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1.
Tumor microenvironment in thyroid cancer: Immune cells, patterns, and novel treatments.
Febrero, B, Ruiz-Manzanera, JJ, Ros-Madrid, I, Hernández, AM, Orenes-Piñero, E, Rodríguez, JM
Head & neck. 2024
Abstract
The tumor immune microenvironment of thyroid cancer is the heterogeneous histological space in which tumor cells coexist with host cells. Published data from this review were identified by search and selection database of Pubmed, Elsevier, and Science Direct. Searching was made in two steps using different keywords. In thyroid pathology, the inflammatory response is very important, and might have a key role finding new diagnostic and therapeutic methods, particularly in thyroid cancer. Different immune cells may be more or less present in different types of thyroid cancer and may even have different functions, hence the importance of knowing their presence in different thyroid tumor pathologies. Cancer-related inflammation could be a useful target for new diagnostic and therapeutic strategies by analyzing peritumoral and intratumoral immune cells in different types of thyroid tumors. Moreover, novel strategies for thyroid cancer treatments, such as monoclonal antibodies targeting checkpoint inhibitors, are emerging as promising alternatives.
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2.
Is unicentric familial papillary thyroid microcarcinoma different from multicentric?
Ríos, A, Ruiz-Pardo, J, Balaguer-Román, A, Puñal, JA, Moreno, P, Mercader, E, Ferrero, E, Morlán, MA, Martín, J, Durán, M, et al
Endocrine. 2023;(3):613-621
Abstract
BACKGROUND Familial papillary thyroid microcarcinoma (FPTMC) appears to be more aggressive than sporadic papillary thyroid microcarcinoma (SPTMC). However, there are authors who indicate that unicentric FPTMC has a similar prognosis to SPTMC. The objective is to analyze whether unicentric FPTMC has a better prognosis than multicentric FPTMC. DESIGN AND METHODS Type of study: National multicenter longitudinal analytical observational study. STUDY POPULATION Patients with FPTMC. STUDY GROUPS Two groups were compared: Group A (unicentric FPTMC) vs. Group B (multicentric FPTMC). STUDY VARIABLES It is analyzed whether between the groups there are: a) differentiating characteristics; and b) prognostic differences. STATISTICAL ANALYSIS Cox regression analysis and survival analysis. RESULTS Ninety-four patients were included, 44% (n = 41) with unicentric FPTMC and 56% (n = 53) with multicentric FPTMC. No differences were observed between the groups according to socio-familial, clinical or histological variables. In the group B a more aggressive treatment was performed, with higher frequency of total thyroidectomy (99 vs. 78%; p = 0.003), lymph node dissection (41 vs. 15%; p = 0.005) and therapy with radioactive iodine (96 vs. 73%; p = 0.002). Tumor stage was similar in both groups (p = 0.237), with a higher number of T3 cases in the group B (24 vs. 5%; p = 0.009). After a mean follow-up of 90 ± 68.95 months, the oncological results were similar, with a similar disease persistence rate (9 vs. 5%; p = 0.337), disease recurrence rate (21 vs. 8%; p = 0.159) and disease-free survival (p = 0.075). CONCLUSIONS Unicentric FPTMC should not be considered as a SPTMC due to its prognosis is similar to multicentric FPTMC.
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Heavy Metal and Rice in Gluten-Free Diets: Are They a Risk?
Bascuñán, KA, Orosteguí, C, Rodríguez, JM, Roncoroni, L, Doneda, L, Elli, L, Araya, M
Nutrients. 2023;(13)
Abstract
A gluten-free diet (GFD) is the treatment of choice for gluten-related disorders. It has been associated with macro- and micronutrient deficiencies. Recently, consumption of arsenic-contaminated rice has raised concern because of the potential greater risk that it may represent for people on GFDs, whose rice consumption is high, since it is a fundamental cereal in GFDs. We reviewed the data published over the last 20 years in Medline and Scielo, in English, French and Spanish, on four metals (As, Hg, Cd, and Pb), to assess whether the evidence suggests that celiac disease or consumption of a GFD is associated with increased levels of blood/urinary metal concentrations. The review revealed a few articles that were directly related to the four metals and their relationships with a GFD. The evidence supports that rice-based products are a relevant source of As and other metals. Clinical studies and evaluations based on NHANES have indicated that persons on GFDs have higher As and Hg blood/urinary levels, suggesting that the diet and not the disease is responsible for it. The levels described are statistically significant compared to those of persons on complete diets, but far from toxic levels. The question of whether higher exposure to heavy metals associated with a GFD is biologically relevant remains unanswered and deserves study.
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A randomized pilot trial assessing the reduction of gout episodes in hyperuricemic patients by oral administration of Ligilactobacillus salivarius CECT 30632, a strain with the ability to degrade purines.
