcome was ILD incidence. ILD is poorly defined and there is overlap with other pulmonary related outcomes including pneumonia, acute respiratory failure (ARF) and pneumonitis, and these were therefore secondary outcomes of interest. For all outcomes, a fixed-effects meta-analysis was performed. Results: For the primary outcome, there is a 173% increased risk of ILD among patients given EGFR inhibitors (RR 2.73, 95% CI: 1.74-4.23, p&lt;0.001) across 15 RCTs that report on ILD incidence. Among secondary endpoints, there is an 86% increased risk of pneumonia (RR 1.86, 95% CI 1.36-2.53, p&lt;0.001), a 19% increased risk of pneumonitis (RR 1.19, 95% CI: 0.62-2.27, p=0.59) and a 33% increased risk of ARF (RR 1.33, 95% CI: 0.65-2.72, p=0.44) among patients given EGFR inhibitors. There is minimal heterogeneity across trials for all above outcomes. Conclusions: EGFR inhibitors play a direct role in causing or contributing to ILD progression in patients with NSCLC who are susceptible to alveolar damage from prior chemoradiation therapy. Additionally, EGFR inhibitors seem to be associated with an increased risk for other pulmonary related events.This research suggests that caution should be undertaken in administering EGFR inhibitors to patients with poor baseline lung function or pre-existing pulmonary disease.
Association of Normal-Weight Central Obesity With All-Cause and Cause-Specific Mortality Among Postmenopausal Women
Authors: Yangbo Sun, Buyun Liu, Linda G. Snetselaar, Robert B. Wallace, Bette J. Caan, Thomas E. Rohan, Marian L. Neuhouser, Aladdin H. Shadyab, Rowan T. Chlebowski, JoAnn E. Manson, Wei Bao
Journal: JAMA Network Open (2019)

<h3>Importance</h3> Current public health guidelines for obesity prevention and control focus on promoting a normal body mass index (BMI), rarely addressing central obesity, which is reflected by high waist circumference (WC) and common in the general population. Studies of the association of normal-weight central obesity with long-term health outcomes are sparse. <h3>Objective</h3> To examine associations of normal-weight central obesity with all-cause and cause-specific mortality in postmenopausal women in the United States. <h3>Design, Setting, and Participants</h3> A nationwide prospective cohort study of 156 624 postmenopausal women enrolled in the Women’s Health Initiative at 40 clinical centers in the United States between 1993 and 1998. These women were observed through February 2017. Data analysis was performed from September 15, 2017, to March 13, 2019. <h3>Exposures</h3> Different combinations of BMI (calculated as weight in kilograms divided by height in meters squared; normal weight: BMI, 18.5-24.9; overweight: BMI, 25.0-29.9; and obesity: BMI, ≥30) and WC (normal: WC, ≤88 cm and high: WC, &gt;88 cm). <h3>Main Outcomes and Measures</h3> Mortality from all causes, cardiovascular disease, and cancer. <h3>Results</h3> Of the 156 624 women (mean [SD] age, 63.2 [7.2] years), during 2 811 187 person-years of follow-up, 43 838 deaths occurred, including 12 965 deaths from cardiovascular disease (29.6%) and 11 828 deaths from cancer (27.0%). Compared with women with normal weight and no central obesity and adjusted for demographic characteristics, socioeconomic status, lifestyle factors, and hormone use, the hazard ratio for all-cause mortality was 1.31 (95% CI, 1.20-1.42) among women with normal weight and central obesity, 0.91 (95% CI, 0.89-0.94) among women with overweight and no central obesity, 1.16 (95% CI, 1.13-1.20) for women with overweight and central obesity, 0.93 (95% CI, 0.89-0.94) for women with obesity and no central obesity, and 1.30 (95% CI, 1.27-1.34) for women with obesity and central obesity. Compared with normal weight without central obesity, normal-weight central obesity was associated with higher risk of cardiovascular disease mortality (hazard ratio, 1.25; 95% CI, 1.05-1.46) and cancer mortality (hazard ratio, 1.20; 95% CI, 1.01-1.43). <h3>Conclusions and Relevance</h3> Normal-weight central obesity in women was associated with excess risk of mortality, similar to that of women with BMI-defined obesity with central obesity. These findings underscore the need for future public health guidelines to include the prevention and control of central obesity, even in individuals with normal BMI.
ATP-binding cassette A1 deficiency causes cardiolipin-driven mitochondrial dysfunction in podocytes
Authors: G. Michelle Ducasa, Alla Mitrofanova, Shamroop K. Mallela, Xiaochen Liu, Judith Molina, Alexis Sloan, Christopher E. Pedigo, Mengyuan Ge, Javier Varona Santos, Yanio Hernandez, Jin-Ju Kim, Cyrille Maugeais, Armando J. Mendez, Viji Nair, Matthias Kretzler, George W. Burke, Robert G. Nelson, Yu Ishimoto, Reiko Inagi, Santanu Banerjee, Shaoyi Liu, Hazel H. Szeto, Sandra Merscher, Flavia Fontanesi, Alessia Fornoni
Journal: Journal of Clinical Investigation (2019)

