tbuckley/cabot-search huggingface dataset:
Prevalence of exercise-induced oxygen desaturation after recovery from SARS-CoV-2 pneumonia and use of lung ultrasound to predict need for pulmonary rehabilitation
Authors: A. Carlucci, M. Paneroni, M. Carotenuto, E. Bertella, S. Cirio, A. Gandolfo, C. Simonelli, M. Vigna, C. Lastoria, A. Malovini, B. Fusar Poli, M. Vitacca
Journal: Pulmonology (2021)

Persistence of breathlessness after recovery from SARS-CoV-2 pneumonia is frequent. Recovery from acute respiratory failure (ARF) is usually determined by normalized arterial blood gases (ABGs), but the prevalence of persistent exercise-induced desaturation (EID) and dyspnea is still unknown. We investigated the prevalence of EID in 70 patients with normal arterial oxygen at rest after recovery from ARF due to COVID-19 pneumonia. Patients underwent a 6-min walking test (6MWT) before discharge from hospital. We recorded dyspnea score and heart rate during 6MWT. We also investigated the possible role of lung ultrasound (LU) in predicting EID. Patients underwent a LU scan and scores for each explored area were summed to give a total LU score. In 30 patients (43%), oxygen desaturation was >4% during 6MWT. These patients had significantly higher dyspnea and heart rate compared to non-desaturators. LU score >8.5 was significantly able to discriminate patients with EID. In SARS-CoV-2 pneumonia, ABGs at discharge cannot predict the persistence of EID, which is frequent. LU may be useful to identify patients at risk who could benefit from a rehabilitation program.
Sequential usage of imidazole followed by tamoxifen to enhance the anticancer effect of tamoxifen in estrogen receptor-positive breast cancer cell lines.
Authors: Tarik Inci, Erkan Kahraman, Erdem Goker
Journal: Journal of Clinical Oncology (2021)

e15057 Background: In women, breast cancer is the most commonly diagnosed cancer and the leading cause of cancer death worldwide. Tamoxifen is the most commonly used drug for the endocrine treatment of breast cancer. It reduces the risk of recurrence and death from breast cancer when given to estrogen-receptor-positive breast cancer patients. It has recently been shown that imidazoles, an antifungal drug, possess anticancer potentials, and it can be a novel therapeutic in cancer treatment. However, the effects of combined treatment with imidazole and tamoxifen are unknown in estrogen receptor-positive breast cancer cell lines. Our study aimed to investigate the effects of imidazole and tamoxifen combination in estrogen receptor-positive breast cancer cell lines. Methods: MCF7 cell line, an estrogen receptor-positive breast cancer cell line, was used in this study. Following 24 hours 50 mM imidazole (molecular grade) treatment, 15µM tamoxifen was treated to MCF-7 cells by 72 hours. As control groups, following for 24-hour imidazole alone treated, only medium treated cells for 72 hours were used. MTT assay was performed for the determination of cell viability. Apoptosis was shown using acridine orange/ethidium bromide staining. The cellular morphological alterations were observed on bright-field microscopy using Giemsa staining. Cell migration status was determined using by in vitro scratch assay. Results: MTT assay results showed that tamoxifen alone treatment for 72 hours decreased cell viability by 18 percent (p &lt; 0.001). On the other hand, cell viability is not affected by imidazole alone treatment for 24 hours compared with the control group (p &gt; 0.05). However, it was calculated that 24 hours of imidazole followed by tamoxifen for 72 hours decreased cell viability up to 42 percent (p &lt; 0.001). Tamoxifen alone group, compared with combined treatment with tamoxifen and imidazole, observed an increase of apoptotic cell numbers in combined treatment with tamoxifen and imidazole group, statistically significantly (p &lt; 0.01). It was observed that cellular morphology was affected by combined treatment with tamoxifen and imidazole. Giemsa staining results showed that MCF 7 cells changed their cellular morphology, lost cell-cell contact, differentiated from parental morphology and cellular morphology, and appeared unhealthy. Parallel to these findings, a decrease in cell migration was observed in the combined-treated group compared to the tamoxifen alone group (p &lt; 0.01). Conclusions: Our results showed that sequential usage of imidazole followed by tamoxifen has an enhanced anticancer effect of tamoxifen in estrogen receptor-positive breast cancer cell lines. These results allow us to establish a new hormonal treatment for patients with breast cancer.
Does prior treatment with anti-PD 1 immune check point inhibitors (ICIs) mitigate infection with herpes and SARS-CoV-2 viruses: Clinical evidence supporting basic hypotheses.
Authors: Apoorva Jayarangaiah, Richard J. Gralla, Beth McLellan
Journal: Journal of Clinical Oncology (2021)

