tbuckley/cabot-search huggingface dataset:
Respiratory Drive in Critically Ill Patients. Pathophysiology and Clinical Implications
Authors: Katerina Vaporidi, Evangelia Akoumianaki, Irene Telias, Ewan C. Goligher, Laurent Brochard, Dimitris Georgopoulos
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

Respiratory drive, the intensity of the respiratory center's output, determines the effort exerted in each breath. The increasing awareness of the adverse effects of both strong and weak respiratory efforts during mechanical ventilation on patient outcome brings attention to the respiratory drive of the critically ill patient. Critical illness can affect patients' respiratory drive through multiple pathways, mainly operating through three feedback systems: cortical, metabolic, and chemical. The chemical feedback system, defined as the response of the respiratory center's output to changes in arterial blood gases and pH, is one of the most important determinants of respiratory drive. The purpose of this state-of-the-art review is to describe the determinants of respiratory drive in critically ill patients, review the tools available to assess respiratory drive at the bedside, and discuss the implications of altered respiratory drive during mechanical ventilation. An analysis that relates arterial carbon dioxide levels with brain's response to this stimulus will be presented, contrasting the brain's responses to the patient's ability to generate effective alveolar ventilation, both during unassisted breathing and with different modes of ventilatory assist. This analysis may facilitate comprehension of the pathophysiology of respiratory drive in critically ill patients. As we aim to avoid both over- and under-assistance with mechanical ventilation, considering the patients' respiratory drive at the bedside may improve clinical assessment and management of the patient and the ventilator.
Association of Optimal Blood Pressure With Critical Cardiorenal Events and Mortality in High-Risk and Low-Risk Patients Treated With Antihypertension Medications
Authors: Hae Hyuk Jung
Journal: JAMA Network Open (2019)

<h3>Importance</h3> There are few studies comparing the optimal level of treated blood pressure (BP) between high- and low-risk patients. <h3>Objective</h3> To examine whether optimally treated BP is different according to risk status. <h3>Design, Setting, and Participants</h3> Population-based cohort study using data from the National Health Information Database in Korea from 2002 to 2015 and 2006 to 2017. A total of 1 402 975 adults aged 40 to 79 years who had no known cardiorenal disease were included. <h3>Exposures</h3> Systolic BP treated with antihypertensive medication. <h3>Main Outcomes and Measures</h3> The yearly rates of critical cardiorenal events and all-cause death were estimated according to the levels of treated systolic BP and the presence of 5 risk factors (hypertension, diabetes, hyperlipidemia, proteinuria, and smoking). <h3>Results</h3> During the study periods, 225 103 of 487 412 participants (54.0% male; median [interquartile range] age, 50 [44-59] years) in the primary cohort and 360 503 of 915 563 participants (50.1% male; median [interquartile range] age, 52 [46-60] years) in the secondary cohort received antihypertensive treatment. In total, 28 411 of 51 292 cardiorenal incidents and 33 102 of 72 500 deaths were noted in ever-treated participants. The absolute increase in cardiorenal and mortality risk associated with inadequately treated BP was greater in participants with multiple risk factors than in those with 1 or 0 risk factors. The hazard ratios for critical cardiorenal events increased as the treated systolic BP increased to more than 130 to 140 mm Hg. The hazard ratio for all-cause mortality for patients with 3 or more risk factors and treated systolic BP within the range of 110 to 119 mm Hg was 1.21 (95% CI, 1.07-1.37); 130 to 139 mm Hg, 1.04 (95% CI, 0.98-1.11); 140 to 149 mm Hg, 1.12 (95% CI, 1.05-1.20); 150 to 159 mm Hg, 1.21 (95% CI, 1.11-1.32); and 160 mm Hg or greater, 1.46 (95% CI, 1.32-1.62) compared with high-risk patients with BP of 120 to 129 mm Hg. For participants with 1 or 0 risk factors and treated systolic BP within the range of 110 to 119 mm Hg, the hazard ratio was 1.14 (95% CI, 1.07-1.22); 130 to 139 mm Hg, 0.97 (95% CI, 0.93-1.02); 140 to 149 mm Hg, 1.00 (95% CI, 0.91-1.09); 150 to 159 mm Hg, 1.06 (95% CI, 0.99-1.14); and 160 mm Hg or greater, 1.26 (95% CI, 1.15-1.37). However, when categorized using cardiovascular risk calculators, there was no consistent trend in mortality thresholds of BP across the risk score categories. <h3>Conclusions and Relevance</h3> These results suggest that intensive BP control is appropriate for reducing all-cause mortality in addition to cardiorenal risk in higher- rather than lower-risk patients. However, caution may be required when determining BP targets using current risk calculators.
Comparative Study on Fresenius-ATG Versus Thymoglobuline-ATG for the Graft Versus Host Disease (GVHD) Prophylaxis in Allogeneic Stem Cell Transplantation from Matched Unrelated Donor: A Single Center Experience on 76 Patients
Authors: Nicola Polverelli, Michele Malagola, Alessandro Turra, Cristina Skert, Federica Cattina, Benedetta Rambaldi, Rossella Ribolla, Valeria Cancelli, Francesca Schieppati, Marta Bonetti, Simona Bernardi, Simone Perucca, Camilla Zanaglio, Domenico Russo
Journal: Blood (2016)
The Controversies and Difficulties of Diagnosing Primary Ciliary Dyskinesia
Authors: Amelia Shoemark, Bruna Rubbo, Eric Haarman, Robert A. Hirst, Claire Hogg, Claire L. Jackson, Kim G. Nielsen, Jean-Francois Papon, Philip Robinson, Woolf T. Walker, Jane S. Lucas
Journal: American Journal of Respiratory and Critical Care Medicine (2019)

