Assessment of fatigue in adult patients with sickle cell disease: Use of the functional assessment of chronic illness therapy-Fatigue (FACIT-fatigue) questionnaire.

Few studies have used validated scales to assess the intensity and determinants of fatigue, a major symptom of sickle cell disease (SCD). We aimed to assess the level of basal fatigue in adult patients with SCD, using the Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-Fatigue) questionnaire. We prospectively included 102 stable adult outpatients with SCD over 2 months, who answered the FACIT-Fatigue (ranging from 0 (worst imaginable fatigue) to 52 (no fatigue)) and reported on the intensity of fatigue and its impact on quality of life. The cut-off for significant fatigue was <34. The median [IQR] FACIT-Fatigue score was 29 [22-37], indicating moderate-to-severe fatigue. In a multivariate analysis, the FACIT-Fatigue score was significantly associated with female sex, high body mass index, high level of stress, poor sleep quality, and number of previous episodes of acute chest syndrome, but not with the genotype or the haemoglobin level. Most adult patients with SCD experience significant and sometimes intense fatigue; this is probably due to several factors, including disease activity. Fatigue should be evaluated systematically during consultations and in patient education programmes and as an end-point in therapeutic trials.

Legionnaires Disease in Solid Organ Transplant Recipients: A Decade-Long Nationwide Study in France.

BACKGROUND: Legionnaires disease (LD) is a rare, life-threatening opportunistic bacterial infection that poses a significant risk to patients with impaired cell-mediated immunity such as solid organ transplant recipients. However, the epidemiologic features, clinical presentation, and outcomes of LD in this population are poorly described. RESEARCH QUESTION: What are the clinical manifestations, radiologic presentation, risk factors for severity, treatment, and outcome of LD in solid organ transplant recipients? STUDY DESIGN AND METHODS: In this 10-year multicenter retrospective cohort study in France, where LD notification is mandatory, patients were identified by hospital discharge databases. Diagnosis of LD relied on positive culture findings from any respiratory sample, positive urinary antigen test (UAT) results, positive specific serologic findings, or a combination thereof. Severe LD was defined as admission to the ICU. RESULTS: One hundred one patients from 51 transplantation centers were eligible; 64 patients (63.4%) were kidney transplant recipients. Median time between transplantation and LD was 5.6 years (interquartile range, 1.5-12 years). UAT results were positive in 92% of patients (89/97). Among 31 patients with positive culture findings in respiratory samples, Legionella pneumophila serogroup 1 was identified in 90%. Chest CT imaging showed alveolar consolidation in 98% of patients (54 of 57), ground-glass opacity in 63% of patients (36 of 57), macronodules in 21% of patients (12 of 57), and cavitation in 8.8% of patients (5 of 57). Fifty-seven patients (56%) were hospitalized in the ICU. In multivariate analysis, severe LD was associated with negative UAT findings at presentation (P = .047), lymphopenia (P = .014), respiratory symptoms (P = .010), and pleural effusion (P = .039). The 30-day and 12-month mortality rates were 8% (8 of 101) and 20% (19 of 97), respectively. In multivariate analysis, diabetes mellitus was the only factor associated with 12-month mortality (hazard ratio, 3.2; 95% OR, 1.19-8.64; P = .022). INTERPRETATION: LD is a late and severe complication occurring in solid organ transplant recipients that may present as pulmonary nodules on which diabetes impacts its long-term prognosis.

Long-Term Outcome and Prognosis of Noninfectious Thoracic Aortitis.

