tbuckley/cabot-search huggingface dataset:
Biomarker testing patterns and actionability in advanced non-small cell lung cancer (aNSCLC) at OneOncology (OneOnc).
Authors: Ari M. Vanderwalde, Esprit Ma, Elaine Yu, Tania Szado, Richard Price, Anuj Shah, Craig S. Meyer, Ibrahim M. Abbass, Axel Grothey, Harry Staszewski, Dennis Slater, L. Johnetta Blakely, Lee S. Schwartzberg
Journal: Journal of Clinical Oncology (2021)

287 Background: Recent approvals of targeted treatments (tx) have improved personalized care in aNSCLC. Biomarker testing is crucial for patients (pts) to receive optimal tx expeditiously. This study examined aNSCLC biomarker testing and tx patterns at OneOnc. Methods: Pts diagnosed with aNSCLC (stage ≥ IIIb) from 1/1/2015 to 5/31/2020, aged ≥ 18 years, and with ≥ 1 visit ≤ 90 days of advanced (Adv) diagnosis (Dx) were retrospectively evaluated using the nationwide Flatiron Health electronic health record derived de-identified database from selected OneOnc sites. Descriptive analyses were conducted to evaluate testing patterns for ALK, BRAF, EGFR, KRAS, PD-L1, and ROS-1 biomarkers and actionable mutation tx pattern. Results: Overall 3,860 aNSCLC pts were included, median age was 69 years, 47% females, 66% non-squamous, 29% squamous, 4% histology NOS, and 23% with ECOG performance status 0-1. Of the 3,152 (82%) pts tested for any biomarker, 64% received next-generation sequencing (NGS) vs. 36% received other biomarker tests only. Testing rates varied by biomarker: EGFR (74%), ALK (72%), ROS-1 (66%), PD-L1 (57%), BRAF (56%), KRAS (54%). Pts who received all 6 biomarker tests increased from 12% (2015), 23% (2016), 40% (2017), 41% (2018), 48% (2019) to 56% (2020). Among the tested pts, the median time from Adv Dx to the first test result was 20 days (d) and from specimen collection after Adv Dx to the first test result was 12 d. Pts tested and treated before test result available declined from 28% (2015) to 16% (2020). Of 1,207 pts with actionable mutations, 390 (32%) received tx before the test result: 35% chemotherapy (chemo) only, 28% chemo + cancer immunotherapy (CIT), and 15% CIT only. After the test result, 26% to 81% of pts received no or other tx not specific to actionable mutations [Table]. Conclusions: Findings from this study demonstrated an increase in aNSCLC biomarker testing at OneOnc over time, while 44% pts in 2020 did not receive testing on all 6 biomarkers. Some pts had tx prior to the test result, but this trend appeared to decline. Further studies are warranted to better understand the reasons for pts receiving tx that were not specific to their actionable mutations.[Table: see text]
Procalcitonin and lung ultrasonography point-of-care testing to determine antibiotic prescription in patients with lower respiratory tract infection in primary care: pragmatic cluster randomised trial
Authors: Loïc Lhopitallier, Andreas Kronenberg, Jean-Yves Meuwly, Isabella Locatelli, Yolanda Mueller, Nicolas Senn, Valérie D’Acremont, Noémie Boillat-Blanco
Journal: BMJ (2021)

Abstract Objective To assess whether point-of care procalcitonin and lung ultrasonography can safely reduce unnecessary antibiotic treatment in patients with lower respiratory tract infections in primary care. Design Three group, pragmatic cluster randomised controlled trial from September 2018 to March 2020. Setting 60 Swiss general practices. Participants One general practitioner per practice was included. General practitioners screen all patients with acute cough; patients with clinical pneumonia were included. Interventions Randomisation in a 1:1:1 of general practitioners to either antibiotics guided by sequential procalcitonin and lung ultrasonography point-of-care tests (UltraPro; n=152), procalcitonin guided antibiotics (n=195), or usual care (n=122). Main outcomes Primary outcome was proportion of patients in each group prescribed an antibiotic by day 28. Secondary outcomes included duration of restricted activities due to lower respiratory tract