Biomarkers in Glycogen Storage Diseases: An Update.

Glycogen storage diseases (GSDs) are a group of 19 hereditary diseases caused by a lack of one or more enzymes involved in the synthesis or degradation of glycogen and are characterized by deposits or abnormal types of glycogen in tissues. Their frequency is very low and they are considered rare diseases. Except for X-linked type IX, the different types are inherited in an autosomal recessive pattern. In this study we reviewed the literature from 1977 to 2020 concerning GSDs, biomarkers, and metabolic imbalances in the symptoms of some GSDs. Most of the reported studies were performed with very few patients. Classification of emerging biomarkers between different types of diseases (hepatics GSDs, McArdle and PDs and other possible biomarkers) was done for better understanding. Calprotectin for hepatics GSDs and urinary glucose tetrasaccharide for Pompe disease have been approved for clinical use, and most of the markers mentioned in this review only need clinical validation, as a final step for their routine use. Most of the possible biomarkers are implied in hepatocellular adenomas, cardiomyopathies, in malfunction of skeletal muscle, in growth retardation, neutropenia, osteopenia and bowel inflammation. However, a few markers have lost interest due to a great variability of results, which is the case of biotinidase, actin alpha 2, smooth muscle, aorta and fibroblast growth factor receptor 4. This is the first review published on emerging biomarkers with a potential application to GSDs.

Candida infections in patients with psoriasis and psoriatic arthritis treated with interleukin-17 inhibitors and their practical management.

INTRODUCTION: Interleukin 17A (IL-17A) is a pro-inflammatory cytokine produced by helper T cells (Th17) and other cells of the immune system and exerts pleiotropic effects on multiple cell lines. The role of IL-17 in the pathogenesis of numerous inflammatory disorders is well-documented. IL-17 activates signaling through the IL-17 receptor, which induces other proinflammatory cytokines, antimicrobial peptides, and neutrophil chemokines that are important for antifungal activity. EVIDENCE ACQUISITION: Healthy levels of IL-17 can protect the host against extracellular bacterial and fungal infections in mucous membranes and epithelia. IL-17 deficiency reduces control of certain infections, while excessive IL-17 can produce unwanted inflammatory effects. EVIDENCE SYNTHESIS: Although the efficacy of the therapeutic blockade of this cytokine has been proven in several autoimmune diseases such as psoriasis and psoriatic arthritis, this strategy could also exacerbate fungal infections in such patients. Therefore, a better understanding of IL-17-mediated immunity to Candida is necessary for the development of autoimmune therapeutics that maintain antifungal immunity. CONCLUSIONS: In this review, we include a study of the new anti-IL-17 biological agents (secukinumab, ixekizumab, and bromalizumab) used for moderate-to-severe psoriasis and psoriatic arthritis treatment in clinical practice, as well as pivotal trials with bimekizumab. We study the relationship of these biological agents and the appearance of candidiasis in its various clinical forms.

Pathogenesis and Clinical Relevance of Candida Biofilms in Vulvovaginal Candidiasis.

The ability of Candida spp. to form biofilms is crucial for its pathogenicity, and thus, it should be considered an important virulence factor in vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC). Its ability to generate biofilms is multifactorial and is generally believed to depend on the site of infection, species and strain involved, and the microenvironment in which the infection develops. Therefore, both cell surface proteins, such as Hwp1, Als1, and Als2, and the cell wall-related protein, Sun41, play a critical role in the adhesion and virulence of the biofilm. Immunological and pharmacological approaches have identified the NLRP3 inflammasome as a crucial molecular factor contributing to host immunopathology. In this context, we have earlier shown that Candida albicans associated with hyphae-secreted aspartyl proteinases (specifically SAP4-6) contribute to the immunopathology of the disease. Transcriptome profiling has revealed that non-coding transcripts regulate protein synthesis post-transcriptionally, which is important for the growth of Candida spp. Other studies have employed RNA sequencing to identify differences in the 1,245 Candida genes involved in surface and invasive cellular metabolism regulation. In vitro systems allow the simultaneous processing of a large number of samples, making them an ideal screening technique for estimating various physicochemical parameters, testing the activity of antimicrobial agents, and analyzing genes involved in biofilm formation and regulation (in situ) in specific strains. Murine VVC models are used to study C. albicans infection, especially in trials of novel treatments and to understand the cause(s) for resistance to conventional therapeutics. This review on the clinical relevance of Candida biofilms in VVC focuses on important advances in its genomics, transcriptomics, and proteomics. Moreover, recent experiments on the influence of biofilm formation on VVC or RVVC pathogenesis in laboratory animals have been discussed. A clear elucidation of one of the pathogenesis mechanisms employed by Candida biofilms in vulvovaginal candidiasis and its applications in clinical practice represents the most significant contribution of this manuscript.

