Impact of Early Intrapatient Variability of Tacrolimus Concentrations on the Risk of Graft-Versus-Host Disease after Allogeneic Stem Cell Transplantation Using High-Dose Post-Transplant Cyclophosphamide

Tacrolimus (Tac) is a pivotal immunosuppressant agent used to prevent graft-versus-host disease (GVHD) after allogeneic stem cell transplantation (alloHSCT). Tac is characterized by a narrow therapeutic window and a high inter-patient and intra-patient pharmacokinetic variability (IPV). Although high IPV of Tac concentrations has been associated with adverse post-transplant outcomes following solid organ transplantation, the effects of Tac IPV on alloHSCT recipients have not been determined. Tac IPV was therefore retrospectively evaluated in 128 alloHSCT recipients receiving high-dose post-transplant cyclophosphamide (PTCy) and the effects of Tac IPV on the occurrence of acute GVHD (aGVHD) were analyzed. Tac IPV was calculated from pre-dose concentrations (C0) measured during the first month after Tac initiation. The cumulative rates of grades II-IV and grades III-IV aGVHD at day +100 were 22.7% and 7%, respectively. Higher Tac IPV was associated with a greater risk of developing GVHD, with patients having IPV > 50th percentile having significantly higher rates of grades II-IV (34.9% vs. 10.8%; hazard ratio [HR] 3.858, p < 0.001) and grades III-IV (12.7% vs. 1.5%; HR 9.69, p = 0.033) aGVHD than patients having IPV ? 50th percentile. Similarly, patients with IPV > 75th percentile had higher rates of grades II-IV (41.9% vs. 16.5%; HR 3.30, p < 0.001) and grades III-IV (16.1% vs. 4.1%; HR 4.99, p = 0.012) aGVHD than patients with IPV ? 75th percentile. Multivariate analyses showed that high Tac IPV (>50th percentile) was an independent risk factor for grades II-IV (HR 2.99, p = 0.018) and grades III-IV (HR 9.12, p = 0.047) aGVHD. Determination of Tac IPV soon after alloHSCT could be useful in identifying patients at greater risk of aGVHD

The avoidance of G-CSF and the addition of prophylactic corticosteroids after autologous stem cell transplantation for multiple myeloma patients appeal for the at-home setting to reduce readmission for neutropenic fever

Background Autologous stem cell transplantation (ASCT) remains the standard of care for young multiple myeloma (MM) patients; indeed, at-home ASCT has been positioned as an appropriate therapeutic strategy. However, despite the use of prophylactic antibiotics, neutropenic fever (NF) and hospital readmissions continue to pose as the most important limitations in the outpatient setting. It is possible that the febrile episodes may have a non-infectious etiology, and engraftment syndrome could play a more significant role. The aim of this study was to analyze the impact of both G-CSF withdrawal and the addition of primary prophylaxis with corticosteroids after ASCT. Methods Between January 2002 and August 2018, 111 MM patients conditioned with melphalan were managed at-home beginning +1 day after ASCT. Three groups were established: Group A (n = 33) received standard G-CSF post-ASCT; group B (n = 32) avoided G-CSF post-ASCT; group C (n = 46) avoided G-CSF yet added corticosteroid prophylaxis post-ASCT. Results The incidence of NF among the groups was reduced (64%, 44%, and 24%; P2 (OR 6.1; P = 0.002) and G-CSF avoidance plus corticosteroids (OR 0.1; P60 years (OR 14.6; P = 0.04) and G-CSF avoidance plus corticosteroids (OR 0.07; P = 0.05). Conclusions G-CSF avoidance and corticosteroid prophylaxis post ASCT minimize the incidence of NF in MM patients undergoing at-home ASCT. This approach should be explored in a prospective randomized clinical trial

Small Bowel Enteroscopy - A Joint Clinical Guideline by the Spanish and Portuguese Small-Bowel Study Groups

The present evidence-based guidelines are focused on the use of device-assisted enteroscopy in the management of small-bowel diseases. A panel of experts selected by the Spanish and Portuguese small-bowel study groups reviewed the available evidence focusing on the main indications of this technique, its role in the management algorithm of each indication, and its diagnostic and therapeutic yield. A set of recommendations was issued accordingly.info:eu-repo/semantics/publishedVersio

Small bowel enteroscopy - A joint clinical guideline from the spanish and portuguese small bowel study groups

