tbuckley/cabot-search huggingface dataset:
IN DIABETIC PATIENTS MULTIPLE ARTERIAL GRAFTS IMPROVE LONG-TERM SURVIVAL COMPARED WITH CONVENTIONAL CORONARY ARTERY BYPASS SURGERY OR STENTS
Authors: Chaim Locker, Hartzell Schaff, Brian Lahr, Robert Frye, Richard Daly, Sameh M. Said, John Stulak, Amir Lerman, Joseph Dearani, Malcolm Bell
Journal: Journal of the American College of Cardiology (2018)
Laser-assisted delivery of synergistic combination chemotherapy in in vivo skin
Authors: Emily Wenande, Joshua Tam, Brijesh Bhayana, Steven Kyle Schlosser, Emily Ishak, William A. Farinelli, Agata Chlopik, Mai P. Hoang, Omar R. Pinkhasov, Peter Caravan, R. Rox Anderson, Merete Haedersdal
Journal: Journal of Controlled Release (2018)
Human genetic variants and age are the strongest predictors of humoral immune responses to common pathogens and vaccines
Authors: Petar Scepanovic, Cécile Alanio, Christian Hammer, Flavia Hodel, Jacob Bergstedt, Etienne Patin, Christian W. Thorball, Nimisha Chaturvedi, Bruno Charbit, Laurent Abel, Lluis Quintana-Murci, Darragh Duffy, Matthew L. Albert, Jacques Fellay
Journal: Genome Medicine (2018)

Humoral immune responses to infectious agents or vaccination vary substantially among individuals, and many of the factors responsible for this variability remain to be defined. Current evidence suggests that human genetic variation influences (i) serum immunoglobulin levels, (ii) seroconversion rates, and (iii) intensity of antigen-specific immune responses. Here, we evaluated the impact of intrinsic (age and sex), environmental, and genetic factors on the variability of humoral response to common pathogens and vaccines. We characterized the serological response to 15 antigens from common human pathogens or vaccines, in an age- and sex-stratified cohort of 1000 healthy individuals (Milieu Intérieur cohort). Using clinical-grade serological assays, we measured total IgA, IgE, IgG, and IgM levels, as well as qualitative (serostatus) and quantitative IgG responses to cytomegalovirus, Epstein-Barr virus, herpes simplex virus 1 and 2, varicella zoster virus, Helicobacter pylori, Toxoplasma gondii, influenza A virus, measles, mumps, rubella, and hepatitis B virus. Following genome-wide genotyping of single nucleotide polymorphisms and imputation, we examined associations between ~ 5 million genetic variants and antibody responses using single marker and gene burden tests. We identified age and sex as important determinants of humoral immunity, with older individuals and women having higher rates of seropositivity for most antigens. Genome-wide association studies revealed significant associations between variants in the human leukocyte antigen (HLA) class II region on chromosome 6 and anti-EBV and anti-rubella IgG levels. We used HLA imputation to fine map these associations to amino acid variants in the peptide-binding groove of HLA-DRβ1 and HLA-DPβ1, respectively. We also observed significant associations for total IgA levels with two loci on chromosome 2 and with specific KIR-HLA combinations. Using extensive serological testing and genome-wide association analyses in a well-characterized cohort of healthy individuals, we demonstrated that age, sex, and specific human genetic variants contribute to inter-individual variability in humoral immunity. By highlighting genes and pathways implicated in the normal antibody response to frequently encountered antigens, these findings provide a basis to better understand disease pathogenesis. ClinicalTrials.gov , NCT01699893
NanoTRAIL‐Oncology: A Strategic Approach in Cancer Research and Therapy
Authors: Yesi Shi, Xin Pang, Junqing Wang, Gang Liu
Journal: Advanced Healthcare Materials (2018)

Abstract TRAIL is a member of the tumor necrosis factor superfamily that can largely trigger apoptosis in a wide variety of cancer cells, but not in normal cells. However, insufficient exposure to cancer tissues or cells and drug resistance has severely impeded the clinical application of TRAIL. Recently, nanobiotechnology has brought about a revolution in advanced drug delivery for enhanced anticancer therapy using TRAIL. With the help of materials science, immunology, genetic engineering, and protein engineering, substantial progress is made by expressing fusion proteins with TRAIL, engineering TRAIL on biological membranes, and loading TRAIL into functional nanocarriers or conjugating it onto their surfaces. Thus, the nanoparticle‐based TRAIL (nanoTRAIL) opens up intriguing opportunities for efficient and safe bioapplications. In this review, the mechanisms of action and biological function of TRAIL, as well as the current status of TRAIL treatment, are comprehensively discussed. The application of functional nanotechnology combined with TRAIL in cancer therapy is also discussed.
Could you tell me what training I need to succeed in medical informatics and whether it helps to be a clinician?
Authors: Mohammad Al-Ubaydli
Journal: BMJ (2004)

