tbuckley/cabot-search huggingface dataset:
Association of Albuminuria With Major Adverse Outcomes in Adults With Congenital Heart Disease
Authors: Saurabh Rajpal, Laith Alshawabkeh, Nureddin Almaddah, Caroline M. Joyce, Keri Shafer, Michelle Gurvitz, Sushrut S. Waikar, Finnian R. Mc Causland, Michael J. Landzberg, Alexander R. Opotowsky
Journal: JAMA Cardiology (2018)

Albuminuria is associated with adverse outcomes in diverse groups of patients, but the importance of albuminuria in the emerging population of increasingly complex adults with congenital heart disease (ACHD) remains unknown.To assess the prevalence, risk factors, and prognostic implications of albuminuria in ACHD.This prospective study assessed a cohort of ambulatory patients aged 18 years and older who were examined at an ACHD referral center and enrolled in the Boston ACHD Biobank between May 17, 2012, to August 5, 2016. Albuminuria was defined as an urine albumin-to-creatinine (ACR) ratio of 30 mg/g or more.Death or nonelective cardiovascular hospitalization, defined as overnight admission for heart failure, arrhythmia, thromboembolic events, cerebral hemorrhage, and/or disease-specific events.We measured the ACR of 612 adult patients with CHD (mean [SD] age, 38.6 [13.4] years; 308 [50.3%] women). Albuminuria was present in 106 people (17.3%) and was associated with older age (patients with ACR <30 mg/g: mean [SD]: 37.5 [13.2] years; vs patients with ACR ≥30 mg/g: 43.8 [13.1] years; P < .001), presence of diabetes mellitus (ACR <30 mg/g: 13 of 506 [2.6%]; vs ≥30 mg/g: 11 of 106 [10.4%]; P < .001), lower estimated glomerular filtration rate (ACR <30 mg/g: median [interquartile range (IQR)]: 103.3 [90.0-116.4] mL/min/1.73 m2; ACR ≥30 mg/g: 99.1 [78.8-108.7] mL/min/1.73 m2; P = .002), and cyanosis (ACR <30 mg/g: 23 of 506 [5.1%]; vs ACR ≥30 mg/g: 21 of 106 [22.6%]; P < .001). After a mean (SD) follow-up time of 270 (288) days, 17 patients (2.5%) died, while 68 (11.1%) either died or experienced overnight inpatient admission. Albuminuria predicted outcome, with 30 of 106 patients with albuminuria (28.3%) affected vs 38 of 506 patients without albuminuria (7.5%; hazard ratio [HR], 3.0; 95% CI, 1.9-4.9; P < .001). Albuminuria was also associated with increased mortality (11 of 106 [10.4%]; vs 6 of 506 [1.2%] in patients with and without albuminuria, respectively; HR, 6.4; 95% CI, 2.4-17.3; P < .001). Albuminuria was associated with the outcomes only in patients with a biventricular circulation (HR, 4.5; 95% CI, 2.5-8.0) and not those with single-ventricle circulation (HR, 1.0; 95% CI, 0.4-2.8; P = 0.01 compared with biventricular circulation group). Among 133 patients (21.7%) in NYHA functional class 2, albuminuria was strongly associated with death or nonelective hospitalization.Albuminuria is common and is associated with increased risk for adverse outcome in patients with ACHD with biventricular circulation. Albuminuria appears especially useful in stratifying risk in patients categorized as NYHA functional class 2.
Mapping the burden of cholera in sub-Saharan Africa and implications for control: an analysis of data across geographical scales
Authors: Justin Lessler, Sean M Moore, Francisco J Luquero, Heather S McKay, Rebecca Grais, Myriam Henkens, Martin Mengel, Jessica Dunoyer, Maurice M'bangombe, Elizabeth C Lee, Mamoudou Harouna Djingarey, Bertrand Sudre, Didier Bompangue, Robert S M Fraser, Abdinasir Abubakar, William Perea, Dominique Legros, Andrew S Azman
Journal: The Lancet (2018)