Rodríguez, JM, Garranzo, M, Segura, J, Orgaz, B, Arroyo, R, Alba, C, Beltrán, D, Fernández, L
Frontiers in microbiology. 2023;:1111652
Abstract
INTRODUCTION Hyperuricemia and gout are receiving an increasing scientific and medical attention because of their relatively high prevalence and their association with relevant co-morbidities. Recently, it has been suggested that gout patients have an altered gut microbiota. The first objective of this study was to investigate the potential of some Ligilactobacillus salivarius strains to metabolize purine-related metabolites. The second objective was to evaluate the effect of administering a selected potential probiotic strain in individuals with a history of hyperuricemia. METHODS Inosine, guanosine, hypoxanthine, guanine, xanthine, and uric acid were identified and quantified by high-performance liquid chromatography analysis. The uptake and biotransformation of these compounds by a selection of L. salivarius strains were assessed using bacterial whole cells and cell-free extracts, respectively. The efficacy of L. salivarius CECT 30632 to prevent gout was assessed in a pilot randomized controlled clinical trial involving 30 patients with hyperuricemia and a history of recurrent gout episodes. Half of the patients consumed L. salivarius CECT 30632 (9 log10 CFU/day; probiotic group; n = 15) for 6 months while the remaining patients consumed allopurinol (100-300 mg/daily; control group; n = 15) for the same period. The clinical evolution and medical treatment received by the participants were followed, as well as the changes in several blood biochemical parameters. RESULTS L. salivarius CECT 30632 was the most efficient strain for inosine (100%), guanosine (100%) and uric acid (50%) conversion and, therefore, it was selected for the pilot clinical trial. In comparison with the control group, administration of L. salivarius CECT 30632 resulted in a significant reduction in the number of gout episodes and in the use of gout-related drugs as well as an improvement in some blood parameters related to oxidative stress, liver damage or metabolic syndrome. CONCLUSION Regular administration of L. salivarius CECT 30632 reduced serum urate levels, the number of gout episodes and the pharmacological therapy required to control both hyperuricemia and gout episodes in individuals with a history of hyperuricemia and suffering from repeated episodes of gout.
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Use of N-Acetylcysteine at high doses as an oral treatment for patients hospitalized with COVID-19.
Izquierdo, JL, Soriano, JB, González, Y, Lumbreras, S, Ancochea, J, Echeverry, C, Rodríguez, JM
Science progress. 2022;(1):368504221074574
Abstract
Infection by SARS-CoV-2 causing coronavirus disease 2019 (COVID-19) can be associated with serious and life-threatening conditions, including acute respiratory distress syndrome (ARDS). Severity and mortality have been related to a cytokine storm, an imbalance of oxidative stress, and a pro-thrombotic state.We conducted an observational retrospective cohort study from a community-based large population of hospitalized COVID-19 PCR + patients admitted from March 01, 2020, to January 24, 2021, with integrated primary to tertiary care information in Castilla la Mancha, Spain. We explored the potential benefits of the antioxidant, anti-inflammatory and anti-thrombotic drug N-acetylcysteine (NAC) administered orally in high doses (600 mg every 8 h), added to standard of care in COVID-19 patients by using the free text information contained in their electronic health records (EHRs).Out of 19,208 patients with a diagnosis of COVID-19 hospitalized, we studied 2071 (10.8%) users of oral NAC at high doses. COVID-19 patients treated with NAC were older, predominantly male, and with more comorbidities such as hypertension, dyslipidemia, diabetes, and COPD when compared with those not on NAC (all p < 0.05). Despite greater baseline risk, use of NAC in COVID-19 patients was associated with significantly lower mortality (OR 0.56; 95%CI 0.47-0.67), a finding that remained significant in a multivariate analysis adjusting by baseline characteristics and concomitant use of corticosteroids. There were no significant differences with the use of NAC on the mean duration of hospitalization, admission to the intensive care unit or use of invasive mechanical ventilation. The observed association signaling to better relevant outcomes in COVID-19 patients treated with NAC at high doses should be further explored in other settings and populations and in randomized controlled trials.
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The Gut‒Breast Axis: Programming Health for Life.
Rodríguez, JM, Fernández, L, Verhasselt, V
Nutrients. 2021;(2)
Abstract
The gut is a pivotal organ in health and disease. The events that take place in the gut during early life contribute to the programming, shaping and tuning of distant organs, having lifelong consequences. In this context, the maternal gut plays a quintessence in programming the mammary gland to face the nutritional, microbiological, immunological, and neuroendocrine requirements of the growing infant. Subsequently, human colostrum and milk provides the infant with an impressive array of nutrients and bioactive components, including microbes, immune cells, and stem cells. Therefore, the axis linking the maternal gut, the breast, and the infant gut seems crucial for a correct infant growth and development. The aim of this article is not to perform a systematic review of the human milk components but to provide an insight of their extremely complex interactions, which render human milk a unique functional food and explain why this biological fluid still truly remains as a scientific enigma.
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Ligilactobacillus salivarius PS2 Supplementation during Pregnancy and Lactation Prevents Mastitis: A Randomised Controlled Trial.
