Enzymatic biomarkers of oxidative stress in patients with depressive disorders. A systematic review.

Oxidative stress (OS) results from the imbalance between the production of reactive oxygen species and the body's antioxidant mechanisms and is associated with various diseases, including depression. Antioxidants protect cells by neutralizing free radicals and include enzymatic components such as superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), glutathione reductase (GR), and glutathione S-transferase (GST). The concentration of these biomarkers can quantify OS. This research aimed to gather available information published in the last ten years about the concentration of enzymatic OS biomarkers in samples from patients with depressive disorders. METHOD: A systematic review was conducted following the PRISMA guidelines, including original scientific articles that evaluated enzymatic OS biomarkers in participants with depressive disorders, using the keywords and boolean operators "superoxide dismutase" OR "catalase" OR "glutathione" AND "depress*" in the databases PubMed, SAGE Journals, DOAJ, Scielo, Dialnet, and Redalyc. RESULTS: The initial search showed 614 results, with only 28 articles meeting the selection criteria. It was observed that all evaluated oxidative stress enzymatic markers showed a significant increase or decrease in patients with depressive disorders, due to a wide variability in the depressive disorders studied, the type of biological sample analyzed, and the techniques used. CONCLUSION: There is evidence of the relationship between enzymatic OS biomarkers and depressive disorders, but additional studies are needed to clarify the nature of this relationship, particularly considering the different types of depressive disorders.

Clinical standards for the diagnosis and management of asthma in low- and middle-income countries.

BACKGROUND: The aim of these clinical standards is to aid the diagnosis and management of asthma in low-resource settings in low- and middle-income countries (LMICs).METHODS: A panel of 52 experts in the field of asthma in LMICs participated in a two-stage Delphi process to establish and reach a consensus on the clinical standards.RESULTS: Eighteen clinical standards were defined: Standard 1, Every individual with symptoms and signs compatible with asthma should undergo a clinical assessment; Standard 2, In individuals (>6 years) with a clinical assessment supportive of a diagnosis of asthma, a hand-held spirometry measurement should be used to confirm variable expiratory airflow limitation by demonstrating an acute response to a bronchodilator; Standard 3, Pre- and post-bronchodilator spirometry should be performed in individuals (>6 years) to support diagnosis before treatment is commenced if there is diagnostic uncertainty; Standard 4, Individuals with an acute exacerbation of asthma and clinical signs of hypoxaemia or increased work of breathing should be given supplementary oxygen to maintain saturation at 94-98%; Standard 5, Inhaled short-acting beta-2 agonists (SABAs) should be used as an emergency reliever in individuals with asthma via an appropriate spacer device for metered-dose inhalers; Standard 6, Short-course oral corticosteroids should be administered in appropriate doses to individuals having moderate to severe acute asthma exacerbations (minimum 3-5 days); Standard 7, Individuals having a severe asthma exacerbation should receive emergency care, including oxygen therapy, systemic corticosteroids, inhaled bronchodilators (e.g., salbutamol with or without ipratropium bromide) and a single dose of intravenous magnesium sulphate should be considered; Standard 8, All individuals with asthma should receive education about asthma and a personalised action plan; Standard 9, Inhaled medications (excluding dry-powder devices) should be administered via an appropriate spacer device in both adults and children. Children aged 0-3 years will require the spacer to be coupled to a face mask; Standard 10, Children aged <5 years with asthma should receive a SABA as-needed at step 1 and an inhaled corticosteroid (ICS) to cover periods of wheezing due to respiratory viral infections, and SABA as-needed and daily ICS from step 2 upwards; Standard 11, Children aged 6-11 years with asthma should receive an ICS taken whenever an inhaled SABA is used; Standard 12, All adolescents aged 12-18 years and adults with asthma should receive a combination inhaler (ICS and rapid onset of action long-acting beta-agonist [LABA] such as budesonide-formoterol), where available, to be used either as-needed (for mild asthma) or as both maintenance and reliever therapy, for moderate to severe asthma; Standard 13, Inhaled SABA alone for the management of patients aged >12 years is not recommended as it is associated with increased risk of morbidity and mortality. It should only be used where there is no access to ICS.The following standards (14-18) are for settings where there is no access to inhaled medicines. Standard 14, Patients without access to corticosteroids should be provided with a single short course of emergency oral prednisolone; Standard 15, Oral SABA for symptomatic relief should be used only if no inhaled SABA is available. Adjust to the individual's lowest beneficial dose to minimise adverse effects; Standard 16, Oral leukotriene receptor antagonists (LTRA) can be used as a preventive medication and is preferable to the use of long-term oral systemic corticosteroids; Standard 17, In exceptional circumstances, when there is a high risk of mortality from exacerbations, low-dose oral prednisolone daily or on alternate days may be considered on a case-by-case basis; Standard 18. Oral theophylline should be restricted for use in situations where it is the only bronchodilator treatment option available.CONCLUSION: These first consensus-based clinical standards for asthma management in LMICs are intended to help clinicians provide the most effective care for people in resource-limited settings.

