tbuckley/cabot-search huggingface dataset:
Respiratory disease, and treatment / thematic poster session tracheostomy is associated with a decrease in sedation requirements for intubated COVID-19 patients
Authors: C. Morton, M. A. Pisani, M. Doyle, J. Puchalski
Journal: American Journal of Respiratory and Critical Care Medicine (2021)

Introduction - The ideal timing of tracheostomy for intubated COVID-19 patients is highly debated. The duration of intubation varies greatly but is frequently prolonged and data suggests that sedation requirements are high in these patients. Tracheostomy, rather than ongoing oral intubation, may be beneficial by decreasing the amount of sedation needed. We hypothesize that tracheostomy placement in patients requiring prolonged intubation secondary to COVID-19 significantly reduces the amount of sedation required post-procedure.Methods - We retrospectively evaluated 32 COVID-19 patients that underwent tracheostomy for prolonged intubation at a single tertiary care center. Bedside tracheostomy was performed by two experienced operators from March- June 2020. We captured total daily amounts of sedation 7 days prior to and following tracheostomy. Benzodiazepines, opiates, antipsychotics and other hypnotics (e.g. propofol, ketamine, etc) were recorded. Individual medications were compared in addition to total amounts of benzodiazepines and opiates after converting to equivalent dosing. Paired t-tests were used to determine whether there were significant changes in the average daily dose of each medication or group of medications pre vs. post tracheostomyResults - The average age of our patients was 57 (SD=11.13), 26 (83.9%) were male and 20 (62.5%) were Hispanic. The average time to tracheostomy was 28 days (SD=8.5) after intubation. There was a significant decrease in both benzodiazepine and opiate use after tracheostomy. The average daily use of benzodiazepines decreased by 17.5 mg lorazepam equivalents (SD=34.2, p=.01) and opiates by 157.5 mg morphine equivalents (sd=339.3, p=.01) . There was no significant difference in antipsychotic or other hypnotic drug doses. 23 patients (71.9%) were liberated from the ventilator (average of 24 days post-tracheostomy) and 16 were decannulated (average 42 days post-tracheostomy) at 6-month follow-up. Five (15.6%) of the 32 patients died, and all deaths were prior to hospital discharge. Discussion - Tracheostomy significantly decreased both benzodiazepine and opiate dosing for COVID-19 patients at our institution. COVID patients with severe respiratory failure should be considered for tracheostomy to help prevent over-sedation and facilitate ventilator liberation and decannulation. Limiting sedation in these patients has the potential to lower the incidence of delirium, improve mobility and shorten the duration of ventilation. These improvements may translate into shorter ICU stays and improved survival. References:Chao, Tiffany N et al. “Tracheotomy in Ventilated Patients With COVID-19.” Annals of surgery vol. 272,1 (2020): e30-e32.Cagino, Leigh M., et al. ' Annals of the American Thoracic Society ja (2020). .
Destiny of Elderly Patients with Lymphoma Indicated for Autologous Stem Cell Transplantation (ASCT)
Authors: Robert Pytlik, Kamila Polgarova, Marie Trnkova, Pavel Klener, Petra Blahovcova, Blanka Vackova, Eva Konířová, Benešová Kateřina, Marek Trněný
Journal: Blood (2017)
Abstract 455: FGF23-induced Cardiac Hypertrophy is Reversible
Authors: Alexander Grabner, Saurav Singh, Karla Schramm, Christopher Yanucil, Brian Czaya, Joshua Hare, Christian Faul
Journal: Circulation Research (2016)