BackgroundCholera remains a persistent health problem in sub-Saharan Africa and worldwide. Cholera can be controlled through appropriate water and sanitation, or by oral cholera vaccination, which provides transient (∼3 years) protection, although vaccine supplies remain scarce. We aimed to map cholera burden in sub-Saharan Africa and assess how geographical targeting could lead to more efficient interventions.MethodsWe combined information on cholera incidence in sub-Saharan Africa (excluding Djibouti and Eritrea) from 2010 to 2016 from datasets from WHO, Médecins Sans Frontières, ProMED, ReliefWeb, ministries of health, and the scientific literature. We divided the study region into 20 km × 20 km grid cells and modelled annual cholera incidence in each grid cell assuming a Poisson process adjusted for covariates and spatially correlated random effects. We combined these findings with data on population distribution to estimate the number of people living in areas of high cholera incidence (>1 case per 1000 people per year). We further estimated the reduction in cholera incidence that could be achieved by targeting cholera prevention and control interventions at areas of high cholera incidence.FindingsWe included 279 datasets covering 2283 locations in our analyses. In sub-Saharan Africa (excluding Djibouti and Eritrea), a mean of 141 918 cholera cases (95% credible interval [CrI] 141 538–146 505) were reported per year. 4·0% (95% CrI 1·7–16·8) of districts, home to 87·2 million people (95% CrI 60·3 million to 118·9 million), have high cholera incidence. By focusing on the highest incidence districts first, effective targeted interventions could eliminate 50% of the region's cholera by covering 35·3 million people (95% CrI 26·3 million to 62·0 million), which is less than 4% of the total population.InterpretationAlthough cholera occurs throughout sub-Saharan Africa, its highest incidence is concentrated in a small proportion of the continent. Prioritising high-risk areas could substantially increase the efficiency of cholera control programmes.FundingThe Bill & Melinda Gates Foundation .
More trainees decide not to enter specialty training straight after foundation programme
Authors: Abi Rimmer
Journal: BMJ (2014)

The proportion of doctors in training who chose not to move straight from the foundation programme into specialty training rose again in 2014, official figures show.

Figures from the UK Foundation Programme Office (UKFPO) showed that the proportion of foundation year 2 (F2) doctors who moved into a specialty training post in August 2014 was 59%—down from 64% in 2013, 67% in 2012, and 71% in 2011.12

The proportion of F2 doctors who did not enter specialty training and were still seeking …
Combined chemoradiotherapy and PARP inhibition in pancreatic cancer to induce a synchronous inflammatory cytokine response.
Authors: Eric Anderson, Zhenqiu Liu, Paul Noe, Yuzu Kubota, Wensha Yang, Nicholas N. Nissen, Andrew Eugene Hendifar, Stephen L. Shiao, Richard Tuli
Journal: Journal of Clinical Oncology (2018)

29 Background: Outcomes remain poor for patients with locally advanced pancreas cancer despite advances in combined modality therapy. Radiation and chemotherapy remain the mainstay of treatment for unresectable locally advanced pancreas cancer, and the addition of various agents is currently being assessed in clinical trials. There is increasing evidence that local inflammation and host immune response play a role in anti-tumor activity. We aimed to assess the impact of combined chemoradiotherapy and PARP inhibition on inflammatory cytokine production in pancreas cancer patients. Methods: A clinical trial of concurrent use of a PARP inhibitor with chemoradiation was performed on a cohort of 34 patients. Serum samples were collected at baseline and weekly during intensity modulated radiotherapy treatment. Concentrations of various inflammatory cytokines were measured in picograms per milliliter using a chemiluminescent assay. Comparisons between average percentage change from baseline to peak change of serum cytokine concentration across all patients was performed using a paired T test. Results: Multiple inflammatory cytokines experienced a statistically significant increase after patient treatment. Peak serum increase occurred within 3-5 weeks after treatment initiation for the majority of cytokines tested. The most significantly increased pro-angiogenic cytokines included placental growth factor (p = 2.21x10 -6 ) and vascular endothelial growth factor (p = 1.19x10 -4 ), which peaked at weeks 4 and 5, respectively. Multiple members of the interleukin family also increased significantly. Both IL-7 (p = 1.89x10 -4 ) and IL-17a (p = 7.26x10 -4 ) peaked at weeks 4. IL-5 (p = 8.84x10 -5 ) and IL-15 (p = 1.26x10 -15 ) peaked at weeks 3 and 4, respectively. Conclusions: Patients receiving combined PARP inhibitor and chemoradiation experience a stereotyped increase in inflammatory cytokine signaling that peaks at approximately 1 month after initiation of treatment. Changes in serum inflammatory cytokines may serve as biomarkers of response to treatment and could underpin future combined treatment modalities including immunomodulating agents.
Randomised phase III trial of vinflunine plus capecitabine versus capecitabine alone in patients with advanced breast cancer previously treated with an anthracycline and resistant to taxane
Authors: M. Martin, M. Campone, I. Bondarenko, D. Sakaeva, S. Krishnamurthy, L. Roman, L. Lebedeva, J.-C. Vedovato, M. Aapro
Journal: Annals of Oncology (2018)
Literacy-Adapted Cognitive Behavioral Therapy Versus Education for Chronic Pain at Low-Income Clinics
Authors: Beverly E. Thorn, Joshua C. Eyer, Benjamin P. Van Dyke, Calia A. Torres, John W. Burns, Minjung Kim, Andrea K. Newman, Lisa C. Campbell, Brian Anderson, Phoebe R. Block, Bentley J. Bobrow, Regina Brooks, Toya T. Burton, Jennifer S. Cheavens, Colette M. DeMonte, William D. DeMonte, Crystal S. Edwards, Minjeong Jeong, Mazheruddin M. Mulla, Terence Penn, Laura J. Smith, Deborah H. Tucker
Journal: Annals of Internal Medicine (2018)

