tbuckley/cabot-search huggingface dataset:
Combination therapy with temsirolimus and trabectedin for recurrent clear cell carcinoma of the ovary: A phase II study with biomarker analysis.
Authors: Masashi Takano, Hiroko Kouta, Kazuya Kudoh, Tsunekazu Kita, Ryoko Kikuchi, Morikazu Miyamoto, Tomoyuki Yoshikawa, Tomoko Goto, Kenichi Furuya, Yutaka Tamada, Arata Suga, Yoshihiro Kikuchi
Journal: Journal of Clinical Oncology (2015)

5583 Background: Recurrent clear cell carcinoma (RCCC) of the ovary showed exceedingly chemo-resistant phenotype, especially in the case with recurrent or refractory to previous therapy. A phase II trial to evaluate the effect of combination therapy with temsirolimus and trabectedin for patients with RCCC was performed. Methods: Eligible patients were as follows: (a) ECOG PS = 0~2 (b) histologically confirmed ovarian clear cell adenocarcinoma (c) diagnosed as platinum-resistant ovarian cancer (d) written informed consent. Patients with RCCC were treated with weekly regimen using two drugs: 15mg/m2 of temsirolimus and 0.15mg/m2 of trabectedin (3 weeks, one week rest). Treatment was continued until development of progressive disease (PD) or unmanageable adverse effects. There was no significant difference of serum level of VEGF according to the response evaluation. Biomarker analyses including serum VEGF and BNP were also conducted. Results: A total of 21 patients were analyzed in the present study. There were no cases that discontinued the therapy due to toxicities. Median age was 59 years (range: 30-69), and median number of previous chemotherapy was 3 (range: 1-6). All cases were assessable by RECIST and CTCAE. One patient (5%) had a complete response (CR), and two cases (10%) achieved a partial response (PR), and 6 patients (29%) had a stable disease (SD) beyond three months, resulting in clinical benefit rate (CBR; CR+PR+SD > 3month) of 43%. Median response duration in CBR case was 3.5 months (range: 3-40+). There were no cases that developed toxicities more than grade2. There was no significant difference of serum level of VEGF according to the response evaluation. Conclusions: Combination therapy with temsirolimus and trabectedin was a candidate for salvage therapy for patients with RCCC. These results warrant further study in such clinical settings with biomarker analyses.
Contralateral breast cancer (CBC) incidence and risk in New Zealand (NZ).
Authors: Abbey Jebb, Ian Campbell, Rachel Shirley, Mark Barrios, David James Porter
Journal: Journal of Clinical Oncology (2015)

e17669 Background: Patients with unilateral breast cancer (UBC) are at increased risk of developing CBC. Several factors have been identified that influence this risk, however reports are inconsistent. CBC rates and patient outcome in NZ are unknown. Methods: NZ cancer registers provided information for patients with UBC diagnosed between June 2000 and December 2012. Patients without metastases who develop a subsequent second primary cancer in the contralateral breast were classed as having CBC. Logistic regression was performed to delineate association between variables and CBC diagnosis. Survival differences were determined by log rank test. Results: 10,374 patients had UBC, median follow-up 4.6 years. 48 women (0.46%) developed CBC, six within a year of UBC diagnosis (0.05%), and 30 by year 5 (0.3%). Variables associated with CBC development include being postmenopausal (HR 2.2, p = 0.02), pT stage 4 (HR 8.6, p = 0.00), and prior treatment with endocrine therapy (HR 2.0, p = 0.04). Having a first degree relative with breast or ovarian cancer was associated with CBC (HR 2.1, p = 0.02), however diagnosis in any less immediate relative/s was not (HR 1.2, p = 0.53). Lobular histology was not associated with CBC development (HR1.4, p = 0.45). Compared to all other ethnic groups, Maori showed a non-significant trend toward CBC development (HR 2.1, p = 0.06). Being premenopausal and having fewer nodes removed at UBC diagnosis were associated with reduced CBC rate (HR 0.4 and 0.24 respectively, p = < 0.05). BRCA testing was performed infrequently in this population (1.6% of patients), and no patient who developed CBC had a documented BRCA mutation. Mortality was greater in those with CBC (33.3% cf. 16%, HR 1.7, p = 0.09), as was disease specific mortality (18.8% cf. 8.5%, HR 1.75, p = 0.18). Development of metastases was far more common than CBC (ratio 26:1). Conclusions: The incidence of CBC in the NZ population is much lower than in historical series, and is vastly outnumbered by the incidence of metastatic cancer. Patients with CBC have increased overall and disease specific mortality. Several factors were identified in our population that were associated with CBC development. The risk of CBC in patients with a positive family history but no BRCA mutation remains undefined.
What type of environmental assessment and modification prevents falls in community dwelling older people?
Authors: Alison Pighills, Avril Drummond, Shelley Crossland, David J Torgerson
Journal: BMJ (2019)

