Oxford-AstraZeneca COVID-19 vaccine: need of a reasoned and effective vaccine campaign.

OBJECTIVES: A strong COVID-19 vaccine campaign is needed to reach the herd immunity and reduce this pandemic infection. STUDY DESIGN: In the Foch Hospital, France, in February 2021, 451 healthcare workers were vaccinated by a first dose of AstraZeneca vaccine. METHODS: Adverse effects were reported to our pharmaco-vigilance circuit, by an online and anonymous questionnaire following the first weeks of the vaccinal campaign to healthcare workers. RESULTS: Two hundred seventy-four (60.8%) of them reported multiple adverse effects. Main adverse effects reported were feverish state/chills (65.7%), fatigue/physical discomfort (62.4%), arthralgia/muscle pain (61.0%) and fever (44.5%). CONCLUSIONS: On March 2021 many European countries suspended AstraZeneca vaccine for one week due to safety uncertainty. Thus, confidence in its efficacy is undermined. However, the benefit/risk balance is clearly in favor of vaccination.

[Evolution and progress of lung transplantation: An analysis of a cohort of 600 lung transplant patients at the Hospital Foch]. / Évolution et progrès en transplantation pulmonaire : étude de la cohorte de 600 premiers patients transplantés pulmonaires à l'hôpital Foch.

Lung transplantation is deemed to be the only effective therapy that improves survival for patients with end stage lung disease. The aim of our study was to examine the progress achieved over the last two decades and to demonstrate the effectiveness and safety of this treatment. METHODS: A retrospective analysis of a cohort of 600 consecutive lung transplant patients treated at the hospital Foch (Suresnes, France) between 1988 and 2014. They were split into three groups of 200 patients each: 1988-2004, 2004-2011, 2011-2014. RESULTS: Time and mortality on waiting list, perioperative mortality, the incidence of acute rejection in the first year and chronic lung allograft dysfunction (CLAD) at 5 years posttransplantation, have all decreased. Global survival at 1 and 5 years for the 600 patients increased from 78% and 57% to 86% and 75% respectively for the 200 last patients. Patients with cystic fibrosis have a better 5 year survival than those with emphysema or pulmonary fibrosis (68% vs. 54 % for emphysema and 37% for fibrosis). For the last 200 patients, 5 year survival is 81% for CF patients, 78 % for emphysema and 47% for fibrosis. Emergency transplantation had a 60% 5 years survival. Proliferative complications, arterial hypertension and renal function impairment are being monitored long term. CONCLUSION: The twenty-five years experience shows a consistent improvement in the results of lung transplantation which is now accepted as the only effective curative treatment for end stage lung disease.

Immediate postoperative extubation in bilateral lung transplantation: predictive factors and outcomes.

BACKGROUND: We reviewed our experience with tracheal extubation in the operating room (E-OR) among cystic fibrosis patients requiring bilateral lung transplantation to evaluate safety and determine predictive factors of E-OR. METHODS: The charts of 89 recipients (from May 2007 to June 2013) were analysed. Patients were divided into E-OR and E-ICU (intensive care unit extubation) groups. Data are expressed as numbers (percentages) or medians [25th-75th percentiles]. RESULTS: There were 41 patients in the E-OR group (46%). Donor and recipient characteristics were similar between groups. Intraoperative complications occurred less frequently in the E-OR group, and fluid and transfusion requirements were lower. Postoperative courses were different in the E-OR group, including a lower rate of grade 3 primary graft dysfunction (0 compared with 19 patients, P<0.0001) and shorter ICU (5.0 [3.7-7.2] compared with 11.5 [7.0-15.5] days) and hospital stays (22.0 [18.0-25.5] compared with 33.0 [25.0-56.5] days, respectively; P<0.0001 for both). The 1 yr survival rates were similar: 95% in the E-OR group and 98% in the E-ICU group. A statistical model built on a development cohort of 60 randomly selected patients predicted 95% of E-OR instances in this cohort and 82% of E-OR instances in the validation cohort (28 patients). Predictive factors were complications during single-lung ventilation (second graft implantation), complications during bipulmonary ventilation (end of surgery), and the ratio of arterial partial pressure of oxygen to fractional inspired oxygen (end of surgery). CONCLUSIONS: Our protocol allowed for extubation of 46% of bilateral lung transplant patients without increased postoperative risks.

