tbuckley/cabot-search huggingface dataset:
Lymphovascular invasion as a prognostic indicator in stage I non small cell lung cancer: A systematic review and meta analysis.
Authors: Nathan M Mollberg, Carrie Bennette, Eric Howell, Leah M. Backhus, Mark K. Ferguson
Journal: Journal of Clinical Oncology (2013)

7535 Background: Identification of pathologic features able to predict outcomes in resected stage I non-small cell lung cancer (NSCLC) may help to further stratify patients into risk groups, allowing for further refinement of adjuvant treatment recommendations. We performed a systematic review and meta-analysis to evaluate whether the presence of lymphovacular invasion (LVI) is associated with disease outcome in stage I NSCLC patients. Methods: A systematic search of the literature was performed (1990 to December 2012; Medline/Embase) using search terms related to lymphovascular invasion, lung cancer and prognosis. Studies were considered eligible if they reported the outcome of lung cancer in patients with LVI compared to those without. Pooled Hazard Ratios (HR) were estimated with a random effects model. Two different endpoints were independently analyzed: recurrence-free survival (RFS) and overall survival (OS). We analyzed both unadjusted and adjusted effect estimates, for a total of four separate meta-analyses. Several studies presented multiple results (i.e. adjusted and unadjusted and/or recurrence-free and overall survival) and were therefore included in more than one pooled analysis. Results: Of 2,878 titles identified, 20 articles met the inclusion criteria. Of these, 5 studies were excluded from the analysis due to duplication of results (n=4) and lack of data to calculate HR (n=1). The unadjusted models consisted of 808 (RFS) and 1675 (OS) patients, while the adjusted models consisted of 1,545 (RFS) and 2,601 (OS). The unadjusted pooled effect of LVI was significantly associated with worse both RFS (HR: 4.71, 95% Confidence Interval (CI): 3.08-7.21), and OS (HR: 3.05, 95% CI: 2.34-3.98). Adjusting for potential confounders yielded the same results with both RFS (HR: 2.49, 95% CI: 1.6-3.89), and OS (HR: 1.80, 95% CI: 1.44-2.25) being significantly worse for patients exhibiting LVI in their pathologic specimens. Conclusions: The present study indicates that LVI is an adverse prognostic factor in patients with surgically managed stage I lung cancer. Based on these results, the use of LVI as a stratifying factor in future prospective lung cancer trials seems to be justifiable.
Abstract 12645: Tipiracil Inhibits Platelet Activation and Thrombosis Without Impairing Hemostasis
Authors: Wei Li, Abu Hasanat Md Zulfiker, Hong Yue
Journal: Circulation (2018)

Introduction: The current anti-platelet drugs inhibit platelet function permanently and have systemic side effects including thrombocytopenia and hemorrhage. There is a significant clinical interes...
POOLED FREQUENCY OF STROKE WITHIN 30-DAYS FOLLOWING MECHANICAL CIRCULATORY SUPPORT WITH IMPELLA 5.0®/LD® DEVICE: A SYSTEMATIC REVIEW AND META-ANALYSIS OF STUDIES PUBLISHED IN THE LAST DECADE (2009-2019)
Authors: Rupak Desai, Rushikkumar Bhuva, Upenkumar Patel, Ahmed Mahmood, Muhammad Uzair Lodhi, Hee Kong Fong, Tarang Parekh, Kishorbhai Gangani, Rajesh Sachdeva, Gautam Kumar
Journal: Journal of the American College of Cardiology (2020)
Safety and long-term maintenance of anti-HER2 immunity following booster inoculations of the E75 breast cancer vaccine.
Authors: Raetasha Sheavette Dabney, Diane F Hale, Timothy J Vreeland, Guy T. Clifton, Alan K. Sears, Ritesh Patil, Sathibalan Ponniah, Nathan M. Shumway, George Earl Peoples, Elizabeth Ann Mittendorf
Journal: Journal of Clinical Oncology (2012)