Biomarkers of Inflammation in Obesity-Psoriatic Patients.

Psoriasis is a common chronic inflammatory multisystemic disease with a complex pathogenesis consisting of genetic, immunological, and environmental components. It is associated with a number of comorbidities, including diabetes, metabolic syndrome, obesity, and myocardial infarction. In addition, the severity of psoriasis seems to be related to the severity of obesity. Patients with higher levels of obesity show poorer response to systemic treatments of psoriasis. Several studies have demonstrated that white adipose tissue is a crucial site of the formation of proinflammatory adipokines such as leptin, adiponectin, and resistin and classical cytokines such as interleukin- (IL-) 6 and tumour necrosis factor-α. In psoriasis, due to the proliferation of Th1, Th17, and Th22 cells, IL-22, among others, is produced in addition to the abovementioned cytokines. With respect to leptin and resistin, both of these adipokines are present in high levels in obese persons with psoriasis. Further, the plasma levels of leptin and resistin are related to the severity of psoriasis. These results strongly suggest that obesity, through proinflammatory pathways, is a predisposing factor to the development of psoriasis and that obesity aggravates existing psoriasis. Different inflammatory biomarkers link psoriasis and obesity. In this paper, the most important ones are described.

Myxoid liposarcoma associated with adalimumab treatment: A case report.

Biological agents that suppress inflammation, such as tumour necrosis factor (TNF-α) inhibitors, are being successfully used at an increasing frequency for the treatment of chronic inflammatory diseases, such as psoriasis. However, these drugs are not free of side effects, and although the general rates of malignancy in patients using anti-TNF-α therapies are not high, certain tumours of cutaneous origin, particularly carcinomas, have been reported. We herein present the case of a 47-year-old female patient with moderate-to-severe psoriasis for 20 years under treatment with adalimumab administered at the standard dose of 40 mg, injected subcutaneously each fortnight, with good efficacy. To the best of our knowledge, this is the first reported case of a low-grade (grade 1) myxoid liposarcoma in a patient receiving treatment with adalimumab since 2009. A review of the relevant literature was also conducted. Continuous investigation of such cases is crucial in order to elucidate the iatrogenic risk of rare cancers, such as myxoid liposarcoma, in patients undergoing treatment with currently available as well as future biological therapies.

Effect of VSL#3 Probiotic in a Patient with Glycogen Storage Disease Type Ia and Irritable Bowel Disease-like Disease.

Gut Inflammatory bowel disease (IBD) is a group of chronic gastrointestinal disorders characterised by relapsing and remitting inflammation of the gastrointestinal tract. The two most common types of IBDs are ulcerative colitis and Crohn's disease. Patients with glycogen storage disease (GSD) type Ia present with gastrointestinal symptoms such as recurrent abdominal pain, bloating and changes in stool form or frequency, which is clinically difficult to distinguish from IBD. We report the case of a 36-year-old man with GSD type Ia and IBD-like disease. A commercial probiotic (VSL#3®) was chosen as a nutritional supplement treatment because of its high content of microbial species and strains. Three different tests were performed: normal-dose, no-dose and half-dose tests. The study periods for the normal-dose, no-dose and half-dose tests were 4 weeks from the treatment initiation, 72 h from the end of the previous period and 4 weeks to 6 months after the end of the 72-h period, respectively. When the probiotic treatment was stopped, he experienced several symptoms similar to those before the start of the treatment. The intestinal symptoms were less severe with the half-dose nutritional supplement treatment than with no treatment. Probiotics may reduce the number of irritable gut episodes and improve the patient's well-being and overall quality of life. More studies are needed to determine whether the improvement in more severe cases of GSD is due mainly to changes in the composition of the gut microbiota, as in this patient.