[Pneumocystis jirovecii pneumonia in non-HIV infected patients: a study of 41 cases]. / Pneumocystose pulmonaire chez des patients immunodéprimés non infectés par le VIH : étude de 41 cas.

BACKGROUND: The increasing use of immunosuppressive and cytotoxic therapies leads to a growing number of opportunistic infections especially Pneumocystis jirovecii pneumonia (PCP). The purpose of our study was to describe the population involved, and to assess clinical, biological, and mortality data. METHODS: We collected retrospectively the whole medical file of all PCP cases diagnosed in non-HIV infected patients, in two French University Hospitals in the last decade (1999-2009). Diagnosis was made on standard coloration and/or immunofluorescence analysis of bronchoalveolar lavage fluid (BAL). RESULTS: Forty-one patients were included in the study, mean age 56 (±12.5) years, sex ratio 0.71 men/woman. Underlying diseases were as follow: 12 patients (29%) were renal transplant recipients, 13 (32%) were treated for solid cancers, and 16 (39%) suffered from various diseases (three allogenic bone-marrow transplantation, 11 hematological malignancies, one pulmonary transplantation, one vasculitis). Twelve patients died (i.e. 29%). Median lymphocyte count was 542/mm(3). More than 85% patients received corticosteroids at a median cumulative 6-month dose of 2700mg. Seven patients (17%) had a PCP prophylaxis. Clinical worsening at day 5 (P<0.003), poor control of the underlying disease (P<0.015), WHO performans status superior than 2 (P<0.025), high temperature (P<0.04), and high oxygen flow (P<0.042) were linked to a poor prognosis. DISCUSSION/CONCLUSION: The prognosis factors found are mostly linked to the patients' clinical severity. We would like to highlight: first, near to 30% mortality rate, secondly, a lack of prophylaxis in 34 patients, reflecting the difficulty to define PCP's risk in non HIV-infected patients.

[H1N1 (2009) influenza A infection in transplant recipient patients: a comparative study versus non-transplanted patients]. / Grippe A/H1N1 2009 chez des patients transplantés : étude comparative versus des patients non transplantés.

OBJECTIVE: To compare H1N1 (2009) influenza A infection characteristics between transplant recipient patients and non-transplanted patients. To assess the evolution of transplanted patients up to 6 months following infection. METHODS: Patients diagnosed with confirmed influenza A infection from three Parisian transplant centers between September 1st, 2009 and February 15th, 2010. Clinical symptoms, biological, and radiological findings, and management were analysed and retrospectively compared between transplanted (T) and non-transplanted patients (NT). The evolution was assessed by a follow-up questionnaire, CT results 1 to 3 months after influenza infection and FEV1 variation. RESULTS: Seventy patients were included. Thirteen patients had an allograft (lung: eight, kidney: four, stem cells: one): (1) hospitalization: 100% (13 out of 13) in group T, 54% (31 out of 57) in group NT (P=0.0013); (2) pneumonia: 62% (eight out of 13) in group T, 26% (eight out of 57) in group NT (P=0.004); (3) mortality rate among hospitalized patients: 7.7% (one out of 13) in the group T, 9.7% (three out of 57) in group NT (P=NS); (4) chest CT scan abnormalities remained in four lung transplanted patients; (5) a minimum 10% decrease in FEV1 was detected in four lung transplant recipients. CONCLUSION: Our results suggest that H1N1(2009) influenza A infection in transplant recipient patients compared to non-transplanted patients: (1) more often leads to hospitalization; (2) is more frequently associated with pneumonia; (3) is responsible for a persistent graft functional impairment in lung transplant recipients; (4) has a low mortality rate similar to admitted non-transplanted patients.

Accuracy of pulse oximetry in the intensive care unit.