2529 Background: We have completed accrual and are in the follow up portion of phase I/II clinical trials evaluating the E75 HER2 peptide vaccine. E75 has been proven safe, capable of stimulating HER2 immunity, and effective in decreasing breast cancer recurrence rates. During the conduct of this trial, it was noted that E75-specific immunity waned after the Primary Vaccine Series (PVS) which corresponded with late recurrences. To maintain long-term immunity, a voluntary booster program was started. Here we present analysis of the booster inoculations. Methods: The trial enrolled node-positive or high-risk, node-negative breast cancer patients (pts) with tumors expressing any level of HER2 (IHC 1-3+). HLA-A2/A3+ pts comprised the vaccine group (VG), HLA-A2/A3- pts were followed as the control group (CG). The VG received 4-6 monthly inoculations of E75+GM-CSF. Volunteer booster program pts (BG) received inoculations every 6 months after the PVS. Pts were monitored for toxicities, in vivo responses by local reactions (LR) and DTH, and in vitro responses measured by enumeration of E75 specific cytotoxic T lymphocytes. Results: 53 pts received at least 1 booster, 34 received 2, 24 three, 20 four, 12 five, and 8 at least 6. 24% of pts had no local toxicity, 73% Grade 1 (G1), 3% G2. 74% had no systemic toxicity, 35% G1, 1% G2. LRs increased significantly from the initial vaccine (R1) during PVS to each booster (B) (R1: 59.5±3.1 v B1: 89.2±3.3, p&lt;0.001; v B2: 95.15±5, p&lt;0.001; v B3: 86.63±5.5, p&lt;0.001; v B4: 83.26±4.6, p=&lt;0.001; v B5: 80.67±6.7, p=0.006; v B6: 78.75±9.4, p=0.04). Dimer values increased from the end of PVS to each post-booster value (pre B1:1.29±0.25 v post B1: 1.46±0.38; post B2: 1.41±0.4; post B3: 1.84±0.35; post B4: 2.23±0.4; post B5:1.94±0.31; post B6: 2.73±0.09, p=0.02). At median 60 months, the recurrence rate for BG was 3.8% vs 18.9% in the CG (p=0.01). Conclusions: Booster inoculations are well-tolerated and appear to assist in the maintenance of long term peptide-specific immunity. Boosted pts have improved recurrence rates. Based on the success of this program, we have incorporated the practice of booster inoculations in our current cancer vaccine trials.
A SYSTEMATIC REVIEW AND META-ANALYSIS OF PROGNOSTIC IMPACT OF BASELINE ANEMIA ON IN-HOSPITAL OUTCOMES IN PATIENTS WITH ST ELEVATION MYOCARDIAL INFARCTION UNDERGOING PERCUTANEOUS CORONARY INTERVENTION
Authors: Azka Latif, Muhammad Ahsan, Vikas Kapoor, Noman Lateef, Omar Kousa, Mamuna Faizi, Hassan Haji, Venkata Andukuri, Mark Holmberg
Journal: Journal of the American College of Cardiology (2020)
Effect of obatoclax (GX15-070) on cell survival, apoptosis, and prosurvival autophagy in head and neck squamous cell carcinoma (HNSCC).
Authors: Victor Y. Yazbeck, Changyou Li, Daniel E Johnson
Journal: Journal of Clinical Oncology (2013)

