tbuckley/cabot-search huggingface dataset:
Особенности вегетативной регуляции у больных с хроническим панкреатитом в сочетании с хроническим бронхитом по результатам частотного анализа вариабельности ритма сердца
Authors: N.B. Gubergrits, Ye.S. Zykova
Journal: GASTROENTEROLOGY (2013)

Обследовано 60 больных хроническим панкреатитом в сочетании с хроническим бронхитом. На основе проведения частотного анализа вариабельности сердечного ритма получены данные относительно наличия вегетативной дисфункции у пациентов. Показано, что имеет место усиление влияния парасимпатического отдела вегетативной нервной системы.
Lentiviral expression of TRAIL in human mesenchymal stem cells (MSC) induces apoptosis in interacting colon carcinoma cells
Authors: Jana Luetzkendorf, Lutz Mueller, Thomas Mueller, Katrin Reichelt, Hans-Joachim Schmoll
Journal: Cancer Research (2008)

4608  RATIONALE: It has been previously shown that MSC are potent vehicles for delivery of antineoplastic mediators. For clinical use an efficient gene transfer as well as transgenes without systemic toxicity are required. Lentiviral transduction allows stable transgene expression at high levels even in resting cells. The use of TRAIL promises low toxicity as most non-malignant cells are resistant to TRAIL-induced apoptosis. Here we show that lentivirally TRAIL-transduced MSC can induce apoptosis in colon carcinoma cells in vitro and delay tumor growth in vivo.  METHODS: Human bone marrow MSC were transduced with the TRAIL cDNA using a lentiviral system. Transduced cells were analyzed for TRAIL expression (flow cytometry, western blot), proliferation (growth kinetics) and in vitro differentiation capacity (cytochemistry) as well as for soft agar growth. For coculture and in vivo studies the TRAIL-sensitive colon carcinoma cell line DLD-1 was used. In direct coculture of dsRed-DLD-1 with TRAIL-MSC and of dsRed-DLD-1 with WT-MSC over 72h the ratio of DLD-1 cells and MSC was determined (flow cytometry). Apoptosis was verified with annexin-V staining and western blot. Subcutaneous xenografts of DLD-1 mixed with WT- or TRAIL-MSC were generated in nude mice.  RESULTS: After lentiviral transduction TRAIL-MSC showed stable TRAIL expression over up to 10 passages without signs of apoptosis, growth delay or malignant transformation. TRAIL-MSC retained an identical expression of cell surface antigens as well as proliferation and differentiation capacity when compared to non-transduced MSC. Lentiviral TRAIL expression was functional in vitro as seen in direct cocultures. DLD-1 cells underwent apoptosis after reaching cell-cell contact with TRAIL-MSC while incubation of DLD-1 cells with TRAIL-MSC supernatant did not result in apoptosis. The absolute number of DLD-1 cells decreased significantly during direct coculture with TRAIL-MSC in contrast to continued increase of DLD-1 cells in cocultures with WT-MSC. Thus the observed decrease in the number of tumor cells was due to apoptosis and not growth inhibition. In preliminary animal studies DLD-1 xenografts containing TRAIL-MSC showed an altered tumor stroma and a growth delay when compared to xenografts containing WT-MSC.  CONCLUSIONS: We show for the first time that lentivirally transduced MSC can express antineoplastic mediators without changes in their characteristic properties. Secondly, we demonstrate that lentiviral TRAIL expression in MSC can induce apoptosis in TRAIL-sensitive tumor cells by direct cellular interaction. We therefore suggest that TRAIL-MSC may serve as a new therapeutic tool with a low risk of systemic toxicity and should be further evaluated for clinical applications under GMP-conditions.
Wide Complex Tachycardia With Unexpected Break in the Negative QRS Concordance in the Chest Leads
Authors: János Tomcsányi, Emil Toldy-Schedel, Péter Arányi
Journal: JAMA Internal Medicine (2021)

