tbuckley/cabot-search huggingface dataset:
TRANSCAVAL IMPELLA-PROTECTED LEFT MAIN PCI WITH ROTATIONAL ATHERECTOMY FOLLOWED BY TAVR AND RENAL ARTERY STENTING IN AN ELDERLY FEMALE WITH CARDIOGENIC SHOCK AND RENAL FAILURE DUE TO SEVERE AORTIC STENOSIS AND REGURGITATION
Authors: Pavan Isanaka, Matthew Cauchi, Jason Foerst, Sulaiman Rathore, Joseph Rowe
Journal: Journal of the American College of Cardiology (2020)
Phase I study of an anti-angiogenic agent with a novel mechanism of action E7820: Safety, pharmacokinetics (PK) and pharmacodynamic (PD) studies in patients (pts) with solid tumors
Authors: M. M. Mita, A. C. Mita, A. Ricart, J. Rodon, E. Till, C. Okereke, P. Desai, E. Zang, E. K. Rowinsky, C. Takimoto
Journal: Journal of Clinical Oncology (2006)

3048 Background: E7820 is a first-in-class oral antiangiogenic sulfonamide that inhibits alpha-2 integrin expression, endothelial cell proliferation and is active against human breast and pancreatic cancer xenografts. Methods: The objectives of the study were to evaluate the safety, tolerability, to determine the maximum tolerated dose (MTD) to characterize the PK behavior, to assess PD markers and to explore the antitumor activity. Results: Thirty pts (18 male/12 female; age range 40–83) received E7820 at doses ranging from 10 to 200 mg daily continuously, in a 28 day cycle. A total of 93 cycles were administered (range 1–15); 4 pts underwent intrapatient dose escalation. Dose-limiting toxicities (DLT) at 100 mg/day included grade (gr) 3 elevated liver enzymes and gr 3 hemoptysis. At the 200 mg dose level, 2 pts experienced hematological toxicity, including gr 4 thrombocytopenia and neutropenia. One of these patients with cervical cancer and a vaginal fistula had gr 4 thrombocytopenia, neutropenia and gr 3 anemia with a fatal bleed from her pelvic tumor. Other gr 3/4 adverse events included: nausea, vomiting, fatigue, hypoxia, chest pain, abdominal pain, ileus, anemia, neutropenia, hypoalbuminemia, elevated transaminases and alkaline phosphatases. Disease stabilization beyond cycle 4 was observed in 6 pts, with 3 lasting for 6+ months. T max ranged from 1.3–5.3 hr and the t 1/2 is 5.7 to 11.9 hr. C max and AUC increased dose proportionaly up to 70 mg, however accumulation was seen at 200 mg. At higher doses (70–200 mg) plasma concentrations exceed levels active in preclinical models in vivo. Preliminary analysis of alpha-2 integrin expression showed marked (∼50%) and sustained decreases beyond day 28 in 3 of 4 pts at 200 mg, while moderate (&lt;30%) and less consistent decreases were observed in 2/3 and 3/6 pts at 70 mg and 100 mg dose levels, respectively. No changes in integrin levels were observed at E7820 doses &lt; 40 mg. Conclusions: Up to 100 mg/day E7820 has a good safety profile in pts with solid malignancies. MTD was established at 100 mg/day. Patient treatment and PD analyses are ongoing. [Table: see text]
PLACENTAL VASCULAR LESIONS AND MATERNAL CORONARY MICROVASCULAR FUNCTION BY MYOCARDIAL CONTRAST ECHOCARDIOGRAPHY 8-10 YEARS AFTER DELIVERY
Authors: Malamo Countouris, Nikki de Jong, Judith Brands, Xucai Chen, Kathryn L. Berlacher, Janet Catov, Flordeliza S. Villanueva
Journal: Journal of the American College of Cardiology (2020)
Combined Effect of PNPLA3, TM6SF2, and HSD17B13 Variants on Risk of Cirrhosis and Hepatocellular Carcinoma in the General Population
Authors: Helene Gellert‐Kristensen, Tom G. Richardson, George Davey Smith, Børge G. Nordestgaard, Anne Tybjærg‐Hansen, Stefan Stender
Journal: Hepatology (2020)