e13587 Background: Approximately 500,000 new cases of head and neck cancer are diagnosed annually worldwide, with 300,000 deaths per year. Patients with recurrent and metastatic disease have a dismal prognosis with a median survival of less than one year. Current standard of care involves a platinum-based regimen for patients with good performance status, but is usually difficult to tolerate. Novel therapeutic approaches are in great need for this patient population. The antiapoptotic BCL-2 family proteins, including BCL-2, BCL-XL, and MCL-1 are involved in oncogenesis and chemoresistance and are overexpressed in HNSCC. Obatoclax is a pan-BCL2 inhibitor capable of inhibiting MCL-1, in addition to BCL-2 and BCL-XL. Methods: We determined the activity of obatoclax in 4 well-characterized HNSCC cell lines (UMSCC-1, Cal-33, 1483, UMSCC-22A). Cell viability was determined by MTT assay and apoptosis by Annexin-V binding, FACS analysis, and immunoblotting. Autophagy was assessed by immunofluorescence and immunoblotting. Results: All 4 HNSCC cell lines were highly sensitive to single-agent obatoclax with IC 50 ’s ranging from 50-200 nM. Obatoclax induced apoptosis in all cell lines as evidenced by increased Annexin-V binding at 48 hours in a dose-dependent manner from less than 10% in vehicle treated cells to 30-60% in cells treated with obatoclax. Processing/activation of caspase-3 and cleavage of PARP protein was also observed. In addition, obatoclax induced prosurvival autophagy in all cell lines and the addition of the autophagy inhibitor chloroquine enhanced obatoclax cytotoxicity. In vivo studies of obatoclax using human HNSCC xenograft tumors is currently underway. Conclusions: This preclinical study suggests that obatoclax might have therapeutic value in HNSCC, as a single agent or in combination with an autophagy inhibitor.
A CASE OF FULMINANT CARDIAC SARCOIDOSIS RESEMBLING GIANT CELL MYOCARDITIS
Authors: Ginger Jiang, Qizhe Cai, Edward Grandin, Prashant Rao, Arturo Diaz, Peter J. Zimetbaum, Sachin Shah, Paul VanderLaan, Arthur Garan, Marwa A. Sabe
Journal: Journal of the American College of Cardiology (2020)
Very long term outcome of patients with gastric marginal zone B cell lymphoma of mucosa associated tissue (MALT) following Helicobacter pylori (Hp) eradication therapy
Authors: C. Chini, I. Proserpio, M. E. Giudici, G. Pinotti, B. Pozzi, C. Capella
Journal: Journal of Clinical Oncology (2006)

7531 Background: Hp infection plays a decisive role in the pathogenesis of low-grade gastric MALT lymphoma and eradication therapy has become a widely accepted initial treatment of stage I disease. The aim of this study was to evaluate the long term outcome of patients (pts) with localized gastric MALT lymphoma exclusively treated with Hp eradication therapy. Methods: a prospective series of 62 newly diagnosed IE gastric MALT lymphoma pts (29M/33F) with median age of 63 years (range 27–87), referred to our department from June 1991 to January 2004 were evaluable for the study. Diagnosis was histologically proved and Hp status was evaluated. Staging was performed according to the modified Ann Arbor system. All pts received the triple eradicating therapy (OMC: omeprazole 20 mg bid, metronidazole 400 mg bid and clarithromycin 500 mg bid or OAC: omeprazole 20 mg bid, amoxycillin 1,000 mg bid and clarithromycin 500 mg bid) for one week. Response, evaluated every 6 months with multiple biopsies, was graded according to the Wotherspoon’s histologic scoring system. Results: Hp was eradicated in all patients, but 8 pts required a second line antibiotic therapy; symptoms disappeared or markedly diminished and endoscopic features improved in all pts. Histological remission (score 0–2) was observed in 57 pts (91.9%) after a median time of 6 months (range 2–72); 5 pts (8.1%) who failed to respond were referred to other treatments. With a median follow-up time of 76 months (range 12–162) the histological remission persists in 27/57 pts (47,4%); 21/57 pts (36.8%) have a continuous histological score fluctuation (from 0 to 4); 8/57 (14%) pts had an histological relapse (score 5) after a median time of 12 months (range 6–48) without Hp reinfection and 6 of them had a second spontaneous histological remission. The OS at 76 months is 93%. Only one patient died for an high grade gastric MALT lymphoma transformation. Conclusion: the majority of pts with gastric MALT lymphoma have a favourable long term outcome, independently of the pathological remission; eradication therapy may offer a real chance of cure. Watch and wait policy in agreement pts who failed to respond could be considered an option outside of clinical trial. No significant financial relationships to disclose.
Evaluation of patterns of failure and subjective salivary function in patients treated with intensity modulated radiotherapy for head and neck squamous cell carcinomas
Authors: M. E. Daly, Y. Lieskovsky, T. Pawlicki, J. Yau, H. Pinto, M. Kaplan, A. Koong, D. R. Goffinet, L. Xing, Q. Le
Journal: Journal of Clinical Oncology (2006)

