Drug development strategies for the treatment of obesity: how to ensure efficacy, safety, and sustainable weight loss

The prevalence of obesity has increased worldwide, and approximately 25%-35% of the adult population is obese in some countries. The excess of body fat is associated with adverse health consequences. Considering the limited efficacy of diet and exercise in the current obese population and the use of bariatric surgery only for morbid obesity, it appears that drug therapy is the only available method to address the problem on a large scale. Currently, pharmacological obesity treatment options are limited. However, new antiobesity drugs acting through central nervous system pathways or the peripheral adiposity signals and gastrointestinal tract are under clinical development. One of the most promising approaches is the use of peptides that influence the peripheral satiety signals and brain-gut axis such as GLP-1 analogs. However, considering that any antiobesity drug may affect one or several of the systems that control food intake and energy expenditure, it is unlikely that a single pharmacological agent will be effective as a striking obesity treatment. Thus, future strategies to treat obesity will need to be directed at sustainable weight loss to ensure maximal safety. This strategy will probably require the coadministration of medications that act through different mechanisms.Instituto de Salud Carlos IIIXunta de GaliciaFundación Mutua Madrileñ

Effects of a Community-Based Behavioral Intervention with a Traditional Atlantic Diet on Cardiometabolic Risk Markers: A Cluster Randomized Controlled Trial (“The GALIAT Study”)

The Atlantic diet, the traditional dietary pattern in northern Portugal and northwest Spain, has been related to metabolic health and low ischemic heart disease mortality. The Galiat Study is a randomized controlled trial aimed to assess the effects of the Atlantic diet on anthropometric variables, metabolic profile, and nutritional habits. The dietary intervention was conducted in 250 families (720 adults and children) and performed at a primary care center. Over six months, families randomized to the intervention group received educational sessions, cooking classes, written supporting material, and foods that form part of the Atlantic diet, whereas those randomized to the control group followed their habitual lifestyle. 213 families (92.4%) completed the trial. Adults in the intervention group lost weight as opposed to controls who gained weight (adjusted mean difference −1.1 kg, p < 0.001) and total serum cholesterol (adjusted mean difference −5.2 mg/dL, p = 0.004). Significant differences in favor of the intervention were found in other anthropometric variables and low-density lipoprotein cholesterol, but changes in triglycerides, high-density lipoprotein cholesterol, inflammation markers, blood pressure, and glucose metabolism were not observed. A family-based nutritional intervention based on the Atlantic diet showed beneficial effects on adiposity and the lipid profileThis project received funding from the ERDF-Innterconecta for Galicia Program (ITC-20133014 & ITC-20151009), managed by the Centre for the Development of Industrial Technology (CDTI), Spanish Ministry of Economy, Industry and CompetitivenessS

A clustering approach to analyse the environmental and energetic impacts of Atlantic recipes - A Galician gastronomy case study