Got a career or related problem that needs answering? Can't find the right person to point you in the right direction? Log on to the Advice Zone ( www.bmjcareers.com/advicezone ) for reliable medical careers advice. You can post a question or see if one of our 300 advisers has already answered a similar question. Here is a selection of questions and answers posted on the site.
A comparison of linezolid lung tissue concentrations among patients with drug-resistant tuberculosis
Authors: Russell R. Kempker, M. Tobias Heinrichs, Ketino Nikolaishvili, Irina Sabulua, Nino Bablishvili, Shota Gogishvili, Zaza Avaliani, Brent P. Little, Adam Bernheim, Hartmut Derendorf, Henry M. Blumberg, Sergo Vashakidze, Charles A. Peloquin
Journal: European Respiratory Journal (2018)

Linezolid has become a frequent component of treatment regimens for drug-resistant tuberculosis and is a group C drug in the latest World Health Organization treatment guidelines [1]. However, linezolid has a narrow therapeutic index and there is no consensus on the optimal dose for patients with tuberculosis [2, 3]. A better understanding of lung tissue penetration could provide insight into ideal dosing and the utility of linezolid in patients with severe lung lesions. To evaluate target site lung concentrations of linezolid, we utilised the technique of microdialysis, which facilitates the measurement of unbound (pharmacologically active) extracellular drug concentrations at the site of disease. Among TB patients undergoing surgical resection, linezolid concentrations in lung tissue were half of serum values [http://ow.ly/Anlb30hEpW4][1] [1]: http:/
Two distinct clinical trajectories of inflammatory thyroiditis evoked by checkpoint blockade in malignant melanoma.
Authors: Anna Claire Olsson-Brown, Rosemary Lord, Joseph J Sacco, Mark Christopher Coles, Jonathan Wagg, Munir Pirmohamed
Journal: Journal of Clinical Oncology (2018)

131 Background: Oncological immune checkpoint inhibitors (CPI) commonly cause immune related adverse events (irAEs). Thyroid irAEs have a significant clinical impact requiring therapeutic intervention and clinical coordination whilst often causing treatment delays. Methods: Retrospective review of all patients treated with CPIs (pembrolizumab, nivolumab +/- ipilimumab) for metastatic melanoma at the Clatterbridge Cancer Centre, UK identified patients experiencing thyroid irAEs. Clinical/biochemical course (T4 and thyroid stimulating hormone (TSH) levels) and autoantibody titers were evaluated to identify characterisable trajectories. Results: From February 2016 to May 2017, 103 patients received anti-PD1 therapy; 90 receiving monotherapy and 13 combination. Thyroid irAEs were seen in 13(14.4%) and 3(23%) patients respectively. Two distinct trajectories were identified: a hyperthyroid phase with subsequent hypothyroidism (HH) and de novo hypothyroidism (DN). There were no outliers. HH was the predominant pattern (75%) and the sole manifestation in combination therapy. In the HH cohort 69% of patients were female. The peak T4 was 39.3pmol/L occurring, on average, 7.5 weeks after CPI initiation. T4 levels declined within 6-21 days and hypothyroidism occurred within 8 weeks. The DN cohort was exclusively female. Thyroid irAE occurred 12 weeks after CPI initiation. Baseline TSH in HH (2.49mU/l) was significantly lower than DN (5.77mU/l); p = 0.0092. Positive thyroid autoantibodies were detected in 5 patients across both groups. One patient (HH) had symptomatic thyroid dysfunction. Corticosteroids conveyed no benefit. All patients had permanent dysfunction requiring long term levothyroxine replacement. All continued with immunotherapy treatment; however notable irAE-related treatment hiatuses occurred. Conclusions: Retrospective review revealed two distinct thyroid irAE trajectories, HH and DN. The trajectories may have biochemical predictors, are rarely associated with symptoms and appear unrelated to thyroid autoantibodies. Trajectory identification will optimise patient outcomes, reduce ineffective steroid use and promote early hormone replacement.
Impact of adjuvant chemotherapy with S-1 on survival in patients with type 4 and large type 3 gastric cancer.
Authors: Hayato Omori, Sanae Kaji, Rie Makuuchi, Tomoyuki Irino, Yutaka Tanizawa, Etsuro Bando, Taiichi Kawamura, Masanori Terashima
Journal: Journal of Clinical Oncology (2018)

