Persistent COVID-19: a case report of an immunocompromised patient and a literature review.

Introduction Immunocompromised patients can show prolonged shedding of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and persistent symptoms, which is called persistent COVID-19. Case presentation We report a case of an immunocompromised patient who was treated for mantle cell lymphoma and was suffering from B-cell depletion. The patient developed persistent COVID-19, which was confirmed by real-time polymerase chain reaction (RT-PCR) tests in only sputum and bronchoalveolar fluid which remained positive for at least 112 days. The patient was successfully treated with SARS-CoV-2 convalescent plasma. Conclusion It could be of interest to investigate the RT-PCR results of SARS-CoV-2 in sputum/bronchoalveolar lavage samples from immunocompromised patients with unexplained pneumonia.

Efficacy and Safety of Rituximab-Based Treatments in Angioedema With Acquired C1-Inhibitor Deficiency.

BACKGROUND: Angioedema (AE) due to acquired C1-inhibitor (C1-INH) deficiency (AAE-C1-INH) is related to excessive consumption of C1-INH or to anti-C1-INH antibodies, and is frequently associated with lymphoproliferative syndromes or monoclonal gammopathies. Standard of care for prophylactic treatment in this condition is not established. Rituximab may be effective to prevent attacks, especially if the lymphoid hemopathy is controlled, but data are scarce. OBJECTIVE: To evaluate efficacy of rituximab in AAE-C1-INH. METHODS: A retrospective multicenter study was carried out in France, including patients with AAE-C1-INH treated with rituximab between April 2005 and July 2019. RESULTS: Fifty-five patients with AAE-C1-INH were included in the study, and 23 of them had an anti-C1-INH antibody. A lymphoid malignancy was identified in 39 patients, and a monoclonal gammopathy in 9. There was no associated condition in 7 cases. Thirty patients received rituximab alone or in association with chemotherapy (n = 25). Among 51 patients with available follow-up, 34 patients were in clinical remission and 17 patients had active AE after a median follow-up of 3.9 years (interquartile range, 1.5-7.7). Three patients died. The presence of anti-C1-INH antibodies was associated with a lower probability of AE remission (hazard ratio, 0.29 [95% CI, 0.12-0.67]; P = .004). Relapse was less frequent in patients with lymphoma (risk ratio, 0.27 [95% CI, 0.09-0.80]; P = .019) and in patients treated with rituximab and chemotherapy (risk ratio, 0.31 [95% CI, 0.12-0.79]; P = .014). CONCLUSIONS: Rituximab is an efficient and well-tolerated therapeutic option in AE, especially in lymphoid malignancies and in the absence of detectable anti-C1-INH antibodies.

Tocilizumab versus anakinra in COVID-19: results from propensity score matching.

Background: Tocilizumab and anakinra are anti-interleukin drugs to treat severe coronavirus disease 2019 (COVID-19) refractory to corticosteroids. However, no studies compared the efficacy of tocilizumab versus anakinra to guide the choice of the therapy in clinical practice. We aimed to compare the outcomes of COVID-19 patients treated with tocilizumab or anakinra. Methods: Our retrospective study was conducted in three French university hospitals between February 2021 and February 2022 and included all the consecutive hospitalized patients with a laboratory-confirmed severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection assessed by RT-PCR who were treated with tocilizumab or anakinra. A propensity score matching was performed to minimize confounding effects due to the non-random allocation. Results: Among 235 patients (mean age, 72 years; 60.9% of male patients), the 28-day mortality (29.4% vs. 31.2%, p = 0.76), the in-hospital mortality (31.7% vs. 33.0%, p = 0.83), the high-flow oxygen requirement (17.5% vs. 18.3%, p = 0.86), the intensive care unit admission rate (30.8% vs. 22.2%, p = 0.30), and the mechanical ventilation rate (15.4% vs. 11.1%, p = 0.50) were similar in patients receiving tocilizumab and those receiving anakinra. After propensity score matching, the 28-day mortality (29.1% vs. 30.4%, p = 1) and the rate of high-flow oxygen requirement (10.1% vs. 21.5%, p = 0.081) did not differ between patients receiving tocilizumab or anakinra. Secondary infection rates were similar between the tocilizumab and anakinra groups (6.3% vs. 9.2%, p = 0.44). Conclusion: Our study showed comparable efficacy and safety profiles of tocilizumab and anakinra to treat severe COVID-19.

