Microbiota composition in the lower respiratory tract is associated with severity in patients with acute respiratory distress by influenza.

Several factors are associated with the severity of the respiratory disease caused by the influenza virus. Although viral factors are one of the most studied, in recent years the role of the microbiota and co-infections in severe and fatal outcomes has been recognized. However, most of the work has focused on the microbiota of the upper respiratory tract (URT), hindering potential insights from the lower respiratory tract (LRT) that may help to understand the role of the microbiota in Influenza disease. In this work, we characterized the microbiota of the LRT of patients with Influenza A using 16S rRNA sequencing. We tested if patients with different outcomes (deceased/recovered) and use of antibiotics differ in their microbial community composition. We found important differences in the diversity and composition of the microbiota between deceased and recovered patients. In particular, we detected a high abundance of opportunistic pathogens such as Granulicatella, in patients either deceased or with antibiotic treatment. Also, we found antibiotic treatment correlated with lower diversity of microbial communities and with lower probability of survival in Influenza A patients. Altogether, the loss of microbial diversity could generate a disequilibrium in the community, potentially compromising the immune response increasing viral infectivity, promoting the growth of potentially pathogenic bacteria that, together with altered biochemical parameters, can be leading to severe forms of the disease. Overall, the present study gives one of the first characterizations of the diversity and composition of microbial communities in the LRT of Influenza patients and its relationship with clinical variables and disease severity.

Mycobacterium tuberculosis Cell Wall Antigens Induce the Formation of Immune Complexes and the Development of Vasculitis in an Experimental Murine Model.

Tuberculosis (TB) of the central nervous system (CNS) presents high mortality due to brain damage and inflammation events. The formation and deposition of immune complexes (ICs) in the brain microvasculature during Mycobacterium tuberculosis (Mtb) infection are crucial for its pathobiology. The relevance of ICs to Mtb antigens in the pathogenesis of CNS-TB has been poorly explored. Here, we aimed to establish a murine experimental model of ICs-mediated brain vasculitis induced by cell wall antigens of Mtb. We administered a cell wall extract of the prototype pathogenic Mtb strain H37Rv to male BALB/c mice by subcutaneous and intravenous routes. Serum concentration and deposition of ICs onto blood vessels were determined by polyethylene glycol precipitation, ELISA, and immunofluorescence. Histopathological changes in the brain, lung, spleen, liver, and kidney were evaluated by hematoxylin and eosin staining. Our results evidenced that vasculitis developed in the studied tissues. High serum levels of ICs and vascular deposition were evident in the brain, lung, and kidneys early after the last cell wall antigen administration. Cell wall Mtb antigens induce strong type III hypersensitivity reactions and the development of systemic vasculitis with brain vascular changes and meningitis, supporting a role for ICs in the pathogenesis of TB.

Unravelling the Contribution of the rs7041 and rs4588 Polymorphisms of the GC Gene and Serum VDBP Levels for Developing Metabolic Syndrome in the Mexican Population.

Metabolic syndrome (MetS) is a multifactorial disorder integrated by a constellation of cardiovascular risk factors. The genetic and environmental determinants of MetS are not fully elucidated. This study investigated the association of two common single nucleotide polymorphisms (SNPs) on GC, rs7041 and rs4588, derived haplotypes, and serum vitamin D binding protein (VDBP) levels with the susceptibility to suffer MetS in Mexican adults. We included 1924 individuals; clinical and biochemical data were obtained through standard methods. Genotyping was performed through predesigned TaqMan assays. Logistic regression models were used to assess the associations of interest. Prevalence of MetS was 52.9% in the whole population, being more frequent in women. We observed that some association results differed between sexes. The GG genotype of the rs7041 was associated with increased odds of MetS in women. For the rs4588, the CA genotype had a protective effect against MetS in women. The haplotype GC2 was associated with reduced odds for MetS and some of its components in women. Our data suggest that VDBP serum levels were influenced by genotypes/haplotypes and this interplay seems to influence the risk of MetS. Our data provide reliable evidence regarding the association of GC polymorphisms with MetS risk in Mexican women.

Longitudinal Analysis of Urinary Cytokines and Biomarkers in COVID-19 Patients with Subclinical Acute Kidney Injury.

