tbuckley/cabot-search huggingface dataset:
Annals Consult Guys - Syncope: How Do I Figure This One Out?
Authors: Geno J. Merli, Howard H. Weitz
Journal: Annals of Internal Medicine (2017)

Web Exclusives20 June 2017Annals Consult Guys - Syncope: How Do I Figure This One Out?FREEGeno J. Merli, MD and Howard H. Weitz, MDGeno J. Merli, MDSearch for more papers by this author and Howard H. Weitz, MDSearch for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/W17-0006 SectionsSupplemental MaterialAboutVisual Abstract ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail Annals Consult Guys brings a new perspective to the art and science of medicine with lively discussion and analysis of real-world cases and situations. They address medically relevant topics—whether they be poignant, thought-provoking, or just plain entertaining.For more videos from and information on Annals Consult Guys, visit go.annals.org/ConsultGuys. Comments0 CommentsSign In to Submit A Comment Rasan CheralaBrown university19 May 2022 Thank you Thanks for this well done case on identifying key features of vasovagal syncope! Author, Article, and Disclosure InformationAffiliations: Disclosures: Geno J. Merli, MD, reports the following: Research grants/contracts: Bristol-Myers Squibb, Janssen, Portola; Consultancies: Bristol-Myers Squibb, Janssen. Howard H. Weitz, MD, reports that he has no financial relationships or interests to disclose. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetails Metrics Cited byCorrection: Annals Consult Guys—Measuring Lipids: To Fast or Not to Fast 20 June 2017Volume 166, Issue 12Page: CG1KeywordsDisclosureResearch grantsResearch reporting guidelinesSyncope ePublished: 20 June 2017 Issue Published: 20 June 2017 Copyright & PermissionsCopyright © 2017 by American College of Physicians. All Rights Reserved.Loading ...
Administration of Fibrinogen Concentrate During Cardiac Surgery—Reply
Authors: Süleyman Bilecen, Arno Nierich
Journal: JAMA (2017)

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
Tau deletion promotes brain insulin resistance
Authors: Elodie Marciniak, Antoine Leboucher, Emilie Caron, Tariq Ahmed, Anne Tailleux, Julie Dumont, Tarik Issad, Ellen Gerhardt, Patrick Pagesy, Margaux Vileno, Clément Bournonville, Malika Hamdane, Kadiombo Bantubungi, Steve Lancel, Dominique Demeyer, Sabiha Eddarkaoui, Emmanuelle Vallez, Didier Vieau, Sandrine Humez, Emilie Faivre, Benjamin Grenier-Boley, Tiago F. Outeiro, Bart Staels, Philippe Amouyel, Detlef Balschun, Luc Buee, David Blum
Journal: The Journal of Experimental Medicine (2017)

The molecular pathways underlying tau pathology–induced synaptic/cognitive deficits and neurodegeneration are poorly understood. One prevalent hypothesis is that hyperphosphorylation, misfolding, and fibrillization of tau impair synaptic plasticity and cause degeneration. However, tau pathology may also result in the loss of specific physiological tau functions, which are largely unknown but could contribute to neuronal dysfunction. In the present study, we uncovered a novel function of tau in its ability to regulate brain insulin signaling. We found that tau deletion leads to an impaired hippocampal response to insulin, caused by altered IRS-1 and PTEN (phosphatase and tensin homologue on chromosome 10) activities. Our data also demonstrate that tau knockout mice exhibit an impaired hypothalamic anorexigenic effect of insulin that is associated with energy metabolism alterations. Consistently, we found that tau haplotypes are associated with glycemic traits in humans. The present data have far-reaching clinical implications and raise the hypothesis that pathophysiological tau loss-of-function favors brain insulin resistance, which is instrumental for cognitive and metabolic impairments in Alzheimer’s disease patients.
Outcomes of Severe Hemophilia a Patients on Continuous Prophylaxis Relative to Inhibitor Status in the Community Counts Registry
Authors: Marilyn J. Manco-Johnson, Vanessa R. Byams, Roshni Kulkarni, Brandi Dupervil, Becky Dudley, Tyler W. Buckner, Diane Aschman, Meredith Oakley, Mariam Voutsis, Steven Humes
Journal: Blood (2016)
Genomic Alterations in Fatal Forms of Non-Anaplastic Thyroid Cancer: Identification of <i>MED12</i> and <i>RBM10</i> as Novel Thyroid Cancer Genes Associated with Tumor Virulence
Authors: Tihana Ibrahimpasic, Bin Xu, Iñigo Landa, Snjezana Dogan, Sumit Middha, Venkatraman Seshan, Shyam Deraje, Diane L. Carlson, Jocelyn Migliacci, Jeffrey A. Knauf, Brian Untch, Michael F. Berger, Luc Morris, R. Michael Tuttle, Timothy Chan, James A. Fagin, Ronald Ghossein, Ian Ganly
Journal: Clinical Cancer Research (2017)

