tbuckley/cabot-search huggingface dataset:
Should Metformin Be First-line Therapy for Patients With Type 2 Diabetes and Chronic Kidney Disease?
Authors: Chester B. Good, Leonard M. Pogach
Journal: JAMA Internal Medicine (2018)

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
Stage IV colorectal cancer: An NCDB analysis of the surgical treatment of peritoneal carcinomatosis versus liver metastases.
Authors: Samer A Naffouje, George I. Salti
Journal: Journal of Clinical Oncology (2017)

e15067 Background: Traditionally, peritoneal carcinomatosis (PC) secondary to colorectal cancer (CRC) was perceived as a terminal disease, for which the only palliation was offered. With the emergence of new surgical approaches such as cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC), surgical intervention in select patients with ‘curative’ intent was made possible. In this study, we compared the outcomes of the surgical intervention on stage IV CRC patients with isolated liver metastases (LM) to those with PC only. Methods: The National Cancer Database (NCDB) for CRC was analyzed excluding patients with PMP. Patients with isolated LM or with PC were identified, then divided into 2 treatment groups per the current treatment of each scenario: LM patients treated with surgery±chemotherapy (LM group), and PC patients treated with surgery+chemo±HIPEC (PC group). Results: 21,829 patients were identified; 18,932 fell in the LM group, and 2,897 in the PC group. Mean age in the LM and PC groups was 62.94±13.54 vs. 59.59±13.73. No significant difference was noted in the 30-day readmission rates (6.0% vs. 6.6%; p = 0.103). LM group had higher rates of 30- and 90-day mortality (4.3% vs. 0.3% and 8.6% vs. 1.8%, respectively; p &lt; 0.0001), but a slightly shorter hospitalization (7.70±8.64 vs. 7.92±7.07; p = 0.024) Median overall survival was not different between the groups (27.3 vs. 25.36 months; p = 0.214). Conclusions: Surgery with systemic and IP chemotherapy can be a viable treatment option in stage IV CRC patients with PC with comparable short-term and survival outcomes to the widely accepted liver resection in patients with isolated LM.
Patterns and predictors of attendance at a comprehensive, multi-disciplinary supportive care program for men with prostate cancer and their partners.
Authors: Lindsay Hedden, Phil Pollock, Maria Spillane, Monita Sundar, Alan So, Peter C. Black, Martin Gleave, Larry Goldenberg, Celestia S. Higano
Journal: Journal of Clinical Oncology (2018)

6 Background: Men diagnosed with prostate cancer (PC) face treatment-related sequlae that affect their health and quality of life. The Vancouver Prostate Centre’s (VPCs) Prostate Cancer Supportive Care (PCSC) Program is a comprehensive program for men and their partners that aims to address these challenges. Our objective is to examine registration rates, and the timing/intensity of follow-up with the program, and to explore clinical/sociodemographic factors associated with participation and non-participation. Methods: We used charts for all men who registered with the PCSC program (“registrants”), and a random sample of men who sought PC-related care at the VPC but did not register with the program (“non-registrants”) from Jan 2013-Dec 2016. Registrants were classified as “attenders” (came to PCSC information session/clinic visit), or “non-attenders” (did not attend). We used multivariate logistic regression to quantify the effect of diagnostic, treatment and sociodemographic characteristics on registration. We produced an unadjusted Kaplan-Meier estimator to assess the probability of program attendance over the disease trajectory for those who registered. We used Cox proportional hazards regression to examine impact of the same factors on timing of program participation and a binary logistic model to examine which factors impact program attendance. Results: Preliminary results suggest that 17% of the men who enroll in the program do not subsequently use any services. Program participation continues for more than four years after diagnosis and varies based on Gleason score (Chi Square (CS) = 20.9, p = 0.01), risk score (CS = 11.5, p = 0.02), and clinical T stage (CS = 14.0, p &lt; 0.001). We found no difference participation by age, age at diagnosis, travel distance to clinic or treatment modality. Complete results will be available at the time of presentation. Conclusions: One in six men who register for supportive care do not end up using any despite the program being free of charge. Drivers of non-participation appear to be clinical, with lower risk patients being more likely to chose not to participate, though further investigation is required.
Bringing a creative writing intervention for young adult cancer survivors online.
Authors: Mallory C Casperson, Jennifer Peckham
Journal: Journal of Clinical Oncology (2018)