We hypothesized that a genetic risk score (GRS) for fatty liver disease influences the risk of cirrhosis and hepatocellular carcinoma (HCC). Three genetic variants (patatin-like phospholipase domain-containing protein 3 [PNPLA3] p.I148M; transmembrane 6, superfamily member 2 [TM6SF2] p.E167K; and hydroxysteroid 17-beta dehydrogenase 13 [HSD17B13] rs72613567) were combined into a risk score, ranging from 0 to 6 for risk-increasing alleles.We examined the association of the risk score with plasma markers of liver disease and with cirrhosis and HCC in 110,761 individuals from Copenhagen, Denmark, and 334,691 individuals from the UK Biobank. The frequencies of risk scores of 0, 1, 2, 3, 4, and 5 or 6 were 5%, 25%, 41%, 23%, 5.5%, and 0.5%, respectively. A higher GRS was associated with an increase in plasma alanine aminotransferase (ALT) level of 26% in those with score 5 or 6 versus 0. In meta-analysis of the Copenhagen studies and the UK Biobank, individuals with scores 1, 2, 3, 4, and 5 or 6 had odds ratios (ORs) for cirrhosis of 1.6 (95% confidence interval [CI], 1.3, 1.9), 2.0 (95% CI, 1.8, 2.2), 3.1 (95% CI, 2.7, 3.5), 5.2 (95% CI, 4.2, 6.4), and 12 (95% CI, 7.7, 19), respectively, as compared with those with a score of 0. The corresponding ORs for HCC were 1.2 (95% CI, 0.9, 1.7), 1.0 (95% CI, 0.7, 1.3), 2.4 (95% CI, 1.9, 3.0), 3.3 (95% CI, 2.2, 5.0), and 29 (95% CI, 17, 51).A GRS for fatty liver disease confers up to a 12-fold higher risk of cirrhosis and up to a 29-fold higher risk of HCC in individuals from the general population.
IMPACT OF EARLY DIURETIC ADMINISTRATION ON IN-HOSPITAL MORTALITY AND LENGTH OF HOSPITAL STAY AMONG PATIENTS WITH ACUTE CONGESTIVE HEART FAILURE: A META-ANALYSIS
Authors: Adnan Ahmed, Dhiran Verghese, Faisal Ali, Manojna Nimmagadda, Rohan Bodapati, Arshad Muhammad Iqbal
Journal: Journal of the American College of Cardiology (2020)
Association between physical activity and risk of hospitalisation in bronchiectasis
Authors: Victoria Alcaraz-Serrano, Elena Gimeno-Santos, Giulia Scioscia, Albert Gabarrús, Adria Navarro, Beatriz Herrero-Cortina, Rosanel Amaro, Laia Fernández-Barat, Antoni Torres
Journal: European Respiratory Journal (2020)

Background Patients with bronchiectasis have a less active lifestyle than healthy peers, but the association with hospital admission has not been explored. The aim of this study was to investigate the association between 1) any physical activity variable; and 2) sedentary time, with hospitalisation due to exacerbation in adults with bronchiectasis. Methods In this prospective observational study, baseline lung function, quality of life, exercise tolerance, severity of bronchiectasis and physical activity were recorded. Physical activity was objectively assessed over a week using a SenseWear armband and the results were expressed in steps·day –1 and sedentary time. Number of hospitalisations due to a bronchiectasis exacerbation and time to first event were recorded after 1-year follow-up. Results Sixty-four patients with bronchiectasis were analysed, of whom 15 (23%) were hospitalised during the follow-up. Hospitalised patients showed poor baseline clinical and severity outcomes, fewer steps walked per day and more sedentary behaviour than the non-hospitalised group. Patients who walked ≤6290 steps·day –1 or spent ≥7.8 h·day –1 in sedentary behaviour had an increased risk of hospital admission due to bronchiectasis exacerbation at 1-year follow-up. Specifically, ≥7.8 h·day –1 of sedentary behaviour was associated with a 5.9-fold higher risk of hospital admission in the following year. Conclusions Low levels of physical activity and high sedentary time at baseline were associated with a higher risk of hospitalisation due to bronchiectasis exacerbation. If these findings are validated in future studies, it might be appropriate to include physical activity and sedentary behaviour as an item in severity scores.
Surgical oncology outcomes: The role of nurse practice environments
Authors: C. R. Friese, L. H. Aiken
Journal: Journal of Clinical Oncology (2006)

