tbuckley/cabot-search huggingface dataset:
A phase Ib/II, multicenter, open-label study of DSP-7888 dosing emulsion in combination with immune checkpoint inhibitors (CPI) nivolumab or pembrolizumab in adult patients (pts) with advanced solid tumors, including platinum-resistant ovarian cancer (PROC).
Authors: Makoto Origuchi, Chris Korth, Zhonggai Li, Edgar E. Braendle
Journal: Journal of Clinical Oncology (2020)

TPS6099 Background: DSP-7888 is a therapeutic cancer vaccine composed of two synthetic peptides derived from Wilms’ tumor 1 (WT1) to promote both cytotoxic and helper T-lymphocyte-mediated immune responses against WT1-expressing tumors. WT1 is overexpressed in various solid tumors, including ovarian cancer. Combining cancer vaccines like DSP-7888 with a CPI may reduce resistance to immunomodulators and improve clinical benefit. A phase Ib/II study is being conducted to evaluate DSP-7888 in combination with a CPI in pts with advanced solid tumors, including PROC (NCT03311334). Methods: This phase Ib/II, open-label, multicenter, two-part dose-search/dose-expansion study investigates DSP-7888 + nivolumab or pembrolizumab in pts with advanced solid tumors (phase Ib), including PROC (phase II). The phase Ib primary objectives are safety, tolerability, and identification of the recommended phase II dose (RP2D). The phase II primary objective is evaluation of objective response rate (ORR); secondary objectives are clinical activity, safety, and tolerability. Pts aged ≥18 years with unresectable, metastatic cancer approved for treatment with nivolumab (phase Ib, Arm 1, n=6–12, 7 enrolled) or pembrolizumab (phase Ib, Arm 2, n=6–12, 6 enrolled), or with PROC (phase II) are eligible. Phase II will enroll ~40 pts into two groups based on programmed death-ligand 1 status (combined positive score of ≥10 [Group 1] or &lt;10 [Group 2]). Clinical activity will be assessed continuously using Bayesian analysis and actual enrollment may increase by ~20 pts/group based on this analysis. Pts in phase II will receive DSP-7888 intradermally (RP2D from phase Ib) once a week (wk) for 6 wks in the induction phase then every 3 wks in the maintenance phase. Beginning Day 1, pembrolizumab will be administered intravenously every 3 wks. In phase II, objective disease will be assessed every 6 wks for 24 wks, then every 12 wks until progression. Endpoints include ORR (per RECIST v1.1) (primary), duration of response, disease control rate (DCR), progression-free survival (PFS), 6-month PFS rate (per RECIST v1.1), and overall survival, immune (i)ORR, iDCR, and iPFS (per iRECIST) (secondary). Exploratory endpoints include blood and tumor tissue biomarkers. Safety and tolerability, assessed by adverse events, will be evaluated throughout the duration of the study and follow-up. This study is currently recruiting patients. Clinical trial information: NCT03311334.
Three (Not So) Easy Pieces
Authors: Donald R. Bordley
Journal: Annals of Internal Medicine (2020)

On Being a Doctor2 June 2020Three (Not So) Easy PiecesDonald R. Bordley, MDDonald R. Bordley, MDUniversity of Rochester, Rochester, New York (D.R.B.)Search for more papers by this authorAuthor, Article, and Disclosure Informationhttps://doi.org/10.7326/M20-0097 Audio Reading - “Three (Not So) Easy Pieces” Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads “Three (Not So) Easy Pieces” by Donald R. Bordley, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail A short time before I retired 18 months ago, I decided to resume an old activity long neglected. In high school and college, I had played acoustic guitar, folk music and blues. I was self-taught and played by ear. I thought that returning to the guitar would exercise a part of my brain that was long unused and help keep me occupied and youthful in retirement. I was unprepared for the terror that lay ahead and the 45-year journey back to medical school it would trigger.My university's school of music has a branch devoted to teaching members of the ... Author, Article, and Disclosure InformationAffiliations: University of Rochester, Rochester, New York (D.R.B.)Corresponding Author: Donald R. Bordley, MD, Department of Medicine, 601 Elmwood Avenue, Box MED, Rochester, NY 14642; e-mail, [email protected]rochester.edu. PreviousarticleNextarticle Advertisement Audio Reading - “Three (Not So) Easy Pieces” Audio. Virginia L. Hood, MD, a physician from the University of Vermont, reads “Three (Not So) Easy Pieces” by Donald R. Bordley, MD Your browser does not support the audio element. Audio player progress bar Step backward in current audio track Play current audio trackPause current audio track Step forward in current audio track Mute current audio trackUnmute current audio track 00:00/ FiguresReferencesRelatedDetails Metrics 2 June 2020Volume 172, Issue 11Page: 763KeywordsBrainChildrenDeceptionExerciseInpatientsMemoryOral medicine ePublished: 2 June 2020 Issue Published: 2 June 2020 Copyright & PermissionsCopyright © 2020 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Values of fractional exhaled nitric oxide plus serum procalcitonin and C-reactive protein in the evaluation of asthma
Authors: Li-min Zhao, Li-jun Ma, Ji-zhen Wu, Xian-liang Chen, Hong-yan Niu
Journal: BMJ (2012)