Medication reconciliation in the geriatric unit: impact on the maintenance of post-hospitalization prescriptions.

Background Medication reconciliation prevents medication errors at care transition points. This process improves communication with general practitioners regarding the reasons for therapeutic changes, allowing those changes to be maintained after hospital discharge. Objective To investigate the impact of medication reconciliation in geriatrics on the sustainability of therapeutic optimization after hospital discharge. Setting This study was conducted in a geriatric unit in a University Hospital Centre in France. Method This was a retrospective study. For 6 months, all patients over 65 years who underwent the process of medication reconciliation performed by a clinical hospital pharmacist and a physician at admission and discharge, were included. A comparison between drug prescriptions at hospital discharge and the first prescription made outside the hospital was made to identify any differences. Main outcome measure The main outcome measures were the provision of the results of the medication reconciliation performed in the hospital to the relevant general practitioner, the subsequent acceptance of that information, the type of medication discrepancies one month after discharge and the therapeutic classes affected by the modifications. Results Among the 112 patients, medication reconciliation allowed us to identify and correct 87 unintentional discrepancies at admission (88% corrected) and 54 at discharge (92% corrected). Patients were discharged to homes or nursing homes (61%), geriatric rehabilitation units (38%) or psychiatric clinics (1%). A general practitioner wrote the first prescription renewal a mean of 36 ± 23 days after discharge, having been made aware of the medication reconciliation in only 24% of the cases (received and taken into account). The impact was a decrease in the number of patients with at least one discrepancy. Twenty-five percent of general practitioners who were aware about the medication reconciliation process accepted all therapeutic changes, while only 7% of those who were not informed did so (p = 0.02). The number of medication discrepancies observed was correlated with the number of medications for which prescriptions were renewed (p < 0.01). Conclusion Medication reconciliation involving therapeutic optimization and the justification of changes is essential to ensure the safety of the prescriptions written for patients. However, its impact after discharge is hampered by the fact that the results are often not received or taken into account by general practitioners. Taking medication reconciliation into account was associated with a significant increase in prescriptions that maintained therapeutic changes made in the hospital, confirming the positive impact of communication between care providers on therapeutic optimization.

Cytokine Signature in Schnitzler Syndrome: Proinflammatory Cytokine Production Associated to Th Suppression.

Background: Schnitzler syndrome (SchS) is a rare autoinflammatory disease characterized by urticarial exanthema, bone and joint alterations, fever and monoclonal IgM gammopathy. Overactivation of the interleukin(IL)-1 system is reported, even though the exact pathophysiological pathways remain unknown. Objective: To determine ex vivo cytokine profiles of Peripheral Blood Mononuclear Cells (PBMCs) from SchS patients prior to treatment and after initiation of anti-IL-1 therapy (anakinra). The sera cytokine profile was studied in parallel. Methods: We collected blood samples from thirty-six untreated or treated SchS. PBMCs were cultured with and without LPS or anti-CD3/CD28. Cytokine levels were evaluated in serum and cell culture supernatants using Luminex technology. Results: Spontaneous TNFα, IL-6, IL-1ß, IL-1α, and IL-1RA release by PBMCs of SchS patients were higher than in controls. LPS-stimulation further induced the secretion of these cytokines. In contrast, after T-cell stimulation, TNFα, IL-10, IFNγ, IL-17A, and IL-4 production decreased in SchS patients compared to healthy controls, but less in treated patients. Whereas IL-1ß serum level was not detected in most sera, IL-6, IL-10, and TNFα serum levels were higher in patients with SchS and IFNγ and IL-4 levels were lower. Of note, IL-6 decreased after treatment in SchS (p = 0.04). Conclusion: Our data strengthen the hypothesis of myeloid inflammation in SchS, mediated in particular by IL-1ß, TNFα, and IL-6, associated with overproduction of the inhibitors IL-1RA and IL-10. In contrast, we observed a loss of Th1, Th2, and Th17 cell functionalities that tends to be reversed by anakinra.

