Publications by authors named "Paul-Michel Mertes"

97 Publications

Use and interpretation of acute and baseline tryptase in perioperative hypersensitivity and anaphylaxis.

J Allergy Clin Immunol Pract 2021 Mar 18. Epub 2021 Mar 18.

Division of Allergy and Clinical Immunology, Brigham and Women's Hospital, Boston, MA; Harvard Medical School, Boston, MA. Electronic address:

Paired acute and baseline serum or plasma tryptase sampling and determination have recently been included as a mechanistic approach in the diagnostic and management guidelines of perioperative immediate hypersensitivity and anaphylaxis. The timing of this paired sampling is clearly defined in international consensus statements, with the optimal window for acute tryptase sampling between 30 minutes and 2 hours after the initiation of symptoms, while baseline tryptase should be measured in a sample collected before the event (pre-op) or at least 24 hours after all signs and symptoms have resolved. A transient elevation of the acute tryptase level greater than [2 + (1.2xbaseline tryptase level)] supports the involvement and activation of mast cells. Here, we provide the clinical, pathophysiological, and technical rationale for the procedure and interpretation of paired acute and baseline tryptase. Clinical examples, up-to-date knowledge of hereditary α-tryptasemia as a frequent cause of baseline tryptase of 7 μg/L and higher, mastocytosis, other clonal myeloid disorders, cardiovascular or renal failure, and technical improvements resulting in continued lowering of the 95th percentile value are discussed. Clues for improved management of perioperative immediate hypersensitivity and anaphylaxis include (i) sustained dissemination and implementation of updated guidelines; (ii) preoperative sample storage for deferred analysis; (ii) referral for thorough allergy investigation, screening for mast cell-related disorders and recommendations for future anesthetic procedures; (iii) sustained collaboration between anesthesiologists, immunologists, and allergists.
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http://dx.doi.org/10.1016/j.jaip.2021.03.011DOI Listing
March 2021

Hemodynamic Management During Kidney Transplantation: A French Survey.

Transplant Proc 2021 Feb 6. Epub 2021 Feb 6.

Department of Nephrology and Kidney Transplantation, Nouvel Hôpital Civil, University Hospitals of Strasbourg, Strasbourg, France.

Background: Hypovolemia or excess fluid load during kidney transplantation may have detrimental effects on the recipient and graft. The aim of our survey was to examine hemodynamic monitoring during kidney transplantation (KT) in French KT centers.

Basic Procedures: The online survey covered the organization of anesthesia, the type of hemodynamic monitoring available in each center, the frequency of use of each hemodynamic parameter, and the hemodynamic algorithm used to manage fluid administration.

Main Findings: Twenty-four centers answered the survey (70% of all the 34 French KT centers) and reported performing 2029 KTs in 2016. Anesthesia for KT was performed either by a general team (n = 12, 48%) or less often, by a specific team during open hours (n = 7, 28%), a specific 24-hour/24-hour team (n = 5, 20%), or an emergency team (n = 1, 4%). The centers reported that up to 8 different hemodynamic monitoring techniques were available for KT. Central venous pressure (CVP) is the most frequently used hemodynamic parameter (1278 KT, 63%). Among the 17 centers using CVP monitoring, 9 had no specific algorithm and the other 8 centers used a different algorithm to manage fluids with CVP. The total fluids administered during KT varied from 1000 mL to 3500 mL.

Conclusions: CVP was still the main hemodynamic parameter used in France during KT in 2016. Our results suggest that a large randomized controlled trial should be performed to specifically address the question of hemodynamic management during KT.
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http://dx.doi.org/10.1016/j.transproceed.2021.01.008DOI Listing
February 2021

Impact of High-Dose Prophylactic Anticoagulation in Critically Ill Patients With Coronavirus Disease 2019 Pneumonia.

Chest 2021 Jan 16. Epub 2021 Jan 16.

Department of Anesthesiology and Critical Care, European Georges Pompidou Hospital, Assistance Publique-Hôpitaux de Paris, Paris University, Paris, France.

Background: Because of the high risk of thrombotic complications (TCs) during severe acute respiratory syndrome coronavirus 2 infection, several scientific societies have proposed to increase the dose of preventive anticoagulation, although arguments in favor of this strategy are inconsistent.

Research Question: What is the incidence of TC in critically ill patients with coronavirus disease 2019 (COVID-19) and what is the relationship between the dose of anticoagulant therapy and the incidence of TC?

Study Design And Methods: All consecutive patients referred to eight French ICUs for COVID-19 were included in this observational study. Clinical and laboratory data were collected from ICU admission to day 14, including anticoagulation status and thrombotic and hemorrhagic events. The effect of high-dose prophylactic anticoagulation (either at intermediate or equivalent to therapeutic dose), defined using a standardized protocol of classification, was assessed using a time-varying exposure model using inverse probability of treatment weight.

Results: Of 538 patients included, 104 patients experienced a total of 122 TCs with an incidence of 22.7% (95% CI, 19.2%-26.3%). Pulmonary embolism accounted for 52% of the recorded TCs. High-dose prophylactic anticoagulation was associated with a significant reduced risk of TC (hazard ratio, 0.81; 95% CI, 0.66-0.99]) without increasing the risk of bleeding (HR, 1.11; 95% CI, 0.70-1.75).

Interpretation: High-dose prophylactic anticoagulation is associated with a reduction in thrombotic complications in critically ill COVID-19 patients without an increased risk of hemorrhage. Randomized controlled trials comparing prophylaxis with higher doses of anticoagulants are needed to confirm these results.

Trial Registry: ClinicalTrials.gov; No.: NCT04405869; URL: www.clinicaltrials.gov.
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http://dx.doi.org/10.1016/j.chest.2021.01.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7832130PMC
January 2021

Learn from the First Wave to Surf the Next One Optimally.

Eur J Vasc Endovasc Surg 2021 02 27;61(2):316. Epub 2020 Nov 27.