Left ventricular hypertrophy (LVH) is a common feature of cardiovascular disease in chronic kidney disease (CKD) and affects up to 90% of patients by the time they reach dialysis. Serum levels of fibroblast growth factor (FGF) 23 continuously rise as patients progress to renal failure. We have previously shown that FGF23 can activate FGF receptor (FGFR) 4 and the PLCgamma/calcineurin/NFAT signaling cascade in cardiac myocytes and induce hypertrophy in vitro and in vivo. Administration of an isoform-specific FGFR4 blocking antibody in the 5/6 nephrectomy rat model of CKD immediately after surgery protects rats from developing LVH, and delivery of a pan-FGFR blocker in CKD rats two weeks after surgery reverses LVH. To further study the reversibility of cardiac FGF23 effects, we elevated serum FGF23 levels in mice by administration of a high phosphate (2%) diet for three months. Animals developed LVH, as evident by significantly increased LV wall thickness and myocyte cross sectional area. When mice were switch from high phosphate to normal chow, the LVH phenotype resolved and cardiac parameters were comparable to those of mice that constantly received a normal diet. Furthermore, isolated cardiac myocytes recovered within 24 hours from FGF23-induced hypertrophy upon removal of FGF23. Finally, the FGFR4 blocking antibody was capable of reversing FGF23-induced hypertrophy in vitro. Our data indicate that FGF23-induced LVH is reversible and treatable. Interfering with FGF23/FGFR4 signaling in the heart might provide a novel therapeutic strategy to tackle cardiac injury in CKD. We propose that progression and reversibility of cardiac injury might depend on the duration of cardiac FGF23/FGFR4 activation.
Effect of Bedside Compared With Outside the Room Patient Case Presentation on Patients' Knowledge About Their Medical Care
Authors: Christoph Becker, Martina Gamp, Philipp Schuetz, Katharina Beck, Alessia Vincent, Seraina Hochstrasser, Kerstin Metzger, Madlaina Widmer, Emanuel Thommen, Beat Mueller, Christoph A. Fux, Jörg D. Leuppi, Rainer Schaefert, Wolf Langewitz, Marten Trendelenburg, Tobias Breidthardt, Jens Eckstein, Michael Osthoff, Stefano Bassetti, Sabina Hunziker
Journal: Annals of Internal Medicine (2021)

Although bedside case presentation contributes to patient-centered care through active patient participation in medical discussions, the complexity of medical information and jargon-induced confusion may cause misunderstandings and patient discomfort.To compare bedside versus outside the room patient case presentation regarding patients' knowledge about their medical care.Randomized, controlled, parallel-group trial. (ClinicalTrials.gov: NCT03210987).3 Swiss teaching hospitals.Adult medical patients who were hospitalized.Patients were randomly assigned to bedside or outside the room case presentation.The primary endpoint was patients' average knowledge of 3 dimensions of their medical care (each rated on a visual analogue scale from 0 to 100): understanding their disease, the therapeutic approach being used, and further plans for care.Compared with patients in the outside the room group (n = 443), those in the bedside presentation group (n = 476) reported similar knowledge about their medical care (mean, 79.5 points [SD, 21.6] vs. 79.4 points [SD, 19.8]; adjusted difference, 0.09 points [95% CI, -2.58 to 2.76 points]; P = 0.95). Also, an objective rating of patient knowledge by the study team was similar for the 2 groups, but the bedside presentation group had higher ratings of confusion about medical jargon and uncertainty caused by team discussions. Bedside ward rounds were more efficient (mean, 11.89 minutes per patient [SD, 4.92] vs. 14.14 minutes per patient [SD, 5.65]; adjusted difference, -2.31 minutes [CI, -2.98 to -1.63 minutes]; P < 0.001).Only Swiss hospitals and medical patients were included.Compared with outside the room case presentation, bedside case presentation was shorter and resulted in similar patient knowledge, but sensitive topics were more often avoided and patient confusion was higher. Physicians presenting at the bedside need to be skilled in the use of medical language to avoid confusion and misunderstandings.Swiss National Foundation (10531C_ 182422).
Abstract 446: Estrogen and Estrogen Receptor Protect the Female Heart From Ischemia/reperfusion Injury by Increasing the Activity of Mitochondrial p38β and MnSOD
Authors: Tao Luo, Han Liu, Jin K Kim
Journal: Circulation Research (2016)

Background: We have previously demonstrated a novel in-vitro mechanism of how 17β-estradiol (E2) protects cultured neonatal cardiomyocytes from H/R by identifying a functionally active mitochondrial pool of p38β and E2-driven upregulation of manganese superoxide (MnSOD) activity via p38β. This protective mechanism leads to E2-mediated suppression of reactive oxygen species and attenuates apoptosis. However, little is known about these cytoprotective actions of E2 in the heart after myocardial I/R in vivo . The aim of this study is to determine whether the cardioprotective effects of E2 involve the interaction of mitochondrial p38β and MnSOD in the heart in vivo . Methods and Results: Left coronary ligation for 45 min and reperfusion for 24 hr was used to produce myocardial I/R injury in ovariectomized female mice with or without E2 pellet (0.1 mg/pellet). TTC staining showed that the infarct size was approximately 30% of the left ventricle at risk in untreated mice after I/R. The infarct size was reduced by more than half in the E2-treated group. Western blotting showed that the phosphorylation of p38β (p-p38β) in the heart homogenate was upregulated by E2, compared to the untreated mice, while the total p38β protein level was not altered. Mitochondrial p-p38β isolated from the hearts decreased after I/R, while E2 administration attenuated this effect. The total protein level of MnSOD decreased after I/R, regardless of E2 treatment. However, the MnSOD activity was normalized by E2 treatment, suggesting that E2 specifically increased the enzymatically active subset of MnSOD. Physical interaction between mitochondrial p38β and MnSOD was found by using co-immunoprecipitation from the hearts of the studied animals. Estrogen receptor (ER) α, β and double knockout female mice exhibited larger infarct size after I/R injury than that of WT mice while no significant difference was observed between the knockout mice. Loss of both ERs led to reduced activity of mitochondrial p38β and MnSOD at the baseline and after myocardial I/R. Conclusion: This work offers in-vivo evidence to our previously detailed mechanistic data that the protective effects of estrogen and ER against cardiac I/R injury involve the regulation of MnSOD activity via mitochondrial p38β.
Alpha-1 antitrypsin deficiency: clarifying the role of the putative protective threshold
Authors: Alessandro N. Franciosi, Daniel Fraughen, Tomás P. Carroll, Noel G. McElvaney
Journal: European Respiratory Journal (2021)

