tbuckley/cabot-search huggingface dataset:
Marked factor V activity elevation in severe <scp>COVID</scp>‐19 is associated with venous thromboembolism
Authors: Jonathan A. Stefely, Bianca B. Christensen, Tasos Gogakos, Jensyn K. Cone Sullivan, Gabriella G. Montgomery, John P. Barranco, Elizabeth M. Van Cott
Journal: American Journal of Hematology (2020)

Coagulopathy causes morbidity and mortality in patients with coronavirus disease 2019 (COVID-19) due to severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. Yet, the mechanisms are unclear and biomarkers are limited. Early in the pandemic, we observed markedly elevated factor V activity in a patient with COVID-19, which led us to measure factor V, VIII, and X activity in a cohort of 102 consecutive inpatients with COVID-19. Contemporaneous SARS-CoV-2-negative controls (n = 17) and historical pre-pandemic controls (n = 260-478) were also analyzed. This cohort represents severe COVID-19 with high rates of ventilator use (92%), line clots (47%), deep vein thrombosis or pulmonary embolism (DVT/PE) (23%), and mortality (22%). Factor V activity was significantly elevated in COVID-19 (median 150 IU/dL, range 34-248 IU/dL) compared to contemporaneous controls (median 105 IU/dL, range 22-161 IU/dL) (P < .001)-the strongest association with COVID-19 of any parameter studied, including factor VIII, fibrinogen, and D-dimer. Patients with COVID-19 and factor V activity >150 IU/dL exhibited significantly higher rates of DVT/PE (16/49, 33%) compared to those with factor V activity ≤150 IU/dL (7/53, 13%) (P = .03). Within this severe COVID-19 cohort, factor V activity associated with SARS-CoV-2 load in a sex-dependent manner. Subsequent decreases in factor V were linked to progression toward DIC and mortality. Together, these data reveal marked perturbations of factor V activity in severe COVID-19, provide links to SARS-CoV-2 disease biology and clinical outcomes, and nominate a candidate biomarker to investigate for guiding anticoagulation therapy in COVID-19.
Neurofilament light as an outcome predictor after cardiac arrest: a post hoc analysis of the COMACARE trial
Authors: Lauri Wihersaari, Nicholas J. Ashton, Matti Reinikainen, Pekka Jakkula, Ville Pettilä, Johanna Hästbacka, Marjaana Tiainen, Pekka Loisa, Hans Friberg, Tobias Cronberg, Kaj Blennow, Henrik Zetterberg, Markus B. Skrifvars, Raili Laru-Sompa, Anni Pulkkinen, Mikko Reilama, Sinikka Tolmunen, Minna Bäcklund, Jonna Heinonen, Johanna Hästbacka, Pekka Jakkula, Nina Lundbom, Marcus Norrgård, Marjatta Okkonen, Ville Pettilä, Markus B. Skrifvars, Tarja Suhonen, Marjaana Tiainen, Tuukka Tikka, Marjut Timonen, Jussi Toppila, Miia Valkonen, Erika Wilkman, Teemu Hult, Tuomas Oksanen, Stepani Bendel, Elina Halonen, Sari Rahikainen, Saija Rissanen, Eija Vaskelainen, Tanja Eiserbeck, Sirkku Heino, Helena Jyrkönen, Matti Reinikainen, Johanna Räsänen, Tero Surakka, Talvikki Koskue, Petteri Kujala, Pekka Loisa, Marika Lähde, Jari Kalliomäki, Sari Karlsson, Atte Kukkurainen, Simo Varila
Journal: Intensive Care Medicine (2020)

