Polymyalgia rheumatica and giant cell arteritis following COVID-19 vaccination: Results from a nationwide survey.

We conducted a national in-depth analysis including pharmacovigilance reports and clinical study to assess the reporting rate (RR) and to determine the clinical profile of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) in COVID-19-vaccinated individuals. First, based on the French pharmacovigilance database, we estimated the RR of PMR and GCA cases in individuals aged over 50 who developed their initial symptoms within one month of receiving the BNT162b2 mRNA, mRNA-1273, ChAdOx1 nCoV-19, and Ad26.COV2.S vaccines. We then conducted a nationwide survey to gather clinical profiles, therapeutic management, and follow-up data from individuals registered in the pharmacovigilance study. A total of 70 854 684 COVID-19 vaccine doses were administered to 25 260 485 adults, among which, 179 cases of PMR (RR 7. 1 cases/1 000 000 persons) and 54 cases of GCA (RR 2. 1 cases/1 000 000 persons) have been reported. The nationwide survey allowed the characterization of 60 PMR and 35 GCA cases. Median time to the onset of first symptoms was 10 (range 2-30) and 7 (range 2-25) days for PMR and GCA, respectively. Phenotype, GCA-related ischemic complications and -large vessel vasculitis as well as therapeutic management and follow-up seemed similar according to the number of vaccine shots received and when compared to the literature data of unvaccinated population. Although rare, the short time between immunization and the onset of first symptoms of PMR and GCA suggests a temporal association. Physician should be aware of this potential vaccine-related phenomenon.

Effective Anti-SARS-CoV-2 Immune Response in Patients With Clonal Mast Cell Disorders.

BACKGROUND: Mast cells are key players in innate immunity and the TH2 adaptive immune response. The latter counterbalances the TH1 response, which is critical for antiviral immunity. Clonal mast cell activation disorders (cMCADs, such as mastocytosis and clonal mast cell activation syndrome) are characterized by abnormal mast cell accumulation and/or activation. No data on the antiviral immune response in patients with MCADs have been published. OBJECTIVE: To study a comprehensive range of outcomes in patients with cMCAD with PCR- or serologically confirmed coronavirus disease 2019 and to characterize the specific anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immune response in this setting. METHODS: Clinical follow-up and outcome data were collected prospectively over a 12-month period by members of the French Centre de Référence des Mastocytoses rare disease network. Anti-SARS-CoV-2-specific T-cell activity was measured with an ELISA, and humoral responses were evaluated by assaying circulating levels of specific IgG, IgA, and neutralizing antibodies. RESULTS: Overall, 32 patients with cMCAD were evaluated. None required noninvasive or mechanical ventilation. Two patients were admitted to hospital for oxygen and steroid therapy. The SARS-CoV-2-specific immune response was characterized in 21 of the 32 patients. Most had high counts of circulating SARS-CoV-2-specific, IFN-γ-producing T cells and high titers of neutralizing antispike IgGs. The patients frequently showed spontaneous T-cell IFN-γ production in the absence of stimulation; this production was correlated with basal circulating tryptase levels (a marker of the mast cell burden). CONCLUSIONS: Patients with cMCADs might not be at risk of severe coronavirus disease 2019, perhaps due to their spontaneous production of IFN-γ.

Whole genome sequencing to decipher the virulence phenotype of hypervirulent Klebsiella pneumoniae responsible for liver abscess, Marseille, France.

We described three clinical cases of pyogenic liver abscess caused by hypervirulent Klebsiella pneumoniae (hvKp) successfully treated by prolonged antibiotherapy, in which one case was complicated by endophthalmitis. Whole genome sequencing helped to confirm the diagnosis of these hvKp strains, which belong to clonal complexes CC86 and CC23 and carried hvKp-associated genes (magA and/or rmpA). This syndrome is increasingly reported in France and Europe and raises questions about the source of infection.

Covid-19-Associated Retinopathy: A Case Report.