infection within 14 days. Results 60 general practitioners included 469 patients (median age 53 years (interquartile range 38-66); 278 (59%) were female). Probability of antibiotic prescription at day 28 was lower in the procalcitonin group than in the usual care group (0.40 v 0.70, cluster corrected difference −0.26 (95% confidence interval −0.41 to −0.10)). No significant difference was seen between UltraPro and procalcitonin groups (0.41 v 0.40, −0.03 (−0.17 to 0.12)). The median number of days with restricted activities by day 14 was 4 days in the procalcitonin group and 3 days in the usual care group (difference 1 day (95% confidence interval −0.23 to 2.32); hazard ratio 0.75 (95% confidence interval 0.58 to 0.97)), which did not prove non-inferiority. Conclusions Compared with usual care, point-of-care procalcitonin led to a 26% absolute reduction in the probability of 28 day antibiotic prescription without affecting patients’ safety. Point-of-care lung ultrasonography did not further reduce antibiotic prescription, although a potential added value cannot be excluded, owing to the wide confidence intervals. Trial registration ClinicalTrials.gov NCT03191071 .
Transportation barriers to health care and mortality risk among the U.S. adults with history of cancer.
Authors: Changchuan Jiang, Lei Deng, Qian Wang, Stuthi Perimbeti, Xuesong Han
Journal: Journal of Clinical Oncology (2021)

121 Background: Lack of transportation delayed medical care for approximately 6 million Americans in 2017. Prior studies showed cancer survivors tend to have more healthcare service use, higher medical cost, and adverse clinical outcomes. It is important to understand the prevalence of, risk factors for, and long-term health consequences of transportation barrier to health care among cancer survivors. Methods: We identified cohorts of adult with history of cancer (n = 25,317) and adults without history of cancer (n = 422,797) from the 2000-2014 National Health Interview Survey (NHIS). Transportation barriers were measured as medical care delay due to lack of transportation in the past 12 months using a survey question. The prevalence of transportation barriers was estimated using multivariable logistic models. Risk of mortality estimated with weighted Cox’s proportional hazards models with age as the time scale, adjusting for sex, race/ethnicity, educational attainment, marital status, region, comorbidities, and survey year. All analyses accounted for complex survey design using SAS statistical software, version 9.4 (SAS Institute Inc.), and SAS callable SUDAAN 11.0.3. Results: After adjustment for sociodemographic factors and comorbidities, the prevalence of transportation barrier were significantly higher among cancer survivors than among respondents without cancer history (2.1% vs 1.6%, p = 0.001, adjusted odd ratio [OR], 1.22; 95% confidence interval (95CI): 1.10-1.35). Cancer survivors with transportation barrier were more likely to be younger, female, Hispanic or Asian/Pacific Islander, less educated, unmarried, public insurance beneficiary or uninsured, and with more comorbidities. Among all participants, cancer survivors with transportation barrier had the highest adjusted mortality risk (hazard ratio [HR]: 2.12, 95CI: 1.81-2.49); followed by cancer survivors without transportation barrier (HR: 1.53, 95CI: 1.42-1.65); and adults without a cancer history with transportation barrier (HR: 1.50; 95CI: 1.45-1.55) compared with adults with neither a cancer history nor transportation barrier. Conclusions: Transportation barriers to health care had a disproportionate impact on cancer survivors, especially those who are underserved, and who have more medical needs. Increased risk of mortality was observed among adults with and without a cancer history who delayed care due to lack of transportation. It highlights the need for efforts to mitigate transportation barriers to medical care during a time of rapid change in transportation and telehealth technology.