BACKGROUND: Aortitis is a group of disorders characterized by the inflammation of the aorta. The large-vessel vasculitides are the most common causes of aortitis. Aortitis long-term outcomes are not well known. OBJECTIVES: The purpose of this study was to assess the long-term outcome and prognosis of noninfectious surgical thoracic aortitis. METHODS: This was a retrospective multicenter study of 5,666 patients with thoracic aorta surgery including 217 (3.8%) with noninfectious thoracic aortitis (118 clinically isolated aortitis, 57 giant cells arteritis, 21 Takayasu arteritis, and 21 with various systemic autoimmune disorders). Factors associated with vascular complications and a second vascular procedure were assessed by multivariable analysis. RESULTS: Indications for aortic surgery were asymptomatic aneurysm with a critical size (n = 152 [70%]), aortic dissection (n = 28 [13%]), and symptomatic aortic aneurysm (n = 30 [14%]). The 10-year cumulative incidence of vascular complication and second vascular procedure was 82.1% (95% CI: 67.6%-90.6%), and 42.6% (95% CI: 28.4%-56.1%), respectively. Aortic arch aortitis (HR: 2.08; 95% CI: 1.26-3.44; P = 0.005) was independently associated with vascular complications. Descending thoracic aortitis (HR: 2.35; 95% CI: 1.11-4.96; P = 0.031) and aortic dissection (HR: 3.08; 95% CI: 1.61-5.90; P = 0.002) were independently associated with a second vascular procedure, while treatment with statins after aortitis diagnosis (HR: 0.47; 95% CI: 0.24-0.90; P = 0.028) decreased it. After a median follow-up of 3.9 years, 19 (16.1%) clinically isolated aortitis patients developed features of a systemic inflammatory disease and 35 (16%) patients had died. CONCLUSIONS: This multicenter study shows that 82% of noninfectious surgical thoracic aortitis patients will experience a vascular complication within 10 years. We pointed out specific characteristics that identified those at highest risk for subsequent vascular complications and second vascular procedures.

Acute chest syndrome in adult patients with sickle cell disease: The relationship with the time to onset after hospital admission.

Data on acute chest syndrome (ACS) in adult sickle cell disease patients are scarce. In this study, we describe 105 consecutive ACS episodes in 81 adult patients during a 32-month period and compare the characteristics as a function of the time to onset after hospital admission for a vaso-occlusive crisis (VOC), that is early-onset episodes (time to onset ≤24 h, 42%) versus secondary episodes (>24 h, 58%; median [interquartile range] time to onset: 2 [2-3] days). The median age was 27 [22-34] years, 89% of the patients had an S/S or S/ß0 -thalassaemia genotype; 81% of the patients had a history of ACS (median: 3 [2-5] per patient), only 61% were taking a disease-modifying treatment at the time of the ACS. Fever and chest pain were noted in respectively 54% and 73% of the episodes. Crackles (64%) and bronchial breathing (32%) were the main abnormal auscultatory findings. A positive microbiological test was found for 20% of episodes. Fifty percent of the episodes required a blood transfusion; ICU transfer and mortality rates were respectively 29% and 1%. Secondary and early-onset forms of ACS did not differ significantly. Disease-modifying treatments should be revaluated after each ACS episode because the recurrence rate is high.

Impact of the First COVID-19 Pandemic Wave on Hospitalizations and Deaths Caused by Geriatric Syndromes in France: A Nationwide Study.

BACKGROUND: The fear of contracting coronavirus disease 2019 (COVID-19) and the preventive measures taken during the health crisis affected both people's lifestyles and the health system. This nationwide study aimed to investigate the impact of the first wave of the COVID-19 pandemic on hospitalizations and mortality related to geriatric syndromes (GS) in older adults in France. METHODS: The French National Health Data System was used to compare hospital admissions (excluding the main diagnosis of COVID-19) and mortality rates (using multiple-cause and initial-cause analyses, and both including or excluding confirmed/probable COVID-19) related to 10 different GS (dementia, other cognitive disorders and symptoms, delirium/disorientation, depression, undernutrition/malnutrition, dehydration, pressure ulcer, incontinence, fall/injury and femoral neck fracture) from January to September 2020 to rates observed in previous years. Analyses were stratified by age, sex, place of residence or place of death, and region. RESULTS: Hospitalization rates for all GS decreased during the first lockdown compared to the same periods in 2017-19 (from -59% for incontinence to -13% for femoral neck fractures). A dose-response relationship was observed between reduced hospitalizations and COVID-19-related mortality rates. Conversely, for almost all GS studied, excess mortality without COVID-19 was observed during this lockdown compared to 2015-17 (from +74% for delirium/disorientation to +8% for fall/injury), especially in nursing homes and at home. CONCLUSIONS: In France, during the first lockdown, a substantial decrease in hospitalizations for GS was accompanied by excess mortality. This decline in the use of services, which persisted beyond lockdown, may have a mid- and long-term impact on older adults' health.

JAK inhibitors in difficult-to-treat adult-onset Still's disease and systemic-onset juvenile idiopathic arthritis.

