tbuckley/cabot-search huggingface dataset:
General Versus Local Anesthesia With Conscious Sedation in Transcatheter Aortic Valve Implantation
Authors: Holger Thiele, Thomas Kurz, Hans-Josef Feistritzer, Georg Stachel, Philipp Hartung, Philipp Lurz, Ingo Eitel, Christoph Marquetand, Holger Nef, Oliver Doerr, Ursula Vigelius-Rauch, Alexander Lauten, Ulf Landmesser, Sascha Treskatsch, Mohamed Abdel-Wahab, Marcus Sandri, David Holzhey, Michael Borger, Jörg Ender, Hüseyin Ince, Alper Öner, Roza Meyer-Saraei, Rainer Hambrecht, Andreas Fach, Thomas Augenstein, Norbert Frey, Inke R. König, Reinhard Vonthein, Yvonne Rückert, Anne-Kathrin Funkat, Steffen Desch, Astrid E. Berggreen, Matthias Heringlake, Suzanne de Waha-Thiele
Journal: Circulation (2020)

Background: In clinical practice, local anesthesia with conscious sedation (CS) is performed in roughly 50% of patients undergoing transcatheter aortic valve replacement. However, no randomized data assessing the safety and efficacy of CS versus general anesthesia (GA) are available. Methods: The SOLVE-TAVI (Comparison of Second-Generation Self-Expandable Versus Balloon-Expandable Valves and General Versus Local Anesthesia in Transcatheter Aortic Valve Implantation) trial is a multicenter, open-label, 2×2 factorial, randomized trial of 447 patients with aortic stenosis undergoing transfemoral transcatheter aortic valve replacement comparing CS versus GA. The primary efficacy end point was powered for equivalence (equivalence margin 10% with significance level 0.05) and consisted of the composite of all-cause mortality, stroke, myocardial infarction, infection requiring antibiotic treatment, and acute kidney injury at 30 days. Results: The primary composite end point occurred in 27.2% of CS and 26.4% of GA patients (rate difference, 0.8 [90% CI, −6.2 to 7.8]; P equivalence =0.015). Event rates for the individual components were as follows: all-cause mortality, 3.2% versus 2.3% (rate difference, 1.0 [90% CI, −2.9 to 4.8]; P equivalence &lt;0.001); stroke, 2.4% versus 2.8% (rate difference, −0.4 [90% CI, −3.8 to 3.8]; P equivalence &lt;0.001); myocardial infarction, 0.5% versus 0.0% (rate difference, 0.5 [90% CI, −3.0 to 3.9]; P equivalence &lt;0.001), infection requiring antibiotics 21.1% versus 22.0% (rate difference, −0.9 [90% CI, −7.5 to 5.7]; P equivalence =0.011); acute kidney injury, 9.0% versus 9.2% (rate difference, −0.2 [90% CI, −5.2 to 4.8]; P equivalence =0.0005). There was a lower need for inotropes or vasopressors with CS (62.8%) versus GA (97.3%; rate difference, −34.4 [90% CI, −41.0 to −27.8]). Conclusions: Among patients with aortic stenosis undergoing transfemoral transcatheter aortic valve replacement, use of CS compared with GA resulted in similar outcomes for the primary efficacy end point. These findings suggest that CS can be safely applied for transcatheter aortic valve replacement. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02737150.
The road ahead in genetics and genomics
Authors: Amy L. McGuire, Stacey Gabriel, Sarah A. Tishkoff, Ambroise Wonkam, Aravinda Chakravarti, Eileen E. M. Furlong, Barbara Treutlein, Alexander Meissner, Howard Y. Chang, Núria López-Bigas, Eran Segal, Jin-Soo Kim
Journal: Nature Reviews Genetics (2020)
Fibroblasts as a source of self-antigens for central immune tolerance
Authors: Takeshi Nitta, Masanori Tsutsumi, Sachiko Nitta, Ryunosuke Muro, Emma C. Suzuki, Kenta Nakano, Yoshihiko Tomofuji, Shinichiro Sawa, Tadashi Okamura, Josef M. Penninger, Hiroshi Takayanagi
Journal: Nature Immunology (2020)
Epidemiology of COVID-19 Among Incarcerated Individuals and Staff in Massachusetts Jails and Prisons
Authors: Monik C. Jiménez, Tori L. Cowger, Lisa E. Simon, Maya Behn, Nicole Cassarino, Mary T. Bassett
Journal: JAMA Network Open (2020)

