Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 102
Filtrar
1.
Lancet ; 2024 May 02.
Artículo en Inglés | MEDLINE | ID: mdl-38705160

RESUMEN

BACKGROUND: Adding ibrutinib to standard immunochemotherapy might improve outcomes and challenge autologous stem-cell transplantation (ASCT) in younger (aged 65 years or younger) mantle cell lymphoma patients. This trial aimed to investigate whether the addition of ibrutinib results in a superior clinical outcome compared with the pre-trial immunochemotherapy standard with ASCT or an ibrutinib-containing treatment without ASCT. We also investigated whether standard treatment with ASCT is superior to a treatment adding ibrutinib but without ASCT. METHODS: The open-label, randomised, three-arm, parallel-group, superiority TRIANGLE trial was performed in 165 secondary or tertiary clinical centres in 13 European countries and Israel. Patients with previously untreated, stage II-IV mantle cell lymphoma, aged 18-65 years and suitable for ASCT were randomly assigned 1:1:1 to control group A or experimental groups A+I or I, stratified by study group and mantle cell lymphoma international prognostic index risk groups. Treatment in group A consisted of six alternating cycles of R-CHOP (intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous cyclophosphamide 750 mg/m2 on day 1, intravenous doxorubicin 50 mg/m2 on day 1, intravenous vincristine 1·4 mg/m2 on day 1, and oral prednisone 100 mg on days 1-5) and R-DHAP (or R-DHAOx, intravenous rituximab 375 mg/m2 on day 0 or 1, intravenous or oral dexamethasone 40 mg on days 1-4, intravenous cytarabine 2 × 2 g/m2 for 3 h every 12 h on day 2, and intravenous cisplatin 100 mg/m2 over 24 h on day 1 or alternatively intravenous oxaliplatin 130 mg/m2 on day 1) followed by ASCT. In group A+I, ibrutinib (560 mg orally each day) was added on days 1-19 of R-CHOP cycles and as fixed-duration maintenance (560 mg orally each day for 2 years) after ASCT. In group I, ibrutinib was given the same way as in group A+I, but ASCT was omitted. Three pairwise one-sided log-rank tests for the primary outcome of failure-free survival were statistically monitored. The primary analysis was done by intention-to-treat. Adverse events were evaluated by treatment period among patients who started the respective treatment. This ongoing trial is registered with ClinicalTrials.gov, NCT02858258. FINDINGS: Between July 29, 2016 and Dec 28, 2020, 870 patients (662 men, 208 women) were randomly assigned to group A (n=288), group A+I (n=292), and group I (n=290). After 31 months median follow-up, group A+I was superior to group A with 3-year failure-free survival of 88% (95% CI 84-92) versus 72% (67-79; hazard ratio 0·52 [one-sided 98·3% CI 0-0·86]; one-sided p=0·0008). Superiority of group A over group I was not shown with 3-year failure-free survival 72% (67-79) versus 86% (82-91; hazard ratio 1·77 [one-sided 98·3% CI 0-3·76]; one-sided p=0·9979). The comparison of group A+I versus group I is ongoing. There were no relevant differences in grade 3-5 adverse events during induction or ASCT between patients treated with R-CHOP/R-DHAP or ibrutinib combined with R-CHOP/R-DHAP. During maintenance or follow-up, substantially more grade 3-5 haematological adverse events and infections were reported after ASCT plus ibrutinib (group A+I; haematological: 114 [50%] of 231 patients; infections: 58 [25%] of 231; fatal infections: two [1%] of 231) compared with ibrutinib only (group I; haematological: 74 [28%] of 269; infections: 52 [19%] of 269; fatal infections: two [1%] of 269) or after ASCT (group A; haematological: 51 [21%] of 238; infections: 32 [13%] of 238; fatal infections: three [1%] of 238). INTERPRETATION: Adding ibrutinib to first-line treatment resulted in superior efficacy in younger mantle cell lymphoma patients with increased toxicity when given after ASCT. Adding ibrutinib during induction and as maintenance should be part of first-line treatment of younger mantle cell lymphoma patients. Whether ASCT adds to an ibrutinib-containing regimen is not yet determined. FUNDING: Janssen and Leukemia & Lymphoma Society.