e24045 Background: We present the initial clinical evidence of likely mitigation of viral infections in patients with non-small cell lung cancer (NSCLC) who previously responded to pembrolizumab. This may constitute a late beneficial effect of ICI treatment, and may identify patients with decreased risk for poor outcomes from major viral infections.While prior clinical reports are lacking, there is abundant laboratory evidence that: 1) immune checkpoint inhibition of the PD-1-mediated signaling pathway augments the response of antigen-specific T cells which likely leads to enhanced viral clearance (Dyke, Eur J Clin Immunol 2017); and 2) high levels of PD-1 positive CD-8 T cells have been demonstrated in HIV, Hepatitis B &amp; C infections, akin to the PD-1 positive tumor-reactive tumor infiltrating cells described in host directed mechanisms against cancer (Rao, Int J Inf Dis 2017). Methods: We report the limited pattern and shortened course of three instances of herpetic infection, and one occurrence of SARS-CoV-2, which suggest enhanced mitigation of viral infection in patients previously treated with ICIs. We have seen no other cases of such limited and rapidly clearing herpes in our thoracic oncology practice. Results: Patient characteristics: ages 38 – 78; 1 female; all stage IV extent; 1 with squamous cell carcinoma and the others had adenocarcinoma/sarcomatoid carcinoma NSCLC; PDL-1 tumor proportion scores &gt; 90% except for the 1 patient with squamous cell carcinoma who had a PDL-1 score &lt; 1%. One patient received only pembrolizumab; the others also received cisplatin-based combination chemotherapy. All responded well to anticancer treatment, were off all treatment for &gt; 1 year, and continue to do well 2 – 5 years after diagnosis. Three infections diagnosed as Herpes zoster presented in each case with only one or two vesicles within a single dermatome. Each infection was diagnosed 48 – 72 hours after eruption, was only minimally symptomatic, and cleared within one or two days. The case of documented SARS-CoV-2 occurred in a 60 year old woman with NSCLC and COPD who was off ICI therapy for 3 years with a complete response. She had minimal COVID-19 symptoms which cleared within 3 days. Conclusions: We conclude that: 1) these cases suggest mitigation of viral infections in patients with NSCLC who had prior anticancer benefit with pembrolizumab, and constitute a long term positive effect of ICIs; 2) these results support the pre-clinical findings and hypotheses of enhanced antiviral immune response with ICI agents; and 3) prospective evaluation of large populations of patients with cancer receiving ICIs is warranted to determine if this benefit is reproducible, what proportion of patients benefit, the magnitude of benefit, and to guide in prospective antiviral treatment in the highly vulnerable NSCLC population.
Abstract 14397: Diabetic Patients Have Significantly Higher Rates of Alzheimer’s Dementia, a Risk That is Attenuated by Treatment Approach
Authors: Thomas J Bunch, Heidi T May, Tami Bair, John Carlquist, Brian G Crandall, J P Weiss, Jeffrey S Osborn, Charles Mallender, Jeffrey L Anderson, Joseph B Muhlestein, Donald L Lappe, John D Day
Journal: Circulation (2013)

Introduction: Atrial fibrillation (AF) adversely impacts risk of mortality, stroke, heart failure, and dementia. Recently, AF diabetic patients were shown to have much higher rates of silent stroke...
Does the precision oncology medicine development pathway deliver value for health systems?
Authors: Raymond Henderson, Declan French, Elaine Stewart, Dave Smart, Adam Idica, Jordan Clark, Markus Eckstein, Mark Lawler
Journal: Journal of Clinical Oncology (2021)