This cohort study describes the COVID-19 burden among incarcerated individuals and staff in Massachusetts jails and prisons and assesses the association of COVID-19 case rates with decarceration and testing rates.
The NIMH global mental health research community and COVID-19
Authors: Atif Rahman, John A Naslund, Theresa S Betancourt, Candace J Black, Anant Bhan, William Byansi, Hongtu Chen, Bradley N Gaynes, Carlos Gomez Restrepo, Lídia Gouveia, Syed Usman Hamdani, Lisa A Marsch, Inge Petersen, Ozge Sensoy Bahar, Laura Shields-Zeeman, Fred Ssewamala, Milton L Wainberg
Journal: The Lancet Psychiatry (2020)
Covid-19 also a chance to assess risk reduction or prevention treatments
Authors: Louisa Polak
Journal: BMJ (2020)

I agree with Moynihan and colleagues1 that the pandemic offers a “natural experiment in less medical care,” and that the results may help identify some interventions that do more harm than good to most people. I also agree that the financial crisis will focus our minds on the desirability of maximising value for money.

I am, however, …
Para-aortal Ganglion Mimicking a Lymph Node Metastases on 68Ga-PSMA PET/CT
Authors: Gregor Schweighofer Zwink, Gundula Rendl, Nikolaus Schmeller, Christian Pirich
Journal: Clinical Nuclear Medicine (2020)

Abstract PSMA-based nuclear medicine imaging impacts increasingly the clinical decision process in prostate cancer patients. A well-known PSMA pitfall is uptake into autonomic ganglia. The intensity of uptake, the shape, and the exact location of the correlating structure in CT are supposed to aid discriminating between ganglia and lymph node metastases. In this patient, we found intense uptake in a nodular shaped para-aortal soft tissue lesion suspicious of a lymph node metastases at staging as well as restaging. After secondary resection, the lesion was histologically proven an autonomic ganglion with intense PSMA expression.
Biomodulation of capecitabine by weekly paclitaxel and carboplatin in patients with advanced solid tumor malignancies: A dose-escalating phase I study
Authors: M. B. Lustberg, J. Nuovo, J. P. Thomas, P. J. Monk, S. Kim, M. Villalona-Calero, T. Bekaii-Saab
Journal: Journal of Clinical Oncology (2009)

