tbuckley/cabot-search huggingface dataset:
Phase II study of docetaxel and carboplatin in elderly patients with advanced non-small cell lung cancer: Final results
Authors: N. Yoshimura, S. Kudoh, T. Kimura, S. Mitsuoka, T. Yana, K. Hirata
Journal: Journal of Clinical Oncology (2007)

18161 Background: Single-agent chemotherapy has been considered as standard treatment for elderly patients with non-small cell lung cancer (NSCLC). However recent subset analyses suggest that platinum-based combination chemotherapy may be safely administered to the elderly with good performance status (PS). We evaluated the efficacy and safety of carboplatin and docetaxel in a phase II study of elderly patients aged 70 years or older. Methods: Chemotherapy-naive patients aged =70 years with advanced NSCLC (IIIB-IV), ECOG performance status (PS) of 0–2, a measurable lesion, and adequate organ functions were enrolled. Patients received carboplatin (AUC 5) and docetaxel (60 mg/m 2 ) administered on day 1 every 3 weeks. The primary endpoint was response rate (RR). This study, with a planned sample size of 25, had 80% power to support the hypothesis that the true RR was &gt;30%, and 5% significance to deny the hypothesis that the true RR was &lt;10%. Results: Between October 2003 and April 2006, 30 elderly patients with NSCLC were enrolled in the study and all patients were treated. Demographics: M/F 20/10; PS 0/1/2 2/23/5; median age 75 (range 70–84). Median number of treatment cycles was 3.5. Responses in the 30 evaluable patients included 1CR; 13PR; for an objective RR of 46.7% (95% CI 28.8–64.6%). By January 4, 2007, 21 (70.0%) of 30 patients had died. Median follow-up for survival was 8.4 months. The median time to tumor progression was 4.4 months, and the median survival was 9.9 months. The 1-year survival rate was 43.3%.Grade 3/4 hematologic toxicities included leukopenia (80.0%), neutropenia (86.7%), anemia (16.7%) and thrombocytopenia (3.3%). Non-hematologic toxicities were mild with no grade 4 toxicities; grade 3 nausea (10.0%), anorexia (30.0%), diarrhea (13.3%), fatigue (6.7%), allergic reaction (6.7%), pneumonitis (3.3%), febril neutropenia (16.7%) and infection (10.0%) were observed. Conclusions: The combination of carboplatin and docetaxel was safe and promising for the treatment of chemotherapy-naive elderly patients with advanced NSCLC. This regimen warrants further evaluation in a phase III trial. No significant financial relationships to disclose.
Extranodal (EN) and spleen disease by FDG-PET/CT is associated with early clinical failure in untreated follicular lymphoma (FL).
Authors: Frederique St-Pierre, Stephen M Broski, Betsy LaPlant, Kay Ristow, Matthew John Maurer, William R Macon, Thomas Matthew Habermann, Stephen M. Ansell, Carrie A. Thompson, Ivana N. M. Micallef, Grzegorz S. Nowakowski, Thomas E. Witzig
Journal: Journal of Clinical Oncology (2019)

7554 Background: Predicting early clinical failure in patients with untreated FL is important but difficult. Lymphoma involvement of EN sites is better detected by FDG-PET/CT than CT alone, but PET parameters are not part of the usual predictive indices. We aimed to determine the incidence and patterns of spleen and EN disease using PET/CT, and learn if they are useful in predicting early clinical failure. Methods: PET/CT images from 613 cases of newly diagnosed FL between 2003 – 2016 were retrospectively reviewed. The location, pattern, and number of EN sites, as well as splenic involvement, were recorded. Associations with outcomes were assessed using event-free survival (EFS) and overall survival (OS). Results: 49% (301/613) of patients had PET/CT-detected EN involvement, and 28% (171/613) had spleen involvement. Presence of ≥2 EN sites, spleen, bone, or soft tissue involvement, as well as a multifocal on diffuse pattern of bone involvement by imaging, were univariate predictors of EFS; presence of ≥2 EN sites and bone involvement pattern were also predictive of OS. In a multivariate analysis with FLIPI-2 factors, spleen involvement, pattern of bone involvement, and soft tissue involvement independently predicted a lower EFS (Table). When the multivariate analysis was performed using PRIMA-PI factors, the presence of ≥2 EN sites was an adverse independent prognostic factor for OS (HR 2.28; 95% CI 1.01-5.18; p=0.05). Conclusions: Baseline PET/CT identifies EN and spleen sites of disease that can predict early clinical failure of FL. These results may be useful to better identify high-risk patients and guide appropriate therapy. [Table: see text]
Association of SNP genotype in ABCB1 with completion of intraperitoneal chemotherapy in ovarian and primary peritoneal cancer.
Authors: Sergio Enderica Gonzalez, Saravut John Weroha, Matthew J. Maurer, Ann M. Moyer, Ellen L. Goode, David N. Rider, Rui Qin, Paul Haluska, Brian Addis Costello
Journal: Journal of Clinical Oncology (2012)

