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1.
Artigo em Inglês | MEDLINE | ID: mdl-31529073

RESUMO

OBJECTIVES: Temporal artery biopsy (TAB) is a reference test for the diagnosis of GCA but reveals inflammatory changes only in a subset of patients. The lack of knowledge of TAB sensitivity hampers comparisons with non-invasive techniques such as temporal artery ultrasonography. We performed a systematic literature review and meta-analysis to estimate the sensitivity of TAB in GCA and to identify factors that may influence the estimate. METHODS: A systematic literature review involved searching electronic databases and cross-references. Eligibility criteria included publications reporting at least 30 GCA cases fulfilling the original or modified 1990 ACR classification criteria. The pooled proportion of TAB-positive GCA cases was calculated by using aggregated-data meta-analysis with a random-effects model and assessment of heterogeneity with the I2 statistic. Subgroup analyses and meta-regression were used to examine the effect of patient and study characteristics on TAB positivity. RESULTS: Among 3820 publications screened, 32 studies (3092 patients) published during 1993-2017 were analysed. The pooled proportion of TAB-positive GCA cases was 77.3% (95% CI: 71.8, 81.9%), with high between-study heterogeneity (I2 = 90%). The proportion of TAB-positive cases was slightly higher in publications before than in 2012 and after (P = 0.001). CONCLUSION: The estimated sensitivity of 77% provides indirect evidence that TAB is not less sensitive than temporal artery imaging. The unexplained high between-study heterogeneity could result from differences in TAB sampling, processing or interpretation. The decrease in TAB-positive GCA cases over time could reflect an increasing propensity for clinicians to accept a GCA diagnosis without proof by TAB.

2.
Crit Care ; 23(1): 306, 2019 09 06.
Artigo em Inglês | MEDLINE | ID: mdl-31492179

RESUMO

BACKGROUND: Acute respiratory failure is the leading reason for intensive care unit (ICU) admission in immunocompromised patients, and the need for invasive mechanical ventilation has become a major clinical endpoint in randomized controlled trials (RCTs). However, data are lacking on whether intubation is an objective criteria that is used unbiasedly across centers. This study explores how this outcome varies across ICUs. METHODS: Hierarchical models and permutation procedures for testing multiple random effects were applied on both data from an observational cohort (the TRIAL-OH study: 703 patients, 17 ICUs) and a randomized controlled trial (the HIGH trial: 776 patients, 31 ICUs) to characterize ICU variation in intubation risk across centers. RESULTS: The crude intubation rate varied across ICUs from 29 to 80% in the observational cohort and from 0 to 86% in the RCT. This center effect on the mean ICU intubation rate was statistically significant, even after adjustment on individual patient characteristics (observational cohort: p value = 0.013, median OR 1.48 [1.30-1.72]; RCT: p value 0.004, median OR 1.51 [1.36-1.68]). Two ICU-level characteristics were associated with intubation risk (the annual rate of intubation procedure per center and the time from respiratory symptoms to ICU admission) and could partly explain this center effect. In the RCT that controlled for the use of high-flow oxygen therapy, we did not find significant variation in the effect of oxygenation strategy on intubation risk across centers, despite a significant variation in the need for invasive mechanical ventilation. CONCLUSION: Intubation rates varied considerably among ICUs, even after adjustment on individual characteristics.

3.
Comput Biol Med ; 111: 103339, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31442762

RESUMO

In randomized clinical trials (RCT), the analysis is based on the intent-to-treat principle to avoid any selection bias in the constitution of groups. However, estimates of overall survival can be biased when significant crossover occurs because the separation of randomized groups is lost. To handle these switches, the inverse probability of censoring weighting (IPCW) method has been proposed; however, it is still poorly used in RCT, notably because of its complex implementation. In particular, for time-to-event outcomes, it can be difficult to format data, especially when time-dependent covariates have to be managed, with different measurement times between patients. This paper aims to present the R package ipcwswitch with some guidance for the analysis of the treatment effect on survival in a hypothetical setting where all patients would have continued to take the randomization treatment. After a brief recall of the key principles of the IPCW method, each step of the implementation is described using a toy example. The guidelines are illustrated in a case study that aimed at evaluating the benefit of therapy based on tumour molecular profiling for advanced cancers, SHIVA01.