Background: Chronic pain is common and challenging to treat. Although cognitive behavioral therapy (CBT) is efficacious, its benefit in disadvantaged populations is largely unknown. Objective: To evaluate the efficacy of literacy-adapted and simplified group CBT versus group pain education (EDU) versus usual care. Design: Randomized controlled trial. (ClinicalTrials.gov: NCT01967342) Setting: Community health centers serving low-income patients in Alabama. Patients: Adults (aged 19 to 71 years) with mixed chronic pain. Interventions: CBT and EDU delivered in 10 weekly 90-minute group sessions. Measurements: Self-reported, postintervention pain intensity (primary outcome) and physical function and depression (secondary outcomes). Results: 290 participants were enrolled (70.7% of whom were women, 66.9% minority group members, 72.4% at or below the poverty level, and 35.8% reading below the fifth grade level); 241 (83.1%) participated in posttreatment assessments. Linear mixed models included all randomly assigned participants. Members of the CBT and EDU groups had larger decreases in pain intensity scores between baseline and posttreatment than participants receiving usual care (estimated differences in change scores—CBT: −0.80 [95% CI −1.48 to −0.11]; P = 0.022; EDU: −0.57 [CI, −1.04 to −0.10]; P = 0.018). At 6-month follow-up, treatment gains were not maintained in the CBT group but were still present in the EDU group. With regard to physical function, participants in the CBT and EDU interventions had greater posttreatment improvement than those receiving usual care, and this progress was maintained at 6-month follow-up. Changes in depression (secondary outcome) did not differ between either the CBT or EDU group and the usual care group. Limitations: Participants represented a single health care system. Self-selection bias may have been present. Conclusion: Simplified group CBT and EDU interventions delivered at low-income clinics significantly improved pain and physical function compared with usual care. Primary Funding Source: Patient-Centered Outcomes Research Institute.
Medical marriages—good
Authors: A Soni
Journal: BMJ (2007)

We welcome your rapid responses, whether in direct response to an article in Career Focus or as a way of sharing your own ideas. As long as it isn9t libellous or offensive, we9ll post it on our website. We print a selection of rapid reponses here and the writer of the best each month wins an <i>Oxford Handbook</i> of their choice. Letter of the month prize is donated by OUP.
c15-153: Randomized phase IB/II study of enzalutamide with and without ribociclib in patients with metastatic castrate resistant, chemotherapy naïve prostate cancer that retains RB expression.
Authors: William Kevin Kelly, James Luke Godwin, Jean H. Hoffman-Censits, Karen E. Knudsen, Renee De Leeuw, Benjamin E. Leiby, Traci Southwell, Christine Hubert, David C. Smith, Gurkamal S. Chatta, Jahan Aghalar, Howard I. Scher, Rohit Bose, Karen A. Autio, Wassim Abida, Susan F. Slovin
Journal: Journal of Clinical Oncology (2018)

