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SESSION TITLE: Sepsis: Beyond 30cc/kg and Antibiotics SESSION TYPE: Rapid Fire Original Inv PRESENTED ON: 10/19/2022 11:15 am - 12:15 pm PURPOSE: The Sepsis Prediction Model (SPM) is a proprietary decision support tool created by Epic Systems. The basis of the SPM is a Predicting Sepsis Score (PSS) calculated from demographic, comorbidity, vitals, labs, medication, and procedural data. We assessed the diagnostic accuracy and timeliness of the PSS for sepsis as defined by Centers for Disease Control (CDC) Adult Sepsis Event (ASE) criteria. The performance of the PSS was compared to, Systemic Inflammatory Response Syndrome (SIRS), quick Sequential Organ Failure Assessment (qSOFA), and SOFA scores. METHODS: Retrospective review of 62,460 adults admitted to 4 Wake Forest Baptist Health System hospitals from June 1, 2019 through December 31, 2020 with PSS scores calculated every 15 minutes. A sepsis event was defined as receipt of 4 or more days of antimicrobials, blood cultures collected within 48 hours of initial antimicrobial administration, and at least one organ dysfunction. This definition of sepsis was modified to also include Covid-19 infection with organ dysfunction. Time zero was defined as time of first contact for the healthcare encounter. 30-day readmissions, facility transfers, and deaths in the Emergency Department were excluded. RESULTS: The prevalence of sepsis in the sample was 4.5%. The optimal PSS threshold based on Youden’s J statistic was a score of 8 (sensitivity 0.72, specificity 0.74, Youden’s J 0.46). SIRS (sensitivity 0.90, specificity 0.42), qSOFA (sensitivity 0.64, specificity 0.69), and SOFA (sensitivity 0.89, specificity 0.43) had a Youden’s J statistic for sepsis of 0.32, 0.33, and 0.32, respectively. At a PSS score of ≥ 8, median time to score positivity among those who reached that score (28.4% of sample) was 217 minutes (IQR 74-1477 minutes). For SIRS, qSOFA and SOFA, median time to score positivity was 54 minutes (IQR 24-456), 360 minutes (IQR 53-1593) and 107 minutes (IQR 39-474), respectively. CONCLUSIONS: Discrimination of the PSS for detection of sepsis was highest at a threshold score of 8. Overall, the PSS discriminated better than SIRS, qSOFA and SOFA. Positive SIRS and SOFA scores occurred at an earlier time-point than PSS score. The time to positivity appears to limit the tool’s best expected performance to improve time to initial antimicrobial and compliance with the 3-hour sepsis bundle. CLINICAL IMPLICATIONS: Clinical application of the Epic SPM to improve adherence with sepsis treatment goals is constrained by time to positive screen as compared to other screening tools. DISCLOSURES: No relevant relationships by Alain Bertoni No relevant relationships by Kristin Lenoir No relevant relationships by Beverly Levine No relevant relationships by Morgana Mongraw-Chaffin No relevant relationships by Adam Schertz Stock Ownership Interest relationship with Johnson & Johnson Please note: years Added 04/15/2022 by Karl Thomas, value=Ownership interest stock ownership relationship with Gilead Sciences Please note: years Added 04/15/2022 by Karl Thomas, value=Ownership Stock ownership interest relationship with Bristol-Myers Squibb Please note: years Added 04/15/2022 by Karl Thomas, value=Ownership interest Stock Ownership Interest relationship with Pfizer Please note: years Added 04/15/2022 by Karl Thomas, value=Ownership interest Stock Ownership Interest relationship with Doximity Please note: 1 year Added 04/15/2022 by Karl Thomas, value=Ownership interest No relevant relationships by Brian Wells No relevant relationships by Jack White
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Introduction: During COVID-19 pandemic, acute acral chilblain-like lesions (ACBLL), reminiscent of lupus pernio, were observed during both first and second COVID-19 peak among patients with highly suspected (but mostly unconfirmed) infection with SARS-CoV-2.The aetiology of this phenomenon has not been elucidated yet and pathogenetic mechanism remains unknown. Several studies have investigated cytokine and chemokine profile in patients with COVID-19 but an accurate characterization of ACBLL patients is lacking. Objectives: We aimed to describe the clinical, laboratory and immunological features of children presenting with ACBLL referred to our Institute during the COVID-19 pandemic spread. Methods: We prospectively collected data of children referred to our Institute from April 1st 2020 to February 28th 2021. We investigate the presence of SARS-CoV2 infection through RT-PCR from nasopharingeal swabs and three different serologic kit. All patients underwent a laboratory work-up including coagulation, viral serology and autoantibodies panel. Finally, we analysed