### What you need to know

One third of people over the age of 65 experience a fall.1 The health and social care costs of falls are increasing with longevity.23 Falls are one of the leading causes of morbidity and death caused by injury in people over 75. Nearly a quarter of older people who fall are concerned about further falls, and some restrict activity. This can result in physical deconditioning, increased risk of future falls, institutionalisation, and reduced quality of life.4

Box 1 lists features that predispose older people to falls.5

Box 1 
### Risk factors for falls in community dwelling older people

#### We categorise falls risk asRETURN TO TEXT

Risk factors for falls can be categorised as

Environmental …
Abstract P047: Circulating Testosterone and Sex Hormone-Binding Globulin Concentrations and Risk of Type 2 Diabetes, Cardiovascular Disease, and All-Cause Mortality in US Women
Authors: Jun Li, Jie Hu, Tianyi Huang, Susan E Hankinson, Frank B Hu, JoAnn E Manson, Kathryn M Rexrode, Shelley S Tworoger
Journal: Circulation (2019)

Introduction: It remains unclear whether circulating testosterone and sex hormone-binding globulin (SHBG) are associated with cardiometabolic disease risk and mortality. Hypothesis: Higher SHBG and lower testosterone levels are associated with reduced risk of incident type 2 diabetes (T2D), cardiovascular disease (CVD), and all-cause mortality in women. Methods: Baseline testosterone and SHBG measures were available on 11,314 women from the Nurses’ Health Study I and II, who were part of 9 separate nested case-control studies and were free of CVD, T2D, and cancer at study baseline. Total testosterone was assayed by a radioimmunoassay or liquid chromatography tandem mass spectrometry; SHBG was measured by an immunoassay. Free testosterone was calculated based on a standard clinical formula. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regressions, adjusted for study design characteristics, established risk factors and confounders including menopausal statues, hormone therapy, and continuous body mass index. Results: During up to 22 years of follow-up (215,120 person-years), 891 incident T2D cases, 1,089 CVD cases (fatal myocardial infarction, nonfatal coronary heart disease, and fatal/nonfatal stroke), and 1,818 deaths occurred. In multivariable analyses, circulating SHBG levels were inversely associated with incident T2D (comparing the highest to lowest quartiles, HR [95% CI]: 0.34 [0.24-0.47]; P trend &lt;0.001) and all-cause mortality (HR: 0.78 [0.65-0.95]; P trend =0.03). Total testosterone was inversely associated with T2D (HR: 0.71 [0.53-0.96]; P trend =0.04), while free testosterone was positively associated with T2D (HR: 1.99 [1.44-2.75]; P trend &lt;0.001) and all-cause mortality (HR: 1.22 [1.00-1.48]; P trend =0.02). No association was observed between SHBG, nor free or total testosterone and CVD. Conclusions: Lower circulating levels of SHBG and higher levels of free testosterone were associated with increased risk of T2D and all-cause mortality, but not CVD, in women.
Reducing the Burden of Fellowship Interviews
Authors: Niel F. Miele
Journal: JAMA (2019)

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 HomeNew OnlineCurrent IssueFor Authors Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More 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 journal
Bioprinting of Cell‐Laden Microfiber: Can It Become a Standard Product?
Authors: Lei Shao, Qing Gao, Chaoqi Xie, Jianzhong Fu, Meixiang Xiang, Yong He
Journal: Advanced Healthcare Materials (2019)

