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  • 1
    In: Critical Care, Springer Science and Business Media LLC, Vol. 24, No. 1 ( 2020-12)
    Abstract: Awake prone positioning (awake-PP) in non-intubated coronavirus disease 2019 (COVID-19) patients could avoid endotracheal intubation, reduce the use of critical care resources, and improve survival. We aimed to examine whether the combination of high-flow nasal oxygen therapy (HFNO) with awake-PP prevents the need for intubation when compared to HFNO alone. Methods Prospective, multicenter, adjusted observational cohort study in consecutive COVID-19 patients with acute respiratory failure (ARF) receiving respiratory support with HFNO from 12 March to 9 June 2020. Patients were classified as HFNO with or without awake-PP. Logistic models were fitted to predict treatment at baseline using the following variables: age, sex, obesity, non-respiratory Sequential Organ Failure Assessment score, APACHE-II, C-reactive protein, days from symptoms onset to HFNO initiation, respiratory rate, and peripheral oxyhemoglobin saturation. We compared data on demographics, vital signs, laboratory markers, need for invasive mechanical ventilation, days to intubation, ICU length of stay, and ICU mortality between HFNO patients with and without awake-PP. Results A total of 1076 patients with COVID-19 ARF were admitted, of which 199 patients received HFNO and were analyzed. Fifty-five (27.6%) were pronated during HFNO; 60 (41%) and 22 (40%) patients from the HFNO and HFNO + awake-PP groups were intubated. The use of awake-PP as an adjunctive therapy to HFNO did not reduce the risk of intubation [RR 0.87 (95% CI 0.53–1.43), p  = 0.60]. Patients treated with HFNO + awake-PP showed a trend for delay in intubation compared to HFNO alone [median 1 (interquartile range, IQR 1.0–2.5) vs 2 IQR 1.0–3.0] days ( p  = 0.055), but awake-PP did not affect 28-day mortality [RR 1.04 (95% CI 0.40–2.72), p  = 0.92]. Conclusion In patients with COVID-19 ARF treated with HFNO, the use of awake-PP did not reduce the need for intubation or affect mortality.
    Type of Medium: Online Resource
    ISSN: 1364-8535
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2020
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  • 2
    In: JAMA, American Medical Association (AMA), Vol. 327, No. 18 ( 2022-05-10), p. 1782-
    Abstract: In nonurban areas with limited access to thrombectomy-capable centers, optimal prehospital transport strategies in patients with suspected large-vessel occlusion stroke are unknown. Objective To determine whether, in nonurban areas, direct transport to a thrombectomy-capable center is beneficial compared with transport to the closest local stroke center. Design, Setting, and Participants Multicenter, population-based, cluster-randomized trial including 1401 patients with suspected acute large-vessel occlusion stroke attended by emergency medical services in areas where the closest local stroke center was not capable of performing thrombectomy in Catalonia, Spain, between March 2017 and June 2020. The date of final follow-up was September 2020. Interventions Transportation to a thrombectomy-capable center (n = 688) or the closest local stroke center (n = 713). Main Outcomes and Measures The primary outcome was disability at 90 days based on the modified Rankin Scale (mRS; scores range from 0 [no symptoms] to 6 [death] ) in the target population of patients with ischemic stroke. There were 11 secondary outcomes, including rate of intravenous tissue plasminogen activator administration and thrombectomy in the target population and 90-day mortality in the safety population of all randomized patients. Results Enrollment was halted for futility following a second interim analysis. The 1401 enrolled patients were included in the safety analysis, of whom 1369 (98%) consented to participate and were included in the as-randomized analysis (56% men; median age, 75 [IQR, 65-83] years; median National Institutes of Health Stroke Scale score, 17 [IQR, 11-21] ); 949 (69%) comprised the target ischemic stroke population included in the primary analysis. For the primary outcome in the target population, median mRS score was 