Department of Vascular Surgery and Kidney Transplantation, University Hospital of Strasbourg, Strasbourg, France; Groupe Européen de Recherche sur les Prothèses Appliquées à la Chirurgie Vasculaire, Strasbourg, France.

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http://dx.doi.org/10.1016/j.ejvs.2020.11.032DOI Listing
February 2021

Cerebrospinal Fluid Features in Patients With Coronavirus Disease 2019 and Neurological Manifestations: Correlation with Brain Magnetic Resonance Imaging Findings in 58 Patients.

J Infect Dis 2021 02;223(4):600-609

Service d'Imagerie, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Background: Neurological manifestations are common in patients with coronavirus disease 2019 (COVID-19), but little is known about pathophysiological mechanisms. In this single-center study, we examined neurological manifestations in 58 patients, including cerebrospinal fluid (CSF) analysis and neuroimaging findings.

Methods: The study included 58 patients with COVID-19 and neurological manifestations in whom severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) reverse-transcription polymerase chain reaction screening and on CSF analysis were performed. Clinical, laboratory, and brain magnetic resonance (MR) imaging data were retrospectively collected and analyzed.

Results: Patients were mostly men (66%), with a median age of 62 years. Encephalopathy was frequent (81%), followed by pyramidal dysfunction (16%), seizures (10%), and headaches (5%). CSF protein and albumin levels were increased in 38% and 23%, respectively. A total of 40% of patients displayed an elevated albumin quotient, suggesting impaired blood-brain barrier integrity. CSF-specific immunoglobulin G oligoclonal band was found in 5 patients (11%), suggesting an intrathecal synthesis of immunoglobulin G, and 26 patients (55%) presented identical oligoclonal bands in serum and CSF. Four patients (7%) had a positive CSF SARS-CoV-2 reverse-transcription polymerase chain reaction. Leptomeningeal enhancement was present on brain MR images in 20 patients (38%).

Conclusions: Brain MR imaging abnormalities, especially leptomeningeal enhancement, and increased inflammatory markers in CSF are frequent in patients with neurological manifestations related to COVID-19, whereas SARS-CoV-2 detection in CSF remained scanty.
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http://dx.doi.org/10.1093/infdis/jiaa745DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7798956PMC
February 2021

ICU re-organisation to face the first COVID-19 epidemic wave in a tertiary hospital.

Anaesth Crit Care Pain Med 2020 Dec 1;39(6):731-732. Epub 2020 Oct 1.

Pôle Anesthésie-Réanimation & Médecine Péri-Opératoire, Hôpitaux Universitaires de Strasbourg, Strasbourg, France; Équipe d'Accueil 3072, Institut de Physiologie, FMTS (Fédération de Médecine Translationnelle de Strasbourg), Faculté de Médecine, Université de Strasbourg (UNISTRA), France.

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http://dx.doi.org/10.1016/j.accpm.2020.09.005DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7527284PMC
December 2020

Mast cell activation tests: a new tool in the investigation of suspected perioperative allergic reactions?

Br J Anaesth 2020 12 26;125(6):856-859. Epub 2020 Sep 26.

Leeds Institute of Medical Research at St James's, University of Leeds, Leeds, UK.

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http://dx.doi.org/10.1016/j.bja.2020.08.044DOI Listing
December 2020

Epidemiology and outcome of patients admitted to intensive care after anaphylaxis in France: a retrospective multicentre study.

Br J Anaesth 2020 12 12;125(6):1025-1033. Epub 2020 Sep 12.

Service d'Anesthésie-Réanimation Chirurgicale, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

Background: Few data are available on patients who have experienced anaphylaxis and were admitted to ICUs. The purpose of this observational study was to describe the epidemiology and management of these patients.

Methods: This was a multicentre retrospective study carried out in 23 French ICUs between 2012 and 2017. All patients who suffered anaphylaxis and were transferred to an ICU were included. Data were collected using an electronic database after approval by an ethics committee.

Results: A total of 339 patients were included, and 17 (5%) died secondary to anaphylaxis. The main triggers were drugs (77%), contrast media (11%), and food (7%). Epinephrine was administered before ICU admission in 88% of patients with Grade III anaphylaxis and 100% of patients with Grade IV anaphylaxis. Most patients with Grades III and IV anaphylaxes did not receive the recommended dose of i.v. fluid of 30 ml kg within the first 4 h of ICU admission. The time to epinephrine administration was not statistically different between survivors and non-survivors, but non-survivors received a higher dose of epinephrine (median: 5 [3-10] vs 3 [2-7] mg; P<0.0001), which suggests that some forms of anaphylactic shock may be resistant to epinephrine. In multivariate analysis, only lactate concentration at ICU admission was a predictor of death (odds ratio: 1.47 [1.15-1.88]; P=0.002).

Conclusions: Lactate concentration at ICU admission appeared to be the most reliable criterion for assessing prognosis. Epinephrine is widely used during anaphylaxis, but the volume of fluid resuscitation was consistently lower than recommended.

Clinical Trial Registration: NCT04290507.
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http://dx.doi.org/10.1016/j.bja.2020.08.024DOI Listing
December 2020

Neurologic and neuroimaging findings in patients with COVID-19: A retrospective multicenter study.

Neurology 2020 09 17;95(13):e1868-e1882. Epub 2020 Jul 17.