A 53-year-old man presented with acute loss of vision, negative scotoma and dyschromatopsia in his left eye. He reported contact with people with severe respiratory syndrome - coronavirus-2 (SARS-CoV-2) 8 days prior symptoms. Funduscopic examination revealed several retinal hemorrhages. Spectral-domain optical coherence tomography showed lesions consistent with acute macular neuroretinopathy and paracentral acute middle maculopathy. Quickly after his presentation, SARSCov-2 was confirmed by chest computed tomography-scan and RT-PCR in this patient. Thrombotic complications associated with Covid-19 infection have high incidence and may involve the retina. We described a case of retinal involvement associated with Covid-19 infection. PRÉCIS: Funduscopic examination revealed retinal hemorrhages in a man with loss of vision. Optical coherence tomography showed an acute macular neuroretinopathy and paracentral acute middle maculopathy. Coronavirus disease was confirmed by chest computed tomography-scan and RT-PCR.

Nailfold videocapillaroscopy alterations in dermatomyositis, antisynthetase syndrome, overlap myositis, and immune-mediated necrotizing myopathy.

INTRODUCTION/OBJECTIVES: The aim of our study was to investigate possible differences in nailfold videocapillaroscopy (NVC) features between patients with dermatomyositis (DM), overlap myositis (OM), antisynthetase syndrome (ASS), and immune-mediated necrotizing myopathy (IMNM). METHODS: We performed a cross-sectional monocentric study. All patients with inflammatory myopathies (IMs) over a 6-month period were analyzed by NVC for giant and ramified capillaries, tortuosities, capillary density, disorganization, and scleroderma pattern. Clinical, biological, and pathological characteristics were retrospectively recorded. Patients were classified as having DM, OM, ASS, or IMNM for comparison. Patients were also compared with a group of patients with systemic sclerosis (SSc). RESULTS: NVC was analyzed in DM (n = 17), OM (n = 8), ASS (n = 12), and IMNM (n = 6). Vascular disorganization and avascular zones were observed only in DM (11.8%) and OM (62.5%). The percentage of patients with giant capillaries was higher in OM (n = 4/8) than in DM (n = 3/17) and absent in ASS and IMNM. Frequency of ramified capillaries, tortuosities, hemorrhages, or thrombosis was not different between subgroups. A scleroderma pattern was only observed in OM patients. CONCLUSION: In this limited series of patients, we observed that DM and OM NVC abnormalities are different from ASS and IMNM. We could not determine NVC specific patterns associated with myositis-specific antibody subtypes of DM because of the small number of patients.Key Points• Nailfold videocapillaroscopy abnormalities are different in subgroups of inflammatory myopathies.• Giant capillaries, disorganization, and major capillary loss are observed in overlap myositis and dermatomyositis but not in antisynthetase syndrome (ASS) or immune-mediated necrotizing myopathy.• Nailfold videocapillaroscopy abnormalities in overlap myositis (with the exclusion of ASS) are close to systemic sclerosis.

Clinical and biological features in PIEZO1-hereditary xerocytosis and Gardos channelopathy: a retrospective series of 126 patients.

We describe the clinical, hematologic and genetic characteristics of a retrospective series of 126 subjects from 64 families with hereditary xerocytosis. Twelve patients from six families carried a KCNN4 mutation, five had the recurrent p.Arg352His mutation and one had a new deletion at the exon 7-intron 7 junction. Forty-nine families carried a PIEZO1 mutation, which was a known recurrent mutation in only one-third of the cases and private sequence variation in others; 12 new probably pathogenic missense mutations were identified. The two dominant features leading to diagnosis were hemolysis that persisted after splenectomy and hyperferritinemia, with an inconstant correlation with liver iron content assessed by magnetic resonance imaging. PIEZO1-hereditary xerocytosis was characterized by compensated hemolysis in most cases, perinatal edema of heterogeneous severity in more than 20% of families and a major risk of post-splenectomy thrombotic events, including a high frequency of portal thrombosis. In KCNN4-related disease, the main symptoms were more severe anemia, hemolysis and iron overload, with no clear sign of red cell dehydration; therefore, this disorder would be better described as a 'Gardos channelopathy'. These data on the largest series to date indicate that PIEZO1-hereditary xerocytosis and Gardos channelopathy are not the same disease although they share hemolysis, a high rate of iron overload and inefficient splenectomy. They demonstrate the high variability in clinical expression as well as genetic bases of PIEZO1-hereditary xerocytosis. These results will help to improve the diagnosis of hereditary xerocytosis and to provide recommendations on the clinical management in terms of splenectomy, iron overload and pregnancy follow-up.

