tbuckley/cabot-search huggingface dataset:
Green respiratory healthcare: need for proportionality
Authors: Martyn R Partridge
Journal: Thorax (2020)

The Montreal Protocol on Substances That Deplete the Ozone Layer was an example of an amazing international collaboration that has already led to improvements in the ozone layer, although the full effects will not be seen for decades. As part of the process, large numbers of medical aerosols were reformulated such that chlorofluorocarbons were replaced as propellants in pressurised metered dose inhalers (pMDIs) by new hydrofluoroalkane (HFA) propellants. This involved a massive commitment by the pharmaceutical industry to ensure that those with respiratory ill health continued to receive their medication in familiar but improved inhalers. However, these HFA propellants have a global warming effect, and this has led specialist societies and health service leaders to more recently call for prescribers and patients to consider switching from pMDIs to inhaler devices without propellants, although many patients will still need a pMDI for use in an emergency.1 Others have recently additionally drawn attention to the benefits of using small-volume HFA 134a pMDIs or those containing …
Ability of the combined clinical cell-cycle risk score to identify patients that benefit from multi versus single modality therapy in NCCN intermediate and high-risk prostate cancer.
Authors: Jonathan David Tward, Thorsten Schlomm, Stephen Bardot, Stephen J. Freedland, Lauren Lenz, Todd Cohen, Steven Stone, Jay Bishoff
Journal: Journal of Clinical Oncology (2020)

346 Background: Prolaris combines RNA expression analysis of cell cycle progression genes with clinicopathologic information to create a combined clinical cell-cycle risk score (CCR). We evaluated the ability of CCR to predict metastasis (mets) in men for whom guidelines indicate that multimodality therapy (MTx) should be considered. Methods: A commercial cohort (N=15669) of National Comprehensive Cancer Network unfavorable intermediate-risk (UFI) and high-risk (HR) men revealed a distribution of 70.5% and 29.5% respectively. A CCR threshold of 2.112 was selected so that 29.5% of these men were above the threshold. MTx was defined as combined use of androgen deprivation therapy with radiation (RT) or surgery, or with adjuvant RT. Associations were evaluated in a 718-person retrospective, multi-institutional database of Prolaris-tested UFI and HR men. Kaplan-Meier (KM) analyses and Cox regressions were used to estimate the effects of prognostic covariates. Results: Median follow-up was 5.13 years. CCR predicted mets in the full cohort (HR =3.8 [2.7,5.2], p&lt;10 −15 ) and after accounting for CAPRA (HR=4.3 [2.7,7.0], p&lt; 10 −7 ). CCR also was a significant predictor of mets in patients who received STx, as a continuous predictor (HR=4.0 [2.6,6.1], p&lt;10 −9 ) and when dichotomized at the threshold (HR=15.9 [5.4,46.5], p&lt; 10 −9 ). The KM probability of mets by 10 years for those below and above the threshold was 4.3% and 20.4% respectively. MTx reduced patients’ risk of mets (HR=0.46 [0.22,0.97], p=0.04), and treatment benefit can be evaluated as a function of CCR score (Table). Conclusions: The CCR score prognosticates a clinically meaningful different risk of metastasis for those receiving MTx versus STx. Approximately 27% and 73% of people with HR or UFI risk cancer have CCR scores below the risk threshold and may consider STx after considering the difference in risk of mets.[Table: see text]
Liberal Versus Restrictive Red Blood Cell Transfusion Thresholds in Hematopoietic Cell Transplantation: A Randomized, Open Label, Phase III, Noninferiority Trial
Authors: Jason Tay, David S. Allan, Elizabeth Chatelain, Doug Coyle, Mohamed Elemary, Adrienne Fulford, William Petrcich, Timothy Ramsay, Irwin Walker, Anargyros Xenocostas, Alan Tinmouth, Dean Fergusson
Journal: Journal of Clinical Oncology (2020)