2569 Background: A principal determinant of the therapeutic index with capecitabine-based treatment is the grade of thymidine phosphorylase (TP) activity in malignant tissue. The beneficial interactions of paclitaxel and carboplatin in upregulation of TP promise to make capecitabine more tumor specific and to provide the expected synergy. On the basis of the time-dependency and transiency for this upregulation we performed a phase I study of capecitabine in combination with weekly paclitaxel and carboplatin (CTX). Methods: Patients with advanced solid tumors received carboplatin on day 1, paclitaxel on days 1, 8, 15 and capecitabine orally twice a day on days 8–21, every 4 weeks. There were 5 planned dose levels (DL 1–5). Paclitaxel was escalated from 60 mg/m 2 to 80 mg/m 2 (DL 4) then 100 mg/m2 (DL 5). Capecitabine from 500 mg/m 2 bid to 750 mg/2 bid (DL 2) then 1000 mg/m2 bid (DL 3–5). Carboplatin dose was fixed at AUC 6. Paraffin-embedded tissue was evaluated for expression of TP, thymidylate synthase and dihydropyrimidine dehydrogenase by immunohistochemistry. Results: 32 patients from Ohio State University (OSU) were enrolled. 84% had prior therapy. The most common grade 3/4 toxicities were neutropenia (59%), leukopenia (56%), and fatigue (16%). DLTs included neutropenic fever (1), prolonged neutropenia or thrombocytopenia (2) and diarrhea (1). The MTD was at DL 2. There were 10 confirmed responses [4 CR (esophagus, stomach, unknown primary and ampullary); 6 PRs (Pancreas (3), unknown primary, anal and esophagus] and stabilization of disease &gt; 3 months in 12 patients. In normal tissue, there was no difference in expression levels of both TS and TP. On the other hand, in cancer tissue, TP levels seem to correlate with response whereas TS did not. Conclusions: CTX demonstrates acceptable tolerability. The recommended doses for phase II studies are capecitabine 750 mg/m 2 bid, paclitaxel 60 mg/m 2 /week and carboplatin AUC=6. The acceptable toxicity profile in this dose schedule, and the promising antitumor activity observed warrant further evaluation of this regimen. Two phase II trials are already underway at OSU using this regimen for patients with pancreatic cancer and adenocarcinomas of unknown primary, the latter already actively enrolling patients. Pretreatment tumoral TP levels may help predict patients that are more likely to respond to CTX. Correlation of IHC data with responses will be presented at the meeting. [Table: see text]
Exploratory subset analysis according to prior endocrine treatment of two randomized phase II trials comparing gefitinib (G) with placebo (P) in combination with tamoxifen (T) or anastrozole (A) in hormone receptor-positive (HR+) metastatic breast cancer (MBC)
Authors: M. Cristofanilli, R. Schiff, V. Valero, R. Iacona, J. Yu, G. Speake, I. Smith, C. K. Osborne
Journal: Journal of Clinical Oncology (2009)

1014 Background: Preclinical and clinical data suggest that increased EGFR and HER-2 activity contribute to acquired resistance to endocrine therapy. Strata of two clinical trials recently showed that the addition of G to T or A in HR+ MBC prolonged progression free-survival (PFS). Certain preclinical data also suggested that G should be combined with T or A from the start of endocrine therapy rather than waiting for resistance to develop. To examine this clinically a post hoc analysis compared the subsets of patients (pts) who had received prior endocrine therapy (may have already upregulated HER receptors) to those that were endocrine therapy naïve (not yet upregulated HER receptors). Methods: One trial evaluated G (250 mg/day orally) + A (1 mg/day orally) versus A+P ( NCT00077025 ) and one trial evaluated G (250 mg/day orally) + T (20 mg/day orally) versus T+P ( NCT00229697 ). Post hoc analysis of PFS was performed in two pt subgroups; previously treated with endocrine therapy (ET) and endocrine naïve (EN). The PFS HR and associated 95% CI and p-value for G relative to P were estimated using the Cox proportional hazards model along with interaction test for treatment by subset. Results: In the ET subgroup of the G+A versus A+P study, 31 PFS events were reobserved in 51 pts (hazard ratio [HR] 0.65 95% CI 0.32, 1.33; median PFS: G+A 11.2 mo, A+P 7.1 mo). In the EN subgroup, 23 PFS events were reobserved in 42 pts (HR 0.39, 95% CI 0.16, 0.97; median PFS: G+A 20.2 mo, A+P 8.4 mo). The interaction test p-value was 0.28. In the ET subgroup of the G+T versus T+P study, 95 PFS events were reobserved in 131 pts (HR 1.22, 95% CI 0.81, 1.86; median PFS: G+T 9.4 mo, T+P 10.9 mo). In the EN subgroup, 106 PFS events were reobserved in 158 patients (HR 0.78, 95% CI 0.52, 1.15; median PFS: G+T 12.1 mo, T+P 8.9 mo). The interaction test p-value was 0.13. Conclusions: The EN pt subgroups of both trials demonstrated prolonged PFS when G was combined with A or with T compared with A or T alone, respectively. A further prospective clinical trial of EGFR inhibition combined with endocrine therapy in EN pts with HR+ MBC is warranted on the basis of these findings. [Table: see text]
The natural history of metastatic progression in men with PSA-recurrent prostate cancer after radical prostatectomy: 25-year follow-up
Authors: E. S. Antonarakis, B. J. Trock, Z. Feng, E. B. Humphreys, M. A. Carducci, A. W. Partin, P. C. Walsh, M. A. Eisenberger
Journal: Journal of Clinical Oncology (2009)

