Strategies to Improve Therapeutic Adherence in Polymedicated Patients over 65 Years: A Systematic Review and Meta-Analysis.

BACKGROUND: Part of the population over 65 years of age suffer from several pathologies and are therefore polymedicated. In this systematic review and metanalysis, we aimed to determine the efficacy of several strategies developed to improve adherence to pharmacological treatment in polymedicated elderly people. DESIGN: Web Of Science, PubMed and the Cochrane Library were searched until 2 January 2024. In total, 17 of the 1508 articles found evaluated the efficacy of interventions to improve adherence to medication in polymedicated elderly patients. Methodological quality and the risk of bias were rated using the Cochrane risk of bias tool. Open Meta Analyst® software was used to create forest plots of the meta-analysis. RESULTS: In 11 of the 17 studies, an improvement in adherence was observed through the use of different measurement tools and sometimes in combination. The most frequently used strategy was using instructions and counselling, always in combination, in a single strategy used to improve adherence; one involved the use of medication packs and the other patient follow-up. In both cases, the results in improving adherence were positive. Five studies using follow-up interventions via visits and phone calls showed improved adherence on the Morisky Green scale compared to those where usual care was received [OR = 1.900; 95% CI = 1.104-3.270] (p = 0.021). DISCUSSION: There is a high degree of heterogeneity in the studies analyzed, both in the interventions used and in the measurement tools for improving adherence to treatment. Therefore, we cannot make conclusions about the most efficacious strategy to improve medication adherence in polymedicated elderly patients until more evidence of single-intervention strategies is available.

Association between missense variants of uncertain significance in the CHEK2 gene and hereditary breast cancer: a cosegregation and bioinformatics analysis.

Inherited mutations in the CHEK2 gene have been associated with an increased lifetime risk of developing breast cancer (BC). We aim to identify in the study population the prevalence of mutations in the CHEK2 gene in diagnosed BC patients, evaluate the phenotypic characteristics of the tumor and family history, and predict the deleteriousness of the variants of uncertain significance (VUS). A genetic study was performed, from May 2016 to April 2020, in 396 patients diagnosed with BC at the University Hospital Lozano Blesa of Zaragoza, Spain. Patients with a genetic variant in the CHEK2 gene were selected for the study. We performed a descriptive analysis of the clinical variables, a bibliographic review of the variants, and a cosegregation study when possible. Moreover, an in-depth bioinformatics analysis of CHEK2 VUS was carried out. We identified nine genetic variants in the CHEK2 gene in 10 patients (two pathogenic variants and seven VUS). This supposes a prevalence of 0.75% and 1.77%, respectively. In all cases, there was a family history of BC in first- and/or second-degree relatives. We carried out a cosegregation study in two families, being positive in one of them. The bioinformatics analyses predicted the pathogenicity of six of the VUS. In conclusion, CHEK2 mutations have been associated with an increased risk for BC. This risk is well-established for foundation variants. However, the risk assessment for other variants is unclear. The incorporation of bioinformatics analysis provided supporting evidence of the pathogenicity of VUS.

Ponatinib, chemotherapy, and transplant in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia.

