tbuckley/cabot-search huggingface dataset:
Prediction of progression of interstitial lung disease in patients with systemic sclerosis: the SPAR model
Authors: Wanlong Wu, Suzana Jordan, Mike Oliver Becker, Rucsandra Dobrota, Britta Maurer, Håvard Fretheim, Shuang Ye, Elise Siegert, Yannick Allanore, Anna-Maria Hoffmann-Vold, Oliver Distler
Journal: Annals of the Rheumatic Diseases (2018)

Objectives To identify the predictive clinical characteristics and establish a prediction model for the progression of mild interstitial lung disease (ILD) in patients with systemic sclerosis (SSc). Methods Patients with SSc from two independent prospective cohorts were included in this observational study. All patients fulfilled the 2013 American College of Rheumatology/European League Against Rheumatism criteria, had mild ILD at baseline diagnosed by High-Resolution Computed Tomography (HRCT), available baseline and ≥1 annual follow-up pulmonary function tests and no concomitant pulmonary hypertension or airflow obstruction. ILD progression was defined as a relative decrease in forced vital capacity (FVC)%≥15%, or FVC%≥10% combined with diffusing capacity for carbon monoxide %≥15% at 1-year follow-up. Candidate predictors for multivariate logistic regression were selected by expert opinion based on clinical significance. A prediction model for ILD progression was established in the derivation cohort and validated in the multinational validation cohort. Results A total of 25/98 and 25/117 patients with SSc showed ILD progression in the derivation cohort and the validation cohort, respectively. Lower SpO 2 after 6 min walk test (6MWT) and arthritis ever were identified as independent predictors for ILD progression in both cohorts. The optimal cut-off value of SpO 2 after 6MWT for predicting ILD progression was determined as 94% by receiver operating characteristic curve analysis. The derived SPAR model combining both predictors (SPO 2 and ARthritis) increased the prediction rate from 25.5% to 91.7% with an area under the curve (95% CI) of 0.83 (0.73 to 0.93). Conclusions The evidence-based SPAR prediction model developed in our study might be helpful for the risk stratification of patients with mild SSc-ILD in clinical practice and cohort enrichment for future clinical trial design.
Making sense of telemedicine in the management of COPD
Authors: Jean Bourbeau, Raquel Farias
Journal: European Respiratory Journal (2018)

<b>We should see telemedicine as an adjunct to self-management approaches, assisting proper healthcare coaching and helping patients to be more adherent in problem solving, decision making and acting earlier in the course of COPD exacerbations</b>http://ow.ly/UNv530k2LcY
Results from a phase I study of andecaliximab in combination with paclitaxel in patients with previously untreated metastatic breast cancer.
Authors: Erika Paige Hamilton, Alberto Bessudo, Daniel Bruetman, Michael S. Gordon, Ravindranath Patel, Adeboye H Adewoye, JieJane Liu, Alexander Starodub, Manish R. Patel
Journal: Journal of Clinical Oncology (2018)

1032 Background: Matrix metalloproteinase-9 (MMP-9) is highly expressed in several advanced cancers, including metastatic breast cancer, and confers an adverse prognosis. In a preclinical breast cancer model, inhibition of MMP-9 was demonstrated with tumor growth inhibition. Andecaliximab (ADX) is a chimeric antibody directed against MMP-9, engineered to remove T cell epitopes and reduce risk of immunogenicity. In this phase I multi-cohort study, we hypothesized that the combination of ADX with standard of care chemotherapy (paclitaxel) should be safe and tolerable, and demonstrate clinical activity in patients with previously untreated metastatic breast cancer. (Clinicaltrials.gov NCT# 01803282) Methods: We enrolled 15 eligible (13 female) patients with radiographically measurable disease and previously untreated metastatic breast cancer. The median age was 59 years (range 23-81). Patients were treated with 800 mg ADX IV every 2 weeks + paclitaxel (80mg/m2 on days 1, 8, and 15 of a 28-day cycle). The primary endpoints of this study were safety and tolerability. Exploratory endpoints were investigator assessed objective response rate (ORR), progression free survival (PFS), and overall survival (OS). Results: As of September 22, 2017, the median ADX treatment duration for this study was 5.3 months. The most common adverse events were alopecia (60%), fatigue (60%), constipation (47%), neutropenia (40%), diarrhea (33%), and nausea (33%). Serious adverse events (SAEs) were reported in 33% of patients. The most common SAEs were acute kidney injury and atrial fibrillation (7% each). The median PFS was 7.4 months (90% CI 5.3-8.6 months) and the overall response rate was 53% (95%CI 30-76%) with 7% complete response rate. The median OS was not reached at the time. Study treatment continues in 27% of patients. Conclusions: Combination of ADX with paclitaxel was safe and effective in first-line treatment of patients with metastatic breast cancer. Updated data will be presented at the time of the meeting. Clinical trial information: NCT01803282.
Epacadostat (E) plus pembrolizumab (P) versus pembrolizumab alone in patients (pts) with unresectable or metastatic melanoma: Results of the phase 3 ECHO-301/KEYNOTE-252 study.
Authors: Georgina V. Long, Reinhard Dummer, Omid Hamid, Thomas Gajewski, Christian Caglevic, Stéphane Dalle, Ana Arance, Matteo S. Carlino, Jean-Jacques Grob, Tae Min Kim, Lev V. Demidov, Caroline Robert, James M. G. Larkin, James Anderson, Janet E. Maleski, Mark M. Jones, Scott J. Diede, Tara C. Mitchell
Journal: Journal of Clinical Oncology (2018)