4.
J Eval Clin Pract ; 2019 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-31466139

RESUMO

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is an important public health problem. The French organization, combining OHCA basic life support (BLS) and advanced life support (ALS), has been recently questioned. The study was conducted to evaluate the association between early ALS (E-ALS) arrival and good neurological outcome at 1 month in nontraumatic OHCA patients. MATERIALS AND METHODS: Retrospective cohort study using data from RéAC, multicentre OHCA database since June 2011. Adult patients with nontraumatic cardiac arrest were identified, and firefighters' (BLS) arrival time was recorded. The main analysis was performed after multiple imputation, using propensity score matching with a variable ratio. Sensitivity analyses were also performed. The exposure was early ALS (E-ALS), start of ALS before. or simultaneously with BLS. The primary outcome was the cerebral performance category (CPC) at day 30 after the cardiac arrest (1-2 vs 3-5), while cumulative incidence of return of spontaneous circulation (ROSC) defined secondary outcomes. RESULTS: Between January 2013 and January 2016, a total of 30 672 adult nontraumatic OHCA with resuscitation were identified, from whom 20 804 were included, 2711 in the E-ALS group and 18 093 in the control group. Based on the matched sample, patients in the E-ALS group had a significantly lower rate of good neurological outcome than those in the control group (OR, 0.95; 95% CI, 0.93-0.96). Sensitivity analyses were mostly consistent with this result. Cumulative incidence of ROSC was higher in delayed ALS (D-ALS) group. CONCLUSIONS: This study showed that patients in the E-ALS group were less likely to have a good neurological outcome. One explanation of this unexpected result could be the total duration of resuscitation performed, which may be interrupted prematurely in cases of E-ALS.

5.
Neurology ; 93(4): e388-e397, 2019 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-31239360

RESUMO

OBJECTIVE: To identify independent predictors of clinical or cerebral lesion progression in a large sample of adult patients with moyamoya angiopathy (MMA) prior to decisions regarding revascularization surgery. METHODS: Ninety participants (median age, 37.5 years) were assessed at baseline and followed for a median time of 42.8 months. Incident ischemic and hemorrhagic strokes, death, as well as any incident ischemic and hemorrhagic lesions on MRI were recorded. Multiple demographic, clinical, and cerebral imaging measures at baseline were considered as potential predictors of clinical or cerebral tissue change at follow-up. Data were analyzed based on the Andersen-Gill counting process model, followed by internal validation of the prediction model. RESULTS: Among multiple potential predictive measures considered in the analysis, Asian origin, a history of TIAs, and a reduction in hemodynamic reserve, as detected by imaging, were found to be significantly associated with an increased risk of combined clinical and imaging events. While the model estimated the risk of clinical or cerebral lesion progression to be approximately 0.5% per year when none of these factors was present, this risk exceeded 20% per year when all factors were present. CONCLUSION: A simple combination of demographic, clinical, and cerebral perfusion imaging measures may aid in predicting the risk of incident stroke and cerebral lesion progression in adult patients with MMA. These results may help to improve therapeutic decisions and aid in the design of future trials in adults with this rare condition.