5536 Background: Conventional RT (CRT) for head and neck squamous cell carcinoma (HNSCC) is associated with severe late side effects which can worsen quality of life of surviving patients. Intensity-modulated radiotherapy (IMRT) allows the delivery of tumoricidal doses to the target volume while maintaining tolerable doses to critical organs. Several previous studies have demonstrated promising results for tumor control and disease free survival for HNSCC treated with IMRT. In this study, we correlated patterns of failure with target volume delineations in HNSCC treated with IMRT at our instittuion and evaluated subjective xerostomia outcomes after IMRT as compared to CRT. Material and Methods: Between 1/00 and 4/05, 69 patients with newly diagnosed non-metastatic HNSCC underwent curative parotid sparing IMRT at Stanford University. Sites included were oropharynx (39), oral cavity (8), larynx (8), hypopharynx (8) and unknown primary (6). Forty-six patients received definitive IMRT (66 Gy, 2.2 Gy/fraction), and 23 patients received post-operative IMRT (60.2 Gy, 2.15 Gy/fraction). Fifty-one patients also received concomitant chemotherapy. Post-treatment salivary gland function was evaluated by a validated xerostomia questionnaire (XQ) in 29 IMRT and 75 matched non-IMRT patients &gt; 6 months after completing RT. Results: At a median follow-up of 17 months for living patients (range 6.5–60), 7 locoregional failures were observed, 5 in the gross target volume (GTV), 1 in the clinical target volume (CTV), and 1 at the junction of the IMRT and supraclavicular fields. The 2-year Kaplan Meier estimates of locoregional control and overall survival were 92% and 80% for definitive IMRT and 85% and 85% for post-op IMRT patients, respectively. The mean total XQ score was significantly better for IMRT than for non-IMRT patients (p = 0.006). Conclusions: The predominant pattern of failure in IMRT treated patients is in the GTV. Parotid sparing with IMRT resulted in decreased subjective xerostomia and may improve quality of life in irradiated HNSCC patients. No significant financial relationships to disclose.
THE DYNAMIC NATURE OF APICAL POUCH IN APICAL HYPERTROPHIC CARDIOMYOPATHY: INSIGHTS FROM CONTRAST-ENHANCED EXERCISE ECHOCARDIOGRAPHY
Authors: Mahmoud Ali, Patrycja Galazka, Bijoy Khandheria, A. Jamil Tajik, Renuka Jain
Journal: Journal of the American College of Cardiology (2020)
Potential impact of different methodologies for detecting EGFR mutations in selecting chemotherapy for patients with lung cancer.
Authors: Ryan P. Bender, Anatole Ghazalpour, Zheng Tan, Zoran Gatalica, Les Paul, Sandeep K. Reddy, Michael Castro
Journal: Journal of Clinical Oncology (2013)