3 (IQR, 2-5) vs 3 (IQR, 2-5) (adjusted common odds ratio [OR], 1.03; 95% CI, 0.82-1.29). Of 11 reported secondary outcomes, 8 showed no significant difference. Compared with patients first transported to local stroke centers, patients directly transported to thrombectomy-capable centers had significantly lower odds of receiving intravenous tissue plasminogen activator (in the target population, 229/482 [47.5%] vs 282/467 [60.4%]; OR, 0.59; 95% CI, 0.45-0.76) and significantly higher odds of receiving thrombectomy (in the target population, 235/482 [48.8%] vs 184/467 [39.4%]; OR, 1.46; 95% CI, 1.13-1.89). Mortality at 90 days in the safety population was not significantly different between groups (188/688 [27.3%] vs 194/713 [27.2%]; adjusted hazard ratio, 0.97; 95% CI, 0.79-1.18). Conclusions and Relevance In nonurban areas in Catalonia, Spain, there was no significant difference in 90-day neurological outcomes between transportation to a local stroke center vs a thrombectomy-capable referral center in patients with suspected large-vessel occlusion stroke. These findings require replication in other settings. Trial Registration ClinicalTrials.gov Identifier: NCT02795962
    Type of Medium: Online Resource
    ISSN: 0098-7484
    RVK:
    Language: English
    Publisher: American Medical Association (AMA)
    Publication Date: 2022
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    detail.hit.zdb_id: 2018410-4
    SSG: 5,21
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  • 3
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 53, No. 12 ( 2022-12), p. 3728-3740
    Abstract: We aim to compare the outcome of patients from urban areas, where the referral center is able to perform thrombectomy, with patients from nonurban areas enrolled in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion). Methods: Patients with suspected large vessel occlusion stroke, as evaluated by a Rapid Arterial Occlusion Evaluation score of ≥5, from urban catchment areas of thrombectomy-capable centers during RACECAT trial enrollment period were included in the Stroke Code Registry of Catalonia. Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with an ischemic stroke. Secondary outcomes included mortality at 90 days, rate of thrombolysis and thrombectomy, time from onset to thrombolysis, and thrombectomy initiation. Propensity score matching was used to assemble a cohort of patients with similar characteristics. Results: The analysis included 1369 patients from nonurban areas and 2502 patients from urban areas. We matched 920 patients with an ischemic stroke from urban areas and nonurban areas based on their propensity scores. Patients with ischemic stroke from nonurban areas had higher degrees of disability at 90 days (median [interquartle range] modified Rankin Scale score, 3 [2–5] versus 3 [1–5], common odds ratio, 1.25 [95% CI, 1.06–1.48] ); the observed average effect was only significant in patients with large vessel stroke (common odds ratio, 1.36 [95% CI, 1.08–1.65]). Mortality rate was similar between groups(odds ratio, 1.02 [95% CI, 0.81–1.28] ). Patients from nonurban areas had higher odds of receiving thrombolysis (odds ratio, 1.36 [95% CI, 1.16–1.67]), lower odds of receiving thrombectomy(odds ratio, 0.61 [95% CI, 0.51–0.75] ), and longer time from stroke onset to thrombolysis (mean difference 38 minutes [95% CI, 25–52]) and thrombectomy(mean difference 66 minutes [95% CI, 37–95] ). Conclusions: In Catalonia, Spain, patients with large vessel occlusion stroke triaged in nonurban areas had worse neurological outcomes than patients from urban areas, where the referral center was able to perform thrombectomy. Interventions aimed at improving organizational practices and the development of thrombectomy capabilities in centers located in remote areas should be pursued. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02795962.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2022
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  • 4
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 54, No. 3 ( 2023-03), p. 770-780
