Background COVID-19 may present with a variety of clinical syndromes, however, the upper airway and the lower respiratory tract are the principle sites of infection. Previous work on respiratory ...viral infections demonstrated that airway inflammation results in the release of volatile organic compounds as well as nitric oxide. The detection of these gases from patients' exhaled breath offers a novel potential diagnostic target for COVID-19 that would offer real-time screening of patients for COVID-19 infection. Methods and findings We present here a breath tester utilizing a catalytically active material, which allows for the temporal manifestation of the gaseous biomarkers' interactions with the sensor, thus giving a distinct breath print of the disease. A total of 46 Intensive Care Unit (ICU) patients on mechanical ventilation participated in the study, 23 with active COVID-19 respiratory infection and 23 non-COVID-19 controls. Exhaled breath bags were collected on ICU days 1, 3, 7, and 10 or until liberation from mechanical ventilation. The breathalyzer detected high exhaled nitric oxide (NO) concentration with a distinctive pattern for patients with active COVID-19 pneumonia. The COVID-19 "breath print" has the pattern of the small Greek letter omega (). The "breath print" identified patients with COVID-19 pneumonia with 88% accuracy upon their admission to the ICU. Furthermore, the sensitivity index of the breath print (which scales with the concentration of the key biomarker ammonia) appears to correlate with duration of COVID-19 infection. Conclusions The implication of this breath tester technology for the rapid screening for COVID-19 and potentially detection of other infectious diseases in the future.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Abstract
Context
The coronavirus disease 2019 (COVID-19) pandemic has created a need for remote blood glucose (BG) monitoring in the intensive care unit (ICU).
Objective
To evaluate feasibility and ...patient safety of a hybrid monitoring strategy of point-of-care (POC) BG plus continuous glucose monitor (CGM) in the ICU.
Design
Retrospective analysis.
Setting
ICU of an academic medical center.
Patients
Patients with COVID-19 on IV insulin.
Intervention
After meeting initial validation criteria, CGM was used for IV insulin titration and POC BG was performed every 6 hours or as needed.
Main Outcome Measures
Outcomes included frequency of POC BG, workflow, safety, and accuracy measures.
Results
The study included 19 patients, 18 with CGM data, mean age 58 years, 89% on mechanical ventilation, 37% on vasopressors, and 42% on dialysis. The median time to CGM validation was 137 minutes (interquartile range IQR 114-206). During IV insulin, the median number of POC values was 7 (IQR 6-16) on day 1, and declined slightly thereafter (71% reduction compared with standard of 24/day). The median number of CGM values used nonadjunctively to titrate IV insulin was 11.5 (IQR 0, 15) on day 1 and increased thereafter. Time in range 70 to 180 mg/dL was 64 ± 23% on day 1 and 72 ± 16% on days 2 through 7, whereas time <70 mg/dL was 1.5 ± 4.1% on day 1 and <1% on days 2 through 7.
Conclusions
This study provides data to support that CGM using a hybrid protocol is feasible, accurate, safe, and has potential to reduce nursing and staff workload.
This trial comparing treatment strategies that emphasized the use of vasopressors or intravenous fluids for early treatment of sepsis-induced hypotension showed no difference in 90-day mortality ...before discharge home.
Fluid and vasopressor management in septic shock remains controversial. In this randomized controlled trial, we evaluated the efficacy of dynamic measures (stroke volume change during passive leg ...raise) to guide resuscitation and improve patient outcome.
Will resuscitation that is guided by dynamic assessments of fluid responsiveness in patients with septic shock improve patient outcomes?
We conducted a prospective, multicenter, randomized clinical trial at 13 hospitals in the United States and United Kingdom. Patients presented to EDs with sepsis that was associated hypotension and anticipated ICU admission. Intervention arm patients were assessed for fluid responsiveness before clinically driven fluid bolus or increase in vasopressors occurred. The protocol included reassessment and therapy as indicated by the passive leg raise result. The control arm received usual care. The primary clinical outcome was positive fluid balance at 72 hours or ICU discharge, whichever occurred first.