PURPOSE Evidence regarding red blood cell (RBC) transfusion practices and their impact on hematopoietic cell transplantation (HCT) outcomes are poorly understood. PATIENTS AND METHODS We performed a noninferiority randomized controlled trial in four different centers that evaluated patients with hematologic malignancies requiring HCT who were randomly assigned to either a restrictive (hemoglobin [Hb] threshold &lt; 70 g/L) or liberal (Hb threshold &lt; 90 g/L) RBC transfusion strategy between day 0 and day 100. The noninferiority margin corresponds to a 12% absolute difference between groups in Functional Assessment of Cancer Therapy-Bone Marrow Transplant (FACT-BMT) score relative to baseline. The primary outcome was health-related quality of life (HRQOL) measured by FACT-BMT score at day 100. Additional end points were collected: HRQOL by FACT-BMT score at baseline and at days 7, 14, 28, 60, and 100; transplantation-related mortality; length of hospital stay; intensive care unit admissions; acute graft-versus-host disease; Bearman toxicity score; sinusoidal obstruction syndrome; serious infections; WHO Bleeding Scale; transfusion requirements; and reactions to therapy. RESULTS A total of 300 patients were randomly assigned to either restrictive-strategy or liberal-strategy treatment groups between 2011 and 2016 at four Canadian adult HCT centers. After HCT, mean pre-transfusion Hb levels were 70.9 g/L in the restrictive-strategy group and 84.6 g/L in the liberal-strategy group ( P &lt; .0001). The number of RBC units transfused was lower in the restrictive-strategy group than in the liberal-strategy group (mean, 2.73 units [standard deviation, 4.81 units] v 5.02 units [standard deviation, 6.13 units]; P = .0004). After adjusting for transfusion type and baseline FACT-BMT score, the restrictive-strategy group had a higher FACT-BMT score at day 100 (difference of 1.6 points; 95% CI, −2.5 to 5.6 points), which was noninferior compared with that of the liberal-strategy group. There were no significant differences in clinical outcomes between the transfusion strategies. CONCLUSION In patients undergoing HCT, the use of a restrictive RBC transfusion strategy threshold of 70 g/L was as effective as a threshold of 90 g/L and resulted in similar HRQOL and HCT outcomes with fewer transfusions.
Prognostic significance of rate of tumor marker (TM) decline during high-dose chemotherapy (HDCT) for relapsed germ cell tumors (rGCT).
Authors: Nabil Adra, Sandra K. Althouse, Rafat Abonour, Mohammad Issam Abu Zaid, Hao Liu, Nasser H. Hanna, Lawrence Einhorn
Journal: Journal of Clinical Oncology (2020)

403 Background: Rate of serum TM decline is prognostic in patients (pts) with GCT receiving first-line chemotherapy. We investigated the prognostic value of TM decline in rGCT treated with HDCT+peripheral-blood stem-cell transplant (PBSCT). Methods: 462 consecutive pts with rGCT treated with HDCT+PBSCT at Indiana University between 1/2004-1/2019. All pts were planned for 2 consecutive HDCT courses with carboplatin+etoposide per protocol (N Engl J Med 2007;357:340-8). Pts with elevated AFP and/or hCG were included (N=347). Slope and half-life (T 1/2 ) were calculated for weekly AFP+hCG during HDCT starting with peak value at days 1-7 to avoid interference from lysis. T 1/2 AFP≤7 days and hCG≤3 days were categorized satisfactory (SAT). Progression-free (PFS) and overall survival (OS) were compared for SAT vs unsatisfactory (UNSAT) using log-rank test and analyzed using Kaplan-Meier. Uni- and multivariable analysis using Cox regression model was performed. Results: 347 pts had elevated TM: 312 had non-seminoma and 35 had seminoma. Median age was 31 (range, 17-58). Primary site: testis (292), mediastinum (26), retroperitoneum/other (29). Metastatic sites included retroperitoneum (277), lung (233), liver (83), brain (77), and bone (21). At initiation of HDCT, 77 pts had elevated AFP, 222 elevated hCG, and 48 elevated both AFP+hCG. Median AFP 9 (1-21,347) and hCG 113 (1-178,140). 314 pts (91%) completed 2 planned cycles of HDCT. Overall, 46/347 pts had SAT decline (13 for AFP; 30 for hCG; 3 for both). Pts with SAT TM decline had superior outcomes compared to UNSAT: 2-yr PFS 69% vs 45% (p=0.006) and 2-yr OS 75% vs 51% (p=0.006). When evaluating each TM separately, SAT decline in hCG had superior outcomes vs UNSAT: 2-yr PFS 74% vs 47% (p=0.002). There was statistically non-significant difference for AFP: 2-yr PFS 48% vs 42% (p=0.65). In univariable analysis, UNSAT decline of hCG, but not AFP, was an adverse prognostic factor for PFS: HR=2.51 (95% CI, 1.40-4.51); p=0.002. Multivariable analysis will be presented. Conclusions: SAT rate of TM decline, particularly in hCG, predicts superior outcomes in rGCT undergoing HDCT+PBSCT. Pts with UNSAT TM decline are at higher risk for relapse and death.
John Wyn Owen: former director of the NHS in Wales, who introduced the concept of “health gain”
Authors: John Illman
Journal: BMJ (2020)

John Wyn Owen approached his death in the same way as his life as director of the NHS in Wales; director general of the New South Wales Health Department in Australia; and secretary of the Nuffield Trust in London.