166 Background: Studies show the importance of age-specific, young adult cancer (YAC) psychosocial interventions. They demonstrate psychological interventions “reduce emotional stress and increase coping skills needed to adjust to life after a cancer diagnosis."(Peckham JL, et al. JAYAO. 2017;6:50-52.) With YAC survivors spread around the country, many lack access to such interventions. This feasibility study considered online delivery of a structured, long term writing intervention in YAC survivors and the perceived participant benefit. Methods: Lacuna Loft held three structured, creative writing workshops over 10 weeks, 10 weeks, and 8 weeks. An online video chat platform delivered the workshops, allowing participant connection via video and voice. The workshop followed the methods used in Unspoken Ink.(Peckham JL, et al. JAYAO. 2017;6:50-52.) Each week used a different cancer topic and several prompts were given. Participants completed questionnaires at the start and end of each workshop. Results: Over three writing workshops, twenty-one people completed a workshop, five participated in multiple, and ninety expressed interest in future workshops. People from nine states and three countries participated. The online platform allowed writers to join from any location including the hospital. Participants expressed a decrease in feelings of isolation at the completion of a workshop as well as an increase in feelings of connection to other YAC survivors. All participants stated they would refer another YAC survivor to the workshop. The online nature of the program proved inconsequential. Conclusions: Research shows that structured writing workshops for YAC survivors “to explore their cancer experiences may be an effective psychosocial intervention.”(Peckham JL, et al. JAYAO. 2017;6:50-52.) This study used online video chat platform to deliver the workshop and connect participants. All participants expressed decreased feelings of isolation and increased feelings of connection to their YAC survivor peers at the conclusion. Most had never participated in an online group previous to this online workshop. Online delivery of structured writing interventions thus allows for more wide-spread accessibility of psychosocial interventions for YAC survivors.
Mortality of Mice after Total-Body Irradiation as Influenced by Alterations in Total Dose, Fractionation, and Periodicity of Treatment&lt;xref ref-type="fn" rid="fn1"&gt;&lt;sup&gt;2&lt;/sup&gt;&lt;/xref&gt;
Authors: Henry S. Kaplan, Mary B. Brown
Journal: JNCI Journal of the National Cancer Institute (1952)

Journal Article Mortality of Mice after Total-Body Irradiation as Influenced by Alterations in Total Dose, Fractionation, and Periodicity of Treatment Get access Henry S. Kaplan, M. D., Henry S. Kaplan, M. D. Department of Radiology, Stanford University School of Medicine, San Francisco, Calif. Search for other works by this author on: Oxford Academic PubMed Google Scholar Mary B. Brown Mary B. Brown Department of Radiology, Stanford University School of Medicine, San Francisco, Calif. Search for other works by this author on: Oxford Academic PubMed Google Scholar JNCI: Journal of the National Cancer Institute, Volume 12, Issue 4, February 1952, Pages 765–775, https://doi.org/10.1093/jnci/12.4.765 Published: 01 February 1952 Article history Received: 25 September 1951 Published: 01 February 1952
Cognitive-Behavioral Analysis System of Psychotherapy, Drug, or Their Combination for Persistent Depressive Disorder: Personalizing the Treatment Choice Using Individual Participant Data Network Metaregression
Authors: Toshi A. Furukawa, Orestis Efthimiou, Erica S. Weitz, Andrea Cipriani, Martin B. Keller, James H. Kocsis, Daniel N. Klein, Johannes Michalak, Georgia Salanti, Pim Cuijpers, Elisabeth Schramm
Journal: Psychotherapy and Psychosomatics (2018)