Fibroblasts from patients with Tangier disease carrying ATP-binding cassette A1 (ABCA1) loss-of-function mutations are characterized by cardiolipin accumulation, a mitochondrial-specific phospholipid. Suppression of ABCA1 expression occurs in glomeruli from patients with diabetic kidney disease (DKD) and in human podocytes exposed to DKD sera collected prior to the development of DKD. We demonstrated that siRNA ABCA1 knockdown in podocytes led to reduced oxygen consumption capabilities associated with alterations in the oxidative phosphorylation (OXPHOS) complexes and with cardiolipin accumulation. Podocyte-specific deletion of Abca1 (Abca1fl/fl) rendered mice susceptible to DKD, and pharmacological induction of ABCA1 improved established DKD. This was not mediated by free cholesterol, as genetic deletion of sterol-o-acyltransferase-1 (SOAT1) in Abca1fl/fl mice was sufficient to cause free cholesterol accumulation but did not cause glomerular injury. Instead, cardiolipin mediates ABCA1-dependent susceptibility to podocyte injury, as inhibition of cardiolipin peroxidation with elamipretide improved DKD in vivo and prevented ABCA1-dependent podocyte injury in vitro and in vivo. Collectively, we describe a pathway definitively linking ABCA1 deficiency to cardiolipin-driven mitochondrial dysfunction. We demonstrated that this pathway is relevant to DKD and that ABCA1 inducers or inhibitors of cardiolipin peroxidation may each represent therapeutic strategies for the treatment of established DKD.
A phase I study of the safety and pharmacodynamic effects of everolimus in combination with lenalidomide in patients with advanced solid malignancies.
Authors: Taofeek Kunle Owonikoko, R Donald Harvey, John S Kauh, Colleen Margaret Lewis, Mohammed S Hossain, Adebowale O Akintayo, A. Rene Merriewether, Zhengjia Chen, Natalyn Nicole Hawk, Nabil F. Saba, Wayne Harris, Dong Moon Shin, Bassel F El-Rayes, Chunzi Huang, Sagar Lonial, David H. Lawson, Fadlo Raja Khuri, Edmund K. Waller, Suresh S. Ramalingam
Journal: Journal of Clinical Oncology (2012)

2576 Background: Everolimus (E), an mTOR inhibitor, and Lenalidomide (L) are both potent anti cancer agents with immunomodulatory effects. Preclinical evidence of enhanced cytotoxicity of the combination of an mTOR inhibitor and lenalidomide provided the rationale for this phase I study. Methods: Patients with advanced solid malignancies, ECOG performance status (PS) 0-2 and adequate organ function were eligible. Using standard 3+3 dose escalation schema, patients were treated in cohorts of three with increasing doses of E (5mg, 10mg) and L (10, 15, 20, 25mg) on day 1-28 of a 28-day cycle. Treatment cycles were repeated until disease progression by RECIST criteria or intolerable toxicity. Pharmacodynamic (PD) effects of treatment on circulating B and T lymphocytes subsets were assessed by multiparameter flow cytometry at baseline and after 2 cycles. Results: We enrolled 21 patients (thyroid-5, salivary gland-5, colon-4, sarcoma-2, and others-5); median age-58 (29-74); male-13; ECOG PS of 0, 1, 2 (3/17/1). Salient grade 3/4 toxicities included rash (67%), anemia (19%) and vomiting (5%) without dose limiting toxicities. The median number of completed cycles was 3 (1 - ≥15) and best response in 14 of 18 evaluable patients was stable disease (range 2- ≥14 months); median PFS was 116 days (14- ≥498). The RP2D of E and L was defined as 10mg and 25mg once daily, respectively. PD endpoint analysis after 2 cycles of treatment showed a significant increase in activated cytotoxic T cell subset (CD8+ICOS1+) in patients with salivary or thyroid cancers compared to other tumor types (+2051.0 vs. +394 vs. -1687.4 respectively; p=0.0303) and a trend for an increase in patients with non-progressing tumors (+661.7 vs. -384.1; p=0.0988). Other significant correlations were: Changes in total B-cells (CD3-CD19+) with PFS; NK cells with age (p=0.0211) and activated T cells (CD3+CD69+; CD3+CD62L-; p=0.01) with gender. Conclusions: The combination of E and L is well tolerated at the recommended single agent doses and showed promising efficacy in neuroendocrine and salivary adenoidcystic carcinoma. Modulation of activated T cell subsets (CD8+ICOS1+) correlates with efficacy of these agents.
Toll-like receptor 7 and 9 (TLR 7 and TLR 9) expression in biopsies of in situ cervical cancer.
Authors: Mario Adan Moreno-Eutimio, Raul Aragon-Franco, Constantino Lopez-Macias, Alejandro J. Silva, Horacio Astudillo
Journal: Journal of Clinical Oncology (2012)