We welcome the correspondence from Lavie and Amirav (1), highlighting the difficulties diagnosing primary ciliary dyskinesia (PCD) and the role of high-speed video analysis (HSVA). As members of the European Respiratory Society (ERS) PCD Diagnostic Task Force (2) and/or large PCD Centres, we agree that HSVA has an important role that is not recognized by the American Thoracic Society (ATS) PCD Diagnostic Guideline (3). This risks a large proportion of false-negative “missed” diagnoses and a sizable number of false-positive cases; we make additional important observations.
Fropofol prevents disease progression in mice with hypertrophic cardiomyopathy
Authors: Yiyuan Huang, Haisong Lu, Xianfeng Ren, Fazhao Li, Weiming Bu, Wenjie Liu, William P Dailey, Harumi Saeki, Kathleen Gabrielson, Roselle Abraham, Roderic Eckenhoff, Wei Dong Gao
Journal: Cardiovascular Research (2019)

Increased myofilament contractility is recognized as a crucial factor in the pathogenesis of hypertrophic cardiomyopathy (HCM). Direct myofilament desensitization might be beneficial in preventing HCM disease progression. Here, we tested whether the small molecule fropofol prevents HCM phenotype expression and disease progression by directly depressing myofilament force development.Force, intracellular Ca2+, and steady-state activation were determined in isolated trabecular muscles from wild-type (WT) and transgenic HCM mice with heterozygous human α-myosin heavy chain R403Q mutation (αMHC 403/+). αMHC 403/+ HCM mice were treated continuously with fropofol by intraperitoneal infusion for 12 weeks. Heart tissue was analysed with histology and real-time PCR of prohypertrophic and profibrotic genes. Fropofol decreased force in a concentration-dependent manner without significantly altering [Ca2+]i in isolated muscles from both WT and αMHC 403/+ HCM mouse hearts. Fropofol also depressed maximal Ca2+-activated force and increased the [Ca2+]i required for 50% activation during steady-state activation. In whole-animal studies, chronic intra-abdominal administration of fropofol prevented hypertrophy development and diastolic dysfunction. Chronic fropofol treatment also led to attenuation of prohypertrophic and profibrotic gene expression, reductions in cell size, and decreases in tissue fibrosis.Direct inhibition of myofilament contraction by fropofol prevents HCM disease phenotypic expression and progression, suggesting that increased myofilament contractile force is the primary trigger for hypertrophy development and HCM disease progression.
AB0197 Sonographic assessment of steroid injection therapy
Authors: E Filippucci, A Farina, F Salaffi, C Cervini, W Grassi
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> Ultrasonography (US) is an excellent technique to look around and inside joints and tendons in patients with chronic arthritis.<sup>1</sup> Power Doppler imaging combined with conventional grey-scale US could play a role in functional and quantitative assessment of synovitis.<sup>2,3</sup> <h3>Objectives</h3> The aim of this study was to assess sonographic changes induced by steroid injection therapy. <h3>Methods</h3> Seven joints of 5 patients with active synovitis were studied. A visual analogue scale (VAS) (ranging from 0 to 10) and a tenderness score (ranging from 0 to 10) were assessed as measures of disease activity. Sonographic evaluation was performed with an AU-5 Harmonic, Esaote Biomedica (Genoa, Italy) equipped with a 13-MHz linear transducer. Power Doppler examination was performed just before the ultrasound guided injection with triamcinolone acetonide. Power Doppler settings were standardised with a pulse repetition frequency of 1000 Hz. Colour gain was initially set at a level just below the disappearance of colour noise deep to cortical bone. Joint cavity widening and power Doppler colour signal were scored from 0 to 4. Ultrasound examination was repeated in the second week after the steroid injection. Statistical evaluation was performed by the Wilcoxon signed-rank test. <h3>Results</h3> All the affected joints showed both