108 Background: In a phase 1/2 study, the combination of E, a selective oral inhibitor of the IDO1 enzyme, plus P, a PD-1 inhibitor, suggested promising antitumor activity with minimal additive toxicity. ECHO-301/KEYNOTE-252 (NCT02752074) is a phase 3, randomized, double-blind study evaluating the efficacy and safety of E + P vs placebo + P in pts with untreated unresectable or metastatic melanoma. Methods: Pts had histologically confirmed unresectable stage III or IV melanoma and were treatment naive for advanced or metastatic disease, except for pts with the BRAF V600 mutation who could have received prior BRAF/MEK therapy. Pts were stratified by PD-L1 expression and BRAF mutation status (BRAF mutant with prior BRAF-directed therapy, BRAF mutant without prior BRAF-directed therapy, and BRAF wild type) and randomized 1:1 to E 100 mg BID + P 200 mg Q3W or matched E placebo + P 200 mg Q3W. Response was assessed per RECIST v1.1 and irRECIST (both by central review). The primary endpoints were PFS per RECIST v1.1 and OS. Secondary endpoints were ORR per RECIST v1.1, duration of response, and safety. This is the final analysis for PFS and interim analysis for OS. Results: A total of 706 pts were randomized (354 to E + P and 352 to placebo + P); 72.5% of tumors were PD-L1 positive, 44.5% BRAF mutant (12.2% received prior BRAF/MEK therapy). Median follow-up was ~14 mo. E + P did not result in a significantly longer PFS vs placebo + P (median 4.7 vs 4.9 mo; HR=1.00; CI, 0.83-1.21; P=0.517). PFS rate at 12 mo was 37% in both groups. Findings were consistent across PD-L1 and BRAF subgroups. OS was not expected to reach statistical significance based on the results of this interim analysis (HR=1.13; CI, 0.86-1.49; P=0.807). The OS rate at 12 mo was 74% in both groups. ORR was 34.2% and 31.5% in the E + P and placebo + P groups, respectively. Grade ≥3 treatment-related AEs occurred in 21.8% of patients receiving E + P and 17.0% receiving placebo + P. Conclusions: The addition of E to P did not result in greater clinical benefit over P alone in pts with unresectable or metastatic melanoma. The safety profile was consistent with that observed in previously reported studies of this combination. Clinical trial information: NCT02752074.
Treatment of childhood adrenocortical carcinoma (ACC) with surgery plus retroperitoneal lymph node dissection (RPLND) and multiagent chemotherapy: Results of the Children’s Oncology Group ARAR0332 protocol.
Authors: Carlos Rodriguez-Galindo, Alberto S. Pappo, Mark D. Krailo, Farzana Pashankar, Eliana Maria Monteiro Caran, John Hicks, Mary B McCarville, Christopher Bertero Weldon, David Malkin, Gerard Zambetti, Antonio Conclaves de Oliveira Filho, Michael P LaQuaglia, Maria Jose Mastellaro, Raul Correa Ribeiro
Journal: Journal of Clinical Oncology (2016)