98 Background: The prognosis of patients with linitis plastica (type 4) and large ulcero-invasive-type (type 3) gastric cancer is reported to be extremely poor. In stage II/III gastric cancer, adjuvant chemotherapy with S-1 is a standard treatment in Japan. However, the efficacy of postoperative chemotherapy with S-1 in these types of patients with dismal prognosis is unknown. The aim of this study is to evaluate the impact of adjuvant chemotherapy with S-1 on survival in type 4 and large type 3 gastric cancer patients. Methods: A total of 152 patients with clinically resectable type 4 and large type 3 gastric cancer who underwent R0 or R1 surgery from 2002 to 2014 were included. The survival outcome between patents with surgery alone and patients who received adjuvant S-1 was compared using a 1:1 propensity score matching method. Results: Patients with adjuvant S-1 were significantly younger (67 vs 74 y, p = 0.009), had higher incidence of T4 (90 vs 62%, p &lt; 0.001), N2-3 (84 vs 63%, p = 0.008), and cytology positive (52 vs 29%, p = 0.006) than in surgery alone patients. Before matching, median survival time (MST) was not different in surgery alone (n = 52) and adjuvant S-1 (n = 100) (31.3 vs 35.8 months, p = 0.41). Propensity score matching yielded 48 patients (24 patients in each group). After matching, baseline characteristics were well balanced between the two groups. Survival in patients with adjuvant S-1 was significantly better than in surgery alone patients (MST: 50.3 vs 15.4 months, p = 0.002). Cox proportional hazard analysis revealed adjuvant S-1 treatment was selected as independent prognostic factor (HR: 0.38, 95%CI: 0.18-0.76, p = 0.006), as well as lavage cytology (HR: 3.9, 95%CI: 1.8-8.9, p &lt; 0.001). Conclusions: Adjuvant chemotherapy with S-1 may have a strong impact on survival in type 4 and large type 3 gastric cancer patients. The efficacy of this treatment will be further demonstrated in the future clinical trials.
Adolescent Sexting Research
Authors: Joris Van Ouytsel, Michel Walrave, Koen Ponnet
Journal: JAMA Pediatrics (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 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
Respiratory Symptoms in Young Adults and Future Lung Disease. The CARDIA Lung Study
Authors: Ravi Kalhan, Mark T. Dransfield, Laura A. Colangelo, Michael J. Cuttica, David R. Jacobs, Bharat Thyagarajan, Raul San Jose Estepar, Rola Harmouche, Jorge Onieva Onieva, Samuel Y. Ash, Yuka Okajima, Carlos Iribarren, Stephen Sidney, Cora E. Lewis, David M. Mannino, Kiang Liu, Lewis J. Smith, George R. Washko
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: There are limited data on factors in young adulthood that predict future lung disease.Objectives: To determine the relationship between respiratory symptoms, loss of lung health, and incident respiratory disease in a population-based study of young adults.Methods: We examined prospective data from 2,749 participants in the CARDIA (Coronary Artery Risk Development in Young Adults) study who completed respiratory symptom questionnaires at baseline and 2 years later and repeated spirometry measurements over 30 years.Measurements and Main Results: Cough or phlegm, episodes of bronchitis, wheeze, shortness of breath, and chest illnesses at both baseline and Year 2 were the main predictor variables in models assessing decline in FEV1 and FVC from Year 5 to Year 30, incident obstructive and restrictive lung physiology, and visual emphysema on thoracic computed tomography scan. After adjustment for covariates, including body mass index, asthma, and smoking, report of any symptom was associated with −2.71 ml/yr excess decline in FEV1 (P < 0.001) and −2.18 in FVC (P < 0.001) as well as greater odds of incident (prebronchodilator) obstructive (odds ratio [OR], 1.63; 95% confidence interval [CI], 1.24–2.14) and restrictive (OR, 1.40; 95% CI, 1.09–1.80) physiology. Cough-related symptoms (OR, 1.56; 95% CI, 1.13–2.16) were associated with greater odds of future emphysema.Conclusions: Persistent respiratory symptoms in young adults are associated with accelerated decline in lung function, incident obstructive and restrictive physiology, and greater odds of future radiographic emphysema.
Half of ophthalmology trainees think surgical training is inadequate
Authors: Helen Jaques
Journal: BMJ (2013)

Half of ophthalmology trainees do not believe that they will be adequately prepared for independent practice by the end of their training, a study published in BMJ Open has found.1

The survey of 40 trainee ophthalmologists who had completed three or more years of specialty training in four deaneries in England (response rate 83%) also found significant regional variation in trainees’ surgical experience, confidence in operating, and surgical outcomes. Of those who responded, only half believed that the current training programme would sufficiently prepare them surgically.