5008 Background: In men with prostate specific antigen (PSA) recurrence following radical prostatectomy (RP) and no other therapy, the natural history of metastatic progression was previously described in 1999. We now report data reflecting up to 25 years of follow-up. Methods: We performed a retrospective analysis of 774 men treated with RP between 4/1982 and 7/2008 who developed PSA recurrence (&gt;0.2 ng/ml) and never received adjuvant or salvage therapy. We investigated factors influencing the development of metastases. Results: Mean follow-up after RP was 8.5 y (median 8 y). Of 774 men with PSA recurrence, 295 (38%) developed metastases, and 433 had data on PSA doubling time (PSADT), forming our cohort. The mean time from RP to PSA recurrence in the entire cohort was 4.2 y (median 3 y). In those who developed metastases, the mean time from PSA recurrence to metastasis was 3.1 y (median 2 y). The mean PSA at the time of metastasis was 90.3 ng/ml (median 31.4 ng/ml). In Cox regression analysis: PSADT, Gleason score, and time to PSA progression were predictive of the development of metastases ( Table ). In Kaplan-Meier survival analysis, the median actuarial time from PSA recurrence to metastasis was 10 y (95% CI 9 - 15 y). Median actuarial metastasis-free survival from PSA recurrence for men with PSADT &lt;3 mo, 3 - 8.9 mo, 9 - 14.9 mo, and &gt;15 mo was 1 y (95% CI 0 - 1 y), 4 y (95% CI 2 - 6 y), 9 y (95% CI 7 - 13 y), and 15 y (95% CI 12 - 20 y), respectively. Conclusions: PSADT, Gleason score, and time to PSA progression are strong independent predictors of metastasis-free survival in men with PSA-recurrent prostate cancer. These data facilitate patient counseling and logical risk-based treatment planning. They also provide the background for appropriate selection of patients, treatments, and endpoints for clinical trials. [Table: see text] No significant financial relationships to disclose.
Response to Comment on Mizokami-Stout et al. The Contemporary Prevalence of Diabetic Neuropathy in Type 1 Diabetes: Findings From the T1D Exchange. Diabetes Care 2020;43:806–812
Authors: Kara R. Mizokami-Stout, Zoey Li, Nicole Foster, Lynn Ang, Rodica Pop-Busui
Journal: Diabetes Care (2020)

We thank Professor Kostev for his comments (1) on our manuscript that evaluated the contemporary prevalence of diabetic peripheral neuropathy (DPN) in 5,936 participants with type 1 diabetes (T1D) in the T1D Exchange Clinic Registry (2). As described, we found a DPN prevalence of 11% as defined by the Michigan Neuropathy Screening Instrument Questionnaire (MNSIQ) (2). Our study highlighted several nonglycemic risks factors including hypertriglyceridemia (odds ratio [OR] 1.03, 95% CI 1.01, 1.05) and smoking (OR 1.83, 95% CI 1.18, 2.82) and other complications including retinopathy (OR 1.46, 95% CI 1.14, 1.88) and cardiovascular disease (CVD) (OR 1.73, 95% CI 1.24, 2.42) (2).