6105 Background: Increased attention has focused on the role of hospital characteristics on cancer patient outcomes. We examined two cancer-specific credentials, as well registered nurse practice environments, on outcomes of care. Methods: Through secondary analysis of existing data from hospital claims, the tumor registry, and a statewide of survey of nurses (RNs), we studied 30-day mortality (D) and failure to rescue (death given a complication) (FTR) for surgical oncology patients treated in 164 Pennsylvania hospitals from 1998–1999 (N=24,618). We compared D and FTR rates by a hospital’s NCI cancer center designation, American College of Surgeon’s (ACoS) cancer program approval and categorized scores on the Practice Environment Scale of the Nursing Work Index (PES-NWI). The PES-NWI scales measure RN participation in hospital affairs, RN foundations for quality of care, nurse manager leadership/support, staffing/resource adequacy, and RN-physician relations. Multivariate logistic regression models examined predictors of D and FTR, controlling for 25 patient variables. Standard errors were corrected for patient clustering in hospitals. Results: NCI centers had lower D and FTR rates (p &lt; .01). ACoS hospitals had lower D and FTR rates (ns). Hospitals with low scores on PES-NWI scales had the poorest outcomes (p &lt; .01). In logistic regression models, significant predictors included unfavorable PES-NWI Scores for D (OR=1.32, 95% CI: 1.06–1.65) and FTR (OR=1.39, 95% CI:1.03–1.88), and NCI centers for D (OR=0.64, 95% CI: 0.50–0.83) and FTR (OR=0.67, 95% CI: 0.47–0.96). The NCI effect lost significance when environment was included. ACoS program effects were small (OR= 0.99, p = .90) for both outcomes. Conclusions: Favorable outcomes in NCI centers may be partly explained by practice environments. The practice environment of RNs significantly predicts surgical oncology patient outcomes, and should be a focus of quality improvement activities. No significant financial relationships to disclose.
Reversal of TGFβ1-Driven Profibrotic State in Patients with Pulmonary Fibrosis
Authors: Harold A Chapman, Ying Wei, Genevieve Montas, Darren Leong, Jeffrey A Golden, Binh N Trinh, Paul J Wolters, Claude J Le Saux, Kirk D Jones, Nancy K Hills, Elena Foster, Justin M Oldham, Angela L Linderholm, Prerna Kotak, Martin Decaris, Scott Turner, Jin-Woo Song
Journal: New England Journal of Medicine (2020)

EGCG and Pulmonary Fibrosis Nine patients who were scheduled to undergo lung biopsy for pulmonary fibrosis were given epigallocatechin gallate (EGCG) for 2 weeks. Levels of fibrotic markers in lung...
22P Safety profile and therapeutic efficacy of CYP11A1 inhibitor ODM-208 in cellular models and intact male dogs
Authors: M. Karimaa, R. Riikonen, M. Ramela, H-M. Metsänkylä, S. Mansikka-Savolainen, P. Rummakko, R. Oksala
Journal: Annals of Oncology (2020)
Differential frequency of breast cancer molecular profiling by socioeconomic status in San Diego, California.
Authors: Gregory Sumpao Vosganian, Joshua Daniel Rosenberg, Radha Verman, Jill Waalen, James R. Mason
Journal: Journal of Clinical Oncology (2012)