The average rate of …
GP trainers are invited to observe college exam, RCGP says
Authors: Abi Rimmer
Journal: BMJ (2014)

GP trainers are being invited to observe groups of candidates taking the membership examination for the Royal College of General Practitioners (MRCGP), the college’s chief examiner has said.

Speaking at the conference of the British Association of Doctors of Indian Origin (BAPIO) in Manchester on Sunday 30 November, Pauline Foreman, the royal college’s chief examiner, said that she hoped to rebuild confidence in the exam.

The rate of failure in the exam was found to be much higher among ethnic minority candidates …
Protective Role of Myelocytic Nitric Oxide Synthases against Hypoxic Pulmonary Hypertension in Mice
Authors: Takaaki Ogoshi, Masato Tsutsui, Takashi Kido, Mayuko Sakanashi, Keisuke Naito, Keishi Oda, Hiroshi Ishimoto, Sohsuke Yamada, Ke-Yong Wang, Yumiko Toyohira, Hiroto Izumi, Hiroaki Masuzaki, Hiroaki Shimokawa, Nobuyuki Yanagihara, Kazuhiro Yatera, Hiroshi Mukae
Journal: American Journal of Respiratory and Critical Care Medicine (2018)

Rationale: Nitric oxide (NO), synthesized by NOSs (NO synthases), plays a role in the development of pulmonary hypertension (PH). However, the role of NO/NOSs in bone marrow (BM) cells in PH remains elusive.Objectives: To determine the role of NOSs in BM cells in PH.Methods: Experiments were performed on 36 patients with idiopathic pulmonary fibrosis and on wild-type (WT), nNOS (neuronal NOS)−/−, iNOS (inducible NOS)−/−, eNOS (endothelial NOS)−/−, and n/i/eNOSs−/− mice.Measurements and Main Results: In the patients, there was a significant correlation between higher pulmonary artery systolic pressure and lower nitrite plus nitrate levels in the BAL fluid. In the mice, hypoxia-induced PH deteriorated significantly in the n/i/eNOSs−/− genotype and, to a lesser extent, in the eNOS−/− genotype as compared with the WT genotype. In the n/i/eNOSs−/− genotype exposed to hypoxia, the number of circulating BM-derived vascular smooth muscle progenitor cells was significantly larger, and transplantation of green fluorescent protein–transgenic BM cells revealed the contribution of BM cells to pulmonary vascular remodeling. Importantly, n/i/eNOSs−/−-BM transplantation significantly aggravated hypoxia-induced PH in the WT genotype, and WT-BM transplantation significantly ameliorated hypoxia-induced PH in the n/i/eNOSs−/− genotype. A total of 69 and 49 mRNAs related to immunity and inflammation, respectively, were significantly upregulated in the lungs of WT genotype mice transplanted with n/i/eNOSs−/−-BM compared with those with WT-BM, suggesting the involvement of immune and inflammatory mechanisms in the exacerbation of hypoxia-induced PH caused by n/i/eNOSs−/−-BM transplantation.Conclusions: These results demonstrate that myelocytic n/i/eNOSs play an important protective role in the pathogenesis of PH.
EFFECT OF ROSUVASTATIN AND EICOSAPENTAENOIC ACID ON NEOATHEROSCLEROSIS: THE LINK-IT TRIAL
Authors: Koji Kuroda, Hiromasa Ohtake, Masakazu Shinohara, Masaru Kuroda, Shigeyasu Tsuda, Takayoshi Toba, Natsuko Tahara, Yuto Shinkura, Kenzo Uzu, Yoshinori Nagasawa, Yuichiro Nagano, Hiroyuki Yamamoto, Kenichi Yanaka, Yoshiro Tsukiyama, Akira Nagasawa, Ryuji Toh, Ishida Tatsuro, Toshiro Shinke, Ken-Ichi Hirata
Journal: Journal of the American College of Cardiology (2018)
Clinical features of hemobilia in unresectable pancreatic cancer (uPC).
Authors: Gen Kimura, Izumi Ohno, Kensuke Inamura, Kazuo Watanabe, Kumiko Umemoto, Yuko Suzuki, Mitsuhito Sasaki, Hideaki Takahashi, Yusuke Hashimoto, Hiroshi Imaoka, Shuichi Mitsunaga, Tatsushi Kobayashi, Masafumi Ikeda
Journal: Journal of Clinical Oncology (2018)