2.
Updates Surg ; 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38565830

RESUMEN

Appendicitis is one of the most common abdominal emergencies. Evidence is controversial in determining if the in-hospital time delay to surgery can worsen the clinical presentation of appendicitis. This study aimed to clarify if in-hospital surgical delay significantly affected the proportion of complicated appendicitis in a large prospective cohort of patients treated with appendectomy for acute appendicitis. Patients were grouped into low, medium, and high preoperative risk for acute appendicitis based on the Alvarado scoring system. Appendicitis was defined as complicated in cases of perforation, abscess, or diffuse peritonitis. The primary outcome was correlation of in-hospital delay with the proportion of complicated appendicitis. The study includes 804 patients: 278 (30.4%) had complicated appendicitis and median time delay to surgery in low-, medium-, and high-risk group was 23.15 h (13.51-31.48), 18.47 h (10.44-29.42), and 13.04 (8.13-24.10) h, respectively. In-hospital delay was not associated with the severity of appendicitis or with the presence of postoperative complications. It appears reasonably safe to delay appendicectomy for acute appendicitis up to 24 h from hospital admission. Duration of symptoms was a predictor of complicated appendicitis and morbidity. Timing for appendicectomy in acute appendicitis should be calculated from symptoms onset rather than hospital presentation.

3.
J Enzyme Inhib Med Chem ; 39(1): 2301772, 2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-38221792

RESUMEN

The viral genome of the SARS-CoV-2 coronavirus, the aetiologic agent of COVID-19, encodes structural, non-structural, and accessory proteins. Most of these components undergo rapid genetic variations, though to a lesser extent the essential viral proteases. Consequently, the protease and/or deubiquitinase activities of the cysteine proteases Mpro and PLpro became attractive targets for the design of antiviral agents. Here, we develop and evaluate new bis(benzylidene)cyclohexanones (BBC) and identify potential antiviral compounds. Three compounds were found to be effective in reducing the SARS-CoV-2 load, with EC50 values in the low micromolar concentration range. However, these compounds also exhibited inhibitory activity IC50 against PLpro at approximately 10-fold higher micromolar concentrations. Although originally developed as PLpro inhibitors, the comparison between IC50 and EC50 of BBC indicates that the mechanism of their in vitro antiviral activity is probably not directly related to inhibition of viral cysteine proteases. In conclusion, our study has identified new potential noncytotoxic antiviral compounds suitable for in vivo testing and further improvement.


Asunto(s)
COVID-19 , Proteasas de Cisteína , Humanos , SARS-CoV-2 , Cisteína Endopeptidasas/metabolismo , Proteínas no Estructurales Virales/química , Antivirales/farmacología , Antivirales/química , Inhibidores de Proteasas/farmacología , Inhibidores de Proteasas/química , Simulación del Acoplamiento Molecular
4.
EClinicalMedicine ; 67: 102393, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38152413

RESUMEN

Background: Infections are the main reason for mortality during acute leukaemia treatment and invasive aspergillosis (IA) is a major concern. Allogeneic stem cell transplantation (alloSCT) is a standard therapy and often is the only live-saving procedure in leukaemia patients. The profound immunodeficiency occurring after alloSCT led to high IA-associated mortality in the past. Therefore, patients with IA were historically considered transplant-ineligible. Recently, there has been improvement of anti-fungal management including novel anti-fungal agents. As a result, more leukaemia patients with IA are undergoing alloSCT. Outcome has not been prospectively assessed. Methods: We performed a prospective study in acute leukaemia patients undergoing alloSCT to analyse the impact of a prior history of probable or proven IA (pre-SCT IA). The primary endpoint was 1-year non-relapse mortality (NRM). Relapse free survival and overall survival were analysed as secondary endpoints. Findings: 1439 patients were included between 2016 and 2021. The incidence of probable or proven pre-SCT IA was 6.0% (n = 87). The cumulative incidence of 1-year NRM was 17.3% (95% CI 10.2-26.0) and 11.2% (9.6-13.0) for patients with and without pre-SCT IA. In multivariate analyses the hazard ratio (HR) for 1-year NRM was 2.1 (1.2-3.6; p = 0.009) for patients with pre-SCT IA. One-year relapse-free survival was inferior in patients with pre-SCT IA (59.4% [48.3-68.9] vs. 70.4 [67.9-72.8]; multivariate HR 1.5 [1.1-2.1]; p = 0.02). Consequently, 1-year overall survival was lower in patients with pre-SCT IA: (68.8% [57.8-77.4] vs. 79.0% [76.7-81.1]; multivariate HR 1.7 [1.1-2.5]; p = 0.01). Interpretation: Pre-SCT IA remains to be significantly associated with impaired alloSCT outcome. On the other hand, more than two thirds of patients with pre-SCT IA were alive at one year after alloSCT. IA is not anymore an absolute contraindication for alloSCT because the majority of patients with IA who undergo alloSCT benefit from this procedure. Funding: There was no external funding source for this study.