morphological (joint cavity widening) and functional (colour signal) features of active synovitis. A significant decrease of joint cavity widening (p = 0.045), VAS (p = 0.003), and tenderness score (p = 0.0024) was detected. Power Doppler score did not show a significant change (p = 0.091). However, a clearly evident decrease of colour signal was observed in 3 out of 5 patients. <h3>Conclusion</h3> Our study confirms the clinical efficacy of steroid injection therapy. Grey-scale US seems to be able to carefully detect morphological changes induced by steroid injection therapy. Although this preliminary report shows that power Doppler score is not significantly changed after steroid injection, we believe that further studies on a larger group of patients are needed to better assess the role of power Doppler US in disease activity monitoring. <h3>References</h3> Gibbon WW, Wakefield RJ. Ultrasound in inflammatory disease. Radiol Clin North Am. 1999;37:633–51 Hau M, Schultz H, Tony HP, Keberle M, Jahns R, Haerten R, Jenett M. Evaluation of pannus and vascularization of the metacarpophalangeal and proximal interphalangeal joints in rheumatoid arthritis by high-resolution ultrasound (multidimensional linear array). Arthritis Rheum. 1999;42:2303–8 Newman JS, Laing TJ, McCarthy CJ, Adler RS. Power Doppler sonography of synovitis: assessment of therapeutic response-preliminary observations. Radiology 1996;198:582–4
Parental insights into phase I pediatric oncology clinical trials: Findings from a phenomenological study.
Authors: Stacey Crane, James Croop, Jill Lunsford Lee, Jamie Walski, Joan Haase
Journal: Journal of Clinical Oncology (2019)

e21534 Background: Phase I clinical trials (P1Ts) are an essential step in the validation of novel therapies to treat childhood cancer. Children with cancer participate in P1Ts when no known curative therapy remains for their cancer. It is important to understand the experiences of children with advanced cancer and their families in P1Ts to ensure that participation supports the participants well-being. Methods: An empirical phenomenology study, using an adapted Colaizzi method, was conducted of 11 parents lived experiences of their childs participation in pediatric oncology P1Ts. Parents were recruited from two pediatric academic medical centers in the Midwest United States and from national childhood cancer groups not affiliated with either medical center. Parents participated in individual interviews (mean length 59.1 minutes), with one broad data-generating question. Demographics and the childs clinical trial records provided additional context for understanding the experiences. This presentation describes the study themes identified that were specifically related to pediatric oncology P1T processes and logistics. Results: Parents experiences during the P1Ts were primarily positive. However, data analysis revealed five aspects of P1T participation that were problematic for parents to varying degrees. These aspects were: (1) Learning About Clinical Trials, (2) Being Referred to Another Institution, (3) Undergoing Research-Only Procedures, (4) Complying with the Trial Requirements, and (5) Taking Oral Medications. Conclusions: While overall experiences during P1T participation were positive, improvements can be made that could potentially enhance participants experiences. In particular, enhancing the education provided to participants during on-trial processes and minimizing the logistical burdens associated with P1T requirements may help to address problematic aspects of P1Ts.
Re: Jonas Hugosson, Monique J. Roobol, Marianne Månsson, et al. A 16-yr Follow-up of the European Randomized Study of Screening for Prostate Cancer. Eur Urol 2019;76:43–51
Authors: Alberto Donzelli, Gianluca Castelluzzo, Giulia Giudicatti
Journal: European Urology (2019)
Immunotherapy for pediatric brain tumors: past and present
Authors: Jessica B Foster, Peter J Madsen, Meenakshi Hegde, Nabil Ahmed, Kristina A Cole, John M Maris, Adam C Resnick, Phillip B Storm, Angela J Waanders
Journal: Neuro-Oncology (2019)

