Corpus overview


MeSH Disease

Human Phenotype


    displaying 1 - 10 records in total 16
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    Design and rationale of a randomized, double-blind, placebo-controlled, Phase 2/3 study to evaluate the safety and efficacy of dociparstat sodium (DSTAT) in adults TRANS with acute lung injury MESHD associated with severe COVID-19

    Authors: Joseph A. Lasky; Jyotsna Fuloria; Marion E. Morrison; Randall Lanier; Odin Naderer; Tom Brundage; Allen Melemed

    doi:10.21203/ Date: 2020-08-01 Source: ResearchSquare

    Background: The COVID-19 Global Pandemic caused by the novel coronavirus, SARS-CoV-2, and the consequent morbidity and mortality attributable to progressive hypoxemia HP and subsequent respiratory failure HP, threaten to overrun hospital critical care units globally. New agents that can address the hyperinflammatory “cytokine storm” and hypercoagulable pathology seen in these patients may be a promising approach to treat patients, minimize hospital stays, and ensure hospital wards and critical care units are able to operate effectively.  Dociparstat sodium (DSTAT) is a glycosaminoglycan derivative of heparin with robust anti-inflammatory properties, including the potential to address underlying causes of coagulation disorders with substantially reduced risk of bleeding complications compared to commercially available forms of heparin. Methods: This study is a randomized, double-blind, placebo-controlled, Phase 2/3 trial to determine the safety and efficacy of DSTAT added to standard of care versus placebo, in adults TRANS with COVID-19 who require hospitalization and supplemental oxygen therapy. The Phase 2 portion will enroll 12 participants in each of two dose escalating cohorts, to confirm the safety of DSTAT in this population. Following a data monitoring committee review of the data, an additional 50 participants will be enrolled. Contingent upon positive results, the Phase 3 portion of the study will enroll approximately 450 participants randomized 1:1 to DSTAT or placebo. The primary endpoint, agreed on by the US FDA, is the proportion of participants who survive and do not require mechanical ventilation through day 28. Discussion: Advances in standard of care regimens and the recent emergency MESHD use authorization of remdesivir and positive data with dexamethasone, has likely contributed to an increasing proportion of patients who are surviving without the need for mechanical ventilation. Therefore, examining the time to improvement of NIAID score will be essential to provide a more continuous measure of drug effect on recovery. Additional analysis of other endpoints, including supportive biomarkers (e.g., IL-6, HMGB1, soluble RAGE, D-dimer) will be performed at the conclusion of Phase 2 to further define the effect of DSTAT in patients hospitalized with COVID-19 infection MESHD. Trial Registration: identifier NCT04389840, Registered 13 May 2020,

    Mortality rate among critically ill patients with COVID-19 in a medical system with adequate hospital resources: a prospective observational study

    Authors: Christina Routsi; Eleni Magira; Stelios Kokkoris; Ilias Siembos; Charikleia Vrettou; Dimitris Zervakis; Eleni Ischaki; Sotiris Malahias; Ioanna Sigala; Andreas Asimakos; Theodora Daidou; Panagiotis Kaltsas; Evangelia Douka; Adamandia Sotiriou; Vassiliki Markaki; Prodromos Temberikidis; Apostolos Koroneos; Panagiotis Politis; Zafiria Mastora; Efrosini Dima; Theodoros Tsoutsouras; Ioannis Papahatzakis; Panagiota Gioni; Athina Strilakou; Aikaterini Maraguti; Eleftheria Mizi; Ageliki Kanavou; Aikaterini Sarri; Evdokia Gavrielatou; Spyros Mentzelopoulos; Ioannis Kalomenidis; Vassilios Papastamopoulos; Anastasia Kotanidou; Spyros G Zakynthinos