Abstract Hydrogel microfibers have many fascinating applications as microcarriers for drugs, factors, and cells, such as 3D cell culture, building micro‐organoids, and transplantation therapy due to their simple structures. It is unknown whether cell‐laden fiber can become a standard‐use product like woundplast. Here, from the technical and practical view, the elements required for user‐oriented microfibers are first discussed: i) the materials used should promote cell functionalization and be easily processed; ii) follow a manufacturing method for mass fabrication; iii) have the ability to be stored long‐term and be available for immediate use. Here, it is demonstrated that bioactive microfibers can be simply fabricated with coaxial bioprinting using gelatin methacrylate due to its tunable biological and mechanical properties. Additionally, programmed microfibers and 3D constructs with controllable composition can also be fabricated. These microfibers can be used to directly build organoids and complex co‐culture tissue models. In the present study, vascular organoid, angiogenic sprouts, and tumor angiogenesis are demonstrated. It is also demonstrated, for the first time, that the cell‐laden microfibers can be stored long‐term via cryopreservation. These results show that cell‐laden structures can be developed as a novel type of organoid product, which will open more avenues for tissue engineering and clinical organ repair.
One Month of Rifapentine plus Isoniazid to Prevent HIV-Related Tuberculosis
Authors: Susan Swindells, Ritesh Ramchandani, Amita Gupta, Constance A. Benson, Jorge Leon-Cruz, Noluthando Mwelase, Marc A. Jean Juste, Javier R. Lama, Javier Valencia, Ayotunde Omoz-Oarhe, Khuanchai Supparatpinyo, Gaerolwe Masheto, Lerato Mohapi, Rodrigo O. da Silva Escada, Sajeeda Mawlana, Peter Banda, Patrice Severe, James Hakim, Cecilia Kanyama, Deborah Langat, Laura Moran, Janet Andersen, Courtney V. Fletcher, Eric Nuermberger, Richard E. Chaisson
Journal: New England Journal of Medicine (2019)

Tuberculosis is the leading killer of patients with human immunodeficiency virus (HIV) infection. Preventive therapy is effective, but current regimens are limited by poor implementation and low completion rates.We conducted a randomized, open-label, phase 3 noninferiority trial comparing the efficacy and safety of a 1-month regimen of daily rifapentine plus isoniazid (1-month group) with 9 months of isoniazid alone (9-month group) in HIV-infected patients who were living in areas of high tuberculosis prevalence or who had evidence of latent tuberculosis infection. The primary end point was the first diagnosis of tuberculosis or death from tuberculosis or an unknown cause. Noninferiority would be shown if the upper limit of the 95% confidence interval for the between-group difference in the number of events per 100 person-years was less than 1.25.A total of 3000 patients were enrolled and followed for a median of 3.3 years. Of these patients, 54% were women; the median CD4+ count was 470 cells per cubic millimeter, and half the patients were receiving antiretroviral therapy. The primary end point was reported in 32 of 1488 patients (2%) in the 1-month group and in 33 of 1498 (2%) in the 9-month group, for an incidence rate of 0.65 per 100 person-years and 0.67 per 100 person-years, respectively (rate difference in the 1-month group, -0.02 per 100 person-years; upper limit of the 95% confidence interval, 0.30). Serious adverse events occurred in 6% of the patients in the 1-month group and in 7% of those in the 9-month group (P = 0.07). The percentage of treatment completion was significantly higher in the 1-month group than in the 9-month group (97% vs. 90%, P<0.001).A 1-month regimen of rifapentine plus isoniazid was noninferior to 9 months of isoniazid alone for preventing tuberculosis in HIV-infected patients. The percentage of patients who completed treatment was significantly higher in the 1-month group. (Funded by the National Institute of Allergy and Infectious Diseases; BRIEF TB/A5279 ClinicalTrials.gov number, NCT01404312.).
What does acne genetics teach us about disease pathogenesis?
Authors: J.E.A. Common, J.N. Barker, M.A.M. Steensel
Journal: British Journal of Dermatology (2019)