247 Background: Hemobilia is a life-threatening, although rare event in uPC patient(pt)s. However, there are few reports about it. The purpose of this study was to identify it’s clinical features in uPC at our institute. Methods: Data of 2066 pts who received treatment for uPC between April 2008 and August 2017 were reviewed retrospectively from the electronic medical records. Hemobilia was determined when extravasation was detected from the biliary tree artery on contrast-enhanced computed tomography (CT) or angiography. Blood clot seen in the bile duct on endoscopy was also included. Pts whose bleeding was diagnosed due to tumor invasion of the stomach or duodenum by endoscopy were excluded. CT and angiography were reviewed by an experienced radiologist. Results: Eleven pts developed hemobilia; there were no pts before 2013. All of them received gemcitabine plus nab-paclitaxel (GnP) as first-line chemotherapy. Eight pts developed hemobilia during GnP, three had it after disease progression. Every pt had at least one symptom of Quinke’s triad; upper gastrointestinal hemorrhage (n = 8, 73%), biliary colic (n = 4, 36%), and jaundice (n = 6, 55%). The median time to hemobilia after the start of GnP was 198 days (range: 43-559 days). A covered self-expanding metal stent (cSEMS) was placed in the lower common bile duct in all pts. The median time to bleeding after cSEMS placement was 87 days (range: 30-467 days). Eight pts showed pseudoaneurysm(PA). In 7 of these pts, were diagnosed by CT, the remaining by interventional radiology(IR). IR was employed initially in 6 of the 8 pts, and hemostasis was successful in all. Two pts underwent cSEMS placement and was unsuccessful in both. Of these 2 pts, one underwent IR, with successful hemostasis. Of the remaining 3 pts, 2 pts had hemostasis without treatment, and one had cSEMS placement that was successful for hemostasis. Conclusions: In our study, hemobilia was only seen after 2014. Hemobilia developed after the start of GnP in all of the pts. Pts who showed PA, successful hemostasis was obtained in all cases that underwent IR. Hemobilia should be kept in mind as a cause of upper GI bleeding in uPC pts, especially those with a biliary stent and history of GnP. IR was effective for the management of hemobilia associated with PA.
Pertuzumab, trastuzumab, and standard anthracycline- and taxane-based chemotherapy for the neoadjuvant treatment of patients with HER2-positive localized breast cancer (BERENICE): a phase II, open-label, multicenter, multinational cardiac safety study
Authors: S.M. Swain, M.S. Ewer, G. Viale, S. Delaloge, J.-M. Ferrero, M. Verrill, R. Colomer, C. Vieira, T.L. Werner, H. Douthwaite, D. Bradley, M. Waldron-Lynch, A. Kiermaier, J. Eng-Wong, C. Dang
Journal: Annals of Oncology (2017)

BackgroundAnti-HER2 therapies are associated with a risk of increased cardiac toxicity, particularly when part of anthracycline-containing regimens. We report cardiac safety of pertuzumab, trastuzumab, and chemotherapy in the neoadjuvant treatment of HER2-positive early breast cancer.Patients and methodsBERENICE (NCT02132949) is a nonrandomized, phase II, open-label, multicenter, multinational study in patients with normal cardiac function. In the neoadjuvant period, cohort A patients received four cycles of dose-dense doxorubicin and cyclophosphamide, then 12 doses of standard paclitaxel plus four standard trastuzumab and pertuzumab cycles. Cohort B patients received four standard fluorouracil/epirubicin/cyclophosphamide cycles, then four docetaxel cycles with four standard trastuzumab and pertuzumab cycles. The primary end point was cardiac safety during neoadjuvant treatment, assessed by the incidence of New York Heart Association class III/IV heart failure and of left ventricular ejection fraction declines (≥10 percentage-points from baseline and to a value of <50%). The main efficacy end point was pathologic complete response (pCR, ypT0/is ypN0). Results are descriptive.ResultsSafety populations were 199 and 198 patients in cohorts A and B, respectively. Three patients [1.5%; 95% confidence interval (CI) 0.31% to 4.34%] in cohort A experienced four New York Heart Association class III/IV heart failure events. Thirteen patients (6.5%; 95% CI 3.5% to 10.9%) in cohort A and four (2.0%; 95% CI 0.6% to 5.1%) in cohort B experienced at least one left ventricular ejection fraction decline. No new safety signals were identified. pCR rates were 61.8% and 60.7% in cohorts A and B, respectively. The highest pCR rates were in the HER2-enriched PAM50 subtype (75.0% and 73.7%, respectively).ConclusionTreatment with pertuzumab, trastuzumab, and common anthracycline-containing regimens for the neoadjuvant treatment of early breast cancer resulted in cardiac and general safety profiles, and pCR rates, consistent with prior studies with pertuzumab.Clinical Trial InformationNCT02132949