Little is known about patients with sickle cell disease (SCD) who require intensive care unit (ICU) admission. The goals of this study were to assess outcomes in patients admitted to the ICU for ...acute complications of SCD and to identify factors associated with adverse outcomes. This multicenter retrospective study included consecutive adults with SCD admitted to one of 17 participating ICUs. An adverse outcome was defined as death or a need for life-sustaining therapies (non-invasive or invasive ventilation, vasoactive drugs, renal replacement therapy, and/or extracorporeal membrane oxygenation). Factors associated with adverse outcomes were identified by mixed multivariable logistic regression. We included 488 patients admitted in 2015-2017. The main reasons for ICU admission were acute chest syndrome (47.5%) and severely painful vaso-occlusive event (21.3%). Sixteen (3.3%) patients died in the ICU, mainly of multi-organ failure following a painful vaso-occlusive event or sepsis. An adverse outcome occurred in 81 (16.6%; 95% confidence interval 95% CI, 13.3%-19.9%) patients. Independent factors associated with adverse outcomes were low mean arterial blood pressure (adjusted odds ratio aOR, 0.98; 95% CI 0.95-0.99; p = 0.027), faster respiratory rate (aOR, 1.09; 95% CI 1.05-1.14; p < 0.0001), higher haemoglobin level (aOR, 1.22; 95% CI 1.01-1.48; p = 0.038), impaired creatinine clearance at ICU admission (aOR, 0.98; 95% CI 0.97-0.98; p < 0.0001), and red blood cell exchange before ICU admission (aOR, 5.16; 95% CI 1.16-22.94; p = 0.031). Patients with SCD have a substantial risk of adverse outcomes if they require ICU admission. Early ICU admission should be encouraged in patients who develop abnormal physiological parameters.
Objective
To evaluate the usefulness of 2‐18F‐fluoro‐2‐deoxy‐d‐glucose–positron emission tomography/computed tomography (FDG‐PET/CT) in IgG4‐related disease (IgG4‐RD) for the staging of the disease ...and the followup under treatment.
Methods
All patients included in the French IgG4‐RD registry who underwent ≥1 FDG‐PET/CT scan were included in the study. Clinical, biologic, pathologic, radiologic, and FDG‐PET/CT qualitative and quantitative findings were retrospectively collected and analyzed.
Results
Twenty‐one patients were included in the study and 46 FDG‐PET/CT examinations were evaluated. At either diagnosis or relapse, all evaluated patients presented abnormal 18F‐FDG uptake in typical IgG4‐RD localizations. In most cases, FDG‐PET/CT was more sensitive than conventional imaging to detect organ involvement, especially in arteries, salivary glands, and lymph nodes. In few cases (small‐sized lesions and brain or kidney contiguous lesions), false‐negative results were noted. Evaluation before and after treatment showed in most cases a good correlation of FDG‐PET/CT results with treatment response and disease activity.
Conclusion
This large retrospective study shows that FDG‐PET/CT imaging is useful for the staging of IgG4‐RD. Moreover, FDG‐PET/CT is useful to assess the response to treatment during followup.
Clinical features, complications and treatments of Gaucher's disease (GD), a rare autosomal-recessive disorder due to a confirmed lysosomal enzyme (glucocerebrosidase) deficiency, are described.
All ...patients with known GD, living in France, with ≥ 1 consultations (1980-2010), were included in the French GD registry, yielding the following 4 groups: the entire cohort, with clinical description; and its subgroups: patients with ≥ 1 follow-up visits, to investigate complications; recently followed (2009-2010) patients; and patients treated during 2009-2010, to examine complications before and during treatment. Data are expressed as medians (range) for continuous variables and numbers (%) for categorical variables.
