Quantitation of plasma lipopolysaccharides (LPSs) might be used to document Gram-negative bacterial infection. In the present work, LPS-derived 3-hydroxymyristate was extracted from plasma samples ...with an organic solvent, separated by reversed phase HPLC, and quantitated by MS/MS. This mass assay was combined with the limulus amebocyte lysate (LAL) bioassay to monitor neutralization of LPS activity in biological samples. The described HPLC/MS/MS method is a reliable, practical, accurate, and sensitive tool to quantitate LPS. The combination of the LAL and HPLC/MS/MS analyses provided new evidence for the intrinsic capacity of plasma lipoproteins and phospholipid transfer protein to neutralize the activity of LPS. In a subset of patients with systemic inflammatory response syndrome, with documented infection but with a negative plasma LAL test, significant amounts of LPS were measured by the HPLC/MS/MS method. Patients with the highest plasma LPS concentration were more severely ill. HPLC/MS/MS is a relevant method to quantitate endotoxin in a sample, to assess the efficacy of LPS neutralization, and to evaluate the proinflammatory potential of LPS in vivo.
Background
Prone position (PP) is highly recommended in moderate-to-severe ARDS. However, the optimal duration of PP sessions remains unclear. We searched to evaluate the time required to obtain the ...maximum physiological effect, and to search for parameters related to patient survival in PP.
Methods and results
It was a prospective, monocentric, physiological study. We included in the study all prone-positioned patients in our ICU between June 2016 and January 2018. Pulmonary mechanics, data from volumetric capnography and arterial blood gas were recorded before prone positioning, 2 h after proning, before return to a supine position (SP) and 2 h after return to SP. Dynamic parameters were recorded before proning and every 30 min during the session until 24 h. 103 patients (ARDS 95%) were included performing 231 PP sessions with a mean length of 21.5 ± 5 h per session. They presented a significant increase in pH, static compliance and P
a
O
2
/F
i
O
2
with a significant decrease in P
a
CO
2
, P
plat
, phase 3 slope of the volumetric capnography, P
et
CO
2
,
V
D
/
V
T-phy
and Δ
P
. The beneficial physiological effects continued after 16 h of PP and at least up to 24 h in some patients. The evolution of the respiratory parameters during the first session and also during the pooled sessions did not find any predictor of response to PP, whether before, during or 2 h after the return in SP.
Conclusions
PP sessions should be prolonged at least 24 h and be extended in the event that the P
a
O
2
/F
i
O
2
ratio at 24 h remains below 150, especially since no criteria can predict which patient will benefit or not from it.
Trial registration
The trial has been registered on 28 June 2016 in ClinicalTrials.gov (NCT 02816190) (
https://clinicaltrials.gov/ct2/show/NCT02816190?term=propocap&rank=1
).
Cardiac amyloidosis is defined by extracellular deposition of misfolded proteins in the heart. The most frequent cases of cardiac amyloidosis are caused by transthyretin and light chain amyloidosis. ...This condition is underdiagnosed, and its incidence has been continuously rising in recent studies because of the aging of the population and the development of noninvasive multimodal diagnostic tools. Amyloid infiltration affects all cardiac tunics and causes heart failure with preserved ejection fraction, aortic stenosis, arrythmia, and conductive disorder. Innovative, specific therapeutic approaches have demonstrated an improvement in affected organs and the global survival of patients. This condition is no longer considered rare and incurable. Thus, better knowledge of the disease is mandatory. This review will provide a digest of the clinical signs and symptoms of cardiac amyloidosis, the diagnostic tools used to confirm the diagnosis, and current symptomatic and etiopathogenic management considerations according to guidelines and recommendations.
The coronavirus disease 2019 (COVID-19) pandemic has affected millions of people worldwide. A clinical series of Kawasaki-like multisystem inflammatory syndrome (MIS), occurring after SARS-CoV-2 ...infection, have been described in children (MIS-C) and adults (MIS-A), but the pathophysiology remains unknown.
We describe a case of post-COVID-19 MIS-A in a 46-year-old man with biopsy-proven renal thrombotic microangiopathy (TMA). Specific complement inhibition with eculizumab was initiated promptly and led to a dramatic improvement of renal function.