6.
Crit Care ; 23(1): 211, 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31182133

RESUMO

BACKGROUND: Mottling score, a tissue perfusion parameter, is correlated with outcome in septic shock patients. However, its predictive value on mortality according to prognostic covariates such as vasopressor dose and other tissue perfusion parameters remains unknown. METHODS: Mottling score and tissue perfusion parameters were recorded at ICU admission (H0), H-6, H 12, and H-24 and used to assess the predictive value of mottling score on 14-day mortality in a development cohort. Results were then validated in an independent cohort of septic shock patients in Brazil. RESULTS: Overall, 259 patients with sepsis or septic shock were included, 14-day mortality was 37%. Factors associated with death were mottling score (OR 2.26 [95% CI, 1.72-2.97]), arterial lactate level (OR 1.29 [1.11-1.5]), and urine output < 0.5 ml/Kg/h (OR 3.03 [1.37-6.69]). The C statistic for the model was 0.90 in the development cohort and 0.76 in the validation cohort. The predictive value of mottling score was not affected by vasopressor doses (p for interaction = 0.33): OR for mottling score ranged from 2.34 [1.10-3.15] in patients without vasopressor to 3.84 [1.98-7.43] in patients infused with high doses of vasopressor (> 0.8 µg/kg/min). There was no difference in the effect of mottling score on mortality according to mean arterial pressure, heart rate, cardiac index, and urine output, but we found a significant interaction between arterial lactate level and mottling score (p = 0.04). The predictive value of the mottling score remains significant when using the recent SEPSIS-3 definition of septic shock. Finally, a decrease of mottling score during resuscitation was significantly associated with better outcome after adjustment on SOFA score (p = 0.001). CONCLUSIONS: Our results support the high prognostic value of mottling score for 14-day mortality in septic patients, whatever vasopressor dosage and other perfusion parameters. Mottling score variations during resuscitation are also predictive of mortality.

8.
Eur Respir J ; 54(1)2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31109985

RESUMO

OBJECTIVE: We wished to explore the use, diagnostic capability and outcomes of bronchoscopy added to noninvasive testing in immunocompromised patients. In this setting, an inability to identify the cause of acute hypoxaemic respiratory failure is associated with worse outcome. Every effort should be made to obtain a diagnosis, either with noninvasive testing alone or combined with bronchoscopy. However, our understanding of the risks and benefits of bronchoscopy remains uncertain. PATIENTS AND METHODS: This was a pre-planned secondary analysis of Efraim, a prospective, multinational, observational study of 1611 immunocompromised patients with acute respiratory failure admitted to the intensive care unit (ICU). We compared patients with noninvasive testing only to those who had also received bronchoscopy by bivariate analysis and after propensity score matching. RESULTS: Bronchoscopy was performed in 618 (39%) patients who were more likely to have haematological malignancy and a higher severity of illness score. Bronchoscopy alone achieved a diagnosis in 165 patients (27% adjusted diagnostic yield). Bronchoscopy resulted in a management change in 236 patients (38% therapeutic yield). Bronchoscopy was associated with worsening of respiratory status in 69 (11%) patients. Bronchoscopy was associated with higher ICU (40% versus 28%; p<0.0001) and hospital mortality (49% versus 41%; p=0.003). The overall rate of undiagnosed causes was 13%. After propensity score matching, bronchoscopy remained associated with increased risk of hospital mortality (OR 1.41, 95% CI 1.08-1.81). CONCLUSIONS: Bronchoscopy was associated with improved diagnosis and changes in management, but also increased hospital mortality. Balancing risk and benefit in individualised cases should be investigated further.

9.
Crit Care ; 23(1): 152, 2019 05 02.
Artigo em Inglês | MEDLINE | ID: mdl-31046842

RESUMO

BACKGROUND: It is unclear whether influenza infection and associated co-infection are associated with patient-important outcomes in critically ill immunocompromised patients with acute respiratory failure. METHODS: Preplanned secondary analysis of EFRAIM, a prospective cohort study of 68 hospitals in 16 countries. We included 1611 patients aged 18 years or older with non-AIDS-related immunocompromise, who were admitted to the ICU with acute hypoxemic respiratory failure. The main exposure of interest was influenza infection status. The primary outcome of interest was all-cause hospital mortality, and secondary outcomes ICU length of stay (LOS) and 90-day mortality. RESULTS: Influenza infection status was categorized into four groups: patients with influenza alone (n = 95, 5.8%), patients with influenza plus pulmonary co-infection (n = 58, 3.6%), patients with non-influenza pulmonary infection (n = 820, 50.9%), and patients without pulmonary infection (n = 638, 39.6%). Influenza infection status was associated with a requirement for intubation and with LOS in ICU (P < 0.001). Patients with influenza plus co-infection had the highest rates of intubation and longest ICU LOS. On crude analysis, influenza infection status was associated with ICU mortality (P < 0.001) but not hospital mortality (P = 0.09). Patients with influenza plus co-infection and patients with non-influenza infection alone had similar ICU mortality (41% and 37% respectively) that was higher than patients with influenza alone or those without infection (33% and 26% respectively). A propensity score-matched analysis did not show a difference in hospital mortality attributable to influenza infection (OR = 1.01, 95%CI 0.90-1.13, P = 0.85). Age, severity scores, ARDS, and performance status were all associated with ICU, hospital, and 90-day mortality. CONCLUSIONS: Category of infectious etiology of respiratory failure (influenza, non-influenza, influenza plus co-infection, and non-infectious) was associated with ICU but not hospital mortality. In a propensity score-matched analysis, influenza infection was not associated with the primary outcome of hospital mortality. Overall, influenza infection alone may not be an independent risk factor for hospital mortality in immunosuppressed patients.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31144997