Among the 562 registry patients, 265 (49.6%) were females; 454 (85.0%) had type 1, 22 (4.1%) type 2, 37 (6.9%) perinatal-lethal type and 21 (3.9%) type 3. Median ages at first GD symptoms and diagnosis, respectively, were 15 (0-77) and 22 (0-84) years for all types. The first symptom diagnosing GD was splenomegaly and/or thrombocytopenia (37.6% and 26.3%, respectively). Bone-marrow aspiration and/or biopsy yielded the diagnosis for 54.7% of the patients, with enzyme deficiency confirming GD for all patients. Birth incidence rate was estimated at 1/50,000 and prevalence at 1/136,000. For the 378 followed patients, median follow-up was 16.2 (0.1-67.6) years. Major clinical complications were bone events (BE; avascular necrosis, bone infarct or pathological fracture) for 109 patients, splenectomy for 104, and Parkinson's disease for 14; 38 patients died (neurological complications for 15 type-2 and 3 type-3 patients, GD complications for 11 type-1 and another disease for 9 type-1 patients). Forty-six had monoclonal gammopathy. Among 283 recently followed patients, 36 were untreated and 247 had been treated during 2009-2010; 216 patients received treatment in December 2010 (126 with imiglucerase, 45 velaglucerase, 24 taliglucerase, 21 miglustat). BE occurred before (130 in 67 patients) and under treatment (60 in 41 patients) with respective estimated frequencies (95% CI) of first BE at 10 years of 20.3% (14.1%-26.5%) and 19.8% (13.5%-26.1%).
This registry enabled the epidemiological description of GD in France and showed that BE occur even during treatment.
Abstract
Objectives
This study aimed to examine the sensitivity of muscle biopsy (MB) in ANCA-associated vasculitis (AAV), identify factors predicting MB positivity and assess the prognostic value of ...a positive MB.
Methods
We conducted a single-centre retrospective study of AAV with an MB performed at diagnosis. AAV classification granulomatosis with polyangiitis (GPA), microscopic polyangiitis (MPA), eosinophilic granulomatosis with polyangiitis (EGPA) followed the European Medicines Agency algorithm. A logistic regression model was used to identify the factors associated with MB positivity. Survival curves were generated using the Kaplan–Meier method.
Results
Among 276 AAV patients (1995–2018), 101 had an MB. Seventy-eight patients were included: 33 with GPA, 25 with MPA and 20 with EGPA. MB samples were positive in 45 cases (58%): 17 GPA, 16 MPA and 12 EGPA. Univariate analysis focussed on GPA and MPA, revealed that the MB yield was higher in females 22/31 (71%) vs 11/27 (41%); P = 0.02 and in anti-MPO patients 25/37 (68%) vs 6/19 (32%) for anti-PR3; P = 0.01. By multivariate analysis, three factors predicted MB positivity: anti-MPO ANCA odds ratio (OR) 10.67 (CI 2.09, 81.68), female sex OR 5.3 (CI 1.16, 32.35) and neutrophil count OR 1.33 (CI 1.07, 1.8). MB positivity had no impact on relapse, death or end-stage renal disease–free survival.
Conclusions
MB is a safe and efficient diagnostic tool for AAV. Predictors of MB yield include ANCA type, sex and neutrophil count. MB cannot substitute for kidney biopsy when indicated, but should be considered in other cases.
Background:
Giant cell arteritis (GCA) is the most common systemic vasculitis. Relapses are frequent. The aim of this study was to identify relapse risk factors in patients with GCA with complete ...large-vessel imaging at diagnosis.
Methods:
Patients with GCA followed in our institution between April 1998 and April 2018 were included retrospectively. We included only patients who had undergone large vascular imaging investigations at diagnosis by computed tomography (CT)-scan and/or positron emission tomography (PET)-scan and/or angio-magnetic resonance imaging (MRI). Clinical, biological, and radiological data were collected. Relapse was defined as the reappearance of GCA symptoms, with concomitant increase in inflammatory markers, requiring treatment adjustment. Relapsing patients (R) and non-relapsing patients (NR) were compared. Relapse and multiple relapses (>2) risk factors were identified in multivariable Cox analyses.