Role of selected salivary inflammatory cytokines in the diagnosis and prognosis of oral squamous cell carcinoma. A Systematic Review and Meta-analysis.

BACKGROUND: Oral squamous cell carcinoma (OSCC) is gradually increasing its incidence in our society. Unfortunately, this entity is diagnosed at an advanced stage in most patients, a fact that implies greater difficulty in its treatment and a worse prognosis. This systematic review aims to assess whether the cytokines IL-6, IL-8 and TNF-α are potential salivary biomarkers that allow early diagnosis of cancer. MATERIAL AND METHODS: An electronic search was performed in three databases (Pubmed, Scopus and Web of Science). We used the following keywords: "salivary cytokines", "saliva cytokines", "salivary interleukins", "biomarkers", "oral squamous cell carcinoma" and "diagnosis", combined with the Boolean operators "AND" and "OR". RESULTS: 128 publications were found and finally 23 articles were included in the review and 15 in the meta-analysis. It has been observed that the majority of OSCC patients express higher salivary concentrations of IL-6, IL-8 and TNF-α compared to the control (CL) and premalignant lesion (OPML) groups. It has also been observed that the different premalignant lesions do not have statistically significant differences in the salivary concentration of the cytokines, and on the other hand, differences have been observed between the different TNM stages. The meta-analysis has shown that the difference in concentration of IL-6, IL-8 and TNF-α is statistically significant between the CL group and the OSCC, and also between the CL group and OPML. CONCLUSIONS: There is sufficient evidence to affirm that IL-6, IL-8 and TNF-α are useful salivary cytokines in the early diagnosis and prognosis of OSCC. Although future studies are necessary to establish greater reliability of these biomarkers and thus be able to develop a valid diagnostic test.

Diabetes mellitus: Lessons from COVID-19 for monkeypox infection.

BACKGROUND AND AIMS: Type 2 Diabetes Mellitus is known to be linked to malfunctioning antiviral defense; however, its association with the severity of monkeypox is poorly understood. In this review, we discuss key immunological mechanisms in the antiviral response affected by poor glucose control that could impact the susceptibility and severity of monkeypox infection, leading to a heightened emphasis on the use of the available antidiabetic drugs. METHODS: We searched PubMed and Google scholar for articles published from January 1985 to August 2022. No criteria for publication data were set, and all articles in English were included. RESULTS: Currently, there are no studies about the risk or consequences of monkeypox infection in the diabetic population. A high incidence of diabetes is reported in countries such as China, India, Pakistan, EUA, Indonesia, Brazil, Mexico, Bangladesh, Japan, and Egypt, where unfortunately imported cases of monkeypox have been reported and the infection continues to spread. CONCLUSIONS: High incidence of diabetes together with the cessation of smallpox vaccination has left large numbers of the human population unprotected against monkeypox. The best option for the population remains confined to the prevention of infection as well as the use of hypoglycemic agents that have also been shown to improve immune mechanisms associated with viral protection.

Treatment of recurrent aphtous stomatitis: A systematic review.