e21061 Background: Previous reports demonstrate inferior outcomes for cancer patients of low socioeconomic status (SES). The development of breast tumor molecular profiling has optimized anticancer therapy but its effect on outcome for those with barriers to care is unknown. Methods: Breast cancer patients appropriate for OncotypeDX testing (Genomic Health, Inc) were identified from The Scripps Health Tumor Registry. High SES was defined as patients residing in zip codes with a median household income in the top quartile for the county according to the San Diego Association of Governments. Low SES was defined as patients residing in zip codes with median income in the bottom quartile or with Medical as primary insurance. The frequency of OncotypeDX testing, result, therapy prescribed, relapse and cancer specific death rates are reported. Statistical analysis was performed by unpaired t-test; p values≤0.05 were considered significant. Results: 2,192 early-stage breast cancer patients were identified; 167 met criteria. Patients were younger (p&lt;0.0001) and a lower rate of OncotypeDX testing was noted in the low SES group (p=0.028); no difference in stage was observed. All patients were prescribed anti hormone therapy but the low SES group received chemotherapy more frequently (p=0.0075). No difference in relapse rate and no deaths attributable to cancer were noted. Conclusions: We observed a lower rate of OncotypeDX use in the low SES cohort. While the cause is unclear, the higher rate of chemotherapy use in this group may represent overtreatment. Determining a survival impact attributable to this difference requires longer follow-up. Our data demonstrate the need for prospective analysis of tumor profiling use in low SES individuals to ensure early stage breast cancer patients receive optimal therapy. [Table: see text]
Stromal Cells Covering Omental Fat-Associated Lymphoid Clusters Trigger Formation of Neutrophil Aggregates to Capture Peritoneal Contaminants
Authors: Lucy Helen Jackson-Jones, Peter Smith, Jordan Raymond Portman, Marlène Sophie Magalhaes, Katie Jude Mylonas, Matthieu Marie Vermeren, Mark Nixon, Beth Emily Pollot Henderson, Ross Dobie, Sonja Vermeren, Laura Denby, Neil Cowan Henderson, Damian James Mole, Cécile Bénézech
Journal: Immunity (2020)

The omentum is a visceral adipose tissue rich in fat-associated lymphoid clusters (FALCs) that collects peritoneal contaminants and provides a first layer of immunological defense within the abdomen. Here, we investigated the mechanisms that mediate the capture of peritoneal contaminants during peritonitis. Single-cell RNA sequencing and spatial analysis of omental stromal cells revealed that the surface of FALCs were covered by CXCL1+ mesothelial cells, which we termed FALC cover cells. Blockade of CXCL1 inhibited the recruitment and aggregation of neutrophils at FALCs during zymosan-induced peritonitis. Inhibition of protein arginine deiminase 4, an enzyme important for the release of neutrophil extracellular traps, abolished neutrophil aggregation and the capture of peritoneal contaminants by omental FALCs. Analysis of omental samples from patients with acute appendicitis confirmed neutrophil recruitment and bacterial capture at FALCs. Thus, specialized omental mesothelial cells coordinate the recruitment and aggregation of neutrophils to capture peritoneal contaminants.
NEO-SINUS FLOW STASIS CORRELATES WITH LEAFLET THROMBOSIS ACROSS MULTIPLE TRANSCATHETER AORTIC VALVES
Authors: Vahid Sadri, Phillip Trusty, Sanchita S. Bhat, Md Tausif Salim, Norihiko Kamioka, Rahul Sharma, Raj R. Makkar, Ajit Yoganathan
Journal: Journal of the American College of Cardiology (2020)
Analysis of fracture risk factors from the ’Arimidex’, Tamoxifen, Alone or in Combination (ATAC) trial: 5-year data
Authors: A. Howell
Journal: Journal of Clinical Oncology (2006)