In hospitalized COVID-19 patients, disease progression leading to acute kidney injury (AKI) may be driven by immune dysregulation. We explored the role of urinary cytokines and their relationship with kidney stress biomarkers in COVID-19 patients before and after the development of AKI. Of 51 patients, 54.9% developed AKI. The principal component analysis indicated that in subclinical AKI, epidermal growth factor (EGF) and interferon (IFN)-α were associated with a lower risk of AKI, while interleukin-12 (IL-12) and macrophage inflammatory protein (MIP)-1ß were associated with a higher risk of AKI. After the manifestation of AKI, EGF and IFN-α remained associated with a lower risk of AKI, while IL-1 receptor (IL-1R), granulocyte-colony stimulating factor (G-CSF), interferon-gamma-inducible protein 10 (IP-10) and IL-5 were associated with a higher risk of AKI. EGF had an inverse correlation with kidney stress biomarkers. Subclinical AKI was characterized by a significant up-regulation of kidney stress biomarkers and proinflammatory cytokines. The lack of EGF regenerative effects and IFN-α antiviral activity seemed crucial for renal disease progression. AKI involved a proinflammatory urinary cytokine storm.

The rs776746 variant of CYP3A5 is associated with intravenous midazolam plasma levels and higher clearance in critically ill Mexican paediatric patients.

WHAT IS KNOWN AND OBJECTIVE: Midazolam is a drug that is metabolized by cytochrome P450 (CYP450) enzymes, particularly CYP3A4 and CYP3A5. The presence of single-nucleotide polymorphisms (SNPs) in the genes encoding these enzymes, such as CYP3A4*1B which is associated with low enzyme expression and activity and CYP3A5*3, has been associated with decrease in enzymatic activity and reduced drug clearance, with potential effects on drug levels and/or toxicity. The present study was conducted to determine the frequencies of the allelic variants of the CYP3A4 (rs2740574) and CYP3A5 (rs776746) genes and their effects on the plasma levels and clearance of intravenous midazolam in critically ill Mexican paediatric patients. METHODS: Seventy-two DNA samples were genotyped by real-time PCR with TaqMan probes. Plasma midazolam levels were determined at 3 and 24 h post infusion by high-performance liquid chromatography. RESULTS AND DISCUSSION: The allelic variant rs776746 (CYP3A5*3) was associated with high midazolam plasma levels; the median concentration in patients with the normal genotype (CC) <0.01 ng/ml (Q25 0.01-Q75 196.09), whereas patients with the allelic variant (TT+TC) had a median midazolam concentration of 320.3 ng/ml (Q25 37.51-Q75 529.51), p = 0.001. The median pharmacokinetic clearance rates were 0.10 L/kg/h (Q25 0.01-Q75 0.34) in patients with the allelic variant (TT+TC) and 0.03 L/kg/h (Q25 0.002-Q75 0.13) in patients with the normal genotype (CC), p = 0.042. WHAT IS NEW AND CONCLUSION: This is the first study that reports the frequency of the rs776746 polymorphism in critically ill paediatric patients, which is relevant, since carriers of the *1 allele synthesizing a functional enzyme may need higher doses to achieve adequate sedation. Our results show that compared with carriers of the normal allele, patients with the CYP3A5*3 allelic variant (rs776746) had increased plasma midazolam levels at 3 h after infusion discontinuation (320.3 ng/ml) and greater clearance (0.10 L/kg/h) of the drug.

Analysis of CYP450 gene allelic variants can predict ifosfamide toxicity in Mexican paediatric patients.

Context: Ifosfamide (IFA) is an effective antineoplastic for solid tumours in children, although it is associated with high levels of systemic toxicity and causes death in some cases. Objective: The aim of this study was to determine whether the presence of certain allelic variants of genes CYP2B6, CYP2C9, CYP3A4 and CYP3A5 increases the risk of toxicity in children with solid tumours treated with ifosfamide.Materials and methods: A total of 131 DNA samples were genotyped by real-time polymerase chain reaction (RT-PCR) using TaqMan probes. Toxicity was assessed using WHO criteria, and survival analysis was performed using Kaplan-Meier curves.Results: The rs3745274 allelic variant in CYP2B6 was associated with haematological toxicity, affecting neutrophils; CYP3A4 variant rs2740574 was also associated with toxicity, affecting both leukocytes and neutrophils. Additionally, the CYP3A5 gene variant rs776746 was found to affect haemoglobin.Conclusions: Our results show that allelic variants rs3745274 (CYP2B6), rs2740574 (CYP34) and rs776746 (CYP3A5) increase the risk for high haematological toxicity.Clinical trial registration: 068/2013.