BACKGROUND: Recurrent Aphtous Stomatitis (RAS) is the most common process affecting the oral mucosa. It is painful, multifactorial and generally recurrent. The aim of this systematic review is to know the last treatment approaches and their effectivity. MATERIAL AND METHODS: we compared the outcome of different kind of treatments in terms of the improvement of the lesions, reduction of the size of those lesions and the time needed for their healing. Inclusion criteria were: clinical trials, articles written in English or Spanish and published less than 5 years ago. RESULTS: we used the following keywords: "treatment", "aphtous stomatitis", "canker sores"; combined with Boolean operators AND y OR. We selected 28 articles for reading the whole text, and after applying the eligibility criteria, we selected 17 articles for our revision. Among all the treatments, we emphasize the barrier method based in compound of cellulose rubber and a calcium/sodium copolymer PVM/MA, with which the difference in the 3rd and 7th day was of -6,29 ± 0,14 points in the pain score. The treatment with insulin and chitosan gel, brought a pain suppression on the third day, with no reactivation of the pain during the whole study. The application of a film composed of polyurethane and sesame oil with chitosan, brought a reduction in the size of the lesions of 4,54 ± 2,84mm on the 6th day compared with the situation before the beginning of the treatment. The different kinds of laser, which produced a reduction in the pain score just at the beginning of the treatment up to 8,1 ± 1,6 points, and a reduction of the size of the lesions of 4,42 ± 1,02mm on the 7th day. CONCLUSIONS: Besides the classic treatments for RAS, we have to take into account other treatment modalities, above all the different kinds of laser.

Incidence rate of metastases in the oral cavity: a review of all metastatic lesions in the oral cavity.

BACKGROUND: Metastases in the oral cavity are rare and account for only 1 to 3% of all malignant lesions in this area. The primary location from which most metastases have been described in the oral cavity in adult patients include lungs, breasts, kidneys and colon. MATERIAL AND METHODS: A systematic search of the literature was carried out following the PRISMA statement in PubMed database. Clinical trials and case series published in the last 10 years [2010-2020] were eligible to be selected. The headings and keywords used in the searches were "cancer" AND "oral metastases", "incidence" AND "oral metastases", "oral metastases" AND "jaw bone", "oral metastases" AND "soft tissue". RESULTS: For the study of the incidence of metastases in the oral cavity, 9 reports of clinical trials and 7 retrospective studies of case series have been included in this article. The primary locations from which more metastases have been described in the oral cavity are lungs (30.6% or 183 cases), breasts (22.2% or 133 cases), liver (15.5% or 93 cases), prostate (9 % or 54 cases), thyroid glands (8.1% or 49 cases), kidneys (7.3% or 44 cases), skin (2.3% or 14 cases), soft tissues (2% or 12 cases), colon (2% or 12 cases) and gastrointestinal (0.6% or 4 cases). These metastases have a predilection for hard tissues. The clinical presentation of these lesions varies from painless granulomatous lesions to lytic areas in the jaws. CONCLUSIONS: Although metastases in the oral cavity is an uncommon pathology, early diagnosis is needed so that in the event that it is the first manifestation, it allows the primary tumor to be diagnosed as soon as possible.

Update and optimization of active surveillance in prostate cancer in 2021. / Actualización y optimización de la vigilancia activa en cáncer de próstata en 2021.

INTRODUCTION AND OBJECTIVES: Within the paradigm shift of the last decade in the management of prostate cancer (PCa), perhaps the most relevant event has been the emergence of active surveillance (AS) as a mandatory strategy in low-risk disease. We carry out a critical review of the clinical, pathological and radiological improvements that allow optimizing AS in 2021. MATERIAL AND METHODS: Critical narrative review of the literature on improvement issues and controversial aspects of AS. RESULTS: Adequate use of traditional criteria, optimized by enhanced biopsy and calculation of the prostate volume technique thanks to multiparametric magnetic resonance imaging (mpMRI) allow a better selection of patients for AS. This management should not be limited to patients under 60years of age, and patients with intermediate-risk PCa should be carefully selected to be included. Biopsies are still required in the follow-up, which can be personalized according to risk patterns. The pathologist must identify the cribriform or intraductal histology on biopsies in order to exclude these patients from AS, in the same way as with patients with alterations in DNA repair genes. CONCLUSIONS: Controversial indications such as the inclusion of patients from intermediate-risk groups, or the transition to active treatment due to exclusive progression in tumor volume, should be further optimized. It is possible that the future competition of tissue biomarkers, the refinement of objective parameters of mpMRI and the validation of PSA kinetics calculators may sub-stratify risk groups.