Purpose: Patients with anaplastic thyroid cancer (ATC) have a very high death rate. In contrast, deaths from non-anaplastic thyroid (NAT) cancer are much less common. The genetic alterations in fatal NAT cancers have not been reported.Experimental Design: We performed next-generation sequencing of 410 cancer genes from 57 fatal NAT primary cancers. Results were compared with The Cancer Genome Atlas study (TCGA study) of papillary thyroid cancers (PTCs) and to the genomic changes reported in ATC.Results: There was a very high prevalence of TERT promoter mutations, comparable with that of ATC, and these co-occurred with BRAF and RAS mutations. A high incidence of chromosome 1q gain was seen highlighting its importance in tumor aggressiveness. Two novel fusion genes DLG5-RET and OSBPL1A-BRAF were identified. There was a high frequency of mutations in MED12 and these were mutually exclusive to TERT promoter mutations and also to BRAF and RAS mutations. In addition, a high frequency of mutations in RBM10 was identified and these co-occurred with RAS mutations and PIK3CA mutations. Compared with the PTCs in TCGA, there were higher frequencies of mutations in TP53, POLE, PI3K/AKT/mTOR pathway effectors, SWI/SNF subunits, and histone methyltransferases.Conclusions: These data support a model, whereby fatal NAT cancers arise from well-differentiated tumors through the accumulation of key additional genetic abnormalities. The high rate of TERT promoter mutations, MED12 mutations, RBM10 mutations, and chromosome 1q gain highlight their likely association with tumor virulence. Clin Cancer Res; 23(19); 5970-80. ©2017 AACR.
Neutrophil-guided dosing of anthracycline/cyclophosphamide chemotherapy in breast cancer: A feasibility study.
Authors: Johanna Maria van Pelt-Sprangers, Corry Leunis, Felix De Jongh
Journal: Journal of Clinical Oncology (2014)