Interleukin-2 and other cytokines in candidiasis: expression, clinical significance, and future therapeutic targets.

Susceptibility to Candida spp. infection is largely determined by the status of host immunity, whether immunocompromised/immunodeficient or immunocompetent. Interleukin-2 (IL-2), a potent lymphoid cell growth factor, is a four-α-helix bundle cytokine induced by activated T cells with two important roles: the activation and maintenance of immune responses, and lymphocyte production and differentiation. We reviewed the roles of cytokines as immune stimulators and suppressors of Candida spp. infections as an update on this continuously evolving field. We performed a comprehensive search of the Cochrane Central Register of Controlled Trials, Medline (PubMed), and Embase databases for articles published from March 2010 to March 2016 using the following search terms: interleukins, interleukin-2, Candida spp., and immunosuppression. Data from our own studies were also reviewed. Here, we provide an overview focusing on the ability of IL-2 to induce a large panel of trafficking receptors in skin inflammation and control T helper (Th)2 cytokine production in response to contact with Candida spp. Immunocompromised patients have reduced capacity to secrete Th1-related cytokines such as IL-2. The ability to secrete the Th1-related cytokine IL-2 is low in immunocompromised patients. This prevents an efficient Th1 immune response to Candida spp. antigens, making immunocompromised patients more susceptible to candidal infections.

Recent advances in melanoma research via "omics" platforms.

Melanoma has a high mortality rate and metastatic melanoma is highly resistant to conventional therapies. "Omics" fields such as proteomics and microRNA and exosome studies have provided new knowledge to complement the information generated by genomic studies. This work aimed to review the current status of biomarker discovery for melanoma through multi-"omics" platforms. A few sets of novel microRNAs and proteins are described, some of them with important implications in suppressing melanoma at different stages. Upregulation of genes involved in angiogenesis, immunosuppressive factors, modification of stroma, capture of melanoma cells in lymph nodes and factors responsible for tumour cell recruitment have been identified in exosomes, among molecules with other functions. A remarkable series of proteins involved in epithelial-mesenchymal/mesenchymal-epithelial transitions, inflammation, motility, proliferation and progression processes, centrosome amplification, aneuploidy, inhibition of CD8+ effector T-cells, and metastasis in general were identified. Genomic and protein-protein interactions or metabolome levels were not analysed. Proteomics tools such as Orbitrap shotgun mass spectrometry or deep mining proteomic analysis utilizing high-resolution reversed phase nanoseparation in combination with mass spectrometry are also discussed. The application of these tools together with bioinformatics approaches applied to the clinical setting will enable the implementation of personalized medicine in the near future.

Advances in Immunotherapy for Melanoma: A Comprehensive Review.

Melanomas are tumors originating from melanocytes and tend to show early metastasis secondary to the loss of cellular adhesion in the primary tumor, resulting in high mortality rates. Cancer-specific active immunotherapy is an experimental form of treatment that stimulates the immune system to recognize antigens on the surface of cancer cells. Current experimental approaches in immunotherapy include vaccines, biochemotherapy, and the transfer of adoptive T cells and dendritic cells. Several types of vaccines, including peptide, viral, and dendritic cell vaccines, are currently under investigation for the treatment of melanoma. These treatments have the same goal as drugs that are already used to stimulate the proliferation of T lymphocytes in order to destroy tumor cells; however, immunotherapies aim to selectively attack the tumor cells of each patient. In this comprehensive review, we describe recent advancements in the development of immunotherapies for melanoma, with a specific focus on the identification of neoantigens for the prediction of their elicited immune responses. This review is expected to provide important insights into the future of immunotherapy for melanoma.

[Application of an obesity treatment protocol for 2 years]. / Aplicación de un protocolo de tratamiento de obesidad durante 2 años.