Technical opinion of the Asociación Mexicana de Gastroenterología on soy plant-based beverages. / Posición técnica de la Asociación Mexicana de Gastroenterología sobre las bebidas vegetales a base de soya.

There has been a recent increase in the consumption of cow's milk substitutes, specifically plant-based beverages, which have erroneously been named "plant milks". Plant-based beverages do not have a standard of identity, and so their nutritional composition can vary from one brand to another, even within the same category. The aim of the present narrative review was to produce a technical opinion to serve as a frame of reference for sustaining the recommendation of soy plant-based beverages. Nutrition and gastroenterology experts that belong to the Asociación Mexicana de Gastroenterología jointly commented on and analyzed themes on plant-based beverages, and on soy drinks in particular, including their nutritional characteristics, consumption in children, and potential growth and development alterations, as well as soy drink consumption in adults and its association with gastrointestinal alterations and other conditions. Plant-based beverages, including those made from soy, are not a replacement for breastmilk or breastmilk substitutes. Soy beverages are considered safe and can enrich the varied diet of its consumers, as long as they are considered an additional liquid portion of the diet. They can be ingested by adults and children above two years of age that present with cow's milk protein allergy or lactose intolerance.

Antifungal sensitivity and species of yeasts in oral mucosa of street mixed-breed dogs.

The aim of this research is to verify the yeast species isolated from oral mucosa in street mixed-breed dogs and to determine the antifungal profiles. After capturing and sedating the animals, oral mucosa samples were collected from fifty dogs and the materials were inoculated on Sabouraud dextrose agar with chloramphenicol. Forty-three yeast strains were isolated and identified trough the API-20C AUX method. Thirty-seven (86.1%) of the yeasts belonged to genus Candida, five (11.6%) to genus Trichosporon and only one strain (2.3%) to genus Malassezia. The sensitivity profiles to anifungals (amphotericin B, itraconanole, ketoconazole, fluconazole and variconazole) were determined through Etest® method. This study found resistance of some yeasts to amphotericin B and a good susceptibility to voriconazole and ketoconazole. Some of these antifungals are used in veterinary medical practice. This research is the first investigation on street mixed-breed dogs regarding yeast identifications and antifungals profiles.

Serum Amyloid A1 as a Potential Intracranial and Extracranial Clinical Severity Biomarker in Traumatic Brain Injury.

Extracranial injury is frequently present in patients with traumatic brain injury (TBI). However, no reliable biomarker exists nowadays to evaluate the magnitude and extension of extracranial injury as well as the identification of patients who are at risk of developing secondary injuries. The purpose of this study was to identify new possible peptide biomarkers by mass spectrometry analysis in patients with TBI and ascertain whether the novel biomarker discovered by peptide mass fingerprinting, serum amyloid A1 (SAA1), is capable of reflecting the condition of the patient and both intracranial and extracranial injury extension. Demographic characteristics, clinical data, and serum samples were prospectively collected from 120 patients with TBI (Glasgow Coma Scale [GCS] score 3-15) on admission. Biomarkers were quantified by enzyme-linked immunosorbent assay. Intracranial lesion volume was measured from the semiautomatic segmentation of hematoma on computed tomography (CT) using Analyze software. Functional outcome was evaluated using the Glasgow Outcome Scale (GOS) at hospital discharge and GOS extended scores at 6 months. The SAA1 levels were significantly associated with intracranial (GCS score at admission, lesion load measured with cranial CT, and pupil responsiveness) and extracranial clinical severity (all Abbreviated Injury Scale regions, Injury Severity Score, major extracranial injury, polytrauma, and orthopedic fractures presence), along with systemic secondary insults and functional outcome. SAA1 was is associated with the volume of traumatic intracranial lesions. The SAA1 levels were correlated with astroglial S100ß and glial fibrillary acidic protein (GFAP), neuronal neuron-specific enolase (NSE), and axonal total tau (T-tau) and phosphorylated neurofilament heavy chain (pNF-H) injury markers. SAA1 predicts unfavorable outcome and mortality at hospital discharge (area under the curve [AUC] = 0.90, 0.82) and 6 months (AUC = 0.89). SAA1 can be established as a marker for the overall patient condition due to its involvement in the neuroendocrine axis of the systemic response to craniocerebral trauma.