Promising results have been shown with the combination of ponatinib and chemotherapy in adults with Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL). The PONALFIL (Ponatinib With Chemotherapy for Young Adults Ph Positive Acute Lymphoblastic Leukemia) trial combined ponatinib (30 mg/d) with standard induction and consolidation chemotherapy followed by allogeneic hematopoietic stem cell transplant (alloHSCT) in newly diagnosed Ph+ ALL patients aged 18 to 60 years. Ponatinib was only given pre-emptively after alloHSCT. Primary end points were hematologic and molecular response before alloHSCT and event-free survival (EFS), including molecular relapse as event. Thirty patients (median age, 49 years; range, 19-59 years) entered the trial. All exhibited hematologic response, and alloHSCT was performed in 26 patients (20 in complete molecular response and 6 in major molecular response). Only 1 patient died (of graft-versus-host disease), and 5 patients exhibited molecular relapse after alloHSCT. No tyrosine kinase inhibitor was given after HSCT in 18 of 26 patients. Twenty-nine patients are alive (median follow-up, 2.1 years; range, 0.2-4.0 years), with 3-year EFS and overall survival (OS) of 70% (95% confidence interval, 51-89) and 96% (95% confidence interval, 89-100), respectively. Comparison of the PONALFIL and the ALLPh08 (Chemotherapy and Imatinib in Young Adults With Acute Lymphoblastic Leukemia Ph [BCR-ABL] Positive; same schedule, using imatinib as the tyrosine kinase inhibitor) trials by propensity score showed significant improvement in OS for patients in PONALFIL (3-year OS, 96% vs 53%; P = .002). The most frequent grade 3 to 4 adverse events were hematologic (42%), infectious (17%), and hepatic (22%), with only one vascular occlusive event. The combination of chemotherapy with ponatinib followed by alloHSCT is well tolerated, with encouraging EFS in adults with newly diagnosed Ph+ ALL. Cross-trial comparison suggests improvement vs imatinib (clinicaltrials.gov identifier #NCT02776605).

The Efficacy and Effectiveness of Education for Preventing and Treating Non-Specific Low Back Pain in the Hispanic Cultural Setting: A Systematic Review.

A systematic review was conducted to assess the efficacy and effectiveness of education programs to prevent and treat low back pain (LBP) in the Hispanic cultural setting. Electronic and manual searches identified 1148 unique references. Nine randomized clinical trials (RCTs) were included in this review. Methodological quality assessment and data extraction followed the recommendations from the Cochrane Back Pain Review Group. Education programs which were assessed focused on active management (3 studies), postural hygiene (7), exercise (4) and pain neurophysiology (1). Comparators were no intervention, usual care, exercise, other types of education, and different combinations of these procedures. Five RCTs had a low risk of bias. Results show that: (a) education programs in the school setting can transmit potentially useful knowledge for LBP prevention and (b) education programs for patients with LBP improve the outcomes of usual care, especially in terms of disability. Education on pain neurophysiology improves the results of education on exercise, and education on active management is more effective than "sham" education and education on postural hygiene. Future studies should assess the comparative or summatory effects of education on exercise, education on pain neurophysiology and education on active management, as well as explore their efficiency.

Comparation of different malnutrition screening tools according to GLIM criteria in cancer outpatients.

BACKGROUND: Many studies have assessed different malnutrition screening tools in oncologic patients. However, very few have been carried out using the new GLIM criteria for malnutrition. The objective of our study is to compare the most recommended screening tools with respect to the new GLIM criteria for malnutrition in cancer patients. METHODS: Observational, cross-sectional, and single-center study carried out at the Medical Oncology Department at the Lozano Blesa Hospital in Zaragoza. We recruited 165 patients with tumors of the upper-gastrointestinal-tract, colorectal, and head-and-neck region undergoing outpatient treatment. All of them received MST, MUST, Nutriscore, MNA and CONUT screening tools, as well as the GLIM diagnostic criteria, which was used as the gold standard. RESULTS: MNA-SF showed the best sensitivity (0.99) and lowest specificity while CONUT had the best specificity (0.89) and lowest sensitivity to detect cancer-related malnutrition. We observed high variability in the diagnostic capabilities of Nutriscore when tumor location was considered, reducing sensitivity in patients with colorectal cancer compared to those with tumors of the upper-gastrointestinal-tract or head-and-neck location (0.25, 0.83, and 0.91 respectively). The highest index of agreement between the screening tools was found between MST, MUST and Nutriscore tests. Regarding the GLIM criteria, the highest agreement index was presented by MUST tool (0.66), while CONUT presented the lowest (0.12). CONCLUSIONS: Selecting the screening tool according to the type of cancer and its location may allow us to optimize its use and increase its performance, exploiting the advantages of each of them in the different populations.