From the Hôpitaux Universitaires de Strasbourg (S.K., F.L., S.B., F.-D.A., T.W.), Service d'imagerie 2, Hôpital de Hautepierre; Engineering Science, Computer Science and Imaging Laboratory (S.K., N.M.), UMR 7357, University of Strasbourg-CNRS; Service de Neurologie (M. Anheim), Hôpitaux Universitaires de Strasbourg; Institut de Génétique et de Biologie Moléculaire et Cellulaire (M. Anheim), INSERM-U964/CNRS-UMR7104/Université de Strasbourg, Illkirch; Fédération de Médecine Translationnelle de Strasbourg (M. Anheim), Université de Strasbourg; Hôpitaux universitaires de Strasbourg (H.M., F.M., J.H.), Service de Médecine Intensive Réanimation, Nouvel Hôpital Civil; INSERM (French National Institute of Health and Medical Research) (H.M., F.M.), UMR 1260, Regenerative Nanomedicine, Fédération de Médecine Translationnelle de Strasbourg; Médecine Intensive-Réanimation (M.S., F.S.), Hôpital de Hautepierre, Hôpitaux Universitaires de Strasbourg; Service de Neuroradiologie (H.O., F.B., J.M.), Hôpitaux Civils de Colmar; Service d'Imagerie (A. Khalil, A.G.), Unité de Neuroradiologie, Assistance Publique-Hôpitaux de Paris, Hôpital Bichat Claude Bernard; Université Paris Diderot (A. Khalil), Paris; Service de Neurologie (S. Carré, C.L.), Centre Hospitalier de Haguenau; Service de Radiologie (M. Alleg), Centre Hospitalier de Haguenau; Service de Neuroradiologie, (E.S., R.A., F.Z.) Hôpital Central, CHU de Nancy; CHIC Unisanté (L.J., P.N., Y.T.M.), Hôpital Marie Madeleine, Forbach; Neuroimaging Department (G.H., J. Benzakoun, C.O., G. Boulouis, M.E.-G., B.K.), GHU Paris Psychiatrie et Neurosciences, Hôpital Sainte-Anne, Université de Paris, INSERM U1266, F-75014; CHU Rennes (J.-C.F., B.C.-N.), Department of Neuroradiology; CHU Rennes (A.M.), Medical Intensive Care Unit; Department of Neuroradiology (P.-O.C., F.R., P.T.), University Hospital of Dijon, Hôpital François Mitterrand; Service de Radiologie (C.B.), CHU de Saint-Etienne; Service de Réanimation (X.F.), CH de Roanne; Service de Neuroradiologie (G.F., S.S.), CHU de Limoges; Radiology Department (I.d.B., G. Bornet), Hôpital Privé d'Antony; Department of Diagnostic and Interventional Neuroradiology (H.D.), University Hospital, Nantes; Neuroradiology Department (J. Berge), CHU de Bordeaux; Service de Neuroradiologie (A. Kazémi), CHU de Lille; Assistance Publique Hôpitaux de Paris (N.P.), Service de Neuroradiologie, Hôpital Pitié-Salpêtrière; Sorbonne Université (N.P.), Univ Paris 06, UMR S 1127, CNRS UMR 7225, ICM, F-75013; Service de Neuroradiologie Diagnostique (A.L.), Foundation A. Rothschild Hospital, Paris; EA CHIMERE 7516 (J.-M.C.), Université de Picardie Jules Verne; Service de NeuroRadiologie, pôle Imagerie Médicale, Centre Hospitalo-Universitaire d'Amiens; Hôpitaux Universitaires de Strasbourg (P.-E.Z., M.M.), UCIEC, Pôle d'Imagerie, Strasbourg; Observatoire Français de la Sclérose en Plaques (J.-C.B.), Lyon; Nephrology and Transplantation Department (S. Caillard), Hôpitaux Universitaires de Strasbourg; Inserm UMR S1109 (S. Caillard), LabEx Transplantex, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg; Hôpitaux Universitaires de Strasbourg (O.C., P.M.M.), Service d'Anesthésie-Réanimation, Nouvel Hôpital Civil; Hôpitaux Universitaires de Strasbourg (S.F.-K.), Laboratoire de Virologie Médicale; Radiology Department (M.O.), Nouvel Hôpital Civil, Strasbourg University Hospital; CHU de Strasbourg (N.M.), Service de Santé Publique, GMRC, F-67091 Strasbourg; Immuno-Rhumatologie Moléculaire (S.F.-K., J.H.), INSERM UMR_S1109, LabEx TRANSPLANTEX, Centre de Recherche d'Immunologie et d'Hématologie, Faculté de Médecine, Fédération Hospitalo-Universitaire OMICARE, Fédération de Médecine Translationnelle de Strasbourg, Université de Strasbourg; MRI Center (F.C.), Centre Hospitalier Lyon Sud, Hospices Civils de Lyon; and Université Lyon 1 (F.C.), CREATIS-LRMN, CNRS/UMR/5220-INSERM U630, Villeurbanne, France.

Objective: To describe neuroimaging findings and to report the epidemiologic and clinical characteristics of patients with coronavirus disease 2019 (COVID-19) with neurologic manifestations.

Methods: In this retrospective multicenter study (11 hospitals), we included 64 patients with confirmed COVID-19 with neurologic manifestations who underwent a brain MRI.

Results: The cohort included 43 men (67%) and 21 women (33%); their median age was 66 (range 20-92) years. Thirty-six (56%) brain MRIs were considered abnormal, possibly related to severe acute respiratory syndrome coronavirus. Ischemic strokes (27%), leptomeningeal enhancement (17%), and encephalitis (13%) were the most frequent neuroimaging findings. Confusion (53%) was the most common neurologic manifestation, followed by impaired consciousness (39%), presence of clinical signs of corticospinal tract involvement (31%), agitation (31%), and headache (16%). The profile of patients experiencing ischemic stroke was different from that of other patients with abnormal brain imaging: the former less frequently had acute respiratory distress syndrome ( = 0.006) and more frequently had corticospinal tract signs ( = 0.02). Patients with encephalitis were younger ( = 0.007), whereas agitation was more frequent for patients with leptomeningeal enhancement ( = 0.009).

Conclusions: Patients with COVID-19 may develop a wide range of neurologic symptoms, which can be associated with severe and fatal complications such as ischemic stroke or encephalitis. In terms of meningoencephalitis involvement, even if a direct effect of the virus cannot be excluded, the pathophysiology seems to involve an immune or inflammatory process given the presence of signs of inflammation in both CSF and neuroimaging but the lack of virus in CSF.

Clinicaltrialsgov Identifier: NCT04368390.
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http://dx.doi.org/10.1212/WNL.0000000000010112DOI Listing
September 2020

Coronavirus Disease 2019: Associated Multiple Organ Damage.