e11527 Background: Proper dosing of anticancer drugs is complex due to narrow therapeutic margins and substantial inter-individual variability (IIV) in treatment effects. Neutropenia is the dose-limiting toxicity of anthracycline/cyclophosphamide-based chemotherapy (ACC). In practice, an inappropriate low dose of ACC is not routinely detected. Retrospective data suggest a strong association between treatment-related neutropenia and survival in breast cancer patients (1-4). Therefore, we started a prospective study of neutrophil-guided dose escalation of ACC in 30 female patients with breast cancer. Methods: Breast cancer patients referred for 3-weekly ACC were invited to participate. After informed consent, the 1st treatment cycle was administered in a standard BSA-based dose. Absolute neutrophil count (ANC) was measured at baseline and at days 8, 11 and 15. For patients with grade 0-2 neutropenia and no other dose-limiting toxicity, we intended a 10-25% dose escalation (using a pre-specified dosing algorithm depending on ANC values) in the 2nd cycle and another 10-25% dose escalation in the 3rd cycle. Results: Thirty patients, age 37-65 [mean, 53 ± 7.8] years; BSA 1.50-2.14 [mean, 1.80 ± 0.14] m2, were treated with adjuvant FEC (fluorouracil 500 mg/m2, epirubicin 100 mg/m2, cyclophosphamide 500 mg/m2; n= 24) or AC (doxorubicin 60 mg/m2, cyclophosphamide 600 mg/m2; n= 4), or with palliative FAC (fluorouracil 500 mg/m2, doxorubicin 50 mg/m2, cyclophosphamide 500 mg/m2; n = 2). Nadir range was 0.03 – 1.28, (mean, 0.40 ± 0.31) x109/L, and was reached on day 11 in 3 patients and on day 15 in 27 patients. Grade 3-4 neutropenia was observed in 28/30 patients after the 1stcycle. Two of them had febrile neutropenia and were hospitalized. Dose escalation was feasible in 2 patients (+30% and +15% respectively) without complications or excessive toxicity. Conclusions: IIV in neutropenia after treatment with ACC was less than expected. Asymptomatic grade 3-4 neutropenia was observed in most patients with breast cancer treated with ACC according to presently advocated BSA-based doses. Neutrophil-guided dosing is unlikely to improve outcome of current standard ACC regimens in patients with breast cancer. Clinical trial information: NL32077.101.10.
The Persisting Challenge of Socioeconomic Inequalities in Health Across the Life Course
Authors: Rebecca Hardy
Journal: JAMA Pediatrics (2017)

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 Pediatrics 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 Pediatrics journal
Driving, glaucoma, and the law
Authors: N. P Jones, J. Marsden, J. Kwartz
Journal: BMJ (1995)

Driving, glaucoma, and the law Regular checks on medical fitness to drive needed EDITOR,-Potamitis and colleagues draw attention to widespread ignorance about regulations con- cerning visual fields for driving.'Because drivers are required to pass a visual acuity test as part of their driving test, however, most are aware of visual acuity as a component of visual function and of its relevance to driving.This does not necessarily imply greater compliance with the regulation concerning visual acuity than with those concerning visual fields.We recorded visual acuity (with glasses if wom) in consecutive patients attending the accident and emergency service at Manchester Royal Eye Hospital.Over one month 1426 patients were tested, of whom 177 had a visual acuity insufficient for legal driving.Most of these patients did not drive, but 42 still drove a car.Of these 42, 21 were "borderline" failures (6/12 in the better eye) but the remaining 21 would definitely have failed a standard numberplate reading test.All these patients had evidence of chronic visual loss, which was correctable by refraction in only some cases.Clearly, patients with acute eye problems may have acute visual deterioration.Such deterioration, however, is almost invariably unilateral.For driving a car, acceptable vision is only required in one eye.There was no evidence to suggest that these data were invalidated by acute, temporary visual loss in these patients.Potamitis and colleagues rightly recommend that greater information should be made available to drivers, both from the Driver and Vehicle Licensing Agency and from ophthalmologists.The key role of optometrists should also be made clear.The authors comment that patients need more information and imply that this will in itself improve driving safety by resulting in voluntary withdrawal on the part of unfit drivers, but this is merely an assumption.Do we not need regular checks on medical aspects of fitness to drive, even for people under retirement age?
Outcomes of Chronic Phase Chronic Myeloid Leukemia Patients Following Tyrosine Kinase Inhibitors Dose-Reductions
Authors: Jee Hyun Kong, Hanna Jean Khoury, Elliott F. Winton, Leonard T. Heffner, Manila Gaddh, Martha Arellano, Fuad El-Rassi, Audrey S Kim, Anand Jillella, Imre Bodó, Vamsi Kota
Journal: Blood (2016)
Does personalized melanoma genomic risk information trigger conversations about skin cancer prevention and skin examination with family, friends and health professionals?
Authors: A.K. Smit, L.A. Keogh, A.J. Newson, P.N. Butow, K. Dunlop, R.L. Morton, J. Kirk, D. Espinoza, A.E. Cust
Journal: British Journal of Dermatology (2017)