Estudio retrospectivo del uso de antimicrobianos en pacientes que fallecen en un servicio de oncología / A retrospective study of the use of antimicrobials in patients dying in an oncology department

Introducción: Las infecciones al final de la vida constituyen una importante causa de morbimor- talidad y las indicaciones de antibioterapia en este contexto no están claras. Objetivos: El objetivo del estudio es describir el uso de antibióticos en la etapa final de la vida en pacientes hospitalizados por cáncer y analizar su relación con las características de la en- fermedad oncológica, el estado funcional y la probabilidad de alta al ingreso. Metodología: Se trata de un estudio retrospectivo de todos los pacientes fallecidos en planta de oncología médica acotado a un periodo de 7 meses comprendidos entre el 1 de mayo y el 31 de diciembre de 2019. El número total de pacientes incluidos fue 101. Se evaluó el porcentaje de pacientes que recibieron tratamiento antibiótico durante su ingreso y el tiempo transcurrido entre la última dosis y el exitus letalis. Resultados: La edad media fue de 65,3 años y el 54,5 % eran hombres. El 23,7 % de los pacientes presentaban ECOG < 2, el 63,3 % ECOG ≥ 2. La localización más frecuente de tumor primario fue el pulmón (38,6 %). El 53 % de los pacientes recibían tratamiento oncológico con quimioterapia paliativa en el momento del ingreso, encontrándose el 66,3 % en situación de progresión de la enfermedad. En el 72,3 % de los pacientes la probabilidad de alta al ingreso era baja. El foco infeccioso de sospecha principal fue el respiratorio (27,7 %) seguido del abdominal (18,8 %). El 58,4 % recibió tratamiento antibiótico durante el ingreso en el que fallecieron. El antimicrobiano usado con mayor frecuencia fue la amoxicilina-clavulánico (36,2 %). Respecto a la búsqueda del microorganismo responsable del probable cuadro infeccioso del paciente, se extrajo he- mocultivo en 23 pacientes (23 %), urocultivo en 12 (12 %), coprocultivo en 7 (7 %) y cultivo de esputo, en 10 pacientes (10 %). Se aislaron microorganismos en 9 hemocultivos, 4 urocultivos, un coprocultivo y 2 cultivos de esputo respectivamente. [...]. (AU)

Objectives: To describe the use of antibiotics at the end of life and analyze its relationship with the characteristics of the oncological disease, functional status and probability of discharge upon admission. Methodology: A retrospective study of deceased patients in the oncology ward limited to a period of 7 months between May 1 and December 31, 2019. The number of patients included was 101. The percentage of patients who received antibiotic treatment during their admission and the time elapsed between the last dose and exitus lethalis were evaluated. Results: Mean age was 65.3 years and 54.5 % were men; 23.7 % had an ECOG < 2, 63.3 % ≥ 2. The most frequent location of the primary tumor was the lung (38.6 %); 53 % of the patients received palliative chemotherapy at the time of admission, and 66.3 % were in disease progression. In 72.3 % the probability of discharge upon admission was low. The main suspected infectious focus was respiratory (27.7 %) followed by the abdomen (18.8 %); 58.4 % received antibiotic treatment. The most frequently used antimicrobial was amoxicillin-clavulanate (36.2 %). Regarding the search for the microorganism responsible for the patient’s probable infectious condition, a blood culture was obtained in 23 patients (23 %), a urine culture in 12 (12 %), a stool culture in 7 (7 %) and a sputum culture in 10 patients (10 %). Microorganisms were isolated in 9 blood cultures, 4 urine cultures, one stool culture, and 2 sputum cultures, respectively. The most frequently isolated microorganisms in the positive cultures were: Escherichia coli (4), Pseudomonas aeruginosa (2) and Clostridium perfringens (2). [...] (AU)

Programa Mejor Casero: educación alimentaria a través de clases de cocina en la Ciudad Autónoma de Buenos Aires / Better Homemade Program: food education through cooking classes in the Autonomous City of Buenos Aires