&lt;b&gt;&lt;i&gt;Background:&lt;/i&gt;&lt;/b&gt; Persistent depressive disorder is prevalent, disabling, and often difficult to treat. The cognitive-behavioral analysis system of psychotherapy (CBASP) is the only psychotherapy specifically developed for its treatment. However, we do not know which of CBASP, antidepressant pharmacotherapy, or their combination is the most efficacious and for which types of patients. This study aims to present personalized prediction models to facilitate shared decision-making in treatment choices to match patients’ characteristics and preferences based on individual participant data network metaregression. &lt;b&gt;&lt;i&gt;Methods:&lt;/i&gt;&lt;/b&gt; We conducted a comprehensive search for randomized controlled trials comparing any two of CBASP, pharmacotherapy, or their combination and sought individual participant data from identified trials. The primary outcomes were reduction in depressive symptom severity for efficacy and dropouts due to any reason for treatment acceptability. &lt;b&gt;&lt;i&gt;Results:&lt;/i&gt;&lt;/b&gt; All 3 identified studies (1,036 participants) were included in the present analyses. On average, the combination therapy showed significant superiority over both monotherapies in terms of efficacy and acceptability, while the latter 2 treatments showed essentially similar results. Baseline depression, anxiety, prior pharmacotherapy, age, and depression subtypes moderated their relative efficacy, which indicated that for certain subgroups of patients either drug therapy or CBASP alone was a recommendable treatment option that is less costly, may have fewer adverse effects and match an individual patient’s preferences. An interactive web app (https://kokoro.med.kyoto-u.ac.jp/CBASP/prediction/) shows the predicted disease course for all possible combinations of patient characteristics. &lt;b&gt;&lt;i&gt;Conclusions:&lt;/i&gt;&lt;/b&gt; Individual participant data network metaregression enables treatment recommendations based on individual patient characteristics.
Identification and functional characterization of a novel MUTYH gene mutation.
Authors: Kevin McDonnell, Joseph A. Chemler, Monica L. Marvin, Ralph H. Stern, Leon Raskin, David H. Sherman, Stephen B. Gruber
Journal: Journal of Clinical Oncology (2012)

e12026 Background: Biallelic germline mutations in MUTYH result in the autosomal recessive syndrome of MUTYH associated polyposis (MAP).Three well-known, common mutations account for the vast majority of identifiable germline mutations, and serve as the basis for current genetic testing strategies. Comprehensive sequencing of MUTYH often identifies variants of uncertain pathologic significance, and studies to determine the pathogenicity of newly identified variants may offer valuable clinical information and mechanistic insights. In the present study we seek to describe the base-excision repair function of a novel MUTYH (p.C306W) mutation identified in a patient with multiple colon polyps and a family history of colon cancers. Methods: A 50 year old patient with &gt;50 adenomas underwent clinical and laboratory evaluation to assess for germline genetic mutations. We performed Sanger sequencing of tumor and germline DNA together with targeted restriction enzyme digest of germline DNA and fragment DNA sequencing of the alleles. We prepared MUTYH proteins with protein liquid chromatography and assessed their mismatched adenine excision repair capacity employing a glycosylase assay. Results: Analysis of the patient's germline DNA revealed an absence of APC mutations, and the presence of the previously well characterized p.G396D MUTYH mutation as well as a novel p.C306W mutation. Targeted restriction enzyme digest demonstrated trans configuration of the p.G396D and p.C306W MUTYH mutations. Mismatched adenine excision functionality of wildtype MUTYH, known mutant controls p.G396D and p.Y179C, and putative mutant p.C306W were assessed in the glycosylase assay. Consistent with previous experimental observations, relative to wildtype MUTYH, the p.G396D and p.Y179C MUTYH mutants demonstrated attenuated adenine excision activities of 43% and 0%, respectively. Comparable to the activity of the pY179C mutant, the novel p.C306D mutant demonstrated 0% adenine excision activity. Subsequent tumor analysis demonstrated G:C to T:A transversion in the APC gene in somatic DNA derived from an adenoma. Conclusions: Experimental and clinical data demonstrate that p.C306D MUTYH is a pathogenic mutation contributing to the phenotype of MAP.
National practice pattern and outcome of very early breast cancer.
Authors: Mahvish Muzaffar, Kevin O'Brien, Abdul Rafeh Naqash, Jan H. Wong, Nasreen A. Vohra, Darla K. Liles
Journal: Journal of Clinical Oncology (2018)