5077 Background: A standard of care (SOC) for the adjuvant treatment of ovarian and primary peritoneal cancer is a platinum-based intravenous (IV) chemotherapy doublet. Intraperitoneal (IP) chemotherapy is also a SOC, but the high incidence of grade 3/4 adverse events has limited its acceptance among clinicians. To identify genetic markers for completion of IP chemotherapy, we analyzed SNPs in four genes known to play a role in metabolism of platinum or taxane drugs. Methods: Patients diagnosed with primary or recurrent stage III or IV epithelial ovarian or primary peritoneal cancer who had primary or secondary debulking surgery at Mayo Clinic (Rochester, MN) between January 2007 and February 2009 followed by IP chemotherapy were included in this study. A cycle was defined as IV paclitaxel (135mg/m 2 ) on day one, IP cisplatin (100mg/ m 2 ) on day two, and IP paclitaxel (60mg/ m 2 ) on day eight. With prior consent from the patient, peripheral blood was obtained before treatment for extraction of germline DNA. Using a custom Illumina BeadXpress 96-plex panel, SNPs in GSTM1 (N=7), ABCB1 (N=57), CYP3A4 (N=7), and CYP2C8 (N=25) were genotyped. The association between SNPs in these subsets of genes and completion of IP chemotherapy was analyzed using linear regression. Results: Thirty-seven patients were included in this study and 16 (43.2%) completed IP chemotherapy. Twenty-two out of the fifty-seven ABCB1 SNP’s were associated with the number of cycles (p&lt;0.15). There were no significant associations for GSTM1, CYP3A4 and CYP2C8 SNP’s. The minor A allele at missense SNP rs2229109 in the ABCB1 gene was present in five (31.2%) who completed treatment and only one (4.8%) who did not (p&lt;0.007). However, the later was due to catheter complication. There was no association between rs2229109 and overall or progression-free survival. Conclusions: Our findings suggest that SNP rs2229109 in ABCB1 gene is associated with completion of IP chemotherapy, and potentially, less toxicity from chemotherapy. Thus, these patients may be optimal candidates for IP chemotherapy. Further studies in a larger population are needed.
Effect of concomitant medications on overall survival in patients with cancer undergoing immunotherapy.
Authors: Daniel Spakowicz, Marium Husain, Gabriel Tinoco, Sandip H. Patel, Jarred Thomas Burkart, Claire F. Verschraegen, Kari Lynn Kendra, Sarah Hoffman, Jennifer Philippon, Dionisia Marie Quiroga, Gregory Alan Otterson, Dwight Hall Owen
Journal: Journal of Clinical Oncology (2019)

94 Background: The response to Immunotherapy (IO) is known to be affected by concomitant medications including corticosteroids and antibiotics. We evaluated the medication history of patients undergoing IO to explore other medications that affect overall survival and to estimate the relative impact of each medication when given in combination. Methods: A retrospective review of patients with advanced cancer who received IO from 2011 to 2017 at the Ohio State University was performed with IRB approval. Data were extracted from the medical record, including medication history 180 days around the start of IO therapy. Data were collected in a REDCap database. Overall Survival (OS) was calculated from the initiation of IO. Cox Proportional-Hazards models were used and evaluated by log-rank test at alpha = 0.05. All calculations were performed using the survival and survminer packages in R. Results: Patients who received antibiotics or corticosteroids had decreased OS (p = 0.019 and p = 0.043, respectively) across several cancer types. Medications that were not significantly associated with OS included statins (p = 0.38), proton pump inhibitors (p = 0.94), H2 blockers (p = 0.27) and NSAIDS (p = 0.46). A total of 159 patients had complete data for all medications suitable for modeling relative effects. 149 (94%) of patients received antibiotics within 180 days of IO and 19 (12%) received both corticosteroids and antibiotics. The combination of corticosteroids and antibiotics had lower median OS than antibiotics alone or neither medication (p &lt; 0.0018). A Cox Proportional Hazards model of antibiotics and corticosteroids, controlling for age, BMI and ECOG performance status, showed antibiotics, age and BMI to be significant predictors. Conclusions: Antibiotics and corticosteroids near the start of IO reduced overall survival, and the combination reduced the median overall survival further. However, a combined model that controlled for age, BMI and ECOG showed antibiotics, age and BMI to have a significant effect on OS. Though preliminary, these results suggest that antibiotics and corticosteroids may be affecting OS in the context of IO through overlapping pathways.
Planning for survivorship after checkpoint inhibitors: A multidisicplinary education initiative.
Authors: Tara Perloff, Monique Dawkins, Mary Hurd, Jennifer Wang, Sigrun Hallmeyer
Journal: Journal of Clinical Oncology (2019)