Fundamentos: El hábito de cocinar en el hogar ha sido relacionado con consumos alimentarios más saludables. El programa Mejor Casero se propone incentivar la cocina casera como una estrategia de promoción de una alimentación sostenible, promoviendo la adquisición de habilidades para preparar comidas saludables por parte de la población. El objetivo de este trabajo es describir los resultados de la evaluación del programa en la Ciudad Autónoma de Buenos Aires. Métodos: Estudio descriptivo cuali-cuantitativo transversal. Se realizaron encuestas auto-administradas y entrevistas semi-estructuradas a los asistentes a las clases de cocina. Resultados: El 72,1% de los encuestados refirió haber adquirido información nueva en el taller y el 73,8% se percibió capaz de replicar la receta aprendida. Las figuras del cocinero y del nutricionista se encontraron entre los aspectos más valorados del programa. La simplicidad de la preparación fue el principal determinante para la elección de una receta y las principales fuentes de consulta fueron los videos en redes sociales. Conclusiones: Las clases de cocina constituyen una instancia en la que los participantes del programa adquieren información nueva sobre preparación de alimentos, lo que podría contribuir a mejorar la calidad dela alimentación de los asistentes y los integrantes del hogar. (AU)

Background: The habit of cooking at home has been linked to healthier food intake. The Better Homemade program aims to encourage home cooking as a strategy to promote sustainable food, promoting the acquisition of skills to prepare healthy meals by the population. The objective of this work is to describe the results of the evaluation of the program in the Autonomous City of Buenos Aires. Methods: Descriptive quali-quantitative cross-sectional study. Self-administered surveys and semi-structured interviews were conducted among those attending cooking classes. Results: 72.1% of the respondents reported having acquired new information in the workshop and 73.8%perceived themselves capable of replicating the learned recipe. The cook and nutritionist figures were among the most valued aspects of the program. The simplicity of the preparation was the main determinant for the choice of a recipe and the main sources for consultation were videos on social networks. Conclusions: The cooking classes constitute an instance in which the program participants acquire new information about food preparation, which could contribute to improving the quality of the diet of the attendees and the members of their household. (AU)

Efficacy of Acetylcholinesterase Inhibitors on Cognitive Function in Alzheimer's Disease. Review of Reviews.

Alzheimer's disease (AD) is the most common form of dementia over the age of 65. It is estimated that 115.4 million people will be affected by AD by 2050. Acetylcholinesterase inhibitors (AChEI) are the only available and approved treatment for AD. The aim of the present study was to analyse the evidence on the efficacy of the AChEI in the treatment of cognitive symptoms of Alzheimer's disease. For that purpose, a review of review of the systematic reviews (SRs) on this topic was carried out by Web of Science, PubMed, and The Cochrane Library, among others, were searched until 24 September 2021. Thirteen of the 1773 articles evaluated the efficacy of AChEI on cognitive function and/or general condition and/or behavioural disturbances of patients with mild to moderate AD. Methodological quality and risk of bias were rated using the ROBIS scale. The quality of the identified studies was high for nine of them, unclear for two, and finally only in two of the 13 studies did we detect low quality. Overall, AChEI showed very low efficacy in improving cognition in patients with mild to moderate AD. Better results were obtained in improving global state, with donepezil being the most effective treatment. No improvements in behavioural disturbances were found. Few high-quality reviews provide clear evidence of the effects of AChEI on cognition, global change, behaviour, and mortality. The data suggest that AChEI stabilize or slow cognitive deterioration, improving global status. In addition, data indicate that the use of AChEI decreases mortality in patients with mild to moderate AD. However, there is no evidence that they improve patient behaviour. Donepezil is the best therapeutic alternative at a dose of 10 mg/day.

Outcomes and prognostic factors of adults with refractory or relapsed T-cell acute lymphoblastic leukemia included in measurable residual disease-oriented trials.