A total of 60 patients with an acute attack of asthma were studied.On presentation,fractional exhaled nitric oxide (FeNO) and the serum concentrations of procalcitonin (PCT) and C-reactive protein (CRP) were measured.And sputum culture was also performed.The patients were re-evaluated while returning to their clinical remission states.They were classified into 2 groups:patients with bacterial infection (group A) and those with nonbacterial infection (group B).The levels of FeNO were significantly higher in patients with acute exacerbation than those in remission.No difference existed between groups A and B ( P ＞ 0.05 ).The levels of PCT and CRP of group A with acute exacerbation were significantly higher than those of group B( all P ＜0.05).While in remission,the levels of PCT and CRP decreased significantly in group A ( P ＜ 0.05 ) ; But compared with exacerbation,the levels of PCT and CRP showed no change in group B (P ＞0.05).And no differences existed between two groups while in remission (P ＞ 0.05 ).An elevation of FeNO indicates the acute exacerbation of asthma.And the increased serum levels of PCT and CRP are associated with bacterial infection.

Key words: 
Asthma;  Bacterial infections;  Diagnostic techniques and procedures
Etiology of neonatal infection related to premature rupture of membranes
Authors: Na Yang, Jing Liu, Jun-jin Huang, Gang Wu
Journal: BMJ (2012)

Objective To investigate the common pathogens in neonatal infections with premature rupture of membranes (PROM).Methods From May 2007 to November 2010,16 356 neonates who were admitted to Bayi Children's Hospital were assigned to this study. The related clinical and laboratory information were recorded,including PROM and its time of duration,results of blood culture and other clinical data.Results A total of 3432 patients accompanyed with PROM among 16 356 infants (21.0％).There were 1060 full-term neonates (30.9％ ) and 2372 premature infants (69.1％ ) among 3432 PROM cases.The incidence of infectious disease was 35.8％ ( 1227/3432 ) in infants with PROM.The overall positive rate of blood culture was 7.6％ ( 260/3432 ) in infants with PROM:10.5％ ( 111/1060 ) in term infants and 6.3％ (149/2372) in premature infants ( x2 =18.370,P =0.000).The common pathogenic organisms were gram positive ( G + ) cocci ( 58.5％ ) and gram negative ( G- ) bacilli ( 33.8％ ) ( x2 =31.695,P =0.000 ).The most common organisms included Staphylococcus epidermidis,Staphylococcus homis,Klebsiella pneumoniae,Escherichia coli and Hemolytic staphylococci,accounting for 75.8％ of the total blood culture positive patients.Fungal infection accounted for 7.7％ of the total infectious diseases,which was all in premature infants. The blood culture-positive rate in patients with PROM duration ＜24 h,≥24 hand ≥72 h were 7.7％ ( 119/1544),7.2％ (99/1382),and 9.6％ (42/439) ( x2 =2.701,P =0.259 ),respectively.Conclusions G + coccus is the most common pathogenic bacteria of neonatal infection related to PROM,followed by G- bacillus.Fungi are detected mainly in premature infants.The blood culture-positive rate may not increase with the extension of time of PROM.