98 Background: Survivorship care plans are a key piece of coordinated, patient-centered care delivery. As with other cancer treatment modalities, patients with metastatic disease who achieve durable benefit with immunotherapy (IO) treatment may experience late physical and psychosocial effects which can negatively impact quality of life. An online education program was created to educate the multidisciplinary cancer care team on the nuances related to survivorship for patients who are treated with checkpoint inhibitors. Methods: A medical oncologist, oncology nurse, oncology social worker and patient developed a curriculum to identify challenges and solutions for survivorship care planning, prepare care teams for nuances related to survivorship for IO patients, and optimize coordination and communication between the care team and the patient. In June 2018, a live-online 1-hour webcast that included a panel discussion with presentation slides, participant polling, and live ‘ask the panel’ questions was produced and made available on-demand. Results: A total of 149 learners viewed the webcast; 86 of these learners participated in the live webinar and 63 watched on-demand. To date, an estimated 590 patients per month are impacted by this education. Learners were actively engaged for an average of 35 minutes (out of 52 minutes). Most learners indicated specializing in oncology (49%), were practicing physicians (39%), and saw 1-10 new patients on an IO therapy each week (59%) in a hospital-based setting (42%). Due to the education provided, learners reported improvements in their ability to identify challenges and solutions for IO survivorship care planning (97%) and handle nuances related to survivorship for patients on cancer immunotherapies (88%). Learners also demonstrated improved comprehension via case study by identifying the most common, concerning side-effect for a high-risk melanoma patient treated with ipilimumab and nivolumab. Conclusions: Continued refinement of care coordination practices related to survivorship is recommended to improve the long-term management of patients who are treated with checkpoint inhibitors.
Associations of Blood Pressure and Cholesterol Levels During Young Adulthood With Later Cardiovascular Events
Authors: Yiyi Zhang, Eric Vittinghoff, Mark J. Pletcher, Norrina B. Allen, Adina Zeki Al Hazzouri, Kristine Yaffe, Pallavi P. Balte, Alvaro Alonso, Anne B. Newman, Diane G. Ives, Jamal S. Rana, Donald Lloyd-Jones, Ramachandran S. Vasan, Kirsten Bibbins-Domingo, Holly C. Gooding, Sarah D. de Ferranti, Elizabeth C. Oelsner, Andrew E. Moran
Journal: Journal of the American College of Cardiology (2019)

Blood pressure (BP) and cholesterol are major modifiable risk factors for cardiovascular disease (CVD), but effects of exposures during young adulthood on later life CVD risk have not been well quantified. The authors sought to evaluate the independent associations between young adult exposures to risk factors and later life CVD risk, accounting for later life exposures. The authors pooled data from 6 U.S. cohorts with observations spanning the life course from young adulthood to later life, and imputed risk factor trajectories for low-density lipoprotein (LDL) and high-density lipoprotein cholesterols, systolic and diastolic BP starting from age 18 years for every participant. Time-weighted average exposures to each risk factor during young (age 18 to 39 years) and later adulthood (age ≥40 years) were calculated and linked to subsequent risks of coronary heart disease (CHD), heart failure (HF), or stroke. A total of 36,030 participants were included. During a median follow-up of 17 years, there were 4,570 CHD, 5,119 HF, and 2,862 stroke events. When young and later adult risk factors were considered jointly in the model, young adult LDL ≥100 mg/dl (compared with <100 mg/dl) was associated with a 64% increased risk for CHD, independent of later adult exposures. Similarly, young adult SBP ≥130 mm Hg (compared with <120 mm Hg) was associated with a 37% increased risk for HF, and young adult DBP ≥80 mm Hg (compared with <80 mm Hg) was associated with a 21% increased risk. Cumulative young adult exposures to elevated systolic BP, diastolic BP and LDL were associated with increased CVD risks in later life, independent of later adult exposures.
Dientamoeba fragilis – the most common intestinal protozoan in the Helsinki Metropolitan Area, Finland, 2007 to 2017
Authors: Jukka-Pekka Pietilä, Taru Meri, Heli Siikamäki, Elisabet Tyyni, Anne-Marie Kerttula, Laura Pakarinen, T Sakari Jokiranta, Anu Kantele
Journal: Eurosurveillance (2019)