Despite high complete remission (CR) rates with frontline therapy, relapses are frequent in adults with T-cell acute lymphoblastic leukemia (T-ALL) with limited salvage options. We analyzed the outcomes and prognostic factors for CR to salvage therapy and overall survival (OS) of patients with R/R T-ALL included in two prospective measurable residual disease-oriented trials. Seventy-five patients (70 relapsed, 5 refractory) were identified. Relapses occurred in bone marrow, isolated or combined in 50 patients, and in the central nervous system (CNS; isolated or combined) in 20. Second CR was attained in 30/75 patients (40%). Treatment with FLAG-Ida and isolated CNS relapse were independently associated with a higher CR rate after first salvage therapy. The median OS was 6.2 (95% confidence interval [CI], 3.9-8.6) months, with a 4-year OS probability of 18% (95% CI, 9%-27%). No differences in survival were observed according to the treatment with hematopoietic stem cell transplantation in patients in CR after first salvage therapy. Multivariable analysis showed a ≥12-month interval between first CR and relapse, CR after first salvage therapy and isolated CNS relapse as favorable prognostic factors for OS with hazard ratios (HR) (95% CI) of 1.931 (1.109-3.362), 2.958 (1.640-5.334), and 2.976 (1.157-7.655), respectively. This study confirms the poor outcomes of adults with R/R T-ALL among whom FLAG-Ida was the best of the rescue therapies evaluated. Late relapse, CR after first rescue therapy and isolated CNS relapse showed prognostic impact on survival. More effective rescue therapies are needed in adults with R/R T-ALL.

Effect of the deletion of lprG and p55 genes in the K10 strain of Mycobacterium avium subspecies paratuberculosis.

The lprG-p55 operon of Mycobacterium tuberculosis, M. bovis and M. avium strain D4ER has been identified as a virulence factor involved in the transport of toxic compounds. LprG is a lipoprotein that modulates the host immune response against mycobacteria, whereas P55 is an efflux pump that provides resistance to several drugs. In the present study we search for, and characterize, lprg and p55, putative virulence genes in Mycobacterium avium subsp. paratuberculosis (MAP) to generate a live-attenuated strain of MAP that may be useful in the future as live-attenuated vaccine. For this purpose, we generated and evaluated two mutants of MAP strain K10: one mutant lacking the lprG gene (ΔlprG) and the other lacking both genes lprG and p55 (ΔlprG-p55). None of the mutant strains showed altered susceptibility to first-line and second-line antituberculosis drugs or ethidium bromide, only the double mutant had two-fold increase in clarithromycin susceptibility compared with the wild-type strain. The deletion of lprG and of lprG-p55 reduced the replication of MAP in bovine macrophages; however, only the mutant in lprG-p55 grew faster in liquid media and showed reduced viability in macrophages and in a mouse model. Considering that the deletion of both genes lprG-p55, but not that of lprG alone, showed a reduced replication in vivo, we can speculate that p55 contributes to the survival of MAP in this animal model.

GLIM vs ESPEN criteria for the diagnosis of early malnutrition in oncological outpatients.

BACKGROUND & AIMS: Malnutrition is one of the most prevalent problems among oncological patients. It reduces the response to treatments and negatively impacts survival. In 2019, a consensus criteria for diagnosing malnutrition (GLIM criteria) were proposed by most scientific nutrition societies. The objective of our work is 1) to assess the diagnostic capacity of the GLIM criteria in ambulatory patients with cancer and 2) to compare the GLIM with the ESPEN criteria to evaluate the contributions of these new criteria with respect to the existing ones. METHODS: Observational, cross-sectional, and single-center study carried out at the Medical Oncology Department in the Lozano Blesa Clinical Hospital in Zaragoza (Spain). One hundred and sixty-five outpatients with tumors in the upper gastrointestinal tract, head and neck, and colorectal locations were recruited. All of them received the MST, MUST, and Nutriscore screening tools along with the ESPEN and GLIM diagnostic criteria. RESULTS: The prevalence of malnutrition was 46.7% according to the GLIM criteria and 21.2% using the ESPEN tool. Patients diagnosed by GLIM had a higher body mass index (BMI, 24.3 kg/m2) and muscle mass (MM, 16.1 kg/m2) than those diagnosed by ESPEN (21.2 kg/m2 and 14.3 kg/m2 respectively, both p = 0.001). The MST, MUST, and Nutriscore tools had a higher degree of concordance with GLIM compared to ESPEN (MST 0.53 vs 0.26; MUST 0.36 vs 0.66; Nutriscore 0.28 vs 0.54). CONCLUSIONS: The found prevalence of malnutrition in cancer patients is higher using the GLIM instead of ESPEN criteria. This disparity can be explained at least in part by the difficulty of the ESPEN criteria for malnutrition to diagnose patients with high baseline BMI or MM. The use of criteria with greater sensitivity, such as the new GLIM criteria, could help early diagnosis and thus early intervention in cancer patients.