Contribution of an Early Internal Medicine Rotation to the Clinical Reasoning Learning for Young Residents.

Clinical reasoning is the cornerstone of medical practice, and achieving this competence depends on a large number of factors. Internal medicine departments provide junior doctors with plentiful and varied patients, offering a comprehensive basis for learning clinical reasoning. In order to evaluate the usefulness of an early rotation at internal medicine departments, we compared, via script concordance tests, the evolution of residents' clinical reasoning after an initial internal medicine rotation compared to rotations through other medical specialties. Twenty-two residents were tested after six months of their internal medicine rotation and compared to twenty-five residents that had the first rotation in another specialty (control). We showed a significant difference in the improvement of the script concordance tests scores (p=0.015) between the beginning and the end of their first rotation between the internal medicine and the control groups, and this implies the lower improvement of clinical reasoning skills and spontaneous learning slope of the junior doctors in other departments.

Diagnostic biologique des angioedèmes bradykiniques : les recommandations du CREAK.

Bradykinin mediated angioedema (BK-AE) can be associated either with C1Inhibitor deficiency (hereditary and acquired forms), either with normal C1Inh (hereditary form and drug induced AE as angiotensin converting enzyme inhibitors…). In case of high clinical suspicion of BK-AE, C1Inh exploration must be done at first: C1Inh function and antigenemy as well as C4 concentration. C1Inh deficiency is significant if the tests are below 50 % of the normal values and controlled a second time. In case of C1Inh deficiency, you have to identify hereditary from acquired forms. C1q and anti-C1Inh antibody tests are useful for acquired BK-AE. SERPING1 gene screening must be done if a hereditary angioedema is suspected, even if there is no family context (de novo mutation 15 %). If a hereditary BK-AE with normal C1Inh is suspected, F12 and PLG gene screening is suitable.

Transfusion practices in geriatric short stay unit before and after the French national health authority guidelines of 2014.

Anemia is the most common hematological pathology in geriatrics. Its prevalence increases with age. It is considered as a fragility factor because leading to loss of autonomy and other complications. Transfusion is a common practice in geriatrics. In 2014, the French national health authority guidelines recommended hemoglobin concentration rates for transfusion on the elderly over 80 years-old. The objective of this study is to compare transfusion practices in geriatric short-stay units, before and after these guidelines were edited. METHODS: Retrospective descriptive study in two geriatric short stay units, including patients aged 80 years-old or over, transfused in 2012 and 2015. RESULTS: 103 patients were included. More than 30% patients had a chronic heart failure, and there was no significant difference on general characteristics between the groups in the two years. Compared to 2012, the transfused population in 2015 was more fragile with a higher Charlson comorbidity index (p=0.005). The main symptoms of anemia bad tolerance were cardiovascular symptoms. The average pre-transfusion hemoglobin concentration was 7.9 g/dL in 2015, 8 g/dL in 2012 (p=0.63). By 2015, 72.3% transfusions respected the hemoglobin thresholds recommended in guidelines, compared to 50% in 2012 (p=0.023). Transfusion thresholds in our study were lower than those recommended; 13 adverse reactions were identified, 12 of them were heart failure. There was no significant difference in transfusion benefit between the two years. CONCLUSION: This study helped describe profile of elderly transfused patients, their geriatric characteristics and the transfusion data, without showing any changes in transfusion practices following the guidelines, despite a more fragile population in 2015. It seems difficult, because of the diversity in the geriatric population, to have a single threshold of hemoglobin recommended, only non-specific symptoms of intolerance and to consider only the cardiovascular comorbidities to decide whether or not to provide a transfusion.