Association of primary prophylactic (PP) granulocyte-colony stimulating factor (G-CSF) use with chemotherapy dose modifications and relative dose intensity (RDI) among breast cancer patients receiving high-risk regimens for febrile neutropenia (FN).
Authors: Jaime Shaw, Jennifer Schenfeld, Akhila Balasubramanian, Renee Jaramillo, Darcie Sandschafer, Michael Anthony Kelsh, Reshma L. Mahtani
Journal: Journal of Clinical Oncology (2021)

314 Background: FN is a primary driver of chemotherapy modification and reduced RDI. Breast cancer patients often receive regimens with high risk ( &gt; 20%) for FN. PP G-CSF use is recommended to decrease incidence of infection, as manifested by FN. Real-world evidence describing the association of G-CSF with reduced RDI in breast cancer patients is lacking. Methods: We retrospectively analyzed Flatiron Health Electronic Health Record data from 2011 to 2019 of adult female breast cancer patients initiating high-risk for FN chemotherapy regimens. PP G-CSF (pegfilgrastim, filgrastim, or biosimilars) use was assessed in the first and subsequent cycles of chemotherapy overall and by modality (on-body injector [OBI] vs. pre-filled syringe [PFS]). Standard dose was defined by NCCN guidelines. RDI was defined with respect to dose and timing of delivery: (delivered dose intensity/standard dose intensity)*100 and categorized as &lt; 85% vs ≥85%. Characteristics were described by G-CSF use and adjusted relative risks (ARRs) were estimated for the association between G-CSF use and RDI, adjusting for age, serum hemoglobin, ECOG, HER2 status, and HR status. Results: There were 27,812 breast cancer patients included with a median age of 57 years. Most (90%) received PP-G-CSF. Four cycles of TC (docetaxel + cyclophosphamide) was the most common regimen prescribed (36%) and 82% of these patients received PP-G-CSF support in the first cycle, with OBI given more often than PFS (62% vs 38%). Second most common was dd AC-T Q1W (doxorubicin + cyclophosphamide followed by paclitaxel) and 98% of these patients received PP G-CSF (59% OBI vs 41% PFS). 80% of G-CSF users (vs 48% of those with no G-CSF) completed 4 or more cycles of chemotherapy (all regimens had ≥4 planned cycles). G-CSF users had a significant reduction in risk of RDI &lt; 85% in Cycle 1 (ARR: 0.60; 95% confidence interval [CI]: 0.43 – 0.85) and Cycle 2 (ARR: 0.76; 95% CI: 0.59 – 0.97). At the overall chemotherapy course level, the risk of RDI &lt; 85% was not significantly different by G-CSF use (ARR: 0.83; 95% CI: 0.63 - 1.08). There was no significant difference in risk of reduced RDI between OBI and PFS (ARR: 1.13; 95% CI: 0.94 - 1.35). Conclusions: This study revealed that 90% of breast cancer patients receiving high-risk for FN chemotherapy received PP-G-CSF support and completed more cycles than those who did not receive G-CSF. G-CSF users had lower risk of a reduced RDI in Cycles 1 and 2.