OBJECTIVES: Excessive and inappropriate production of pro-inflammatory cytokines plays a key role in Still's disease. Janus kinase inhibitor (JAKi) agents mainly block pro-inflammatory cytokine pathways, notably IL-6 and IFN. The objective was to assess the efficacy and safety of JAKi agents in difficult-to-treat systemic JIA or adult-onset Still's disease (AOSD). METHODS: This retrospective study was based on a national survey conducted in the departments of rheumatology, paediatric rheumatology and internal medicine of French hospitals regarding systemic JIA and AOSD patients who received JAKi agents. The data were collected with a standardized questionnaire and analysed at different times (treatment initiation, months 1, 3 and 6 and the end of follow-up). RESULTS: Nine patients (seven adults) were included. All patients showed inadequate response to CS or conventional synthetic or biologic DMARDs. Baricitinib was used in five patients, ruxolitinib in two, tofacitinib in two and upadacitinib in one. A JAKi was used combined with CS in all but two patients. A JAKi was associated with anakinra and CS in one patient, and with MTX, anakinra and CS in another. The median (range) follow-up was 16 (1-33) months. Two cases out of nine showed complete remission, 3/9 partial response and 4/9 treatment failure. At the last visit, CS could be decreased but not stopped. Tolerance of the JAKi was acceptable (no severe adverse events). CONCLUSION: JAKi agents may be a therapeutic option for some patients with difficult-to-treat Still's disease, especially those with partial response to medium- or high-dose CS or biologics.

Risks and Benefits of Prophylactic Transfusion before Cholecystectomy in Sickle Cell Disease.

Preoperative transfusion (PT) reduces acute postoperative vaso-occlusive events (VOE) in sickle cell disease (SCD), but exposes patients to alloimmunization, encouraging a recent trend towards transfusion sparing. The aim of this study was to investigate the benefit-risk ratio of PT before cholecystectomy on the occurrence of postoperative VOE. Adult SCD patients who underwent cholecystectomy between 2008 and 2019 in our center were included. Patients' characteristics, collected retrospectively, were compared according to PT. A total of 79 patients were included, 66% of whom received PT. Gallbladder histopathology found chronic cholecystitis (97%) and gallstones (66%). Transfused patients underwent more urgent surgeries and had experienced more painful vaso-occlusive crises (VOC) in the month before surgery (p = 0.05). Four (8.5%) post-transfusion alloimmunizations occurred, and two of them caused a delayed hemolytic transfusion reaction (DHTR) (4.3%). The occurrence of postoperative VOE was similar between the groups (19.2% vs. 29.6%, p = 0.45). Though not statistically significant, a history of hospitalized VOC within 6 months prior to surgery seemed to be associated to postoperative VOE among non-transfused patients (75% vs. 31.6%, p = 0.10). PT before cholecystectomy exposes to risks of alloimmunization and DHTR that could be avoided in some patients. Recent VOCs appear to be associated with a higher risk of postoperative VOE and prompt the preemptive transfusion of these patients.

Neurological complications of varicella zoster virus reactivation: Prognosis, diagnosis, and treatment of 72 patients with positive PCR in the cerebrospinal fluid.

BACKGROUND: VZV infection can involve every level of the neurologic system: from the central nervous system (CNS) to the peripheral nervous system (PNS), including aseptic meningitis. Prognosis seems to differ between these neurological involvements. Prognostic factors remain unknown. METHODS: This is a retrospective multicenter study including all patients with a positive VZV polymerase chain reaction (PCR) in the cerebrospinal fluid (CSF) from eight centers in Paris (France) between 2011 and 2018. Unfavorable outcome was defined as mortality linked to VZV or incomplete recovery. Modified Rankin Scale (mRS) evaluated disability before and after the infection, with the difference designated as Rankin Delta. RESULTS: Seventy-two patients were included (53% male, median age 51 years, median mRS 0). Immunosuppression was reported in 42%. The clinical spectrum included 26 cases of meningitis, 27 instances of CNS involvement, 16 of PNS involvement, and 3 isolated replications (positive PCR but no criteria for neurological complications from VZV). Antiviral treatment was administered to 69 patients (96%). Sixty-two patients completed follow-up. Death linked to VZV occurred in eight cases. Unfavorable outcome (UO) occurred in 60% and was significantly associated with a higher prior mRS (Odd-ratio (OR) 3.1 [1.4-8.8] p = .012) and the presence of PNS or CNS manifestations (OR 22 [4-181] p = .001, OR 6.2 [1.3-33] p = .03, respectively, compared to meningitis). In the CSF, higher protein level (p < .0001) was also significantly associated with a higher Rankin Delta. CONCLUSIONS: Neurological complications of VZV with evidence of CSF viral replication are heterogeneous: aseptic meningitis has a good prognosis, whereas presence of CNS and PNS involvement is associated with a higher risk of mortality and of sequelae, respectively.