Reproducibility study of nocturnal blood pressure dipping in patients with high cardiovascular risk.

It has been shown that in most people there is a physiological reduction in blood pressure during nighttime sleep, it falling by approximately 10% compared to daytime values (dippers). On the other hand, in some people, there is no nighttime reduction (non-dippers). Various studies have found an association between being a non-dipper and a higher risk of cardiovascular disease, but few have assessed whether the nocturnal pattern is maintained over time. From the database of the TAHPS study, data were available on 225 patients, each of whom underwent 24-hour ambulatory blood pressure monitoring (ABPM) on four occasions over a period of 5 months. We studied the reproducibility of the nocturnal BP dipping pattern with mixed linear analysis and also calculated the concordance in the classification of patients as dippers or non-dippers. The intraclass correlation coefficients between the different ABPM recordings were 0.482 and 0.467 for systolic and diastolic blood pressure, respectively. Two-thirds (67%) and 70% of the patients classified, respectively, as dippers or non-dippers based on systolic and diastolic blood pressure readings in the first ABPM recording were found to have the same classification based on the subsequent recordings. We conclude that the reproducibility of nocturnal dipping patterns and concordance of dipper vs non-dipper status in individual patients is modest and therefore that we should be cautious about recommending treatments or interventions based on these patterns.

Development of a lateral flow immunochromatography test for the rapid detection of bovine tuberculosis.

Detection of specific antibodies would be a useful test strategy for bovine tuberculosis (bTB) as a complement to the single skin test. We developed a lateral flow immunochromatography (LFIC) test for rapid bTB detection based on the use of a conjugate of gold nanoparticles with a recombinant G protein. After evaluating 3 Mycobacterium bovis (MB) antigens: ESAT-6, CFP-10 and MPB83 for the control line, we selected MPB83 given it was the most specific. The performance of the test was analyzed with 820 bovine sera, 40 sera corresponding to healthy animals, 5 sera from animals infected with Mycobacterium avium subsp. paratuberculosis (MAP) and 775 sera of animals from herds with bTB. All these sera were also submitted to a validated bTB-ELISA using whole-cell antigen from MB. From the 775 sera of animals from herds with bTB, 87 sera were positive by the bTB-ELISA, 45 were positive by LFIC and only 5 animals were positives by skin test (TST). To confirm bTB infection in the group of TST (-), bTB-ELISA (+) and LFIC (+) animals, we performed postmortem examination in 15 randomly selected animals. Macroscopically, these 15 animals had numerous small and large yellow-white granulomas, characteristic of bTB, and the infection was subsequently confirmed by PCR in these tissues with lesions (gold standard). No false positive test result was detected with the developed LFIC either with the sera from healthy animals or from animals infected with MAP demonstrating that it can be a useful technique for the rapid identification of animals infected with bTB.

Chemotherapy or allogeneic transplantation in high-risk Philadelphia chromosome-negative adult lymphoblastic leukemia.