Impact of a pharmacist-led medication review on hospital readmission in a pediatric and elderly population: study protocol for a randomized open-label controlled trial.

BACKGROUND: Early hospital readmission of patients after discharge is a public health problem. One major cause of hospital readmission is dysfunctions in integrated pathways between community and hospital care that can cause adverse drug events. Furthermore, the French ENEIS 2 study showed that 1.3% of hospital stays originated from serious adverse drug events in 2009. Pharmacy-led medication reviews at hospital transitions are an effective means of decreasing medication discrepancies when conducted at admission or discharge. However, it is difficult to assess the true impact of pharmacist-led medication reviews in specific high-risk populations, such as pediatric and geriatric populations. In such a context, it is important to demonstrate the effectiveness of medication reconciliation as part of a standardized medication review process-in pediatric and elderly populations-on all-cause readmissions in a large randomized controlled clinical trial. The aim of this study is to assess the impact of the pharmacist-led medication review on the rate of readmissions and/or death after hospital discharge and patient treatment satisfaction. METHODS/DESIGN: The study is a randomized controlled clinical trial. A total of 1400 hospitalized patients will be randomized in two groups: (1) the experimental group (group receiving a pharmacist-led medication review) and (2) the control group (group receiving usual care). The pharmacist-led medication review process includes medication reconciliation, treatment review and medication liaison service. The primary endpoint will be the rate of readmissions and/or death at 30 days following initial hospitalization discharge. The secondary endpoints will be the rate of hospital readmission, the rate of emergency department visits, the rate of mortality, the number of consultations and patient treatment satisfaction at 30 days following initial hospitalization discharge. DISCUSSION: A randomized controlled trial provides the most extensive evidence on the impact of pharmacist-led medication reviews on early hospital readmission for extreme age populations. TRIAL REGISTRATION: Current Controlled Trials, NCT02734017 . Registered on 4 May 2016.

Diagnosis and treatment of upper airway oedema caused by acute angio-oedema in the emergency department: a French consensus statement.

Angio-oedema is a transitory, localized, noninflammatory oedema of subcutaneous tissue or mucous. When the oedema affects the mouth, lips, tongue or larynx, it can result in fatal asphyxiation in the absence of specific treatment. Oedema secondary to plasma extravasation is usually mediated by either histamine or bradykinin. As laboratory tests are not available in an emergency setting, the implicated mediator cannot be readily determined. The challenge for the emergency physician is to determine the aetiological type, evaluate severity and initiate adapted treatment by means of a structured approach. A team of experts from the French Reference Centre for Angio-oedema reached a consensus for recommendations for the diagnostic and therapeutic strategy to be adopted by emergency departments faced with angio-oedema of the upper airways in adults. The experts defined 11 important questions. Responses were rated using a two-round Delphi methodology. The 11 recommendations were related to triage on admission, a step-by-step diagnostic protocol, definition of attack severity, discouragement of instrumental examination, prioritization of treatment for severe attacks according to clinical signs and anticipation of access to specific treatments by the hospital. Angio-oedema of the upper airways can be fatal and requires anticipation by the emergency department. A search for the aetiology, an evaluation of clinical symptoms and the availability of the treatments are challenges justifying these recommendations.

A nationwide study of acquired C1-inhibitor deficiency in France: Characteristics and treatment responses in 92 patients.