5.
J Plankton Res ; 45(6): 832-852, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-38084301

RESUMEN

The patterns of species diversity of plankton functional groups (PFGs) remain poorly understood although they matter greatly for marine ecosystem functioning. Here, we use an ensemble of empirical species distribution models for 845 plankton species to estimate the global species richness of three phytoplankton and 11 zooplankton functional groups as a function of objectively selected environmental predictors. The annual mean species richness of all PFGs decreases from the low to the high latitudes, but the steepness and the shape of this decrease vary significantly across PFGs. Pteropods, small copepods (Oithonids and Poecilostomatoids) and Salps have the steepest latitudinal gradients, whereas Amphipods and the three phytoplankton groups have the weakest ones. Temperature, irradiance and nutrient concentration are the first-order control on the latitudinal richness patterns, whilst the environmental conditions associated to upwelling systems, boundary currents and oxygen minimum zones modulate the position of the peaks and troughs in richness. The species richness of all PFGs increases with net primary production but decreases with particles size and the efficiency of the biological carbon pump. Our study puts forward emergent biodiversity-ecosystem functioning relationships and hypotheses about their underlying drivers for future field-based and modelling research.

6.
Leukemia ; 37(2): 433-440, 2023 02.
Artículo en Inglés | MEDLINE | ID: mdl-36653509

RESUMEN

The standard treatment for young patients with untreated PTCLs is based on anthracycline containing-regimens followed by high-dose-chemotherapy and stem-cell-transplantation (HDT + SCT), but only 40% of them can be cured. Romidepsin, a histone-deacetylase inhibitor, showed promising activity in relapsed PTCLs; in first line, Romidepsin was added with CHOP. We designed a study combining romidepsin and CHOEP as induction before HDT + auto-SCT in untreated PTCLs (PTCL-NOS, AITL/THF, ALK-ALCL), aged 18-65 years. A phase Ib/II trial was conducted to define the maximum tolerated dose (MTD) of Ro-CHOEP, and to assess efficacy and safety of 6 Ro-CHOEP as induction before HDT. The study hypothesis was to achieve a 18-month PFS of 70%. Twenty-one patients were enrolled into phase Ib; 7 dose-limiting toxicities were observed, that led to define the MTD at 14 mg/ms. Eighty-six patients were included in the phase II. At a median follow-up of 28 months, the 18-month PFS was 46.2% (95%CI:35.0-56.7), and the 18-month overall survival was 73.1% (95%CI:61.6-81.7). The overall response after induction was 71%, with 62% CRs. No unexpected toxicities were reported. The primary endpoint was not met; therefore, the enrollment was stopped at a planned interim analysis. The addition of romidepsin to CHOEP did not improve the PFS of untreated PTCL patients.


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma de Células T Periférico , Humanos , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Trasplante de Células Madre Hematopoyéticas/métodos , Linfoma de Células T Periférico/tratamiento farmacológico , Trasplante de Células Madre
7.
Limnol Oceanogr ; 67(8): 1647-1669, 2022 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-36247386

RESUMEN

Plankton imaging systems supported by automated classification and analysis have improved ecologists' ability to observe aquatic ecosystems. Today, we are on the cusp of reliably tracking plankton populations with a suite of lab-based and in situ tools, collecting imaging data at unprecedentedly fine spatial and temporal scales. But these data have potential well beyond examining the abundances of different taxa; the individual images themselves contain a wealth of information on functional traits. Here, we outline traits that could be measured from image data, suggest machine learning and computer vision approaches to extract functional trait information from the images, and discuss promising avenues for novel studies. The approaches we discuss are data agnostic and are broadly applicable to imagery of other aquatic or terrestrial organisms.