Open Forum Infect Dis 2020 Jul 21;7(7):ofaa249. Epub 2020 Jun 21.

Service d'Anesthésie-Réanimation, Nouvel Hôpital Civil, Hôpitaux Universitaires de Strasbourg, Strasbourg, France.

A 56-year-old man presented a particularly severe and multisystemic case of coronavirus disease 2019 (COVID-19). In addition to the common lung and quite common pulmonary embolism and kidney injuries, he presented ocular and intestinal injuries that, to our knowledge, have not been described in COVID-19 patients. Although it is difficult to make pathophysiological hypotheses about a single case, the multiplicity of injured organs argues for a systemic response to pulmonary infection. A better understanding of physiopathology should feed the discussion about therapeutic options in this type of multifocal damage related to severe acute respiratory syndrome coronavirus 2.
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http://dx.doi.org/10.1093/ofid/ofaa249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7336548PMC
July 2020

In-ICU COVID-19 patients' characteristics for an estimation in post-ICU rehabilitation care requirement.

Anaesth Crit Care Pain Med 2020 08 13;39(4):479-480. Epub 2020 Jun 13.

Pôle Anesthésie Réanimation Chirurgicale, service de Réanimation Chirurgicale, Hôpitaux Universitaires de Strasbourg NHC, 67000 Strasbourg, France; EA 3072, Institut de Physiologie, FMTS (Fédération de médecine translationnelle de Strasbourg), Faculté de Médecine de Strasbourg, Université de Strasbourg, Strasbourg, France. Electronic address:

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http://dx.doi.org/10.1016/j.accpm.2020.06.002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7293481PMC
August 2020

Brain MRI Findings in Severe COVID-19: A Retrospective Observational Study.

Radiology 2020 11 16;297(2):E242-E251. Epub 2020 Jun 16.

From the Hôpitaux Universitaires de Strasbourg, Service d'Imagerie 2, Hôpital de Hautepierre, Strasbourg, France (S.K.).

Background Brain MRI parenchymal signal abnormalities have been associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Purpose To describe the neuroimaging findings (excluding ischemic infarcts) in patients with severe coronavirus disease 2019 (COVID-19) infection. Materials and Methods This was a retrospective study of patients evaluated from March 23, 2020, to April 27, 2020, at 16 hospitals. Inclusion criteria were () positive nasopharyngeal or lower respiratory tract reverse transcriptase polymerase chain reaction assays, () severe COVID-19 infection defined as a requirement for hospitalization and oxygen therapy, () neurologic manifestations, and () abnormal brain MRI findings. Exclusion criteria were patients with missing or noncontributory data regarding brain MRI or brain MRI showing ischemic infarcts, cerebral venous thrombosis, or chronic lesions unrelated to the current event. Categorical data were compared using the Fisher exact test. Quantitative data were compared using the Student test or Wilcoxon test. < .05 represented a significant difference. Results Thirty men (81%) and seven women (19%) met the inclusion criteria, with a mean age of 61 years ± 12 (standard deviation) (age range, 8-78 years). The most common neurologic manifestations were alteration of consciousness (27 of 37, 73%), abnormal wakefulness when sedation was stopped (15 of 37, 41%), confusion (12 of 37, 32%), and agitation (seven of 37, 19%). The most frequent MRI findings were signal abnormalities located in the medial temporal lobe in 16 of 37 patients (43%; 95% confidence interval [CI]: 27%, 59%), nonconfluent multifocal white matter hyperintense lesions seen with fluid-attenuated inversion recovery and diffusion-weighted sequences with variable enhancement, with associated hemorrhagic lesions in 11 of 37 patients (30%; 95% CI: 15%, 45%), and extensive and isolated white matter microhemorrhages in nine of 37 patients (24%; 95% CI: 10%, 38%). A majority of patients (20 of 37, 54%) had intracerebral hemorrhagic lesions with a more severe clinical presentation and a higher admission rate in intensive care units (20 of 20 patients [100%] vs 12 of 17 patients without hemorrhage [71%], = .01) and development of the acute respiratory distress syndrome (20 of 20 patients [100%] vs 11 of 17 patients [65%], = .005). Only one patient had SARS-CoV-2 RNA in the cerebrospinal fluid. Conclusion Patients with severe coronavirus disease 2019 and without ischemic infarcts had a wide range of neurologic manifestations that were associated with abnormal brain MRI scans. Eight distinctive neuroradiologic patterns were described. © RSNA, 2020.
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http://dx.doi.org/10.1148/radiol.2020202222DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7301613PMC
November 2020

Decompressive hemicraniectomy for acute ischemic stroke in a patient implanted with a left ventricular assist device: a case report.

BMC Cardiovasc Disord 2020 06 10;20(1):281. Epub 2020 Jun 10.

Pôle Anesthésie Réanimation Chirurgicale, service de Réanimation Chirurgicale, Hôpitaux Universitaires de Strasbourg NHC, 1, Place de l'Hôpital, 67000, Strasbourg, France.

Background: Thromboembolic ischemic stroke (IS) is one of the most feared complications of left ventricular assist device (LVAD) placement and represents a challenge to surgical management because of concomitant anticoagulant therapy.

Case Presentation: A 39-year-old man presented with cardiogenic shock following an out-of-hospital cardiac arrest. After a period of stabilization, the patient was referred for LVAD placement. Upon recovery from anesthesia, he presented with acute neurological deficits suggestive of IS. A brain computed tomography confirmed the diagnosis, and an emergency decompressive hemicraniectomy (DHC) was performed. Anticoagulation was managed empirically. The patient's neurological status progressively improved and he was referred for heart transplantation at five months from DHC. One month later, cranioplasty was performed.

Conclusions: This report suggests an anticoagulation management approach in combination with decompressive craniectomy after IS in a patient with LVAD placement was successful. An optimized anticoagulation management and collaborative team-based practice may contribute to successful outcomes in complex cases.
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http://dx.doi.org/10.1186/s12872-020-01576-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7285430PMC
June 2020

Minimally invasive surgery for left ventricular assist device implantation is safe and associated with a decreased risk of right ventricular failure.