Dysregulated expression of hypoxia-inducible factors augments myofibroblasts differentiation in idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is an age-related, progressive and lethal disease, whose pathogenesis is associated with fibroblasts/myofibroblasts foci that produce excessive extracellular matrix accumulation in lung parenchyma. Hypoxia has been described as a determinant factor in its development and progression. However, the role of distinct members of this pathway is not completely described. METHODS: By western blot, quantitative PCR, Immunohistochemistry and Immunocitochemistry were evaluated, the expression HIF alpha subunit isoforms 1, 2 & 3 as well, as their role in myofibroblast differentiation in lung tissue and fibroblast cell lines derived from IPF patients. RESULTS: Hypoxia signaling pathway was found very active in lungs and fibroblasts from IPF patients, as demonstrated by the abundance of alpha subunits 1 and 2, which further correlated with the increased expression of myofibroblast marker αSMA. In contrast, HIF-3α showed reduced expression associated with its promoter hypermethylation. CONCLUSIONS: This study lends further support to the involvement of hypoxia in the pathogenesis of IPF, and poses HIF-3α expression as a potential negative regulator of these phenomena.

Analysis of heat shock protein 70 gene polymorphisms Mexican patients with idiopathic pulmonary fibrosis.

BACKGROUND: Idiopathic pulmonary fibrosis (IPF) is a fatal lung disease of unknown etiology. Genetic variation within different major histocompatibility complex (MHC) loci contributes to the susceptibility to IPF. The effect of 70 kDa heat shock proteins (HSP70) gene polymorphisms in the susceptibility to IPF is unknown. The aim of this study was to explore the association between HSP70 polymorphisms and IPF susceptibility in the Mexican population. METHODS: Four HSP70 single nucleotide polymorphisms (SNPs) were evaluated using real time PCR assays in 168 IPF patients and 205 controls: +2763 C>T of HSPA1L (rs2075800), +2437 of HSP HSPA1L A>G (rs2227956), +190 of HSPA1A G>C (rs1043618) and +1267 of HSPA1B G>A (rs1061581). RESULTS: The analysis of the recessive model revealed a significant decrease in the frequency of the genotype HSPA1B AA (rs1061581) in IPF patients (OR = 0.27, 95 % CI = 0.13-0.57, Pc = 0.0003) when compared to controls. Using a multivariate logistic regression analysis in a codominant model the HSPA1B (rs1061581) GA and AA genotypes were associated with a lower risk of IPF compared with GG (OR = 0.22, 95 % CI = 0.07-0.65; p = 0.006 and OR = 0.17, 95 % CI = 0.07-0.41; p = <0.001). Similarly, HSPA1L (rs2227956) AG genotype (OR = 0.34, 95 % CI = 0.12-0.99; p = 0.04) and the dominant model AG + GG genotypes were also associated with a lower risk of IPF (OR = 0.24, 95 % CI = 0.08-0.67; p = 0.007). In contrast, the HSPA1L (rs2075800) TT genotype was associated with susceptibility to IPF (OR = 2.52, 95 % CI = 1.32-4.81; p = 0.005). CONCLUSION: Our findings indicate that HSPA1B (rs1061581), HSPA1L (rs2227956) and HSPA1 (rs1043618) polymorphisms are associated with a decreased risk of IPF.

Analysis of association of MEF2C, SOST and JAG1 genes with bone mineral density in Mexican-Mestizo postmenopausal women.

BACKGROUND: Osteoporosis, a disease characterized by low bone mineral density (BMD), is an important health problem in Mexico. BMD is a highly heritable trait, with heritability estimates of 50-85%. Several candidate genes have been evaluated to identify those involved in BMD variation and the etiology of osteoporosis. This study investigated the possible association of single-nucleotide polymorphisms (SNPs) in the MEF2C, SOST and JAG1genes with bone mineral density (BMD) variation in postmenopausal Mexican-Mestizo women. METHODS: Four hundred unrelated postmenopausal women were included in the study. Risk factors were recorded and BMD was measured in total hip, femoral neck and lumbar spine using dual-energy X-ray absorptiometry. In an initial stage, a total of twenty-five SNPs within or near SOST gene and seven SNPs in the JAG1 gene were genotyped using a GoldenGate assay. In a second stage, three MEF2C gene SNPs were also genotyped and SOST and JAG1 gene variants were validated. Real time PCR and TaqMan probes were used for genotyping. RESULTS: Linear regression analyses adjusted by age, body mass index and ancestry estimates, showed that five SNPs in the SOST gene were significantly associated with BMD in total hip and femoral neck but not lumbar spine. The lowest p value was 0.0012, well below the multiple-test significance threshold (p=0.009), with mean effect size of -0.027 SD per risk allele. We did not find significant associations between BMD and MEF2C/JAG1 gene variants [rs1366594 "A" allele: ß=0.001 (95% CI -0.016; 0.017), P=0.938; rs2273061 "G" allele: ß=0.007 (95% CI -0.007; 0.023), p=0.409]. CONCLUSIONS: SOST polymorphisms may contribute to total hip and femoral neck BMD variation in Mexican postmenopausal women. Together, these and prior findings suggest that this gene may contribute to BMD variation across populations of diverse ancestry.