Acquired angioedema (AAE) due to C1-inhibitor (C1INH) deficiency is rare. Treatment options for acute attacks are variable and used off-label. Successful treatment of the associated lymphoma with rituximab seems to prevent acute attacks in subjects with AAE. The aim of this study was to describe AAE manifestations, its associated diseases, and patients' responses to treatments in a representative cohort.A retrospective nationwide study was conducted in France. The inclusion criteria were recurrent angioedema attacks and an acquired decrease in functional C1INH <50% of the reference value.A total of 92 cases were included, with a median age at onset of 62 years. Facial edema and abdominal pain were the most frequent symptoms. Fifteen patients were hospitalized in the intensive care unit because of laryngeal edema, and 1 patient died. Anti-C1INH antibodies were present in 43 patients. The associated diseases were primarily non-Hodgkin lymphoma (n = 44, with 24 splenic marginal zone lymphomas) and monoclonal gammopathy of undetermined significance (n = 24). Three patients had myeloma, 1 had amyloid light-chain (of immunoglobulin) (AL) amyloidosis, 1 patient had a bronchial adenocarcinoma, and 19 patients had no associated disease. Icatibant relieved the symptoms in all treated patients (n = 26), and plasma-derived C1INH concentrate in 19 of 21 treated patients. Six patients experienced thromboembolic events under tranexamic acid prophylaxis. Rituximab prevented angioedema in 27 of 34 patients as a monotherapy or in association with chemotherapy. Splenectomy controlled AAE in 7 patients treated for splenic marginal zone lymphoma. After a median follow-up of 4.2 years, angioedema was on remission in 52 patients.AAE cases are primarily associated with indolent lymphoma-especially splenic marginal zone lymphoma-and monoclonal gammopathy of undetermined significance but not with autoimmune diseases or other conditions. Icatibant and plasma-derived C1INH concentrate control attacks; splenectomy and immunochemotherapy prevent angioedema in lymphoma setting.

Hereditary angioedema and lupus: A French retrospective study and literature review.

Hereditary angioedema (HAE) is a rare genetic disorder that is primarily caused by a defect in the C1 inhibitor (C1-INH). The recurrent symptoms are subcutaneous edema and abdominal pain. Laryngeal edema, which can also occur, is life threatening if it goes untreated. HAE can be associated with some inflammatory and autoimmune disorders, particularly lupus. The aim of this study was to describe cases of lupus among HAE patients in France and to perform a literature review of lupus and HAE studies. Case detection and data collection (a standardized form) were performed, thanks to the French Reference Center for Kinin-related angioedema. Data were collected from 6 patients with type 1 HAE and lupus in France; no cases of systemic lupus erythematosus were reported. In the literature review, 32 cases of lupus combined with HAE were identified, including 26 female patients. The median patient age at the time of first reported HAE symptoms and at diagnosis were 17.5 years (range, 9-41 years) and 19 years (range, 9-64 years), respectively for our 6 patients and 14 years (range, 3-30 years) and 17 years (range, 7-48 years), respectively, for the literature review. The clinical manifestations of HAE were mainly abdominal pain (83% in our patients vs 47% in the literature) and edema of the limbs (83% vs 38%). The C4 levels were low (for 100% of our cases vs 93% in the literature). Eighteen patients in the literature demonstrated HAE symptoms prior to the lupus onset vs 5 for our patients. The mean patient age at lupus onset was 20 years (range, 13-76 years) for our patients and 19.5 years (range, 1-78 years) in the literature, respectively. In the literature, 81% of the patients had skin manifestations, 25% had renal involvement and 28% received systemic steroids to treat lupus. Treatment with danazol did not modify the clinical expression of lupus. The association between lupus and HAE is a rare but not unanticipated event. Patients are often symptomatic for HAE before developing lupus. Lupus cases associated with HAE share some characteristics of lupus cases related to other complement deficiencies, such as the absence of severity and the predominance of cutaneous symptoms.

NS3 protease of genotype 3 subtype h HCV identified in southeastern France.