e18818 Background: While there is increasing evidence that precision cancer medicines (PCMs) can be more effective than “one-size-fits-all” (OSFA) oncology medicines, questions persist as to their cost, availability, and overall patient benefit. We determined whether using a PCM approach to medicines discovery/development delivers medicines within cost constraints of health systems. R&amp;D costs of developing a medicine are a subject of debate, with average estimates ranging from $314 million (M) - $2.8 billion (B). Methods: Data on oncology medicines approved (2011-2020) by the US Food and Drug Administration (FDA) were analyzed, employing two approaches to estimate R&amp;D costs to bring the medicine to market: (i) Securities and Exchange Commission (SEC) data were compiled from 10-K and 10-Q financial performance filings on the medicine’s development cost through its R&amp;D lifetime. (ii) Employing a base figure of $100,271 (the estimated cost per patient in a phase III clinical trial), costs were calculated, based on data from clinicaltrials.gov. Trial data were split into clinical trial phases and probability of trial success calculated, along with preclinical costs. Cost-of-capital (CoC) approach was applied and if appropriate an orphan drug tax credit (ODTC) was subtracted from the total. Results: 19 PCMs and 11 OSFA oncology drugs listed by the National Cancer Institute which had complete data were analyzed from 22 companies (Table). Initial costs from SEC data suggest a 50% reduced development spend for PCM, ($605M; range = $181M-$1.1B) (Clinical Trial Modelling Analysis: $604M ($63M-$2.29B)), compared to an OSFA oncology drug development spend ($877M; $333M-$3.34B) (Modelling Analysis: $597M ($41M-$1.64B)). Once preclinical costs were added total R&amp;D costs capitalized and ODTC subtracted, there was an 83% increase in costs, from $2.44B ($614M-$5.23B) (Modelling Analysis: $3.1B ($209M-$11.52 B)) for PCMs to $4.46B ($1.59-$14.9B) (Modelling Analysis: $3.92B ($282-$12.74B) for OSFA oncology drugs. SEC data are more accurate, as they capture real data, rather than modelling assumptions. Conclusions: Our results provide an estimate of the R&amp;D spend required to bring an oncology medicine to market. R&amp;D cost of a PCM is below the top range of prior estimates published, while R&amp;D cost of an OSFA oncology medicine is almost twice the cost of a PCM, emphasizing the potential for PCM treatments to deliver care at greater value to patients and health systems.[Table: see text]
難治性の心嚢水貯留に対する経皮的心膜切開術(Percutaneous Balloon Pericardiotomy)の一例
Authors: 端孝樹, 井上一郎, 河越卓司, 石原正治, 嶋谷祐二, 栗栖智, 中村秀志, 吉田賢司, 光波直也
Journal: Circulation (2004)
Assessing financial difficulty in patients with multiple myeloma: Preliminary results of ALLIANCE A231602CD.
Authors: Rena M. Conti, Shaylene McCue, Travis Dockter, Bruce D. Rapkin, Stacie Dusetzina, Antonia Vickery Bennett, Gabriela Gracia, Michelle E. Johnson, Sarah A. Martin, George J. Chang, Paul G. Richardson, Robert J. Behrens, Elisa S. Weiss
Journal: Journal of Clinical Oncology (2021)

8031 Background: New orally administered anticancer treatments have launched in recent years, promising gains in survival and quality of life, but with high prices. Financial difficulties encountered over the course of cancer diagnosis and treatment is a growing concern. These difficulties include inability to pay for basic necessities, presence of medical debt, and high out of pocket burdens relative to income. The primary objective of this study was to estimate the proportion of patients with multiple myeloma (MM) who experience financial difficulties in the past 12 months. Methods: Data collection entailed a comprehensive, theoretically grounded telephone survey and companion medical chart abstraction. Subjects included individuals with a current diagnosis of MM whose current or recent treatment included pharmaceutical-based care and who were not enrolled in a treatment-based trial. Practices eligible to recruit respondents included 44 NCORP affiliates of the Alliance. 14 geographically diverse NCORP affiliates participated between 11/2019 and 6/2020. The primary endpoint of the study was the proportion of subjects who reported financial difficulty in the past 12 months, as measured by the EORTC QLQ-C30 item #28. This proportion and 95% Wilson score confidence interval were estimated for all MM patients who responded to the financial difficulty question ((# reported financial difficulty)/(total # in that category who answered the question)). NCI Central IRB approved this study. Results: 393 subjects were recruited. 304 subjects completed the survey (77.4% response rate). Mean age was 67.5 years (SD 9.8), 143 (46.4%) were female, 24 (7.8%) self-reported race as ‘Black or African American’, 82 (26.6%) reported insured by government insurance Medicare only, 116 (38.2%) reported highest education as high school or below, and 94 (30.5%) reported high income. Mean time from diagnosis to survey enrollment was 3.6 years (SD 4.5). 292 (95.1%) were currently receiving treatment and 192 (62.5%) reported currently receiving a pre-defined ‘expensive’ oral pharmaceutical-based cancer treatment. 20.2% (95% CI:16.1%, 25.0%) reported financial difficulties. Conclusions: This is the first national study to systematically assess the prevalence of financial difficulties and its correlates among MM patients. Approximately 1 in 5 surveyed patients reported financial difficulties. Results of this study aim to inform efforts to improve financial navigation and resources for cancer patients.
Estimation of Excess Mortality Rates Among US Assisted Living Residents During the COVID-19 Pandemic
Authors: Kali S. Thomas, Wenhan Zhang, David M. Dosa, Paula Carder, Philip Sloane, Sheryl Zimmerman
Journal: JAMA Network Open (2021)

