The availability of multiple treatments for type 1 Gaucher disease increases the need for real-life studies to evaluate treatment efficacy and safety and provide clinicians with more information to ...choose the best personalized therapy for their patients.
To determine whether treatment with eliglustat produces, in adult GD1 patients, ans optimal response in daily clinical practice.
We designed a real-life study with 2 years of follow-up (TRAZELGA GEE-ELI-2017-01) to uniformly evaluate the response and adverse events to eliglustat treatment. This study, conducted in 30 patients across Spain and previously treated with other therapies, included the evaluation of safety and efficacy by assessing visceral enlargement, bone disease (DEXA and T and Z scores), concomitant treatments and adverse events, as well as a quality of life evaluation (SF-36). In addition, the quantification of classical biomarkers (chitotriosidase activity, CCL18/PARC and glucosylsphingosine (GluSph)) and new candidates for GD biomarkers (YKL-40, cathepsin S, hepcidin and lipocalin-2 determined by immunoassay) were also assessed. Non-parametric statistical analysis was performed and p < 0.05 was considered statistically significant.
Thirty patients were enrolled in the study. The median age was 41.5 years and the male-female ratio was 1.1:1. 84% of the patients had received ERT and 16% SRT as previous treatment. The most common symptoms at baseline were fatigue (42%) and bone pain (38%), no patient had a bone crisis during the study, and two years after switching, 37% had reduced their use of analgesics. Patient-reported outcomes showed a significant increase in physical function scores (p = 0.027) and physical pain scores (p = 0.010). None of the enrolled patients discontinued treatment due to adverse events, which were mild and transient in nature, mainly gastrointestinal and skin dryness. None of the biomarkers show a significant increase or decompensation after switching. CCL18/PARC (p = 0.0012), YKL-40 (p = 0.00004) and lipocalin-2 (p = 0.0155) improved after two years and GluSph after one year (p = 0.0008) and two years (p = 0.0245) of oral therapy.
In summary, this real-life study, showed that eliglustat maintains stability and can improve quality of life with few side effects. Significant reductions in classic and other novel biomarkers were observed after two years of therapy.
Background
Estimating the national burden of influenza disease is challenging. We aimed to estimate the disease burden of seasonal influenza in Spain, at the primary care and hospital level, over the ...6 influenza seasons after 2009 pandemic.
Methods
We used data from the Spanish Influenza Sentinel Surveillance System to estimate weekly influenza rates and the number of influenza‐like illness (ILI) and mild confirmed influenza cases (MCIC). From the surveillance of severe hospitalized confirmed influenza cases (SHCIC), we obtained hospitalization rates and total number of SHCIC, intensive care unit (ICU) admissions and deaths in influenza hospitalized patients. We estimated both mild and severe influenza cases, overall, and by age‐group (<5, 5‐14, 15‐64, and ≥65 years).
Results
The highest cumulative rates of MCIC were observed in <15 years (1395‐3155 cases/100 000 population in 5‐14 years) and the lowest in ≥65 years (141‐608 cases/100 000 population). SHCIC rates revealed a characteristic U‐shaped distribution, with annual average hospitalization rates of 16.5 and 18.9 SHCIC/100, 000 p in 0‐4 years, and ≥65 years, respectively. We estimated an annual average of 866 868 cases of ILI attended in primary care (55% were MCIC), 3616 SHCIC, 1232 ICU admissions, and 437 deaths in SHCIC. The percentage of ICU admission among SHCIC was highest at 15‐64 years (42%), while the hospitalization fatality rate ranged from 1% in 0‐4 years to 18% in ≥65 years.
Conclusions
The ongoing Spanish Influenza Surveillance System allowed obtaining crucial information regarding the impact of mild and severe influenza in Spain.