563 Background: The Completed Treatment Analysis of the ATAC trial at 68 months’ median follow-up confirmed that initial adjuvant treatment with anastrozole has significant efficacy and tolerability advantages compared with tamoxifen (ATAC Trialists’ Group. Lancet 2005; 365: 60–2). In the ATAC trial, the rate of all fracture types for anastrozole was higher than with tamoxifen. To better understand the impact of fracture risk factors on actual fracture rates, we undertook an analysis of the risk factors for all reported fractures in the ATAC trial up to 5 years. Methods: The analysis followed a time-to-event approach, using the Cox model with forward selection of prognostic covariates, together with the likelihood ratio test at the 5% significance level. Considered risk factors were age, body mass index (by tertile), previous hormone replacement therapy, concomitant medications (vitamin D, calcium, thiazides, statins, corticosteroids, thyroid hormones, bisphosphonates, antiepileptics, anxiolytics), geographical region (very high, high, or moderate and low hip fracture risk areas) (Kanis et al. J Bone Miner Res 2002; 17: 1237–44), smoking, and trial therapy (anastrozole or tamoxifen). Hazard ratios and associated 95% confidence intervals were obtained from the final model, which contained all statistically significant factors. Results: Of 6186 women, 524 (8.5%) had a fracture. Statistically significant predictors of fracture were age, region, and trial therapy ( Table ). A significant decrease in fracture risk was also observed in statin users although this decrease may not have been due to statin use, but rather to related factors. Conclusions: It is essential that individuals at high risk of fracture be identified so that they can receive appropriate evaluation and treatment. Profiling of risk as described here could enable the development of risk scores that would allow the identification and close observation of patients at high risk of fracture prior to commencing adjuvant therapy. [Table: see text] [Table: see text]
Adding Alirocumab to Rosuvastatin Helps Reduce the Vulnerability of Thin-Cap Fibroatheroma
Authors: Yoichiro Sugizaki, Hiromasa Otake, Hiroyuki Kawamori, Takayoshi Toba, Yuichiro Nagano, Yoshiro Tsukiyama, Ken-ichi Yanaka, Hiroyuki Yamamoto, Akira Nagasawa, Hiroyuki Onishi, Ryo Takeshige, Shinsuke Nakano, Yoichiro Matsuoka, Kosuke Tanimura, Yu Takahashi, Yusuke Fukuyama, Toshiro Shinke, Tatsuro Ishida, Ken-ichi Hirata
Journal: JACC. Cardiovascular imaging (2020)
Allogeneic stem cell transplantation improves cerebro-vascular disease in two sickle cell anemia patients
Authors: L. Kraut, A. Al-Momen, W. Nürnberger, L. Boguth, E. Erken, A. A. Fauser
Journal: Journal of Clinical Oncology (2006)

16524 Background: Sickle cell anemia (SCA) patients are at high risk for vaso-occlusion with cerebral vascular complications like strokes being one of the most devastating clinical events. Prophylactic transfusions might prevent strokes resp. improve cerebro-vascular status in SCA patients. Allogeneic stem cell transplantation (SCT) is considered a therapeutic option with curative intention of SCA, and thus also to improve cerebro-vascular complications by preventing further strokes, as demonstrated by two cases in our center. Methods: Transcranial Doppler sonography (TCD) and cerebral magnetic resonance angiography (MRA) were used to assess cerebro-vascular disease status prior, during and post related SCT of 2 SCA patients. Results: Two sibling SCA patients (male resp. female, aged 13 and 11 years resp.) both suffered from multiple cerebral microinfarcts during the course of their disease, the boy additionally suffered from two strokes. Prior to related SCT in 2004 with unaffected siblings, both patients were assessed by MRA and TCD. The diagnostic data revealed a hypoplastic ACI (right side) in both children as prominent pathological feature, in combination with different grades of stenosises of ACM, AV and ACI (left side), for example. The evaluation of cerebro-vascular status 3–4 months post SCT showed a persisting stenosis of right ACI in both patients, whereas circulation in the cerebrum resp. flow velocity profiles in other intracranial arteries significantly improved or turned to normal. The course of SCT was rather uncomplicated in the immediate post-transplant period except clinically controlled acute GvHD grade III in one patient. Currently, i.e. 18 resp. 21 months after transplant, the children are in good clinical condition. Conclusions: The results of allogeneic SCT in 2 SCA patients suggest that cerebro-vascular disease does not progress after SCT resp. shows major improvement by SCT. Regular follow up is necessary to assess long term results of cerebro-vascular status in these patients. No significant financial relationships to disclose.
Commentary on ‘Comparison of the safety and efficacy of single-stage endoscopic retrograde cholangiopancreatography plus laparoscopic cholecystectomy versus two-stage ERCP followed by laparoscopic cholecystectomy six-to eight weeks later: A randomized controlled trial’ (Int J Surg 2020;76:37–44)
Authors: Meer M Chisthi
Journal: International Journal of Surgery (2020)
COLCHICINE INHIBITS NEUTROPHIL EXTRACELLULAR TRAP FORMATION IN ACUTE CORONARY SYNDROME PATIENTS POST PERCUTANEOUS CORONARY INTERVENTION
Authors: Bradley Tucker, Kaivan Vaidya, Rahul Kurup, Chinmay Khandkar, Jennifer Barraclough, Ashish Misra, Mary Kavurma, Gonzalo Martinez, Kerry-Anne Rye, Blake Cochran, Sanjay Patel
Journal: Journal of the American College of Cardiology (2020)
A first-in-human phase 1 dose escalation study of spartalizumab (PDR001), an anti–PD-1 antibody, in patients with advanced solid tumors
Authors: Aung Naing, Justin F Gainor, Hans Gelderblom, Patrick M Forde, Marcus O Butler, Chia-Chi Lin, Sunil Sharma, Maria Ochoa de Olza, Andrea Varga, Matthew Taylor, Jan H M Schellens, Hongqian Wu, Haiying Sun, Antonio P Silva, Jason Faris, Jennifer Mataraza, Scott Cameron, Todd M Bauer
Journal: Journal for ImmunoTherapy of Cancer (2020)