Acne vulgaris is a highly prevalent inflammatory skin disorder with a complex pathogenesis, characterized by comedones, papules, pustules and nodules. Familial preponderance clearly indicates a genetic basis for acne vulgaris, but until recently solid genetic associations were lacking. The advent of high‐resolution genotyping array technologies has allowed for large‐scale studies with both family‐based and cross‐sectional designs. These studies have revealed genetic loci encompassing genes that could be active in biological pathways and processes underlying acne vulgaris. However, specific functional consequences of those variants remain elusive. In parallel, investigations into rare disorders and syndromes that incorporate features of acne or acne‐like lesions have recently accelerated our understanding of disease pathogenesis. The genes revealed by these rare disorders highlight mechanisms cardinal for pilosebaceous biology and therefore anchor our insights from genetic association studies for acne vulgaris. The next phase of research will require more in‐depth mechanistic investigations of loci and genes implicated in acne phenotypes to define the key molecular players driving the disorder. Concurrently, new treatments for acne vulgaris could be developed by dissecting the candidate molecular pathways to identify druggable targets.
Recommendations for analytical antiretroviral treatment interruptions in HIV research trials—report of a consensus meeting
Authors: Boris Julg, Lynda Dee, Jintanat Ananworanich, Dan H Barouch, Katharine Bar, Marina Caskey, Donn J Colby, Liza Dawson, Krista L Dong, Karine Dubé, Joseph Eron, John Frater, Rajesh T Gandhi, Romas Geleziunas, Philip Goulder, George J Hanna, Richard Jefferys, Rowena Johnston, Daniel Kuritzkes, Jonathan Z Li, Udom Likhitwonnawut, Jan van Lunzen, Javier Martinez-Picado, Veronica Miller, Luis J Montaner, Douglas F Nixon, David Palm, Giuseppe Pantaleo, Holly Peay, Deborah Persaud, Jessica Salzwedel, Karl Salzwedel, Timothy Schacker, Virginia Sheikh, Ole S. Søgaard, Serena Spudich, Kathryn Stephenson, Jeremy Sugarman, Jeff Taylor, Pablo Tebas, Caroline T Tiemessen, Randall Tressler, Carol D Weiss, Lu Zheng, Merlin L Robb, Nelson L Michael, John W Mellors, Steven G Deeks, Bruce D Walker
Journal: The Lancet HIV (2019)
A white ring around a naevus
Authors: Fei Han, Fei Wang
Journal: BMJ (2019)

A 23 year old man presented with a white ring around a congenital melanocytic naevus on the left cheek. The white ring had been present for three months. The naevus, present at birth, had grown relatively proportionally with the patient and became hairy when he reached 14. Examination revealed a dark brown, smooth, regular, well demarcated hairy naevus measuring 1.2 cm×0.8 cm in diameter, surrounded by a 0.3-0.8 cm white ring of depigmented skin below …
Long-term follow-up after radiotherapy for prostate cancer with and without rectal hydrogel spacer: A pooled prospective evaluation of quality of life.
Authors: Zachary A Seymour, Stephanie Daignault, Walter Bosch, Hiram Alberto Gay, Jeff M. Michalski, Daniel A. Hamstra, Michael Pinkawa
Journal: Journal of Clinical Oncology (2019)