    doi:10.21203/ Date: 2020-08-01 Source: ResearchSquare

    Background: For critically ill patients with coronavirus disease MESHD 2019 (COVID-19) who require intensive care unit (ICU) admission, mortality rates vary widely depending on many factors, among which hospital resources and clinical setting seem important. We sought to determine the outcome of critically ill patients admitted in the usual multidisciplinary ICUs of a big referral for COVID-19 tertiary-care hospital with adequate resources.Methods: We performed a prospective observational study of all adult TRANS patients with COVID-19 consecutively admitted to four COVID-designated ICUs at Evangelismos Hospital, Athens, Greece, from March 11 to April 27, 2020.Results: Among 50 critically ill patients, ICU and hospital mortality for the entire cohort was 32% (16/50), whereas 66% (33/50) of patients were discharged alive from the ICU and 2% (1/50) were still treated in the ICU until June 16, 2020. ICU and hospital mortality for those who received invasive mechanical ventilation was 39% (16/41). Patients who eventually died had already increased risk of death MESHD on ICU admission, as suggested by the high values of the Acute Physiology and Chronic Health Evaluation II and Sequential Organ Failure Assessment scores, the presence of current malignancy and occurrence of cardiac arrest HP in 44% (7/16) of patients, and the general need for circulatory support by noradrenaline. Median PaO2/FiO2 on ICU admission for the entire cohort was 121 mmHg [interquartile range (IQR), 86-171 mmHg] and most patients had moderate and severe acute respiratory distress HP syndrome MESHD (ARDS) according to the Berlin Definition. The primary cause of death MESHD of all patients was multi-organ failure, most commonly due to sepsis MESHD sepsis HP, whereas none died from refractory hypoxemia HP, neurologic dysfunction or withdrawal of life support. Hospital stay was long in patients who survived [median 24 days (IQR, 15-35 days)] and was frequently complicated by bacteremias MESHD bacteremias HP [36% (12/33)].Conclusion: Severely ill COVID-19 patients with moderate and severe ARDS may have equal or even lower mortality rates compared to ARDS due to other causes, when they are admitted in general ICUs with experienced and adequate staff without limitations in hospital resources, where established ARDS therapies are used. 

    Increased expression of hypoxia MESHD-induced factor 1α mRNA and its related genes in myeloid blood SERO cells from critically ill COVID-19 patients

    Authors: Keiko Taniguchi-Ponciano; Eduardo Vadillo; Héctor Mayani; César Raúl Gonzales-Bonilla; Javier Torres; Abraham Majluf; Guillermo Flores-Padilla; Niels Wacher-Rodarte; Juan Carlos Galan; Eduardo Ferat-Osorio; Francisco Blanco-Favela; Constantino Lopez-Macias; Aldo Ferreira-Hermosillo; Claudia Ramirez-Renteria; Eduardo Peña-Martínez; Gloria Silva-Román; Sandra Vela-Patiño; Carlos Mata-Lozano; Roberto Carvente-Garcia; Lourdes Basurto-Acevedo; Renata Saucedo; Patricia Piña-Sanchez; María Antonieta Chavez-Gonzalez; Daniel Marrero-Rodríguez; Moisés Mercado

    doi:10.21203/ Date: 2020-07-15 Source: ResearchSquare

    Since its emergence, in December 2019, COVID-19 has resulted in more than 12 million people infected and has killed more than 570000. Hypoxemia HP has been identified as one of the main clinical manifestations of this disease MESHD, especially in severe cases. We have previously reported that in critically ill COVID-19 patients there is a shift towards an immature myeloid profile in peripheral blood SERO cells, including band neutrophils, immature monocytes, metamyelocytes, monocyte-macrophages, monocytoid precursors, and promyelocytes-myelocytes, which, together with mature monocytes and segmented neutrophils, comprise the vast majority of blood SERO cells in these patients. Such an immature myeloid profile may be the result of a physiological response known as emergency MESHD myelopoiesis. In the present study, we performed scRNAseq from leukocytes from five critically ill COVID-19 patients and characterized the expression of hypoxia MESHD-inducible factor1α (HIF1α) mRNA and its transcriptionally regulated genes. HIF1α is a master transcription factor involved in the cellular response to hypoxia MESHD. We herein report that these cellular subsets express high levels of HIF1α mRNA and several of their transcriptional targets, including those related to inflammation MESHD, such as CXCL8, CXCR1, CXCR2, and CXCR4; those potentially involved  in virus sensing, such as TLR2 and TLR4; and those related to metabolism, such as SLC2A3, PFKFB3, PGK1, GAPDH and SOD2. The up-regulation and participation of HIF1α in relevant events such as inflammation MESHD, immunometabolism, and TLR make it a potential molecular marker for COVID-19 severity and, interestingly, could represent a potential target for molecular therapy. 