e12530 Background: Very early breast cancer(VEBC) which is ≤ 1cm (T1aN0, T1bN0) are associated with excellent disease specific outcomes. We sought to analyze the outcome for patients with VEBC in the National Cancer Data Base (NCDB). Methods: We used NCDB to identify female patients with T1aN0/T1bN0 stage I breast cancer treated between 2004 and 2013. 89,678 patients met our inclusion criteria. We excluded patients with missing breast cancer subtype or survival/followup information. We performed a univariate, multivariate analysis, and survival differences were estimated by the Kaplan-Meier method and associated log-rank test; p < 0.05 indicated statistical significance Results: The median age was 63 years in this study cohort.81% of patients were white, 64% of patients had T1b N0 while 36% had T1aN0 stage,88% were ER positive and majority of patients had grade 1 or 2 cancer. Around 80% of patients were ER+/HER2-,8% ER+/HER2+,3% ER-/HER2+ and 9% were ER-/HER2-.Majority of patients underwent lumpectomy 70% while 30% underwent mastectomy.88% of patients also received radiation therapy and 20% of patients received chemotherapy. The 5-year overall survival was 92% for T1aN0 and 90% for T1bN0 (p = 0.036),91% for ER+/HER2-,92% for ER-/Her2+, and 89% in ER-/HER2-(p < .0001). The survival varied with age 95% for age ≤40 yrs., 97% for 41-55, 94% for 56-70yrs, and age > 70yr was associated with inferior 5-year survival of 80%(p < .0001), Cox hazard model showed the factors associated with inferior outcome are ER negativity (HR 1.45, p < .0142), black race (HR 1.40, p < .0001), high grade tumor (HR 1.20, p = 0.0033) no endocrine therapy (HR 1.72, p < .0001), and administration of chemotherapy (HR 1.27, p = 0.0001) Conclusions: VEBC is associated with excellent outcome but this analysis does demonstrate some heterogeneity in outcome. Older age, ER negativity, and black race was associated with inferior outcome.30% of patients underwent some type of mastectomy in this study, and administration of chemotherapy in the overall cohort was associated with inferior outcome, which also raises the question of over treatment in VEBC.
Clinical and molecular markers in COPD
Authors: I. Gonçalves, M.J. Guimarães, M. van Zeller, F. Menezes, J. Moita, P. Simão
Journal: Pulmonology (2018)

Chronic obstructive pulmonary disease (COPD) is a complex and heterogeneous disease, and there is a clinical need for validated markers and biomarkers that can contribute to the assessment of patients, risk prediction, treatment guidance, and assessment of response. Although according to the 2018 GOLD guidelines clinically useful biomarkers for COPD patients in stable condition have yet to be identified, several clinical markers and biomarkers have been proposed for COPD. These include isolated clinical markers, such as symptoms and Health Status assessment, exercise tests, function tests and imaging, and also composite scores and molecular markers. However, and despite strong efforts to identify useful markers in an attempt to improve prognostic and therapeutic approaches, results have not been consistent and expectations of relying on these markers in near future are faint. Current approaches to COPD have shifted from treating the disease to treating the individual patient. There is a clear need to identify treatable traits, focusing more on the patient and not on the disease, in order to implement an increasingly personalized treatment of COPD in the clinic, leading to true precision medicine. There is a need to identify combinations of clinical markers and biomarkers, genetic markers, and phenotypes that can guide the personalized therapy of COPD patients. This critical review will therefore focus not only on currently established markers and biomarkers in COPD but also on possible future approaches toward precision medicine.
IDH mutation status is associated with distinct vascular gene expression signatures in lower-grade gliomas
Authors: Lei Zhang, Liqun He, Roberta Lugano, Kenney Roodakker, Michael Bergqvist, Anja Smits, Anna Dimberg
Journal: Neuro-Oncology (2018)