The present evidence-based guidelines are focused on the use of device-assisted enteroscopy in the management of small-bowel diseases. A panel of experts selected by the Spanish and Portuguese small bowel study groups reviewed the available evidence focusing on the main indications of this technique, its role in the management algorithm of each indication and on its diagnostic and therapeutic yields. A set of recommendations were issued accordingly.Estas recomendações baseadas na evidência detalham o uso da enteroscopia assistida por dispositivo no manejo clínico das doenças do intestino delgado. Um conjunto de Gastrenterologistas diferenciados em patologia do intestino delgado foi selecionado pelos grupos de estudos Espanhol e Português de intestino delgado para rever a evidência disponível sobre as principais indicações desta técnica, o seu papel nos algoritmos de manejo de cada indicação e sobre o seu rendimento diagnóstico e terapêutico. Foi gerado um conjunto de recomendações pelos autores

Timing and Tempo of Early and Successive Adaptive Radiations in Macaronesia

The flora of Macaronesia, which encompasses five Atlantic archipelagos (Azores, Canaries, Madeira, Cape Verde, and Salvage), is exceptionally rich and diverse

Assessing the impact of COVID-19 on liver cancer management (CERO-19).

BACKGROUND & AIMS: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems and it may have heavily impacted patients with liver cancer (LC). Herein, we evaluated whether the schedule of LC screening or procedures has been interrupted or delayed because of the COVID-19 pandemic. METHODS: An international survey evaluated the impact of the COVID-19 pandemic on clinical practice and clinical trials from March 2020 to June 2020, as the first phase of a multicentre, international, and observational project. The focus was on patients with hepatocellular carcinoma or intrahepatic cholangiocarcinoma, cared for around the world during the first COVID-19 pandemic wave. RESULTS: Ninety-one centres expressed interest to participate and 76 were included in the analysis, from Europe, South America, North America, Asia, and Africa (73.7%, 17.1%, 5.3%, 2.6%, and 1.3% per continent, respectively). Eighty-seven percent of the centres modified their clinical practice: 40.8% the diagnostic procedures, 80.9% the screening programme, 50% cancelled curative and/or palliative treatments for LC, and 41.7% modified the liver transplantation programme. Forty-five out of 69 (65.2%) centres in which clinical trials were running modified their treatments in that setting, but 58.1% were able to recruit new patients. The phone call service was modified in 51.4% of centres which had this service before the COVID-19 pandemic (n = 19/37). CONCLUSIONS: The first wave of the COVID-19 pandemic had a tremendous impact on the routine care of patients with liver cancer. Modifications in screening, diagnostic, and treatment algorithms may have significantly impaired the outcome of patients. Ongoing data collection and future analyses will report the benefits and disadvantages of the strategies implemented, aiding future decision-making. LAY SUMMARY: The coronavirus disease 2019 (COVID-19) pandemic has posed unprecedented challenges to healthcare systems globally. Herein, we assessed the impact of the first wave pandemic on patients with liver cancer and found that routine care for these patients has been majorly disrupted, which could have a significant impact on outcomes

Surviving in isolation: genetic variation, bottlenecks and reproductive strategies in the Canarian endemic Limonium macrophyllum (Plumbaginaceae)

Oceanic archipelagos are typically rich in endemic taxa, because they offer ideal conditions for diversification and speciation in isolation. One of the most remarkable evolutionary radiations on the Canary Islands comprises the 16 species included in Limonium subsection Nobiles, all of which are subject to diverse threats, and legally protected. Since many of them are single-island endemics limited to one or a few populations, there exists a risk that a loss of genetic variation might limit their longterm survival. In this study, we used eight newly developed microsatellite markers to characterize the levels of genetic variation and inbreeding in L. macrophyllum, a species endemic to the North-east of Tenerife that belongs to Limonium subsection Nobiles. We detected generally low levels of genetic variation over all populations (HT = 0.363), and substantial differentiation among populations (FST = 0.188;RST = 0.186) coupled with a negligible degree of inbreeding (F = 0.042). Obligate outcrossing may have maintained L. macrophyllum relatively unaffected by inbreeding despite the species’ limited dispersal ability and the genetic bottlenecks likely caused by a prolonged history of grazing. Although several factors still constitute a risk for the conservation of L. macrophyllum, the lack of inbreeding and the recent positive demographic trends observed in the populations of this species are factors that favour its future persistence

Modeling of red blood cell life-spans in hematologically normal populations

Despite the impact of red blood cell (RBC) Life-spans in some disease areas such as diabetes or anemia of chronic kidney disease, there is no consensus on how to quantitatively best describe the process. Several models have been proposed to explain the elimination process of RBCs: random destruction process, homogeneous life-span model, or a series of 4-transit compartment model. The aim of this work was to explore the different models that have been proposed in literature, and modifications to those. The impact of choosing the right model on future outcomes prediction--in the above mentioned areas--was also investigated. Both data from indirect (clinical data) and direct life-span measurement (biotin-labeled data) methods were analyzed using non-linear mixed effects models. Analysis showed that: (1) predictions from non-steady state data will depend on the RBC model chosen; (2) the transit compartment model, which considers variation in life-span in the RBC population, better describes RBC survival data than the random destruction or homogenous life-span models; and (3) the additional incorporation of random destruction patterns, although improving the description of the RBC survival data, does not appear to provide a marked improvement when describing clinical data