This case report presents the electrocardiographic findings in a 74-year-old woman with hypertension who presented with palpitations and chest discomfort and no history of angina, myocardial infarction, or dysrhythmia.
Real-time imaging of asthmatic epithelial cells identifies migratory deficiencies under type-2 conditions
Authors: Mingzhu Jin, Simon Watkins, Yolanda Larriba, Callen Wallace, Claudette St. Croix, Xiuxia Zhou, Jinming Zhao, Shyamal Peddada, Sally E. Wenzel
Journal: Journal of Allergy and Clinical Immunology (2021)
Prognostic and predictive biomarker developments in multiple myeloma
Authors: Craig T. Wallington-Beddoe, Rachel L. Mynott
Journal: Journal of Hematology & Oncology (2021)

Abstract New approaches to stratify multiple myeloma patients based on prognosis and therapeutic decision-making, or prediction, are needed since patients are currently managed in a similar manner regardless of individual risk factors or disease characteristics. However, despite new and improved biomarkers for determining the prognosis of patients, there is currently insufficient information to utilise biomarkers to intensify, reduce or altogether change treatment, nor to target patient-specific biology in a so-called predictive manner. The ever-increasing number and complexity of drug classes to treat multiple myeloma have improved response rates and so clinically useful biomarkers will need to be relevant in the era of such novel therapies. Therefore, the field of multiple myeloma biomarker development is rapidly progressing, spurred on by new technologies and therapeutic approaches, and underpinned by a deeper understanding of tumour biology with individualised patient management the goal. In this review, we describe the main biomarker categories in multiple myeloma and relate these to diagnostic, prognostic and predictive applications.
Safety and Antibody Response After 1 and 2 Doses of BNT162b2 mRNA Vaccine in Recipients of Allogeneic Hematopoietic Stem Cell Transplant
Authors: Amandine Le Bourgeois, Marianne Coste-Burel, Thierry Guillaume, Pierre Peterlin, Alice Garnier, Marie C. Béné, Patrice Chevallier
Journal: JAMA Network Open (2021)
Environmental allergens trigger type 2 inflammation through ripoptosome activation
Authors: Michael Brusilovsky, Mark Rochman, Yrina Rochman, Julie M. Caldwell, Lydia E. Mack, Jennifer M. Felton, Jeff E. Habel, Aleksey Porollo, Chandrashekhar Pasare, Marc E. Rothenberg
Journal: Nature Immunology (2021)
Abstract 14860: Prednisone Wean After Heart Transplantation - Is There a Risk for Antibody Formation?
Authors: Omeed Elboudwarej, Jignesh Patel, Ashley Osborne, Frank Liou, Nancy Reinsmoen, Jon Kobashigawa
Journal: Circulation (2013)

BACKGROUND: Prednisone (pred) withdrawal after heart transplantation (HTx) is usually limited to select patients (pts) demonstrating low or no rejection (rejn) rates, are not highly sensitized, or ...
Pain tools are problematic in dementia
Authors: Claud Regnard
Journal: BMJ (2021)

Nguyen and colleagues’ overview of the management of patients with behavioural and psychological symptoms of dementia is both helpful and comprehensive, until it comes to assessing pain.1