Effect of N-Acetylcysteine on Cisplatin Toxicity: A Review of the Literature.

N-acetylcysteine (NAC) is a membrane-permeable cysteine precursor capable of enhancing the intracellular cysteine pool, enhancing cellular glutathione (GSH) synthesis, and thus potentiating the endogenous antioxidant mechanism. Late administration of NAC after cisplatin has been shown in different in vivo studies to reduce the side effects caused by various toxicities at different levels without affecting the antitumor efficacy of platinum, improving total and enzymatic antioxidant capacity and decreasing oxidative stress markers. These characteristics provide NAC with a rationale as a potentially effective chemo protectant in cisplatin-based therapeutic cycles. NAC represents a potential candidate as a chemoprotective agent to decrease toxicities secondary to cisplatin treatment. It suggests that it could be used in clinical trials, whereby the effective dose, timing, and route should be adjusted to optimize chemoprotection. This review provides an overview of the effect of NAC on cisplatin toxicity, a drug widely used in the clinic in adults and children.

Immunotherapy for Pediatric Gliomas: CAR-T Cells Against B7H3: A Review of the Literature.

BACKGROUND: B7H3 is a co-stimulatory molecule for immune reactions found on the surface of tumor cells in a wide variety of tumors. Preclinical and clinical studies have reported it as a tumor target towards which various immunotherapy modalities could be directed. So far, good results have been obtained in hematological neoplasms; however, a contrasting situation is evident in solid tumors, including those of the CNS, which show high refractoriness to current treatments. The appearance of cellular immunotherapies has transformed oncology due to the reinforcement of the immune response that is compromised in people with cancer. OBJECTIVE: This article aims to review the literature to describe the advancement in knowledge on B7H3 as a target of CAR-T cells in pediatric gliomas to consider them as an alternative in the treatment of these patients. RESULTS: Although B7H3 is considered a suitable candidate as a target agent for various immunotherapy techniques, there are still limitations in using CAR-T cells to achieve the desired success. CONCLUSION: Results obtained with CAR-T cells can be further improved by the suggested proposals; therefore, more clinical trials are needed to study this new therapy in children with gliomas.

Factors Influencing Mortality in Children with Central Nervous System Tumors: A Cohort Study on Clinical Characteristics and Genetic Markers.

Multidrug resistance (MDR) commonly leads to cancer treatment failure because cancer cells often expel chemotherapeutic drugs using ATP-binding cassette (ABC) transporters, which reduce drug levels within the cells. This study investigated the clinical characteristics and single nucleotide variant (SNV) in ABCB1, ABCC1, ABCC2, ABCC4, and ABCG2, and their association with mortality in pediatric patients with central nervous system tumors (CNST). Using TaqMan probes, a real-time polymerase chain reaction genotyped 15 SNPs in 111 samples. Patients were followed up until death or the last follow-up day using the Cox proportional hazards model. An association was found between the rs1045642 (ABCB1) in the recessive model (HR = 2.433, 95% CI 1.098-5.392, p = 0.029), and the ICE scheme in the codominant model (HR = 9.810, 95% CI 2.74-35.06, p ≤ 0.001), dominant model (HR = 6.807, 95% CI 2.87-16.103, p ≤ 0.001), and recessive model (HR = 6.903, 95% CI 2.915-16.544, p = 0.038) significantly increased mortality in this cohort of patients. An association was also observed between the variant rs3114020 (ABCG2) and mortality in the codominant model (HR = 5.35, 95% CI 1.83-15.39, p = 0.002) and the dominant model (HR = 4.421, 95% CI 1.747-11.185, p = 0.002). A significant association between the ICE treatment schedule and increased mortality risk in the codominant model (HR = 6.351, 95% CI 1.831-22.02, p = 0.004, HR = 9.571, 95% CI 2.856-32.07, p ≤ 0.001), dominant model (HR = 6.592, 95% CI 2.669-16.280, p ≤ 0.001), and recessive model (HR = 5.798, 95% CI 2.411-13.940, p ≤ 0.001). The genetic variants rs3114020 in the ABCG2 gene and rs1045642 in the ABCB1 gene and the ICE chemotherapy schedule were associated with an increased mortality risk in this cohort of pediatric patients with CNST.