We elected to use the MNSIQ because it is a simple, noninvasive measure of DPN that has …
Contemporary Management of Severe Acute Kidney Injury and Refractory Cardiorenal Syndrome
Authors: Jacob C. Jentzer, Azra Bihorac, Samuel B. Brusca, Gaspar Del Rio-Pertuz, Kianoush Kashani, Amir Kazory, John A. Kellum, Michael Mao, Brad Moriyama, David A. Morrow, Hena N. Patel, Aniket S. Rali, Sean van Diepen, Michael A. Solomon
Journal: Journal of the American College of Cardiology (2020)
Reply to Brandon A. Mahal, Anthony V. D’Amico, and Paul L. Nguyen’s Letter to the Editor re: Neal D. Shore, Fred Saad, Michael S. Cookson, et al. Oral Relugolix for Androgen Deprivation Therapy in Advanced Prostate Cancer. N Engl J Med 2020;382:2187–96
Authors: Neal D. Shore, David Dearnaley, Bertrand Tombal
Journal: European Urology (2020)
Systemic lupus erythematosus and COVID-19: what we know so far
Authors: Giuseppe A. Ramirez, Luca Moroni, Emanuel Della-Torre, Maria Gerosa, Lorenzo Beretta, Enrica P. Bozzolo, Lorenzo Dagna
Journal: Annals of the Rheumatic Diseases (2020)

We read with interest the recent report by Mathian et al 1 about 17 patients with systemic lupus erythematosus (SLE) and COVID-19, which has paved the way to a constellation of articles aiming to find clues on potential peculiarities in COVID-19 epidemiology and course among patients with SLE. An ongoing debate has also recently grown on the role of hydroxychloroquine (HCQ), with increasing data disconfirming a protective effect of this drug towards severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in general and specifically also in patients with SLE.2 3 We were thus prompted to summarise the evidence published so far on this latter topic to look for recurrent clinical or epidemiological patterns among different studies/cohorts. To this aim, we analysed all studies published in the English literature until June, 30th 2020 and identified 20 articles describing a total of 4059 patients with SLE, 255 of whom with a PCR-confirmed or presumptive (ie, based on symptoms or radiological findings) diagnosis of …
大動脈弁閉鎖不全に対し, 弁置換術を施行した Fabry 病の一例
Authors: 高橋伸幸, 陽 村上, 俊夫 島田, 慎一 井上, 庸子 太田, 修三 大畑, 広 中村, 優美 清水, 晴美 加藤, 伸之 公受, 豊 石橋
Journal: Circulation (2003)
A population-based phenome-wide association study of cardiac and aortic structure and function
Authors: Wenjia Bai, Hideaki Suzuki, Jian Huang, Catherine Francis, Shuo Wang, Giacomo Tarroni, Florian Guitton, Nay Aung, Kenneth Fung, Steffen E. Petersen, Stefan K. Piechnik, Stefan Neubauer, Evangelos Evangelou, Abbas Dehghan, Declan P. O’Regan, Martin R. Wilkins, Yike Guo, Paul M. Matthews, Daniel Rueckert
Journal: Nature Medicine (2020)
Abstract 18232: The Magnitude of Hyperemic Microvascular Resistance Determines the Functional Consequences of Fractional Flow Reserve-Positive Coronary Stenoses, as Well as the Optimal Fractional Flow Reserve Cut-Off Value for Stenosis-Specific Inducible Myocardial Ischemia
Authors: Tim P van de Hoef, Froukje Nolte, Martijn A van Lavieren, Martijn Meuwissen, Steven A Chamuleau, Michiel Voskuil, José P Henriques, Karel T Koch, Robbert J de Winter, Jos A Spaan, Maria Siebes, Jan G Tijssen, Jan J Piek
Journal: Circulation (2013)