The definition of the term gastronomy encompasses both the knowledge of food and its handling, preparation and consumption. Beyond a sense of cultural identity and tradition, gastronomy also represents a pole of tourist attraction. This is the case of Galicia, a region in north-western Spain. Within this framework, local dishes, which include distinctive elements of the Atlantic diet, have gained popularity. This research delves into the sustainability of 60 Galician recipes by performing a hierarchical cluster analysis to study their carbon footprint, the energy return on investment ratio and cost. The life cycle assessment methodology was followed to account for the carbon footprint and the energy return on investment ratio of the recipes. The scope was bounded to the cradle-to-fork phases through the life cycle: production of the ingredients, transport, and meal preparation. The functional unit selected was one serving of a Galician meal. The results suggest that the recipes could be classified into three main groups according to the presence of a greater or lesser amount of animal-based products. Cluster 1 comprises 10 meat recipes. Cluster 2 encompasses 31 recipes rich in fish with some vegetables and moderate consumption of red meat and dairy products. Cluster 3 includes 22 vegetable-based recipes. The higher the portion of animal products in the recipes (mainly red meat), the higher the costs and carbon footprint and the lower the energy return on investment ratio. Conversely, plant-based recipes tend to reduce greenhouse gases emissions and increase cost competitiveness and energy efficiency indicators. Based on this study, the food service could promote eco-labelling that support and certify restaurant menus. This research could also provide transformative climate education for sustainable food for consumers, giving advice to improve food-based dietary guidelines in SpainThe Galiat project received funding from the ERDF-Interconecta for Galicia Program (ITC-20133014 & ITC-20151009), managed by the Centre for the Development of Industrial Technology (CDTI), Spanish Ministry of Economy, Industry and Competitiveness. The authors thank the participating companies that assisted in this study; these include the Belarmino Fernández Iglesias Hostelry School, Bodegas Terras Gauda, Bodegas Pazo de Rivas, Conservas A Rosaleira, Conservas Friscos, Aceites Olei, and Quescrem. C.C.-F. would like to thank the Ministry of Science, Innovation and Universities for financial support (Grant reference FPU 19/06648). C.C-F, S.G.-G., G.F. and M.T.M. belong to the Galician Competitive Research Group (GRC ED431C 2017/29) and to the Cross-disciplinary Research in Environmental Technologies (CRETUS Research Center, ED431E 2018/01). All these programs are co-funded by FEDER (EU)S

Cryopreservation of unrelated donor hematopoietic stem cells: the right answer for transplantations during the COVID-19 pandemic?

Cryopreservation was recommended to ensure continuity of unrelated donor (UD) hematopoietic stem cell transplantation (HSCT) during COVID-19 pandemic. However, its impact on clinical outcomes and feasibility was not well known. We compared 32 patients who underwent UD HSCT using cryopreserved peripheral blood stem cells (PBSC) during the COVID-19 pandemic with 32 patients who underwent UD HSCT using fresh PBSC in the previous period. Median neutrophil engraftment was 17.5 and 17.0 days with cryopreserved and fresh grafts, respectively. Non-significant delays were found in platelet recovery days (25.5 versus 19.0; P = 0.192) and full donor chimerism days (35.0 and 31.5; P = 0.872) using cryopreserved PBSC. The rate of acute graft-versus-host disease at 100 days was 41% (95% CI [21-55%]) in cryopreserved group versus 31% (95% CI [13-46%]) in fresh group (P = 0.380). One-hundred days progression-relapse free survival and overall survival did not differ significantly. During COVID-19 pandemic, six frozen UD donations were not transfused and logistical and clinical issues regarding cryopreservation procedure, packaging, and transporting appeared. In summary, UD HSCT with cryopreserved PBSC was safe during this challenging time. More efforts are needed to ensure that all frozen grafts are transplanted and cryopreservation requirements are harmonized

Risk factors and outcome of COVID-19 in patients with hematological malignancies

Background: Prognostic factors of poor outcome in patients with hematological malignancies and COVID-19 are poorly defned. Patients and methods: This was a Spanish transplant group and cell therapy (GETH) multicenter retrospective observational study, which included a large cohort of blood cancer patients with laboratory-confrmed SARS-CoV-2 infection through PCR assays from March 1st 2020 to May 15th 2020. Results: We included 367 pediatric and adult patients with hematological malignancies, including recipients of autologous (ASCT) (n=58) or allogeneic stem cell transplantation (allo-SCT) (n=65) from 41 hospitals in Spain. Median age of patients was 64 years (range 1-93.8). Recipients of ASCT and allo-SCT showed lower mortality rates (17% and 18%, respectively) compared to non-SCT patients (31%) (p=0.02). Prognostic factors identifed for day 45 overall mortality (OM) by logistic regression multivariate analysis included age>70 years [odds ratio (OR) 2.1, 95% con‑ fdence interval (CI) 1.2-3.8, p=0.011]; uncontrolled hematological malignancy (OR 2.9, 95% CI 1.6-5.2, p20 mg/dL (OR 3.3, 95% CI 1.7-6.4, p<0.0001). In multivariate analysis of 216 patients with very severe COVID-19, treatment with azithromycin or low dose corticosteroids was associated with lower OM (OR 0.42, 95% CI 0.2-0.89 and OR 0.31, 95% CI 0.11-0.87, respectively, p=0.02) whereas the use of hidroxycloroquine did not show signifcant improvement in OM (OR 0.64, 95% CI 0.37-1.1, P=0.1). Conclusions: In most patients with hematological malignancies COVID-19 mortality was directly driven by older age, disease status, performance status, as well as by immune (neutropenia) parameters and level of infammation (high CRP). Use of azithromycin and low dose corticosteroids may be of value in very severe COVID-19