VALUE of LABORATORY PARAMETERS in the CLINICAL MONITORING of PATIENTS with SARS-COV-2 INFECTION (COVID-19)
Authors: M. M. Carbonell, E. G. Gomez, A. G. Martinez, C. H. Mata, S. M. C. Ramos, M. C. Marin, A. L. Pena, C. R. Lefler, A. J. G. Ortego, S. F. P. Marino, N. F. Mosteirin, J. M. C. Villas
Journal: HemaSphere (2021)

Background: Association between some analytical parameters and clinical evolution of patients infected by SARS-COV-2 is a controversial issue. Aims: Review the relationship between laboratory parameters and severity and/or lethality of the COVID-19. Methods: Observational, cross-sectional and retrospective study. Data obtained from electronic health record of patients over18 years of age admitted in our hospital, between March and May 2020 with suspected SARS-COV-2 infection. After descriptive statistical study, we did an inferential analysis using Mann-Whitney U test for independent samples, in order to verify association between the results of analytical parameters and the clinical severity (defined by hospitalization in conventional ward vs. intensive care units (ICU)) and/or lethality (alive vs. death at the end of the study). Results: 668 patients were included, 345 men (52%) and 323 women (48%), with a median age of 70 years. 80% of patients had previous comorbidities,10% were admitted to the ICU, and17% died. Differences were found in hematimetric parameter between the different groups: leukocytes (103/μl): 8.3 in ICU patients vs. 6.5 in those admitted to the ward;platelet count (103/μl) of182l in death patients vs. 223 in survivors;hemostasis parameters: D-dimer (DD) (μg/L) of1379 and1236 in deceased and admitted to the ICU respectively, compared to 734 and 786 in survivors and not admitted to ICU;and biochemical figures (increase in C-reactive protein (CRP), lactate dehydrogenase (LDH) or cardiac enzymes, the latter, especially, in patients who were deceased, with a median ultrasensitive troponin I (ng/L) of 34.75 vs. 7.1 in survivors. The differences were statistically significant (p value <0.01). Summary/Conclusion: Correlation exist between severity of infection and the increase in leukocytes, neutrophils, DD, CRP and LDH, and lymphopenia, in our sample. Decrease in the platelet count and the increase in cardiac enzymes were associated with an increased risk of mortality.
Application of omics technology to combat the COVID‐19 pandemic
Authors: Jingjing Yang, Yunzheng Yan, Wu Zhong
Journal: MedComm (2021)

Abstract As of August 27, 2021, the ongoing pandemic of coronavirus disease 2019 (COVID‐19), caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2), has spread to over 220 countries, areas, and territories. Thus far, 214,468,601 confirmed cases, including 4,470,969 deaths, have been reported to the World Health Organization. To combat the COVID‐19 pandemic, multiomics‐based strategies, including genomics, transcriptomics, proteomics, and metabolomics, have been used to study the diagnosis methods, pathogenesis, prognosis, and potential drug targets of COVID‐19. In order to help researchers and clinicians to keep up with the knowledge of COVID‐19, we summarized the most recent progresses reported in omics‐based research papers. This review discusses omics‐based approaches for studying COVID‐19, summarizing newly emerged SARS‐CoV‐2 variants as well as potential diagnostic methods, risk factors, and pathological features of COVID‐19. This review can help researchers and clinicians gain insight into COVID‐19 features, providing direction for future drug development and guidance for clinical treatment, so that patients can receive appropriate treatment as soon as possible to reduce the risk of disease progression.
A mutation in the SAA1 promoter causes hereditary amyloid A amyloidosis
Authors: Jakub Sikora, Tereza Kmochová, Dita Mušálková, Michal Pohludka, Petr Přikryl, Hana Hartmannová, Kateřina Hodaňová, Helena Trešlová, Lenka Nosková, Lenka Mrázová, Viktor Stránecký, Mariia Lunová, Milan Jirsa, Eva Honsová, Surendra Dasari, Ellen D. McPhail, Nelson Leung, Martina Živná, Anthony J. Bleyer, Ivan Rychlík, Romana Ryšavá, Stanislav Kmoch
Journal: Kidney International (2021)
Prognosis of unexpected positive intraoperative cultures in arthroplasty revision: A large multicenter cohort
Authors: Mikel Mancheño-Losa, Jaime Lora-Tamayo, Marta Fernández-Sampedro, Dolors Rodríguez-Pardo, Ernesto Muñoz-Mahamud, Laura Soldevila, Mariona Palou, José María Barbero, María Dolores Del Toro, José Antonio Iribarren, Beatriz Sobrino, Alicia Rico-Nieto, Laura Guío-Carrión, Lucía Gómez, Rosa Escudero-Sánchez, María José García-País, Alfredo Jover-Sáenz, Julia Praena, Josu Miren Baraia-Etxaburu, Álvaro Auñón, Elena Múñez-Rubio, Oscar Murillo
Journal: Journal of Infection (2021)
Overall survival benefits of advances in NSCLC systemic treatments: Younger versus older adults.