e19006 Background: Mutation analysis of the kinase domain of EGFR (exons 18-21) is a standard recommended procedure for patients diagnosed with non-small cell lung cancer (NSCLC). NSCLC patients whose tumor harbors certain EGFR mutations have notable responses to EGFR inhibitors. Several different methodologies are available as published assays or commercially available kits and include Sanger Sequencing, allele specific PCR (ASP) and restriction fragment length polymorphism (RFLP). Differences in the design of these three assays dictate which clinically relevant mutations will be detected. Methods: Sanger Sequencing of EGFR found 518 potentially clinically actionable mutations and 45 variants of unknown significance of the 4307 samples tested. To assess which clinically relevant EGFR mutations will be detected by the ASP and RFLP, we performed an in silico analysis of all observed mutations against the design specification of the ASP and RFLP assays. The RFLP assay used in this assessment was developed in our laboratory and is designed to detect all G719 mutations, all exon 19 deletions, all exon 20 insertions and the specific mutations T790M, L858R, L861R and L861Q. A commercially available ASP kit designed to detect 29 mutations in the kinase domain was also analyzed in this study. Results: Based on the performance characteristics assumed by the RFLP and ASP assays, the analytical sensitivities for detecting clinically actionable mutations of the two methodologies are 98.8% and 86.7% respectively, when compared to Sanger Sequencing. It is notable that the RFLP assay missed the S768I mutation (0% detected) whereas the assay did not detect some G719 mutations, exon 19 deletions, and exon 20 insertions (76.3, 86.6 and 35.3% detected respectively). Conclusions: Sequencing is still the preferred method of mutation detection in EGFR for NSCLC as it is the most comprehensive. However, if tumor nuclei are limited a more sensitive method than sequencing is required; EGFR mutation detection by RFLP would identify more of the potentially clinically relevant mutations than ASP. The ASP method would produce false negative results in 13.3% of patients expected to respond to EGFR inhibitors.
COSTS OF PERIPROCEDURAL COMPLICATIONS IN PATIENTS TREATED ELECTIVELY WITH TRANSFEMORAL TRANSCATHETER AORTIC VALVE REPLACEMENT: A NATIONWIDE ANALYSIS OF REAL-WORLD DATA
Authors: Alexis K. Okoh, Setri Fugar, Supreet Singh, Sameer Hirji, Ahmed Kolkailah, Swaiman Singh, Bruce Haik, Tsuyoshi Kaneko, Leonard Lee, Mark Russo
Journal: Journal of the American College of Cardiology (2020)
FROM ELECTRONIC MEDICAL RECORD INTEGRATION TO REIMBURSEMENT: PRACTICAL IMPLICATIONS OF CHRONIC CARE MANAGEMENT THROUGH A REMOTE PATIENT MONITORING (CPT 99091) CARDIOVASCULAR PROGRAM
Authors: Sanjeev P. Bhavnani, Travis Cohoon, Christine Shen, Rola Khedraki, Stephen Hu
Journal: Journal of the American College of Cardiology (2020)
Does anatomic segmentectomy have better outcomes than wedge resections in stage I NSCLC patients treated by sub-lobar resection?
Authors: Bora Lim, Suhail M. Ali, John M. Varlotto, Kristin Higgins, Malcolm M. DeCamp, Abram Recht, John Charles Flickinger, Michael Reed, Jennifer Toth, Christopher Ryan Kelsey
Journal: Journal of Clinical Oncology (2013)

e18506 Background: As compared to wedge resection (WR), anatomic segmentectomy (AS) may result in a more thorough resection because it allows bronchial and vascular dissection in a manner similar to a lobectomy and greater access for lymphadedectomy. The purpose of our study is to assess if AS allows for lower loco-regional (LR)/distant (DR) recurrences, improved overall survival (OS), and greater ability to resect lymph nodes as compared to WR. Methods: A multi-institutional database of consecutive patients undergoing surgical resection with negative margins for Stage I NSCLC FROM 1998-2009 was used. 2,300 patients had stage I NSCLC(&lt;4cm) underwent surgical resection from which 267 received either AS or WR and were investigated. Variables studied to assess their impact on LR, DR, and OS included age, sex, surgical procedure, hilar node (N1) sampling, histology, LVI, tumor size, tumor grade, and visceral pleural involvement. Cox proportional hazard modeling was used for multivariate analysis. Results: Median follow-up was 188 weeks. The frequency of AS and WR were 3.3% and 12.7%, respectively. We compared LR and DR. There were higher numbers of N1 and N2 removed nodes in patients who underwent AS (p&lt;0.05). There was no significant difference in rates of LR (p=0.58), DR (p=0.4), or OS (p =0.24) between WR and AS in multivariate analysis. Conclusions: Despite more extensive lymphadenectomy, AS is associated with similar rates of LR, DR and OS as WR. [Table: see text]
Socioeconomic differences in health-care use and outcomes for stroke and ischaemic heart disease in China during 2009–16: a prospective cohort study of 0·5 million adults
Authors: Muriel Levy, Yiping Chen, Robert Clarke, Derrick Bennett, Yunlong Tan, Yu Guo, Zheng Bian, Jun Lv, Canqing Yu, Liming Li, Winnie Yip, Zhengming Chen, Borislava Mihaylova
Journal: The Lancet Global Health (2020)