Our case suggests that that TMA could play a central role in the pathophysiology of post-COVID-19 MIS-A, making complement blockers an interesting therapeutic option.
Hypoxia is common during daily nursing procedures (DNPs) routinely performed on mechanically ventilated patients. The impact of automated ventilation on the incidence and severity of blood oxygen ...desaturation during DNPs remains unknown.
A prospective randomized controlled crossover trial was carried out in a French intensive care unit to compare blood oxygen pulse saturation (SpO
) during DNPs performed on patients mechanically ventilated in automated and conventional ventilation modes (AV and CV, respectively). All patients with FiO
≤ 60% and without prone positioning or neuromuscular blocking agents were included. Patients underwent two DNPs on the same day using AV (INTELLiVENT-ASV®) and CV (volume control, biphasic positive airway pressure, or pressure support ventilation) in a randomized order. The primary outcome was the percentage of time spent with SpO
in the acceptable range of 90-95% during the DNP.
Of the 265 included patients, 93% had been admitted for a medical pathology, the majority for acute respiratory failure (52%). There was no difference between the two periods in terms of DNP duration, sedation requirements, or ventilation parameters, but patients had more spontaneous breaths and lower peak airway pressures during the AV period (p < 0.001). The percentage of time spent with SpO
in the acceptable range during DNPs was longer in the AV period than in the CV period (48 ± 37 vs. 43 ± 37, percentage of DNP period; p = 0.03). After adjustment, AV was associated with a higher number of DNPs carried out with SpO
in the acceptable range (odds ratio, 1.82; 95% CI, 1.28 to 2.6; p = 0.001) and a lower incidence of blood oxygen desaturation ≤ 85% (adjusted odds ratio, 0.50; 95% CI, 0.30 to 0.85; p = 0.01).
AV appears to reduce the incidence and severity of blood oxygen desaturation during daily nursing procedures (DNPs) in comparison to CV.
This study was registered in clinical-trial.gov ( NCT03176329 ) in June 2017.
Little is known on the outcome and risk factors for mortality of patients admitted in Intensive Care units (ICUs) for Acute cholangitis (AC).
Retrospective multicenter study included adults admitted ...in eleven intensive care units for a proven AC from 2005 to 2018. Risk factors for in-hospital mortality were identified using multivariate analysis.
Overall, 382 patients were included, in-hospital mortality was 29%. SOFA score at admission was 8 5-11. Biliary obstruction was mainly related to gallstone (53%) and cancer (22%). Median total bilirubin and PCT were respectively 83 µmol/L 50-147 and 19.1 µg/L 5.3-54.8. Sixty-three percent of patients (n = 252) had positive blood culture, mainly Gram-negative bacilli (86%) and 14% produced extended spectrum beta lactamase bacteria. At ICU admission, persisting obstruction was frequent (79%) and biliary decompression was performed using therapeutic endoscopic retrograde cholangiopancreatography (76%) and percutaneous transhepatic biliary drainage (21%). Adjusted mortality significantly decreased overtime, adjusted OR for mortality per year was 0.72 0.54-0.96 (p = 0.02). In a multivariate analysis, factors at admission associated with in-hospital mortality were: SOFA score (OR 1.14 95% CI 1.05-1.24 by point, p = 0.001), lactate (OR 1.21 95% CI 1.08-1.36, by 1 mmol/L, p < 0.001), total serum bilirubin (OR 1.26 95% CI 1.12-1.41, by 50 μmol/L, p < 0.001), obstruction non-related to gallstones (p < 0.05) and AC complications (OR 2.74 95% CI 1.45-5.17, p = 0.002). Time between ICU admission and biliary decompression > 48 h was associated with in-hospital mortality (adjusted OR 2.73 95% CI 1.30-6.22, p = 0.02).
In this large retrospective multicenter study, we found that AC-associated mortality significantly decreased overtime. Severity of organ failure, cause of obstruction and local complications of AC are risk factors for mortality, as well as delayed biliary drainage > 48 h.
Purpose
This is a subanalysis of a previous study which compared the effectiveness of trimetoprim-sulfametoxazole (TMP-SMX) with all other regimens for treatment of ventilator-associated pneumonia ...(VAP). Aim of the current study was to focus on the effectiveness of a strategy based on TMP-SMX as de-escalation from β-lactam including regimens.