El uso precoz de la tomografía computarizada en el manejo de la diverticulitis aguda Early use of CT in the management of acute diverticulitis of the colon

Objetivo: valorar el uso precoz de la tomografía computarizada (TC) para el diagnóstico, estadificación y manejo de la diverticulitis aguda. Material y métodos: realizamos un estudio prospectivo de 102 pacientes con el diagnóstico clínico de diverticulitis aguda de colon izquierdo. La diverticulitis aguda fue inicialmente dividida en tres estadios. Los pacientes fueron reestadiados en los estadios I, IIa, IIb y III de acuerdo a los hallazgos encontrados en la TC. El diagnóstico se confirmó después intraoperatoriamente, por colonoscopia o estudio con bario. Resultados: fueron incluidos 102 pacientes (52 mujeres y 50 hombres) con una edad media de 59,4 (DS ± 14,96). En 84 (82,35%) pacientes con el diagnóstico clínico de diverticulitis aguda se confirmó este diagnóstico con un error diagnóstico del 17,65% (n = 18). La diverticulitis aguda se diagnosticó con la TC en el 84,3% (n = 86). La TC tuvo una sensibilidad del 100% y especificidad del 88,9%. La TC cambió la estadificación clínica en un 38% debido a una infraestadificación del 13% y una sobreestadificación del 25%, que llega al 60 y al 50% en los estadios clínicos II y III, respectivamente. La reclasificación o reestadificación de los pacientes de acuerdo con los hallazgos en la TC tiene una consecuencia importante en la indicación quirúrgica. Conclusiones: la estadificación clínica precoz de la diverticulitis con la TC evita errores de diagnóstico clínico en el 17,65%. La TC modifica la estadificación clínica de severidad en el 38% evitando la cirugía innecesaria y el retraso en el tratamiento quirúrgico.Objectives: to assess the early use of CT for the diagnosis, staging, and management of acute diverticulitis. Materials and methods: a prospective study of 102 patients with a clinical diagnosis of acute diverticulitis of the left colon. Acute diverticulitis was initially divided into 3 clinical stages. Patients were restaged according to CT findings into stages I, IIa, IIb, and III. Diagnosis was subsequently confirmed intraoperatively or by colonoscopy or barium studies. Results: 102 patients (52 females and 50 males, mean age of 59.4 (SD + 14.96 years)) were included; 84 (82.35%) patients with a clinical diagnosis of acute diverticulitis were confirmed to suffer this disease for a diagnostic error of 17.65% (n=18). Acute diverticulitis was diagnosed by CT in 84.3% (n=86). CT had a sensitivity of 100% and a specificity of 88.9%. CT changed clinical stage for 38% of patients - because of understaging in 13% and of overstaging in 25%. When stages II and III were analyzed separately, 60 and 50% were overstaged, respectively. The reclassification of patients according to CT results had a significant impact on treatment. Conclusions: Early clinical staging with CT avoids diagnostic clinical errors in 17.65% of patients. CT changes the initial clinical staging of acute episodes in 38% of cases, thus avoiding unnecessary delays in surgery for severe cases, and unnecessary surgeries for mild cases

Capítulo 10. Las aguas subterráneas en el Campo de Cartagena-Mar Menor

El agua subterránea constituye un recurso natural clave para el medio ambiente y el desarrollo económico de la cuenca del río Segura, que satisface entorno al 35% de la demanda total para riego. En la cuenca del Campo de Cartagena-Mar Menor, el recurso subterráneo desempeña además un papel estratégico especialmente en periodos de sequía, al amortiguar en un rango del 30-75%, las variaciones de los recursos procedentes del Trasvase Tajo-Segura. Las interrelaciones de los acuíferos del Campo de Cartagena con la laguna costera del Mar Menor y las implicaciones ambientales derivadas de su uso intensivo ha incrementado el interés científico, a la vez que emerge la necesidad de cumplir con las obligaciones legales derivadas de la Directiva Marco del Agua. En la actualidad la adopción efectiva de diferentes medidas de adaptación y mitigación encaminadas a mejorar la gestión de la cuenca y del Mar Menor precisa de Sistemas de Soporte a la Decisión basados en un mayor conocimiento hidrogeológico del acuífero multicapa y de los patrones y dinámicas de uso y consumo de agua.Postprint (published version