Spartalizumab is a humanized IgG4κ monoclonal antibody that binds programmed death-1 (PD-1) and blocks its interaction with PD-L1 and PD-L2. This phase 1/2 study was designed to assess the safety, pharmacokinetics, and preliminary efficacy of spartalizumab in patients with advanced or metastatic solid tumors.In the phase 1 part of the study, 58 patients received spartalizumab, intravenously, at doses of 1, 3, or 10 mg/kg, administered every 2 weeks (Q2W), or 3 or 5 mg/kg every 4 weeks (Q4W).Patients had a wide range of tumor types, most commonly sarcoma (28%) and metastatic renal cell carcinoma (10%); other tumor types were reported in ≤3 patients each. Most patients (93%) had received prior antineoplastic therapy (median three prior lines) and two-thirds of the population had tumor biopsies negative for PD-L1 expression at baseline. The maximum tolerated dose was not reached. The recommended phase 2 doses were selected as 400 mg Q4W or 300 mg Q3W. No dose-limiting toxicities were observed, and adverse events included those typical of other PD-1 antibodies. The most common treatment-related adverse events of any grade were fatigue (22%), diarrhea (17%), pruritus (14%), hypothyroidism (10%), and nausea (10%). Partial responses occurred in two patients (response rate 3.4%); one with atypical carcinoid tumor of the lung and one with anal cancer. Paired tumor biopsies from patients taken at baseline and on treatment suggested an on-treatment increase in CD8+ lymphocyte infiltration in patients with clinical benefit.Spartalizumab was well tolerated at all doses tested in patients with previously treated advanced solid tumors. On-treatment immune activation was seen in tumor biopsies; however, limited clinical activity was reported in this heavily pretreated, heterogeneous population. The phase 2 part of this study is ongoing in select tumor types.NCT02404441.
Toll‐like receptor signalling has inverted U‐shaped response over time with the Western environment
Authors: Jing Guo, Yong Song, Aarti Saiganesh, Belinda J. Hales, Anthony Bosco, Peter N. Le Souëf, Guicheng Zhang
Journal: Allergy (2020)

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1 YEAR FOLLOW UP RESULTS OF ARTIM HF TRIAL (ANGIOTENSIN RECEPTOR NEPRILYSIN INHIBITOR EFFECT ON TEI INDEX &amp; LEFT VENTRICULAR MASS IN HEART FAILURE)
Authors: Anushri Kaul, Rajendra Kumar Gokhroo, Tarik M.T., Kailash C., Rajesh N., Ashish K., Manish G., Subhash C
Journal: Journal of the American College of Cardiology (2020)
Decision Making for Treatment of Persistent Sciatica
Authors: Andrew J. Schoenfeld, James D. Kang
Journal: New England Journal of Medicine (2020)

Lumbar disk herniations are among the most frequent causes of sciatica.1,2 Fortunately for patients, sciatica is generally self-limited and resolves within 3 months in 70 to 90% of patients.2 When symptoms do not improve, surgical diskectomy has been an accepted treatment since it was first described in the Journal nearly a century ago.3 During the past 20 years, several studies, including the Maine Lumbar Spine Study,4 and clinical trials, including the Spine Patient Outcomes Research Trial (SPORT),5-7 have characterized the outcomes of surgical and nonsurgical treatment in patients with sciatica and lumbar disk herniation. These and other reports have supported . . .