tbuckley/cabot-search huggingface dataset:
Nonadherence in the era of severe asthma biologics and thermoplasty
Authors: Joy Lee, Tunn Ren Tay, Naghmeh Radhakrishna, Fiona Hore-Lacy, Anna Mackay, Ryan Hoy, Eli Dabscheck, Robyn O'Hehir, Mark Hew
Journal: European Respiratory Journal (2018)

Nonadherence to inhaled preventers impairs asthma control. Electronic monitoring devices (EMDs) can objectively measure adherence. Their use has not been reported in difficult asthma patients potentially suitable for novel therapies, i.e. biologics and bronchial thermoplasty. Consecutive patients with difficult asthma were assessed for eligibility for novel therapies. Medication adherence, defined as taking &gt;75% of prescribed doses, was assessed by EMD and compared with standardised clinician assessment over an 8-week period. Among 69 difficult asthma patients, adherence could not be analysed in 13, due to device incompatibility or malfunction. Nonadherence was confirmed in 20 out of 45 (44.4%) patients. Clinical assessment of nonadherence was insensitive (physician 15%, nurse 28%). Serum eosinophils were higher in nonadherent patients. Including 11 patients with possible nonadherence (device refused or not returned) increased the nonadherence rate to 31 out of 56 (55%) patients. Severe asthma criteria were fulfilled by 59 out of 69 patients. 47 were eligible for novel therapies, with confirmed nonadherence in 16 out of 32 (50%) patients with EMD data; including seven patients with possible nonadherence increased the nonadherence rate to 23 out of 39 (59%). At least half the patients eligible for novel therapies were nonadherent to preventers. Nonadherence was often undetectable by clinical assessments. Preventer adherence must be confirmed objectively before employing novel severe asthma therapies.
Outcomes of multidisciplinary treatment in penile cancer: Experience from Thailand.
Authors: Wichien Sirithanaphol, Kachit Pachirat, Ukrit Rompsaithong, Pakorn Kiatsopit, Supanut Lumbiganon, Aumkhae Sookprasert, Jarin Chindaprasirt
Journal: Journal of Clinical Oncology (2018)

555 Background: Penile cancer is relatively more common in Thailand compared to western countries. We report multidisciplinary treatment outcomes of penile squamous cell carcinoma at a regional center in northeast of Thailand. Methods: Using an institutional database, a total of 68 patients with squamous cell carcinoma of penis treated during 2009-2015 were identified. Patient demographics, pathological data, and treatment modality were reviewed. Survival data was calculated using the Kaplan-Meier method. Results: Median age was 53 years (25-89 years) and the median follow-time was 2.7 years. At presentation, 39 patients (57.4%) were node positive, and 9 (13.2%) had metastatic disease. Management was penile preserving surgery in 13 patients, partial penectomy in 36 patients, total penectomy in 15 patients, and palliative with radiation and/or chemotherapy in 4 patients. The 3-year overall survival for patients with N0-1 and N2-3 was 86% and 35% respectively. For those with high risk (N2/N3) non-metastatic disease, multimodality treatment improved overall survival significantly compared with surgery alone (13.7 mo vs 8.6 mo; HR 0.32, p-value = 0.04) Conclusions: Patients present with locally advanced disease had a poor prognosis. Multidisciplinary management improved overall survival N2/N3 patients.
THREE-DIMENSIONAL ECHOCARDIOGRAPHY LEFT VENTRICULAR EJECTION FRACTION IMPROVES PATIENT SELECTION OF IMPLANTABLE CARDIOVERTER DEFIBRILLATORS OVER TWO-DIMENSIONAL EJECTION FRACTION
Authors: Hugo Rodriguez Zanella, Eleonora Secco, Francesca Boccalini, Denisa Muraru, Patrizia Aruta, Emanuele Bertaglia, José Antonio Arias-Godínez, Erick Alexanderson Rosas, Julio Cesar Sauza Sosa, Oscar Calvillo Argüelles, Sabino Iliceto, Luigi Badano
Journal: Journal of the American College of Cardiology (2018)
Abstract 10763: Electrocardiographic Markers of Myocardial Infarction Size
Authors: Daniel C Lee, Christine M Albert, Dhiraj Narula, Alan H Kadish, Edwin Wu, Gopi Panicker, Jeffrey J Goldberger
Journal: Circulation (2015)