The field of cancer immunotherapy has progressed at an accelerated rate over the past decade. Pediatric brain tumors thus far have presented a formidable challenge for immunotherapy development, given their typically low mutational burden, location behind the blood-brain barrier in a unique tumor microenvironment, and intratumoral heterogeneity. Despite these challenges, recent developments in the field have resulted in exciting preclinical evidence for various immunotherapies and multiple clinical trials. This work reviews the history and advances in active immunotherapy, checkpoint blockade, and adoptive T-cell therapy for pediatric brain tumors, including ongoing clinical trials.
Incidence of Breakthrough Invasive Fungal Infections after Posaconazole Prophylaxis in Allogeneic Stem Cell Transplant Patients
Authors: Rayaz Ahmed, Sanghmitra Thakur, Jyotsna Kapoor, Narendra Agrawal, Pallavi Mehta, Shinto Francis Thekuddan, Ambar Garg, Dinesh Bhurani
Journal: Blood (2018)
Imaging challenges of immunotherapy and targeted therapy in patients with brain metastases: response, progression, and pseudoprogression
Authors: Norbert Galldiks, Martin Kocher, Garry Ceccon, Jan-Michael Werner, Anna Brunn, Martina Deckert, Whitney B Pope, Riccardo Soffietti, Emilie Le Rhun, Michael Weller, Jörg C Tonn, Gereon R Fink, Karl-Josef Langen
Journal: Neuro-Oncology (2019)

The advent of immunotherapy using immune checkpoint inhibitors (ICIs) and targeted therapy (TT) has dramatically improved the prognosis of various cancer types. However, following ICI therapy or TT-either alone (especially ICI) or in combination with radiotherapy-imaging findings on anatomical contrast-enhanced MRI can be unpredictable and highly variable, and are often difficult to interpret regarding treatment response and outcome. This review aims at summarizing the imaging challenges related to TT and ICI monotherapy as well as combined with radiotherapy in patients with brain metastases, and to give an overview on advanced imaging techniques which potentially overcome some of these imaging challenges. Currently, major evidence suggests that imaging parameters especially derived from amino acid PET, perfusion-/diffusion-weighted MRI, or MR spectroscopy may provide valuable additional information for the differentiation of treatment-induced changes from brain metastases recurrence and the evaluation of treatment response.
Creation and development of the National Cancer Control Plan in Russia.
Authors: Alexander Petrovsky, Sergei Tjulandin, Alexey Tryakin, Ivan S. Stilidi, Mikhail Davydov, Maria Avksentieva, Yulia Ledovskih
Journal: Journal of Clinical Oncology (2019)