Risk factors and outcome of COVID-19 in patients with hematological malignancies

Background: Prognostic factors of poor outcome in patients with hematological malignancies and COVID-19 are poorly defined. Patients and methods: This was a Spanish transplant group and cell therapy (GETH) multicenter retrospective observational study, which included a large cohort of blood cancer patients with laboratory-confirmed SARS-CoV-2 infection through PCR assays from March 1st 2020 to May 15th 2020. Results: We included 367 pediatric and adult patients with hematological malignancies, including recipients of autologous (ASCT) (n = 58) or allogeneic stem cell transplantation (allo-SCT) (n = 65) from 41 hospitals in Spain. Median age of patients was 64 years (range 1-93.8). Recipients of ASCT and allo-SCT showed lower mortality rates (17% and 18%, respectively) compared to non-SCT patients (31%) (p = 0.02). Prognostic factors identified for day 45 overall mortality (OM) by logistic regression multivariate analysis included age > 70 years [odds ratio (OR) 2.1, 95% confidence interval (CI) 1.2-3.8, p = 0.011]; uncontrolled hematological malignancy (OR 2.9, 95% CI 1.6-5.2, p 20 mg/dL (OR 3.3, 95% CI 1.7-6.4, p < 0.0001). In multivariate analysis of 216 patients with very severe COVID-19, treatment with azithromycin or low dose corticosteroids was associated with lower OM (OR 0.42, 95% CI 0.2-0.89 and OR 0.31, 95% CI 0.11-0.87, respectively, p = 0.02) whereas the use of hidroxycloroquine did not show significant improvement in OM (OR 0.64, 95% CI 0.37-1.1, P = 0.1). Conclusions: In most patients with hematological malignancies COVID-19 mortality was directly driven by older age, disease status, performance status, as well as by immune (neutropenia) parameters and level of inflammation (high CRP). Use of azithromycin and low dose corticosteroids may be of value in very severe COVID-19

Consensus document on the primary prevention of cow's milk protein allergy in infants aged less than 7 days

Introduction: Cow's milk protein allergy (CMPA) is the most frequent food allergy in the first year of life. There is no clear consensus regarding its prevention. A recommendation to avoid CMP in the first week of life as a preventive measure in alt infants, regardless of their atopic risk, has recently been published. The purpose of this document is to issue a recommendation on the use of extensively hydrolyzed CMP formulas in the first week of life for the primary prevention of CMPA.Methods: A group of experts was formed with members proposed by the Spanish Association of Pediatrics (AEP), the Spanish Society of Clinical Immunology and Allergology and Pediatric Asthma (SEICAAP), the Spanish Society of Pediatric Gastroenterology, Hepatology and Nutrition (SEGHNP) and the Spanish Society of Neonatology (SENEO). The group conducted a critical review of the evidence on the subject published in the last 10 years.Results: The search yielded 72 studies, of which 66 were rejected for not meeting the inclusion criteria. The final review included 6 documents: 3 clinical trials and 3 systematic reviews, 2 of them with meta-analysis. There was no evidence of a statistically significant reduction in the incidence of CMPA in the infants who received hypoallergenic formulae or exclusive breastfeeding.Conclusion: Based on the current evidence, it is not possible to draw clear conclusions about the effect of avoiding CMP in the first week of life for prevention of CMPA. Although there are data that suggest a certain beneficial effect of avoiding CMPA in atopic risk infants, these results are not conclusive enough to extend the recommendation to the general population. (C) 2022 Asociacion Espanola de Pediatria. Published by Elsevier Espana, S.L.U