[Abnormal urine color assessment: The urine wheel]. / Orientation diagnostique devant une coloration anormale des urines : la roue à urines 2.0.

Looking at the urine for diagnostic purposes, once performed by ancient Egyptians, can still provide some valuable clues in modern medicine. Several diseases have been named after their associated urine color and this underlines the clinical value of visual urine inspection: blue diaper disease, purple urine bag syndrome, black urine disease or porphyria. Abnormal urine color could be challenging for the clinician: it may reveal neoplastic disease (urologic cancer; melanoma), cell lysis (rhabdomyolysis; hemolysis), infection (lymphatic filariasis; malaria), enzyme deficiency (porphyria; alkaptonuria), medication or food intake. In this article, we present the diagnostic approach, the mechanisms involved and the main causes of abnormal urine color.

Ketoacidosis in a non-diabetic lactating woman: A case report and literature review.

We report the case of a 36-year-old woman who developed non-diabetic ketoacidosis following a low carbohydrate diet in order to lose weight while actively breast feeding her newborn. She was admitted in intensive care unit because of severe metabolic acidosis. She rapidly recovered after refeeding process. Lactation ketoacidosis, a special condition that occurs in non-diabetic breastfeeding women, is rare and life-threatening. This report highlights the importance of nutritional education of lactating women in the post-partum period.

Catastrophic adult-onset Still's disease as a distinct life-threatening clinical subset: case-control study with dimension reduction analysis.

OBJECTIVES: Adult-onset Still's disease (AOSD) is a rare systemic inflammatory disorder. Diagnosing AOSD can be challenging, as disease presentation and clinical course are highly heterogeneous. For unclear reasons, a few patients develop life-threatening complications. Our objective was to determine whether these cases resulted from therapeutic delay or could represent a peculiar AOSD subset. METHODS: We conducted a multicentre retrospective study of 20 AOSD patients with organ failure requiring intensive care unit admission and 41 control AOSD patients without organ failure. Clinico-biological data at hospital admission were explored using supervised analyses and unsupervised dimension reduction analysis (factor analysis of mixed data, FAMD). RESULTS: Disease duration before admission was shorter in patients with life-threatening AOSD (median, 10 vs 20 days, p = 0.007). Disease duration before AOSD therapy initiation also tended to be shorter (median, 24 vs 32 days, p = 0.068). Despite this shorter disease duration, FAMD, hierarchical clustering and univariate analyses showed that these patients exhibited distinctive characteristics at first presentation, including younger age; higher frequency of splenomegaly, liver, cardiac and/or lung involvement; less frequent arthralgia; and higher ferritin level. In multivariate analysis, 3 parameters predicted life-threatening complications: lack of arthralgia, younger age and shorter time between fever onset and hospitalisation. CONCLUSION: This study suggests that life-threatening complications of AOSD occur very early, in a peculiar subset, which we propose to name catastrophic adult-onset Still's disease (CAOSD). Its exact burden may be underestimated and remains to be clarified through large multicentre cohorts. Further studies are needed to identify red flags and define the optimal therapeutic strategy.

COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases treated with rituximab: a cohort study.