Receiving information about genomic risk of melanoma might trigger conversations about skin cancer prevention and skin examinations. To explore conversations prompted by receiving personalized genomic risk of melanoma with family, friends and health professionals. We used a mixed‐methods approach. Participants without a personal history and unselected for a family history of melanoma (n =103, aged 21–69 years, 53% women) completed questionnaires 3 months after receiving a personalized melanoma genomic risk assessment. Semistructured interviews were undertaken with 30 participants in high, average and low genomic risk categories, and data were analysed thematically. From the questionnaires, 74% of participants communicated their genomic risk information with family, and 49% with friends. Communication with a health professional differed by risk level: 41%, 16% and 12% for high, average and low risk, respectively (P = 0·01). Qualitative analysis showed that perceived 'shared risk' and perceived interest of family and friends were motivations for discussing risk or prevention behaviours. The information prompted conversations with family and health professionals about sun protection and skin checks, and general conversations about melanoma risk with friends. Reasons for not discussing with family included existing personal or family health concerns, or existing high levels of sun protection behaviour among family members. Personalized melanoma genomic risk information can prompt risk‐appropriate discussions about skin cancer prevention and skin examinations with family and health professionals. Sharing this information with others might increase its impact on melanoma prevention and skin examination behaviours, and this process could be used to encourage healthy behaviour change within families.
Mechanisms of resistance (MoR) to DNA damaging therapy (tx) in BRCA1/2-deficient (d) metastatic breast cancer (MBC).
Authors: Adrienne Gropper Waks, Ofir Cohen, Karla Helvie, Maxwell R. Lloyd, Lori Marini, Coyin Oh, Nelly Oliver, Neal Ian Lindeman, Ursula A. Matulonis, Ian E. Krop, Levi A. Garraway, Eric P. Winer, Nancy U. Lin, Nikhil Wagle
Journal: Journal of Clinical Oncology (2016)

542 Background: BRCA-d cancers are deficient in homologous recombination and susceptible to tx that cause DNA damage (platinum chemotx and poly (ADP-ribose) polymerase inhibitors (PARPi)). MoR to DNA damaging tx in BRCA-d breast cancer are not well characterized. Methods: We obtained metastatic tumor biopsies from 51 ER+ MBC patients (pts) on a prospective tissue collection protocol, as well as matched primary tumors. On each tumor we performed whole exome and transcriptome sequencing (WES/RNASeq) and a targeted sequencing panel (TSP) for 300 genes. WES was performed on germline DNA from blood. 5 BRCA-d tumors with acquired resistance to DNA damaging tx were identified. Results: Clinical and genomic features are summarized in the Table. In pt 1, post-olaparib sequencing showed 2 acquired somatic BRCA2 alterations, each of which independently restores the BRCA2 open reading frame (ORF); neither was detected in the pre-olaparib tumor. This pt was refractory to subsequent tx with carboplatin. In pts 2 and 3, no reversions in BRCA1/2 were detected in the resistant tumors; analysis is underway to identify other MoR. Sequencing is pending in pts 4 and 5. Conclusions: In 1/3 sequenced pts, PARPi resistance was acquired through convergent evolution to 2 distinct genomic mechanisms reconstituting the BRCA2 ORF, demonstrating intratumoral heterogeneity in MoR. In 2/3 sequenced pts, both with acquired platinum resistance, there was no apparent post-tx BRCA1/2 genomic reversion. Reversion of BRCA loss may predict resistance to subsequent DNA damaging tx. Genomic profiling of post-resistance metastatic biopsies can yield clinically and biologically relevant information due to tumor evolution. Tx (duration) Germline alteration Somatic alterations in resistant sample (WES/TSP) 1 Olaparib (326 d) BRCA2 4 basepair (bp) deletion (del), exon 11 BRCA2 loss of heterozygosity (LOH) BRCA2 15 bp in-frame indel, exon 11* BRCA2 1627 bp in-frame del, exon 11* 2 Carboplatin (282 d) BRCA1 2 bp del, exon 2 BRCA1 LOH 3 Cisplatin (459 d) None BRCA2 splice site mutation, exon 9 BRCA2 LOH 4 Carboplatin (183 d) BRCA2 (clinical test/WES pending) Pending 5 Rucaparib (955 d) BRCA2 2 bp del, exon 26 Pending *encompassing germline 4 bp del
A systematic review of pharmacogenetic studies on the response to biologics in patients with psoriasis
Authors: L.J. van Vugt, J.M.P.A. van den Reek, M.J.H. Coenen, E.M.G.J. de Jong
Journal: British Journal of Dermatology (2017)