Neurological Involvement in Childhood Evans Syndrome.

PURPOSE: Immune thrombocytopenic purpura (ITP) and autoimmune hemolytic anemia (AIHA) are associated in the definition of Evans syndrome (ES). The occurrence of neurological involvement in this population is poorly described and suggests an underlying primary immunodeficiency (PID). We aimed to describe the clinical manifestations, evolution, and PID profiles of these patients. METHODS: OBS'CEREVANCE is a French, nationwide prospective cohort that includes children with chronic ITP, AIHA, and ES. Patients with a neurological involvement were described. Centralized radiological and pathological reviews and genetic analyses were performed. RESULTS: On October 2016, eight patients (7/181 ES, 1/371 AIHA, and 0/615 ITP) were identified, all male, with a median age (range) at cytopenia onset of 11.5 years (1.6-15.8). Neurological symptoms appeared with a median delay of 6 years (2.5-18) after cytopenia and were polymorphic: seizures (n = 4), cranial nerve palsy (n = 2), Brown-Sequard syndrome (n = 2), intracranial pressure (n = 2), vertigo (n = 1), and/or sensory neuropathy (n = 1). Magnetic resonance imaging (MRI) showed inflammatory lesions, confirmed by pathology for five patients with macrophagic or lymphoplasmocytic infiltrates. All patients had other relevant immunopathological manifestations: pulmonary nodules (n = 6), lymphoproliferation (n = 4), abnormal immunophenotype (n = 8), and hypogammaglobulinemia (n = 7). Treatment consisted of steroids that improved symptomatology and MRI. Five patients relapsed and three had an asymptomatic radiological progression. A PID was identified in 3/8 patients: 22q11.2 microdeletion (n = 1) and CTLA deficiency (n = 2). CONCLUSION: Neurological involvement is a rare and severe late event in the course of childhood ES, which can reveal an underlying PID. Imaging and pathology examination highlight a causative immune dysregulation that may guide targeted therapeutic strategies.

Autoimmune diseases in myelodysplastic syndrome favors patients survival: A case control study and literature review.

BACKGROUND: We conducted a monocentric retrospective study of patients with myelodysplastic syndromes (MDS) and autoimmune or inflammatory disorders (AIMs) and a literature review. We analyzed the association with subgroups of the WHO 2016 MDS classification and patient's survival in a case control study. Risk factors associated with survival were analyzed by uni- and multivariate analysis. RESULTS: From all MDS patients 11% presented with AIMs. These were heterogeneous and the most frequent where polyarthritis (25%) and autoimmune cytopenias (17%). No difference for frequency and type of AIMs was observed for the WHO 2016 MDS subgroups (p = .3). In the case control study WHO classification, karyotype abnormalities, IPSS-R and IPSS were similar in both groups. The overall survival from MDS diagnosis was better in the group with AIMs [10.3 ±â€¯0.6 (IC95% 6.2-12.9) versus 4.8 ±â€¯1.1 years (IC95% 4.2-8.7), p = .04]. The better survival was restricted to MDS with low or intermediate-1 IPSS [11.1 ±â€¯1.5 (IC95% 9.9-NR) versus 8.7 ±â€¯1.3 years (IC95% 4.8-10.3), p = .006]. The better survival was only observed when AIMs diagnosis was timely associated or appeared after MDS diagnosis (p = .04). Factors associated with a better overall survival and survival without AML were steroid dependence [respectively HR = 0.042, p = .003, (IC95% 0.005-0.33) and HR = 0.07, p = .002, (IC95% 0.013-0.39)], a diagnosis of AIMs and MDS timely associated [respectively HR = 0.05, p = .009, (IC95% 0.006-0.478) and HR = 0.1, p = .008, (IC95% 0.018-0.54)] or a diagnosis of AIMs after MDS [respectively HR = 0.024, p = .009, (IC95% 0.001-0.39) and HR = 0.04, p = .008, (IC95% 0.003-0.43)]. CONCLUSION: Autoimmune and inflammatory diseases associated to MDS are heterogeneous. AIMs diagnosed after or concomitantly to MDS seems associated with a better survival. Prospective studies are necessary to demonstrate that autoimmunity is associated to a better control of the MDS clone.