BACKGROUND: Various observations have suggested that the course of COVID-19 might be less favourable in patients with inflammatory rheumatic and musculoskeletal diseases receiving rituximab compared with those not receiving rituximab. We aimed to investigate whether treatment with rituximab is associated with severe COVID-19 outcomes in patients with inflammatory rheumatic and musculoskeletal diseases. METHODS: In this cohort study, we analysed data from the French RMD COVID-19 cohort, which included patients aged 18 years or older with inflammatory rheumatic and musculoskeletal diseases and highly suspected or confirmed COVID-19. The primary endpoint was the severity of COVID-19 in patients treated with rituximab (rituximab group) compared with patients who did not receive rituximab (no rituximab group). Severe disease was defined as that requiring admission to an intensive care unit or leading to death. Secondary objectives were to analyse deaths and duration of hospital stay. The inverse probability of treatment weighting propensity score method was used to adjust for potential confounding factors (age, sex, arterial hypertension, diabetes, smoking status, body-mass index, interstitial lung disease, cardiovascular diseases, cancer, corticosteroid use, chronic renal failure, and the underlying disease [rheumatoid arthritis vs others]). Odds ratios and hazard ratios and their 95% CIs were calculated as effect size, by dividing the two population mean differences by their SD. This study is registered with ClinicalTrials.gov, NCT04353609. FINDINGS: Between April 15, 2020, and Nov 20, 2020, data were collected for 1090 patients (mean age 55·2 years [SD 16·4]); 734 (67%) were female and 356 (33%) were male. Of the 1090 patients, 137 (13%) developed severe COVID-19 and 89 (8%) died. After adjusting for potential confounding factors, severe disease was observed more frequently (effect size 3·26, 95% CI 1·66-6·40, p=0·0006) and the duration of hospital stay was markedly longer (0·62, 0·46-0·85, p=0·0024) in the 63 patients in the rituximab group than in the 1027 patients in the no rituximab group. 13 (21%) of 63 patients in the rituximab group died compared with 76 (7%) of 1027 patients in the no rituximab group, but the adjusted risk of death was not significantly increased in the rituximab group (effect size 1·32, 95% CI 0·55-3·19, p=0·53). INTERPRETATION: Rituximab therapy is associated with more severe COVID-19. Rituximab will have to be prescribed with particular caution in patients with inflammatory rheumatic and musculoskeletal diseases. FUNDING: None.

Efficacy and safety of rituximab in peripheral ulcerative keratitis associated with rheumatoid arthritis.

OBJECTIVE: Peripheral ulcerative keratitis (PUK) is a rare but severe ocular complication of rheumatoid arthritis (RA). It can be considered as an ocular manifestation of rheumatoid vasculitis (RV). Our case series aimed to evaluate the efficacy of rituximab (RTX) for PUK occurring in patients with RA. METHODS: Study population were patients with RA-associated PUK treated with RTX 1000 mg on days 1 and 15 at least once after the diagnosis. We identified patients referred to the rheumatology and ophthalmology departments of our hospital between February 2014 and June 2020. We also included patients referred by their specialist after being contacted through the Club Rhumatismes et Inflammation. Demographic data and clinical and biological features were retrospectively collected. RESULTS: We included seven patients (three men and four women, median age 58 years). All but one had a long-standing RA with a median disease duration of 13.9 years (IQR 0-30.2). RA was erosive in six out of seven patients. All patients had rheumatoid factors and anticitrullinated peptides antibodies were positive in six of them. PUK was complicated by corneal perforation in three patients and required surgery. After a median follow-up of 29.8 months (IQR 5-75), corneal inflammation was controlled in all patients. PUK recurred in one patient, 8 months after a single infusion of RTX. 71% of the patients presented a good articular response. No patient developed other manifestations of RV. No serious adverse event related to RTX was observed. CONCLUSION: RTX appears to be an efficient and safe therapeutic option in the treatment of RA-associated PUK.

[Usefulness of immature platelet fraction measurement for diagnosis and monitoring of iron deficiency associated thrombocytopenia: about two cases]. / Apport de la mesure de la fraction de plaquettes immatures dans le diagnostic et le suivi des thrombopénies ferriprives : à propos de deux cas.

Iron deficiency anemia is frequently associated with thrombocytosis. However, in some rare cases of very severe iron deficiency, a thrombocytopenia may occur. This condition may lead to a misdiagnosis of immune thrombocytopenic purpura and thus to unnecessary tests in this context. Here we report two patients who presented with iron deficiency associated thrombocytopenia rapidly corrected after martial supplementation. We then discuss the value of measuring immature platelet fraction (IPF), which represents the population of newly formed platelets containing a greater amount of residual RNA. For both cases, low IPF values at admission indicated a central origin of thrombocytopenia with decreased platelet production, which is the pathophysiological mechanism of iron deficiency associated thrombocytopenia.