TPS384 Background: Current data suggests RB function is often attenuated in tumors through hyperphosphorylation; thus, RB activity can be “re-awakened” in RB+ tumors by suppressing key kinases that phosphorylate RB (CDK4/6). Recent findings identified perturbations of the RB tumor suppressor as a major mechanism of androgen receptor (AR) deregulation and castration-resistant prostate cancer (CRPC) formation. Our preclinical studies indicate RB+ tumors are exquisitely responsive to CDK4/6 inhibitors, revealing tumor-specific cytostatic and cytotoxic effects. These analyses strongly support the use of CDK4/6 inhibitors to activate the RB pathway, and impede the transition to CRPC. We hypothesize the CDK4/6 inhibitor ribociclib (ribo) in combination with enzalutamide (enz) in patients (pts) with progressive metastatic CRPC (mCRPC) that retains RB expression will significantly increase the efficacy of enz. Methods: This is a phase IB/II study of pts with mCRPC with RB+ tumors who have not received chemotherapy. Since ribo and enz have not been combined together in pts, the standard doses of enz and a traditional 3x3 dose escalation schema will be used in phase I to establish the safe dose of the combination; this dose will be used in phase II. Since both drugs are metabolized via the liver, plasma concentrations of ribo and enz will be monitored. To determine if ribo will improve the clinical activity in pts treated with enz, a randomized (1:1) phase II study using enz as the control arm vs. the combination will follow. This study will evaluate an early clinical activity readout, thus the primary phase II endpoint will be a proportion of pts with ≥ 50% PSA decline at 12 weeks. Secondary endpoints are rPFS, PSA PFS, OS and safety. If there is clinical activity noted, further randomized testing will be required to establish ribo clinical benefit in combination with enz. 5 sites are participating, managed by the Prostate Cancer Clinical Trials Consortium. Dose Levels 1 and 2 have been completed without any DLTs in the phase I portion of the study. A review of Dose Level 3 is planned for October 2017. Clinical trial information: NCT02555189.
Questioning the Benefits of Private Vehicle Transportation vs Emergency Medical Services Transportation
Authors: Jamie E. Anderson, Joseph M. Galante, Edgardo S. Salcedo
Journal: JAMA Surgery (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 Surgery 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 Surgery journal
S6K1 phosphorylation-dependent degradation of Mxi1 by β-Trcp ubiquitin ligase promotes Myc activation and radioresistance in lung cancer
Authors: Yumei Huang, Kaishun Hu, Sheng Zhang, Xiaorong Dong, Zhongyuan Yin, Rui Meng, Yingchao Zhao, Xiaofang Dai, Tao Zhang, Kunyu Yang, Li Liu, Kai Huang, Shaojun Shi, Yu Zhang, Junjie Chen, Gang Wu, Shuangbing Xu
Journal: Theranostics (2018)

Rationale:Mxi1 is regarded as a potential tumor suppressor protein that antagonizes the transcriptional activity of proto-oncogene Myc.However, the clinical significances and underlying mechanisms by which Mxi1 is regulated in lung cancer remain poorly understood.Methods: Mass spectrometry analysis and immunoprecipitation assay were utilized to detect the protein-protein interaction.The phosphorylation of Mxi1 was evaluated by in vitro kinase assays.Poly-ubiquitination of Mxi1 was examined by in vivo ubiquitination assay.Lung cancer cells stably expressing wild-type Mxi1 or Mxi1-S160A were used for functional analyses.The expression levels of Mxi1 and S6K1 were determined by immunohistochemistry in lung cancer tissues and adjacent normal lung tissues.Results: We found that Mxi1 is downregulated and correlated with poor prognosis in lung cancer.Using tandem affinity purification technology, we provided evidence that β-Trcp E3 ubiquitin ligase interacts with and promotes the ubiquitination and degradation of Mxi1.Furthermore, we demonstrated that Mxi1 is phosphorylated at S160 site by the protein kinase S6K1 and subsequently degraded via the ubiquitin ligase β-Trcp.Moreover, a phosphorylation mutant form of Mxi1 (Mxi1-S160A), which cannot be degraded by S6K1 and β-Trcp, is much more stable and efficient in suppressing the transcriptional activity of Myc and radioresistance in lung cancer cells.More importantly, a strong inverse correlation between S6K1 and Mxi1 expression was observed in human lung cancer tissues.Conclusion: Our findings not only establish a crosstalk between the mTOR/S6K1 signaling pathway and Myc activation, but also suggest that targeting S6K1/Mxi1 pathway is a promising therapeutic strategy for the treatment of lung cancer.
Accumulation of tumor infiltrating myeloid-derived suppressor cells associates with changes in the immune landscape of clear cell renal cell carcinoma.
Authors: Lin Lin, Paul G Pavicic, Patricia A. Rayman, Charles Tannenbaum, Brian I. Rini, Thomas Hamilton, James Finke, C. Marcela Diaz-Montero
Journal: Journal of Clinical Oncology (2018)