Background: Myocardial infarction (MI) size is an important determinant of mortality in post-MI patients, but the current gold standard test, cardiovascular magnetic resonance imaging (CMR) , is expensive and not widely available. We sought to determine whether information from a readily available standard 12-lead electrocardiogram (ECG) could be utilized to estimate infarct size on CMR. Methods: Patients with a clinical history of MI enrolled in the DETERMINE Trial and Registry who had CMR and ECG performed were included. Patients with left bundle branch block were excluded. Candidate ECGs markers, which may signify the presence of MI [Q waves (Qw), fragmented QRS (fQRS), and T wave inversion (TWI) ] were examined for correlations with MI as a percent of LV (MI%) quantified by late gadolinium enhanced CMR. Contiguous Qw (cQw MI) and TWI (cTWI) in a coronary distribution and Qw and TWI in individual leads were examined separately in linear regression models. Results: Of the 540 patients (mean age 62±11 years, 78% men, and mean LVEF=40±11%) included in the analysis, 334 had cQw MI, 225 had fQRS, 235 had cTWI, and 92 had none of these ECG markers. Patients without any of these ECG markers had an infarct size of 9.2±6.5% as compared to 14.6±7.6%, 18.6±9.1%, and 20.3±9.5% for those with one (n=175), two (n= 200), or all three (n= 73) ECG markers (P&lt;0.001). By multivariate linear regression, the presence of cQwMI, fQRS, and cTWI were independently associated with an increase in MI% by 6.7%, 3.4%, and 4.9%, respectively. On per lead analysis, multivariate linear regression demonstrated a significant continuous relationship between MI% and the number of leads affected by Qw, fQRS, and TWI. MI% was 8.8% when all leads were free of candidate ECG markers and increased by 1.6%, 0.6%, and 0.6% for each lead affected by Qw, fQRS, and TWI, respectively (see table). Conclusion: In patients with prior MI, Qw, fQRS, and TWI on ECG are independently associated with an increase in MI% measured by CMR.
A bacteriophage cocktail targeting<i>Escherichia coli</i>reduces<i>E. coli</i>in simulated gut conditions, while preserving a non-targeted representative commensal normal microbiota
Authors: Tomasz Cieplak, Nitzan Soffer, Alexander Sulakvelidze, Dennis Sandris Nielsen
Journal: Gut Microbes (2018)

Antibiotics offer an efficient means for managing diseases caused by bacterial pathogens. However, antibiotics are typically broad spectrum and they can indiscriminately kill beneficial microbes in body habitats such as the gut, deleteriously affecting the commensal gut microbiota. In addition, many bacteria have developed or are developing resistance to antibiotics, which complicates treatment and creates significant challenges in clinical medicine. Therefore, there is a real and urgent medical need to develop alternative antimicrobial approaches that will kill specific problem-causing bacteria without disturbing a normal, and often beneficial, gut microbiota. One such potential alternative approach is the use of lytic bacteriophages for managing bacterial infections, including those caused by multidrug-resistant pathogens. In the present study, we comparatively analysed the efficacy of a bacteriophage cocktail targeting Escherichia coli with that of a broad-spectrum antibiotic (ciprofloxacin) using an in vitro model of the small intestine. The parameters examined included (i) the impact on a specific, pre-chosen targeted E. coli strain, and (ii) the impact on a selected non-targeted bacterial population, which was chosen to represent a defined microbial consortium typical of a healthy small intestine. During these studies, we also examined stability of bacteriophages against various pH and bile concentrations commonly found in the intestinal tract of humans. The bacteriophage cocktail was slightly more stable in the simulated duodenum conditions compared to the simulated ileum (0.12 vs. 0.58 log decrease in phage titers, respectively). It was equally effective as ciprofloxacin in reducing E. coli in the simulated gut conditions (2-3 log reduction), but had much milder (none) impact on the commensal, non-targeted bacteria compared to the antibiotic.
Mitochondrial Etiology of Psychiatric Disorders—Reply
Authors: Douglas C. Wallace, Dimitra Chalkia, Larry N. Singh
Journal: JAMA Psychiatry (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 Psychiatry 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 Psychiatry journal
Radium-223 retreatment in an international, open-label, phase 1/2 study in patients with castration-resistant prostate cancer and bone metastases: 2-year follow-up.
Authors: A. Oliver Sartor, Daniel Heinrich, Neil Mariados, María José Méndez-Vidal, Daniel Keizman, Camilla Thellenberg Karlsson, Avivit Peer, Giuseppe Procopio, Stephen Jay Frank, Kalevi Pulkkanen, Eli Rosenbaum, Stefano Severi, Jose Manuel Trigo Perez, Lucia Trandafir, Volker Jean Wagner, Rui Li, Luke T. Nordquist
Journal: Journal of Clinical Oncology (2018)