    Role of interleukin 6 as a predictive factor for a severe course of Covid-19: retrospective data analysis of patients from a Long-term Care Facility during Covid-19 Outbreak

    Authors: Peter Sabaka; Alena Koščálová; Igor Straka; Julius Hodosy; Robert Lipták; Barbora Kmotorková; Mária Kachlíková; Alica Kušnírová

    doi:10.21203/ Date: 2020-07-13 Source: ResearchSquare

    Background: Covid-19 is a disease MESHD with high morbidity and mortality among elderly TRANS residents of long-term care facilities (LTCF). During an outbreak of SARS-CoV-2 infection MESHD in the LTCF an effective screening tool is essential to identify the patients at risk for severe illness and death MESHD. We explored the role of interleukin 6 (IL-6) as a predictive factor for severe disease MESHD during the outbreak of Covid-19 in one LTCF in Slovakia.Methods: We conducted a retrospective data analysis of all laboratory- confirmed cases TRANS of COVID-19, diagnosed during the outbreak in one LTCF in Slovakia between April 11, 2020, and May 5, 2020. Within 24 hours after the diagnosis of Covid-19, clinical and laboratory screening was performed in the LTCF by trained clinicians to identify patients in need of hospitalization. Patients with oxygen saturation below 90% were immediately referred to the hospital. Patients staying in the LFTC were monitored daily and those that developed hypoxemia HP were transferred to the hospital. We analyzed the association between the level of IL-6 at the initial assessment and development of hypoxemia HP during the course of the disease MESHD and determined the cut-off of the IL-6 able to predict the development of hypoxemia HP requiring oxygen therapy or ventilatory support.Results: Fifty-three patients (11 men, 42 women) with diagnosed Covid-19 were included in the analysis. 19 (53%) patients developed hypoxemia HP during the course of the disease MESHD. Patients with hypoxemia HP had significantly higher concentrations of IL-6 at initial screening. The concentration of IL-6 > 24 pg/mL predicted the development of hypoxemia HP with the sensitivity SERO of 100% and specificity of 88.9%. The positive and negative predictive values SERO were 76.9%, and 100% respectively.Conclusions: The concentration of IL-6 > 24 pg/mL at initial assessment predicted the development of hypoxemia HP requiring hospitalization with excellent sensitivity SERO and good specificity. IL-6 appears as a potential negative predictive factor for the development of the severe form of Covid-19 and might serve for early identification of patients in need of hospitalization. Further studies are needed to evaluate the robustness of the use of IL-6 as an effective screening tool for the severe course of Covid-19.

    Cumulative oxygen deficit is a novel biomarker for the timing of invasive mechanical ventilation in COVID-19 patients with respiratory distress HP: a time-dependent propensity score analysis

    Authors: Huiqing Ge; Jiancang Zhou; Fangfang Lv; Junli Zhang; Jun Yi; Changming Yang; Lingwei Zhang; Yuhan Zhou; Qing Pan; Zhongheng Zhang

    doi:10.21203/ Date: 2020-07-13 Source: ResearchSquare

    Background and objectives: The timing of invasive mechanical ventilation (IMV) is controversial in COVID-19 patients with acute respiratory hypoxemia HP. The study aimed to develop a novel biomarker called cumulative oxygen deficit (COD) for the initiation of IMV.Methods: The study was conducted in four designated hospitals for treating COVID-19 patients in Jingmen, Wuhan, from January to March 2020. COD was defined to account for both the magnitude and duration of hypoxemia HP. A higher value of COD indicated more oxygen deficit. The predictive performance SERO of COD was calculated in multivariable Cox regression models. Time-dependent propensity score matching was performed to explore the effectiveness of IMV versus other non-invasive respiratory supports on survival outcome.Results: A number of 111 patients including 80 in the non-IMV group and 31 in the IMV group were included. Patients with IMV had significantly lower PaO2 (62 (49, 89) vs. 90.5 (68, 125.25) mmHg; p < 0.001), and higher COD (-6.87 (-29.36, 52.38) vs. -231.68 (-1040.78, 119.83)) than patients without IMV. As compared to patients with COD < 0, patients with COD > 30 had higher risk of fatality (HR: 3.79, 95% CI: 2.57 to 16.93; p = 0.037) , and those with COD > 50 were 10 times more likely to die (HR: 10.45, 95% CI: 1.28 to 85.37; p = 0.029). The Cox regression model performed in the time-dependent propensity score matched cohort showed that IMV was associated with half of the hazard of death MESHD than those without IMV (HR: 0.56; 95% CI: 0.16 to 1.93; p = 0.358).Conclusions: The study developed a novel biomarker COD which considered both magnitude and duration of hypoxemia HP, to assist the timing of IMV in patients with COVID-19. We suggest IMV should be the preferred ventilatory support once the COD reaches 30.

    Case Report – Inferior Mesenteric Vein Thrombosis MESHD and COVID-19

    Authors: Aureo do Carmo Filho; Bruno da Silva Cunha

    id:10.20944/preprints202006.0282.v1 Date: 2020-06-21 Source:

    Since its inception in December 2019, Covid-19 has challenged the global scientific community. Some treatments were used in this infection MESHD, but doubts still persist regarding the use of medications 1. More severe cases complicate with endothelial dysfunction, excess thrombin synthesis and decreased fibrinolysis which, associated with hypoxemia HP, lead to a hypercoagulability HP state 2 and some authors indicate the use of anticoagulants for these 3. For mild cases, doubts remain regarding this indication. We will report the case of a patient with mild symptoms of covid-19, complicated by inferior mesenteric vein thrombosis MESHD.