RESUMO

OBJECTIVES: To report current practices regarding mechanical ventilation in patients treated with extracorporeal membrane oxygenation (ECMO) for severe acute respiratory distress syndrome (ARDS) and their association with 6-month outcomes. METHODS: International, multi-center, prospective cohort study of patients undergoing ECMO for ARDS during a one-year period in 23 international intensive care units (ICUs). MEASUREMENTS AND MAIN RESULTS: We collected demographics, daily pre- and per-ECMO mechanical ventilation settings and use of adjunctive therapies, ICU- and 6-month-outcome data for 350 patients (median ± standard deviation pre-ECMO PaO2/FiO2 71±34 mmHg). Pre-ECMO use of prone positioning and neuromuscular blockers were 26% and 62%, respectively. Tidal volume (6.4±2.0 vs 3.7±2.0 ml/kg), plateau pressure (32±7 vs 24±7cmH2O), driving pressure (20±7 vs. 14±4 cmH2O), respiratory rate (26±8 vs 14±6 breaths/min) and mechanical power (26.1±12.7 vs. 6.6±4.8 J/min) were markedly reduced after ECMO initiation. Six-month survival was 61%. No association was found between ventilator settings during the first 2 days of ECMO and survival in multivariable analysis. A time-varying Cox model retained older age, higher fluid balance, higher lactate, and more need for renal replacement therapy along the ECMO course as being independently associated with 6-month mortality. A higher tidal volume and lower driving pressure (likely markers of static compliance improvement) across the ECMO course were also associated with better outcomes. CONCLUSION: Ultra-protective lung ventilation on ECMO was largely adopted across medium to high case-volume ECMO centers. In contrast with previous observations, mechanical ventilation settings during ECMO did not impact patients' prognosis in this context.

12.
J Am Acad Dermatol ; 80(6): 1544-1549, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30981429

RESUMO

BACKGROUND: Paraneoplastic pemphigus (PNP) occurs more often in patients with hematologic malignancies (HMs) than in patients with solid cancer. Lung bronchiolitis obliterans (BO) is a severe complication of PNP. OBJECTIVE: To determine the precise clinical and biologic features of HM-associated PNP and identify factors associated with mortality and survival. METHODS: Systematic review of previously described cases of PNP associated with HMs. RESULTS: A total of 144 patients were included. The HMs were non-Hodgkin lymphoma (52.78%), chronic lymphocytic leukemia (22.92%), Castleman disease (18.60%), and other underlying hematologic malignancy (5.70%). The mortality rate was 57%, and most deaths occurred within the first year after the diagnosis of PNP. Multivariate analysis showed that (1) the presence of antienvoplakin antibodies and BO were significantly associated with death, and (2) a toxic epidermal necrolysis-like clinical pattern, bullous pemphigoid-like clinical pattern, and BO were significantly associated with decreased survival. LIMITATION: Only case reports with sufficient mortality data were included. CONCLUSION: PNP associated with HM has a high mortality rate. The toxic epidermal necrolysis-like and BO-associated forms are independent survival factors in PNP associated with HMs.