178 Background: Radium-223 (Ra-223) treatment (tx) is indicated for patients (pts) with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases (mets) (6 × 55 kBq/kg IV injections [inj]; 1 inj q4wk). Early results of an international, open-label, phase 1/2 study (NCT01934790) showed that re-treating pts with Ra-223 was well tolerated with favorable effects on disease progression. Here we report safety and efficacy findings from a 2-year follow-up. Methods: Pts with CRPC and bone mets who completed 6 initial Ra-223 inj with no disease progression in bone and later progressed were eligible for Ra-223 re-tx (6 additional Ra-223 inj), provided that hematologic parameters were adequate. No concomitant cytotoxic agents were allowed; other concomitant agents (eg, abiraterone, enzalutamide) were allowed at investigator discretion. The primary objective was safety. Exploratory objectives were time to radiographic bone progression, radiographic progression-free survival (rPFS), overall survival (OS), time to first symptomatic skeletal event (SSE), and SSE-free survival, all calculated from re-tx start. Pts will be followed for safety up to 7 years after last Ra-223 dose; an active 2-year follow-up evaluated exploratory objectives. Safety results from the active follow-up period and updated efficacy are reported. Results: 44 pts were re-treated with Ra-223; 29 (66%) completed all 6 inj (median number inj = 6). 34 (77%) of 44 pts entered active follow-up, during which no new safety concerns were noted. One new primary malignancy was reported (basal cell carcinoma). There were no serious drug-related adverse events. 19 (43%) of 44 pts had an rPFS event (radiographic progression or death); median rPFS was 9.9 months. Only 5 (11%) of 44 pts had radiographic bone progression; median time to radiographic bone progression was not reached. Median OS was 24.4 months. Median time to first SSE and SSE-free survival were 16.7 and 12.8 months, respectively. Conclusions: Re-treating with Ra-223 was well tolerated in this select pt population, led to minimal hematologic toxicity, and provided continued disease control in bone at 2-year follow-up. Clinical trial information: NCT01934790.
All‐oral direct‐acting antiviral therapy against hepatitis C virus (HCV) in human immunodeficiency virus/HCV–coinfected subjects in real‐world practice: Madrid coinfection registry findings
Authors: Juan Berenguer, Ángela Gil‐Martin, Inmaculada Jarrin, Ana Moreno, Lourdes Dominguez, Marisa Montes, Teresa Aldámiz‐Echevarría, María J. Téllez, Ignacio Santos, Laura Benitez, José Sanz, Pablo Ryan, Gabriel Gaspar, Beatriz Alvarez, Juan E. Losa, Rafael Torres‐Perea, Carlos Barros, Juan V. San Martin, Sari Arponen, María T. de Guzmán, Raquel Monsalvo, Ana Vegas, María T. Garcia‐Benayas, Regino Serrano, Luis Gotuzzo, María Antonia Menendez, Luis M Belda, Eduardo Malmierca, María J. Calvo, Encarnación Cruz‐Martos, Juan J. González‐García
Journal: Hepatology (2018)

We evaluated treatment outcomes in a prospective registry of human immunodeficiency virus/hepatitis C virus (HCV)–coinfected patients treated with interferon‐free direct‐acting antiviral agent–based therapy in hospitals from the region of Madrid between November 2014 and August 2016. We assessed sustained viral response at 12 weeks after completion of treatment and used multivariable logistic regression to identify predictors of treatment failure. We evaluated 2,369 patients, of whom 59.5% did not have cirrhosis, 33.9% had compensated cirrhosis, and 6.6% had decompensated cirrhosis. The predominant HCV genotypes were 1a (40.9%), 4 (22.4%), 1b (15.1%), and 3 (15.0%). Treatment regimens included sofosbuvir (SOF)/ledipasvir (61.9%), SOF plus daclatasvir (14.6%), dasabuvir plus ombitasvir/paritaprevir/ritonavir (13.2%), and other regimens (10.3%). Ribavirin was used in 30.6% of patients. Less than 1% of patients discontinued therapy owing to adverse events. The frequency of sustained viral response by intention‐to‐treat analysis was 92.0% (95% confidence interval, 90.9%‐93.1%) overall, 93.8% (92.4%‐95.0%) for no cirrhosis, 91.0% (88.8%‐92.9%) for compensated cirrhosis, and 80.8% (73.7%‐86.6%) for decompensated cirrhosis. The factors associated with treatment failure were male sex (adjusted odds ratio, 1.75; 95% confidence interval, 1.14‐2.69), Centers for Diseases Control and Prevention category C (adjusted odds ratio, 1.65; 95% confidence interval, 1.12‐2.41), a baseline cluster of differentiation 4–positive (CD4+) T‐cell count <200/mm3 (adjusted odds ratio, 2.30; 95% confidence interval, 1.35‐3.92), an HCV RNA load ≥800,000 IU/mL (adjusted odds ratio, 1.63; 95% confidence interval, 1.14‐2.36), compensated cirrhosis (adjusted odds ratio, 1.35; 95% confidence interval, 0.96‐1.89), decompensated cirrhosis (adjusted odds ratio, 2.92; 95% confidence interval, 1.76‐4.87), and the use of SOF plus simeprevir, SOF plus ribavirin, and simeprevir plus daclatasvir. Conclusion: In this large real‐world study, direct‐acting antiviral agent–based therapy was safe and highly effective in coinfected patients; predictors of failure included gender, human immunodeficiency virus–related immunosuppression, HCV RNA load, severity of liver disease, and the use of suboptimal direct‐acting antiviral agent–based regimens. (Hepatology 2018;68:32‐47).
Importance of detoxification capacity of albumin for assessing state of gastric cancer patients and effective treatment planning.
Authors: Oleg Ivanovich Kit, Irina A. Goroshinskaya, Andrey A. Maslov, Dar'ja E. Medvedeva, Ekaterina Igorevna Surikova, Ludmila A. Nemashkalova, Gennadiy V. Kaminskiy, Irina Tishchenko, Sergey A. Malinin, Lusegen Chilhahyan
Journal: Journal of Clinical Oncology (2018)