Neurofilament light (NfL) is a biomarker reflecting neurodegeneration and acute neuronal injury, and an increase is found following hypoxic brain damage. We assessed the ability of plasma NfL to predict outcome in comatose patients after out-of-hospital cardiac arrest (OHCA). We also compared plasma NfL concentrations between patients treated with two different targets of arterial carbon dioxide tension (PaCO2), arterial oxygen tension (PaO2), and mean arterial pressure (MAP). We measured NfL concentrations in plasma obtained at intensive care unit admission and at 24, 48, and 72 h after OHCA. We assessed neurological outcome at 6 months and defined a good outcome as Cerebral Performance Category (CPC) 1–2 and poor outcome as CPC 3–5. Six-month outcome was good in 73/112 (65%) patients. Forty-eight hours after OHCA, the median NfL concentration was 19 (interquartile range [IQR] 11–31) pg/ml in patients with good outcome and 2343 (587–5829) pg/ml in those with poor outcome, p < 0.001. NfL predicted poor outcome with an area under the receiver operating characteristic curve (AUROC) of 0.98 (95% confidence interval [CI] 0.97–1.00) at 24 h, 0.98 (0.97–1.00) at 48 h, and 0.98 (0.95–1.00) at 72 h. NfL concentrations were lower in the higher MAP (80–100 mmHg) group than in the lower MAP (65–75 mmHg) group at 48 h (median, 23 vs. 43 pg/ml, p = 0.04). PaCO2 and PaO2 targets did not associate with NfL levels. NfL demonstrated excellent prognostic accuracy after OHCA. Higher MAP was associated with lower NfL concentrations.
A machine-learning algorithm for neonatal seizure recognition: a multicentre, randomised, controlled trial
Authors: Andreea M Pavel, Janet M Rennie, Linda S de Vries, Mats Blennow, Adrienne Foran, Divyen K Shah, Ronit M Pressler, Olga Kapellou, Eugene M Dempsey, Sean R Mathieson, Elena Pavlidis, Alexander C van Huffelen, Vicki Livingstone, Mona C Toet, Lauren C Weeke, Mikael Finder, Subhabrata Mitra, Deirdre M Murray, William P Marnane, Geraldine B Boylan
Journal: The Lancet Child & Adolescent Health (2020)

Despite the availability of continuous conventional electroencephalography (cEEG), accurate diagnosis of neonatal seizures is challenging in clinical practice. Algorithms for decision support in the recognition of neonatal seizures could improve detection. We aimed to assess the diagnostic accuracy of an automated seizure detection algorithm called Algorithm for Neonatal Seizure Recognition (ANSeR).
Sy-1365, a Potent and Selective CDK7 Inhibitor, Exhibits Anti-Tumor Activity in Preclinical Models of Hematologic Malignancies, and Demonstrates Interactions with the BCL-XL/BCL2 Mitochondrial Apoptosis Signaling Pathway in Leukemia
Authors: Graeme Hodgson, Liv Johannessen, Nisha Rajagopal, Shanhu Hu, David Orlando, Matthew Eaton, Michael McKeown, Jeffrey W. Tyner, Stephen E Kurtz, Kevin Sprott, Christian Fritz, Emmanuelle Di Tomaso
Journal: Blood (2017)
Abstract 10968: Neuroprotectin D1 Induces Protection After Brain Ischemic Injury in a Mouse Stroke Model by Blocking Mitochondria-mediated Cell Death Pathways
Authors: Hylde Zirpoli, Sergey A Sosunov, Zoya V Niatsetskaya, Korapat Mayurasakorn, Denny Joseph Manual Kollareth, Paul C Norris, Charles N Serhan, Vadim S Ten, Richard J Deckelbaum
Journal: Circulation (2019)

Introduction: Neonatal hypoxic-ischemic (HI) brain injury is a major cause of mortality and morbidity in newborn infants. Neurons may undergo apoptosis in the ischemic area and the penumbra zone af...
Culmination of MG132-induced apoptosis in human lung cancer NCI-H1703 cells depends on a positive feedback of caspase activation and Mcl-1 cleavage
Authors: Bao-Zhu Yuan, Joshua Chapman, Steven Reynolds
Journal: Cancer Research (2008)