Background Despite the global distribution of the intestinal protozoan Dientamoeba fragilis, its clinical picture remains unclear. This results from underdiagnosis: microscopic screening methods either lack sensitivity (wet preparation) or fail to reveal Dientamoeba (formalin-fixed sample). Aim In a retrospective study setting, we characterised the clinical picture of dientamoebiasis and compared it with giardiasis. In addition, we evaluated an improved approach to formalin-fixed samples for suitability in Dientamoeba diagnostics. Methods This study comprised four parts: (i) a descriptive part scrutinising rates of Dientamoeba findings; (ii) a methodological part analysing an approach to detect Dientamoeba -like structures in formalin samples; (iii) a clinical part comparing demographics and symptoms between patients with dientamoebiasis (n = 352) and giardiasis (n = 272), and (iv) a therapeutic part (n = 89 patients) investigating correlation between faecal eradication and clinical improvement. Results The rate of Dientamoeba findings increased 20-fold after introducing criteria for Dientamoeba -like structures in formalin-fixed samples (88.9% sensitivity and 83.3% specificity). A further increase was seen after implementing faecal PCR. Compared with patients with giardiasis, the symptoms in the Dientamoeba group lasted longer and more often included abdominal pain, cramping, faecal urgency and loose rather than watery stools. Resolved symptoms correlated with successful faecal eradication (p &lt; 0.001). Conclusions Previously underdiagnosed, Dientamoeba has become the most frequently recorded pathogenic enteroparasite in Finland. This presumably results from improved diagnostics with either PCR or detection of Dientamoeba -like structures in formalin-fixed samples, an approach applicable also in resource-poor settings. Symptoms of dientamoebiasis differ slightly from those of giardiasis; patients with distressing symptoms require treatment.
Emerging trends in immunotherapy for pediatric sarcomas
Authors: Kyle A. Dyson, Brian D. Stover, Adam Grippin, Hector R. Mendez-Gomez, Joanne Lagmay, Duane A. Mitchell, Elias J. Sayour
Journal: Journal of Hematology & Oncology (2019)

While promising, immunotherapy has yet to be fully unlocked for the preponderance of cancers where conventional chemoradiation reigns. This remains particularly evident in pediatric sarcomas where standard of care has not appreciably changed in decades. Importantly, pediatric bone sarcomas, like osteosarcoma and Ewing’s sarcoma, possess unique tumor microenvironments driven by distinct molecular features, as do rhabdomyosarcomas and soft tissue sarcomas. A better understanding of each malignancy’s biology, heterogeneity, and tumor microenvironment may lend new insights toward immunotherapeutic targets in novel platform technologies for cancer vaccines and adoptive cellular therapy. These advances may pave the way toward new treatments requisite for pediatric sarcomas and patients in need of new therapies.
Epithelial sodium channels in endothelial cells mediate diet-induced endothelium stiffness and impaired vascular relaxation in obese female mice
Authors: James R. Sowers, Javad Habibi, Annayya R. Aroor, Yan Yang, Guido Lastra, Michael A. Hill, Adam Whaley-Connell, Frederic Jaisser, Guanghong Jia
Journal: Metabolism (2019)
Relationship Between HbA[subscript 1c] Level and Peripheral Arterial Disease
Authors: Paul Muntner, Rachel P. Wildman, Kristi Reynolds, Karen B. DeSalvo, Jing Chen, Vivian Fonseca
Journal: Diabetes Care (2005)

OBJECTIVE:--Homeostatic glucose control may play an important role in the development of peripheral arterial disease among individuals without diabetes. We sought to evaluate the association of HbA[subscript 1c] (A1C) with peripheral arterial disease in a representative sample of the U.S. population with and without diabetes. RESEARCH DESIGN AND METHODS--A cross-sectional study was conducted among 4,526 National Health and Nutrition Examination Survey 1999-2002 participants [>/=]40 years of age. Peripheral arterial disease was defined as an ankle-brachial index  /=]7%, respectively. After multivariable adjustment and compared with nondiabetic participants with A1C  /=]7%, respectively. CONCLUSIONS:--An association exists between higher levels of A1C and peripheral arterial disease, even among patients without diabetes. Individuals with A1C levels [>/=]5.3% should be targeted for aggressive risk factor reduction, which may reduce the burden of subclinical cardiovascular disease even among those without diabetes.
Cuts force unpaid carers to use own savings to fund relatives’ care
Authors: Gareth Iacobucci
Journal: BMJ (2019)

Unpaid carers are being forced to use their own income or savings to cover the cost of caring for friends or relatives as well as providing significant levels of care themselves, a report by a UK charity has found.1

Carers UK, which represents unpaid carers in the four UK nations, said that chronic underfunding of the social care system was forcing many carers to buy equipment or products for the person they were caring for, leaving many struggling financially and unable to save for their own retirement.