OBJECTIVE: Pulse oximetry (SpO2) is a standard monitoring device in intensive care units (ICUs), currently used to guide therapeutic interventions. Few studies have evaluated the accuracy of SpO2 in critically ill patients. Our objective was to compare pulse oximetry with arterial oxygen saturation (SaO2) in such patients, and to examine the effect of several factors on this relationship. DESIGN: Observational prospective study. SETTING: A 26-bed medical ICU in a university hospital. PATIENTS: One hundred two consecutive patients admitted to the ICU in whom one or serial arterial blood gas analyses (ABGs) were performed and a reliable pulse oximeter signal was present. INTERVENTIONS: For each ABG, we collected SaO2, SpO2, the type of pulse oximeter, the mode of ventilation and requirement for vasoactive drugs. MEASUREMENTS AND RESULTS: Three hundred twenty-three data points were collected. The mean difference between SpO2 and SaO2 was -0.02% and standard deviation of the differences was 2.1%. From one sample to another, the fluctuations in SpO2 to arterial saturation difference indicated that SaO2 could not be reliably predicted from SpO2 after a single ABG. Subgroup analysis showed that the accuracy of SpO2 appeared to be influenced by the type of oximeter, the presence of hypoxemia and the requirement for vasoactive drugs. Finally, high SpO2 thresholds were necessary to detect significant hypoxemia with good sensitivity. CONCLUSION: Large SpO2 to SaO2 differences may occur in critically ill patients with poor reproducibility of SpO2. A SpO2 above 94% appears necessary to ensure a SaO2 of 90%.

The pharmacokinetics of cisatracurium in patients with acute respiratory distress syndrome.

UNLABELLED: Continuous neuromuscular blockade is often necessary in patients being treated for acute respiratory distress syndrome (ARDS) to optimize oxygenation. In this study, neuromuscular blockade (no response to two responses at the train-of-four stimulation at the orbicularis oculi muscle) was achieved in six patients with ARDS by a continuous infusion of cisatracurium. The plasma concentration of cisatracurium during the infusion averaged 1.00 (0.25-1.45) microg/mL, expressed as median (range). The clearance and half-life were 6.5 (3.3-7.6) mL. min(-1). kg(-1) and 25 (16-48) min, respectively. The laudanosine plasma concentrations were 0.70 (0.12-1.20) microg/mL. The pharmacokinetic variables of cisatracurium are similar to those of patients without organ failure undergoing elective surgery. Plasma laudanosine levels always remained well less that those associated with seizure activity in animal models. Long-term infusion of cisatracurium was not associated with any side effects. Cisatracurium is a suitable muscle relaxant when deep and continuous levels of muscle relaxation are required in patients treated for ARDS. IMPLICATIONS: We studied the pharmacokinetics of cisatracurium in six patients treated for respiratory distress syndrome by continuous muscle relaxation. A deep degree of neuromuscular blockade corresponding to abolition of two responses at the orbicularis oculi to train-of-four stimulation was obtained in all patients. The pharmacokinetic variables observed in these severely ill patients were similar to those of anesthetized patients. No accumulation of laudanosine was seen. Cisatracurium appears to be suitable when continuous muscle relaxation is required in critically ill patients.

A topological invariant to predict the three-dimensional writhe of ideal configurations of knots and links.

We present herein a topological invariant of oriented alternating knots and links that predicts the three-dimensional (3D) writhe of the ideal geometrical configuration of the considered knot/link. The fact that we can correlate a geometrical property of a given configuration with a topological invariant supports the notion that the ideal configuration contains important information about knots and links. The importance of the concept of ideal configuration was already suggested by the good correlation between the 3D writhe of ideal knot configurations and the ensemble average of the 3D writhe of random configurations of the considered knots. The values of the new invariant are quantized: multiples of 4/7 for links with an odd number of components (including knots) and 2/7 plus multiples of 4/7 for links with an even number of components.

The effects of residual pain on oxygenation and breathing pattern during morphine analgesia.

UNLABELLED: To determine the influence of pain on opioid-induced respiratory depression, we studied oxygenation and breathing patterns in 40 patients scheduled for knee surgery during postoperative patient-controlled analgesia (PCA). After 1 h of morphine PCA, patients were randomized to receive either 20 mL of placebo or bupivacaine 0.25% through a crural nerve catheter and allowed to use PCA for one more hour. Abnormal breathing events were identified and characterized by using the Edentrace II device (Nellcor, Jouy-en-Josas, France). The Spo2 below which the patient spent 25% and 50% of a studied period was calculated (Spo2(25), Spo2(50)). Pain relief with regional analgesia increased the incidence of abnormal respiratory events associated with oxygen desaturation: during the second period, the pain score was lower in the bupivacaine group (0.7+/-1 vs 4.1+/-1.2), morphine consumption was larger in the placebo group (4.2+/-1.3 vs 0.7+/-1.4 mg), and there were more abnormal obstructive breathing events in the bupivacaine group (11+/-16 vs 3.7+/-4.3). Spo2(25) and Spo2(50) were lower in the bupivacaine than in placebo group (91.5%+/-2.8% vs 93.1%+/-2.1%, 92.9%+/-2.4% vs 94.2%+/-1.8%). IMPLICATIONS: Pain relief with regional analgesia in patients previously treated with opioids increases the incidence of abnormal respiratory events associated with oxygen desaturation.