Alpha-1 antitrypsin deficiency (AATD) is the only readily identifiable monogenic cause of COPD. To date the only condition-specific treatment for AATD-associated COPD is weekly administration of intravenous plasma-purified human alpha-1 antitrypsin (IV-AAT). Uncertainties regarding which AATD genotypes should benefit from IV-AAT persist. IV-AAT is costly and involves weekly administration of a plasma product. Much of the risk stratification has been centred around the long-accepted hypothesis of a “putative protective threshold” of 11 µM (0.57 g·L −1 ) AAT in serum. This hypothesis has become central to the paradigm of AATD care, although its derivation and accuracy for defining risk of disease remain unclear. We reviewed the literature and examined the association between the 11 µM threshold and clinical outcomes to provide context and insight into the issues surrounding this topic. We found no data demonstrating an increased risk of COPD dependent on the 11 µM threshold. Moreover, an abundance of recent clinical data examining this threshold refutes the hypothesis. Conversely, the use of 11 µM as a treatment target in appropriate ZZ individuals is supported by clinical evidence, although more refined dosing regimens are being explored. Continued use of the 11 µM threshold as a determinant of clinical risk is questionable, perpetuates inappropriate AAT-augmentation practices, may drive increased healthcare expenditure and should not be used as an indicator for commencing treatment. Genotype represents a more proven indicator of risk, with ZZ and rare ZZ-equivalent genotypes independently associated with COPD. New and better risk assessment models are needed to provide individuals diagnosed with AATD with reliable risk estimation and optimised treatment goals.
Cardiologist is struck off for repeated dishonesty
Authors: Clare Dyer
Journal: BMJ (2021)

A consultant cardiologist has been struck off by a medical practitioners tribunal for repeated acts of dishonesty that included altering a letter about a patient’s case to confuse investigators at the NHS trust where he worked.

Ramon Martos Martinez also tried to divert two NHS patients to his private practice, the tribunal found. One patient testified that she felt as though she were “in front of a double glazing salesman” as the cardiologist sought to persuade her of the benefits of going private.

These incidents ultimately caused Martos Martinez to lose his job as an interventional cardiology consultant at University Hospitals of Derby and Burton NHS Foundation Trust. The trust’s investigation also found that …
Problems with Using Polygenic Scores to Select Embryos
Authors: Patrick Turley, Michelle N. Meyer, Nancy Wang, David Cesarini, Evelynn Hammonds, Alicia R. Martin, Benjamin M. Neale, Heidi L. Rehm, Louise Wilkins-Haug, Daniel J. Benjamin, Steven Hyman, David Laibson, Peter M. Visscher
Journal: New England Journal of Medicine (2021)

Companies have recently begun to sell a new service to patients considering in vitro fertilization: embryo selection based on polygenic scores (ESPS). These scores represent individualized predictions of health and other outcomes derived from genomewide association studies in adults to partially predict these outcomes. This article includes a discussion of many factors that lower the predictive power of polygenic scores in the context of embryo selection and quantifies these effects for a variety of clinical and nonclinical traits. Also discussed are potential unintended consequences of ESPS (including selecting for adverse traits, altering population demographics, exacerbating inequalities in society, and devaluing certain traits). Recommendations for the responsible communication about ESPS by practitioners are provided, and a call for a society-wide conversation about this technology is made. (Funded by the National Institute on Aging and others.).
Ferric carboxymaltose for the treatment of iron deficiency in heart failure: a multinational cost‐effectiveness analysis utilising <scp>AFFIRM‐AHF</scp>
Authors: Phil McEwan, Piotr Ponikowski, Jason A. Davis, Giuseppe Rosano, Andrew J.S. Coats, Fabio Dorigotti, Donal O'Sullivan, Antonio Ramirez de Arellano, Ewa A. Jankowska
Journal: European Journal of Heart Failure (2021)