10515 Background: ACC is a rare pediatric malignancy with an aggressive clinical behavior and distinct biology. Treatment for this malignancy has followed the principles of management developed in adults; pediatric-specific studies are scarce. Methods: Study objectives were: 1) To describe the outcome of patients with stage I ACC treated with surgery only; 2) To describe the outcome of stage II patients (completely resected > 200 cc or > 100 g) treated with adrenalectomy and RPLND; and 3) To describe the outcome of patients with stage III/IV treated with mitotane and chemotherapy (eight cycles of cisplatin, etoposide, and doxorubicin). Results: Between 9/2006 and 5/2013, 78 patients (51 females) were enrolled. Stage IV patients were older (median age 13 y vs. 1.5, 2, and 3 y for stages I, II, and III, respectively, p < 0.0001) and presented with lower frequency of virilization (50% vs. 91.3%, 78.6%, and 70.8 for patients with stages I, II, or III, respectively, p = 0.05) and higher frequency of Cushing features (61.5% vs. 20.8%, 13.3%, and 20% for stages I, II, and III, respectively, p = 0.03). Most patients (14/25) with stage III had tumor spillage. 3 y EFS estimates were 88.9%, 53.3%, 77.0%, and 14.3% for stages I, II, III, and IV, respectively. 3 y OS estimates were 92.3%, 86.1%, 100%, and 13.3%, for stages I, II, III, and IV, respectively. The probabilities of mitotane and chemotherapy feasibility events were 10.5% and 31.6%, respectively. Conclusions: Outcome for children with stage I ACC is excellent with surgery only. However, failure rates for patients with localized large tumors (stage II) remain high after surgery, and RPLND does not improve outcome; systemic therapy should be considered for this group of patients. Patients with stage III ACC have an excellent outcome combining surgery and chemotherapy. Patients with stage IV ACC are older and have a poor outcome; thus, new treatments should be developed for this high-risk group. The combination of mitotane and chemotherapy as prescribed in ARAR0332 resulted in significant toxicity; one-third of patients with advanced disease could not complete the scheduled treatment. Clinical trial information: NCT00304070.
Lazaroid (U-74389G) ameliorates lung injury due to lipid peroxidation and nitric oxide synthase-dependent reactive oxygen species generation caused by remote systematic ischemia-reperfusion following thoracoabdominal aortic occlusion
Authors: Fotis Perlikos, Maria Lagiou, Apostolos Papalois, Tatiana Rizou, Christos Kroupis, Ioannis K Toumpoulis
Journal: International Journal of Surgery (2018)
Presence of Human Hepegivirus-1 in a Cohort of People Who Inject Drugs
Authors: Abraham J. Kandathil, David L. Thomas, Ashwin Balagopal
Journal: Annals of Internal Medicine (2018)

Letters16 January 2018Presence of Human Hepegivirus-1 in a Cohort of People Who Inject DrugsAbraham J. Kandathil, PhD, David L. Thomas, MD, MPH, and Ashwin Balagopal, MDAbraham J. Kandathil, PhDJohns Hopkins University, Baltimore, Maryland (A.J.K., D.L.T., A.B.)Search for more papers by this author, David L. Thomas, MD, MPHJohns Hopkins University, Baltimore, Maryland (A.J.K., D.L.T., A.B.)Search for more papers by this author, and Ashwin Balagopal, MDJohns Hopkins University, Baltimore, Maryland (A.J.K., D.L.T., A.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/L17-0527 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE:We greatly appreciate the additional valuable information on the prevalence of HHpgV-1 provided by Drs. Tang and Wang and Dr. Candotti and colleagues. The strong association between HCV and HHpgV-1 is fascinating. Like Drs. Tang and Wang, we hypothesized that there might be viral codependence, as is appreciated for hepatitis B and D virus. The clear example that we reported of sustained HHpgV-1 replication in the absence of HCV RNA proves that HCV replication is not required for HHpgV-1 but leaves open other epidemiologic, and possibly virologic, explanations. As Drs. Tang and Wang and Dr. Candotti and colleagues ... Author, Article, and Disclosure InformationAffiliations: Johns Hopkins University, Baltimore, Maryland (A.J.K., D.L.T., A.B.)Disclosures: Disclosures can be viewed at www.acponline.org/authors/icmje/ConflictOfInterestForms.do?msNum=M17-0085. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoPresence of Human Hepegivirus-1 in a Cohort of People Who Inject Drugs Abraham J. Kandathil , Florian P. Breitwieser , Jaiprasath Sachithanandham , Matthew Robinson , Shruti H. Mehta , Winston Timp , Steven L. Salzberg , David L. Thomas , and Ashwin Balagopal Presence of Human Hepegivirus-1 in a Cohort of People Who Inject Drugs Shixing Tang and Haiying Wang Presence of Human Hepegivirus-1 in a Cohort of People Who Inject Drugs Daniel Candotti , Xuelian Deng , Tingting Li , Syria Laperche , and Virginie Sauvage Metrics Cited byDifference of Intrahost Dynamics of the Second Human Pegivirus and Hepatitis C Virus in HPgV-2/HCV-Coinfected PatientsChronic Human Pegivirus 2 without Hepatitis C Virus Co-infectionMajor Advances in Hepatitis C Treatment but Not Hepatitis B 16 January 2018Volume 168, Issue 2Page: 158-159KeywordsDisclosureDrugsEpidemiologyHepatitis BRNA ePublished: 16 January 2018 Issue Published: 16 January 2018 Copyright & PermissionsCopyright © 2018 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Post neoadjuvant chemotherapy vacuum assisted biopsy in breast cancer: Can it determine pathologic complete response before surgery?
Authors: Marios Konstantinos Tasoulis, Nicola Roche, Jennifer E Rusby, Romney Pope, Steve Allen, Kate Downey, Ashutosh Nerurkar, Peter Osin, Robin Wilson, Fiona MacNeill
Journal: Journal of Clinical Oncology (2018)