Authors: Bonnie Leung, Aria Shokoohi, Zamzam Salam Al-Hashami, Sara Moore, Alexandra Pender, Selina K. Wong, Ying Wang, Jonn Wu, Cheryl Ho
Journal: Journal of Clinical Oncology (2021)

93 Background: Historically, there has been limited systemic therapy options for older adults with cancer attributed to underlying frailty, co-morbidities, poor functional status, and limited social supports. In the past decade, treatment for advanced NSCLC has changed with increasing availability of novel therapeutics associated with improved tolerability and efficacy, such as targeted therapy and immunotherapy. The study goal is to compare the difference in overall survival (OS) between younger adults and older adults with the introduction of novel therapeutic options. Methods: All patients with stage IV NSCLC referred to BC Cancer in 2009, 2011, 2015 and 2017 were included in the study. One-year time points were chosen based on molecular testing implementation and provincial formulary listing: baseline (2009), EGFR testing (2011), ALK testing (2015) and immunotherapy listing (2017). Age was categorized as younger (&lt; 70 years) and older (≥70 years) adults. Baseline demographics, simplified comorbidity score (SCS ≥9 associated with poor prognosis), disease characteristics, and systemic therapy details (agent, duration, line of therapy) were collected retrospectively. Univariate analysis using X 2 and Fisher’s exact tests were used to compare age groups. OS was calculated using the Kaplan-Meier method and compared using the log-rank test. Results: 3325 patients with stage IV NSCLC were identified. Baseline characteristics for patients &lt; 70 y; female 51%, non-squamous 62%, ECOG ≥2 50%, SCS ≥9 29% vs patients ≥70 y; female 49%, non-squamous 57%, ECOG ≥2 61%, SCS ≥9 58%. In the four time cohorts 2009/2011/2015/2017, systemic treatment was delivered to &lt; 70 y 44/53/51/52 % vs ≥70 y 23/25/28/30 %. Median OS with BSC for &lt; 70 y 3.1/2.8/2.8/2.5 m vs ≥70 y 3.8/3.3/3.4/3.1 m (p = 0.10). Median OS with systemic treatment for &lt; 70 y 9.0/10.9/13.9/15.5 m (p &lt; 0.001) vs ≥70 y 11.4/11.7/13.9/14.9 m (p &lt; 0.001). Median OS by type of treatment BSC/chemotherapy only/targeted therapy/immunotherapy; &lt; 70 y 2.8/8.9/21.4/20.2 m vs ≥70 y 3.1/10.1/21.5/20.1 m (p &lt; 0.001). Conclusions: In this real-world retrospective review of patients with advanced NSCLC, there was an increased uptake of systemic therapy for both age groups with the introduction of novel therapeutics. Although there was a smaller proportion of older adults who received systemic therapy, those who received treatment had comparable OS to their young counterpart. The benefit of systemic therapy in both age groups was seen across the different types of treatments. This suggests with careful assessment and selection of appropriate candidates, older adults with advanced NSCLC should receive equitable access to systemic therapy.