8.
Blood ; 140(12): 1378-1389, 2022 09 22.
Artículo en Inglés | MEDLINE | ID: mdl-35737911

RESUMEN

Minimal residual disease (MRD) analysis is a known predictive tool in mantle cell lymphoma (MCL). We describe MRD results from the Fondazione Italiana Linfomi phase 3 MCL0208 prospective clinical trial assessing lenalidomide (LEN) maintenance vs observation after autologous stem cell transplantation (ASCT) in the first prospective comprehensive analysis of different techniques, molecular markers, and tissues (peripheral blood [PB] and bone marrow [BM]), taken at well-defined time points. Among the 300 patients enrolled, a molecular marker was identified in 250 (83%), allowing us to analyze 234 patients and 4351 analytical findings from 10 time points. ASCT induced high rates of molecular remission (91% in PB and 83% in BM, by quantitative real-time polymerase chain reaction [RQ-PCR]). Nevertheless, the number of patients with persistent clinical and molecular remission decreased over time in both arms (up to 30% after 36 months). MRD predicted early progression and long-term outcome, particularly from 6 months after ASCT (6-month time to progression [TTP] hazard ratio [HR], 3.83; P < .001). In single-timepoint analysis, BM outperformed PB, and RQ-PCR was more reliable, while nested PCR appeared applicable to a larger number of patients (234 vs 176). To improve MRD performance, we developed a time-varying kinetic model based on regularly updated MRD results and the MIPI (Mantle Cell Lymphoma International Prognostic Index), showing an area under the ROC (Receiver Operating Characteristic) curve (AUROC) of up to 0.87 using BM. Most notably, PB reached an AUROC of up to 0.81; with kinetic analysis, it was comparable to BM in performance. MRD is a powerful predictor over the entire natural history of MCL and is suitable for models with a continuous adaptation of patient risk. The study can be found in EudraCT N. 2009-012807-25 (https://eudract.ema.europa.eu/).


Asunto(s)
Trasplante de Células Madre Hematopoyéticas , Linfoma de Células del Manto , Adulto , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Cinética , Lenalidomida , Linfoma de Células del Manto/genética , Linfoma de Células del Manto/patología , Linfoma de Células del Manto/terapia , Neoplasia Residual , Estudios Prospectivos , Trasplante Autólogo
9.
Bone Marrow Transplant ; 57(7): 1133-1141, 2022 07.
Artículo en Inglés | MEDLINE | ID: mdl-35513485

RESUMEN

Neurological complications (NCs) represent a diagnostic and clinical challenge in allogeneic hematopoietic stem cell transplant (alloHSCT) patients. We retrospectively analyzed NC incidence, etiology, timing, characteristics, outcome, and long-term effects in 2384 adult patients transplanted in seven Italian institutions between January 2007 and December 2019. Ninety-three (3.9%) patients were affected by 96 NCs that were infectious (29.2%), immune/inflammatory (26%), drug-related (12.5%), cerebrovascular (5.2%), metabolic (3.1%), related to central nervous system disease relapse (11.5%) and malignancy (3.1%), or undefined (9.4%). Six patients (6.4%) had neurological manifestations of chronic graft-versus-host disease (GVHD). NCs occurred on average at day +128 (from -5 to +4063). Early (< day +120) and late NCs had similar frequencies (46.9% vs 53.1%, p = 0.39). Thirty-one patients (33.3%) were affected by acute or chronic GVHD at the NC onset. With a median follow-up of 25.4 (0.4-163) months, the overall mortality due to NCs was 22.6%. The median time between NC onset and death was 36 (1-269) days. Infectious NCs were the main cause (61.9%) of NC-related mortality. A persistent neurological impairment occurred in 20.4% patients, 57.9% of whom being affected by immune/inflammatory NCs. This study highlights the rare, yet severe impact of alloHSCT-associated NCs on patient survival and long-term functional ability.


Asunto(s)
Enfermedades del Sistema Nervioso Central , Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Adulto , Enfermedades del Sistema Nervioso Central/etiología , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/epidemiología , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Humanos , Incidencia , Estudios Retrospectivos , Trasplante Homólogo/efectos adversos
10.
Am J Hematol ; 97(8): 1023-1034, 2022 08.
Artículo en Inglés | MEDLINE | ID: mdl-35617104