Candida tropicalis is an emergent pathogen with a high rate of mortality associated with it; however, less is known about its pathogenic capacity. Biofilm formation (BF) has important clinical ...repercussions, and it begins with adherence to a substrate. The adherence capacity depends principally on the cell surface hydrophobicity (CSH) and, at a later stage, on specific adherence due to adhesins. The ALS family in C. tropicalis, implicated in adhesion and BF, is represented in several CTRG genes. In this study, we determined the biofilm‐forming ability, the primary adherence, and the CSH of C. tropicalis, including six isolates from blood and seven from urine cultures. We also compared the expression of four CTRG ALS‐like genes (CTRG_01028, CTRG_02293, CTRG_03786, and CTRG_03797) in sessile versus planktonic cells, selected for their possible contribution to BF. All the C. tropicalis strains were biofilm producers, related to its filamentation capacity; all the strains displayed a high adherence ability correlated to the CSH, and all the strains expressed the CTRG genes in both types of growth. Urine isolates present, although not significantly, higher CSH, adherence, and biofilm formation than blood isolates. This study reveals that three CTRG ALS‐like genes—except CTRG_03797—were more upregulated in biofilm cells, although with a considerable variation in expression across the strains studied and between the CTRG genes. C. tropicalis present a high biofilm capacity, and the overexpression of several CTRG ALS‐like genes in the sessile cells suggests a role by the course of the biofilm formation.
Background
Myocardial injury is a common finding in COVID‐19 strongly associated with severity. We analysed the prevalence and prognostic utility of myocardial injury, characterized by elevated ...cardiac troponin, in a large population of COVID‐19 patients, and further evaluated separately the role of troponin T and I.
Methods
This is a multicentre, retrospective observational study enrolling patients with laboratory‐confirmed COVID‐19 who were hospitalized in 32 Spanish hospitals. Elevated troponin levels were defined as values above the sex‐specific 99th percentile upper reference limit, as recommended by international guidelines. Thirty‐day mortality was defined as endpoint.
Results
A total of 1280 COVID‐19 patients were included in this study, of whom 187 (14.6%) died during the hospitalization. Using a nonspecific sex cut‐off, elevated troponin levels were found in 344 patients (26.9%), increasing to 384 (30.0%) when a sex‐specific cut‐off was used. This prevalence was significantly higher (42.9% vs 21.9%; P < .001) in patients in whom troponin T was measured in comparison with troponin I. Sex‐specific elevated troponin levels were significantly associated with 30‐day mortality, with adjusted odds ratios (ORs) of 3.00 for total population, 3.20 for cardiac troponin T and 3.69 for cardiac troponin I.
Conclusion
In this multicentre study, myocardial injury was a common finding in COVID‐19 patients. Its prevalence increased when a sex‐specific cut‐off and cardiac troponin T were used. Elevated troponin was an independent predictor of 30‐day mortality, irrespective of cardiac troponin assay and cut‐offs to detect myocardial injury. Hence, the early measurement of cardiac troponin may be useful for risk stratification in COVID‐19.
Abstract 4683
Chromosomal translocations in human tumors frequently produce fusion genes whose chimeric protein products play an essential role in oncogenesis. Recent reports have found a BCR-JAK2 ...fusion gene in cases of chronic or acute myeloid leukemia, but the protein had not been characterized. We describe a BCR-JAK2 fusion gene by fluorescence in situ hybridization and RT-PCR amplification from bone marrow at diagnosis of a patient with acute lymphoblastic leukemia. After induction therapy, real time PCR showed persistent molecular response correlating with hematological remission maintained up to present. BCR-JAK2 is a 110 KDa chimeric protein containing the BCR oligomerization domain fused to the JAK2 tyrosine-kinase domain. In vitro analysis showed that BCR-JAK2 was constitutively phosphorylated and was located to the cytoplasm. BCR-JAK2 transformed the IL-3-dependent murine hematopoietic cell line Ba/F3 into IL-3 independent growth and induced STAT5b phosphorylation and translocation into the cell nuclei. The treatment with a JAK2 inhibitor abrogated BCR-JAK2 and STAT5b phosphorylation, leading to apoptosis of transformed Ba/F3 cells. To test whether BCR-JAK2 has tumorogenic ability in vivo, we performed experiments with nude mice, in which we injected subcutaneously cells transduced with the control vector and cells expressing BCR-JAK2. Notably, we only obtained tumors in the flank injected with BCR-JAK2 expressing cells, thus confirming the tumorogenic activity of the BCR-JAK2 fusion protein. We conclude that BCR-JAK2 is a new tyrosine-kinase that induces proliferation and cell survival, which can be abrogated by JAK2 inhibitors. In vitro studies demonstrate that BCR-JAK2 displays transforming activity. Moreover, the nude mice model reveals its ability to cause tumors.
