tbuckley/cabot-search huggingface dataset:
AB1014 CLINICAL AND LABORATORY PHENOTYPES IN PATIENTS DIAGNOSED WITH SARCOIDOSIS IN A VETERAN’S HOSPITAL
Authors: J. M. Bello-Gualtero, M. Carreno-Jaimes, R. Reyes, P. Medina, M. C. Romero, D. Padilla-Ortiz, Y. M. Chamorro-Melo, D. Rincón-Riaño
Journal: Annals of the Rheumatic Diseases (2020)

Background: Sarcoidosis is a disease which affect any organ or tissue in the body, but is predisposed to lung involvement in up to 90% of cases. Its cause is not yet established, although a multicausal model with genetic, environmental and infectious factors is proposed. Objectives: Determine the clinical, paraclinical characteristics and survival of patients diagnosed with Sarcoidosis treated at the Central Military Hospital. Methods: Historical cohort study of patients who were diagnosed with Sarcoidosis at the Central Military Hospital in the last 5 years. A review of medical records, laboratory results and radiological studies was performed and verification of survival status free of mortality was documented by independent outcomes group. A descriptive analysis was done using standard methods and non-parametric survival was calculated using the Kaplan Meyer method with confidence interval in STATA 15. Results: Twenty patients with confirmatory biopsy of sarcoidosis. Average age 44 ± 15.3 years, 55% (11/20) of the patients were men. Dyspnea was the most frequent reason for consultation 50% (10/20), S. Löfgren 10% (2/20), the lung was the most frequent location 65% (13/20), mild hypercalcemia and normal enzyme converting angiotensin levels were found. 60% of patients had grade 1 commitment on the chest radiograph. 60% (12/20) of the patients received immunosuppressive treatment. The overall survival at 5 years was 92% (95% CI 57-99). Conclusion: Sarcoidosis is a disease of young patients with a slight predominance in men. Pulmonary involvement is the most frequent, followed by mediastinal nodal involvement. Most patients received steroid treatment at some time in their life. The long-term survival of the disease is more than 90%, which indicates its benign course. References: [1]Iannuzzi MC, Rybicki BA, Teirstein AS. Sarcoidosis.N Engl J Med. 2007 Nov 22;357(21):2153-65. [2]Arkema EV, Grunewald J, Kullberg S, Eklund A, Askling J. Sarcoidosis incidence and prevalence: a nationwide register-based assessment in Sweden. Eur Respir J 2016; 48: 1690–1699. Acknowledgments: Not aply Disclosure of Interests: None declared
Abstract 15698: Driving Restrictions Following Defibrillator Implantation: The Patient’s Perspective
Authors: Jenny Bjerre, Simone R Mørk, Anne Mielke, Morten Schou, Christian Jons, Gunnar Gislason, Anne-Christine Ruwald
Journal: Circulation (2017)

Background: Following Implantable Cardioverter Defibrillator (ICD) implantation and after appropriate ICD therapy, patients are temporarily restricted from driving. However, little is known about h...
Ultrafast three-dimensional microbubble imaging <i>in vivo</i> predicts tissue damage volume distributions during nonthermal brain ablation
Authors: Ryan M. Jones, Dallan McMahon, Kullervo Hynynen
Journal: Theranostics (2020)