OBJECTIVE: To evaluate the effectiveness of a clinic protocol used in the Complexo Hospitalario Universitario de Vigo (CHUVI) for obese outpatients. PATIENTS AND METHODS: The study included 47 obese outpatients. All of them were evaluated in clinical department and applied the obesity protocol for a period of 2 years. Variables as weight, BMI and levels of obesity in the initial and final time were evaluated. RESULTS AND DISCUSSION: In obese patients between 26 and 65 years was observed a tendency to reduce their degree of obesity, with significant differences in 2012 compared to 2010. There are differences in behavior between men and women in terms of change in obesity graduation. CONCLUSIONS: In our study we found differences in behavior between men and women in terms of grade change in obesity, in women there is a greater tendency to reduce.

Objetivo: Evaluar la eficacia de un protocolo clínico para pacientes obesos utilizado en la consulta de obesidad del Complexo Hospitalario Universitario de Vigo (CHUVI). Pacientes y métodos: En el estudio participaron 47 pacientes procedentes de la consulta de obesidad del CHUVI. Todos ellos fueron evaluados en consulta y siguieron el protocolo de obesidad durante un periodo de 2 años. Se evaluaron variables como el peso, el IMC y los grados de obesidad en el momento inicial y final. Resultados y discusión: En pacientes obesos entre 26 y 65 años se observa una tendencia a disminuir su grado de obesidad, con diferencias significativas en el 2012 respecto al 2010. Hay diferencias de comportamiento entre hombres y mujeres en cuanto al cambio de graduación en la obesidad. Conclusiones: En nuestro estudio hemos comprobado diferencias de comportamiento entre hombres y mujeres en cuanto al cambio de graduación en la obesidad; en las mujeres hay una mayor tendencia a reducirlo.

Design and development of a nutritional assessment application for smartphones and tablets with Android OS.

BACKGROUND & AIMS: To design and develop a nutritional application for smartphones and tablets with Android operating system for using to in- and outpatients that need a nutritional assessment. To check the validity of the results of such software. METHODS: The application was compiled for version 2.1 of the Android operating system from Google. A cohort of 30 patients was included for evaluating the reliability of the application. The calculations were performed by staff of the Nutrition Unit of the Complexo Hospitalario Universitario de Vigo, manually and through e-Nutrimet software on a smartphone and a tablet. RESULTS: Concordance was absolute between results of different methods obtained using e-Nutrimet on a smartphone and a tablet (Fleiss index κ= 1). The same level of concordance was obtained by comparing handmade and e-Nutrimet made results. CONCLUSIONS: The degree of correlation is good, and it would be extended to all healthcare staff who wants to determine whether a patient has malnutrition, or not. The nutritional assessment software e-Nutrimet does not replace healthcare staff in any case, but could be an important aid in assessing patients who may be in risk of malnutrition, saving time of evaluation.

Introducción y objetivos: Diseñar y desarrollar una aplicación nutricional para smartphones y tablets con Sistema operativo Android® para realizar las valoraciones nutricionales de pacientes ambulatorios y hospitalizados. Verificar y comprobar la validez de los resultados de la aplicación. Métodos: La aplicación se compile para la versión 2.1 del Sistema operativo Android® de Google®. Para evaluar la fiabilidad de la aplicación se incluyeron a 30 pacientes, a los que se le realizó una valoración nutricional. Todos los cálculos fueron efectuados por personal de la Unidad de Nutrición del Complexo Hospitalario Universitario de Vigo, de forma manual y a través del software e-Nutrimet ©, tanto usando un Smartphone como una tablet. Resultados: Se obtuvo una concordancia absoluta entre los resultados de los diferentes métodos obtenidos utilizando la aplicación e-Nutrimet© en smartphones y en tablets (Fleiss index = 1). El mismo nivel de concordancia se obtuvo comparando el método manual como el automatizado mediante el software e-Nutrimet©. Conclusiones: El grado de correlación es muy bueno, permitiendo extender la valoración nutricional usando e-Nutrimet© a todo el personal sanitario que quiera determinar si un paciente presenta malnutrición o no. La aplicación de valoración nutricional e-Nutrimet© no sustituye al personal sanitario en ningún caso, pero podría ser de gran ayuda a la hora de valorar pacientes que pudieran estar en riesgo de malnutrición, ahorrando tiempo en estas valoraciones.