J Thorac Dis 2020 Apr;12(4):1496-1506

Department of Cardiovascular Surgery, University Hospitals of Strasbourg, Strasbourg, France.

Background: Right ventricular failure (RVF) after left ventricular assist device (LVAD) implantation is associated with significant mortality and morbidity. The objective of this study was to determine pre- and postoperative risk factors associated with the occurrence of RVF after LVAD implantation.

Methods: This retrospective study included 68 patients who received LVADs between 2010 and 2018 either for bridge to transplant (40 patients, 58.8%) or bridge to destination therapy (28 patients, 41.2%). RVF after LVAD implantation was defined according to the INTERMACS classification. The primary endpoint was the occurrence of RVF. The secondary endpoints were hospital mortality and morbidity and long-term survival.

Results: The majority of patients (61.8%) had an INTERMACS profile 1 (36.8%) or 2 (25.0%). The LVAD was implanted either by sternotomy (37 patients, 54.4%) or thoracotomy (31 patients, 45.6%). RVF after LVAD implantation was observed in 32 patients (47.1%). In univariate analysis, an elevated serum glutamic oxaloacetic transaminase (SGOT) (P=0.028) and a high preoperative vasoactive inotropic score (VIS) (P=0.028) were significantly associated with an increased risk of RVF, whereas the implantation of LVAD through a thoracotomy approach was associated with a significant reduction in this risk (P=0.006). The multivariate analysis demonstrated that only the thoracotomy approach was significantly associated with decreased risk of RVF (odds ratio =0.33, 95% confidence interval: 0.17-0.96; P=0.042). Hospital mortality was 53.1% and 5.6% in the RVF and control groups, respectively (P<0.0001). The incidence of stroke and postoperative acute renal failure were significantly increased in the RVF group compared with the control group. The survival after LVAD implantation was 33.5%±9.0% and 85.4%±6.0% at 1 year in the RVF and control groups, respectively (P<0.0001).

Conclusions: LVAD implantation by thoracotomy significantly reduced the risk of postoperative RVF. This surgical approach should, therefore, be favored.
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http://dx.doi.org/10.21037/jtd.2020.02.32DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7212123PMC
April 2020

High risk of thrombosis in patients with severe SARS-CoV-2 infection: a multicenter prospective cohort study.

Intensive Care Med 2020 06 4;46(6):1089-1098. Epub 2020 May 4.

Service de Médecine Intensive Réanimation, Nouvel Hôpital Civil, Hôpitaux universitaires de Strasbourg, 1, Place de l'Hôpital, 67091, Strasbourg Cedex, France.

Purpose: Little evidence of increased thrombotic risk is available in COVID-19 patients. Our purpose was to assess thrombotic risk in severe forms of SARS-CoV-2 infection.

Methods: All patients referred to 4 intensive care units (ICUs) from two centers of a French tertiary hospital for acute respiratory distress syndrome (ARDS) due to COVID-19 between March 3rd and 31st 2020 were included. Medical history, symptoms, biological data and imaging were prospectively collected. Propensity score matching was performed to analyze the occurrence of thromboembolic events between non-COVID-19 ARDS and COVID-19 ARDS patients.

Results: 150 COVID-19 patients were included (122 men, median age 63 [53; 71] years, SAPSII 49 [37; 64] points). Sixty-four clinically relevant thrombotic complications were diagnosed in 150 patients, mainly pulmonary embolisms (16.7%). 28/29 patients (96.6%) receiving continuous renal replacement therapy experienced circuit clotting. Three thrombotic occlusions (in 2 patients) of centrifugal pump occurred in 12 patients (8%) supported by ECMO. Most patients (> 95%) had elevated D-dimer and fibrinogen. No patient developed disseminated intravascular coagulation. Von Willebrand (vWF) activity, vWF antigen and FVIII were considerably increased, and 50/57 tested patients (87.7%) had positive lupus anticoagulant. Comparison with non-COVID-19 ARDS patients (n = 145) confirmed that COVID-19 ARDS patients (n = 77) developed significantly more thrombotic complications, mainly pulmonary embolisms (11.7 vs. 2.1%, p < 0.008). Coagulation parameters significantly differed between the two groups.

Conclusion: Despite anticoagulation, a high number of patients with ARDS secondary to COVID-19 developed life-threatening thrombotic complications. Higher anticoagulation targets than in usual critically ill patients should therefore probably be suggested.
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http://dx.doi.org/10.1007/s00134-020-06062-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7197634PMC
June 2020

Medical algorithms: Diagnosis and investigation of perioperative immediate hypersensitivity reactions.

Allergy 2020 08 20;75(8):2139-2142. Epub 2020 Mar 20.

Department of Dermatology and allergy, Danish Anaesthesia Allergy Centre, Allergy Clinic, Gentofte Hospital, Hellerup, Denmark.

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http://dx.doi.org/10.1111/all.14226DOI Listing
August 2020

Management of suspected immediate perioperative allergic reactions: an international overview and consensus recommendations.

Br J Anaesth 2019 Jul 24;123(1):e50-e64. Epub 2019 May 24.

Department of Anaesthesia and Perioperative Medicine, Monash University, Melbourne, Australia; Department of Anaesthesia, Peninsula Health, Melbourne, Australia.