Future state and federal responses to pandemics targeted to long-term care are advised to explicitly identify the experiences of assisted living settings, recognizing that they differ from nursing homes in terms of overriding model of care (eg, social vs medical model) and staffing (eg, lower staffing levels and less nursing care), among other areas. 3In summary, this research calls for specific attention to assisted living in response to pandemics and other emergencies.
Quantitative SARS-CoV-2 anti-spike responses to Pfizer–BioNTech and Oxford–AstraZeneca vaccines by previous infection status
Authors: David W. Eyre, Sheila F. Lumley, Jia Wei, Stuart Cox, Tim James, Anita Justice, Gerald Jesuthasan, Denise O'Donnell, Alison Howarth, Stephanie B. Hatch, Brian D. Marsden, E. Yvonne Jones, David I. Stuart, Daniel Ebner, Sarah Hoosdally, Derrick W. Crook, Tim E.A. Peto, Timothy M. Walker, Nicole E. Stoesser, Philippa C. Matthews, Koen B. Pouwels, A. Sarah Walker, Katie Jeffery
Journal: Clinical Microbiology and Infection (2021)

ObjectivesWe investigated determinants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) anti-spike IgG responses in healthcare workers (HCWs) following one or two doses of Pfizer–BioNTech or Oxford–AstraZeneca vaccines.MethodsHCWs participating in regular SARS-CoV-2 PCR and antibody testing were invited for serological testing prior to first and second vaccination, and 4 weeks post-vaccination if receiving a 12-week dosing interval. Quantitative post-vaccination anti-spike antibody responses were measured using the Abbott SARS-CoV-2 IgG II Quant assay (detection threshold: ≥50 AU/mL). We used multivariable logistic regression to identify predictors of seropositivity and generalized additive models to track antibody responses over time.Results3570/3610 HCWs (98.9%) were seropositive >14 days post first vaccination and prior to second vaccination: 2706/2720 (99.5%) were seropositive after the Pfizer–BioNTech and 864/890 (97.1%) following the Oxford–AstraZeneca vaccines. Previously infected and younger HCWs were more likely to test seropositive post first vaccination, with no evidence of differences by sex or ethnicity. All 470 HCWs tested >14 days after the second vaccination were seropositive. Quantitative antibody responses were higher after previous infection: median (IQR) >21 days post first Pfizer–BioNTech 14 604 (7644–22 291) AU/mL versus 1028 (564–1985) AU/mL without prior infection (p < 0.001). Oxford–AstraZeneca vaccine recipients had lower readings post first dose than Pfizer–BioNTech recipients, with and without previous infection, 10 095 (5354–17 096) and 435 (203–962) AU/mL respectively (both p < 0.001 versus Pfizer–BioNTech). Antibody responses >21 days post second Pfizer vaccination in those not previously infected, 10 058 (6408–15 582) AU/mL, were similar to those after prior infection followed by one vaccine dose.ConclusionsSARS-CoV-2 vaccination leads to detectable anti-spike antibodies in nearly all adult HCWs. Whether differences in response impact vaccine efficacy needs further study.
Adrenal Rests in the Uro-genital Tract of an Adult Population
Authors: Enrico Costantino Falco, Lorenzo Daniele, Jasna Metovic, Enrico Bollito, Giovanni De Rosa, Marco Volante, Mauro Papotti
Journal: Endocrine Pathology (2021)

Abstract Ectopic adrenal rests are a rare condition which can be found in various sites, generally in the retroperitoneum or pelvis along the path of gonadal descent. Their real prevalence is unknown. Males are more commonly affected, at least in the pediatric age. Adrenal rests are usually clinically silent and incidentally found in surgical samples, mostly in the pediatric population, and rarely in adults. With the aim of increasing knowledge and estimating the prevalence of ectopic adrenocortical tissue in the adult population, 44 adrenal rests in the urogenital tract of 40 adults are described. These represent approximately 0.07% of the total number of urogenital and gynecological surgeries performed in the 22 considered years. Adrenal rests were identified in the spermatic cord (10 males) and in paraovarian, parasalpingeal, or infundibulopelvic ligament locations (30 females). All but one was incidental findings. One case regarded an adrenocortical carcinoma arisen in adrenal rests. A literature review of adrenal ectopia in the urogenital tract of adults identified 57 reported cases from 53 patients, with similar clinicopathological features as those of our series, with the exception of a lower incidence of parasalpingeal locations. Despite their limited clinical implications, awareness of ectopic adrenal rests is essential also in adults for at least two reasons: (a) to correctly identify sources of adrenocortical hormone production in case of adrenal insufficiency or hormonal imbalance and (b) to avoid misinterpretations in the diagnostic workup of renal cell carcinoma, adrenocortical tumors, and rare gonadal neoplasms, including Sertoli/Leydig cell tumors.
Further Observations on Ventricular Tachycardia As Studied by Electrical Stimulation of the Heart
Authors: HEIN J. J. WELLENS, K. I. LIE, DIRK DURRER
Journal: Circulation (1974)