B subset cells in patients with chronic granulomatous disease in a Mexican population.

INTRODUCTION: Chronic granulomatous disease (CGD) is a disorder of phagocyte function, characterized by pyogenic infections and granuloma formation caused by defects in NADPH oxidase complex activity. Although the effect of CGD mainly reflects the phagocytic compartment, B cell responses are also impaired in patients with CGD. MATERIALS AND METHODS: Flow cytometric analysis was performed on peripheral blood samples from 35 CGD patients age-matched with healthy controls (HC). The target cells of our study were the naive (IgD+/CD27-), memory (IgD-/CD27+), and B1a (CD5+) cells. Immunoglobulins (Igs) were also measured. This study was performed in a Latin American cohort. RESULTS: We found significantly higher levels of naive B cells and B1a cells, but lower levels of memory B cells were found in CGD patients compared to HC. There was no significant difference of cell percentages per inheritance type. DISCUSSION: Our findings suggest that the deficiency of NADPH oxidase components can affect the differentiation of naive B cells to memory B cells. Consequently, memory cells will be low, which also influenced the expression of CD27 in memory B cells and as a result, the percentage of naive cells increases. An altered phenotype of B lymphocytes in CGD patients may contribute to the opportunistic infections and autoimmune disorders that are seen in this disease.

Microdeletion 22q11.2 syndrome: Does thymus incidental surgical resection affect its immunological profile?

BACKGROUND: The del22q11 syndrome patients present immunological abnormalities associated to thymus alterations. Up to 75% of them present cardiopathies and thymus is frequently removed during surgery. The thymectomy per se has a deleterious effect concerning lymphocyte subpopulations, and T cell function. When compared to healthy controls, these patients have higher infections propensity of variable severity. The factors behind these variations are unknown. We compared immunological profiles of del22q11.2 Syndrome patients with and without thymectomy to establish its effect in the immune profile. METHODS: Forty-six del22q11.2 syndrome patients from 1 to 16 years old, 19 of them with partial or total thymectomy were included. Heart disease type, heart surgery, infections events and thymus resection were identified. Immunoglobulin levels, flow cytometry for lymphocytes subpopulations and TREC levels were determined, and statistical analyses were performed. RESULTS: The thymectomy group had a lower lymphocyte index, both regarding total cell count and when comparing age-adjusted Z scores. Also, CD3+, CD4+ and CD8+ lower levels were observed in this group, the lowest count in those patients who had undergone thymus resection during the first year of life. Their TREC level median was 23.6/µL vs 16.1µL in the non-thymus group (p=0.22). No differences were identified regarding immunoglobulin levels or infection events frequencies over the previous year. CONCLUSION: Patients with del22q11.2 syndrome subjected to thymus resection present lower lymphocyte and TREC indexes when compared to patients without thymectomy. This situation may be influenced by the age at the surgery and the time elapsed since the procedure.

Periodontal treatment on patients with cardiovascular disease: Systematic review and meta-analysis.