Suspected perioperative allergic reactions are rare but can be life-threatening. The diagnosis is difficult to make in the perioperative setting, but prompt recognition and correct treatment is necessary to ensure a good outcome. A group of 26 international experts in perioperative allergy (anaesthesiologists, allergists, and immunologists) contributed to a modified Delphi consensus process, which covered areas such as differential diagnosis, management during and after anaphylaxis, allergy investigations, and plans for a subsequent anaesthetic. They were asked to rank the appropriateness of statements related to the immediate management of suspected perioperative allergic reactions. Statements were selected to represent areas where there is a lack of consensus in existing guidelines, such as dosing of epinephrine and fluids, the management of impending cardiac arrest, and reactions refractory to standard treatment. The results of the modified Delphi consensus process have been included in the recommendations on the management of suspected perioperative allergic reactions. This paper provides anaesthetists with an overview of relevant knowledge on the immediate and postoperative management of suspected perioperative allergic reactions based on current literature and expert opinion. In addition, it provides practical advice and recommendations in areas where consensus has been lacking in existing guidelines.
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http://dx.doi.org/10.1016/j.bja.2019.04.044DOI Listing
July 2019

The use of drug provocation testing in the investigation of suspected immediate perioperative allergic reactions: current status.

Br J Anaesth 2019 Jul 23;123(1):e126-e134. Epub 2019 Apr 23.

Allergy Unit, Allergo-Anaesthesia Unit, Hospital Central de la Cruz Roja, Faculty of Medicine, Alfonso X El Sabio University, ARADyAL, Madrid, Spain.

Suspected perioperative allergic reactions are often severe. To avoid potentially life-threatening re-exposure to the culprit drug, establishing a firm diagnosis and identifying the culprit is crucial. Drug provocation tests are considered the gold standard in drug allergy investigation but have not been recommended in the investigation of perioperative allergy, mainly because of the pharmacological effects of drugs such as induction agents and neuromuscular blocking agents. Some specialised centres have reported benefits of provocation testing in perioperative allergy investigation, but the literature on the subject is limited. Here we provide a status update on the use of drug provocation testing in perioperative allergy, including its use in specific drug groups. This review is based on a literature search and experiences of the authors comprising anaesthesiologists and allergists with experience in perioperative allergy investigation. In addition, 19 participating centres in the International Suspected Perioperative Allergic Reaction Group were surveyed on the use of provocation testing in perioperative allergy investigation. A response was received from 13 centres in eight European countries, New Zealand, and the USA. Also, 21 centres from the Australian and New Zealand Anaesthetic Allergy Group were surveyed. Two centres performed provocation routinely and seven centres performed no provocations at all. Nearly half of the centres reported performing provocations with induction agents and neuromuscular blocking agents. Drug provocation testing is being used in perioperative allergy investigation in specialised centres, but collaborations between relevant specialties and multicentre studies are necessary to determine indications and establish common testing protocols.
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http://dx.doi.org/10.1016/j.bja.2019.03.018DOI Listing
July 2019

An EAACI position paper on the investigation of perioperative immediate hypersensitivity reactions.

Allergy 2019 10 18;74(10):1872-1884. Epub 2019 Jun 18.

Allergy Unit, Department of Dermatology, University Hospital, University of Basel, Basel, Switzerland.

Perioperative immediate hypersensitivity reactions are rare. Subsequent allergy investigation is complicated by multiple simultaneous drug exposures, the use of drugs with potent effects and the many differential diagnoses to hypersensitivity in the perioperative setting. The approach to the investigation of these complex reactions is not standardized, and it is becoming increasingly apparent that collaboration between experts in the field of allergy/immunology/dermatology and anaesthesiology is needed to provide the best possible care for these patients. The EAACI task force behind this position paper has therefore combined the expertise of allergists, immunologists and anaesthesiologists. The aims of this position paper were to provide recommendations for the investigation of immediate-type perioperative hypersensitivity reactions and to provide practical information that can assist clinicians in planning and carrying out investigations.
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http://dx.doi.org/10.1111/all.13820DOI Listing
October 2019

Molecular mechanisms and pathophysiology of perioperative hypersensitivity and anaphylaxis: a narrative review.

Br J Anaesth 2019 Jul 8;123(1):e38-e49. Epub 2019 Mar 8.

Anaesthetic Allergy Referral Centre of Western Australia, Department of Anaesthesia, Sir Charles Gairdner Hospital, Perth, Australia; Department of Pharmacology, University of Western Australia, Perth, Australia.

Perioperative hypersensitivity reactions (POH) constitute a clinical and diagnostic challenge, a consequence of heterogeneous clinical presentations, and multiple underlying pathomechanisms. POH do not necessarily involve an allergen-specific immune response with cross-linking of specific immunoglobulin E (sIgE) antibodies on mast cells and basophils. POH can also result from alternative specific and non-specific effector cell activation/degranulation such as complement-derived anaphylatoxins and off-target occupancy of mast cell, basophil, or both surface receptors. Moreover, POH and anaphylaxis can occur independent from mast cell and basophil degranulation. The manifestations of POH primarily affect the cardiovascular, respiratory, and integumentary systems. POH present within the context of surgical or procedural pathology and the effects of surgical and anaesthetic techniques on pre-existing physiological reserve. The majority of cases of appropriately-treated intraoperative anaphylaxis can be considered a compensated cardiovascular anaphylaxis. With increasing severity of anaphylaxis, maldistribution and hypovolaemia lead to reduced venous return and circulatory failure. Treatment with a combination of epinephrine and i.v. fluid is critical for successful resuscitation, although the excessive use of epinephrine without adequate volume expansion may be deleterious. Neural control of the airways is important in the pathophysiology of bronchospasm. Anticholinergic drug premedication is beneficial in patients with hyperreactive airways. Pulmonary oedema can result from a combination of pulmonary capillary hypertension, incompetence of the alveolocapillary membrane, or both. Angioedema can be distinguished mechanistically into histaminergic and non-histaminergic (e.g. bradykinin-mediated). An understanding of the molecular mechanisms and pathophysiology of POH are essential for the immediate management and subsequent investigation of these cases.
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http://dx.doi.org/10.1016/j.bja.2019.01.031DOI Listing
July 2019

Comparative epidemiology of suspected perioperative hypersensitivity reactions.

Br J Anaesth 2019 07 4;123(1):e16-e28. Epub 2019 Mar 4.

Allergy Unit, S. Martino Policlinic Hospital, Genoa, Italy.