Abstract 19343: Pharmacokinetic and Triglyceride-Lowering Pharmacodynamic Effects of Icosapent Ethyl (Eicosapentaenoic Acid Ethyl Ester) Across Clinical Studies
Authors: Rene Braeckman, Harold E Harold, Christie M Ballantyne, William G Stirtan, Paresh N Soni
Journal: Circulation (2013)

Background: Icosapent ethyl (IPE; formerly AMR101) is a high-purity prescription form of eicosapentaenoic acid (EPA) ethyl ester approved to reduce triglyceride (TG) levels in patients with severe (&gt;=500 mg/dL) hypertriglyceridemia. Objective: To examine the effects of IPE on EPA concentrations in plasma and red blood cells (RBCs) in response to dose and the relationship to TG lowering across 3 clinical studies. Methods: MARINE and ANCHOR were 12-week, phase 3, double-blind studies that randomized patients to IPE 4 g/day, 2 g/day, or placebo. MARINE randomized 229 patients with TG &gt;=500 and &lt;=2000 mg/dL while ANCHOR randomized 702 high-risk patients with TG &gt;=200 and &lt;500 mg/dL despite low-density lipoprotein cholesterol (LDL-C) control while on statin therapy. IPE 4 g/day and 2 g/day was also investigated in 48 healthy subjects for 4 weeks in a phase 1 PK study. Results: In all studies, a greater increase in EPA concentrations in both plasma and RBCs was observed with IPE 4 g/day than with 2 g/day, indicating a dose-dependent increase in EPA exposure. EPA concentration data from healthy volunteers and in patients with hypertriglyceridemia indicate that the PK of EPA are linear with dose. In MARINE and ANCHOR, median percent reductions in TG from baseline were higher with IPE 4 g/day than with 2 g/day and demonstrated a dose-proportional relationship. In plasma and RBCs, a linear PD relationship between EPA levels and TG reduction was also observed, demonstrating a linear concentration-response relationship. The figure shows TG median % change from baseline versus EPA mean % change from baseline in plasma from the ANCHOR study (error bars are 95% CIs). Conclusions: Taken together, the linear-dose-PK and dose-concentration-response PD relationships indicate that the PK/PD of IPE are predictable as the results demonstrate a trend of increasing TG-lowering efficacy with respect to both the IPE dose and EPA concentration in plasma and RBCs.
Assessment of Silicone Particle Migration Among Women Undergoing Removal or Revision of Silicone Breast Implants in the Netherlands
Authors: Henry B. P. M. Dijkman, Inca Slaats, Peter Bult
Journal: JAMA Network Open (2021)

Silicone breast implants have been on the market for breast augmentation or breast reconstruction for approximately 60 years but may lead to medical complications, also called breast implant illness.To evaluate the existence of silicone gel bleed and migration over a long time period, including the period in which the newer cohesive silicone gel breast implants were used.In this single-center case series, capsule tissue and lymph node samples were collected from women who underwent removal or revision of silicone breast implants from January 1, 1986, to August 18, 2020, and data were extracted from the pathological reports and revision of the histology if data were missing. All tissues were examined using standard light microscopy, some extended with modified oil red O staining and energy-dispersive radiographic spectroscopy. A total of 365 women had capsular tissue removed, including 15 patients who also had lymph nodes removed, and 24 women had only lymph nodes removed. Data were analyzed from January to May 2021.Silicone breast implants.The main outcome was presence or absence of silicones inside or outside the capsule. One-way analysis of variance was used to determine significance between groups.Among a total of 389 women with silicone breast implants (mean [SD] age, 50.5 [11.2] years), 384 women (98.8%) had silicone particles present in the tissues, indicating silicone gel bleed. In 337 women (86.6%), silicone particles were observed outside the capsule (ie, in tissues surrounding the capsule and/or lymph nodes), indicating silicone migration. In 47 women (12.1%), silicone particles were only present within the capsule. In 5 women (1.2%), no silicone particles were detected in the tissues. Patients were divided into 2 groups, with 46 women who received cohesive silicone gel breast implants and 343 women who received either an older or a newer type of breast implant. There were no differences in silicone gel bleed or migration between groups (silicone detected outside or inside capsule: 44 women [95.7%] vs 340 women [99.1%]; P = .19).In this case series including women with noncohesive or cohesive silicone gel breast implants, silicone leakage occurred in 98.8% of women, indicating silicone gel bleed, and in 86.6% of women, migration of silicone particles outside the capsule was detected.