BACKGROUND: Atherosclerotic cardiovascular disease is the main cause of mortality in developed countries. It is a chronic and systemic inflammatory disease with a multifactorial etiology. Periodontal disease is one of the many factors that contribute to its development. OBJECTIVE: To analyze the effects of periodontal treatment on cardiovascular risk parameters in patients with atherosclerotic cardiovascular disease. METHODS: A systematic research was conducted in the Pubmed/Medline databases for clinical trials published up to and including the year 2017. RESULTS: Ten articles were included for analysis. Periodontal treatment reduced C-reactive protein levels (77.8% of clinical trials), tumor necrosis factor-alpha (66.7%), interleukin-6 (100%) and leukocytes (50%). Fibrinogen levels also improved considerably (66.7%). Effects on lipid parameters were more limited, whereby only oxidized low density lipoprotein and very low density lipoprotein cholesterol decreased significantly. Meta-analysis showed a statistically significant decreased in C-reactive protein and leukocytes values when patients were submitted to non-surgical periodontal treatment in contrast to receiving no treatment at all (mean difference 1.199 mg/L, 95% confidence interval: 1.100-1.299, p<0.001; and mean difference 0,79 g/L, 95% confidence interval: 0.717-0.879, p<0.001, respectively). CONCLUSIONS: Periodontal treatment has a beneficial effect on some of the biochemical parameters considered to represent cardiovascular risk. Further randomized clinical trials are necessary, with longer follow-up periods including regular periodic monitoring, in order to determine the extent of the impact of periodontal treatment.

Fungal Allergy: Pattern of sensitization over the past 11 years.

INTRODUCTION AND OBJECTIVES: Although the prevalence of sensitization to fungi is not precisely known, it can reach 50% in inner cities and has been identified as a risk factor in the development of asthma. Whereas the prevalence of allergic diseases is increasing, it is unclear whether the same occurs with sensitization to fungi. PATIENTS AND METHODS: A retrospective study was performed at the "Hospital Infantil de México Federico Gómez". From skin tests taken between 2004 and 2015, information was gathered about Alternaria alternata, Aspergillus fumigatus, Candida albicans, Cladosporium herbarum, Mucor mucedo and Penicillium notatum. The participating patients were 2-18 years old, presented some type of allergic condition, and underwent immediate hypersensitivity tests to the fungi herein examined. Descriptive analysis and chi-squared distribution were used. RESULTS: Of the 8794 patients included in the study, 14% showed a negative result to the entire panel of environmental allergens. The remaining 7565 individuals displayed sensitization to at least one fungus, which most frequently was Aspergillus, with a rate of 16.8%. When the patients were divided into age groups, the same trend was observed. The highest percentage of sensitization (58%) toward at least one type of fungus was found in 2014, and the lowest percentage (49.8%) in 2008. CONCLUSION: The rate of sensitization to at least one type of fungus was presently over 50%, higher than that detected in other medical centers in Mexico. This rate was constant over the 11-year study, and Aspergillus exhibited the greatest frequency of sensitization among the patients.

Composition of gut microbiota in obese and normal-weight Mexican school-age children and its association with metabolic traits.

BACKGROUND: Childhood obesity is a serious public health problem in Mexico. Adult gut microbiota composition has been linked to obesity, but few studies have addressed the role of gut microbiota in childhood obesity. OBJECTIVES: The aim of this study is to compare gut microbiota composition in obese and normal-weight children and to associate gut microbiota profiles with amino acid serum levels and obesity-related metabolic traits. METHODS: Microbial taxa relative abundance was determined by 16S rRNA sequencing in 67 normal-weight and 71 obese children aged 6-12 years. Serum amino acid levels were measured by mass spectrometry. Associations between microbiota composition, metabolic parameters and amino acid serum levels were tested. RESULTS: No significant differences in phyla abundances or Firmicutes/Bacteroidetes ratios were observed between normal-weight and obese children. However, Bacteroides eggerthii abundance was significantly higher in obese children and correlated positively with body fat percentage and negatively with insoluble fibre intake. Additionally, Bacteroides plebeius and unclassified Christensenellaceae abundances were significantly higher in normal-weight children. Abundance of both these species correlated negatively with phenylalanine serum levels, a metabolite also found to be associated with obesity in Mexican children. CONCLUSIONS: The study identified bacterial species associated with obesity, metabolic complications and amino acid serum levels in Mexican children.