The need for allogeneic hematopoietic stem cell transplantation (allo-HSCT) in adults with Philadelphia chromosome-negative (Ph-) acute lymphoblastic leukemia (ALL) with high-risk (HR) features and adequate measurable residual disease (MRD) clearance remains unclear. The aim of the ALL-HR-11 trial was to evaluate the outcomes of HR Ph- adult ALL patients following chemotherapy or allo-HSCT administered based on end-induction and consolidation MRD levels. Patients aged 15 to 60 years with HR-ALL in complete response (CR) and MRD levels (centrally assessed by 8-color flow cytometry) <0.1% after induction and <0.01% after early consolidation were assigned to receive delayed consolidation and maintenance therapy up to 2 years in CR. The remaining patients were allocated to allo-HSCT. CR was attained in 315/348 patients (91%), with MRD <0.1% after induction in 220/289 patients (76%). By intention-to-treat, 218 patients were assigned to chemotherapy and 106 to allo-HSCT. The 5-year (±95% confidence interval) cumulative incidence of relapse (CIR), overall survival (OS), and event-free survival probabilities for the whole series were 43% ± 7%, 49% ± 7%, and 40% ± 6%, respectively, with CIR and OS rates of 45% ± 8% and 59% ± 9% for patients assigned to chemotherapy and of 40% ± 12% and 38% ± 11% for those assigned to allo-HSCT, respectively. Our results show that avoiding allo-HSCT does not hamper the outcomes of HR Ph- adult ALL patients up to 60 years with adequate MRD response after induction and consolidation. Better postremission alternative therapies are especially needed for patients with poor MRD clearance. This trial was registered at www.clinicaltrials.gov as # NCT01540812.

Household storage, surplus and supra-household storage in prehistoric and protohistoric societies of the Western Mediterranean.

The objective of this paper is to assess foodstuff storage throughout Recent Prehistory (5600-50 BCE) from the standpoint of the three different types (household, surplus and supra-household) identified in the northeast of the Iberian Peninsula. The volumetric data of the underground silos serves as a proxy to evaluate the link between them and the agricultural systems and technological changes. The study also assesses the ability, and specifically, the will of the ancient communities of the northeastern Iberia to generate domestic and extra-domestic surpluses.

Languedoc lagoon environments and man: Building a modern analogue botanical macroremain database for understanding the role of water and edaphology in sedimentation dynamics of archaeobotanical remains at the Roman port of Lattara (Lattes, France).

A new method to evaluate archaeological wetland sites in a more objective way was tested. Different wetland environments have been sampled in areas of a nature reserve and their macroremain content analysed to build a modern analogue dataset. This dataset was then used to characterise archaeological samples from a navigation channel from the Roman port city Lattara. In the modern analogue samples, the different wetland types (saline/brackish or fresh water) could be differentiated in the correspondence analysis. Within these groups, the sampled area of the littoral (submerged, shoreline, unsubmerged) could also be differentiated. This dataset can therefore provide a basis for the interpretation of the nature and degree of aquatic influence and layer formation processes in archaeobotanical records of coastal sites. In the tested archaeological samples from the navigation channel of Lattara, changes in space and time could be tracked using the modern analogue dataset and geoarchaeological information. The channel lost its fresh water supply and silted up over a short period of time (approx. 100 years).

Treatment of Frail Older Adults and Elderly Patients With Philadelphia Chromosome-negative Acute Lymphoblastic Leukemia: Results of a Prospective Trial With Minimal Chemotherapy.

BACKGROUND: The treatment of acute lymphoblastic leukemia (ALL) in older adults and elderly patients is a challenge, and modern protocols include targeted therapy and immunotherapy in combination with attenuated or minimal chemotherapy. However, frail patients are excluded from these trials, and reports on the outcome of this subgroup of patients are scarce. Our objective was to analyze the outcome of unfit older adults and elderly patients with Philadelphia chromosome-negative ALL included in a prospective trial (ALL-07FRAIL). PATIENTS AND METHODS: Older adults and elderly patients with Charlson Comorbidity Index (CCI) ≥ 4 were included. Induction therapy consisted of vincristine and dexamethasone, and maintenance therapy with mercaptopurine and methotrexate for 2 years. RESULTS: Seventy-two patients with a median age of 67 years (range, 57-89 years) and a median CCI of 5 (range, 4-12) were included. The rates of early withdrawal, early death, resistance, and complete response (CR) were 5%, 10%, 31%, and 54%, respectively. Six patients with CR abandoned the study, 5 died in CR, and 23 relapsed (cumulative relapse incidence 75%). The medians of disease-free and overall survival (OS) were 6.9 months (95% confidence interval [CI], 0.3-13.5 months) and 7.6 months (95% CI, 6.3-8.9 months), respectively. The most frequent toxic events were hematologic (neutropenia 77% and thrombocytopenia 54%, of grade III-IV in all cases). Eastern Cooperative Oncology Group score but not the CCI had significant impact on OS. CONCLUSION: Complete remission with very attenuated chemotherapy can be attained in one-half of older or elderly infirm patients with ALL. These results suggest that some of these patients could benefit from the concomitant or subsequent use of immunotherapy and/or targeted therapy.