3352  Non-small cell lung carcinoma (NSCLC) is the leading cause of cancer death in both men and women in the United States. NSCLC is caused by cigarette smoking as well as occupational and environmental carcinogens. The low sensitivity of NSCLCs, especially in late stage, to different therapeutic modalities requires development of new treatments for this malignancy. Proteasome inhibitors (PIs) have become a rising hope for treating different types of human cancer which are refractory to currently available chemotherapies. Induction of apoptosis via caspase activation is believed to be the major mechanism of PIs’ ability to kill cancer cells. To investigate mechanisms of action of PIs in treating NSCLCs, we treated NCI-H1703, a human NSCLC cell line, with MG132, the most commonly used proteasome inhibitor. It was observed that MG132 concentrations of greater than 0.25 μM caused a significant apoptosis as evidenced by DNA damage, cleavage of caspases 3, 7, 9, 10, Bid and PARP, and mitochondrial release of Smac/DIABLO and Cytochrome c. Among the antiapoptotic Bcl-2 family proteins tested, Bcl-2 and Bcl-XL exhibited no response to MG132 treatment while Mcl-1 showed an increase in protein level to low dose MG132 (0.25 μM) and a decrease in protein level to higher dose MG132 (>0.25 μM). MG132-induced apoptosis was inhibited by over-expression of Bcl-XL, but not by dominant negative FADD, the mediator of death receptor-initiated apoptosis, suggesting that MG132-induced apoptosis is initiated by activation of the mitochondrial pathway. Mcl-1 siRNA enhanced MG132-induced apoptosis, demonstrating that Mcl-1 is a major inhibitor the apoptosis induction. Inhibition of caspases 3 and 9 by either specific caspase inhibitors or corresponding siRNAs inhibited MG132-induced apoptosis and PARP cleavage. It also inhibited cleavage of caspase 10 and Bid, mitochondrial release of Smac/DIABLO and reduction of Mcl-1 to higher dosages of MG132, suggesting the existence of a positive feedback in caspase activation by the initially activated caspases 3 and 9, which leads to further activation of caspases 3 and 9 through caspase 10 and the mitrochondria. The over-activated casapase 3 then subsequently resulted in Mcl-1 cleavage. The note of positive feedback is supported by an observation on the kinetics of changes of all relevant proteins in which cleavage of both caspase 10 and Mcl-1 were found to be late events. Furthermore, in agreement with this note, over-expression of a short form of Mcl-1, equivalent to Mcl-1’s cleavage product, significantly enhanced apoptosis induced by low dose MG132. Collectively, this study demonstrates that culmination of MG132-induced apoptosis depends on a positive feedback for an enhanced caspase activation which converts Mcl-1 from an anti-apoptotic protein into a proapoptotic protein.
Lung Diseases Affecting US Workers Cost Billions Annually
Authors: Bridget M. Kuehn
Journal: JAMA (2020)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
Effect of chemotherapy on the risk of erlotinib-induced skin rash in cancer patients: A meta-analysis
Authors: Y. Jia, M. E. Lacouture, X. Su, S. Wu
Journal: Journal of Clinical Oncology (2009)

9573 Background: Erlotinib, an inhibitor of epidermal growth factor receptor (EGFR) tyrosine kinase, is effective in the treatment of non-small cell lung cancer (NSCLC) as a single agent and pancreatic cancer when combined with chemotherapy. Its application in other types of cancer is also undergoing extensive clinical assessment. Skin rash is a major side effect of erlotinib. This study aims to gain a better understanding of skin toxicity with erlotinib through a systematic review and meta-analysis of randomized controlled clinical trials. Methods: Relevant studies were identified from Medline (1966 to October 2008), Web of Science, and abstracts presented at the American Society of Clinical Oncology Conferences between January, 2004 and October, 2008. Eligible studies included prospective randomized controlled clinical trials in which cancer patients were treated with erlotinib at 150 mg daily as single agent or in combination with other agents. Incidence, relative risk (RR), and 95% confidence intervals were calculated using random-effects or fixed-effects models based on the heterogeneity of included studies. Results: A total of 3,562 patients with a variety of solid tumors from 12 randomized controlled clinical trials were included for analysis. The overall incidence of all-grade skin rash associated with erlotinib was 68.7% (95% CI: 63.0–73.8%) with 8.9% (95% CI: 7.7–10.3%) being high-grade (grade 3 or above). There was a significantly increased risk of skin toxicity with erlotinib in comparison with controls (all-grade: RR 3.1, 95% CI: 2.2–4.3, p &lt; 0.001; high-grade: RR 10.1, 95% CI: 5.5–18.5, p &lt; 0.001). Interestingly, chemotherapy may decrease the risk of skin rash associated with erlotinib. RR of all-grade skin rash was 4.7 (95% CI: 3.6–6.2) for single-agent erlotinib and 2.3 (95% CI: 2.0–2.7) for erlotinib in combination with chemotherapy; RR of high-grade skin rash was 17.3 (95% CI: 3.3–90.5) for single-agent erlotinib and 9.3 (95% CI: 4.8–17.8) for erlotinib in combination. Conclusions: Erlotinib was associated with significantly increased risk of skin toxicity among cancer patients. Its combination with chemotherapy may decrease the risk of skin rashes. No significant financial relationships to disclose.
Treatment of latent M. tuberculosis infection and use of antiretroviral therapy to prevent tuberculosis
Authors: Timothy R. Sterling, Philana Ling Lin
Journal: Journal of Clinical Investigation (2020)