RESUMEN

The phase III study was designed to compare event-free survival (EFS) after treosulfan-based conditioning with a widely applied reduced-intensity conditioning (RIC) busulfan regimen in older or comorbid patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS) undergoing allogeneic hematopoietic cell transplantation (HCT). A previously reported confirmatory interim analysis of the randomized clinical study including 476 patients demonstrated statistically significant noninferiority for treosulfan with clinically meaningful improvement in EFS. Here, the final study results and pre-specified subgroup analyses of all 570 randomized patients with completed longer-term follow-up are presented. Patients presenting HCT-specific comorbidity index >2 or aged ≥50 years were randomly assigned (1:1) to intravenous (IV) fludarabine with either treosulfan (30 g/m2 IV) or busulfan (6.4 mg/kg IV) after stratification by disease risk group, donor type, and participating institution. The primary endpoint was EFS with disease recurrence, graft failure, or death from any cause as events. EFS of patients (median age 60 years) was superior after treosulfan compared to RIC busulfan: 36-months-EFS rate 59.5% (95% CI, 52.2-66.1) vs. 49.7% (95% CI, 43.3-55.7) with a hazard ratio (HR) of 0.64 (95% CI, 0.49-0.84), p = 0.0006. Likewise, overall survival (OS) with treosulfan was superior compared to busulfan: 36-month-OS rate 66.8% vs. 56.3%; HR 0.64 (95% CI, 0.48-0.87), p = 0.0037. Post hoc analyses revealed that these differences were consistent with the confirmatory interim analysis, and thereby the treosulfan regimen appears particularly suitable for older AML and MDS patients.


Asunto(s)
Enfermedad Injerto contra Huésped , Trasplante de Células Madre Hematopoyéticas , Leucemia Mieloide Aguda , Síndromes Mielodisplásicos , Anciano , Busulfano/análogos & derivados , Busulfano/uso terapéutico , Trasplante de Células Madre Hematopoyéticas/métodos , Humanos , Persona de Mediana Edad , Estudios Prospectivos , Acondicionamiento Pretrasplante/métodos , Vidarabina/uso terapéutico
11.
Nat Immunol ; 23(5): 679-691, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35484408

RESUMEN

Here we report the identification of human CD66b-CD64dimCD115- neutrophil-committed progenitor cells (NCPs) within the SSCloCD45dimCD34+ and CD34dim/- subsets in the bone marrow. NCPs were either CD45RA+ or CD45RA-, and in vitro experiments showed that CD45RA acquisition was not mandatory for their maturation process. NCPs exclusively generated human CD66b+ neutrophils in both in vitro differentiation and in vivo adoptive transfer experiments. Single-cell RNA-sequencing analysis indicated NCPs fell into four clusters, characterized by different maturation stages and distributed along two differentiation routes. One of the clusters was characterized by an interferon-stimulated gene signature, consistent with the reported expansion of peripheral mature neutrophil subsets that express interferon-stimulated genes in diseased individuals. Finally, comparison of transcriptomic and phenotypic profiles indicated NCPs represented earlier neutrophil precursors than the previously described early neutrophil progenitors (eNePs), proNeus and COVID-19 proNeus. Altogether, our data shed light on the very early phases of neutrophil ontogeny.


Asunto(s)
Antígenos CD , Médula Ósea , Moléculas de Adhesión Celular , Diferenciación Celular , Neutrófilos , Receptor de Factor Estimulante de Colonias de Macrófagos , Receptores de IgG , Células de la Médula Ósea , COVID-19 , Proteínas Ligadas a GPI , Humanos , Interferones , Neutrófilos/citología
12.
Support Care Cancer ; 30(2): 1521-1527, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-34533630

RESUMEN

PURPOSE: Prevention of chemotherapy-induced nausea and vomiting (CINV) is particularly challenging for patients receiving highly emetogenic preparative regimens before autologous stem cell transplantation (ASCT) due to the daily and continuous emetogenic stimulus of the multiple day chemotherapy. While studies have shown effective prevention of CINV during the conditioning phase with NK1 receptor antagonist (NK1RA)-containing regimens, there have been no studies evaluating antiemetic use during chemomobilization prior to ASCT. METHODS: This multicenter, open-label, phase IIa study evaluated the efficacy of every-other-day dosing of NEPA administered during chemomobilization in patients with relapsed-refractory aggressive non-Hodgkin's lymphoma. Eighty-one patients participated. RESULTS: Response rates were 77.8% for complete response (no emesis and no rescue use), 72.8% for complete control (complete response and no more than mild nausea), 86.4% for no emesis, and 82.7% for no rescue use during the overall phase (duration of chemomobilization through 48 h after). NEPA was well tolerated with no treatment-related adverse events reported. CONCLUSION: NEPA, administered with a simplified every-other-day schedule, show to be very effective in preventing CINV in patients at high risk of CINV undergoing to chemomobilization of hematopoietic stem cells prior to ASCT.