Suspected perioperative hypersensitivity reactions are rare but contribute significantly to the morbidity and mortality of surgical procedures. Recent publications have highlighted the differences between countries concerning the respective risk of different drugs, and changes in patterns of causal agents and the emergence of new allergens. This review summarises recent information on the epidemiology of perioperative hypersensitivity reactions, with specific consideration of differences between geographic areas for the most frequently involved offending agents.
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http://dx.doi.org/10.1016/j.bja.2019.01.027DOI Listing
July 2019

Anaesthetic management of patients with pre-existing allergic conditions: a narrative review.

Br J Anaesth 2019 Jul 13;123(1):e65-e81. Epub 2019 Mar 13.

Department of Anaesthesia and Peri-operative Medicine, Auckland City Hospital, Auckland, New Zealand.

This narrative review seeks to distinguish the clinical patterns of pre-existing allergic conditions from other confounding non-allergic clinical entities, and to identify the potential related risks and facilitate their perioperative management. Follow-up investigation should be performed after a perioperative immediate hypersensitivity to establish a diagnosis and provide advice for subsequent anaesthetics, the main risk factor for perioperative immunoglobulin E (IgE)-mediated anaphylaxis being a previous uninvestigated perioperative immediate hypersensitivity reaction. The concept of cross-reactivity between drugs used in the perioperative setting and food is often quoted, but usually not supported by evidence. There is no reason to avoid propofol in egg, soy, or peanut allergy. The allergenic determinants have been characterised for fish, shellfish, and povidone iodine, but remain unknown for iodinated contrast agents. Iodinated drugs may be used in seafood allergy. Evidence supporting the risk for protamine allergy in fish allergy and in neutral protamine Hagedorn insulin use is lacking. Conversely, cross-reactivity to gelatin-based colloid may occur in α-gal syndrome. Atopy and allergic asthma along with other non-allergic conditions, such as NSAID-exacerbated respiratory disease, chronic urticaria, mastocytosis, and hereditary or acquired angioedema, are not risk factors for IgE-mediated drug allergy, but there is a perioperative risk associated with the potential for exacerbation of the various conditions.
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http://dx.doi.org/10.1016/j.bja.2019.01.020DOI Listing
July 2019

Controversies in Drug Allergy: Drug Allergy Pathways.

J Allergy Clin Immunol Pract 2019 01 17;7(1):46-60.e4. Epub 2018 Dec 17.

Division of Rheumatology, Allergy and Immunology, Department of Medicine, Massachusetts General Hospital, Boston, Mass; Department of Medicine, Harvard Medical School, Boston, Mass. Electronic address:

Drug allergy pathways are standardized approaches for patients reporting prior drug allergies with the aim of quality improvement and promotion of antibiotic stewardship. At the International Drug Allergy Symposium during the 2018 American Academy of Allergy, Asthma, and Immunology/World Allergy Organization Joint Congress in Orlando, Florida, drug allergy pathways were discussed from international perspectives with a focus on beta-lactam allergy pathways and pragmatic approaches for acute care hospitals. In this expert consensus document, we review current pathways, and detail important considerations in devising, implementing, and evaluating beta-lactam allergy pathways for hospitalized patients. We describe the key patient and institutional factors that must be considered in risk stratification, the central feature of pathway design. We detail shared obstacles to widespread beta-lactam allergy pathway implementation and identify potential solutions to address these challenges.
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http://dx.doi.org/10.1016/j.jaip.2018.07.037DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6466632PMC
January 2019

Adjusted calculation model of heparin management during cardiopulmonary bypass in obese patients: A randomised controlled trial.

Eur J Anaesthesiol 2018 08;35(8):613-620

From the Department of Anesthesiology and Intensive Care (MV, EH, TW, FL, CT, OC, P-MM, AS), Laboratory of Haemostasis (LG, LS), Department of Cardiac Surgery, NHC (THM) and Department of BioStatistics (FS), Federation de Medecine Translationelle, University Hospital, Strasbourg, France.

Background: Anticoagulation during cardiopulmonary bypass (CPB) is usually adapted to total body weight (TBW). This may be inaccurate in obese patients and lead to heparin overdose with a risk of bleeding.

Objectives: To validate the efficacy and safety of an adjusted calculation model of heparin dosing based on ideal body weight (IBW) rather than TBW in obese CPB patients, with an expected target mean plasma heparin concentration of 4.5 IU ml after onset of CPB in the experimental group.

Design: Randomised controlled study.

Setting: University hospital.

Patients: Sixty obese patients (BMI ≥ 30 kg m) scheduled for CPB were included from January to June 2016.

Interventions: Patients received a bolus dose of unfractionated heparin of either 300 IU kg of TBW or 340 IU kg of IBW before onset of CPB. Additional adjusted boluses were injected to maintain an activated clotting time (ACT) of at least 400 s.

Main Outcome Measures: Plasma heparin concentration and ACT were measured at different time points. Total heparin doses and transfusion requirements were recorded.

Results: The target heparin concentration of 4.5 IU ml was reached in the IBW group at the onset of CPB and maintained at all time points during CPB. Heparin concentrations were significantly higher in the TBW group after the bolus (6.52 ± 0.97 vs. 4.54 ± 1.13 IU ml, P < 0.001) and after cardioplegia (5.10 ± 1.03 vs. 4.31 ± 1.00 IU ml, P = 0.02). Total heparin doses were significantly higher in the TBW group. Mean ACT was significantly lower in the IBW group but remained over 400 s during CPB. The correlation between heparin and ACT was poor. Peri-operative bleeding and transfusion requirements were comparable. No thrombotic event occurred in the CPB circuit.

Conclusion: The current IBW-adjusted regimen of heparin administration may be used efficiently in obese CPB patients, thereby avoiding overdose which cannot be accurately assessed by ACT monitoring alone.

Trial Registration: ClinicalTrials.gov identifier: NCT02675647.
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http://dx.doi.org/10.1097/EJA.0000000000000784DOI Listing
August 2018

Intramural atrial hematoma complicating transesophageal echocardiography during cardiac arrest.