    Management of life-threatening acute respiratory syndrome and severe MESHD pneumonia MESHD pneumonia HP secondary to COVID-19 in pregnancy: a case report and literature review

    Authors: Salwa Yaqoub; Shamsa Ahmad; Zeena Mansoori; Abdulrouf Pallivalapila; Wessam El Kassem; Muna Maslamani; Mahmoud Abu Jubara; Fathima Minisha; Asma Tarannum; Isaac Babarinsa; Ahmed Abdussalam; Hamdy Sayed; Teresa Rivero; Aftab Mohammad; Binny Thomas; Moza Al Hail

    doi:10.21203/ Date: 2020-06-18 Source: ResearchSquare

    BackgroundAs COVID-19 continues to infect women of all gestational ages TRANS; gravida in labor and the acutely ill parturient are particularly at higher risk of infection TRANS risk of infection TRANS infection MESHD. No therapeutic agent or vaccine is approved to treat COVID-19 till date. Thus, managing COVID-19 and associated complications during pregnancy MESHD is often challenging and requires a multidisciplinary approach to treatment. Case PresentationWe narrate our perspectives on managing a 32-year-old, critically ill obstetric patient at 32-week gestation, diagnosed with acute respiratory distress HP syndrome MESHD (ARDS) secondary to COVID-19 pneumonia MESHD pneumonia HP. Upon confirmation of COVID-19, as per the local protocol antivirals, antimalarial, and antibiotics were commenced. Due to rapidly exacerbating maternal respiratory functions, and potential chances of fetal hypoxemia HP emergency MESHD caesarian was performed. Following delivery, the maternal respiratory functions further deteriorated as she required prolonged mechanical ventilation and initiation of extracorporeal membrane oxygenation until she was clinically stable on day 23. The patient also received convalescent plasma SERO and tocilizumab as a part of the treatment protocol. The newborn was shifted to neonatal intensive care for intubation for respiratory distress HP and was found negative for SARS-CoV-2 and COVID-19 immunoglobulin (Ig). At day 25, the patient was clinically stable and was transferred to step down unit and discharged thereafter. Conclusion Through this case, we present the thought process, multidisciplinary team-based strategy and sequel of managing a complex, critically ill obstetric patient with ARDS and COVID-19 pneumonia MESHD pneumonia HP. We anticipate that this case report will assist other healthcare institutions to manage critically ill patients with COVID-19 pneumonia MESHD pneumonia HP.Key words: COVID-19, maternal, pandemic, perinatal, ECMO, convalescent plasma SERO, pharmacological interventions.

    High-Flow Nasal Cannula therapy: A Feasible Treatment in Vulnerable Older COVID-19 Patients on the Wards

    Authors: Job van Steenkiste; Michael C. van Herwerden; Dolf Weller; Christiaan J. van den Bout; Rikje Ruiter; Jan G. den Hollander; Rachida el Moussaoui; Gert T. Verhoeven; Charlotte van Noord; Marinus van den Dorpel

    doi:10.21203/ Date: 2020-06-08 Source: ResearchSquare

    Background: In the midst of the COVID-19 crisis, many frail elderly TRANS were admitted to our hospital with COVID-19. We sought a treatment for those who had severe respiratory failure HP but were not eligible for invasive mechanical ventilation, due to frailty MESHD, functional status, comorbidity or wish of the patient. We started with applying High-flow nasal cannula (HFNC) treatment on the wards.Methods: A retrospective cohort study amongst COVID-19 adult TRANS patients with respiratory failure HP defined as persisting hypoxemia HP despite maximum conventional oxygen administration requiring invasive mechanical ventilation at the Intensive Care Unit (ICU) but being treated with HFNC as they were non-eligible due to frailty MESHD or wish of the patient.Results: We included 32 patients between March 9 and May 1, 2020. The median age TRANS was 79.0 years (74.5-83.0) with a median of three comorbidities (3-4) and a median Clinical Frailty MESHD Score of 4 out of 9 (3-6). The median SPO2/FiO2 Ratio was 157.5 indicating moderate ARDS. Overall survival rate in the HFNC cohort was 25%. Age TRANS (80.5 (78.0-84.3) vs 69.5 (65.5-74.3) p=0.0040) and hypertension MESHD hypertension HP (92% vs 25%, p=0.0008) were associated with mortality.Conclusion: HFNC can be used as a last resort respiratory management strategy in vulnerable elderly TRANS COVID-19 patients in respiratory failure HP on the wards who failed on conventional high dose oxygen supply and are not eligible for invasive mechanical ventilation. 