Results:
This study included 254 patients (73.2% women), with a median age of 72 years at diagnosis and a median follow up of 32.5 months. At diagnosis, 160 patients (63%) had an inflammatory large-vessel involvement on imaging, 46.1% (117 patients) relapsed at least once, and 21.3% (54 patients) had multiple relapses. The median delay of first relapse after diagnosis was 9 months. The second relapse delay was 21.5 months. NR patients had more stroke at diagnosis than R (p = 0.03) and the brachiocephalic trunk was involved more frequently on CT-scan (p = 0.046), as carotids (p = 0.02) in R patients. Multivariate Cox model identified male gender hazard ratio (HR): 0.51, confidence interval (CI) (0.27–0.96), p = 0.04 as a relapse protective factor, and peripheral musculoskeletal manifestations HR: 1.74 (1.03–2.94), p = 0.004 as a relapse risk factor. Peripheral musculoskeletal manifestations HR: 2.78 (1.23–6.28), p = 0.014, negative temporal artery biopsy HR: 2.29 (1.18–4.45), p = 0.015, large-vessel involvement like upper limb ischemia HR: 8.84 (2.48–31.56), p = 0.001 and inflammation of arm arteries on CT-scan HR: 2.39 (1.02–5.58), p = 0.04 at diagnosis were risk factors of multiple relapses.
Conclusion:
Male gender was a protective factor for GCA relapse and peripheral musculoskeletal manifestations appeared as a relapsing risk factor. Moreover, this study identified a particular clinical phenotype of multi-relapsing patients with GCA, characterized by peripheral musculoskeletal manifestations, negative temporal artery biopsy, and large-vessel involvement with upper limb ischemia or inflammation of arm arteries.
Plain language Summary
At giant cell arteritis diagnosis, large-vessel inflammatory involvement is predictive of multiple relapses
46.1% of patients with GCA relapse, and 21.3% undergo multiple relapses;
Male gender appears as a protective factor for relapsing in GCA;
Peripheral musculoskeletal manifestations are a relapse and multiple relapses risk factor;
A negative temporal artery biopsy is predictive of multiple relapses;
Large-vessel involvement is predictive of multiple relapses.
Background. Although prognosis of Chronic Granulomatous Disease (CGD) has greatly improved, few studies have focused on its long-term outcome. We studied the clinical course and sequelae of CGD ...patients diagnosed before age 16, at various adult time points. Method. Cross-sectional French nationwide retrospective study of patients screened through the National Reference Center for Primary Immunodeficiencies (CEREDIH) registry. Results. Eighty CGD patients (71 males 88.7%, 59 X-linked 73.7%, median age 23.9 years minimum, 16.6; maximum, 59.9) were included, Median ages at diagnosis and last follow-up were 2.52 and 23.9 years, respectively. Seven patients underwent hematopoietic stem cell transplantation. A total of 553 infections requiring hospitalization occurred in 2017 patient-years. The most common site of infection was pulmonary (31%). Aspergillus spp. (17%) and Staphylococcus aureus (10.7%) were the commonest pathogens. A total of 224 inflammatory episodes occurred in 71 patients, mainly digestive (50%). Their characteristics as well as their annual frequency did not vary before and after age 16. Main sequelae were a small adult height and weight and mild chronic restrictive respiratory failure. At age 16, only 53% of patients were in high school. After age 30 years, 9/13 patients were working. Ten patients died during adulthood. Conclusions. Adult CGD patients displayed similar characteristics and rates of severe infections and inflammatory episodes that those of childhood. The high rate of handicap has become a matter of medical and social consideration. Careful follow-up in centers of expertise is strongly recommended and an extended indication of curative treatment by HSCT should be considered.
Sickle cell disease (SCD) induces chronic haemolytic anaemia and intermittent vaso-occlusion that results in tissue ischaemia causing acute, severe pain episodes that can lead to frequent ...hospitalizations. These consequences can have repercussions on family, social, school and/or professional life. Here, we present some of the results of the PHEDRE study (Pharmacodépendance Et DREpanocytose-drug dependence and sickle-cell disease), which is the largest study of patients with SCD in France. This paper intends to describe characteristics of the French SCD population. We also aimed to assess the impact of the disease on the lives of patients using objective and subjective variables.
The PHEDRE study was a national multicentric observational study. Adults, adolescents and children with a confirmed SCD diagnosis were included in the study by their referring doctor. Then, they were interviewed by phone about their socioeconomic status, about the impact of the disease on their lives and about their analgesic and psychoactive drug use.