Recommendations for the prevention and diagnosis of asthma in children: Evidence from international guidelines adapted for Mexico.

BACKGROUND: With the availability of high-quality asthma guidelines worldwide, one possible approach of developing a valid guideline, without re-working the evidence, already analysed by major guidelines, is the ADAPTE approach, as was used for the development of National Guidelines on asthma. METHODS: The guidelines development group (GDG) covered a broad range of experts from medical specialities, primary care physicians and methodologists. The core group of the GDG searched the literature for asthma guidelines 2005 onward, and analysed the 11 best guidelines with AGREE-II to select three mother guidelines. Key clinical questions were formulated covering each step of the asthma management. RESULTS: The selected mother guidelines are British Thoracic Society (BTS), GINA and GEMA 2015. Responses to the questions were formulated according to the evidence in the mother guidelines. Recommendations or suggestions were made for asthma treatment in Mexico by the core group, and adjusted during several rounds of a Delphi process, taking into account: 1. Evidence; 2. Safety; 3. Cost; 4. Patient preference - all these set against the background of the local reality. Here the detailed analysis of the evidence present in BTS/GINA/GEMA sections on prevention and diagnosis in paediatric asthma are presented for three age-groups: children with asthma ≤5 years, 6-11 years and ≥12 years. CONCLUSIONS: For the prevention and diagnosis sections, applying the AGREE-II method is useful to develop a scientifically-sustained document, adjusted to the local reality per country, as is the Mexican Guideline on Asthma.

Cross-over clinical trial for evaluating the safety of camel's milk intake in patients who are allergic to cow's milk protein.

BACKGROUND: Cow's milk protein allergy (CMPA) affects between 0.6 and 0.9% of the general population, and its treatment implies the total elimination of the intake of this protein. Camel's milk has been suggested as an alternative for patients over one year of age who suffer from CMPA due to the difference in the amino acid sequence from that of cow's milk. The objective of this study was to evaluate the safety and tolerability of camel's milk in children with CMPA. METHODS: Crossed clinical trial for the use of camel's milk vs. amino acid formula, carried out at the Dr. Federico Gómez Children's Hospital of Mexico (HIMFG) on patients between one and 18 years of age with diagnosed CMPA confirmed through double-blind, placebo-controlled food challenges (DBPCFCs). Only those whose allergies were confirmed were randomly placed into two groups: those to be administered camel's milk and those to be administered the amino-acid formula for two weeks, followed by a six-week wash-out period, and then a group crossing for a further two weeks. RESULTS: 49 patients with suspected CMPA were included in the study; the diagnosis was confirmed through DBPCFCs in 15 patients, who were those who participated in the study. After having been administered camel's milk, none of the patients presented adverse effects. CONCLUSIONS AND CLINICAL RELEVANCE: Camel's milk is safe and tolerable in patients above one year of age with CMPA and can be considered as a good alternative given the benefit of its taste compared to other formulas.

Clinical impact of the subclonal architecture and mutational complexity in chronic lymphocytic leukemia.

Genome studies of chronic lymphocytic leukemia (CLL) have revealed the remarkable subclonal heterogeneity of the tumors, but the clinical implications of this phenomenon are not well known. We assessed the mutational status of 28 CLL driver genes by deep-targeted next-generation sequencing and copy number alterations (CNA) in 406 previously untreated patients and 48 sequential samples. We detected small subclonal mutations (0.6-25% of cells) in nearly all genes (26/28), and they were the sole alteration in 22% of the mutated cases. CNA tended to be acquired early in the evolution of the disease and remained stable, whereas the mutational heterogeneity increased in a subset of tumors. The prognostic impact of different genes was related to the size of the mutated clone. Combining mutations and CNA, we observed that the accumulation of driver alterations (mutational complexity) gradually shortened the time to first treatment independently of the clonal architecture, IGHV status and Binet stage. Conversely, the overall survival was associated with the increasing subclonal diversity of the tumors but it was related to the age of patients, IGHV and TP53 status of the tumors. In conclusion, our study reveals that both the mutational complexity and subclonal diversity influence the evolution of CLL.