China initiated major health-care reforms in 2009 aiming to provide universal health care for all by 2020. However, little is known about trends in health-care use and health outcomes across different socioeconomic groups in the past decade.We used data from the China Kadoorie Biobank (CKB), a nationwide prospective cohort study of adults aged 30-79 years in 2004-08, in ten regions (five urban, five rural) in China. Individuals who were alive in 2009 were included in the present study. Data for all admissions were obtained by linkage to electronic hospital records from the health insurance system, and to region-specific disease and death registers. Generalised linear models were used to estimate trends in annual hospital admission rates, 28-day case fatality rates, and mean length of stay for stroke, ischaemic heart disease, and any cause in all relevant individuals.512 715 participants were recruited to the CKB between June 25, 2004, and July 15, 2008, 505 995 of whom were still alive on Jan 1, 2009, and contributed to the present study. Among them, we recorded 794 824 hospital admissions (74 313 for stroke, 69 446 for ischaemic heart disease) between 2009 and 2016. After adjustment for demographic, socioeconomic, lifestyle, and morbidity factors, hospitalisation rates increased annually by 3·6% for stroke, 5·4% for ischaemic heart disease, and 4·2% for any cause, between 2009 and 2016. Higher socioeconomic groups had higher hospitalisation rates, but the annual proportional increases were higher in those with lower education or income levels, those enrolled in the urban or rural resident health insurance scheme, and for those in rural areas. Lower socioeconomic groups had higher case fatality rates for stroke and ischaemic heart disease, but greater reductions in case fatality rates than higher socioeconomic groups. By contrast, mean length of stay decreased by around 2% annually for stroke, ischaemic heart disease, and any cause, but decreased to a greater extent in higher than lower socioeconomic groups for stroke and ischaemic heart disease.Between 2009 and 2016, lower socioeconomic groups in China had greater increases in hospital admission rates and greater reductions in case fatality rates for stroke and ischaemic heart disease. Additional strategies are needed to further reduce socioeconomic differences in health-care use and disease outcomes.Wellcome Trust, Medical Research Council, British Heart Foundation, Cancer Research UK, Kadoorie Charitable Foundation, China Ministry of Science and Technology, and Chinese National Natural Science Foundation.
Rethinking Neuropathy in Type 1 Diabetes: Had We Lost Sight of What Matters Most?
Authors: Bruce A. Perkins
Journal: Diabetes Care (2020)

Although animal and human physiological studies have informed potential mechanisms of diabetic neuropathy (1), the real‐world variability in clinical presentation and complexities in measurement have severely hindered a clear understanding of its epidemiology, its impact on the population with type 1 diabetes, and the development of therapies. The most common form—and therefore the one usually referred to simply as “diabetic neuropathy”—is the diffuse, symmetrical, slowly progressive, length‐dependent damage to the peripheral and autonomic nervous system classified technically by the term “diabetic distal symmetrical polyneuropathy” (1). It remains asymptomatic for years, may first present with abnormal sensation symmetrically at the tips of the toes, and may over time spread to the stocking‐and‐glove distribution. It involves injury to different anatomical nerve types that show variable clinical manifestations between individuals. Nerves can be classified as small, thinly myelinated or unmyelinated fibers that make up the autonomic as well as the pain and temperature sensory fibers, while large, myelinated fibers are responsible for other sensory and skeletal muscle functions. Some people have a large fiber–predominant pattern and experience numbness, tingling, or imbalance, while others have small fiber–predominance with burning and stabbing pain, impairment in sensing heat and cold, or a propensity toward clinical autonomic abnormalities like lightheadedness or gastroparesis (1). Some people experience a combination, and regardless of the pattern, people can be asymptomatic for extended periods even though their physical examination or specialized testing reveals marked impairments in nerve structure and function. With progression to foot muscle weakness or clinical autonomic manifestations like dry feet from limited sweat production, the subsequent risk of ulcer, infection, and amputation intensify. Complications like these are feared by people with diabetes more than death itself (2), and of great concern is the recent evidence of a resurgence in amputations (3–5).

To study the outcomes …