13.
CMAJ ; 191(13): E352-E360, 2019 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-30936165

RESUMO

BACKGROUND: Short-term maternal complications of cesarean delivery remain uncertain because of confounding by indication. Our objective was to assess whether cesarean delivery is associated with severe acute intra- or postpartum maternal morbidity compared with vaginal delivery, overall and according to the timing of the cesarean. METHODS: We performed a case-control analysis using data from EPIMOMS, a prospective population-based study of deliveries at 22 gestation weeks or later from 6 regions of France in 2012-2013. Cases of intra- or postpartum severe acute maternal morbidity that were not a result of a condition present before delivery were compared with controls randomly selected in a 1/50 ratio. Associations between delivery modes and severe acute maternal morbidity were estimated in a propensity score-matched sample. RESULTS: Among 182 300 deliveries, we identified 1444 cases and 3464 controls. The proportion of cesarean delivery was significantly higher among cases than controls (36.0% v. 18.2%). In the propensity score-matched analysis, cesarean deliveries were significantly associated with a higher risk of severe acute maternal morbidity (adjusted odds ratio [OR] 1.8, 95% confidence interval [CI] 1.5-2.2). This association increased with maternal age and was particularly marked for women aged 35 years or older (adjusted OR 2.9, 95% CI 1.9-4.4). This increased risk was significant for cesarean deliveries during labour in women of all age groups and for those before labour only in women aged 35 years or older (adjusted OR 5.1, 95% CI 2.3-11.0). INTERPRETATION: Cesarean delivery is associated with a higher risk of severe acute maternal morbidity than vaginal delivery, particularly in women aged 35 years and older. Clinical decisions regarding delivery mode should account for this excess risk accordingly.

14.
Emerg Med J ; 36(5): 306-309, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30910911

RESUMO

OBJECTIVES: We sought to estimate the prevalence of patients with cancer presenting to the emergency department (ED) who are undergoing treatment with immune checkpoint blockade (ICB) therapy; report their chief complaints; describe and estimate the prevalence of immune-related adverse events (IRAEs). METHODS: Four abstractors reviewed the medical records of patients with cancer treated with ICB who presented to an ED in Paris, France between January 2012 and June 2017. Chief complaints, underlying malignancy and ICB characteristics, and the final diagnoses according to the emergency physician were recorded. Abstractors noted if an emergency physician identified that a patient was receiving an ICB and if the emergency physician considered the possibility of an IRAE. The gold standard as to whether an IRAE was the cause was the patients' referring oncologist's opinion that the ED symptoms were attributed to ICB and IRAE according to post-ED medical records. Descriptive statistics were reported. RESULTS: Among the 409 patients treated with ICB at our institution, 139 presented to the ED. Chief complaints were fatigue (25.2%), fever (23%), vomiting (13.7%), diarrhoea (13.7%), dyspnoea (12.2%), abdominal pain (11.5%), confusion (8.6%) and headache (7.9%). Symptoms were due to IRAEs in 20 (14.4%) cases. The most frequent IRAEs were colitis (40%), endocrine toxicity (30%), hepatitis (25%) and pulmonary toxicity (5%). Patients with IRAEs compared with those without them more frequently had melanoma; had received more distinct courses of ICB treatment, an increased number of ICB medications and ICB cycles; and had a shorter time course since the last infusion of ICB. Emergency physicians considered the possibility of an IRAE in 24 (17.3%) of cases and diagnosed IRAE in 10 (50%) of those with later confirmed IRAE. IRAE was more likely to be missed when the referring oncologist was not contacted or when the patient had respiratory symptoms, fatigue or fever. CONCLUSIONS: ICB exposes patients to potentially severe IRAEs. Emergency physicians must identify patients treated with ICB and consider their toxicity when patients present to the ED with symptoms compatible with IRAEs.