    Abstract: We aim to assess whether time of day modified the treatment effect in the RACECAT trial (Direct Transfer to an Endovascular Center Compared to Transfer to the Closest Stroke Center in Acute Stroke Patients With Suspected Large Vessel Occlusion Trial), a cluster-randomized trial that did not demonstrate the benefit of direct transportation to a thrombectomy-capable center versus nearest local stroke center for patients with a suspected large vessel stroke triaged in nonurban Catalonia between March 2017 and June 2020. Methods: We performed a post hoc analysis of RACECAT to evaluate if the association between initial transport routing and functional outcome differed according to trial enrollment time: daytime (8:00 am –8:59 pm ) and nighttime (9:00 pm –7:59 am ). Primary outcome was disability at 90 days, as assessed by the shift analysis on the modified Rankin Scale score, in patients with ischemic stroke. Subgroup analyses according to stroke subtype were evaluated. Results: We included 949 patients with an ischemic stroke, of whom 258 patients(27%) were enrolled during nighttime. Among patients enrolled during nighttime, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days (adjusted common odds ratio [acOR] , 1.620 [95% CI, 1.020–2.551]); no significant difference between trial groups was present during daytime (acOR, 0.890 [95% CI, 0.680–1.163] ; P interaction =0.014). Influence of nighttime on the treatment effect was only evident in patients with large vessel occlusion(daytime, acOR 0.766 [95% CI, 0.548–1.072]; nighttime, acOR, 1.785 [95% CI, 1.024–3.112] ; P interaction 〈 0.01); no heterogeneity was observed for other stroke subtypes ( P interaction 〉 0.1 for all comparisons). We observed longer delays in alteplase administration, interhospital transfers, and mechanical thrombectomy initiation during nighttime in patients allocated to local stroke centers. Conclusions: Among patients evaluated during nighttime for a suspected acute severe stroke in non-urban areas of Catalonia, direct transport to a thrombectomy-capable center was associated with lower degrees of disability at 90 days. This association was only evident in patients with confirmed large vessel occlusion on vascular imaging. Time delays in alteplase administration and interhospital transfers might mediate the observed differences in clinical outcome. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT02795962.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
    RVK:
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2023
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  • 5
    In: Nephrology Dialysis Transplantation, Oxford University Press (OUP), Vol. 32, No. suppl_3 ( 2017-05-01), p. iii538-iii538
    Type of Medium: Online Resource
    ISSN: 0931-0509 , 1460-2385
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2017
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  • 6
    In: Folia Primatologica, Brill, Vol. 85, No. 6 ( 2015-02-14), p. 361-378
    Abstract: Morphometric variation of biological structures has been widely used to determine taxonomic affinities among taxa, and teeth are especially informative for both deep phylogenetic relationships and specific ecological signals. We report 2-dimensional geometric morphometrics (GM) analyses of occlusal crown surfaces of lower molars (M 1 , n = 141; M 2 , n = 158) of cercopithecoid primate species. A 12-landmark configuration, including cusp tips and 8 points of the molar crown contour, were used to evaluate patterns of variation in lower molar shape among cercopithecoid primates and to predict the taxonomic attribution of 2 archaeological macaques from Roman time periods. The results showed that the lower molar shape of cercopithecoid primates reflects taxonomic affinities, mostly at a subfamily level and close to a tribe level. Thus, the cusp positions and crown contour were important elements of the pattern related to interspecific variation. Additionally, the archaeological specimens, attributed to Macaca sylvanus based on osteological information, were classified using the GM molar shape variability of the cercopithecoid primates studied. The results suggest that their molar shape resembled both M. sylvanus and M. nemestrina , and species attribution varied depending on the comparative sample used.