Although many people with dementia are able to express the presence and cause of their distress, that ability is lost when they are ill or in the later stages of the condition. Many tools have been developed to assess pain, but the tools mentioned in …
OS05.3.A Temporal muscle thickness as surrogate parameter of sarcopenia in newly diagnosed glioblastoma patients:translational imaging analysis of the CENTRIC EORTC 26071-22072 and CORE trials
Authors: J Furtner, M Weller, M Weber, T Gorlia, B Nabors, D Reardon, J Tonn, R Stupp, M Preusser
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Temporal muscle thickness (TMT) was described as surrogate parameter of skeletal muscle mass. This study aimed to investigate the prognostic relevance of TMT in patients with newly diagnosed glioblastoma. MATERIAL AND METHODS TMT was assessed in cranial magnetic resonance images (MRI) of 755 pts enrolled in the CENTRIC EORTC 26071-22072 study (n=508) and CORE study (n=247). Predefined sex-specific TMT cutoff values were used to categorize “patients at risk of sarcopenia” and “patients with normal muscle status” at baseline. Furthermore, patients were categorized according to the extent of TMT loss over time. Cox models adjusted for other explanatory variables were used to evaluate the associations with progression-free survival (PFS) and overall survival (OS). RESULTS Overall, 510/755 (67.6%) patients were categorized as “at risk of sarcopenia” and 245/755 (32.4%) patients had normal muscle status at baseline. In both study cohorts patient at risk of sarcopenia at baseline had significantly higher risk of progression and death than patients with normal muscle status (CENTRIC: PFS = HR 0.16, 95% CI: 0.12, 0.21, p&amp;lt;0.001; OS = HR 0.341, 95% CI: 0.27, 0.44, p &amp;lt; 0.001; CORE: PFS = HR 0.29, 95% CI: 0.21, 0.39, p&amp;lt;0.001; OS = HR 0.365, 95% CI: 0.27, 0.49, p&amp;lt;0.001). In multivariate Cox models adjusted for other important prognostic parameters similar results were obtained. In patients at risk for sarcopenia the extent of TMT loss over time showed a significant inverse correlation with median OS times (CENTRIC: p &amp;lt; 0.001, CORE: p = 0.005, log-rank test), but not in patients with normal baseline muscle mass in both study cohorts (CENTRIC: p = 0.538, CORE: p = 0.28, log-rank test). CONCLUSION TMT identifies patients with newly diagnosed glioblastoma at risk for progressive sarcopenia and adverse outcomes. Early intervention for muscle mass preservation including exercise and resistance training as well as nutritional support may prevent skeletal muscle loss and improve patient outcome in this group of patients.
Use of metformin to prolong gestation in preterm pre-eclampsia: randomised, double blind, placebo controlled trial
Authors: Catherine A Cluver, Richard Hiscock, Eric H Decloedt, David R Hall, Sonja Schell, Ben W Mol, Fiona Brownfoot, Tu’uhevaha J Kaitu’u-Lino, Susan P Walker, Stephen Tong
Journal: BMJ (2021)

Abstract Objective To evaluate whether extended release metformin could be used to prolong gestation in women being expectantly managed for preterm pre-eclampsia. Design Randomised, double blind, placebo controlled trial. Setting Referral hospital in Cape Town, South Africa. Participants 180 women with preterm pre-eclampsia between 26+0 to 31+6 weeks’ gestation undergoing expectant management: 90 were randomised to extended release metformin and 90 to placebo. Intervention 3 g of oral extended release metformin or placebo daily, in divided doses, until delivery. Main outcome measure The primary outcome was prolongation of gestation. Results Of 180 participants, one woman delivered before taking any trial drug. The median time from randomisation to delivery was 17.7 days (interquartile range 5.4-29.4 days; n=89) in the metformin arm and 10.1 (3.7-24.1; n=90) days in the placebo arm, a median difference of 7.6 days (geometric mean ratio 1.39, 95% confidence interval 0.99 to 1.95; P=0.057). Among those who continued to take the trial drug at any dose, the median prolongation of gestation in the metformin arm was 17.5 (interquartile range 5.4-28.7; n=76) days compared with 7.9 (3.0-22.2; n=74) days in the placebo arm, a median difference of 9.6 days (geometric mean ratio 1.67, 95% confidence interval 1.16 to 2.42). Among those who took the full dosage, the median prolongation of gestation in the metformin arm was 16.3 (interquartile range 4.8-28.8; n=40) days compared with 4.8 (2.5-15.4; n=61) days in the placebo arm, a median difference of 11.5 days (geometric mean ratio 1.85, 95% confidence interval 1.14 to 2.88). Composite maternal, fetal, and neonatal outcomes and circulating concentrations of soluble fms-like tyrosine kinase-1, placental growth factor, and soluble endoglin did not differ. In the metformin arm, birth weight increased non-significantly and length of stay decreased in the neonatal nursery. No serious adverse events related to trial drugs were observed, although diarrhoea was more common in the metformin arm. Conclusions This trial suggests that extended release metformin can prolong gestation in women with preterm pre-eclampsia, although further trials are needed. It provides proof of concept that treatment of preterm pre-eclampsia is possible. Trial registration Pan African Clinical Trial Registry PACTR201608001752102 https://pactr.samrc.ac.za/ .
P04.09 Frequent inactivating mutations of PBRM1 in meningioma with papillary features
Authors: E Williams, P Brastianos, S Santagata, D Cahill, S Ramkissoon, T Juratli
Journal: Neuro-Oncology (2021)