Assuntos
Antineoplásicos Imunológicos/toxicidade , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/epidemiologia , Neoplasias/tratamento farmacológico , Idoso , Anticorpos Monoclonais/uso terapêutico , Anticorpos Monoclonais/toxicidade , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/toxicidade , Antineoplásicos Imunológicos/uso terapêutico , Serviço Hospitalar de Emergência/organização & administração , Serviço Hospitalar de Emergência/estatística & dados numéricos , Fadiga/etiologia , Feminino , Febre/etiologia , Humanos , Ipilimumab/uso terapêutico , Ipilimumab/toxicidade , Masculino , Pessoa de Meia-Idade , Neoplasias/complicações , Nivolumabe/uso terapêutico , Nivolumabe/toxicidade , Paris/epidemiologia , Prevalência , Estudos Retrospectivos , Vômito/etiologia
15.
Crit Care Med ; 47(6): 809-816, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30889024

RESUMO

OBJECTIVES: We aimed to investigate center effects on hospital mortality of ICU patients with hematologic malignancies and to explore interactions between center and patients characteristics. DESIGN: Multicenter prospective cohort. SETTING: Seventeen ICUs across France and Belgium. PATIENTS: One-thousand eleven patients with hematologic malignancies hospitalized in ICUs. INTERVENTIONS: Reanalysis of the original data using state-of-the-art statistical methods with permutation procedures for testing multiple random effects. MEASUREMENTS AND MAIN RESULTS: Average crude mortality was 39% and varied from 11% to 58% across centers. There was a significant center effect on the mean hospital mortality, after adjustment on individual prognostic factors (p < 0.001; median adjusted odds ratio for center effect 1.57 [interquartile range, 1.24-2.18]). There was also a quantitative interaction between center and the effect of the Sequential Organ Failure Assessment score: higher scores were associated with higher mortality (odds ratio for 1 point = 1.24 on average; 95% CI, 1.15-1.33) but with a magnitude that depended on center (p = 0.028). CONCLUSIONS: Between-center heterogeneity in hospital mortality was confirmed after adjustment for individual prognostic factors. It was partially explained by center experience in treating oncology patients. Interestingly, center effect was similar in magnitude to that of known mortality risk factors.

16.
Haematologica ; 104(8): 1565-1571, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30733271

RESUMO

High-risk myelodysplastic syndrome/acute myeloid leukemia patients have a very poor survival after azacitidine failure. Guadecitabine (SGI-110) is a novel subcutaneous hypomethylating agent which results in extended decitabine exposure. This multicenter phase II study evaluated the efficacy and safety of guadecitabine in high-risk myelodysplastic syndrome and low blast count acute myeloid leukemia patients refractory or relapsing after azacitidine. We included 56 patients with a median age of 75 years [Interquartile Range (IQR) 69-76]. Fifty-five patients received at least one cycle of guadecitabine (60 mg/m2/d subcutaneously days 1-5 per 28-day treatment cycles), with a median of 3 cycles (range, 0-27). Eight (14.3%) patients responded, including two complete responses; median response duration was 11.5 months. Having no or few identified somatic mutations was the only factor predicting response (P=0.035). None of the 11 patients with TP53 mutation responded. Median overall survival was 7.1 months, and 17.9 months in responders (3 of whom had overall survival >2 years). In multivariate analysis, IPSS-R (revised International Prognostic Scoring System) score other than very high (P=0.03) primary versus secondary azacitidine failure (P=0.01) and a high rate of demethylation in blood during the first cycle of treatment (P=0.03) were associated with longer survival. Thus, guadecitabine can be effective, sometimes yielding relatively prolonged survival, in a small proportion of high-risk myelodysplastic syndrome/low blast count acute myeloid leukemia patients who failed azacitidine. (Trial registered at clinicaltrials.gov identifier: 02197676).