Key words: 
Fetal membranes, premature rupture;  Infant, newborn ;  Bacterial infections and mycoss
Covid-19: Push to reopen schools risks new wave of infections, says Independent SAGE
Authors: Jacqui Wise
Journal: BMJ (2020)

<h3>Introduction</h3> We describe the rationale and broad study design of the Indian Diabetes and Metabolic Health (InDiMeT) study, a new prospective, observational study incorporating extensive epigenetic (DNA methylation) and lipidomic signatures to examine their association with the dysregulation of adipose de novo lipogenesis (DNL) in South Asian Indians. The InDiMeT study aims to use a case–control design to identify genetic and modifiable-environmental-lifestyle associated determinants of (1) epigenomic (DNA methylome) dysregulation of adipose DNL in type 2 diabetes mellitus (T2DM) adipose tissue, (2) identify correlates of epigenomic (DNA methylome) dysregulation of adipose DNL in peripheral blood mononuclear cells (PBMCs) from T2DM subjects and (3) elucidate plasma lipidomic correlates of adipose DNL in T2DM that can be used as biomarkers of adipose tissue dysfunction. <h3>Methods and analysis</h3> The InDiMeT study will involve recruitment of 176 normoglycaemic and T2DM individuals who will be undergoing laparoscopic surgery for clinical conditions. Extensive phenotyping of the subjects will be conducted and DNA methylome and lipidomic measurements will be made. The adipose DNL pathway genes are likely to be hypermethylated in patients with T2DM with corresponding reduction of gene expression. Correlates of epigenomic (DNA methylome) dysregulation of adipose DNL pathway in PBMCs and their adipose and plasma lipidomic signatures in T2DM subjects could act as early markers of development of T2DM. <h3>Ethics and dissemination</h3> For the InDiMeT study, ethical approval for addressing the specific aims has been obtained from the Institutional Ethics Committee, St John’s Medical College and Hospital, St John’s National Academy of Health Sciences, Bangalore. Findings from this study will be disseminated through scientific publications in peer-reviewed journals, research conferences and via presentations to stakeholders, patients, clinicians, public and policymakers through appropriate channels.
Cisplatin every three weeks versus weekly cisplatin or carboplatin with definitive radiotherapy for squamous cell carcinoma of the head and neck is associated with improved overall survival in a representative national population.
Authors: Michael Gerard McCusker, Ranee Mehra, Jason K. Molitoris, Rodney Taylor, Kevin J. Cullen, Olga G. Goloubeva
Journal: Journal of Clinical Oncology (2020)

6536 Background: For patients with primary untreated locally advanced head and neck squamous cell carcinoma (PULA-HNSCC), high dose once every 3 weeks cisplatin (HDC; 100 mg/m 2 ) added to curative radiotherapy (RT) prolongs survival, but is associated with severe toxicities. Concurrent chemoradiation (CRT) with low dose weekly cisplatin (LDC; 30-40 mg/m 2 ), carboplatin (C), or RT alone is often substituted for HDC. We estimated and compared overall survival (OS) and acquired toxicities among Medicare beneficiaries treated with CRT using HDC, LDC, C, or RT. Methods: Patients diagnosed from 2004-2011 with PULA-HNSCC (stages III-IVB AJCC 6 th and 7 th editions) of the oropharynx (OPC), hypopharynx (HP), or larynx (L) who received definitive RT or CRT were identified using the linked SEER-Medicare database. An analytic cohort of patients receiving CRT with HDC, LDC, or C was constructed using well-established eligibility criteria. OS was estimated and compared between patients grouped by treatment received utilizing a multivariable stratified propensity scores weighted Cox regression model, including demographic and disease characteristics. Toxicities were compared using exact common odds-ratio and Fisher’s tests. Results: We identified 1,335 patients that received RT: OPC (n = 731), HP (n = 174), or L (n = 430). Out of those, patients were treated with HDC (n = 264), LDC (n = 259), C (n = 353), or RT alone (n = 459). Median OS (years) was 5.61 (95% CI = 4.58-7.69) for HDC, 3.7 (95% CI = 3.1-4.79) for LDC, 3.1 (95% CI = 2.48-3.86) for C, and 1.36 (95% CI = 1.19-1.58) for RT, respectively. OS was significantly greater for HDC than for LDC (HR = 1.35, 95% CI = 1.06-1.72, p= 0.02), C (HR = 1.41, 95% CI = 1.12-1.76, p= 0.003), or RT (HR = 2.1, 95% CI = 1.68-2.61, p= &lt; 0.001). Treatment with HDC compared to LDC was not associated with increased prevalence of dysphagia or neutropenia. HDC was associated with hearing loss when assessed at 9-12 months post-diagnosis ( p =0.03). Conclusions: In SEER-Medicare beneficiaries with PULA-HNSCC of the OPC, HP, or L, OS was significantly better for HDC than LDC when accounting for baseline clinical and demographic characteristics and propensity score weights. Toxicities were similar between regimens, except for an increased incidence of the late acute toxicity of hearing loss in HDC. A regimen of HDC improves OS, but needs to be carefully assessed against increased toxicity risk, with hearing loss in particular.
Association of tumor mutational burden (TMB) and clinical outcomes with pembrolizumab (pembro) versus chemotherapy (chemo) in patients with metastatic triple-negative breast cancer (mTNBC) from KEYNOTE-119.
Authors: Eric P. Winer, Oleg Lipatov, Seock-Ah Im, Anthony Goncalves, Eva Muñoz-Couselo, Keun Seok Lee, Peter Schmid, Laura Testa, Isabell Witzel, Shoichiro Ohtani, Jared Lunceford, Vassiliki Karantza, Jaime Alberto Mejia, Razvan Cristescu, Deepti Aurora-Garg, Petar Jelinic, Lingkang Huang, Javier Cortes
Journal: Journal of Clinical Oncology (2020)