Transcranial magnetic resonance imaging (MRI)-guided focused ultrasound (FUS) thermal ablation is under clinical investigation for non-invasive neurosurgery, though its use is restricted to central brain targets due primarily to skull heating effects.The combination of FUS and contrast agent microbubbles greatly reduces the ultrasound exposure levels needed to ablate brain tissue and may help facilitate the use of transcranial FUS ablation throughout the brain.However, sources of variability exist during microbubble-mediated FUS procedures that necessitate the continued development of systems and methods for online treatment monitoring and control, to ensure that excessive and/or off-target bioeffects are not induced from the exposures.Methods: Megahertz-rate three-dimensional (3D) microbubble imaging in vivo was performed during nonthermal ablation in rabbit brain using a clinical-scale prototype transmit/receive hemispherical phased array system.Results: In-vivo volumetric acoustic imaging over microsecond timescales uncovered spatiotemporal microbubble dynamics hidden by conventional whole-burst temporal averaging.Sonication-aggregate ultrafast 3D source field intensity data were predictive of microbubble-mediated tissue damage volume distributions measured post-treatment using MRI and confirmed via histopathology.Temporal under-sampling of acoustic emissions, which is common practice in the field, was found to impede performance and highlighted the importance of capturing adequate data for treatment monitoring and control purposes. Conclusion:The predictive capability of ultrafast 3D microbubble imaging, reported here for the first time, will enable future microbubble-mediated FUS treatments with unparalleled precision and accuracy, and will accelerate the clinical translation of nonthermal tissue ablation procedures both in the brain and throughout the body.
Five-year Survival Prediction and Safety Outcomes with Enzalutamide in Men with Chemotherapy-naïve Metastatic Castration-resistant Prostate Cancer from the PREVAIL Trial
Authors: Andrew J. Armstrong, Ping Lin, Bertrand Tombal, Fred Saad, Celestia S. Higano, Anthony M. Joshua, Teresa Parli, Brad Rosbrook, Steve van Os, Tomasz M. Beer
Journal: European Urology (2020)

In the PREVAIL study, enzalutamide significantly improved clinical outcomes versus placebo in patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC).To evaluate long-term benefits and risks of enzalutamide in the final prespecified PREVAIL analysis.We conducted a final 5-yr survival analysis of PREVAIL in men with chemotherapy-naïve mCRPC from the enzalutamide (n = 689) and placebo (n = 693) arms.Predictors of the primary outcome of overall survival were estimated using the Kaplan-Meier method. Long-term adverse events over time were analyzed.At the 5-yr data cutoff, 1382 of 1717 (80%) men had died. Enzalutamide reduced the hazard of death by 17% (hazard ratio 0.83; 95% confidence interval [CI] 0.75-0.93; p < 0.001), despite 65%, 54%, and 43% of placebo-treated patients receiving subsequent docetaxel, abiraterone, and enzalutamide, respectively. Median overall survival was 36 mo (95% CI 34-38) in the enzalutamide arm versus 31 mo (95% CI 29-34) in the placebo arm, with a median follow-up of 69 mo. Prognostic modeling showed 5-yr survival rates of 42%, 24%, and 5% for low-, intermediate-, and high-risk groups, respectively. Greater degrees of confirmed prostate-specific antigen declines (≤3 mo) were associated with greater 5-yr survival. A higher incidence of fatal treatment-emergent adverse events was observed with enzalutamide (6.9% vs 3.8%), with an increase in fatal cardiovascular events (1.6% vs 0.4%).With >5 yr of follow-up, enzalutamide continued to demonstrate improved survival in patients with mCRPC despite crossover and multiple subsequent effective therapies, balanced against a slightly higher rate of fatal cardiovascular events. PREVAIL is registered on ClinicalTrials.gov as NCT01212991.We report a maintained long-term survival benefit with enzalutamide and risks with >5 yr of enzalutamide treatment and follow-up in men with metastatic prostate cancer, and identify groups of men with widely different outcomes based on clinical factors.
Effect of echoendoscope angle on success of guidewire manipulation during endoscopic ultrasound-guided hepaticogastrostomy
Authors: Takeshi Ogura, Nobu Nishioka, Saori Ueno, Tadahiro Yamada, Masanori Yamada, Akira Imoto, Akitoshi Hakoda, Kazuhide Higuchi
Journal: Endoscopy (2020)