17.
JAMA ; 321(3): 266-276, 2019 01 22.
Artigo em Inglês | MEDLINE | ID: mdl-30667500

RESUMO

Importance: In children with sickle cell anemia (SCA), high transcranial Doppler (TCD) velocities are associated with stroke risk, which is reduced by chronic transfusion. Whether matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) can reduce velocities in patients with SCA is unknown. Objective: To determine the association of MSD-HSCT with TCD velocities as a surrogate for the occurrence of ischemic stroke in children with SCA. Design, Setting, and Participants: Nonrandomized controlled intervention study conducted at 9 French centers. Patients with SCA were enrolled between December 2010 and June 2013, with 3-year follow-up ending in January 2017. Children with SCA were eligible if younger than 15 years, required chronic transfusions for persistently elevated TCD velocities, and had at least 1 sibling without SCA from the same 2 parents. Families agreed to HLA antigen typing and transplantation if a matched sibling donor was identified or to standard care in the absence of a matched sibling donor. Exposures: MSD-HSCT (n = 32), compared with standard care (n = 35) (transfusions for ≥1 year with potential switch to hydroxyurea thereafter), using propensity score matching. Main Outcomes and Measures: The primary outcome was the highest time-averaged mean of maximum velocities in 8 cerebral arteries, measured by TCD (TCD velocity) at 1 year. Twenty-five of 29 secondary outcomes were analyzed, including the highest TCD velocity at 3 years and normalization of velocities (<170 cm/s) and ferritin levels at 1 and 3 years. Results: Sixty-seven children with SCA (median age, 7.6 years; 35 girls [52%]) were enrolled (7 with stroke history). In the matched sample, highest TCD velocities at 1 year were significantly lower on average in the transplantation group (129.6 cm/s) vs the standard care group (170.4 cm/s; difference, -40.8 cm/s [95% CI, -62.9 to -18.6]; P < .001). Of the 25 analyzed secondary end points, 4 showed significant differences, including the highest TCD velocity at 3 years (112.4 cm/s in the transplantation group vs 156.7 cm/s in the standard care group; difference, -44.3 [95% CI, -71.9 to -21.1]; P = .001); normalization rate at 1 year (80.0% in the transplantation group vs 48.0% in the standard care group; difference, 32.0% [95% CI, 0.2% to 58.6%]; P = .045); and ferritin levels at 1 year (905 ng/mL in the transplantation group vs 2529 ng/mL in the standard care group; difference, -1624 [95% CI, -2370 to -879]; P < .001) and 3 years (382 ng/mL in the transplantation group vs 2170 ng/mL in the standard care group; difference, -1788 [95% CI, -2570 to -1006]; P < .001). Conclusions and Relevance: Among children with SCA requiring chronic transfusion because of persistently elevated TCD velocities, MSD-HSCT was significantly associated with lower TCD velocities at 1 year compared with standard care. Further research is warranted to assess the effects of MSD-HSCT on clinical outcomes and over longer follow-up. Trial Registration: ClinicalTrials.gov Identifier: NCT01340404.


Assuntos
Anemia Falciforme/terapia , Circulação Cerebrovascular/fisiologia , Transplante de Células-Tronco Hematopoéticas , Irmãos , Ultrassonografia Doppler Transcraniana , Aloenxertos , Anemia Falciforme/diagnóstico por imagem , Anemia Falciforme/fisiopatologia , Velocidade do Fluxo Sanguíneo , Criança , Feminino , Ferritinas/sangue , Doença Enxerto-Hospedeiro , Transplante de Células-Tronco Hematopoéticas/efeitos adversos , Humanos , Masculino , Pontuação de Propensão , Qualidade de Vida , Condicionamento Pré-Transplante
18.
Haematologica ; 104(6): 1230-1236, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30655365