567 Background: Neoadjuvant chemotherapy (NAC) is increasingly used in phenotype appropriate early operable breast cancer. Pathologic complete response (pCR) rates of up to 60% have been reported, suggesting that a proportion of patients may require less or even no surgery. In our practice, image-guided vacuum assisted biopsy (VAB) has been used after completion of NAC to assess residual disease and facilitate risk-adaptive surgery. The aim of this analysis was to investigate if post-NAC VAB could reliably identify exceptional responders who may not require surgical intervention. Methods: Retrospective cohort study of breast cancer patients treated with NAC, who had partial/complete imaging response and underwent post-NAC VAB to aid surgical planning, between 01/2013 and 01/2018. pCR was defined as no residual disease in the breast (ypT0). Diagnostic accuracy of VAB was calculated using final surgical pathology as the reference standard. Simple descriptive statistics and nonparametric analyses were performed. Results: 53 patients underwent post-NAC VAB. The overall pCR rate was 41.5% [53.8% for HER2 positive, 72.7% for triple negative (TN) phenotypes]. The post-NAC VAB false negative rate (FNR) was 19.4% (95% CI: 5.5-34.5) and the negative predictive value (NPV) was 76.9% (95% CI: 60.7-93.1) with an overall accuracy of 84.9% (95% CI: 75.3-94.5). Subgroup analysis showed that post-NAC VAB performed best in the TN group (n = 11) [FNR: 0%, NPV: 100%, overall accuracy: 90.9% (95% CI: 73.9-100)]. No significant associations were identified between tumor and technique characteristics and diagnostic performance of VAB. Conclusions: Our data suggest that post-NAC VAB may reliably predict pCR in patients with TN breast cancer. However, its diagnostic accuracy was not maintained across all phenotypes. Refinements and standardization in patient selection and VAB technique and more prospective trials are warranted to further explore the role of post-NAC VAB in supporting minimal or no surgery trials.
Response to: ‘Serum complement factor C5a in IgG4-related disease’ by Fukui <i>et al</i>
Authors: Hisanori Umehara, Mitsuhiro Kawano
Journal: Annals of the Rheumatic Diseases (2018)