Heart Lung 2018 May - Jun;47(3):248-249. Epub 2018 Mar 3.

Department of Cardiology, University Hospitals of Strasbourg, Nouvel Hôpital Civil, Strasbourg, France.

Background: Adequate strategies using either transthoracic (TTE) or transesophageal (TEE) echocardiography in patients receiving cardiopulmonary resuscitation (CPR) is an ongoing area of research.

Objectives: As transthoracic point-of-care ultrasound (POCUS) during cardiac arrest resuscitation might result in an increased duration of interruptions in the delivery of chest compressions; the use of TEE has been proposed as an alternative.

Methods: No technical complications of either TTE nor TEE are so far being reported in the literature.

Results: We report the case of a left intramural atrial hematoma complicating TEE procedure during cardiac arrest. This highlights a unique and to our knowledge, first-in-man, described complicating TEE procedure during CPR.

Conclusions: Further research on the safety of transesophageal echo during CRP is mandatory and the question about any potential harm of particular interest.
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http://dx.doi.org/10.1016/j.hrtlng.2018.01.006DOI Listing
January 2019

Analysis of Transfusion-Related Acute Lung Injury and Possible Transfusion-Related Acute Lung Injury Reported to the French Hemovigilance Network From 2007 to 2013.

Transfus Med Rev 2018 01 15;32(1):16-27. Epub 2017 Jul 15.

Agence Nationale de Sécurité du Médicament, Saint-Denis, France. Electronic address:

Using the French Hemovigilance Network database from 2007 to 2013, we provide information on demographics, incidence, and risk factors of reported transfusion-related acute lung injury (TRALI) and possible TRALI, analyze TRALI mitigation efforts for fresh frozen plasma and platelet concentrates, and consider the impact of platelet additive solutions on TRALI incidence. We applied the Toronto consensus conference definitions for TRALI and possible TRALI. Two TRALI subgroups were considered: "antibody positive" when a donor has human leukocyte antigen (class I or II) and/or human neutrophil antigen antibodies and the recipient has cognate antigen, and "antibody negative" when immunological investigation is negative or not done. The analysis targeted 378 cases, divided into antibody-positive TRALI (n=75), antibody-negative TRALI (n=100), and possible TRALI (n=203). TRALI patients were younger and received more blood components than the general population of transfused patients. Moreover, we identified the following clinical conditions where patients seemed to be at higher risk to develop TRALI: postpartum hemorrhage, acute myeloid leukemia, liver transplantation, allogeneic and autologous hematopoietic stem cells transplantation, polytrauma, and thrombotic microangiopathy. Policy measures intended to reduce antibody-positive TRALI were found effective for apheresis platelet concentrates and fresh frozen plasma but not for whole blood-derived platelet concentrates. The use of platelet additive solutions was associated with a significant reduction in the incidence of TRALI following transfusion of buffy coat-derived platelet concentrates but not following transfusion of apheresis platelets. Our data reinforce the concept that possible TRALI and TRALI, as defined in the Canadian consensus conference, share many characteristics. No specific policy measures are currently directed at mitigation of possible TRALI despite its impact on transfusion safety. Despite TRALI mitigation measures, the overall incidence of TRALI cases reported to the French Hemovigilance system was not significantly reduced. Therefore, additional research is needed to reduce, if not eradicate, all TRALI categories.
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http://dx.doi.org/10.1016/j.tmrv.2017.07.001DOI Listing
January 2018

Epinephrine but not vasopressin attenuates the airway response to anaphylactic shock in rats.

Exp Lung Res 2017 04 25;43(3):158-166. Epub 2017 May 25.

b Service d'Anesthésie-Réanimation Chirurgicale, Pôle Anesthésie, Réanimations Chirurgicales, SAMU-SMUR, Nouvel Hôpital Civil , Hôpitaux Universitaires de Strasbourg , Strasbourg , France.

Purpose: The two life-threatening signs of anaphylactic shock (AS) are severe arterial hypotension and bronchospasm. Guidelines recommend epinephrine as first-line treatment. Arginine vasopressin (AVP) has been proposed as an alternative if epinephrine does not correct arterial hypotension. These two drugs may have beneficial, neutral or deleterious effects on airflow either directly or by modifying factors that regulate vasodilatation and/or edema in the bronchial wall.

Aim Of The Study: To compare the effects of epinephrine and AVP on airflow and airway leakage in a rat model of AS.

Materials And Methods: Thirty-two ovalbumin-sensitized rats were randomized into four groups: control (CON), AS without treatment (OVA), AS treated with epinephrine (EPI), and AS treated with AVP (AVP). Mean arterial pressure (MAP), respiratory resistance and elastance and microvascular leakage in the airways were measured.

Results: All OVA rats died within 20 minutes following ovalbumin injection. Ovalbumin induced severe arterial hypotension and airway obstruction (221 ± 36 hPa.s.L vs. vehicle 52 ± 8 hPa.s.L; p < 0.0001) associated with microvascular leakage distributed throughout the trachea, bronchi and intra-pulmonary airways. EPI and AVP extended survival time; EPI restored a higher level of MAP than AVP. Airway obstruction was attenuated by epinephrine (146 ± 19 hPa.s.L; p < 0.0001), but not by AVP (235 ± 58 hPa.s.L; p = 0.42).

Conclusions: Epinephrine was superior to AVP for alleviating the airway response in a rat model of AS. When bronchospasm and severe arterial hypotension are present during AS, epinephrine should be the drug of choice.
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http://dx.doi.org/10.1080/01902148.2017.1323981DOI Listing
April 2017

Hypersensitivity transfusion reactions due to IgA deficiency are rare according to French hemovigilance data.

J Allergy Clin Immunol 2017 09 13;140(3):884-885. Epub 2017 Apr 13.

Department of Anesthesia and Intensive Care, Hôpitaux Universitaires de Strasbourg, Nouvel Hôpital Civil, Strasbourg, France. Electronic address:

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http://dx.doi.org/10.1016/j.jaci.2017.03.029DOI Listing
September 2017