RESUMO

The use of antihuman T-lymphocyte immunoglobulin in the setting of transplantation from an HLA-matched related donor is still much debated. Acute and chronic graft-versus-host disease are the main causes of morbidity and mortality after allogeneic hematopoietic stem cell transplantation in patients with myelofibrosis. The aim of this study was to evaluate the effect of antihuman T-lymphocyte immunoglobulin in a large cohort of patients with myelofibrosis (n=287). The cumulative incidences of grade II-IV acute graft-versus-host disease among patients who were or were not given antihuman T-lymphocyte immunoglobulin were 26% and 41%, respectively. The corresponding incidences of chronic graft-versus-host disease were 52% and 55%, respectively. Non-adjusted overall survival, disease-free survival and non-relapse mortality rates were 55% versus 53%, 49% versus 45%, and 32% versus 31%, respectively, among the patients who were or were not given antihuman T-lymphocyte immunoglobulin. An adjusted model confirmed that the risk of acute graft-versus-host disease was lower following antihuman T-lymphocyte immunoglobulin (hazard ratio, 0.54; P=0.010) while it did not decrease the risk of chronic graft-versus-host disease. The hazard ratios for overall survival and non-relapse mortality were 0.66 and 0.64, with P-values of 0.05 and 0.09, respectively. Antihuman T-lymphocyte immunoglobulin did not influence disease-free survival, graft-versus-host disease, relapse-free survival or relapse risk. In conclusion, in the setting of matched related transplantation in myelofibrosis patients, this study demonstrates that antihuman T-lymphocyte immunoglobulin decreases the risk of acute graft-versus-host disease without increasing the risk of relapse.

19.
Angiogenesis ; 22(2): 325-339, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-30607696

RESUMO

INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a devastating disease characterized by obliteration of alveolar architecture, resulting in declining lung function and ultimately death. Pathogenic mechanisms involve a concomitant accumulation of scar tissue together with myofibroblasts activation and a strong abnormal vascular remodeling. Endothelial progenitor cells (ECFC subtype) have been investigated in several human lung diseases as a potential actor in IPF. We previously demonstrated that ECFCs are down-regulated in IPF in contrast to healthy controls. We postulated here that ECFCs might behave as a liquid biopsy in IPF patients and that they exert modified vasculogenic properties. METHODS AND RESULTS: ECFCs isolated from controls and IPF patients expressed markers of the endothelial lineage and did not differ concerning adhesion, migration, and differentiation in vitro and in vivo. However, senescent and apoptotic states were increased in ECFCs from IPF patients as shown by galactosidase staining, p16 expression, and annexin-V staining. Furthermore, conditioned medium of IPF-ECFCs had increased level of interleukin-8 that induced migration of neutrophils in vitro and in vivo. In addition, an infiltration by neutrophils was shown in IPF lung biopsies and we found in a prospective clinical study that a high level of neutrophils in peripheral blood of IPF patients was associated to a poor prognosis. CONCLUSION: To conclude, our study shows that IPF patients have a senescent ECFC phenotype associated with an increased IL-8 secretion potential that might contribute to lung neutrophils invasion during IPF.

20.
J Neuromuscul Dis ; 6(1): 55-64, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30562904

RESUMO

BACKGROUND: Duchenne muscular dystrophy (DMD) is an X-linked recessive genetic muscle disorder. Respiratory muscle function is classically affected in this disease. Ultrasound recently emerged as a non-invasive tool to assess diaphragm function. However, there are only a few studies using diaphragm ultrasound (US) in DMD. PURPOSE: We aimed to assess diaphragm ultrasound patterns in DMD, their relationship with age and their association with home mechanical ventilation (HMV). METHODS: We included DMD patients followed at Raymond Poincaré Hospital who benefited from diaphragm ultrasound and pulmonary function tests. RESULTS: There were 110 DMD patients and 17 male sex-matched healthy subjects included. In all, 94% of patients were permanent wheelchair users. Median body mass index (BMI) was 18 kg/m2. DMD patients disclosed a reduced forced vital capacity (VC) (12% of predicted value), and 78% of patients were on HMV. In patients, right and left diaphragmatic motions on deep inspiration were reduced and end expiratory diaphragm thickness was borderline normal. In patients, right and left diaphragmatic thickening fractions (TF) were reduced 12.7% and 15.5%, respectively. Age and end expiratory thickness were significantly inversely associated (p = 0.005 for the right diaphragm, p = 0.018 for the left diaphragm). Diaphragm TF was significantly inversely associated with age (p = 0.001 for the right side, p < 0.0001 for the left side). Right and left inspiratory diaphragm motions were significantly inversely associated with age (p < 0.0001). CONCLUSION: This study describes the severity of diaphragm dysfunction in patients with DMD. Diaphragm US may be a non-invasive outcome measure for DMD.

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