655 Background: Myeloid-derived suppressor cells (MDSC) are capable of inducing profound immune suppression of anti-tumor T cell responses. Here we examined the ability of intratumoral MDSC accumulation to alter the immune landscape of RCC and to identify the factors involved. Methods: Using flow cytometry, 41 clear cell RCC nephrectomy samples were assessed for their total MDSC infiltrate and the percentage of granulocytic (PMN-MDSC) or monocytic (M-MDSC) subsets. RNA isolated from these tumor samples and 4 non-tumor samples was also evaluated for expression levels of immune-related genes using a Nanostring PanCancer immune panel. A multiple linear regression model was used to identify which immune-related genes might be significantly associated with PMN-MDSC intratumoral accumulation. Log-Rank test was used for comparison of survival curves. Results: Genes encoding cytokines, cancer-testis antigens, interleukins, and T cell function were differentially expressed by clear cell RCC and the non-tumor samples. The transcription of 55 immune-related genes was significantly associated (FDR adjusted p &lt; 0.05) with PMN-MDSC infiltration, including mediators of MDSC recruitment such as CXCL1, CXCL3, CXCL5, CXCR2, IL8, LIF, S100A8, CSF3R, and CCR3, and molecules governing MDSC expansion and function such as IL10, C/EBPB, CD44, COX2, and NFATC3. When a statistically significant 10 gene signature was analyzed in the context of patient survival using the TCGA database of clear cell RCC patients (n = 945), a strong association between the expression of these genes and reduced survival was observed. Moreover, this association seemed to be additive, with expression of 7-10 of these genes correlating with poorer survival when compared to patients expressing 3 or less (p &lt; 0.0001). Conclusions: Consistent with previous studies defining the immunoregulatory role of MDSCs, these results suggest that MDSC accumulation can alter the inflammatory state of the tumor, and indicate that mediators associated with the function of PMN-MDSCs can have a negative impact on outcome. Mechanistic studies aimed at identifying the functionally relevant mediators are ongoing.
Posterior Reversible Encephalopathy Syndrome on 18F-FDG PET/CT in a Pediatric Patient With Burkitt’s Lymphoma
Authors: Ehab Saad Aldin, Parren McNeely, Yusuf Menda
Journal: Clinical Nuclear Medicine (2018)

We present a case of posterior reversible encephalopathy syndrome (PRES) in a pediatric patient with Burkitt's lymphoma predominantly involving the bone marrow. F-FDG PET/CT scan obtained after the first cycle of chemotherapy, complicated by acute kidney injury, hypertension, tumor lysis syndrome, and lethargy with focal neurological symptoms, showed a favorable marrow and lymph node response but increased FDG uptake in the bilateral frontal and occipital cortical/subcortical regions. Brain MRI was consistent with PRES. The patient was managed with IV hydration and blood pressure control with symptom resolution. This case shows the F-FDG uptake pattern of PRES in postchemotherapy setting.
E06, A NATURAL ANTIBODY TARGETED TO OXIDIZED PHOSPHOLIPIDS, ATTENUATES CARDIAC ISCHEMIA REPERFUSION INJURY IN MICE
Authors: Calvin Yeang, Xuchu Que, Masahiko Hoshijima, Yusu Gu, William Bradford, Nancy Dalton, Phuong Miu, Joseph Witztum, Kirk Peterson, Sotirios Tsimikas
Journal: Journal of the American College of Cardiology (2018)
GENDER DIFFERENCES IN STEMI OUTCOMES BEFORE AND AFTER IMPLEMENTATION OF A COMPREHENSIVE FOUR-STEP PROGRAM TO IMPROVE STEMI CARE
Authors: Chetan Huded, Kathleen Kravitz, Travis Gullett, Samir Kapadia, Scott Hantz, Stephen Ellis, Venu Menon, Mouin Abdallah, Seth Podolsky, Steve Meldon, Damon Kralovic, Deborah Brosovich, Elizabeth Smith, Umesh Khot
Journal: Journal of the American College of Cardiology (2018)
Somore Trial: Combining Sorafenib (SOR) with Capecitabine (CAP) Yields Highly Encouraging Survival Results and Elevated Metabolic Response Rate in Chemorefractory Metastatic Colorectal Cancer (MCRC)
Authors: A. Deleporte, A. Hendlisz, T. Delaunoit, R. Marechal, M. Peeters, S. Holbrechts, M. van den Eynde, G. Houbiers, M. Moreau, P. Flamen
Journal: Annals of Oncology (2012)
Disagreement With the NICE Decision
Authors: Andrew J. Foy, John M. Mandrola
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