34 Background: The aim of the study was measuring biochemical indices reflecting endotoxicosis syndrome in gastric cancer patients with adenocarcinoma of different grades and signet ring cell carcinoma. Methods: The study included 67 patients with gastric cancer divided into 4 groups depending on the tumor histotype: well- and moderately-differentiated adenocarcinoma (G1-2); poorly-differentiated adenocarcinoma (G3); signet ring cell carcinoma (SRCC); combined gastric tumors; and 12 healthy donors. The content of medium mass molecules (MMM 254 and MMM 280 ), total and effective albumin concentrations (TCA and ECA), toxicity index (IT = TCA/ECA-1) and intoxication factor (IF = MMM 254 /ECA⋅1000) were used to assess the level of endogenous intoxication. The Statistika 6.0 software package was used. Results: IT, reflecting the functional state of the albumin molecule, significantly exceeded the level in donors: by 2.3 times in G1-2, by 3.3 times in G3, by 3.2 times in SRCC (p &lt; 0.01-0.001), by 2.2 times in mixed tumors (p &lt; 0.05). The greatest increase in IT – by 4.6 times – was observed in patients with serosal invasion and tumor spread to the adjacent structures (T4 in the TNM classification). IF, which is an integral indicator of endotoxemia, in all groups of patients was significantly (p &lt; 0.01-0.00001) higher than in donors. The increase was 55.2% in patients with G1-2, 132.7% for G3, 234.6% for T4, 66.8% for SRCC, and 59.6% for mixed tumors. The dynamic observation of patients showed that a sharp increase in the studied parameters was followed by relapses. Conclusions: The increase in IT and IF in all groups of patients indicated an enhancement of endotoxemia in gastric tumors, mainly due to the decreased detoxification capacity of albumin, as high levels of MMM were observed only in some patients. The changes were significantly more expressed in patients with G3, with the maximal changes in all the studied endotoxicosis parameters in T4. The results demonstrated the diagnostic significance of the detoxification ability of albumin for the evaluation of the state of gastric cancer patients and for the adequate treatment planning.
Cultured allogeneic fibroblast injection vs. fibroblasts cultured on amniotic membrane scaffold for dystrophic epidermolysis bullosa treatment
Authors: H. Moravvej, F. Abdollahimajd, M.H. Naseh, Z. Piravar, E. Abolhasani, N. Mozafari, H. Niknejad
Journal: British Journal of Dermatology (2018)