Asunto(s)
Antieméticos , Linfoma no Hodgkin , Náusea , Palonosetrón , Vómitos , Antieméticos/efectos adversos , Antineoplásicos/efectos adversos , Quimioterapia Combinada/efectos adversos , Trasplante de Células Madre Hematopoyéticas , Humanos , Linfoma no Hodgkin/tratamiento farmacológico , Náusea/inducido químicamente , Náusea/prevención & control , Palonosetrón/efectos adversos , Trasplante Autólogo , Resultado del Tratamiento , Vómitos/inducido químicamente , Vómitos/prevención & control
13.
Transplant Proc ; 53(10): 2873-2878, 2021 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-34728075

RESUMEN

BACKGROUND: Renal transplantation is the gold standard treatment for end-stage renal disease, however, in 20% of cases, the graft develops a delayed graft function (DGF) that is associated with both early and late worsening of the outcome. The aim of this study was to examine and validate in a population of transplanted patients the appropriateness of the predictive score systems of DGF available to identify patients who might take advantage of a tailored immunosuppressive therapy. MATERIALS AND METHODS: We conducted a systematic review of the literature to identify articles concerning scoring systems predicting DGF to identify those applicable to the study population and subsequently comparing their appropriateness for defining the most accurate one. RESULTS: From an analysis of the scientific literature, we found 7 scoring systems predicting DGF. Of these, 3 can be calculated for the study population. We enrolled 247 renal transplants in the study. DGF was recorded in 41 cases (15.95%). The Irish score recognized 25 of 41 cases (60.98%), the Jeldres score 41 of 41 cases (100%), and the Chapal score only 7 of 41 (17.07%). Although the Irish score did not identify all cases of DGF, the analysis of data revealed that it is the most accurate, with area under the receiver operating characteristic almost overlapping. CONCLUSIONS: The study resulted in some interesting and promising conclusions about the predictability of DGF, defining the Irish score as the most reliable. This result can be considered the fundamental requirement to develop a custom therapeutic algorithm to be applied to all recipients with higher probability of developing DGF.


Asunto(s)
Fallo Renal Crónico , Trasplante de Riñón , Trasplantes , Funcionamiento Retardado del Injerto/etiología , Supervivencia de Injerto , Humanos , Riñón , Fallo Renal Crónico/diagnóstico , Fallo Renal Crónico/cirugía , Trasplante de Riñón/efectos adversos , Factores de Riesgo
16.
Nat Commun ; 12(1): 5226, 2021 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-34471105

RESUMEN

Marine phytoplankton and zooplankton form the basis of the ocean's food-web, yet the impacts of climate change on their biodiversity are poorly understood. Here, we use an ensemble of species distribution models for a total of 336 phytoplankton and 524 zooplankton species to determine their present and future habitat suitability patterns. For the end of this century, under a high emission scenario, we find an overall increase in plankton species richness driven by ocean warming, and a poleward shift of the species' distributions at a median speed of 35 km/decade. Phytoplankton species richness is projected to increase by more than 16% over most regions except for the Arctic Ocean. In contrast, zooplankton richness is projected to slightly decline in the tropics, but to increase strongly in temperate to subpolar latitudes. In these latitudes, nearly 40% of the phytoplankton and zooplankton assemblages are replaced by poleward shifting species. This implies that climate change threatens the contribution of plankton communities to plankton-mediated ecosystem services such as biological carbon sequestration.