    Type of Medium: Online Resource
    ISSN: 0015-5713 , 1421-9980
    Language: Unknown
    Publisher: Brill
    Publication Date: 2015
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    SSG: 12
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  • 7
    In: Genes, Chromosomes and Cancer, Wiley, Vol. 56, No. 11 ( 2017-11), p. 810-820
    Abstract: The outcome of relapsed adult acute lymphoblastic leukemia (ALL) remains dismal despite new therapeutic approaches. Previous studies analyzing relapse samples have shown a high degree of heterogeneity regarding gene alterations without an evident relapse signature. Bone marrow or peripheral blood samples from 31 adult B‐cell precursor ALL patients at first relapse, and 21 paired diagnostic samples were analyzed by multiplex ligation probe‐dependent amplification (MLPA). Nineteen paired diagnostic and relapse samples of these 21 patients were also analyzed by SNP arrays. A trend to acquire homozygous CDKN2A/B deletions and a significant increase in the number of copy number alterations (CNA) was observed from diagnosis to first relapse. Evolution from an ancestral clone was the main pattern of clonal evolution. Relapse samples were extremely heterogeneous regarding CNA frequencies. However, CDKN2A/B , PAX5 , ETV6 , ATM , IKZF1 , VPREB1, and TP53 deletions and duplications of 1q, 8q, 17q, 21, X/Y PAR1, and Xp were frequently detected at relapse. Duplications of genes involved in cell proliferation, drug resistance and stem cell homeostasis regulation, as well as deletions of KDM6A and STAG2 genes emerged as specific alterations at relapse. Genomics of relapsed adult B‐cell precursor ALL is highly heterogeneous, although some recurrent lesions involved in essential pathways deregulation were frequently observed. Selective and simultaneous targeting of these deregulated pathways may improve the results of current salvage therapies.
    Type of Medium: Online Resource
    ISSN: 1045-2257 , 1098-2264
    URL: Issue
    Language: English
    Publisher: Wiley
    Publication Date: 2017
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    detail.hit.zdb_id: 1492641-6
    SSG: 12
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  • 8
    In: Late Antique Archaeology, Brill, Vol. 8, No. 2 ( 2013-01-25), p. 703-731
    Abstract: The remains of a primate’s burial (a Macaca sylvanus , or a Barbary Macaque) were discovered in 2001 on the site of Les Colomines (Llívia), comprising the skeleton of the animal and some objects arranged as an offering. These offerings included decorated metallic pieces and some bronze military belts typical of the Late Roman period. The grave can be connected with the late antique phase of occupation of Iulia Libica in the 5th–6th c. A.D., and with several military episodes that occurred in the Pyrenees during this period. The macaque may have belonged to an officer. Some of the osteological and biometric studies on the macaque are presented at the end of the paper.
    Type of Medium: Online Resource
    ISSN: 1570-6893 , 2213-4522
    Language: Unknown
    Publisher: Brill
    Publication Date: 2013
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  • 9
    In: Blood, American Society of Hematology, Vol. 128, No. 22 ( 2016-12-02), p. 5281-5281
    Abstract: Background & Objective: Acute Lymphoblastic Leukemia (ALL) is an aggressive neoplasia characterized by a high genetic heterogeneity both at diagnosis and at relapse. Due to the high incidence of relapse in adults and the dismal prognosis beyond recurrence, diagnosis and relapse samples of adult ALL patients were carefully analyzed in order to identify genetic alterations related with drug resistance and disease progression. Patients & Methods: Paired diagnosis-relapse bone marrow samples from 5 adult B-cell precursor ALL (B-ALL) patients were analyzed (Ph+ ALL [n=2], normal karyotype [n=1] , t(1;19)(q23;p13) [n=1] and t(8;13)(p21-22;q12) [n=1] ). Copy Number Alterations (CNA) were studied with Multiplex Ligation-dependent Probe Amplification (MLPA, kits P-335 and P-202 from MRC-Holland, Amsterdam, Netherlands) and Affymetrix CytoScan HD arrays (Affymetrix, Santa Clara, USA). In the array analyses, only the CNA that encompassed at least 25 markers were considered significant. Results: Regarding karyotype, 2 patients (1 Ph+ and 1 t(1;19) at diagnosis) showed the same chromosomal translocations