Background With endoscopic ultrasound-guided hepaticogastrostomy (EUS-HGS), guidewire manipulation might be a critically limiting step for nonexperts. However, the causes of difficult guidewire manipulation remain unclear. The aim of this study was to evaluate factors associated with successful guidewire manipulation. Methods This retrospective cohort study included consecutive patients who underwent EUS-HGS between October 2018 and October 2019. We measured scope angle between the long and needle axes of the echoendoscope using still fluoroscopic imaging immediately after puncturing the intrahepatic bile duct. Factors associated with successful guidewire insertion were assessed by multivariable analysis using logistic regression. Result The influence of the angle between the fine-needle aspiration (FNA) needle and echoendoscope on failed guidewire insertion was assessed using receiver operating characteristic (ROC) curves. Area under the ROC curve was 0.86 (95 % confidence interval [CI] 0.00 – 0.76), and an angle of 135° offered 88.0 % sensitivity and 82.9 % specificity for predicting successful guidewire insertion. According to multivariable analysis, only angle between the FNA needle and echoendoscope &gt; 135° was independently associated with successful guidewire insertion (odd ratio 0.03, 95 %CI 0.01 – 0.14; P &lt; 0.05), whereas sex, puncture site, and diameter of puncture site were not significant factors. After multivariable analysis, all variables were adjusted using age ≥ 70 or &lt; 70 years, yielding the same results. Conclusion The angle between the FNA needle and echoendoscope might be associated with successful guidewire manipulation during EUS-HGS. Adjusting this angle to 135° before puncturing the intrahepatic bile duct might be helpful in achieving successful guidewire manipulation during EUS-HGS.
Megakaryocyte TGFβ1 partitions erythropoiesis into immature progenitor/stem cells and maturing precursors
Authors: Silvana Di Giandomenico, Pouneh Kermani, Nicole Mollé, Maria Mia Yabut, Ghaith Abu-Zeinah, Thomas Stephens, Nassima Messali, Ryan Schreiner, Fabienne Brenet, Shahin Rafii, Joseph M. Scandura
Journal: Blood (2020)
Diabetes and COVID-19: Risks, Management, and Learnings From Other National Disasters
Authors: Jamie Hartmann-Boyce, Elizabeth Morris, Clare Goyder, Jade Kinton, James Perring, David Nunan, Kamal Mahtani, John B. Buse, Stefano Del Prato, Linong Ji, Ronan Roussel, Kamlesh Khunti
Journal: Diabetes Care (2020)

Evidence relating to the impact of COVID-19 in people with diabetes (PWD) is limited but continuing to emerge. PWD appear to be at increased risk of more severe COVID-19 infection, though evidence quantifying the risk is highly uncertain. The extent to which clinical and demographic factors moderate this relationship is unclear, though signals are emerging that link higher BMI and higher HbA1c to worse outcomes in PWD with COVID-19. As well as posing direct immediate risks to PWD, COVID-19 also risks contributing to worse diabetes outcomes due to disruptions caused by the pandemic, including stress and changes to routine care, diet, and physical activity. Countries have used various strategies to support PWD during this pandemic. There is a high potential for COVID-19 to exacerbate existing health disparities, and research and practice guidelines need to take this into account. Evidence on the management of long-term conditions during national emergencies suggests various ways to mitigate the risks presented by these events.
Covid-19: Government will belatedly publish recommendations for protecting ethnic minorities
Authors: Gareth Iacobucci
Journal: BMJ (2020)

The UK government will belatedly publish recommendations for protecting minority ethnic groups from covid-19, amid claims that parliament was misled about the existence of additional material produced alongside a much criticised1 review by Public Health England (PHE).

The announcement came after Raj Bhopal, a professor of public health at Edinburgh University, told BBC News 2 that proposals to safeguard ethnic minorities were laid out in a separate 64 page document that PHE asked him to review four days before it published its main report on 2 June.