The study population consisted of 872 patients (28% were minors). Seventy-two percent of adults were active, and all minors were in school. Many patients presented criteria of severe SCD. Seventy-five percent were homozygous SS, 15% were double heterozygotes SC and 8% were heterozygotes Sβthal, 87% received specific treatment, 58% were hospitalized at least once for vaso-occlusive crisis in the past 12 months, and the number of analgesic drugs taken averaged 3.8. Seventy-five percent of patients reported academic or professional consequences related to their SCD, and 52% reported social consequences.
The impact of SCD on patients' lives can be significant, nevertheless their social integration seems to be maintained. We highlighted respect of recommendations regarding analgesic treatments and only a few patients used tobacco, alcohol or cannabis.
Clinical Trials, NCT02580565; https://clinicaltrials.gov/ Registered 16 October 2015.
Abstract Aim To describe the consecutive pregnancy outcome and treatment in refractory obstetrical antiphospholipid syndrome (APS). Methods Retrospective multicenter open-labelled study from December ...2015 to June 2016. We analyzed the outcome of pregnancies in patients with obstetrical APS (Sydney criteria) and previous adverse obstetrical event despite low-dose aspirin and low-molecular weight heparin LMWH (LMWH) conventional treatment who experienced at least one subsequent pregnancy. Results Forty nine patients with median age 27 years (23 − 32) were included from 8 European centers. Obstetrical APS was present in 71%, while 26% had obstetrical and thrombotic APS. Lupus anticoagulant was present in 76% and triple antiphospholipid antibody (APL) positivity in 45% of patients. Pregnancy loss was noted in 71% with a median age of gestation of 11 (8–21) weeks. The presence of APS non-criteria features (35% vs 17% in pregnancies without adverse obstetrical event; p = 0.09), previous intrauterine death (65% vs 38%; p = 0.06), of LA (90% vs 65%; p = 0.05) were more frequent in pregnancies with adverse pregnancy outcome, whereas isolated recurrent miscarriage profile was more frequent in pregnancies without any adverse pregnancy outcome (15% vs 41%; p = 0.04). In univariate analysis considering all pregnancies (index and subsequent ones), an history of previous intrauterine death was associated with pregnancy loss (odds-ratio 2.51 (95% CI 1.274.96); p = 0.008), whereas previous history of prematurity related to APS (odds-ratio 0.13 95%CI 0.04 0.41, P = 0.006), steroids use during the pregnancy (odds-ratio 0.30 95% CI 0.11–0.82, p = 0.019) and anticardiolipids isolated profile (odds-ratio 0.51 95% CI 0.26–1.03, p = 0.0588) were associated with favorable outcome. In multivariate analysis, only previous history of prematurity, steroids use and anticardiolipids isolated profiles were associated with live-birth pregnancy. Conclusion The main features of refractory obstetrical APS were the high rates of LA and triple APL positivity. Steroids could be effective in this APS profile, but prospective studies are necessary.
Immune thrombocytopenia (ITP) is an acquired bleeding disorder, for which no specific diagnostic test exists. Inherited thrombocytopenia (IT) can mimic ITP and lead to unappropriated management with ...significant morbidity. Here, in small cohorts of these two disorders, we explored whether platelet sialylation and platelet activation could allow to discriminate the two conditions. We also aimed to confirm the value of immature platelet counts in this discrimination. Platelet sialylation and the expression level of P-selectin were assessed by multiparameter flow cytometry. Immature platelets were estimated on a Sysmex XN 9000 analyzer. No significant difference in platelet sialylation was observed between ITP and IT. Contrarily, platelet activation was significantly higher in ITP patients (
p
= 0.008). The immature platelet fraction, as previously demonstrated, was significantly lower in the ITP group compared to the IT group (
p
= 0.014). That statistical significance was achieved in this small pilot study suggests that the two easily available assays of immature platelet count and P-selectin expression could help physicians to reach the proper diagnosis in complex cases of thrombocytopenia.
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