Biologics are indicated for treating moderate‐to‐severe psoriasis. As the number of biologics registered for the treatment of psoriasis increases, so does the need for biomarkers to guide personalized therapeutic decisions. Genetic variants might serve as predictors for treatment response, a field of research known as pharmacogenetics. To assess which genetic variants are associated with response to biologics in patients with psoriasis according to current literature. A systematic search was performed in Embase, MEDLINE, the Cochrane Library and Web of Science. In total, 26 papers were included in this systematic review; 24 original studies and two meta‐analyses. Quality was assessed using a predesigned form and risk of bias was assessed using the Newcastle–Ottawa Scale. The majority of studies reported a candidate gene approach, focusing on polymorphisms in genes related to the therapeutic target or to psoriasis susceptibility. Studied populations were small and results were divergent, especially for studies investigating tumour necrosis factor inhibitors. The evidence for the role of HLA‐Cw6 in ustekinumab efficacy shows minimal heterogeneity, with a higher response rate among patients who were positive for HLA‐Cw6 reported across three of five studies. Pharmacogenetic studies in psoriasis have generated divergent results. Replication of findings in larger cohorts is required. Large‐scale hypothesis‐free searches for genetic biomarkers are needed to uncover the complete genetic background of outcomes for treatment with biologics.
Treatment patterns in metastatic triple-negative breast cancer (mTNBC).
Authors: Shan Jiang, Kala Hill, Della Varghese, Adrian Reg Waldeck, Marc Botteman
Journal: Journal of Clinical Oncology (2017)

e12589 Background: Real-world treatment patterns have not been extensively described in mTNBC. There is no generally accepted standard of care (SoC) in mTNBC or consensus regarding the use of multidrug regimens. We assessed drug-utilization patterns in commercially-insured US patients (pts) with mTNBC. Methods: Adult females with ≥1 breast cancer and ≥1 distant secondary malignant neoplasm diagnosis codes (2011-2015) were identified from the IMS LifeLink claims database. mTNBC status was approximated via receipt of any chemotherapy (chemo) post-metastatic diagnosis (mDx) in absence of pre-/post-mDx hormone replacement therapy/contraceptives or trastuzumab usage. First regimen (FR) was defined as the first chemo agent used post-mDx; chemo agents started ≤30 days of this first agent were counted as combination (combo) FR. Second regimen (SR) was defined as the chemo agent following FR by &gt;30 days, or the same agent if there was a ≥90-day gap after FR. Kaplan-Meier survival curves were used to estimate time to SR initiation. Predictors of FR combo therapy and SR initiation were identified via logistic and Cox proportional hazard (CPH) regressions, respectively. Results: 2,949 pts received FR (median age: 53 years). Progression to SR occurred in 54% and 68% of pts at 12 and 36 months post-FR initiation, respectively. Median (95% CI) time between FR and SR was 81 (75-87) days. 39% and 27% of pts in FR and SR received combo therapy. Patients with age &lt;55, surgery, no radiation, or more comorbidities during the pre-metastatic period were more likely to receive combo FR (Table). Pts with no surgery, more comorbidities, or combo FR, were more likely to start SR. Conclusions: There is no generally accepted SOC in mTNBC.Over half of mTNBC pts do not receive combo therapy and a majority progress to a SR within 1 year. [Table: see text]