In his final weeks he had a medical appointment; the consultant asked if he had any questions. He replied: “What questions should I have?” He asked this question repeatedly in his professional life. A highly skilled listener and a visionary leader, he was acclaimed for leading from the back, like the shepherd quoted by Nelson Mandela, who stays behind his flock, “letting the more nimble go ahead, whereupon the others follow, not realising that they are being directed from behind.”

Owen combined a talent for team building with a passion for public service, reflecting his socialist values and Welsh chapel upbringing. He learnt and spoke Welsh with great …
p16INK4a expression and survival outcomes in patients with penile squamous cell carcinoma: The M.D. Anderson Cancer Center Experience.
Authors: Jad Chahoud, Rachel Pham, Ming Guo, Curtis R. Pickering, Wei Qiao, Abha Khanna, Frederico Netto, Curtis Alvin Pettaway, Priya Rao
Journal: Journal of Clinical Oncology (2020)

5 Background: Penile Squamous Cell Carcinoma (PSCC) is associated with high risk human papillomavirus (HR-HPV) in about 50% of cases. The immunohistochemical test for p16INK4a (p16) is highly correlated with HR-HPV expression and used as prognostic marker for squamous cell carcinomas in various sites. The prognostic role of this marker in PSCC remains unclear. We studied whether the expression of HPV or p16INK4a is associated with survival in a large PSCC cohort. Methods: We conducted a single institution analysis of PSCC patients who received treatment between 1991-2017.Patients with a confirmed diagnosis of PSCC and available tissue were tested for HR-HPV status using the Cobas PCR assay. Histological subtype, tumor grade, LVI and p16 staining patterns were confirmed by an experienced pathologist. Patient characteristics were summarized using descriptive statistics of clinico-pathologic variables. Kaplan-Meier was used to estimate median overall survival (OS) and cancer specific survival (CSS). Log rank test, univariate and multivariate Cox models were applied to identify the prognostic factors for survival. Results: We identified 147 patients with PSCC, with available tissue for testing. The median follow-up was 5.2 years (95% CI; 4.48, 6.68y). Patients with p16(+) tumors showed a significantly longer median OS and CSS in comparison to the p16(–) group (p=0.038 and p=0.012), with respective 5 year OS probability of 73% (95% CI; 0.74, 0.98) in comparison to 56% (95% CI; 0.46, 0.67) and 5 year CSS probability of 89% (95% CI; 0.7, 1) in comparison to 64% (95% CI; 0.54, 0.75). In contrast, HPV status by PCR did not predict survival outcomes, with 5 year CSS probability for HPV(+) of 75% (95% CI; 0.61, 0.91) compared to 65% (95% CI; 0.55, 0.78) for HPV(–) patients. Multivariable analysis to evaluate the association with CSS, showed that p16(+) along with lymph node status was associated with lower risk of death (HR=0.28, 95%CI; 0.09-0.8, p=0.002), and OS (HR=0.49, 95%CI; 0.19-1.24, p=0.13) after adjusting for the covariates. Conclusions: Tumor p16 status was an independent prognostic factor for CSS in our PSCC cohort providing unique information above that of lymph node status alone.
Occurrence of tyrosine kinase inhibitors-induced renal impairment and its predictive value for the prognosis of patients with metastatic renal cell carcinoma.
Authors: Haoran Zhang, Xingming Zhang, Xudong Zhu, Hao Zeng, Zi Li, Pengfei Shen
Journal: Journal of Clinical Oncology (2020)