Acute pancreatitis and pneumonia due to Mycoplasma pneumoniae: a case report.

BACKGROUND: Mycoplasma pneumoniae is a bacterium responsible for 15 to 40 % of acute community-acquired pneumonia in children and 20 % of adult cases. Several extrapulmonary manifestations have been reported. We report a rare case of an adult patient suffering from pneumonia associated with an acute pancreatitis in the setting of Mycoplasma pneumoniae infection. CASE PRESENTATION: A 28-year-old Caucasian woman was referred for anorexia lasting for 1 week. Her past medical history was notable for congenital hydrocephalus with consecutive ventriculo-peritoneal shunt, epilepsia and paraparesis. The patient rapidly deteriorated, presenting with dyspnea, tachypnea, productive cough, abdominal pain, and onset of fever. C-reactive protein was at 270 mg/L, with a rise in serum lipase (670 UI/L, N: 13-60). A computed-tomography scan showed an acute interstitial edematous pancreatitis without necrosis, consistent with grade C on the Balthazar score. Thoracic sections revealed diffuse parenchymal consolidations combined with ground glass opacities. Calcium and triglyceride levels were normal. There was no history of recent trauma, alcoholic intake or drug intoxication. Mycoplasma pneumoniae serological assay showed an elevated IgM titer (22 UA/mL), compatible with recent infection, and cold agglutinins were present. A diagnosis of acute pancreatitis and diffuse interstitial pneumonia caused by an infection with Mycoplasma pneumoniae was considered. Respiratory and abdominal evolution was quickly favorable after initiation of clarithromycin 500 mg bid. CONCLUSIONS: The relationship between Mycoplasma pneumoniae infection and acute pancreatitis has been debated in the literature for many years. This observation, supported by clinical, biological and radiological features, is an additional argument in favor of a non-fortuitous association.

Immune thrombocytopenia in adults: a prospective cohort study of clinical features and predictors of outcome.

This prospective observational cohort study aimed to explore the clinical features of incident immune thrombocytopenia in adults and predictors of outcome, while determining if a family history of autoimmune disorder is a risk factor for immune thrombocytopenia. All adults, 18 years of age or older, recently diagnosed with immune thrombocytopenia were consecutively recruited across 21 hospital centers in France. Data were collected at diagnosis and after 12 months. Predictors of chronicity at 12 months were explored using logistic regression models. The association between family history of autoimmune disorder and the risk of developing immune thrombocytopenia was explored using a conditional logistic regression model after matching each case to 10 controls. One hundred and forty-three patients were included: 63% female, mean age 48 years old (Standard Deviation=19), and 84% presented with bleeding symptoms. Median platelet count was 10×10(9)/L. Initial treatment was required in 82% of patients. After 12 months, only 37% of patients not subject to disease-modifying interventions achieved cure. The sole possible predictor of chronicity at 12 months was a higher platelet count at baseline [Odds Ratio 1.03; 95%CI: 1.00, 1.06]. No association was found between outcome and any of the following features: age, sex, presence of either bleeding symptoms or antinuclear antibodies at diagnosis. Likewise, family history of autoimmune disorder was not associated with incident immune thrombocytopenia. Immune thrombocytopenia in adults has been shown to progress to a chronic form in the majority of patients. A lower platelet count could be indicative of a more favorable outcome.