Stromal vascular fraction technologies and clinical applications.

Introduction: The heterogeneous pool of cells found in the stromal vascular fraction of adipose tissue (SVF) and the purified mesenchymal stromal/stem cells (ASCs) isolated from this pool have increasingly been used as therapeutic tools in regenerative medicine.Areas covered: As SVF and ASCs are different, and should be used in different manners according to various clinical and biological indications, we reviewed the current literature, and focused on the clinical use of SVF to appraise the main medical fields for development. Both enzymatic digestion and mechanical disruption have been used to obtain SVF for non-homologous use. The safety and/or benefits of SVF have been examined in 71 clinical studies in various contexts, mainly musculoskeletal conditions, wound healing, urogenital, and cardiovascular and respiratory diseases. The use of SVF as a therapy remains experimental, with few clinical trials.Expert opinion: SVF provides a cellular and molecular microenvironment for regulation of ASC' activities under different clinical conditions. SVF may enhance angiogenesis and neovascularization in wound healing, urogenital and cardiovascular diseases. In joint conditions, therapeutic benefits may rely on paracrine immune-modulatory and anti-inflammatory mechanisms. Novel point of care methods are emerging to refine SVF in ways that meet the regulatory requirements for minimal manipulation.

Changes in metabolic and inflammatory parameters in a type 1 diabetic patient performing extreme activities / Cambios en parámetros metabólicos e inflamatorios en un paciente diabético tipo 1 realizando actividades extremas

Background: physical activity in type 1 diabetic patients allows a better control of glycaemia and glycosylated hemoglobin, helps to maintain a residual endocrine pancreatic mass and optimizes subsequent insulin requirements. These improvements might be due in part to increases in anti-inflammatory cytokines that could help to minimize β-cell destruction. However, type, intensity and frequency of exercise for type 1 diabetic patients remain to be established. Case report: we present the case of a 48-year-old man diagnosed with type 1 diabetes at the age of 23. He is a professional alpinist and recently was recruited in a program of the Yuri Gagarin Cosmonaut Training Center (Russia) to be the first diabetic astronaut. Metabolic and inflammatory responses were assessed after performing two extreme activities. Discussion: well programmed extreme activities accompanied by a correct dietetic intervention can reduce the adverse metabolic and inflammatory processes that appear due to exercise and diabetes

Introducción: la actividad física en pacientes diabéticos tipo 1 permite un mejor control de la glucemia y hemoglobina glucosilada, ayuda a mantener una masa residual de páncreas endocrino y optimiza las necesidades de insulina. Estas mejoras podrían ser debidas en parte al incremento en citocinas antiinflamatorias que ayudarían a minimizar la destrucción de células β. Sin embargo, el tipo, la intensidad y la frecuencia de ejercicio para pacientes diabéticos tipo 1 no han sido establecidos. Caso clínico: presentamos el caso de un varón de 48 años de edad diagnosticado de diabetes tipo 1 a los 23. Es alpinista profesional y recientemente ha sido reclutado por el Centro de Entrenamiento para Cosmonautas Yuri Gagarin (Rusia) para ser el primer astronauta diabético. Hemos comparado respuestas metabólicas e inflamatorias tras realizar dos actividades extremas. Discusión: actividades extremas bien programadas y con una correcta intervención dietética pueden reducir la descompensación metabólica e inflamatoria causada por la combinación actividad-enfermedad