Asunto(s)
Biodiversidad , Calentamiento Global , Biología Marina , Plancton/clasificación , Animales , Regiones Árticas , Cambio Climático , Ecosistema , Cadena Alimentaria , Fitoplancton , Temperatura , Zooplancton
17.
Sci Rep ; 11(1): 15714, 2021 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-34344925

RESUMEN

Ocean plankton comprise organisms from viruses to fish larvae that are fundamental to ecosystem functioning and the provision of marine services such as fisheries and CO2 sequestration. The latter services are partly governed by variations in plankton community composition and the expression of traits such as body size at community-level. While community assembly has been thoroughly studied for the smaller end of the plankton size spectrum, the larger end comprises ectotherms that are often studied at the species, or group-level, rather than as communities. The body size of marine ectotherms decreases with temperature, but controls on community-level traits remain elusive, hindering the predictability of marine services provision. Here, we leverage Tara Oceans datasets to determine how zooplankton community composition and size structure varies with latitude, temperature and productivity-related covariates in the global surface ocean. Zooplankton abundance and median size decreased towards warmer and less productive environments, as a result of changes in copepod composition. However, some clades displayed the opposite relationships, which may be ascribed to alternative feeding strategies. Given that climate models predict increasingly warmed and stratified oceans, our findings suggest that zooplankton communities will shift towards smaller organisms which might weaken their contribution to the biological carbon pump.

18.
Blood Adv ; 5(16): 3174-3187, 2021 08 24.
Artículo en Inglés | MEDLINE | ID: mdl-34424322

RESUMEN

Adenosine deaminase 2 deficiency (DADA2) is a rare inherited disorder that is caused by autosomal recessive mutations in the ADA2 gene. Clinical manifestations include early-onset lacunar strokes, vasculitis/vasculopathy, systemic inflammation, immunodeficiency, and hematologic defects. Anti-tumor necrosis factor therapy reduces strokes and systemic inflammation. Allogeneic hematopoietic stem/progenitor cell (HSPC) transplantation can ameliorate most disease manifestations, but patients are at risk for complications. Autologous HSPC gene therapy may be an alternative curative option for patients with DADA2. We designed a lentiviral vector encoding ADA2 (LV-ADA2) to genetically correct HSPCs. Lentiviral transduction allowed efficient delivery of the functional ADA2 enzyme into HSPCs from healthy donors. Supranormal ADA2 expression in human and mouse HSPCs did not affect their multipotency and engraftment potential in vivo. The LV-ADA2 induced stable ADA2 expression and corrected the enzymatic defect in HSPCs derived from DADA2 patients. Patients' HSPCs re-expressing ADA2 retained their potential to differentiate into erythroid and myeloid cells. Delivery of ADA2 enzymatic activity in patients' macrophages led to a complete rescue of the exaggerated inflammatory cytokine production. Our data indicate that HSPCs ectopically expressing ADA2 retain their multipotent differentiation ability, leading to functional correction of macrophage defects. Altogether, these findings support the implementation of HSPC gene therapy for DADA2.


Asunto(s)
Adenosina Desaminasa , Vasculitis , Adenosina Desaminasa/genética , Animales , Humanos , Inflamación , Péptidos y Proteínas de Señalización Intercelular , Macrófagos , Ratones
19.
Transplant Proc ; 53(6): 1892-1896, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-34233847

RESUMEN

BACKGROUND: Microvascular damage is the main cause of delayed graft function (DGF) after kidney transplant. Assessing its extent may be helpful in predicting DGF to achieve better postoperative management, especially in terms of an immunosuppressive regimen. Our aim was to explore the capability of intraoperative indocyanine green (ICG) angiography to examine the microvasculature of the kidney. METHODS: We conducted a prospective cohort study on 37 kidney transplant recipients in a high-volume kidney transplant center. During surgery, after graft implant, an ICG angiography was performed through a high-definition Storz camera system (Karl Storz GmbH, Tuttlingen, Germany) with successive quantitative assessment of fluorescence using Icy bioimage analysis. RESULTS: All transplanted kidneys that showed immediate recovery of their function had a fluorescent intensity ≥49.953 with a mean of 96.930 ± 21. The fluorescence intensity for kidneys that showed a delayed recovery of their function never exceeded 55.648, and the mean was 37.718 ± 13. The difference between the 2 groups was statistically significant with a P value < .001. The only kidney that never recovered showed a fluorescence intensity consistently <25.220, the lowest detected. CONCLUSIONS: This study demonstrates that intraoperative ICG angiography may be used to assess the microvasculature of the graft. A statistically significant difference in terms of fluorescent intensity can be highlighted between kidneys that immediately recover their function and those with delayed recovery. Further larger studies are needed to confirm the capability of the technique to predict DGF to optimize the transplanted patients' management.


Asunto(s)
Verde de Indocianina , Trasplante de Riñón , Angiografía , Funcionamiento Retardado del Injerto , Humanos , Riñón , Estudios Prospectivos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...