Abstract BACKGROUND Papillary meningiomas (PM) are rare WHO grade III tumors that are associated with frequent recurrences and metastatic disease in spite of surgery and radiation. Due to their low incidence and scarcity of tumor tissues available for genomic analyses, the genetic alterations associated with PM remain unclear. MATERIAL AND METHODS We mined data collected as part of our clinical comprehensive genomic profiling (CGP) initiative which has to date analyzed 8 PM (&amp;gt;50% papillary morphology) and 22 meningiomas with focal papillary features (10–50%) amongst over 500 additional meningiomas of other subtypes. The samples were analyzed in a CAP/CLIA-accredited laboratory (Foundation Medicine, Cambridge, MA). GCP was performed on hybridization-captured, adaptor ligation-based libraries to a mean coverage depth of &amp;gt;650x for 236 or 315 genes plus the introns from 19 or 28 genes frequently involved in cancer. RESULTS In our cohort of 8 PMs, we identified three cases with inactivation of PBRM1; two cases with a truncating mutation in PBRM1 and one with homozygous deletion of PBRM1. Of the 22 meningiomas with only focal papillary features, 8 cases were PBRM1-mutant. Thus, 11 of 30 cases (36.7%) with at least focal (&amp;gt;10%) papillary morphology had inactivation of PBRM1.In the entire cohort of 562 meningiomas, we identified five additional cases with inactivating alterations in PBRM1 that did not display overt papillary morphology in the H&amp;E sections available for analysis. Thus, 11 of 16 PBRM1-mutant cases (69%) occurred in meningioma with papillary histologic features as opposed to 19 of 546 wild-type cases (3.5%), supporting a significant association between papillary features and PBRM1 mutation (p&amp;lt;0.0001). The majority of PBRM1-mutant meningiomas occurred in female patients (n=10/16, 62.5%), and median age was 51 years. Most cases were located supratentorially (n=10). CONCLUSION We identified the tumor suppressor gene PBRM1 as a recurrently altered gene in meningiomas with papillary histomorphology. Further investigational studies are needed to assess outcomes of PBRM1-mutant meningioma and to determine whether mutation is an independent negative prognostic biomarker.
Evaluating the utility of rule OP-35 to define preventability of ED visits for oncology patients at an academic cancer center.
Authors: Steven Manobianco, Zachary L. Quinn, Valerie Pracilio Csik, Adam F Binder, Nathan Handley
Journal: Journal of Clinical Oncology (2021)