Autologous hematopoietic stem cell transplantation vs intravenous pulse cyclophosphamide in diffuse cutaneous systemic sclerosis: a randomized clinical trial.

IMPORTANCE: High-dose immunosuppressive therapy and autologous hematopoietic stem cell transplantation (HSCT) have shown efficacy in systemic sclerosis in phase 1 and small phase 2 trials. OBJECTIVE: To compare efficacy and safety of HSCT vs 12 successive monthly intravenous pulses of cyclophosphamide. DESIGN, SETTING, AND PARTICIPANTS: The Autologous Stem Cell Transplantation International Scleroderma (ASTIS) trial, a phase 3, multicenter, randomized (1:1), open-label, parallel-group, clinical trial conducted in 10 countries at 29 centers with access to a European Group for Blood and Marrow Transplantation-registered transplant facility. From March 2001 to October 2009, 156 patients with early diffuse cutaneous systemic sclerosis were recruited and followed up until October 31, 2013. INTERVENTIONS: HSCT vs intravenous pulse cyclophosphamide. MAIN OUTCOMES AND MEASURES: The primary end point was event-free survival, defined as time from randomization until the occurrence of death or persistent major organ failure. RESULTS: A total of 156 patients were randomly assigned to receive HSCT (n = 79) or cyclophosphamide (n = 77). During a median follow-up of 5.8 years, 53 events occurred: 22 in the HSCT group (19 deaths and 3 irreversible organ failures) and 31 in the control group (23 deaths and 8 irreversible organ failures). During the first year, there were more events in the HSCT group (13 events [16.5%], including 8 treatment-related deaths) than in the control group (8 events [10.4%], with no treatment-related deaths). At 2 years, 14 events (17.7%) had occurred cumulatively in the HSCT group vs 14 events (18.2%) in the control group; at 4 years, 15 events (19%) had occurred cumulatively in the HSCT group vs 20 events (26%) in the control group. Time-varying hazard ratios (modeled with treatment × time interaction) for event-free survival were 0.35 (95% CI, 0.16-0.74) at 2 years and 0.34 (95% CI, 0.16-0.74) at 4 years. CONCLUSIONS AND RELEVANCE: Among patients with early diffuse cutaneous systemic sclerosis, HSCT was associated with increased treatment-related mortality in the first year after treatment. However, HCST conferred a significant long-term event-free survival benefit. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN54371254.

Efficacy and safety of rituximab given at 1,000 mg on days 1 and 15 compared to the standard regimen to treat adult immune thrombocytopenia.

Rituximab (RTX) is used off-label to treat immune thrombocytopenia (ITP) but the regimen now commonly used in rheumatoid arthritis has not been evaluated in ITP. The aim of this large French multicenter retrospective study was to compare the efficacy and safety of two RTX regimens in adult's ITP. The efficacy of two (RTX) regimens: standard therapy of 375 mg/m(2) weekly for 4 weeks vs. a rheumatoid arthritis (RA) regimen of 1,000 mg on days 1 and 15, to treat ITP was compared. We included adults patients with previously primary ITP treated with RTX instead of treated primary ITP. (CR) was defined as a platelet count >100 × 10(9) /L, and a response (R) by a platelet count of >30 × 10(9) /L with a least a doubling of the baseline value. Of the 107 patients included, 61 (57%) received the standard regimen and 46 (43%) the RA regimen. Baseline characteristics and overall response rates at 3 month (M3) and 12 months (M12) were not significantly different between the groups. At M12, 22/61 patients (36%) treated with the standard regimen and 23/46 (50%) with the RA regimen achieved an overall response (R + CR). The initial pattern of response at M3 was associated with a later pattern of response by M12 in both groups. In multivariate analysis, both a younger age and a low number of previous therapies were associated with a higher likelihood of overall response at M12. Tolerance was good and comparable between the two groups. The RA regimen is an effective and safe alternative to the standard regimen to treat adults with ITP.