Bhopal said that the additional document contained recommendations and evidence from 4000 …
Neutrophil-to-Lymphocyte Ratio as a Prognostic Factor of Disease-free Survival in Postnephrectomy High-risk Locoregional Renal Cell Carcinoma: Analysis of the S-TRAC Trial
Authors: Anup Patel, Alain Ravaud, Robert J. Motzer, Allan J. Pantuck, Michael Staehler, Bernard Escudier, Jean-François Martini, Mariajose Lechuga, Xun Lin, Daniel J. George
Journal: Clinical Cancer Research (2020)

In the S-TRAC trial, adjuvant sunitinib improved disease-free survival (DFS) compared with placebo in patients with locoregional renal cell carcinoma (RCC) at high risk of recurrence. This post hoc exploratory analysis investigated the neutrophil-to-lymphocyte ratio (NLR) for predictive and prognostic significance in the RCC adjuvant setting.Kaplan-Meier estimates and Cox proportional analyses were performed on baseline NLR and change from baseline at week 4 to assess their association with DFS. Univariate P values were two-sided and based on an unstratified log-rank test.609 of 615 patients had baseline NLR values; 574 patients had baseline and week 4 values. Sunitinib-treated patients with baseline NLR <3 had longer DFS versus placebo (7.1 vs. 4.7; HR, 0.71; P = 0.02). For baseline NLR ≥3, DFS was similar regardless of treatment (sunitinib 6.8 vs. placebo not reached; HR, 1.03; P = 0.91). A ≥25% NLR decrease at week 4 was associated with longer DFS versus no change (6.8 vs. 5.3 years; HR, 0.71; P = 0.01). A greater proportion of sunitinib-treated patients had ≥25% NLR decrease at week 4 (71.2%) versus placebo (17.4%). Patients with ≥25% NLR decrease at week 4 received a higher median cumulative sunitinib dose (10,137.5 mg) versus no change (8,168.8 mg) or ≥25% increase (6,712.5 mg).In the postnephrectomy high-risk RCC patient cohort, low baseline NLR may help identify those most suitable for adjuvant sunitinib. A ≥25% NLR decrease at week 4 may be an early indicator of those most likely to tolerate treatment and derive DFS benefit.
Abstract 153: Does the Revision of Resuscitation Guidelines Improve the Outcome of In-Hospital Cardiac Arrest?
Authors: Akihiro Miyake, Hiroshi Nonogi, Yoshihisa Fujimoto, Shinsuke Fujiwara, Takaki Naito, Takaya Morooka, Nobuyuki Hatasako, Naoki Tosaka, Hiroyuki Yokoyama, Shigeki Fujitani
Journal: Circulation (2018)