Abstract Aims Iron deficiency is common in patients with heart failure (HF). In AFFIRM‐AHF, ferric carboxymaltose (FCM) reduced the risk of hospitalisations for HF (HHF) and improved quality of life vs. placebo in iron‐deficient patients with a recent episode of acute HF. The objective of this study was to estimate the cost‐effectiveness of FCM compared with placebo in iron‐deficient patients with left ventricular ejection fraction &lt;50%, stabilised after an episode of acute HF, using data from the AFFIRM‐AHF trial from Italian, UK, US and Swiss payer perspectives. Methods and results A lifetime Markov model was built to characterise outcomes in patients according to the AFFIRM‐AHF trial. Health states were defined using the 12‐item Kansas City Cardiomyopathy Questionnaire (KCCQ‐12). Subsequent HHF were incorporated using a negative binomial regression model with cardiovascular and all‐cause mortality incorporated via parametric survival analysis. Direct healthcare costs (2020 GBP/USD/EUR/CHF) and utility values were sourced from published literature and AFFIRM‐AHF. Modelled outcomes indicated that treatment with FCM was dominant (cost saving with additional health gains) in the UK, USA and Switzerland, and highly cost‐effective in Italy [incremental cost‐effectiveness ratio (ICER) EUR 1269 per quality‐adjusted life‐year (QALY)]. Results were driven by reduced costs for HHF events combined with QALY gains of 0.43–0.44, attributable to increased time in higher KCCQ states (representing better functional outcomes). Sensitivity and subgroup analyses demonstrated data robustness, with the ICER remaining dominant or highly cost‐effective under a wide range of scenarios, including increasing treatment costs and various patient subgroups, despite a moderate increase in costs for de novo HF and smaller QALY gains for ischaemic aetiology. Conclusion Ferric carboxymaltose is estimated to be a highly cost‐effective treatment across countries (Italy, UK, USA and Switzerland) representing different healthcare systems.
Recognising the value of “shared pain”—mandatory covid-19 vaccination should include all NHS workers
Authors: Stephen T Green
Journal: BMJ (2021)

There has been considerable discussion about the wisdom or otherwise of making covid-19 vaccination mandatory in certain settings, especially after Matt Hancock implied that most of the patients in hospital with covid-19 in Bolton had chosen not to be vaccinated.1 That vaccination is to be made compulsory for care home staff in England comes as no surprise.2 It is currently unclear whether this applies to only “frontline care …
Critical evaluation of the Clavien-Dindo classification for postoperative complications in renal tumor surgery, a national multi-center study from Finland
Authors: K. Erkkilä, T. Veitonmäki, E. Ettala, H. Ronkainen, T. Isotalo, T. Nykopp, H. Seikkula, M. Seppänen, M. Tramberg, C. Palmberg Christian, A. Kilponen, D. Pogodin-Hannolainen, S. Mustonen, H. Nisen
Journal: European Urology (2021)
Abstract 2793: The role of IL-10 in obesity-induced T-cell polarization in the prostate tumor microenvironment
Authors: Margaret Kappel, Michael Adkison, Alejandra De Angulo, Peyton Travis, Brittany Harlow, Christopher Jolly, Linda deGraffenried
Journal: Cancer Research (2021)