In modified intent-to-treat analysis that included 83 intervention and 41 usual care eligible patients, fluid balance at 72 hours or ICU discharge was significantly lower (-1.37 L favoring the intervention arm; 0.65 ± 2.85 L intervention arm vs 2.02 ± 3.44 L usual care arm; P = .021. Fewer patients required renal replacement therapy (5.1% vs 17.5%; P = .04) or mechanical ventilation (17.7% vs 34.1%; P = .04) in the intervention arm compared with usual care. In the all-randomized intent-to-treat population (102 intervention, 48 usual care), there were no significant differences in safety signals.
Physiologically informed fluid and vasopressor resuscitation with the use of the passive leg raise-induced stroke volume change to guide management of septic shock is safe and demonstrated lower net fluid balance and reductions in the risk of renal and respiratory failure. Dynamic assessments to guide fluid administration may improve outcomes for patients with septic shock compared with usual care.
NCT02837731.
Background: Zinc deficiency is a cause of immune dysfunction and infection. Previous human studies have shown that the activation of the acute phase response alters zinc metabolism. Whether the ...alteration in zinc metabolism is predictive of disease severity in the setting of critical illness is unclear.Objective: We sought to determine whether differences occur in zinc metabolism at the onset of critical illness between infected (septic) and noninfected subjects.Design: We conducted this prospective study in an adult medical intensive care unit (MICU) at a tertiary care hospital. Subjects were enrolled within 24 h of intensive care unit admission. Subjects who did not meet sepsis criteria were considered for the critically ill control (CIC) arm. After patient consent, blood was immediately collected to measure plasma zinc and cytokine concentrations and zinc transporter gene expression in peripheral blood monocytes. Clinical data during the MICU stay were also recorded.Results: A total of 56 patients were evaluated (22 septic, 22 CIC, and 12 healthy subjects). Plasma zinc concentrations were below normal in CIC patients and further reduced in the septic cohort (57.2 ± 18.2 compared with 45.5 ± 18.1 μg/dL). Cytokine concentrations increased with decreasing plasma zinc concentrations (P = 0.05). SLC39A8 gene expression was highest in patients with the lowest plasma zinc concentrations and the highest severity of illness.Conclusions: The alteration of zinc metabolism was more pronounced in septic patients than in noninfected critically ill patients. Specifically, sepsis was associated with lower plasma zinc concentrations and higher SLC39A8 mRNA expression, which correlated with an increased severity of illness, including cardiovascular dysfunction.
Prompt intravenous fluid therapy is a fundamental treatment for patients with septic shock. However, the optimal approach for administering intravenous fluid in septic shock resuscitation is unknown. ...Two competing strategies are emerging: a liberal fluids approach, consisting of a larger volume of initial fluid (50 to 75 mL/kg 4 to 6 L in an 80-kg adult during the first 6 hours) and later use of vasopressors, versus a restrictive fluids approach, consisting of a smaller volume of initial fluid (≤30 mL/kg ≤2 to 3 L), with earlier reliance on vasopressor infusions to maintain blood pressure and perfusion. Early fluid therapy may enhance or maintain tissue perfusion by increasing venous return and cardiac output. However, fluid administration may also have deleterious effects by causing edema within vital organs, leading to organ dysfunction and impairment of oxygen delivery. Conversely, a restrictive fluids approach primarily relies on vasopressors to reverse hypotension and maintain perfusion while limiting the administration of fluid. Both strategies have some evidence to support their use but lack robust data to confirm the benefit of one strategy over the other, creating clinical and scientific equipoise. As part of the National Heart, Lung, and Blood Institute Prevention and Early Treatment of Acute Lung Injury Network, we designed a randomized clinical trial to compare the liberal and restrictive fluids strategies, the Crystalloid Liberal or Vasopressor Early Resuscitation in Sepsis trial. The purpose of this article is to review the current literature on approaches to early fluid resuscitation in adults with septic shock and outline the rationale for the upcoming trial.