Vascular gene expression patterns in lower-grade gliomas (LGGs; diffuse World Health Organization [WHO] grades II-III gliomas) have not been thoroughly investigated. The aim of this study was to molecularly characterize LGG vessels and determine if tumor isocitrate dehydrogenase (IDH) mutation status affects vascular phenotype.Gene expression was analyzed using an in-house dataset derived from microdissected vessels and total tumor samples from human glioma in combination with expression data from 289 LGG samples available in the database of The Cancer Genome Atlas. Vascular protein expression was examined by immunohistochemistry in human brain tumor tissue microarrays (TMAs) representing WHO grades II-IV gliomas and nonmalignant brain samples. Regulation of gene expression was examined in primary endothelial cells in vitro.Gene expression analysis of WHO grade II glioma indicated an intermediate stage of vascular abnormality, less severe than that of glioblastoma vessels but distinct from normal vessels. Enhanced expression of laminin subunit alpha 4 (LAMA4) and angiopoietin 2 (ANGPT2) in WHO grade II glioma was confirmed by staining of human TMAs. IDH wild-type LGGs displayed a specific angiogenic gene expression signature, including upregulation of ANGPT2 and serpin family H (SERPINH1), connected to enhanced endothelial cell migration and matrix remodeling. Transcription factor analysis indicated increased transforming growth factor beta (TGFβ) and hypoxia signaling in IDH wild-type LGGs. A subset of genes specifically induced in IDH wild-type LGG vessels was upregulated by stimulation of endothelial cells with TGFβ2, vascular endothelial growth factor, or cobalt chloride in vitro.IDH wild-type LGG vessels are molecularly distinct from the vasculature of IDH-mutated LGGs. TGFβ and hypoxia-related signaling pathways may be potential targets for anti-angiogenic therapy of IDH wild-type LGG.
Clinical evaluation of germline polymorphisms (SNPs) associated with disease response to capecitabine in metastatic breast cancer (MBC) (TBCRC 015).
Authors: Noura Choudhury, Patrick Evans, James N. Ingle, Ingrid A. Mayer, Phuong Khanh H. Morrow, Anna Maria Storniolo, Andres Forero-Torres, Catherine H. Van Poznak, Douglas E. Merkel, Elizabeth Claire Dees, Gini F. Fleming, Olwen Mary Hahn, Philip C. Hoffman, Olufunmilayo I. Olopade, Nancy Cox, Rita Nanda, Peter H. O'Donnell
Journal: Journal of Clinical Oncology (2018)

1071 Background: Capecitabine is an effective therapy for advanced breast cancer; however, response prediction is imprecise. In this study, we aimed to identify potential SNPs associated with response in MBC pts treated with capecitabine. Methods: Women with MBC about to receive single-agent capecitabine were enrolled and then dosed at 2000 mg/m2/day for 14 d on/7 d off, until unacceptable toxicity or disease progression. Pts were assessed by RECIST criteria. Primary analysis was a genome-wide association study (GWAS) analysis conducted with best response during treatment (PD vs. PR/CR) and stratified for the presence of liver metastases (mets) and estrogen receptor (ER) status. Genotyping was performed on the Illumina Human OmniExpress chip. Analysis was restricted to Caucasian pts to remove confounding by population stratification. Results: 258 pts from 14 institutions were enrolled. Pt characteristics included median age 57 yrs (range 25-85), 47.4% with liver mets and 74% were ER+. 30 pts were excluded due to incomplete response data. Final analysis was conducted on 136 Caucasian pts. Response was as follows: 4 (1.9%) CR, 27 (13.1%) PR, 104 (50.4%) SD, 71 (34.4%) PD. While no SNPs reached genome-wide significance ( < 6.9 x 10-8), top GWAS signals included a novel SNP upstream of BP1FB2 (p = 0.0007, OR 27.6), an intronic variant SNP in ADAMTS3 (p = 0.0007, OR = 51.6), and an intronic variant in Wnt7a (p = 0.0009, OR 28.4) as associated with response to capecitabine treatment. Wnt7a has been shown to promote tumor aggressiveness through fibroblast activation, and ADAMTS3 is downregulated in breast cancer compared to normal mammary tissue. BP1FB2 has not been previously implicated in breast cancer. Conclusions: We identified several promising markers of disease response in women with MBC treated with capecitabine. Although these SNPs did not achieve genome-wide significance and may be due to false discovery, further investigation is merited to discern whether Wnt7A and ADAMTS3 are merely markers of aggressive MBC or have a more specific role in influencing capecitabine response. Clinical trial information: NCT00977119.