Background: Resuscitation guidelines have been improved every five years using ILCOR international consensus and outcomes for out-of-hospital cardiac arrest improved. However, it remained unknown whether the outcome of in-hospital cardiac arrest has improved. The purpose of this research is to compare the outcomes of multicenter registrations in Japan and to consider the role of rapid response system (RRS). Methods: We compared the two multicenter prospective registrations for adult in-hospital cardiac arrest conducted in Japan. We compared the outcome of Japanese Registry of CPR (J-RCPR,12 hospitals) conducted in the "Guideline 2005" era and Japanese Registry for Survey Of in-hospital Resuscitation Trial (J-RESORT,8 hospitals) conducted in the "Guidelines 2010" era. We searched the number of hospitals participating in the rapid response system multicenter collaborative research (RRS) conducted in Japan. Results: J-RCPR had 491 cases, mean age 71 ± 15 years old, male 63%(311/491), J-RESORT 284 cases, mean age 72 ± 17 years old, male 68%(193/284). ROSC rate was 64.7% (318/491), 77.5% (220/284), respectively (p&lt;0.05). The survival rate after 24 hours was 49.8% (245/491), 50.7% (144/284) (NS), the survival rate after 30 days was 27.8% (137/491), 33.1% (94/284) (NS), and the favorable neurological outcome rate (CPC 1 or CPC 2) was 21.4% (105/491), 22.9% (65/284) (NS), respectively. The proportion of witnessed cardiac arrest was 77.2% (379/491), 81.7% (232/284) (NS), the location of incidence in general wards was 54.0% (265/491), 46.1% (131/284) (NS), and the shockable rhythm was 28.1% (138/491), 22.5% (64/284) (NS), respectively. In both registries, the median interval from the occurrence of cardiac arrest to the initiation of resuscitation was 0 min. The proportion of participating hospitals to RRS was only 6 facilities in 2013 and increased to 41 facilities in 2016, but still less than 1% of the total number of hospitals in Japan. Conclusion: This study showed no improvement in the outcome of in-hospital cardiac arrest and very few hospitals using RRS during the past 10 years. To improve the outcome of the in-hospital cardiac arrest, it is necessary to investigate the nation-wide status of in-hospital cardiac arrest and the effectiveness of RRS.
Novel Hexb-based tools for studying microglia in the CNS
Authors: Takahiro Masuda, Lukas Amann, Roman Sankowski, Ori Staszewski, Maximilian Lenz, Paolo d´Errico, Nicolas Snaidero, Marta Joana Costa Jordão, Chotima Böttcher, Katrin Kierdorf, Steffen Jung, Josef Priller, Thomas Misgeld, Andreas Vlachos, Melanie Meyer-Luehmann, Klaus-Peter Knobeloch, Marco Prinz
Journal: Nature Immunology (2020)
Decreased Neuronal Excitability in Medial Prefrontal Cortex during Morphine Withdrawal is associated with enhanced SK channel activity and upregulation of small GTPase Rac1
Authors: Liang Qu, Yuan Wang, Yang Li, Xin Wang, Nan Li, Shunnan Ge, Jing Wang, Gene-Jack Wang, Nora D. Volkow, Bing Lang, Ping Wang, Hao Wu, Jie Zeng, Jian Fu, Jiaming Li, Yue Zhang, Xuelian Wang
Journal: Theranostics (2020)

Rationale: Neuroadaptations in the medial prefrontal cortex (mPFC) and Nucleus Accumbens (NAc) play a role in the disruption of control-reward circuits in opioid addiction.Small Conductance Calcium-Activated Potassium (SK) channels in the mPFC have been implicated in neuronal excitability changes during morphine withdrawal.However, the mechanism that modulates SK channels during withdrawal is still unknown.Methods: Rats were exposed for one week to daily morphine injections (10 mg•kg -1 s.c.) followed by conditional place preference (CPP) assessment.One week after withdrawal, electrophysiological, morphological and molecular biological methods were applied to investigate the effects of morphine on SK channels in mPFC, including infralimbic (IL), prelimbic (PrL) cortices and NAc (core and shell).We verified the hypothesis that Rac1, a member of Rho family of small GTPases, implicated in SK channel regulation, modulate SK channel neuroadaptations during opiate withdrawal.Results: One week after morphine withdrawal, the neuronal excitability of layer 5 pyramidal neurons in IL was decreased, but not in PrL.Whereas, the excitability was increased in NAc-shell, but not in NAc-core.In mPFC, the expression of the SK3 subunit was enhanced after one-week of withdrawal compared to controls.In the IL, Rac1 signaling was increased during withdrawal, and the Rac1 inhibitor NSC23766 disrupted SK current, which increased neuronal firing.Suppression of Rac1 inhibited morphine-induced CPP and expression of SK channels in IL.Conclusions: These findings highlight the potential value of SK channels and the upstream molecule Rac1, which may throw light on the therapeutic mechanism of neuromodulation treatment for opioid dependence.
Dendritic cells loaded with proliferating autologous tumor cells as patient-specific vaccines in recurrent or metastatic melanoma and renal cell cancer
Authors: Robert O. Dillman, Senthamil R. Selvan, Patric M. Schiltz, Kanoelani Allen, Cheryl Peterson, Cristina De Leon, Carol Depriest, Andrea Beatty, Linda D. Beutel
Journal: Cancer Research (2006)