272 Background: Rule OP-35, which characterizes treatment-related complications of patients receiving outpatient chemotherapy that result in a potentially avoidable emergency department (ED) visit or hospitalization, was developed to encourage practices to build treatment models that reduce such events. However, defining visits as potentially avoidable based on symptoms may not capture the complexity of caring for oncology patients. We aim to evaluate the effectiveness of OP-35 in identifying preventable ED visits by real world standards at an academic institution. Methods: A retrospective analysis was performed reviewing ED visits at the Sidney Kimmel Cancer Center (SKCC) at Thomas Jefferson University for oncology patients from 10/1/2020 to 1/31/2021. Each patient received care at SKCC had received intravenous or oral chemotherapy in the preceding 30 days, and each encounter was classified as potentially avoidable by OP-35 criteria. Two investigators independently conducted chart reviews to determine whether these visits were potentially avoidable, recording whether the patient attempted to contact their care team prior to the ED encounter and assessing if the concern could have been managed in a timely manner in an outpatient setting. The two records were then compared, and the principal investigator served as an arbiter for determining if a visit was potentially avoidable in instances where the investigators disagreed. Results: We reviewed 144 total encounters and excluded events from patients with either acute leukemia or breast cancer on hormone therapy only, leaving 107 encounters for analysis. After evaluating the clinical circumstances, we determined that 29% of these ED encounters were potentially avoidable. Applying New York University Emergency Department Algorithm (NYU-EDA) criteria, 69% of encounters were considered potentially avoidable. Patients called for advice before seeking ED care in 53% of unavoidable encounters compared to 26% of potentially avoidable encounters. An additional 14% of visits deemed unavoidable were from patients sent directly from clinic. For potentially avoidable encounters, 60% of patients were discharged directly from the ED. In comparison, 8% of unavoidable encounters led to discharge from the ED. Pain was the most common reason for encounters and 53% of these visits were considered potentially avoidable. Conclusions: We found that approximately 30% of ED encounters deemed avoidable by OP-35 criteria were considered potentially avoidable following clinician review. In the majority of cases patients were referred to the ED following initial outpatient attempts at management. NYU-EDA criteria for preventability did not correlate with OP-35 nor clinician consensus regarding potentially avoidable encounters. More work remains in refining tools to identify potentially avoidable ED visits for oncology patients.
Human SLE variant<i>NCF1</i>-R90H promotes kidney damage and murine lupus through enhanced Tfh2 responses induced by defective efferocytosis of macrophages
Authors: Linyu Geng, Jian Zhao, Yun Deng, Ivan Molano, Xue Xu, Lingxiao Xu, Phillip Ruiz, Quanzhen Li, Xuebing Feng, Miaojia Zhang, Wenfeng Tan, Diane L Kamen, Sang-Cheol Bae, Gary S Gilkeson, Lingyun Sun, Betty P Tsao
Journal: Annals of the Rheumatic Diseases (2021)

Objectives We previously identified a hypomorphic variant, p.Arg90His (p.R90H) of neutrophil cytosolic factor 1 ( NCF1, a regulatory subunit of phagocyte nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 2 complex), as an putative causal variant for systemic lupus erythematosus (SLE), and established a knock-in (KI) H90 variant in the C57BL/6 background to study how this variant promotes lupus development. Methods Wild type (WT) and KI littermates were assessed for immune profiles and lupus-like features. Disease activity and renal damage of patients with SLE were assessed by systemic lupus erythematosus disease activity index (SLEDAI) and renal items of systemic lupus international collaborating clinics (SLICC), respectively. Results Compared with WT littermates, 5-week-old homozygous KI mice had reduced oxidative burst, splenomegaly, elevated type I interferon (IFN-I) scores, increased ratios of splenic follicular T helper 2 (Tfh2) to either T follicular regulatory (Tfr) or Tfh1 cells, increased ANA + follicular, germinal centre and plasma cells without spontaneous kidney disease up to 1 year of age. Pristane treatment exacerbated the immune dysregulation and induced IFN-I-dependent kidney disease in 36-week-old H90 KI female mice. Decreased efferocytosis of macrophages derived from KI mice and patients with homozygous H90 SLE promoted elevated ratios of Tfh2/Tfr and Tfh2/Tfh1 as well as dysregulated humoral responses due to reduced voltage-gated proton channel 1 (Hv1)-dependent acidification of phagosome pH to neutralise the decreased electrogenic effect of the H90 variant, resulting in impaired maturation and phagosome proteolysis, and increased autoantibody production and kidney damage in mice and patients with SLE of multiple ancestries. Conclusions A lupus causal variant, NCF1-H90, reduces macrophage efferocytosis, enhances Tfh2 responses and promotes autoantibody production and kidney damage in both mice and patients with SLE.
Assessing financial toxicity in patients with metastatic breast cancer: A single institution experience during the COVID-19 pandemic.
Authors: Shruti Sinkar, Faith Too, Kelly Carr, Jessica Jelinek, Elizabeth Saylor, Jacqueline Bacon, Vered Stearns, Karen L. Smith
Journal: Journal of Clinical Oncology (2021)