For its State of Caring 2019 report the …
Abstract 17172: Variability of Index of Microcirculatory Resistance in Patients with Intermediate Coronary Artery Lesions
Authors: Tadashi Murai, Tetsumin Lee, Toshiyuki Iwai, Takamitsu Takagi, Ryo Masuda, Tsunekazu Kakuta
Journal: Circulation (2012)

Background: Although atherosclerosis affects both epicardial coronary arteries and microvasculatures, the relationship between functional significance of epicardial coronary artery stenosis and mic...
Hormone Therapy for Cancer Is a Risk Factor for Relapse of Inflammatory Bowel Diseases
Authors: Jordan E. Axelrad, Ahmad Bazarbashi, James Zhou, Daniel Castañeda, Amandeep Gujral, Dylan Sperling, Jason Glass, Manasi Agrawal, Simon Hong, Garrett Lawlor, David Hudesman, Shannon Chang, Shailja Shah, Vijay Yajnik, Ashwin Ananthakrishnan, Hamed Khalili, Jean-Frederic Colombel, Steven Itzkowitz
Journal: Clinical Gastroenterology and Hepatology (2019)
Emotional and cognitive disturbances in long-term melanoma survivors treated with ipilimumab.
Authors: Anne Rogiers, Gil Awada, Julia Schwarze, Jennifer De Cremer, Laila Ben Salama, Peter Theuns, Bart Neyns
Journal: Journal of Clinical Oncology (2019)

97 Background: Immunotherapy with the CTLA-4 blocking mAb ipilimumab (IPI) has improved the long-term (&gt;3 y) survival of a subpopulation (15-20%) of patients (pts) with metastatic melanoma. Little is known about the psychosocial outcome and the long-term effects of immune-related adverse events in these survivors. Methods: Pts with advanced melanoma (AJCC stages IIIC or IV) who were in complete remission for at least 2 y after treatment initiation, were eligible for this ongoing study. Data on health related quality of life (HRQOL), psychosocial outcome and neurocognitive function (NCF) were collected using 5 validated questionnaires, a semi-structured psychiatric examination (SSPE), and computer-based NCF testing. Results: Test results from 17 pts (5 F/12 M), median age 57 y (range 33-86) were analyzed. Median time since start of IPI was 5.5 y (range 2-7). Seven pts (41%) had elevated scores on the Cognitive Failure Questionnaire (CFQ). Nine pts (53%) had elevated scores on the Hospitalization Depression Scale (HADS) indicating moderate anxiety (4 pts), severe anxiety (2 pts), and moderate depression (3 pts). The SSPE revealed that all 10 pts who were professionally active at the time of diagnosis, had to change or stop work due to their illness. Nine pts (53%) reported persisting emotional distress: anxiety, existential problems, survivor guilt, post-traumatic stress symptoms or daily worrying about the disease. Three pts were referred for suicidal ideation in relation with their disease. Four pts (24%) developed hypophysitis and suffered from comorbid depression (1 pt), adjustment disorder (2 pt), or post-traumatic stress disorder related to the symptoms of hypopituitarism (1 pt). Five years after the incidence of hypophysitis, all pts had elevated scores on the Fatigue Severity Scale, the HADS; and 3 pts on the CFQ. All cases of skin toxicity (8 pts), hepatitis (2 pts), colitis (2 pts), sarcoidosis (2 pts), and Guillain-Barre syndrome (1 pt) resolved without long-term impact on HRQOL. Conclusions: A majority of melanoma survivors treated with IPI continues to suffer from emotional distress and cognitive problems impacting their HRQOL. Timely detection and providing adaptive care is imperative.
Antithrombotic Treatment in Transcatheter Aortic Valve Implantation
Authors: Josep Rodés-Cabau, Harold L. Dauerman, Mauricio G. Cohen, Roxana Mehran, Eric M. Small, Susan S. Smyth, Marco A. Costa, Jessica L. Mega, Michelle L. O'Donoghue, E. Magnus Ohman, Richard C. Becker
Journal: Journal of the American College of Cardiology (2013)