Methods
Retrospective cohort study including patients who were hospitalized for VAP from 2011 to 2019. Patients were distributed in two groups: NO SWITCH TO TMP-SMX group, including patients who received β-lactams for all treatment duration, and SWITCH TO TMP-SMX group, which included patients who switched to TMP-SMX from a β-lactam including regimen after microbiology diagnosis. Three clinical outcomes were analyzed: mortality at 30 days from the start of the antibiotic treatment (T30), mortality at the end of treatment (EoT), and acquisition of multidrug-resistant bacteria during hospitalization in intensive care unit.
Results
Overall, 70 patients were included in the current study, 32/70 (45.7%) in NO SWITCH TO TMP-SMX group and 38/70 (54.3%) in SWITCH TO TMP-SMX group, 37/70 (52.8%) had been already included in the previous study. No significant differences in clinical outcomes and patient’s characteristics were found when the two groups were compared.
Conclusions
De-escalation to TMP-SMX for VAP treatment was not associated with higher mortality at EoT and T30 than standard treatment with β-lactam. Monotherapy with TMP-SMX as de-escalation from broad-spectrum empirical regimens is a β-lactam sparing strategy worthy to be further investigated in either multicenter cohort studies or randomized clinical trials.
Abstract By chelating ionized calcium, citrate allows extracorporeal circuit anticoagulation without a bleeding risk for the patient. Citrate anticoagulation is also associated with a reduced ...activation of leucocytes and platelets. Citrate clearance by citric acid cycle (Krebs cycle) is not modified by renal failure, but is reduced by about 50% in patients with cirrhosis. Toxic effects of citrate result from a decrease in plasma ionized calcium of the patient. The first side effect is a prolongation of the QT interval. Clinical signs of hypocalcemia and hypotension in humans appear below 0.9 mmol/L of plasma ionized calcium.
Fast and reliable assays to precisely define the nature of the infectious agents causing sepsis are eagerly anticipated. New molecular biology techniques are now available to define the presence of ...bacterial or fungal DNA within the bloodstream of sepsis patients. We have used a new technique (VYOO®) that allows the enrichment of microbial DNA before a multiplex polymerase chain reaction (PCR) for pathogen detection provided by SIRS-Lab (Jena, Germany). We analyzed 72 sepsis patients and 14 non-infectious systemic inflammatory response syndrome (SIRS) patients. Among the sepsis patients, 20 had a positive blood culture and 35 had a positive microbiology in other biological samples. Of these, 51.4% were positive using the VYOO® test. Among the sepsis patients with a negative microbiology and the non-infectious SIRS, 29.4% and 14.2% were positive with the VYOO® test, respectively. The concordance in bacterial identification between microbiology and the VYOO® test was 46.2%. This study demonstrates that these new technologies offer great hopes, but improvements are still needed.
We investigated the immunoinflammatory profile of patients successfully resuscitated after cardiac arrest, representing a model of whole-body ischemia/reperfusion syndrome.
Plasma cytokine, ...endotoxin, and ex vivo cytokine production in whole-blood assays was assessed in 61, 35, and 11 patients, respectively. On admission, high levels of plasma interleukin (IL)-6, IL-8, IL-10, and soluble tumor necrosis factor (TNF) receptor type II could discriminate between survivors and nonsurvivors. Among nonsurvivors, the initial need for a vasopressor agent was associated with higher levels of IL-1 receptor antagonist, IL-10, and IL-6 on day 1. Plasma endotoxin was detected in 46% of the analyzed patients within the 2 first days. Endotoxin-induced TNF and IL-6 productions were dramatically impaired in these patients compared with healthy control subjects, whereas an unaltered production was observed with heat-killed Staphylococcus aureus. In contrast, IL-1 receptor antagonist productions were enhanced in these patients compared with healthy control subjects. The productions of T-cell-derived IL-10 and interferon-gamma were also impaired in these patients. Finally, using in vitro plasma exchange between healthy control subjects and patients, we demonstrated that the endotoxin-dependent hyporeactivity was an intrinsic property of patients' leukocytes and that an immunosuppressive activity was also present in their plasma.
Altogether, the high levels of circulating cytokines, the presence of endotoxin in plasma, and the dysregulated production of cytokines found in these patients recall the immunological profile found in patients with sepsis.
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