A note on the tangle model for DNA recombination.

The tangle model developed by Ernst and Sumners provides a rigorous framework to study processive DNA recombination. We suggest here a slight modification of that model. The tangle equations become: N(S) = b(1, 1), N(S + M) = b(2, 1), N(S + M + M) = b(5, 2), N(S + M + M + M) = b(8, 5), N(S + M + M + M + M) = b(11, 7), where M is the mechanism tangle, and S is the substrate tangle, that is the sum of O (outside tangle) and P (parent tangle). The advantage of this revisited model is that it faithfully models the fact that the recombination mechanism is the same during each event of recombination. This leads to new solutions for O and P, some of which are interesting from a biological viewpoint.

Permissive hypercapnia and intravascular oxygenator in the treatment of patients with ARDS.

This open clinical study was aimed at testing the hypothesis that an intravascular oxygenator (IVOX) may help to perform permissive hypoventilation in 10 patients with severe ARDS. After initial evaluation, we tried to reduce ventilator settings before and after IVOX implantation. Before IVOX, poor clinical tolerance and worsening oxygenation did not allow for a significant decrease in ventilator settings. With IVOX, peak inspiratory pressure (PIP) was reduced from 47 to 39 cm H2O (p = 0.005) and minute ventilation from 13 +/- 3.5 to 11 +/- 3 L/min. CO2 removal by IVOX allowed a significant decrease in PaCO2 from 66 +/- 15 to 59 +/- 13 mm Hg. Improvement of oxygenation with IVOX was not significant. Furthermore, interruption of oxygen flow through IVOX did not change oxygenation variables. Tolerance of the IVOX device was good, but insertion of the device was followed by a significant decrease in both cardiac index and pulmonary wedge pressure. In conclusion, IVOX improves tolerance of hypoventilation by limiting hypercapnia in ARDS patients. These preliminary results must be confirmed by a randomized controlled study.

Homo- and heteronuclear two-dimensional NMR studies of the globular domain of histone H1: full assignment, tertiary structure, and comparison with the globular domain of histone H5.

The globular domain of chicken histone H1 (GH1) has been studied by 1H homonuclear and 1H-15N heteronuclear 2D NMR spectroscopy. After the full assignment of the proton and 15N resonances, the tertiary structure of GH1 was determined by an iterative procedure using distance geometry and restrained simulated annealing. The secondary structure elements of GH1, three helices (S5-A16, S24-A34, N42-K56) followed by a beta-hairpin (L59-L73), are folded in a manner very similar to the corresponding parts of the globular domain of chicken histone H5 (GH5) [Clore et al. (1987) EMBO J. 6, 1833-1842; Ramakrishnan et al. (1993) Nature 362, 219-223]. However, subtle differences are detected between the two structures and between the electrostatic potentials surrounding the molecules. The most important differences are located in the loop between the second and third helices, a region that could be responsible for the different affinity for DNA. The most positively charged regions are not found in exactly the same position in GH1 and GH5. Nevertheless, their location seems to agree with the model where nucleosome binding takes place through contact points located at one DNA terminus and close to the dyad axis of the nucleosome [Schwabe & Travers (1993) Curr. Biol. 3, 628-630].

Homo- and heteronuclear two-dimensional NMR studies of the globular domain of histone H1: sequential assignment and secondary structure.

A recombinant 75 amino acid polypeptide corresponding to the globular domain of the chicken histone H1 (GH1) has been studied by 1H homonuclear and 1H-15N heteronuclear 2D NMR spectroscopy. Sequential assignment of the backbone and beta-proton resonances has enabled us to determine the secondary structure of GH1. It was found to consist of three helical regions (T7-S17, L25-Y37, E40-K56) and probably a beta-hairpin (L59-L73). This structure is similar to the structure of the globular domain of histone H5 (GH5) obtained both by NMR spectroscopy [Zarbock et al. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 7628-7632; Clore et al. (1987) EMBO J. 6, 1833-1842] and by X-ray crystallography [Ramakrishnan et al. (1993) Nature 362, 219-223]. The beta-hairpin as suggested for GH1 is also present in the X-ray structure of GH5 but has not been reported for the NMR structure of GH5.