Response to: 'Serum complement factor C5a in IgG4-related disease' by Fukui et alWe appreciate the interest shown by Dr S Fukui and colleagues 1 in our recent paper, 'How to diagnose IgG4-related disease (IgG4-RD) '. 2 IgG4-RD is characterised by increased serum IgG4 concentrations and number of IgG4-positive plasma cells in affected lesions. 3However, its diagnosis can be difficult, because clinical signs vary depending on the organs affected.A Japanese team established comprehensive diagnostic criteria for IgG4-RD, 2011 focusing on the concentration of serum IgG4 (>135 mg/dL), numbers of IgG4-positive cells (>10 cells/ HPF) and ratio of IgG4-positive to IgG-positive cells (>40%) in affected tissues. 4owever, many cases of IgG4-RD with low levels of IgG4 and mimickers of IgG4-RD with increased serum IgG4 have been reported and the concept of IgG4-RD has become blurred.Therefore, new specific markers or new criteria for IgG4-RD are required. 5uman IgG4 has a unique structure distinguished from the other IgG subclasses by lack of interaction with the complement system and inability to activate the classical complement pathway. 6 7However, hypocomplementaemia has been observed in IgG4-RD ever since the concept was first established 8 and is in particular more frequent and sometimes severe in IgG4-related kidney disease. 9A recent study showed that non-IgG4 IgG such as IgG1, which can activate complement, might be involved in the activation of complement in IgG4-RD. 10 Fukui et al reported the significant increase of C5a in IgG4-RD and suggested it for a therapeutic target. 1 However, serum C5a elevation is also a very important feature of active systemic lupus erythematosus (SLE).Since elevated C5a levels in IgG4-RD are much lower than in active lupus cases 11 and only some groups of patients with IgG4-RD have hypocomplementaemia, the production of C5a in SLE and IgG4-RD likely exhibits significant differences in both underlying mechanism and pathogenetic role.Although the details of the pathogenesis of IgG4-RD are unclear at present, recent basic studies have implicated the tolllike receptor (TLR) signalling pathway. 12Activation of C5aR in macrophages inhibits TLR-4 signals resulting in reduction of IL-12, IL-23 and IL-27 production by inflammatory macrophages. 13Thus, the role of cross-talk between innate and acquired immunity through the complement pathway and TLR system is attracting attention in the pathogenesis of IgG4-RD.
Uncovering the Spectrum of Postnatal Zika Infection in Children
Authors: Edwin J. Asturias
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
Hundreds of novel composite genes and chimeric genes with bacterial origins contributed to haloarchaeal evolution
Authors: Raphaël Méheust, Andrew K. Watson, François-Joseph Lapointe, R. Thane Papke, Philippe Lopez, Eric Bapteste
Journal: Genome biology (2018)

Haloarchaea, a major group of archaea, are able to metabolize sugars and to live in oxygenated salty environments. Their physiology and lifestyle strongly contrast with that of their archaeal ancestors. Amino acid optimizations, which lowered the isoelectric point of haloarchaeal proteins, and abundant lateral gene transfers from bacteria have been invoked to explain this deep evolutionary transition. We use network analyses to show that the evolution of novel genes exclusive to Haloarchaea also contributed to the evolution of this group. We report the creation of 320 novel composite genes, both early in the evolution of Haloarchaea during haloarchaeal genesis and later in diverged haloarchaeal groups. One hundred and twenty-six of these novel composite genes derived from genetic material from bacterial genomes. These latter genes, largely involved in metabolic functions but also in oxygenic lifestyle, constitute a different gene pool from the laterally acquired bacterial genes formerly identified. These novel composite genes were likely advantageous for their hosts, since they show significant residence times in haloarchaeal genomes—consistent with a long phylogenetic history involving vertical descent and lateral gene transfer—and encode proteins with optimized isoelectric points. Overall, our work encourages a systematic search for composite genes across all archaeal major groups, in order to better understand the origins of novel prokaryotic genes, and in order to test to what extent archaea might have adjusted their lifestyles by incorporating and recycling laterally acquired bacterial genetic fragments into new archaeal genes.
Poly(2-oxazoline)s based biomaterials: A comprehensive and critical update
Authors: Thomas Lorson, Michael M. Lübtow, Erik Wegener, Malik S. Haider, Solomiia Borova, Daniel Nahm, Rainer Jordan, Marina Sokolski-Papkov, Alexander V. Kabanov, Robert Luxenhofer
Journal: Biomaterials (2018)
Effects of spaceflight and simulated microgravity on microbial growth and secondary metabolism
Authors: Bing Huang, Dian-Geng Li, Ying Huang, Chang-Ting Liu
Journal: Military Medical Research (2018)

Spaceflight and ground-based microgravity analog experiments have suggested that microgravity can affect microbial growth and metabolism. Although the effects of microgravity and its analogs on microorganisms have been studied for more than 50 years, plausible conflicting and diverse results have frequently been reported in different experiments, especially regarding microbial growth and secondary metabolism. Until now, only the responses of a few typical microbes to microgravity have been investigated; systematic studies of the genetic and phenotypic responses of these microorganisms to microgravity in space are still insufficient due to technological and logistical hurdles. The use of different test strains and secondary metabolites in these studies appears to have caused diverse and conflicting results. Moreover, subtle changes in the extracellular microenvironments around microbial cells play a key role in the diverse responses of microbial growth and secondary metabolisms. Therefore, "indirect" effects represent a reasonable pathway to explain the occurrence of these phenomena in microorganisms. This review summarizes current knowledge on the changes in microbial growth and secondary metabolism in response to spaceflight and its analogs and discusses the diverse and conflicting results. In addition, recommendations are given for future studies on the effects of microgravity in space on microbial growth and secondary metabolism.