10524 Background: The absence of the National Cancer Control Plan (NCCP) did not allow to develop оncology in Russia. Methods: Since 2015 experts of the N.N. Blokhin Russian National Comprehancive Center and Russian Oncology Association has initiated the creation of a National Anti-Cancer Strategy. Results: In 2016, the working group presented the first version of this Strategy to the professional community for wide discussion, which was transferred to the Russian Ministry of Health after a broad discussion in 2017. This strategy included prevention, screening, early diagnosis, treatment, rehabilitation and palliative care in patients with malignant tumors. In parallel, we created National Clinical Cancer Guidelines, which were approved by the professional community, and then we submited them to the Ministry of Health in 2017. Also in the period of 2017-2018, updated principles of creating clinical and statistical groups (CSG) were developed based on the calculation of the real costs of each type of surgery, radiation therapy and drug treatment. More than 1,000 different standards we established for each case of hospitalization and their cost has been calculated. Then, based on these calculations, we ranked four types of treatment (surgery, radiation therapy, chemotherapy and chemoradiation), each of which has 3, 5, 10 and 6 levels, respectively. These calculations formed the basis of the NCCP approved by the Government and the President starting from 2019 with an unprecedented additional level of funding of almost 1 trillion rubles (an increase of almost two times). The major goal of the Russian NCCP is to decrease mortality level from 202 to 185 (8,5%) per 100 000 population by the year of 2024. Conclusions: The еffort of the professional community with due consideration and consolidation with the Ministry of Health allows implementation of the NCCP on a national level.
Stratified Intense-Dose- Yttrium-90 Ibritumumab Tiuxetan (90YIT ) with Bendamustine+Fludarabine Nonmyeloablative Conditioning for Allogeneic Stem Cell Transplantation in b-Cell Malignancies
Authors: Issa F. Khouri, Bill Erwin, Alison M Gulbis, Francesco Turturro, S Cheenu Kappadath, Dustin Gress, Rosamar B Valverde, Elias J. Jabbour, Roland L Bassett, Aaron Jessop
Journal: Blood (2016)
Thyroid Function Test Abnormalities During Pregnancy
Authors: Anne R. Cappola, Brian M. Casey
Journal: JAMA (2019)

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European Association of Urology Guidelines on Non-muscle-invasive Bladder Cancer (TaT1 and Carcinoma In Situ) - 2019 Update
Authors: Marko Babjuk, Maximilian Burger, Eva M. Compérat, Paolo Gontero, A. Hugh Mostafid, Joan Palou, Bas W.G. van Rhijn, Morgan Rouprêt, Shahrokh F. Shariat, Richard Sylvester, Richard Zigeuner, Otakar Capoun, Daniel Cohen, José Luis Dominguez Escrig, Virginia Hernández, Benoit Peyronnet, Thomas Seisen, Viktor Soukup
Journal: European Urology (2019)
Engineered Proteins: Protein‐Engineered Functional Materials (Adv. Healthcare Mater. 11/2019)
Authors: Yao Wang, Priya Katyal, Jin Kim Montclare
Journal: Advanced Healthcare Materials (2019)

The review in article 1801374 by Jin Kim Montclare and co-workers discusses protein-engineered functional materials generated using synthetic biology techniques. Recombinant proteins with a particular focus on their ability to assemble into various structures are highlighted. Protein-engineered materials are reviewed from the perspective of domain-based designs as well as physically- and chemically-crosslinked materials—materials bearing sequences for metal temptation and non-canonical amino acids, and their potential applications.
GAPDH Overexpression in the T Cell Lineage Promotes Angioimmunoblastic T Cell Lymphoma through an NF-κB-Dependent Mechanism
Authors: Laura Mondragón, Rana Mhaidly, Gian Marco De Donatis, Marie Tosolini, Pascal Dao, Anthony R. Martin, Caroline Pons, Johanna Chiche, Marie Jacquin, Véronique Imbert, Emma Proïcs, Laurent Boyer, Anne Doye, Frédéric Luciano, Jaap G. Neels, Frédéric Coutant, Nicole Fabien, Laura Sormani, Camila Rubio-Patiño, Jozef P. Bossowski, Florian Muller, Sandrine Marchetti, Elodie Villa, Jean-François Peyron, Philippe Gaulard, François Lemonnier, Vahid Asnafi, Laurent Genestier, Rachid Benhida, Jean-Jacques Fournié, Thierry Passeron, Jean-Ehrland Ricci, Els Verhoeyen
Journal: Cancer Cell (2019)
The Impact of Hydroxyurea on Survival and Risk of Thrombosis Among Older Patients with Essential Thrombocythemia
Authors: Nikolai A. Podoltsev, Mengxin Zhu, Amer M. Zeidan, Rong Wang, Amy J. Davidoff, Smith Giri, Scott Huntington, Steven D. Gore, Xiaomei Ma
Journal: Blood (2017)