No relevant conflicts of interest to declare.
Catheter-related bloodstream infections (CRBSIs) increase morbidity and mortality, prolong hospitalization and generate considerable medical costs. Recent guidelines for CRBSI recommend empirical ...therapy against Gram-positive bacteria (GPB) and restrict coverage for Gram-negative bacteria (GNB) only to specific circumstances.
To investigate predictors of GNB aetiology in CRBSI and to assess the predictors of outcome in patients with CRBSI.
Patients with CRBSI were selected from the PROBAC cohort, a prospective, observational, multicentre national cohort study including patients with bloodstream infections consecutively admitted to 26 Spanish hospitals in a 6 month period (October 2016-March 2017). Outcome variables were GNB aetiology and 30 day mortality. Adjusted analyses were performed by logistic regression.
Six hundred and thirty-one episodes of CRBSI were included in the study. Risk factors independently related to GNB aetiology were central venous catheter (CVC) OR 1.60 (95% CI: 1.05-2.44), P = 0.028, sepsis/septic shock OR: 1.76 (95% CI: 1.11-2.80), P = 0.016, antibiotic therapy in the previous 30 days OR: 1.56 (95% CI: 1.02-2.36), P = 0.037, neutropenia <500/μL OR: 2.01 (95% CI: 1.04-3.87), P = 0.037 and peripheral vascular disease OR: 2.04 (95% CI: 1.13-3.68), P = 0.018. GNB were not associated with increased mortality in adjusted analysis, while removal of catheter OR: 0.24 (95% CI: 0.09-0.61), P = 0.002 and adequate empirical treatment OR: 0.37 (95% CI: 0.18-0.77), P = 0.008 were strong protective factors.
Our study reinforces the recommendation that empirical coverage should cover GNB in patients presenting with sepsis/septic shock and in neutropenic patients. Catheter removal and adequate empirical treatment were both protective factors against mortality in patients with CRBSI.
The enzymatic replacement therapy (ERT) availability for Gaucher disease (GD) has changed the landscape of the disease, several countries have screening programs. These actions have promoted the ...early diagnosis and avoided many complications in pediatric patients. In Spain ERT has been available since 1993 and 386 patients have been included in the Spanish Registry of Gaucher Disease (SpRGD). The aim of this study is to analyze the impact of ERT on the characteristics at time of diagnosis and initial complications in pediatric Gaucher disease patients.
To analyze the impact of ERT on the characteristics at time of diagnosis and initial complications in pediatric Gaucher disease patients.
A review of data in SpRGD from patients' diagnosed before 18 years old was performed. The cohort was split according the year of diagnosis (≤1994, cohort A; ≥1995, cohort B).
A total of 98 pediatric patients were included, GD1: 80, GD3: 18; mean age: 7.2 (0.17-16.5) years, 58 (59.2%) males and 40 (40.8%) females. Forty-five were diagnosed ≤ 1994 and 53 ≥ 1995. Genotype: N370S/N370S: 2 (2.0%), N370S/L444P: 27 (27.5%), N370S/other: 47 (48%), L444P/L444P: 7 (7.1%), L444P/D409H: 2 (2.0%), L444P/other: 3 (6.2%), other/other: 10 (10.2%). The mean age at diagnosis was earlier in patients diagnosed after 1995 (p < 0.001) and different between the subtypes, GD1: 8.2 (0.2-16.5) years and GD3: 2.8 (0.17-10.2) years (p < 0.001). There were more severe patients in the group diagnosed before 1994 (p = 0.045) carrying L444P (2), D409H (2), G377S (1), G195W (1) or the recombinant mutation. The patients' diagnosed ≤1994 showed worse cytopenias, higher chance of bone vascular complications at diagnosis and previous spleen removal. The patients started ERT at a median time after diagnosis of 5.2 years cohort A and 1.6 years cohort B (p < 0.001).
The early diagnosis of Gaucher disease in the era of ERT availability has permitted to reduce the incidence of severe and irreversible initial complication in pediatric patients, and this has permitted better development of these patients. This is the largest pediatric cohort from a national registry.