1013 Background: In the randomized, open-label, phase 3 KEYNOTE-119 study (NCT02555657) , OS was not significantly different with pembro monotherapy versus chemo in second- or third-line settings for mTNBC; however, the pembro treatment effect increased with increasing PD-L1 enrichment. We evaluated the association of TMB with efficacy of pembro monotherapy versus chemo in patients with previously treated mTNBC. Methods: Patients with centrally confirmed TNBC and 1 or 2 prior systemic treatments for metastatic disease were enrolled. Patients were randomly assigned 1:1 to pembro 200 mg Q3W or single-agent chemo per investigator’s choice of capecitabine, eribulin, gemcitabine, or vinorelbine. Association of TMB, as measured by FoundationOne CDx (Foundation Medicine), with response was an exploratory objective evaluated using receiver operator characteristic (ROC) analysis, logistic regression (ORR), and Cox regression (OS; PFS) within treatment arms; estimates of efficacy based on TMB cutpoint used a prespecified cutpoint of 10 mut/Mb. Results: TMB data were available for 253/601 (42.1%) treated patients (pembro, n = 132; chemo, n = 121); baseline characteristics were similar to that of the overall study population. One-sided P values for the association of TMB and clinical outcomes in pembro-treated patients were 0.154 for ORR, 0.014 for PFS, and 0.018 for OS; the area under the ROC curve ([AUROC] 95% CI) for predicting ORR was 0.58 (0.43-0.73). Two-sided P values for the association of TMB and clinical outcomes in chemo-treated patients were 0.114 for ORR, 0.478 for PFS, and 0.906 for OS; AUROC (95% CI) was 0.43 (0.27-0.59). Twenty-six patients had TMB ≥10 mut/Mb. Thus, the prevalence of TMB ≥10 mut/Mb was ~10%. Outcomes based on TMB cutpoint are reported in the Table. Conclusions: Data from this exploratory analysis from KEYNOTE-119 suggest a potential positive association between TMB and clinical benefit with pembro but not chemo in patients with mTNBC. Although precision is limited by sample size and the number of patients with TMB ≥10 mut/Mb, ORR and HRs for OS suggested a trend towards increased benefit with pembro versus chemo in patients with TMB ≥10 mut/Mb. Clinical trial information: NCT02555657 . [Table: see text]
Prevalence of trastuzumab-induced cardiotoxicity in Uruguayan HER2-positive breast cancer patients treated in a real life setting during a 10 year period.
Authors: Natalia Camejo, Cecilia Castillo, Nora Artagaveytia, Crisitian Etcheverría, Jessica Ferradaz, Agustín Ferreira, Analía Fontán, Ana Sofía Gabín, Lucia Beatriz Delgado
Journal: Journal of Clinical Oncology (2020)