e15584 Background: In order to analyze the expression of TLR 7 and TLR 9 in cervix biopsies, we evaluated the expression of these TLRs in cervical carcinoma in situ tissue and peritumoral inflammatory tissue biopsies by immunohistochemistry. Methods: We reviewed 276 uterine cervix biopsies of Clinical Specialties Women's Health Directorate of the Ministry of National Defense (between 2009-2010); the biopsies have the following histopathological diagnosis: 124 CIN I, 68 CIN II, 34 CIN III, 21 invasive cancer and 29 cancer in situ. Results: It was observed that peritumoral inflammatory tissue receptor was expressed positively in 89.6% in cervical cancer tissue in situ, the receptor was expressed positively in 68.9% and the negative expression was 31.1%, proving that in the peritumoral inflammatory tissue compared with in situ cervical cancer was increased expression of TLR 7. In the case of the expression of TLR 9, peritumoral inflammatory tissue, expressed positively in 24 samples and 5 samples were negative expression in the tissue in situ cervical cancer samples identified 20 positive and 9 negative samples. By analyzing the intensity of the expression of TLR 7 in cervical cancer tissue in situ, we found 16 samples with focal positive (+), 3 samples with diffuse positive (+ +) and 1 sample with positive (+ + + ), while in peritumoral inflammatory tissue found 13 samples with focal positive (+), 10 samples with diffuse positive (+ +) and 3 samples with positive results (+++). By analyzing the intensity of the expression of TLR 9 in cervical cancer tissue in situ, we found 14 samples with focal positive (+), 5 samples with diffuse positive (+ +) and 1 sample with positive (+), in contrast to the peritumoral inflammatory tissue was found 7 samples with focal positive (+), 13 samples tested positive diffuse (+ +) and 4 samples with positive results (+++). Conclusions: These results show that no significant difference between the expression of TLR 7 () and TLR 9 () in the peritumoral inflammatory tissue and tissue in situ cervical cancer found a decrease in the expression of TLR 7 and TLR 9 in tissue in situ cervical cancer compared with the expression in the peritumoral tissue inflammation.
Abstract 20559: Effectiveness and Safety of Rivaroxaban 15 mg Compared With Vitamin K Antagonists in Very Elderly Patients With Atrial Fibrillation, a Matched Cohort Study in the French Nationwide Claims Database SNIIRAM
Authors: Laurent Fauchier, Patrick Blin, Frederic Sacher, Caroline Dureau-Pournin, Marie-Agnes Bernard, Regis Lassalle, Cecile Droz-Perroteau, Jean Dallongeville, Nicholas Moore
Journal: Circulation (2017)

Introduction: The real-life benefits and risks of the direct-acting oral anticoagulants for stroke prevention in very elderly patients with non-valvular atrial fibrillation (NVAF) are still debated...
Peroral cholangioscopy of programmed cell death-1 inhibitor-related sclerosing cholangitis: three case reports
Authors: Takumi Onoyama, Yohei Takeda, Masayuki Kato, Mirai Edano, Ryohei Tarumoto, Kazuya Matsumoto, Hajime Isomoto
Journal: Endoscopy (2019)

Programmed cell death-1 (PD-1) inhibitor therapy is indicated for many types of malignancies, but can lead to immune-related adverse events [1] [2]. Recently, PD-1 inhibitor-related cholangitis and its clinical features, including peroral cholangioscopy, were reported [3] [4] [5]. However, the diagnostic criteria of PD-1 inhibitor-related cholangitis are unclear. We herein report peroral cholangiography for three patients with suspected pembrolizumab-related sclerosing chol-angitis.
Patricia Bath: ophthalmologist, inventor, and humanitarian
Authors: Barbara Kermode-Scott
Journal: BMJ (2019)

Credit: UCLA

Had Patricia Bath been born a white man, her achievements in ophthalmology, medicine, and humanitarianism would have deserved an obituary in The BMJ . Given she was born female and African American in a modest home in Harlem, her success in restoring or improving vision for millions was even more impressive.