ObjectivesPatients with cancer are at higher risk for severe COVID-19 infection. COVID-19 surveillance of workers in oncological centres is crucial to assess infection burden and prevent ...transmission. We estimate the SARS-CoV-2 seroprevalence among healthcare workers (HCWs) of a comprehensive cancer centre in Catalonia, Spain, and analyse its association with sociodemographic characteristics, exposure factors and behaviours.DesignCross-sectional study (21 May 2020–26 June 2020).SettingA comprehensive cancer centre (Institut Català d’Oncologia) in Catalonia, Spain.ParticipantsAll HCWs (N=1969) were invited to complete an online self-administered epidemiological survey and provide a blood sample for SARS-CoV-2 antibodies detection.Primary outcome measurePrevalence (%) and 95% CIs of seropositivity together with adjusted prevalence ratios (aPR) and 95% CI were estimated.ResultsA total of 1266 HCWs filled the survey (participation rate: 64.0%) and 1238 underwent serological testing (97.8%). The median age was 43.7 years (p25–p75: 34.8–51.0 years), 76.0% were female, 52.0% were nursing or medical staff and 79.0% worked on-site during the pandemic period. SARS-CoV-2 seroprevalence was 8.9% (95% CI 7.44% to 10.63%), with no differences by age and sex. No significant differences in terms of seroprevalence were observed between onsite workers and teleworkers. Seropositivity was associated with living with a person with COVID-19 (aPR 3.86, 95% CI 2.49 to 5.98). Among on-site workers, seropositive participants were twofold more likely to be nursing or medical staff. Nursing and medical staff working in a COVID-19 area showed a higher seroprevalence than other staff (aPR 2.45, 95% CI 1.08 to 5.52).ConclusionsAt the end of the first wave of the pandemic in Spain, SARS-CoV-2 seroprevalence among Institut Català d’Oncologia HCW was lower than the reported in other Spanish hospitals. The main risk factors were sharing household with infected people and contact with COVID-19 patients and colleagues. Strengthening preventive measures and health education among HCW is fundamental.
Abstract Objective To analyze the results of cardiopulmonary resuscitation (CPR) that included defibrillation during in-hospital cardiac arrest (IH-CA) in children. Methods A prospective multicenter, ...international, observational study on pediatric IH-CA in 12 European and Latin American countries, during 24 months. Data from 502 children between 1 month and 18 years were collected using the Utstein template. Patients with a shockable rhythm that was treated by electric shock(s) were included. The primary endpoint was survival at hospital discharge. Univariate logistic regression analysis was performed to find outcome factors. Results Forty events in 37 children (mean age 48 months, IQR: 7–15 months) were analyzed. An underlying disease was present in 81.1% of cases and 24.3% had a previous CA. The main cause of arrest was a cardiac disease (56.8%). In 17 episodes (42.5%) ventricular fibrillation (VF) or pulseless ventricular tachycardia (pVT) was the first documented rhythm, and in 23 (57.5%) it developed during CPR efforts. In 11 patients (27.5%) three or more shocks were needed to achieve defibrillation. Return of spontaneous circulation (ROSC) was obtained in 25 cases (62.5%), that was sustained in 20 (50.0%); however only 12 children (32.4%) survived to hospital discharge. Children with VF/pVT as first documented rhythm had better sustained ROSC (64.7% vs. 39.1%, p = 0.046) and survival to hospital discharge rates (58.8% vs. 21.7%, p = 0.02) than those with subsequent VF/pVT. Survival rate was inversely related to duration of CPR. Clinical outcome was not related to the cause or location of arrest, type of defibrillator and waveform, energy dose per shock, number of shocks, or cumulative energy dose, although there was a trend to better survival with higher doses per shock (25.0% with <2 J kg−1 , 43.4% with 2–4 J kg−1 and 50.0% with >4 J kg−1 ) and worse with higher number of shocks and cumulative energy dose. Conclusion The termination of pediatric VF/pVT in the IH-CA setting is achieved in a low percentage of instances with one electrical shock at 4 J kg−1 . When VF/pVT is the first documented rhythm, the results of defibrillation are better than in the case of subsequent VF/pVT. No clear relationship between defibrillation protocol and ROSC or survival has been observed. The optimal pediatric defibrillation dose remains to be determined; therefore current resuscitation guidelines cannot be considered evidence-based, and additional research is needed.
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