Background: Although myocardial ischemia is a consequence of both epicardial and microvascular abnormalities, clinical decision-making by fractional flow reserve (FFR) is purportedly based on the extent of epicardial disease only. Nonetheless, FFR is recognized to be sensitive to the magnitude of hyperemic microvascular resistance (HMR), which is not accounted for in FFR-guided diagnostic strategies. We aimed to determine pertinence of hyperemic microvascular resistance for the occurrence of inducible myocardial ischemia in FFR-positive (FFR≤0.80) and FFR-negative (FFR&gt;0.80) lesions, as well as for the optimal FFR cut-off value to identify stenosis-specific inducible myocardial ischemia. Methods: We evaluated 299 coronary lesions by intracoronary pressure and flow velocity measurements to determine FFR and HMR. Myocardial perfusion scintigraphy (MPS) was performed to identify inducible myocardial ischemia. High HMR was defined as HMR&gt;1.9 mmHg/cm/s. The association between FFR and inducible ischemia was evaluated according to the presence of a high or low HMR using logistic regression analysis. Receiver-operating characteristics curve analysis was performed to determine the optimal FFR cut-off value for inducible myocardial ischemia. Results: Overall, the odds ratio of positive versus negative FFR for inducible myocardial ischemia on MPS was 4.6 (95% confidence interval (CI): 2.6-8.0; p&lt;0.001). The odds ratio of positive versus negative FFR for myocardial ischemia amounted to 2.1 (95% CI: 0.5-3.6; p=0.14) when HMR was low, and to 8.1 (95% CI: 4.0-16.5; p&lt;0.001) when HMR was high. The optimal FFR cut-off value for inducible myocardial ischemia was 0.65 when HMR was low, compared with 0.76 when HMR was high. Conclusion: The 0.80 cut-off value provides limited discriminative value, since the odds for myocardial ischemia originating from FFR-positive lesions are to a large extent determined by the magnitude of distal microvascular resistance. The optimal FFR cut-off value to identify stenosis-related inducible myocardial ischemia depends on the magnitude of HMR, and is substantially lower when HMR is low, compared with when HMR is high.
Progress Toward Hepatitis B and Hepatitis C Elimination Using a Catalytic Funding Model — Tashkent, Uzbekistan, December 6, 2019–March 15, 2020
Authors: Rick Dunn, Erkin Musabaev, Homie Razavi, Shakhlo Sadirova, Shokhista Bakieva, Katie Razavi-Shearer, Krestina Brigida, Saleem Kamili, Francisco Averhoff, Muazzam Nasrullah
Journal: MMWR Morbidity and Mortality Weekly Report (2020)

In 2016, the World Health Organization (WHO) set hepatitis elimination targets of 90% reduction in incidence and 65% reduction in mortality worldwide by 2030 (1). Hepatitis B virus (HBV) and hepatitis C virus (HCV) infection prevalences are high in Uzbekistan, which lacks funding for meeting WHO's targets. In the absence of large financial donor programs for eliminating HBV and HCV infections, insufficient funding is an important barrier to achieving those targets in Uzbekistan and other low- and middle-income countries. A pilot program using a catalytic funding model, including simplified test-and-treat strategies, was launched in Tashkent, Uzbekistan, in December 2019. Catalytic funding is a mechanism by which the total cost of a program is paid for by multiple funding sources but is begun with upfront capital that is considerably less than the total program cost. Ongoing costs, including those for testing and treatment, are covered by payments from 80% of the enrolled patients, who purchase medications at a small premium that subsidizes the 20% who cannot afford treatment and therefore receive free medication. The 1-year pilot program set a target of testing 250,000 adults for HBV and HCV infection and treating all patients who have active infection, including those who had a positive test result for hepatitis B surface antigen (HBsAg) and those who had a positive test result for HCV core antigen. During the first 3 months of the program, 24,821 persons were tested for HBV and HCV infections. Among those tested, 1,084 (4.4%) had positive test results for HBsAg, and 1,075 (4.3%) had positive test results for HCV antibody (anti-HCV). Among those infected, 275 (25.4%) initiated treatment for HBV, and 163 (15.2%) initiated treatment for HCV, of whom 86.5% paid for medications and 13.5% received medications at no cost. Early results demonstrate willingness of patients to pay for treatment if costs are low, which can offset elimination costs. However, improvements across the continuum of care are needed to recover the upfront investment. Lessons learned from this program, including the effectiveness of using simplified test-and-treat guidelines, general practitioners in lieu of specialist physicians, and innovative financing to reduce costs, can guide similar initiatives in other countries and help curb the global epidemic of viral hepatitis, especially among low- and middle-income countries.