peripheral blood IFN signature, a panel of inflammatory biomarkers in serum/plasma by a flow cytometry bead array (CXCL10, CXCL9, IL-6, IL-1β,TNFα) and the presence of SARS-CoV2 T specific lymphocytes. Results: We examined 36 children during the first peak, and 11 children during the second COVID-19 peak (F: 28 median age 12 y), at a median delay of 26 days after symptoms onset (2-73 days). Fifteen patients (31%) presented non-specific systemic symptoms preceding ACBLL onset. Nine patients (19%) reported a possible contagion from a close contact. All patients presented stereotypical features resembling classical chilblains with acral erythematousedematous violaceous plaques and nodules localized on the toes (n= 35, 74%), the fingers (n=5, 10%) or on both sites (n=7, 15%). SARSCoV- 2 RNA detection resulted negative except for 2 patients. Furthermore, ten patients observed during the first wave showed a recurrence during the second (F:6), which developed 1-4 weeks after the second COVID-19 peak the clinical features were comparable to those of the previous episode. Five of them (50%) reported nonspecific systemic symptoms before onset and/or close contact with SARS-CoV2 positive subject. Repeated SARS-CoV-2 specific IgG/IgA tests were negative for all patients except for three cases (two of them with positive swabs). Neither common virus serology nor coagulation studies revealed significative results. Two patients presented positive ANA and anti β2 glycoprotein, respectively. A positive IFN signature was detected in 12/ 33 patients (36%).Among the 35 patients tested, the cytokine array showed high levels of IP10 (n= 35, range 12.4-739 pg/ml, n.v. 0.0-0.2 pg/ml) and a mild increase of IL-6 (n=21, range 2.4-401 pg/ml, n.v. 0.5-2.2pg/ml), without alterations of CXCL9, IL-1β and TNFa. The detection of SARS-CoV2 specific lymphocytes showed the presence of SARS-CoV2 specific lymphocytes in 9/17 (52%) patients tested (validated with positive and negative controls), only one of them with a positive serological test. Conclusion: Albeit the pathogenetic mechanism of ACBLL remains to be elucidated, our preliminary results showed a significant increase in serum IP10 levels, not frankly associated with a peripheral blood IFN signature, which is instead a characteristic of pernio-related chilblains. We also proved the presence of a T-specific memory against in 50% of the tested patients, despite the negativity of coltures and serological tests, strengthening the link between SARS-CoV2 infection and this peculiar clinical manifestation.
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Introduction: COVID-19 severe pneumonia has been associated to systemic inflammation and elevation of blood parameters and reminiscent of cytokine storm syndrome. Stimulation of PBMC from patients with severe COVID-19 have shown a high secretion of IL-1β, a pivotal cytokine driving inflammatory phenotypes, which maturation and secretion is regulated by NLRP3 inflammasome. Steroidal anti-inflammatory therapies have shown efficacy in reducing mortality in critically ill patients, however the mechanisms by which SARS-CoV2 virus triggers such an extensive inflammation remain unexplained. Objectives: The overall objective of this study was to investigate if SARS-CoV2 drives inflammation in COVID-19 patients through NLRP3 inflammasome activation and IL-1β secretion. Methods: Samples from SARS-CoV2 infected patients, were collected at day 0 and at 3 and 7 following treatment with anakinra. Fresh monocytes, purified through adherence, were cultured for 3, 6, 18 h in the presence or absence of LPS (100 ng/ml) and MCC950 (10μM). Release of IL-1β, IL-1Ra, IL-6, TNF-α, IL-18 was quantified by ELISA kit. Relative gene expression analysis of ORF3a gene was performed by RT-qPCR. THP-1 cells were transfected with a plasmid containing ORF3a sequence by nucleofection. NLRP3 inflammasome and ASC speck formation were detected by confocal microscopy and/or by FACS analysis. Results: In the present study we show that circulating monocytes from COVID-19 patients display ASC specks, index of NLRP3 activation, and spontaneously secrete IL-1β in vitro. This spontaneous activation reverts following patient's treatment with the IL-1 receptor antagonist anakinra. Transfection of a monocytic cell line with cDNA coding for the ORF3a SARS-CoV2 protein, resulted in NLRP3- dependent ASC speck formation. The involvement of ORF3a in inflammasome activation was further supported by the detection by RT-PCR of ORF3a in monocytes from COVID-19 patients. Conclusion: In summary, these results provide a mechanistic explanation for the strong inflammatory manifestations associated to COVID-19 and further evidence that NLRP3 and IL-1β targeting could represent an effective strategy in this disease.