Initiation and termination of tachycardia was studied by electrical stimulation of the heart in 14 patients with ventricular tachycardia (VT) not related to acute myocardial infarction (group A) and in six patients in whom the tachycardia occurred within 24 hours after the onset of acute myocardial infarction (group B). Results favor re-entry as the mechanism of tachycardia in group A patients. In group B abnormal automaticity seems more likely. In one patient with chronic recurrent VT the arrhythmia could be terminated by a single atrial premature beat. In a patient with Wolff-Parkinson-White syndrome and old myocardial infarction, VT could be initiated by a single atrial premature beat. One patient was studied while having VT during acute myocardial infarction and again five weeks later. In the acute phase of myocardial infarction no evidence for re-entry could be obtained; during the second study, however, ventricular tachycardias could be initiated and terminated by a single ventricular premature beat fulfilling the criteria of re-entry.
Erratum for the Research Article: “ <b>Enhanced drug delivery to the reproductive tract using nanomedicine reveals therapeutic options for prevention of preterm birth</b> ” by H. C. Zierden, J. I. Ortiz, K. DeLong, J. Yu, G. Li, P. Dimitrion, S. Bensouda, V. Laney, A. Bailey, N. M. Anders, M. Scardina, M. Mahendroo, S. Mesiano, I. Burd, G. Wagner, J. Hanes, L. M. Ensign
Journal: Science Translational Medicine (2021)
Darolutamide (DARO) tolerability from extended follow up and treatment response in the phase 3 ARAMIS trial.
Authors: Karim Fizazi, Neal D. Shore, Matthew Raymond Smith, Teuvo Tammela, Christopher Michael Pieczonka, Jeanny B. Aragon-Ching, David Morris, Marie-Aude Le Berre, Shankar Srinivasan, Oana Petrenciuc, Christian Zurth, Iris Kuss
Journal: Journal of Clinical Oncology (2021)

5079 Background: Patients (pts) with nonmetastatic castration-resistant prostate cancer (nmCRPC) need therapy that prolongs survival with little added toxicity, thus preserving quality of life. The second-generation androgen receptor inhibitors (ARIs) including DARO, apalutamide, and enzalutamide offer durable survival in nmCRPC but differences exist in AE profiles (eg, fatigue, falls, fractures, rash, mental impairment, and hypertension) that can limit daily activities. These AEs may require dose modifications and limit pts’ willingness to continue treatment, with an adverse impact on efficacy. DARO is a structurally distinct ARI that significantly extended metastasis-free survival and overall survival (OS) vs placebo (PBO) in ARAMIS (NCT02200614), with minimal AE risk. We report tolerability from extended follow-up and treatment response analyses from ARAMIS. Methods: Pts with nmCRPC (N=1509) were randomized 2:1 to DARO or PBO with androgen deprivation therapy. The ARAMIS trial was unblinded at the primary analysis, after which all pts could receive open-label (OL) DARO. Tolerability was assessed every 16 weeks. Pharmacodynamic modeling investigated the association between treatment response (maximum prostate-specific antigen [PSA] decline from baseline) and OS at 2 years using a Cox proportional hazards model. Results: As shown in the table, DARO remained well tolerated over the double-blind (DB) and OL periods: 98.8% of pts on DARO received the full planned dose and almost all pts with dose modifications were able to resume and re-establish the planned dose (DARO 89.6% vs PBO 89.7%). Discontinuation of DARO due to AEs increased slightly from the DB period (9.0%) to the DB+OL period (10.5%). Pharmacodynamic modeling showed that longer OS was positively associated with maximum PSA decline in DARO-treated pts. Conclusions: DARO remained well tolerated with extended treatment at the recommended dose of 600 mg twice daily. Almost all pts with nmCRPC were able to receive the full planned dose, increasing the likelihood of clinical benefit from effective disease control (PSA decline) and prolonged survival. Tolerability of different ARIs in the real world should be assessed. Clinical trial information: NCT02200614. [Table: see text]