IMPORTANCE: The role of cytomegalovirus (CMV) reactivation in mediating adverse clinical outcomes in nonimmunosuppressed adults with critical illness is unknown. OBJECTIVE: To determine whether ...ganciclovir prophylaxis reduces plasma interleukin 6 (IL-6) levels in CMV-seropositive adults who are critically ill. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, placebo-controlled, randomized clinical trial (conducted March 10, 2011-April 29, 2016) with a follow-up of 180 days (November 10, 2016) that included 160 CMV-seropositive adults with either sepsis or trauma and respiratory failure at 14 university intensive care units (ICUs) across the United States. INTERVENTIONS: Patients were randomized (1:1) to receive either intravenous ganciclovir (5 mg/kg twice daily for 5 days), followed by either intravenous ganciclovir or oral valganciclovir once daily until hospital discharge (n = 84) or to receive matching placebo (n = 76). MAIN OUTCOMES AND MEASURES: The primary outcome was change in IL-6 level from day 1 to 14. Secondary outcomes were incidence of CMV reactivation in plasma, mechanical ventilation days, incidence of secondary bacteremia or fungemia, ICU length of stay, mortality, and ventilator-free days (VFDs) at 28 days. RESULTS: Among 160 randomized patients (mean age, 57 years; women, 43%), 156 patients received 1or more dose(s) of study medication, and 132 patients (85%) completed the study. The mean change in plasma IL-6 levels between groups was −0.79 log10 units (−2.06 to 0.48) in the ganciclovir group and −0.79 log10 units (−2.14 to 0.56) in the placebo group (point estimate of difference, 0 95% CI, −0.3 to 0.3; P > .99). Among secondary outcomes, CMV reactivation in plasma was significantly lower in the ganciclovir group (12% 10 of 84 patients vs 39% 28 of 72 patients); absolute risk difference, −27 (95% CI, −40 to −14), P < .001. The ganciclovir group had more median VFDs in both the intention-to-treat (ITT) group and in the prespecified sepsis subgroup (ITT group: 23 days in ganciclovir group vs 20 days in the placebo group, P = .05; sepsis subgroup, 23 days in the ganciclovir group vs 20 days in the placebo group, P = .03). There were no significant differences between the ganciclovir and placebo groups in duration of mechanical ventilation (5 days for the ganciclovir group vs 6 days for the placebo group, P = .16), incidence of secondary bacteremia or fungemia (15% for the ganciclovir group vs 15% for the placebo group, P = .67), ICU length of stay (8 days for the ganciclovir group vs 8 days for the placebo group, P = .76), or mortality (12% for the ganciclovir group vs 15% for the placebo group, P = .54). CONCLUSIONS AND RELEVANCE: Among CMV-seropositive adults with critical illness due to sepsis or trauma, ganciclovir did not reduce IL-6 levels and the current study does not support routine clinical use of ganciclovir as a prophylactic agent in patients with sepsis. Additional research is necessary to determine the clinical efficacy and safety of CMV suppression in this setting. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01335932
The SARS CoV-2 pandemic has resulted in more than 1.1 million deaths in the USA alone. Therapeutic options for critically ill patients with COVID-19 are limited. Prior studies showed that ...post-infection treatment of influenza A virus-infected mice with the liponucleotide CDP-choline, which is an essential precursor for de novo phosphatidylcholine synthesis, improved gas exchange and reduced pulmonary inflammation without altering viral replication. In unpublished studies, we found that treatment of SARS CoV-2-infected K18-hACE2-transgenic mice with CDP-choline prevented development of hypoxemia. We hypothesize that administration of citicoline (the pharmaceutical form of CDP-choline) will be safe in hospitalized SARS CoV-2-infected patients with hypoxemic acute respiratory failure (HARF) and that we will obtain preliminary evidence of clinical benefit to support a larger Phase 3 trial using one or more citicoline doses.