Jiménez, E, Manzano, S, Schlembach, D, Arciszewski, K, Martin, R, Ben Amor, K, Roelofs, M, Knol, J, Rodríguez, JM, Abou-Dakn, M, et al
Microorganisms. 2021;(9)
Abstract
Mastitis is considered one of the main reasons for unwanted breastfeeding cessation. This study aimed to investigate the preventive effect of the probiotic strain Ligilactobacillus salivarius PS2 on the occurrence of mastitis in lactating women. In this multicountry, multicenter, randomized, double-blind, placebo-controlled trial, 328 women were assigned to the probiotic or the placebo group. The intervention started from the 35th week of pregnancy until week 12 post-partum. The primary outcome was the incidence (hazard) rate of mastitis, defined as the presence of at least two of the following symptoms: breast pain, breast erythema, breast engorgement not relieved by breastfeeding, and temperature > 38 °C. The probability of being free of mastitis during the study was higher in the probiotic than in the placebo group (p = 0.022, Kaplan-Meier log rank test) with 9 mastitis cases (6%) vs. 20 mastitis cases (14%), respectively. The hazard ratio of the incidence of mastitis between both study groups was 0.41 (0.190-0.915; p = 0.029), indicating that women in the probiotic group were 58% less likely to experience mastitis. In conclusion, supplementation of L. salivarius PS2 during late pregnancy and early lactation was safe and effective in preventing mastitis, which is one of the main barriers for continuing breastfeeding.
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Gut microbes and health.
Álvarez, J, Fernández Real, JM, Guarner, F, Gueimonde, M, Rodríguez, JM, Saenz de Pipaon, M, Sanz, Y
Gastroenterologia y hepatologia. 2021;(7):519-535
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Abstract
The human body is populated by myriads of microorganisms throughout its surface and in the cavities connected to the outside. The microbial colonisers of the intestine (microbiota) are a functional and non-expendable part of the human organism: they provide genes (microbiome) and additional functions to the resources of our species and participate in multiple physiological processes (somatic development, nutrition, immunity, etc.). Some chronic non-communicable diseases of developed society (atopias, metabolic syndrome, inflammatory diseases, cancer and some behaviour disorders) are associated with dysbiosis: loss of species richness in the intestinal microbiota and deviation from the ancestral microbial environment. Changes in the vertical transmission of the microbiome, the use of antiseptics and antibiotics, and dietary habits in industrialised society appear to be at the origin of dysbiosis. Generating and maintaining diversity in the microbiota is a new clinical target for health promotion and disease prevention.
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The Microbiota of the Human Mammary Ecosystem.
Fernández, L, Pannaraj, PS, Rautava, S, Rodríguez, JM
Frontiers in cellular and infection microbiology. 2020;:586667
Abstract
Human milk contains a dynamic and complex site-specific microbiome, which is not assembled in an aleatory way, formed by organized microbial consortia and networks. Presence of some genera, such as Staphylococcus, Streptococcus, Corynebacterium, Cutibacterium (formerly known as Propionibacterium), Lactobacillus, Lactococcus and Bifidobacterium, has been detected by both culture-dependent and culture-independent approaches. DNA from some gut-associated strict anaerobes has also been repeatedly found and some studies have revealed the presence of cells and/or nucleic acids from viruses, archaea, fungi and protozoa in human milk. Colostrum and milk microbes are transmitted to the infant and, therefore, they are among the first colonizers of the human gut. Still, the significance of human milk microbes in infant gut colonization remains an open question. Clinical studies trying to elucidate the question are confounded by the profound impact of non-microbial human milk components to intestinal microecology. Modifications in the microbiota of human milk may have biological consequences for infant colonization, metabolism, immune and neuroendocrine development, and for mammary health. However, the factors driving differences in the composition of the human milk microbiome remain poorly known. In addition to colostrum and milk, breast tissue in lactating and non-lactating women may also contain a microbiota, with implications in the pathogenesis of breast cancer and in some of the adverse outcomes associated with breast implants. This and other open issues, such as the origin of the human milk microbiome, and the current limitations and future prospects are addressed in this review.
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Human Milk Microbiota: Origin and Potential Uses.
Fernández, L, Rodríguez, JM
Nestle Nutrition Institute workshop series. 2020;:75-85
Abstract
At the beginning of the 21st century, some pioneer studies provided evidence of the existence of a site-specific human milk microbiota. Hygienically collected milk samples from healthy women contain a relatively low bacterial load, which consist mostly of Staphylococcus, Streptococcus, lactic acid bacteria, and other gram-positive bacteria (Corynebacterium, Propionibacterium, and Bifidobacterium). DNA from strict anaerobic bacteria is also detected in human milk samples. The origin of human milk bacteria still remains largely unknown. Although the infant's oral cavity and maternal skin may provide microbes to milk, selected bacteria of the maternal digestive microbiota may access the mammary glands through oral- and enteromammary pathways involving interactions with immune cells. In addition, when milk is collected using external devices, such as breast pumps, some microorganisms may arise from unhygienic handling as well as from the water used to clean and rinse the devices, for example. The human milk microbiota has a wide spectrum of potential uses. Most of them have been focused on the infant (including the preterm ones), but some bacterial strains present in human milk have also a big potential to be used to improve the mother's health, mainly through the prevention or treatment of infectious mastitis during lactation.