During her career, Patricia Bath confronted the intersection of racism and sexism, according to her daughter, psychiatrist Eraka Bath. Never one to be thwarted, Bath gained a medical degree and started racking up a series of “firsts,” carving a path for women and minorities in ophthalmology, medicine, and academia. She was the first African American to undertake a residency in ophthalmology at New York University. When she received her fellowship, she became the first female ophthalmologist on the faculty of the Charles R Drew University of Medicine and Science (David Geffen School of Medicine, University of California and Los Angeles) and the UCLA Jules Stein Eye Institute. In 1976 she pioneered community ophthalmology, a new, volunteer based specialism …
The reliability of HER2-status determination from core-needle-biopsies and surgical specimens: A comparison of two established test methods (IHC, CISH)
Authors: V. Wolf, R. Groβe, J. Erggelet, H. J. Holzhausen, S. Hauptmann, C. Thomssen
Journal: Journal of Clinical Oncology (2009)

e22141 Background: A milestone of breast-cancer therapy was the discovery of HER-2 entailing special targeted therapy with improved prognosis. The HER-2-status is routinely assessed through immunohistochemistry (IHC; HercepTest) showing protein over-expression and is double-checked with in-situ-hybridisation (ISH) demonstrating gene amplification in equivocal cases. It is questioned whether these methods achieve identical results in core-needle-biopsies and in excisional tumor specimens. Methods: We performed a retrospective comparative study in order to address these questions. From 01/03–06/08 we collected the HercepTest results from both core-needle-biopsy and surgical specimen of 109 breast cancer patients in our institute and compared these to newly evaluated chromogenic ISH (CISH) results for both specimen types in order to assess the reliability of HER-2- diagnosis of both methodological approaches and of specimen type. Results: We found no significant difference in the HER- 2-status determined from either needle-biopsies or surgical specimens irrespective of the test used. For the overall comparison (218 specimens) of HercepTest and CISH we found only slight, non-significant deviations. Four cases were CISH-negative in spite of HercepTest scoring of 3+. Vice versa, five out of the total of 38 (17.4%) CISH-positives did not correspond to the HercepTest results of 0 or 1+. Conclusions: Though not significant, there is some inconsistency in the HER-2-determination depending on the test-method, leaving these cases equivocal. In accordance with the literature, we therefore recommend to at least double-check samples with 2+ in the HercepTest as it is the current standard. Our data support the use of core-needle-biopsy as a reliable tissue sample for HER-2-diagnosis. [Table: see text]
Mycobacterium abscessus infection and potable water [Conference Abstract]
Authors: Rachel Thomson, Carla Tolson, Robyn Carter, Christopher Coulter, Flavia Huygens, Megan Hargreaves
Journal: American Journal of Respiratory and Critical Care Medicine (2012)

Mycobacterium abscessus is a rapidly growing mycobacteria responsible for progressive pulmonary disease, soft tissue and wound infections, and can contaminate clinical specimens. Nontuberculous mycobacteria (NTM) are generally considered environmental organisms though M. abscessus has not featured frequently in environmental studies, particularly those examining potable water. In a study of Brisbane potable water, M. abscessus was isolate from ten different locations. The incidence of disease due to M. abscessus has been increasing in Queensland. Aim: To compare genotypically the M. abscessus isolates obtained from water to those obtained from human clinical specimens. Methods: From a study of Brisbane potable water between 2007 and 2009, ten isolates confirmed as M. abscessus were recovered. In addition, one strain was isolated from a rainwater tank of a patient with disease due to M. avium, and another from the swimming pool of a patient with M. intracellulare disease. A random sample of 74 clinical isolates referred to the QLD Mycobacterial reference laboratory during the same time period was available for comparison using repPCR strain typing (Diversilab). Results: The drinking water isolates formed two distinct strain patterns (A and B) that shared >90% similarity. The tankwater isolate (pattern C) shared >85% similarity with the potable water isolates, but the pool isolate (D) was distinctly different. Fifty-three clinical isolates clustered tightly (>95% similarity) with the Group A potable water isolates, 4 patients with Group B. Thirteen patient isolates clustered with the Rainwater tank isolate. One patient matched the pool isolate. There were a further 3 patient isolates that were unrelated to the water isolates. No differences were found between strain types in terms of geographic origin, gender, age, or site/type of infection. Conclusion: The high degree of similarity between strains of M. abscessus from potable water and strains causing infection in humans from the same area, strengthens the possibility that drinking water may be a source of infection in these patients.
Improving Usability of Health Information Technology—Reply
Authors: Raj M. Ratwani, Jacob Reider, Hardeep Singh
Journal: JAMA (2019)

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