We will conduct a single-site, double-blinded, placebo-controlled, and randomized Phase 1/2 dose-ranging and safety study of Somazina® citicoline solution for injection in consented adults of any sex, gender, age, or ethnicity hospitalized for SARS CoV-2-associated HARF. The trial is named "SCARLET" (Supplemental Citicoline Administration to Reduce Lung injury Efficacy Trial). We hypothesize that SCARLET will show that i.v. citicoline is safe at one or more of three doses (0.5, 2.5, or 5 mg/kg, every 12 h for 5 days) in hospitalized SARS CoV-2-infected patients with HARF (20 per dose) and provide preliminary evidence that i.v. citicoline improves pulmonary outcomes in this population. The primary efficacy outcome will be the S
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ratio on study day 3. Exploratory outcomes include Sequential Organ Failure Assessment (SOFA) scores, dead space ventilation index, and lung compliance. Citicoline effects on a panel of COVID-relevant lung and blood biomarkers will also be determined.
Citicoline has many characteristics that would be advantageous to any candidate COVID-19 therapeutic, including safety, low-cost, favorable chemical characteristics, and potentially pathogen-agnostic efficacy. Successful demonstration that citicoline is beneficial in severely ill patients with SARS CoV-2-induced HARF could transform management of severely ill COVID patients.
The trial was registered at www.
gov on 5/31/2023 (NCT05881135).
Currently enrolling.
To the Editor: Humoral and cellular immune responses con-tribute to overall protective immunity against SARS-CoV-2, with neutralizing antibody playing a key role in preventing viral infection. ...a ...recent study has shown that booster responses to Omicron infection are affected by previous SARS-CoV-2 infec-tions (5). ...having additional information on the types of neutralizing antibody responses induced after infection with different SARS-CoV-2 variants will be helpful in addressing this important issue. In vaccinated Delta-infected patients, neutralization titers against Delta and WA1 were similar, but again were much low-er against BA.1 (17-fold) and BA.2 (9-fold) (Figure 1B). ...both unvaccinated and vaccinated Delta-infected patients had significantly lower neutralizing antibody responses to Omi-cron (as determined by Wilcoxons rank sum test).
Prolonged symptom duration and disability are common in adults hospitalized with severe coronavirus disease 2019 (COVID-19). Characterizing return to baseline health among outpatients with milder ...COVID-19 illness is important for understanding the full spectrum of COVID-19-associated illness and tailoring public health messaging, interventions, and policy. During April 15-June 25, 2020, telephone interviews were conducted with a random sample of adults aged ≥18 years who had a first positive reverse transcription-polymerase chain reaction (RT-PCR) test for SARS-CoV-2, the virus that causes COVID-19, at an outpatient visit at one of 14 U.S. academic health care systems in 13 states. Interviews were conducted 14-21 days after the test date. Respondents were asked about demographic characteristics, baseline chronic medical conditions, symptoms present at the time of testing, whether those symptoms had resolved by the interview date, and whether they had returned to their usual state of health at the time of interview. Among 292 respondents, 94% (274) reported experiencing one or more symptoms at the time of testing; 35% of these symptomatic respondents reported not having returned to their usual state of health by the date of the interview (median = 16 days from testing date), including 26% among those aged 18-34 years, 32% among those aged 35-49 years, and 47% among those aged ≥50 years. Among respondents reporting cough, fatigue, or shortness of breath at the time of testing, 43%, 35%, and 29%, respectively, continued to experience these symptoms at the time of the interview. These findings indicate that COVID-19 can result in prolonged illness even among persons with milder outpatient illness, including young adults. Effective public health messaging targeting these groups is warranted. Preventative measures, including social distancing, frequent handwashing, and the consistent and correct use of face coverings in public, should be strongly encouraged to slow the spread of SARS-CoV-2.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, ODKLJ, OILJ, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK, VSZLJ
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