39 Background: Hydrogel spacers are a tool to improve dosimetry and overall quality of life with limited follow-up in men receiving radiotherapy for prostate cancer. This present study is a pooled analysis of a prospective cohorts with long-term follow-up quality of life (QOL) data with or without hydrogel spacers to minimize dose adjacent organs at risk. Methods: QOL was examined using the Expanded Prostate Cancer Index Composite (EPIC) to compare mean changes from baseline. A total of 215 patients from a randomized multi-institutional trial of radiation with or without hydrogel spacer with a QOL end-point were pooled with 165 non-randomized patients from a single institution with prospective QOL collection in both patients with or without hydrogel spacer. The proportions of men with minimally important differences (MIDs) relative to pre-treatment baseline in each domain were tested using repeated measures logistic models with pre-specified thresholds for clinically significant decline. Results: A total of 380 men were evaluated (64% with spacer and 36% without) with QOL data being available for 199 men beyond 24 months of follow-up (median: 39.5 months, range: 31-71.4 mo). Treatment with spacer was associated with less decline in average long-term bowel QOL (89.4 for control and 94.7 for experimental) with differences at &gt; 2 years meeting the threshold of MID difference between cohorts (Bowel Score Difference from baseline: control = -5.1 spacer = 0.3 Diff = -5.4 p = 0.0003). When evaluated over time men without spacer were more likely to have 1xMID (5 points) declines in bowel QOL (p = 0.01). At long-term follow-up 1xMID was 36% without spacer vs 14% with spacer (p = 0.0006 OR = 3.5) while 2x MID was seen in 19% vs 6% (p = 0.008 OR = 3.6). The use of spacer was associated with improved bowel frequency (p = 0.002), reduced bleeding (p = 0.005) and less overall bowel problems (p = 0.007). Conclusions: In this pooled analysis of QOL after prostate radiotherapy with up to 5-years of follow-up utilization of a hydrogel spacer was associated with preservation of bowel QOL. This QOL benefit was preserved with long-term follow-up.
Impact of reflex testing for EGFR mutations in non-squamous non–small cell lung cancer (NSCLC).
Authors: Parneet Kaur Cheema, Charles Victor, Aastha Dolley, Alison Dziarmaga
Journal: Journal of Clinical Oncology (2015)

e17735 Background: EGFR mutation testing is standard of care in the management of advanced NSCLC. In Ontario, Canada medical oncologists (MO) request EGFR tests at time of first consultation with patients. This often leads to treatment delays and is a barrier to implementing personalized medicine. In attempts to have earlier EGFR results for the MO, some centers began adopting reflex testing, defined as pathologists requesting EGFR testing at time of diagnosis of non-squamous NSCLC histology irrespective of a patient’s NSCLC stage. The objective of this study is to determine if reflex testing of EGFR at the pathologist level improves rates of EGFR testing, and to determine its impact on tests requested by MO. Methods: Observational, retrospective review of the AstraZeneca Canada EGFR database (www.egfr-canada.ca) from April 1st, 2010 to March 31st, 2014. Centers within Ontario that requested EGFR testing through this database and implemented reflex testing with at least 2 years of data including pre and post implementation were included in this study. Rates of test requests and proportions of test characteristics and outcomes were compared prior to and following the introduction of reflex testing using negative binomial and logit-based generalized estimating equations respectively. Results: Seven centers were included, and 2,214 patients had EGFR tests requested. Reflex testing significantly increased the mean number of patients that had EGFR testing per center per month ((4.3 vs 13.1; mean difference of 7.8 (range across all centers: 4.5 to 14.9), p = < 0.001)). Significantly less tests were requested by MO (92% vs 46%), and increased requests by pathologists (6.2% vs 53%); p < 0.001. Reflex testing had no significant impact on EGFR requests for smokers, non-Asians or patients that were Caucasian, smoking, males. Nor did it significantly impact the completion rate of EGFR tests (80.5% vs 81.4%; p = 0.47), rate of inconclusive tests (5.4% vs 5.4%; p = 0.97) or rate of tests cancelled due to tissue not being received by testing lab (6.3% vs 7.2%; p = 0.41). Conclusions: Reflex testing led to increased EGFR testing in patients with NSCLC and successfully led to less tests being requested by MO, although it had no impact on success rates of the test.
Iron overload and liver cancer
Authors: Pedro Molina-Sánchez, Amaia Lujambio
Journal: The Journal of Experimental Medicine (2019)

In this issue of JEM, Muto et al. (https://doi.org/10.1084/jem.20180900) generate a novel mouse model of liver cancer induced by iron overload by deleting the iron-sensing ubiquitin ligase FBXL5 specifically in hepatocytes and exposure to a chemical carcinogen.