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Rationale The pulmonary vasculature is critical for gas exchange, impacts both pulmonary and cardiac function, and has renewed importance due to COVID-19. Pulmonary blood volume is, however, technically difficult to assess, generally requiring invasive methodology for quantification. Prior studies are limited in size and participant enrollment was selective;therefore, variation in the general population is largely unknown. We performed contrast-enhanced dual-energy computed tomography (DECT) in a multicenter, community-based cohort to describe variation in pulmonary perfused blood volume (PBV) in the community. MethodsThe Multi-Ethnic Study of Atherosclerosis (MESA) recruited adults from six sites. The MESA Lung Study invited all MESA participants attending Exam 6 (2017-18), excluding those with kidney disease and contrast allergy, to undergo DECT at functional residual capacity via Siemens Flash or Force scanner: CareDose on, pitch 0.55, 0.25 sec exposure, 0.5mm slice thickness, iterative reconstruction (Admire) with Qr40 Kernel. Half concentration 370mg/ml Iopamidol was delivered at 4ml/s for the full scan, starting 17 seconds prior to scanning, including a ∼4 sec breath hold. PBV was calculated by material decomposition and normalized with iodine concentration in the pulmonary trunk. Generalized linear regression models included age, sex, race/ethnicity, height, weight, smoking status, site, and education.ResultsDECT scans were acquired for 714 participants, 36 of which were excluded due to image quality. Mean age of the remaining 678 participants was 71 years (range 63 - 79), 55% were male, 51% were ever smokers, and the race/ethnic distribution was 41% White, 29% Black, 17% Hispanic, and 13% Asian. Mean PBV was 468 + 151mL. The strongest demographic correlate was lower PBV with greater age (-30 mL per 10 years, 95% CI: -43, -18, p<0.001). Pulmonary PBV was positively associated with height, weight, and male sex (all P<0.001). PBV was lower in former compared to never smokers (p =0.04) and in Black than White participants (p=0.002), but not in Hispanic or Asian participants. There were no consistent differences across education or study site. Results were similar after adjustment for lung function and percent emphysema on CT.ConclusionsTo our knowledge, this is the first assessment of pulmonary PBV in a large, multiethnic, general community sample. Pulmonary PBV assessed by contrast-enhanced DECT was substantially reduced with advancing age and varied with body size, sex, former smoking, and, to a lesser extent, Black race. Understanding variation in pulmonary PBV in the general population may elucidate risk of cardiopulmonary disease and physical function.
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A growing body of research has documented the negative impact of COVID-19 containment measures on children's psychological well-being. The role of parental stress and the specific impact of different parental stressors on children's difficulties are underinvestigated. The current cross-sectional study was aimed at exploring the link between children's (3-17 years of age) emotional difficulties and some specific sources of parental stress after the first lockdown period and which sources of parental stress contribute to children's difficulties. 506 Italian parents filled in an online questionnaire at the end of June 2020. Results showed that the limitation of social interactions and family life arrangements have a significant impact on children's difficulties, suggesting focused interventions aimed at reducing the negative impact of the pandemic on younger generations. © 2021 Franco Angeli Edizioni. All rights reserved.