within a complex karyotype at relapse. On the contrary, the other Ph+ patient showed a normal karyotype at relapse, while 2 patients did not experience any karyotypic change. Regarding immunophenotype, 3/5 patients showed changes on antigen expression from diagnosis to relapse such as expression of markers of immaturity (CD34, TdT positivity and CD38 negativity), loss of lymphoid markers (CD20 and CD22) and/or acquisition of myeloid markers (CD33 and CD66c). Concerning CNA, all relapse samples were genetically related to the diagnosis clone (common clonal origin). All relapsed populations lost CNA detected at diagnosis and/or acquired new CNA but retained some of the CNA showed at diagnosis revealing clonal evolution from ancestral clones. CNA in B-ALL key genes involved in lymphoid development (IKZF1, PAX5, EBF1,VPREB1 and BLNK), proliferation (CDKN2A/B, RB1, CRLF2, C-MYC and ERG), apoptosis (BTG1, TP53 and ATM), hematopoiesis transcription factors (ETV6 and MLL) and histone modifications (KDM6A) were detected, among others. Losses in 9p were the most recurrent event both at diagnosis and at relapse. CDKN2A/B deletions were observed in all relapse samples (3/5 in homozygosis) while PAX5 deletions were present in 4/5 relapsed cases. Interestingly, all relapse samples showed CNA favoring the activation and/or the transcription of proteins involved in the Akt/C-MYC signaling pathway. Another common feature (4/5 patients) were CNA affecting genes involved in drug transport such as several ABC transporter genes and genes related to drug resistance such as PRKDC and RUNX1T1 (in 3/4 of the cases, the CNA appeared exclusively at relapse or were already present at diagnosis and increased their frequency at relapse). CNA in genes that may confer stem cell characteristics (EGR1 and USP16) were another recurrent event at relapse (3/5 samples, 2 of them were not present at diagnosis). CNA affecting the X/Y PAR1 region (CRLF2, CSF2RA and IL3RA) or VPREB1 at 22q11.22 were detected in 3/5 relapse samples, respectively. An important apoptosis cluster at 11q21q24.2 (BIRC2/3, CASP1/4/5/12, hsa-miR-34b/c, ATM and BTG4) was lost in 2/5 relapse samples (one of them was not detected at diagnosis and the other increased its frequency at relapse). Finally, ETV6 deletion (12p13.2) and duplication of Xq26.2q28 (containing ABCD1, BCAP31 and genes coding for several cancer/testis antigens) were observed in 2 relapse samples. Conclusions: SNP arrays analysis of paired B-cell precursor ALL samples at diagnosis and at relapse allows the identification of genetic alterations potentially related with ALL progression. The systematic analysis of relapse samples could contribute to the identification of specific genetic targets with potential therapeutic impact for each patient (personalized medicine). Disclosures Martínez-López: Novartis: Honoraria, Speakers Bureau. Sole:Celgene: Membership on an entity's Board of Directors or advisory committees.
    Type of Medium: Online Resource
    ISSN: 0006-4971 , 1528-0020
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    Language: English
    Publisher: American Society of Hematology
    Publication Date: 2016
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  • 10
    In: British Journal of Haematology, Wiley, Vol. 186, No. 2 ( 2019-07), p. 263-268
    Abstract: The prognostic significance of low‐hypodiploidy has not been extensively evaluated in minimal residual disease (MRD)‐oriented protocols for adult acute lymphoblastic leukaemia (ALL). We analysed the outcome of hypodiploid adult ALL patients treated within Programa Español de Tratamientos en Hematología (PETHEMA) protocols. The 5‐year cumulative incidence of relapse (CIR) of low‐hypodiploid B‐cell precursor (BCP)‐ALL was significantly higher than that of high‐hypodiploids (52% vs. 12%, P  = 0.013). Low‐hypodiploid BCP‐ALL patients aged ≤35 years showed superior survival (71% vs. 21%, P  = 0.026) and lower 5‐year CIR (17% vs. 66%, P  = 0.090) than low‐hypodiploids aged 〉 35 years. Older adults and elderly low‐hypodiploid BCP‐ALL patients show dismal prognosis although achieving an end‐induction good MRD response.
    Type of Medium: Online Resource
    ISSN: 0007-1048 , 1365-2141
    URL: Issue
    RVK:
    Language: English
    Publisher: Wiley
    Publication Date: 2019
    detail.hit.zdb_id: 1475751-5
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