Abstract Background: Prostate cancer remains the second leading cause of cancer related deaths in men and obesity has been shown to severely impact its prognosis. Previous studies in our laboratory have shown that CD4+ T cells polarized under obese conditions are prostate cancer promoting and that this is due in part to suppression of IFNγ and induction of IL-6 in the T cells. Objective: The goal of this study is to determine the role of IL-10 in mediating the impact of obese conditions on T cell phenotype. Methods: A series of in vitro studies were conducted to evaluate the effects of obesity on T cell function and polarization. Splenic CD4+ T-cells from 10-week-old, male, C57BI/6 mice were isolated and stimulated with anti-CD3+/CD28+ antibodies under obese conditions. Gene expression was measured using qPCR and AKT phosphorylation was measured using Western blot analysis. In vivo T-cell function was compared between obese and non-obese male mice. Deletion assays were used to determine the role of IL-10 in mediating the effects observed on T cell phenotype in response to obese conditions. Results: For both the in vitro and in vivo studies, obese conditions suppressed the expression of Th1 biomarkers (IFNγ, IL-2, and T-bet) and upregulated the expression of Th2 biomarkers (IL-6, IL-10, and GATA-3) in CD4+ T cells. Likewise, obese conditions in vitro and in vivo were associated with decreased AKT phosphorylation. Studies are on-going to determine whether inhibiting the IL-10 pathway restores proper T cell activation under obese conditions. Conclusion: Obesity induces T cell dysfunction characterized by a Th1 to Th2 phenotypic shift, resulting in a pro-tumorigenic phenotype, potentially mediated by paracrine IL-10 signaling. These results are important in understanding the mechanisms by which obesity promotes a more aggressive disease, thereby identifying potential targets for improving outcomes. The results from these studies will provide a better understanding of the role of IL-10 as a novel target for preventing prostate cancer in obese subjects and improving overall survival. Citation Format: Margaret Kappel, Michael Adkison, Alejandra De Angulo, Peyton Travis, Brittany Harlow, Christopher Jolly, Linda deGraffenried. The role of IL-10 in obesity-induced T-cell polarization in the prostate tumor microenvironment [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2793.
Secondary Solid Cancers after Allogeneic Hematopoietic Stem Cell Transplantation: A Single Center Experience of 1374 Patients Including 812 Cord Blood Transplant Recipients
Authors: Yuki Asano-Mori, Mitsuhiro Yuasa, Kosei Kageyama, Daisuke Kaji, Aya Nishida, Shinsuke Takagi, Hisashi Yamamoto, Go Yamamoto, Atsushi Wake, Akiko Yoneyama, Shigeyoshi Makino, Naoyuki Uchida, Shuichi Taniguchi
Journal: Blood (2017)
Generation of immortal, IL3-dependent cell lines from embryonic stem (ES) cells expressing a NUP98-HOXD13 fusion gene
Authors: Christopher I. Slape, Lino Tessarollo, Peter D. Aplan
Journal: Cancer Research (2006)

258  NUP98-HOXD13 (NHD13) fusions have been identified in patients with myelodysplastic syndrome (MDS), acute myelogenous leukemia (AML) and chronic myeloid leukemia blast crisis (CML-BC). We generated knock-in mouse embryonic stem (ES) cells which expressed a NHD13 fusion gene. Injection of the NHD13 ES cells into host blastocysts did not generate chimeric mice. This failure suggested that the NHD13 cells induced a differentiation block, thereby preventing contribution to adult mice. To investigate this differentiation block, we used an established two-step in vitro differentiation system that utilizes a combination of cytokines to differentiate ES cells to embryoid bodies, and subsequently to hematopoietic colonies. The NHD13 cells behaved differently than the control ES parental cells in this differentiation system. The majority of the NHD13 colonies were dense aggregates of cells resembling blast colonies (CFC-Bl) morphologically. May-Giemsa stained slides demonstrated that the NHD13 colonies were composed primarily of cells primitive in appearance with a high nuclear/cytoplasm ratio, uncondensed chromatin, and rare cytoplasmic granules. In contrast to the parental ES cells, which could be replated only 3-4 times in methylcellulose with IL3, IL6, SCF and Epo, the NHD13 cells could be replated more than 12 times. Two of these cultures were transferred to liquid culture, where the cells were found to be IL-3 dependent and have a doubling time of approximately 24 hours. The two cell lines (188D and 189L2) have now been in continuous liquid culture for over three years. Immunophenotypic profiles of the cell lines revealed that they express c-kit, demonstrating that the ES cells had begun differentiation toward the hematopoieticlineage. Both cell lines resisted further differentiation in liquid culture following treatment with IL6, SCF, M-CSF, G-CSF, GM-CSF, and Epo, as determined by morphological and FACS analysis. Gene-expression profile analysis showed expression of numerous genes typically expressed in hematopoietic cells, again demonstrating hematopoietic differentiation. The cell lines failed to form tumors when injected into nude mice, in contrast to the parental ES cells and the NHD13 targeted ES cells, which both give rise to teratomas when injected. Expression of a BCR-ABL protein in either 188D or 189L2 removes the dependence on IL3, suggesting that BCR-ABL expression may result in complete transformation, consistent with the finding that some CML-BC patients acquire the NHD13. Together these findings support the hypothesis that expression of a NHD13 fusion gene serves as a relative block to hematopoietic differentiation, and present a model system to study the nature of this block.