2886  We are conducting a phase II trial in patients with metastatic or recurrent melanoma (MM) and renal cell carcinoma (RCC) utilizing a vaccine consisting of autologous dendritic cells (DC) loaded with irradiated proliferating autologous tumor cells (TC) that have been exposed to interferon-γ (IFN-γ) to upregulate HLA and possibly tumor antigens. Short-term TC cultures are established to 108, incubated in the presence of 103 U/mL IFN-γ for 72 hrs, then irradiated and cryopreserved in serum-free medium. DC are generated from peripheral blood by incubating in AIM V medium containing GM-CSF (103 U/mL) and IL-4 (103 U/mL) for 7 days. DC and TC are co-incubated overnight, then cryopreserved in aliquots of about 107 cells. Vial contents are suspended in 500 mg GM-CSF for s.c. injection. After a baseline test of delayed-type hypersensitivity (DTH) to an i.d. injection of 106 irradiated TC, patients receive s.c. vaccinations weekly x 3 and monthly x 5. The DTH test against autologous tumor cells is repeated at week 4 (positive DTH defined as > 10 mm induration) and week 24. Between January 2000 and August 2005, TC lines have been established from 104/211 melanoma and 16/27 renal cell patients. This process has taken 2-9 months. Fifty-five patients (47 MM, 8 RCC) have received 388 vaccinations (338 MM, 50 RCC); 39 patients have completed the entire treatment course (34 MM, 5 RCC). At this time there is one unconfirmed objective response among patients who had measurable disease at the time vaccine therapy was initiated (0/14 MM, 1/6 RCC). The vaccine has been well tolerated except for mild erythema reactions at the injection site, and anaphylactoid-like reactions in two patients. Only one patient exhibited a weak (5mm-9mm) DTH reaction at baseline, while 9/55 have had a weak or >10mm reaction at week 4 or week 24 (7/47 MM, 2/8 RCC). These 55 patients have been followed from 1.3 to 54.2 months. There have been 15 deaths, 8 within one year of starting the vaccine. The median survival has been reached; at the median follow-up since starting treatment of 19.5 months, the survival rate is 71%. Median event-free survival (lack of death or disease progression) is 7.1 months. One patient remains alive with no evidence of disease more than 4 years after presenting with lung and brain metastases, and progressing in the brain and adrenal gland within 8 months of diagnosis despite aggressive biotherapy and chemotherapy before starting the vaccine. This patient-specific DC/autologous TC vaccine is feasible and well tolerated, and the survival rates are encouraging. Accrual of patients with metastatic RCC continues.
Integrated transcriptomic and genomic analysis improves prediction of complete remission and survival in elderly patients with acute myeloid leukemia
Authors: Albin Österroos, My Björklund, Anna Eriksson, Johan Lindberg, Christer Nilsson, Sylvain Mareschal, Mattias Rantalainen, Henrik Grönberg, Sören Lehmann
Journal: Blood Cancer Journal (2020)

Abstract Relevant molecular tools for treatment stratification of patients ≥65 years with acute myeloid leukemia (AML) are lacking. We combined clinical data with targeted DNA- and full RNA-sequencing of 182 intensively and palliatively treated patients to predict complete remission (CR) and survival in AML patients ≥65 years. Intensively treated patients with NPM1 and IDH2 R172 mutations had longer overall survival (OS), whereas mutated TP53 conferred lower CR rates and shorter OS. FLT3-ITD and TP53 mutations predicted worse OS in palliatively treated patients. Gene expression levels most predictive of CR were combined with somatic mutations for an integrated risk stratification that we externally validated using the beatAML cohort. We defined a high-risk group with a CR rate of 20% in patients with mutated TP53 , compared to 97% CR in low-risk patients defined by high expression of ZBTB7A and EEPD1 without TP53 mutations. Patients without these criteria had a CR rate of 54% (intermediate risk). The difference in CR rates translated into significant OS differences that outperformed ELN stratification for OS prediction. The results suggest that an integrated molecular risk stratification can improve prediction of CR and OS and could be used to guide treatment in elderly AML patients.