    In-Ear Measurement of Blood SERO Oxygen Saturation: An Ambulatory Tool Needed To Detect The Delayed Life-Threatening Hypoxaemia in COVID-19

    Authors: Harry J. Davies; Ian Williams; Nicholas S. Peters; Danilo P. Mandic

    id:2006.04231v1 Date: 2020-06-07 Source: arXiv

    Non-invasive ambulatory estimation of blood SERO oxygen saturation has emerged as an important clinical requirement to detect hypoxemia HP in the delayed post-infective phase of COVID-19, where dangerous hypoxia MESHD may occur in the absence of subjective breathlessness. This immediate clinical driver, combined with the general quest for more personalised health data, means that pulse oximetry measurement of capillary oxygen saturation (SpO2) will likely expand into both the clinical and consumer market of wearable health technology in the near future. In this study, we set out to establish the feasibility of SpO2 measurement from the ear canal as a convenient site for long term monitoring, and perform a comprehensive comparison with the right index finger - the conventional clinical measurement site. During resting SpO2 estimation, we found a root mean square difference of 1.47% between the two measurement sites, with a mean difference of 0.23% higher SpO2 in the right ear canal. Through the simultaneous recording of pulse oximetry from both the right ear canal and index finger during breath holds, we observe a substantial improvement in response time between the ear and finger that has a mean of 12.4 seconds and a range of 4.2 - 24.2 seconds across all subjects. Factors which influence this response time, termed SpO2 delay, such as the sex of a subject are also explored. Furthermore, we examine the potential downsides of ear canal blood SERO oxygen saturation measurement, namely the lower photoplethysmogram amplitude, and suggest ways to mitigate this disadvantage. These results are presented in conjunction with previously discovered benefits such as robustness to temperature, making the case for measurement of SpO2 from the ear canal being both convenient and superior to conventional finger measurement sites for continuous non-intrusive long term monitoring in both clinical and everyday-life settings.

    Vascular Obliteration Due To Endothelial And Myointimal Growth In COVID-19

    Authors: Jara Valtueña; Gerardo Martínez-García; Daniel Ruiz-Sánchez; María Garayar-Cantero; Carlos Dueñas; Ángel Aguado-García; Jose María Prieto de Paula; Pilar Manchado López

    doi:10.21203/ Date: 2020-05-28 Source: ResearchSquare

    Background: Severe coronavirus disease MESHD 2019 (Covid-19) is a systemic multi-organ viral invasion. Previous studies found that many patients had a procoagulant state and/or severe hypoxemia HP with relatively well-preserved lung mechanics. Mechanisms underlying the vascular and its surrounding tissue are not well known yet.  Histological data in Covid-19 tissues´ patients are still limited and mainly focused on post-mortem analysis. Since SARS-CoV-2 largely affects cutaneous tissue, we aim to examine in depth skin lesions related to Covid-19 in order to understand better how the disease MESHD might affect living tissue.Methods: Five skin lesions from Covid-19 adult TRANS patients were selected for histological tissue examination. Vast amount of data of immunohistochemistry (IHC) and direct immunofluorescent (DIF) were part of the assessment. Results: A common strong vasculopathic reaction pattern based on prominent vascular endothelial and myointimal cellgrowth was identified. Endothelial cell distortion generated vascular lumen obliteration and a strike erythrocyte and serum SERO extravasation. Extensive significant vascular C4d and C3 deposition throughout vascular cell wall was also identified. A regenerative epidermal hyperplasia MESHD with tissue structure preservation was found. Conclusions: Covid-19 could comprise an obliterative micro-angiopathy consisting on endothelial and myointimal intensive growth with complement activation. This mechanism, together with increased vascular permeability identified, could contribute to obliterative vascular lumen and hemorrhage MESHD in Covid-19. Activation of the complement and angiogenic pathways could have an important role in inducing and maintaining this vasculopathic reaction pattern. Thus, anticoagulation by itself could not completely reverse vascular lumen obliteration, with consequent hemorrhagic increased risk associated. Skin is the largest organ in the body, the most accessible one and can mirror other organs of the body. Findings of this study could contribute to a better understanding of physio-pathological mechanisms underlying SARS-CoV-2 infection MESHD on living tissue and could help further studies find potential targets for specific therapeutic interventions in Covid-19 severe patients. 

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MeSH Disease
Human Phenotype

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