HCV displays considerable levels of nucleotide and amino acid diversity. Recently, the relevance of natural polymorphisms in worldwide isolates has been addressed in view of future protease inhibitor (PI)-based treatments; genotype- and subtype-specific natural polymorphisms within HCV NS3 protease were identified at amino acid sites associated either with resistance to PIs or with compensatory mutations. Here, we describe a case of chronic infection with HCV of genotype 3 subtype h (HCV-3h), formerly only described from three patients originating from Somalia, and we provide the first NS3 protease sequence for such strains. NS3 protease sequences of HCV-3h recovered in the present study harbour specific amino acid residues not encountered in other reference HCV genotypes and subtypes at nine of the 181 NS3 protease positions; none of these amino acids are known to confer resistance to PIs. Of note, 5' untranslated region sequence-based genotyping classifies them into genotype 1.

Antiphosphatidylethanolamine antibodies are associated with an increased odds ratio for thrombosis. A multicenter study with the participation of the European Forum on antiphospholipid antibodies.

A multicenter study was set up to evaluate the prevalence, clinical and biological significance of antiphosphatidylethanolamine antibodies (aPE) in thrombotic patients with or without the main known clinical and biological risk factors for thrombosis. APE and antibodies, defined as the laboratory criteria of antiphospholipid syndrome (APS) -lupus anticoagulant, anticardiolipin and anti-beta(2)-GPI antibodies were measured in 270 patients with thrombosis (234 venous and 37 arterial) and 236 matched controls. APE were found in 15% of thrombotic patients compared to 3% of controls (p < 0.001) with no predominant isotype, no association with the main known clinical or biological risk factors for thrombosis neither with a type of thrombosis, arterial or venous. In a multivariate logistic regression analysis of antibodies, aPE showed the highest association with thrombosis (odds ratio [OR]: 4.2, p < 0.001). Moreover, using a multivariate analysis in a case-control subgroup study on 158 patients, IgGaPE were found to be significantly associated with venous thrombosis (OR:6;p = 0.005). Interestingly, 25 of the 40 aPE-positive patients (63%) were negative for the APS laboratory criteria. Most of them (21/25) had venous thrombosis, recurrent in ten of them. Four patients also suffered from early or late miscarriages. Our results underline the strength of the association between the presence of aPE and thrombosis and suggest their measurement in thrombotic patients, especially when lupus anticoagulant, anticardiolipin or anti-beta(2)-GPI antibodies are absent.

Combined search for anti-beta2-glycoprotein I and anticardiolipin antibodies in antiphospholipid syndrome: contribution to diagnosis.

In this study we sought to assess (1) the diagnostic value of a combined search for anti-beta(2)-glycoprotein (abeta(2)-GPIs) and anticardiolipin antibodies (aCLs) in primary (APS I) and secondary (APS II) antiphospholipid syndrome and (2) the influence of the beta(2)-GPI preparation in the ELISA's results. abeta(2)-GPI and aCL concentrations were assessed in 70 patients with APS and compared with those in 65 patients with systemic lupus erythematosus (SLE) without clinical features of APS. In APS patients (38 with APS I, 32 with APS II), the diagnosis had to have been made at least 3 years earlier; in subjects with SLE, the diagnosis had to have been made at least 5 years earlier. All serum samples were tested for abeta(2) -GPI with the use of an in-house ELISA with an abeta(2) -GPI preparation from human plasma. Samples negative for abeta(2) -GPI were controlled with 2 additional beta(2)-GPI preparations, 1 from human serum and 1 from bovine serum. In APS, abeta(2)-GPIs were more frequent than in SLE (76% and 15%, respectively; P <.0001), mainly with IgG isotype and with significantly higher levels than those found in SLE. The specificity for APS was 92% for IgG abeta(2)-GPIs and 68% for IgG aCLs. The highest association with APS was found for the combination of the 2 markers (odds ratio 29; 95% confidence interval 10-76; P <.0001). Among the APS patients, 6 were positive for aCL only and remained negative regardless of which beta 2 -GPI preparation was used; 1 patient was aCL-negative and only positive with human beta 2 -GPI. These data emphasize the heterogeneity of the APS immunologic profile and the diagnostic possibilities of both antibodies.