693 Background: To investigate the tyrosine kinase inhibitors (TKIs) related renal impairment (RI) on the therapy efficacy and survival of patients with metastatic renal cell carcinoma (mRCC). Methods: Clinical and pathological parameters of patients with mRCC treated with TKIs were retrospectively reviewed. Blood urea nitrogen (BUN), proteinuria(PU) and estimated glomerular filtration rate (eGFR) were defined as main renal function related parameters, and their levels at the time of pre- and post- TKIs treatment were recorded and analyzed. Abnormal BUN, PU and/or eGFR were defined as RI. Primary and secondary treatment outcomes were progression-free survival (PFS) and overall survival (OS), and tumor response was defined as secondary treatment outcome. SPSS 24.0 and GraphPad Prism 7.0a were used for statistical analyses. Results: A total of 110 patients were included in this study. At baseline, patients with abnormal BUN, abnormal eGFR and PU were 25 (22.7%), 27 (25.5%) and 30 (27.3%), respectively, which increased to 46 (41.8%), 55 (50.0%) and 64(58.2%) after TKI treatment. Survival analysis showed that baseline RI had no impact either on prognosis, or the effectiveness of TKIs. On the contrary, for post-treatment RI, PU level, elevated PU, and eGFR level were independently related to PFS and OS. Besides, eGFR decrease &gt;10% was indicated for longer OS time (19.0 vs 41.0 months, p=0.034). Sub-analysis suggested that, among 51 patients without RI pre-TKI therapy, eGFR level (P=0.004), eGFR decrease &gt; 10% (P=0.012), PU level (P=0.014) as well as elevated PU level (P=0.006) were statistically correlated with OS time. However, the similar trend was not identified in those with baseline RI. Furthermore, baseline eGFR level (P=0.020) and eGFR decrease &gt; 10% (P=0.016) within 1y after TKI therapy were identified to be effective biomarkers predicting OS. Conclusions: The occurrence of TKI-induced RI was indicated for better tumor response and survival outcomes, and provide valuable information for the individual treatment of mRCC patients. Thus, routinely monitoring of renal function, especially eGFR and PU, was highly recommended in TKIs-treated mRCC patients.
Response to olaparib or carboplatin in a real-world cohort of men with DNA damage repair (DDR) deficient metastatic castration-resistant prostate cancer (mCRPC).
Authors: Jacob E Berchuck, Rebecca Silver, Ziad Bakouny, Sarah Abou Alaiwi, Anis Hamid, Christopher Sweeney, Matthew L. Freedman, Mark Pomerantz, Mary-Ellen Taplin
Journal: Journal of Clinical Oncology (2020)

43 Background: PARP inhibitors (PARPi) and platinum chemotherapy cause synthetic lethality and result in clinical benefit in men with mCRPC whose tumors harbor deleterious alterations in DDR genes. BRCA2 is the strongest predictor, but data supports a role for BRCA1, ATM, and other genes. PARPi are more expensive than platinum chemotherapy; whether they are more effective is not known. We evaluated outcomes in men with DDR-deficient mCRPC treated with PARPi or platinum chemotherapy. Methods: We identified men treated at Dana-Farber Cancer Institute who received olaparib or carboplatin for mCRPC and underwent tumor mutation profiling. Progression-free survival (PFS) was determined using Prostate Cancer Working Group 3 guidelines. Pathogenic germline or somatic single-nucleotide variants, insertions/deletions, and copy number loss in BRCA2, BRCA1, and ATM, were identified. Log-rank test was utilized to compare differences in PFS. Results: We identified 27 men who received olaparib: 19/27 (70.4%) received prior taxane chemotherapy and 3/27 (11.1%) prior carboplatin; 16 had mono- or bi-allelic alterations in BRCA2 and 2 had alterations in BRCA1 or ATM. We identified 41 men treated with carboplatin: 39/41 (95.1%) received carboplatin in combination with a taxane; 36/41 (87.8%) received prior taxane chemotherapy and 7/41 (17.1%) prior PARPi; 16 had BRCA2 alterations and 5 had alterations in BRCA1 or ATM. Among men with BRCA2 alterations, there was no significant difference in PFS (HR 0.71, 95% CI 0.45-1.11; p = 0.13) between those treated with olaparib (4.9 months [m]) versus carboplatin (5.4 m). Similarly, no difference in PFS (HR 0.80, 95% CI 0.54-1.16; p = 0.24) was observed among men with BRCA2, BRCA1, or ATM alterations treated with olaparib (3.8 m) versus carboplatin (3.6 m). Conclusions: In a small real-world cohort of men with mCRPC harboring deleterious alterations in BRCA2, BRCA1, and ATM, there was no difference in PFS between those treated with olaparib versus carboplatin. These findings support further investigation into the comparative effectiveness and cost-effectiveness of PARPi and platinum chemotherapy in men with DDR-deficient mCRPC.
Abstract 11951: Atrial Fibrillation is Associated With Greater Risk Of Dementia in Older Veterans
Authors: Laure Rouch, Feng Xia, Patrick Stuchlik, Kristine Yaffe
Journal: Circulation (2019)

Introduction: The twin burdens of atrial fibrillation (AF) and dementia are rising as the population ages, yet the association of AF, a potential modifiable risk factor, with incident dementia and ...
Single-arm, phase II study to evaluate the safety and efficacy of sacituzumab govitecan in patients with metastatic castration-resistant prostate cancer who have progressed on second generation AR-directed therapy.
Authors: Joshua Michael Lang, Christos Kyriakopoulos, Susan F. Slovin, Jens C. Eickhoff, Scott Dehm, Scott T. Tagawa
Journal: Journal of Clinical Oncology (2020)