e12537 Background: To estimate the prevalence of Trastuzumab (TTZ) induced cardiotoxicity in Uruguayan women diagnosed with early HER – 2 positive breast cancer (BC) over a period of ten years, treated under the financial coverage of the National Resource Fund (FNR). Methods: A prospective descriptive observational study based on the analysis of an anonymized database provided by the FNR of Uruguayan HER-2 positive early BC patients treated with TTZ between 2006 and 2016. Variables analyzed included: age, menopausal status, stage, presence of cardiovascular risk factors, use or not of anthracyclines, left ventricular ejection fraction prior and during treatment, and temporary or permanent suspension of treatment. Statistical analysis was performed using SPSS Statistics version 25. The variables were assessed through the use of measures of central tendency, dispersion, contingency tables and proportions. To analyze the relationship between the different variables, the Chi-Square test of independence was performed. Results: The analysis included 1401 patients diagnosed with HER-2 + stage I to III breast cancer who received adjuvant TTZ. The mean age at diagnosis was 52.45 years. The prevalence of cardiotoxicity in evaluable patients (1065 pts) was 20.3%. The proportion of patients who had symptomatic heart failure was 3% (32 pts) and in those who discontinued treatment for asymptomatic cardiac toxicity managed to resume trastuzumab prevalence was 92.6 %. About 9,7 % (21 pts) of patients had drop of left ventricular ejection fraction (LVEF) below 50%, whilst 10% drop of LVEF below their baseline levels were found in 75% of patients (162 pts) There is significant difference in the risk of cardiotoxicity according to the type of chemotherapy (anthracycline containing vs non-anthracycline based) (Chi-square = 3.9, p-value &lt; 0.005). There was no evidence of a relationship between cardiovascular risk factors and the development of cardiotoxicity as well there was no evidence between sequential or concurrent use of TTZ with chemotherapy. Conclusions: The prevalence of cardiotoxicity in this study was similar to that reported internationally. The majority of patients did not develop cardiac toxicity and those who presented it did so asymptomatically and reversibly.
Effectiveness of general practitioner team contracted service in management of patients with type 2 diabetes mellitus
Authors: Yuling Li, Lei Lei, Jing Yu
Journal: BMJ (2018)

Objective
To evaluate the effectiveness of general practitioner contracted service in management of patients with type 2 diabetes mellitus (T2DM) in the community.


Methods
From January 2012 to April 2017, 1 625 patients of T2DM (766 males and 859 females with an average age of 62.9 years) were treated in Xinjiekou Community Health Service Center. They were managed by a contracted general practitioner team for one consecutive year, including initial assessment, patient education, disease follow-up and annual assessment. Four classes of diabetes and hypertension knowledge were given, patient self-assessment and nursing scoring were conducted before and after the education, including healthy life habits, diet and exercise. Family self-assessment, knowledge and skills in monitoring blood pressure, blood glucose, drug use, and risk prevention were carried out. Data collection and analysis were based on quarterly and annual follow-up tables.


Results
Before and after management, the mean BMI of 1 625 patients was (25.0±3.1) and (24.6±3.1) kg/m2 (t=13.25, P=0.001), systolic blood pressure was (133.3±10.0) and (122.7±7.7) mmHg (1 mmHg=0.133 kPa, t=43.84, P=0.001), diastolic blood pressure was (82.7±22.1) and (76.1±13.5) mmHg (t=10.46, P=0.001), fast blood glucose was (7.2±2.5) and (6.2±0.9) mmol/L (t=18.50, P=0.001), 2 h-postprandial blood glucose was (9.1±2.1) and (7.8±1.9) mmol/L (t=23.39, P=0.001) and glycated hemoglobin (HbA1c) was (6.8±1.1) and (6.3±2.2)% (t=8.68, P=0.001), all were decreased significantly after management. After management the rates of HbA1c, fasting blood glucose and 2 h-postprandial blood glucose reached the standard were increased (χ2=345.57, P=0.001; χ2=235.13, P=0.001; χ2=354.28, P=0.001). The rates of aerobic exercise, the proportion of 3-5 times a week, exercise time 30-60 minutes/time increased (χ2=1 245.58, P=0.001; χ2=158.38, P=0.001; χ2=264.26, P=0.001). The rates of smoking, drinking, eating fried food, saltiness food, sweetness food decreased (χ2=13.92, P=0.001; χ2=23.88, P=0.001; χ2=311.71, P=0.001; χ2=674.31, P=0.001; χ2=247.86, P=0.001). After management, the rates of blood pressure, blood glucose and waist circumference self-measurement; using food scales, staple measuring, salt spoon, oil spoon and kettle, pedometer were increased significantly. The scores of health, ability, knowledge and comprehensive evaluation after management were also increased significantly (40.3±6.0 vs. 20.9±11.0, t=76.46, P<0.001; 36.4±7.8 vs. 19.4±9.2, t=75.99, P<0.001; 14.8±3.3 vs. 7.6±4.4, t=51.03, P<0.001; 91.5±11.7 vs. 48.0±20.3, t=89.54, P<0.001).


Conclusion
The general practitioner team can effectively improve the self-management ability and achieve better clinical effect in T2DM patients.


Key words: 
Diabetes mellitus, type 2; Community health services; Diseases management