176 Background: Assessment of financial toxicity (FTox) is recommended as a component of comprehensive supportive care for patients with metastatic cancer. FTox is common in patients with metastatic breast cancer (MBC) and is associated with poor quality of life. Available data suggest many patients with cancer have faced financial hardship during the COVID-19 pandemic. Methods: We evaluated FTox using the COmprehensive Score for Financial Toxicity (COST) measure in patients with MBC at Johns Hopkins clinical sites. Respondents were patients with MBC who completed the COST measure as part of the baseline assessment for one of two IRB-approved quality improvement projects initiated during the COVID-19 pandemic: 1) a pilot project evaluating incorporation of patient-reported outcome (PRO) measures into routine care (RC), and 2) a needs assessment prior to attending a multi-disciplinary clinic (MultiD-C) focusing on supportive care. COST scores range from 0-44 with higher scores indicating better financial well-being. FTox was graded as: Grade 0 (G0): &gt;26, Grade 1 (G1): &gt;14-26, Grade 2 (G2): &gt;0-14 and Grade 3 (G3): 0. Results: 40 patients with MBC completed the COST measure May 2020 through April 2021 as a component of RC and 17 patients with MBC completed the COST measure September 2020 through May 2021 in advance of anticipated attendance at the MultiD-C. Median age (range) for RC and MultiD-C respondents was 64 (36-85) and 55 (37-75) years, respectively. 4 (10%) and 4 (24%) of RC and MultiD-C respondents respectively reported household income &lt; $50,000. The majority of respondents in both groups were White [RC: 28 (70%), MultiD-C: 14 (82%)], non-Hispanic [RC: 36 (90%), MultiD-C: 16 (94%)], had more than high school education [RC: 37 (93%), MultiD-C: 17 (100%)] and all were insured. 27 (68%) of RC respondents and 11 (65%) of MultiD-C respondents were receiving oral cancer therapies. COST scores and grading are shown in the Table. Approximately half of the respondents in each group reported their illness has been at least “a little bit” of a financial hardship [RC: 22 (55%), Multi-D: 8 (47%)]. Conclusions: Patients with MBC receiving care during the COVID-19 pandemic frequently report FTox. Implementation of routine assessment for FTox via PRO measures and identification of strategies to support patients with MBC experiencing FTox are priorities both during the pandemic and beyond.[Table: see text]
Clean air for healthy lungs – an urgent call to action: European Respiratory Society position on the launch of the WHO 2021 Air Quality Guidelines
Authors: Zorana Jovanovic Andersen, Ulrike Gehring, Sara De Matteis, Erik Melen, Ana Maria Vicedo-Cabrera, Klea Katsouyanni, Arzu Yorgancioglu, Charlotte Suppli Ulrik, Sylvia Medina, Kjeld Hansen, Pippa Powell, Brian Ward, Barbara Hoffmann
Journal: European Respiratory Journal (2021)

<b>Air pollution poses a major burden to respiratory patients and legislation fails to protect them. Urgent action and alignment of air quality standards with WHO guidelines are needed to ensure healthier lungs and tackle the climate change crisis.</b>https://bit.ly/3B04dKB