TPS251 Background: In patients with mCRPC, androgen receptor (AR) pathway inhibitors such as enzalutamide or abiraterone acetate are often used as first-line systemic therapy. After progression on either of these inhibitors, the likelihood of response to the other is significantly lower than in the first-line setting. Multiple resistance mechanisms have been identified, including the emergence of AR splice variants. Trop2 is a cell-surface antigen that is expressed in &gt; 70% of prostate cancers and is enriched in mCRPC expressing AR splice variants. Sacituzumab govitecan (SG; IMMU-132) is a novel antibody drug conjugate composed of humanized anti-Trop2 antibody conjugated to SN-38 payload by hydrolyzable linker. SG has potential to be an effective therapy after progression on initial AR pathway inhibitors to meet this significant unmet clinical need. Methods: This is a single-arm, open-label, multicenter phase 2 trial (NCT03725761) to determine the efficacy and safety of SG. The primary endpoint is PSA response rate (≥50% PSA decline at or within 9 weeks of starting treatment); secondary endpoints include rPFS and overall survival. 55 subjects with mCRPC who have progressed on second-generation AR-directed therapy in either the hormone sensitive or CRPC setting will be included. Fresh or archived metastatic site biopsy is required. Subjects will be treated with SG IV at 10 mg/kg on Day 1 and Day 8 of 21-day cycles until disease progression. Subjects who receive ≥1 SG dose and have ≥1 PSA post-dose assessment will be included in final efficacy analysis. Circulating tumor cell biomarker studies will be performed throughout treatment and at progression to investigate potential mechanisms of response/resistance to SG. Tumor biopsies at baseline and after 3 therapy cycles will evaluate genomic alterations that predict treatment response. Subjects who remain progression free will undergo repeated evaluations of extent of disease every 9 weeks. The trial is actively accruing. Managed by: Prostate Cancer Clinical Trials Consortium; Funding: Immunomedics; Support: Prostate Cancer Foundation. Clinical trial information: NCT03725761.
Sport Medicine Diagnostic Coding System (SMDCS) and the Orchard Sports Injury and Illness Classification System (OSIICS): revised 2020 consensus versions
Authors: John W Orchard, Willem Meeuwisse, Wayne Derman, Martin Hägglund, Torbjørn Soligard, Martin Schwellnus, Roald Bahr
Journal: British Journal of Sports Medicine (2020)

Coding in sports medicine generally uses sports-specific coding systems rather than the International Classification of Diseases (ICD), because of superior applicability to the profile of injury and illness presentations in sport. New categories for coding were agreed on in the ‘International Olympic Committee (IOC) consensus statement: Methods for recording and reporting of epidemiological data on injury and illness in sports 2020.’ We explain the process for determining the new categories and update both the Sport Medicine Diagnostic Coding System (SMDCS) and the Orchard Sports Injury and Illness Classification System (OSIICS) with new versions that operationalise the new consensus categories. The author group included members from an expert group attending the IOC consensus conference. The primary authors of the SMDCS (WM) and OSIICS (JO) produced new versions that were then agreed on by the remaining authors using expert consensus methodology. The SMDCS and OSIICS systems have been adjusted and confirmed through a consensus process to align with the IOC consensus statement to facilitate translation between the two systems. Problematic areas for defining body part categories included the groin and ankle regions. For illness codes, in contrast to the ICD, we elected to have a taxonomy of ‘organ system/region’ (eg, cardiovascular and respiratory), followed by an ‘aetiology/pathology’ (eg, environmental, infectious disease and allergy). Companion data files have been produced that provide translations between the coding systems. The similar structure of coding underpinning the OSIICS and SMDCS systems aligns the new versions of these systems with the IOC consensus statement and also facilitates easier translation between the two systems. These coding systems are freely available to the sport and exercise research community.
Mir-155 Expression Is Associated with Chemoimmunotherapy Outcome and Is Modulated By Bruton’s Tyrosine Kinase Inhibition with Ibrutinib
Authors: Daphne Guinn, Amy S. Ruppert, Kami J. Maddocks, Samantha Jaglowski, Amber L. Gordon, Thomas S. Lin, Richard A. Larson, Guido Marcucci, Erin K Hertlein, Jennifer A. Woyach, Amy J. Johnson, John C. Byrd
Journal: Blood (2014)