Different methods of fibroblast application have been examined to treat recessive dystrophic epidermolysis bullosa (RDEB). To compare the effects of intradermal injection of cultured allogeneic fibroblasts in healing RDEB wounds with those of fibroblasts seeded on amniotic membrane scaffolds (FAMS) or standard wound care (SWC) with Vaseline® gauze as controls. Seven patients were recruited, and seven wounds were assessed in each patient: three wounds were treated with injection of intradermal fibroblasts, three were treated with FAMS and one was dressed with SWC. Changes in wound size were assessed after 2 and 12 weeks of treatment. Qualitative wound scores (QWS) were used to assess wound severity. Additionally, biopsies and antigen mapping were performed to detect type VII collagen in the dermoepidermal junction. In both treated areas, the QWS and wound size were significantly decreased (P < 0·001), whereas there were no changes in the control group (P = 0·29). After 2 and 12 weeks of treatment, the wound size was significantly decreased in wounds that were treated with fibroblast injection compared with those treated with FAMS (P < 0·001); but no significant changes were found in the control group. Fibroblast injection has been shown to promote healing of RDEB wounds and is superior to FAMS or the control treatment.
The role of the blood platelet-lymphocyte ratio, neutrophil–lymphocyte ratio and platelets in prognosis of metastatic renal cell carcinoma (mRCC).
Authors: Joanna Huszno, Zofia Kolosza
Journal: Journal of Clinical Oncology (2018)

670 Background: Renal cell carcinoma (RCC) accounts for 2–3% of all malignant diseases in adults. In some studies, neutrophil–lymphocyte ratio (NLR), platelet–lymphocyte ratio (PLR) and PLT have been demonstrated to be closely related to poor prognosis of patients with RCC. The objective of this study was to evaluate the blood platelet-lymphocyte ratio (PLR), neutrophil–lymphocyte ratio (NLR) and platelets (PLT) for its prognostic value in patients with metastatic renal cell cancer (mRCC). Methods: We retrospectively reviewed 141 (49 women and 92 men) patients diagnosed with mRCC previously treated with tyrosine kinase inhibitors from MSC Memorial Cancer and Institute of Oncology, Gliwice Branch in years 2006 - 2016. We assessed the prognostic value (overall survival and progression free survival) of pretreatment PLR, NLR and PLT based on univariate analysis. The cut-off value of NLR was ‘elevated’ as &gt; 3.68 and PLR cut-off value was ‘elevated’ as &gt; 144.4. Results: Median time of overall survival (OS) and progression free survival (PFS) were 34.1 months (from 1 to 109 months) and 8.3 months (from 0.4 to 109 months), respectively. The median PFS was shorter in NLR &gt; 3.68 in comparison to NLR &lt; = 3.68 (11.5 vs. 3.6 months, HR = 2.69; 95%CI, 1.76 to 4.12). Similarly, the median OS was lower in NLR &gt; 3.68 (7.8 vs. 36.1 months, p = 0.00003; HR = 3.39; 95%CI, 2.09 to 5.50). The median PFS was shorter in PLR &gt; 144.4 in comparison to PLR &lt; = 144.4 (5.7 vs. 17.6 months; p = 0.00001; HR = 2.62; 95%CI, 1.76 to 3.90). Similarly, OS was worse for PLR &gt; 144.4 (16.6 vs. 71.2 months; p = 0.00001; HR = 3.31; 95%CI, 1.98 to 5.52). Higher value of PLT ( &gt; 400 G/l) was associated with shorter OS median (7.2 vs. 35.3 months; p = 0.001) than standard level of PLT (150-400G/l). Similarly, patients with higher neutrophil level had shorter OS (8.0 vs. 36.1 months, p = 0.0001) and PFS (3.6 vs. 11.5 months, p = 0.0001). Conclusions: Elevated pre-treatment NLR ( &gt; 3.68) and PLR ( &gt; 144.4) are associated with shorter OS and PFS in patients with mRCC treated with kinase inhibitors independently of other prognostic factors. Higher level of PLT ( &gt; 400 G/l) and higher level of neutrophil ( &gt; 6.0 x 10 3 /ul) were also negative prognostic factors.
Safety and immunogenicity of the novel tuberculosis vaccine ID93 + GLA-SE in BCG-vaccinated healthy adults in South Africa: a randomised, double-blind, placebo-controlled phase 1 trial
Authors: Adam Penn-Nicholson, Michele Tameris, Erica Smit, Tracey A Day, Munyaradzi Musvosvi, Lakshmi Jayashankar, Julie Vergara, Simbarashe Mabwe, Nicole Bilek, Hendrik Geldenhuys, Angelique Kany-Kany Luabeya, Ruth Ellis, Ann M Ginsberg, Willem A Hanekom, Steven G Reed, Rhea N Coler, Thomas J Scriba, Mark Hatherill
Journal: The Lancet Respiratory Medicine (2018)
Detection of renin lineage cell transdifferentiation to podocytes in the kidney glomerulus with dual lineage tracing
Authors: Diana G. Eng, Natalya V. Kaverina, Remington R.S. Schneider, Benjamin S. Freedman, Kenneth W. Gross, Jeffrey H. Miner, Jeffrey W. Pippin, Stuart J. Shankland
Journal: Kidney International (2018)