A retrospective pilot evaluation of switching thrombopoietic receptor-agonists in immune thrombocytopenia.

Romiplostim and eltrombopag, the first thrombopoietic receptor-agonists with demonstrated efficacy against immune thrombocytopenia in prospective controlled studies, were recently authorized in most countries for adults with chronic immune thrombocytopenia. So far, no data are available about the potential contribution of switching from romiplostim to eltrombopag or vice versa in terms of efficacy or tolerance. Efficacies and tolerance profiles were evaluated for 46 patients who sequentially received both drugs, switching from one to the other. The reasons for switching were: lack of efficacy for 23 patients, platelet-count fluctuations for 11, side effects for 4, and 8 patients' preferences. For 50-80% of the patients, switching from romiplostim to eltrombopag or eltrombopag to romiplostim effectively impacted the platelet count, with fluctuations disappearing in 54% and side effects resolved in 100%. In 80% of the patients, the 2 thrombopoietic receptor-agonists achieved similar response patterns. Our results confirmed that switching from one thrombopoietic receptor-agonist to the other could be beneficial in clinical practice for patients with severe chronic immune thrombopenia who failed to respond or experienced adverse events to the first. (Clinical Trials.gov identifier: NCT01618734).

A case-control study to assess the risk of immune thrombocytopenia associated with vaccines.

The cause of immune thrombocytopenia (ITP) remains unknown. Studies have suggested immunizations as possible triggering factors of ITP through molecular mimicry. This case-control study explored potential associations between adult ITP and various routinely administered vaccines. A network of internal medicine and hematology centers across France recruited 198 incident (ie, newly diagnosed) cases of ITP between April 2008 and June 2011. These cases were compared with 878 age- and sex-matched controls without ITP recruited in general practice. Information on vaccination was obtained from patients' standardized telephone interviews. Sixty-six of 198 cases (33.3%) and 303 of 878 controls (34.5%) received at least 1 vaccine within the 12 months before the index date. We found no evidence of an increase in ITP after vaccination in the previous 6 or 12 months (adjusted odds ratio [OR] for the previous 12 months = 1.0; 95% confidence interval, 0.7-1.4). When the 2-month time window was used, higher ORs were observed for all vaccines (OR = 1.3). This increase was mainly attributable to the vaccination against diphtheria-tetanus-pertussis-poliomyelitis (OR = 1.5) and was not statistically significant. The results of the present study show that in an adult population, the exposure to common vaccines is on average not associated with an observable risk of developing ITP.

Evaluation of a prototype electronic personal health record for patients with idiopathic thrombocytopenic purpura.

BACKGROUND: Patients with rare diseases often lack information about the disease itself and appropriate health care, leading to poor quality of life. Personal health records provide health information which can then be shared between multiple health care providers. Personal health records may also offer a tool for capturing patients' reported outcomes, thus enhancing their empowerment and improving communication with health care professionals. We conducted a pilot study to evaluate the usability of Sanoia, a freely accessible personal health record, which was customized for patients with the rare disease, idiopathic thrombocytopenic purpura (ITP). METHODS: The Sanoia interface was expanded with ITP-specific tools. A prospective study was conducted at the referent center to evaluate the usability of this new interface (referred to here as the "tool") by patients. Forty-three patients were randomized into groups to use or to not use the tool. Its use was evaluated by a specific questionnaire and by surveying individual patient adherence profiles. Evaluation of health-related quality of life using the ITP patient assessment questionnaire, was performed at baseline and after 1, 3, and 6 months via postal mail. RESULTS: The groups were similar at inclusion in terms of characteristics, including global quality of life. During the study period, the tool was used to update the personal records of 19/28 patients (68%), with a median of two connections to the tool (range 1-12) plus access by various health care professionals (n = 22). In addition, 15/19 (78%) patients used the "personal notes" section at least once. We observed no significant changes in quality of life between patients with or without the tool during the study period. CONCLUSION: This pilot study demonstrates the good usability of the new customized Sanoia interface for patients with ITP. Additional studies will increase its usability further, and its interface could be adapted for use with other rare chronic diseases.