Even with treatment of HIV with antiretroviral therapy (ART), the risk of tuberculosis (TB) reactivation remains higher in HIV-infected than HIV-uninfected persons. In this issue of the JCI, Ganatra et al. explored TB reactivation in the context of ART using TB and simian immunodeficiency virus-coinfected (TB/SIV-coinfected) nonhuman primates. The authors found that treating rhesus macaques with ART restored CD4+ T cells in whole blood, spleen, and bronchoalveolar lavage (BAL) fluid, but not in the lung interstitium. TB risk was not decreased in the coinfected macaques treated with ART for 14-63 days, suggesting that ART does not decrease the short-term risk of reactivation. Reactivation occurred as CD4+ T cells were increasing, which is consistent with observations made in humans. This study provides a potential model for systematic evaluation of TB/SIV coinfection and different treatment regimens and strategies to prevent TB reactivation.
SAT0228 The frequency and outcome of carditis in acute rheumatec fever
Authors: B Heidari
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> In spite of rarity in many areas, acute rheumatic fever (ARF) continues to be one of the most causes of valvular heart disease in the developing countries. Persistence of residual heart disease depends on the severity of carditis at the time of acute attack and the frequency of subsequent recurrences. <h3>Objectives</h3> To determine the frequency and the outcome of carditis in ARF, medical records of patients with ARF diagnosed in Shaheed Beheshti hospital from 1985–1990 were reviewed. <h3>Methods</h3> All admitted and referral patients satisfying the modified Jones criteria for the diagnosis of ARF with follow up period over than one year included the study. Diagnosis of carditis was based on physical findings and auscultation. Presence of residual heart disease was confirmed by clinical exminations during the follow up period and at the time of the last visit. In a few patients echocardiography was performed to document the valvular lesion. <h3>Results</h3> 38 (19 Male, 19 female) patients with median age of 14.5 years (range 5–36) were studied. All patients presented with polyarthritis. Carditis occured in 14 (37%) patients. Mitral regurgitation alone in 10, and in combination with aortic regurgitation and stenosis in 2, aortic stenosis and regurgitation alone in 2. Secondary prophylaxis (SP) was recommended and patients were followed for a mean period of 6 (range 1–15) years. No recurrences were seen in 22 (56%) patients who remained on SP, whereas 6 of 16 noncompliants with SP showed recurrences. five attacks of recurrences observed in 6 noncompliant patients with carditis. Among the 14 patients with carditis, residual valvular disease persisted in all 5 cases of carditis who had recurrences and 3 of 9 patients without recurrence. <h3>Conclusion</h3> RF remains a significant health problem in the developing countries and disease recurrence is an important risk factor for persistence of residual heart disease, so strict adherence to SP is indicated <h3>References</h3> David L. Diagnosis and treatment of rheumnatic fever. Arch Pediatre. 1998;5:681–6 Abbag F, Benjamin B, Kardosh MM, Al-Barki A. Acute rheumatic fever in southern saudi arabia. East Afr Med J. 1998;75:279–81 Richmond P, Harris L. Rheumatic fever in the Kinberley region of Western Australia. J Trop Pediatr. 1998;44:148–52 American Heart Association. Jnes criteria (revised) for guidance in the diagnosis of rhumatic fever. Circulation 1984;69:204A–208A
Implementation science and periodontal practice: Translation of evidence into periodontology
Authors: Julie Frantsve‐Hawley, Satish S. Kumar, D. Brad Rindal, Robert J. Weyant
Journal: Periodontology 2000 (2020)