Efficacy of rituximab in immune thrombocytopenic purpura: a retrospective survey.

We conducted a retrospective survey to assess prescription practice, response rates to rituximab, and the predictive indicators for a response to rituximab therapy in patients with primary or secondary immune thrombocytopenic purpura (ITP). Data were collected retrospectively from 40 consecutive patients with ITP attending our hospital: 29 (72.5%) had primary ITP and 11 (27.5%) had secondary ITP. Rituximab was given either as four weekly injections (375 mg/m(2)) or two injections of 1,000 mg given 2 weeks apart in 30 and 10 patients, respectively. The primary objective was to evaluate overall (OR) and complete response (CR) to rituximab therapy for ITP. OR was excellent and rapid and similar when secondary ITP was excluded from the analysis: OR was achieved in 28 (71.8%) patients and CR in 22 (56.4%). But, at >6 months, of the 28 responders, only 10 of 22 of the evaluable responses (45.5%) were sustained. In addition, except for the nonsignificant occurrence of antinuclear antibodies, no clinical or biological factors were predictive for OR or CR after the rituximab therapy. Twelve patients received a second course of rituximab. Overall, rituximab therapy achieved a response in two thirds of the patients, but the responders exhibited a high rate of early relapses, with no obvious difference according to the regimen of administration or rituximab dose.

Scedosporium apiospermum catheter-related soft-tissue infection: a case report and review of the literature.

We report a case of catheter-related Scedosporium apiospermum soft-tissue infection. This ubiquitous filamentous fungus can cause human infection after traumatic subcutaneous implantation of its conidia or their inhalation in near-drowning cases. It has also been reported as an etiological agent in a growing number of hospital-acquired infections.

Romiplostim safety and efficacy for immune thrombocytopenia in clinical practice: 2-year results of 72 adults in a romiplostim compassionate-use program.

Romiplostim, a thrombopoietic agent with demonstrated efficacy against immune thrombocytopenia (ITP) in prospective controlled studies, was recently licensed for adults with chronic ITP. Only France has allowed romiplostim compassionate use since January 2008. ITP patients could receive romiplostim when they failed to respond to successive corticosteroids, intravenous immunoglobulins, rituximab, and splenectomy, or when splenectomy was not indicated. We included the first 80 patients enrolled in this program with at least 2 years of follow-up. Primary platelet response (platelet count ≥ 50 × 10(9)/L and double baseline) was observed in 74% of all patients. Long-term responses (2 years) were observed in 47 (65%) patients, 37 (79%) had sustained platelet responses with a median platelet count of 106 × 10(9)/L (interquartile range, 75-167 × 10(9)/L), and 10 (21%) were still taking romiplostim, despite a median platelet count of 38 × 10(9)/L (interquartile range, 35-44 × 10(9)/L), but with clinical benefit (lower dose and/or fewer concomitant treatment(s) and/or diminished bleeding signs). A high bleeding score and use of concomitant ITP therapy were baseline factors predicting romiplostim failure. The most frequently reported adverse events were: arthralgias (26%), fatigue (13%), and nausea (7%). Our results confirmed that romiplostim use in clinical practice is effective and safe for severe chronic ITP. This trial was registered at www.clinicaltrials.gov as #NCT01013181.