Abstract The advent of evidence‐based practice in the 1990s led to the development of processes and resources to support the use of high‐quality research in the provision of health care. As the evidence‐based approach to health care continues to evolve, it has become apparent that mere creation and access to scientific knowledge is not sufficient to facilitate its routine adoption in health care. Throughout any health care system, there are inherent barriers preventing the adoption and routine use of new evidence in patient care. These barriers include provider‐level factors, such as knowledge and access to new evidence, as well as each provider's attitudes and beliefs around adopting and applying the evidence with their patients. Importantly, there are also health care system‐level barriers that, even among willing providers, prevent the easy adoption of new evidence and routine application in patient care. In addition to barriers, there are facilitators that help promote adoption of evidence into practice. Understanding and addressing barriers and facilitators to promote adoption of evidence into practice has led to the growth of a new field known as implementation science. Successful application of implementation science in all areas of health care, including periodontology, will help bridge the gap between what are known from clinical research to be effective treatments and what treatments should be applied routinely in clinical practice. This article reviews key concepts in implementation science and how its application in periodontology can facilitate the translation of high‐quality evidence into routine periodontal practice and improved patient outcomes.
FRI0229 Hla antigens’ frequencies in spanish patients with primary sjögren syndrome
Authors: C Fernández-Carballido, JJ Alegre-Sancho, JA Román-Ivorra, S Fernández, L Abad, N Puig
Journal: Annals of the Rheumatic Diseases (2001)

<h3>Background</h3> There are few data about HLA antigens' frequencies in Spanish patients with Primary Sjögren Syndrome (PSS). <h3>Objectives</h3> To evaluate HLA antigens' prevalence in patients with PSS and compare these frequencies with a control population. <h3>Methods</h3> 113 patients with PSS from a Mediterranean city (Valencia, Spain) were consecutively selected. All patients fulfilled 4 or more EEC criteria; 82 fulfilled modified-EEC criteria. HLA serologic typing was carried out and the frequencies obtained in PSS patients were compared with the control population's frequencies (236 healthy blood donnors from the same city). <h3>Results</h3> The antigens' prevalences of PSS patients significatively different from the control group were: <h3>Conclusion</h3> Some HLA antigens in our PSS patients are different from those described in other Mediterranean areas. In our population HLA DR2, DR3 and DR4 are associated with PSS; without differences in DR5 frequencies (Greek population). Moreover, HLA DR7 acts as a protective factor for this disease.
Severe respiratory viral infection induces procalcitonin in the absence of bacterial pneumonia
Authors: Samir Gautam, Avi J Cohen, Yannick Stahl, Patricia Valda Toro, Grant M Young, Rupak Datta, Xiting Yan, Nicholas T Ristic, Santos D Bermejo, Lokesh Sharma, Marcos I Restrepo, Charles S Dela Cruz
Journal: Thorax (2020)

Introduction Procalcitonin expression is thought to be stimulated by bacteria and suppressed by viruses via interferon signalling. Consequently, during respiratory viral illness, clinicians often interpret elevated procalcitonin as evidence of bacterial coinfection, prompting antibiotic administration. We sought to evaluate the validity of this practice and the underlying assumption that viral infection inhibits procalcitonin synthesis. Methods We conducted a retrospective cohort study of patients hospitalised with pure viral infection (n=2075) versus bacterial coinfection (n=179). The ability of procalcitonin to distinguish these groups was assessed. In addition, procalcitonin and interferon gene expression were evaluated in murine and cellular models of influenza infection. Results Patients with bacterial coinfection had higher procalcitonin than those with pure viral infection, but also more severe disease and higher mortality (p&lt;0.001). After matching for severity, the specificity of procalcitonin for bacterial coinfection dropped substantially, from 72% to 61%. In fact, receiver operating characteristic curve analysis showed that procalcitonin was a better indicator of multiple indices of severity (eg, organ failures and mortality) than of coinfection. Accordingly, patients with severe viral infection had elevated procalcitonin. In murine and cellular models of influenza infection, procalcitonin was also elevated despite bacteriologic sterility and correlated with markers of severity. Interferon signalling did not abrogate procalcitonin synthesis. Discussion These studies reveal that procalcitonin rises during pure viral infection in proportion to disease severity and is not suppressed by interferon signalling, in contrast to prior models of procalcitonin regulation. Applied clinically, our data suggest that procalcitonin represents a better indicator of disease severity than bacterial coinfection during viral respiratory infection.
Covid-19: Prime minister agrees to meet bereaved families
Authors: Abi Rimmer
Journal: BMJ (2020)

Boris Johnson has said that he will meet with bereaved families who have lost loved ones to covid-19.

In what seemed to be a u-turn on his previous stance, the prime minister, speaking to Sky News on 26 August, said that he would reply to letters from bereaved families.1

The news comes after Layla Moran, chair of the all party parliamentary group (APPG) on coronavirus and Liberal Democrat member of parliament for Oxford West and Abingdon, wrote to Johnson on 24 August urging him to meet with families.

“The APPG was shocked to learn that, despite …