Challenges in Treating Pediatric Cancer Patients during the COVID-19 Pandemic: Balancing Risks and Care.

The COVID-19 pandemic has resulted in millions of fatalities worldwide. The case of pediatric cancer patients stands out since, despite being considered a population at risk, few studies have been carried out concerning symptom detection or the description of the mechanisms capable of modifying the course of the COVID-19 disease, such as the interaction and response between the virus and the treatment given to cancer patients. By synthesizing existing studies, this paper aims to expose the treatment challenges for pediatric patients with COVID-19 in an oncology context. Additionally, this updated review includes studies that utilized the antiviral agents Remdesivir and PaxlovidTM in pediatric cancer patients. There is no specific treatment designed exclusively for pediatric cancer patients dealing with COVID-19, and it is advisable to avoid self-medication to prevent potential side effects. Managing COVID-19 in pediatric cancer patients is indeed a substantial challenge. New strategies, such as chemotherapy application rooms, have been implemented for children with cancer who were positive for COVID-19 but asymptomatic since the risk of disease progression is greater than the risk of complications from SARS-CoV-2.

[Factors involved in host-pathogen interaction for the risk of Hodgkin lymphoma induced by Epstein Barr virus]. / Factores que participan en la interacción huésped-agente patógeno en el riesgo de Linfoma de Hodgkin inducido por el virus Epstein Barr.

Hodgkin lymphoma (HL) is a neoplasm characterized by malignant cells called Reed Sternberg and Hodgkin's cells in the lymphatic system. Such cells comprise 1% of the tumor while the remainder is made up of lymphocytes, histiocytes, eosinophils and plasma non-neoplastic cells. The annual global incidence of HL is 3-10/100,000 inhabitants and is most commonly found in young adults. The mechanism by which cell transformation is accomplished is not entirely clear; however, some evidences suggest that oncogenic viruses like the Epstein Barr virus (EBV) may have a high impact on the pathogenesis of lymphoproliferation. Genetic and environmental factors could be involved, since it has been found a high incidence of HL among members of the same family. In Mexico, there have been studies to determine the prevalence of EBV in patients with HL and found the presence of this virus in up to 64.2% of the cases. EBV has been detected in the Reed Sternberg cells and Hodgkin cells in 50% of cases of classical HL. There is not a satisfactory explanation for this, but it has been proposed that geographic and immunological variabilities play a role in the positivity of EBV in HL. However, despite recent advances in the field, there is insufficient evidence to show a clear association between host factors, environment and pathogens, and the risk of lymphoproliferation leading to the development of HL. This review aims to give an overview about the risk factors that influence the interaction of host, pathogens and environment in the etiology of HL.

Association Study between Antioxidant Nutrient Intake and Low Bone Mineral Density with Oxidative Stress-Single Nucleotide Variants: GPX1 (rs1050450 and rs17650792), SOD2 (rs4880) and CAT (rs769217) in Mexican Women.

Oxidative stress is essential in developing multiple bone metabolism diseases, including osteoporosis. Single-nucleotide variants (SNVs) have been associated with oxidative stress, promoting an imbalance between the production of reactive oxygen species and the ability to neutralize them, and it has been reported that antioxidant nutrient intake can influence bone mineral density (BMD). This work reports the association between oxidative stress-related SNVs (GPX1-rs1050450, rs17650792, SOD2-rs4880, and CAT-rs769217), BMD, and antioxidant nutrient intake. The study included 1269 Mexican women from the Health Workers Cohort Study. Genotyping was performed using predesigned TaqMan assays. Dietary data were collected using a 116-item semi-quantitative food frequency questionnaire. A dietary antioxidant quality score (DAQS) was used to estimate antioxidant-nutrient intake. Association analysis was estimated via linear, logistic, or quantile regression models. The results showed an association of the rs1050450-A and rs17650792-A alleles with femoral neck BMD (p = 0.038 and p = 0.017, respectively) and the SNV rs4880-A allele with total hip BMD (p = 0.026) in respondents aged 45 years or older. In addition, antioxidant-nutrient intake was associated with the rs4880-GG genotype, being significant for fiber (p = 0.007), riboflavin (p = 0.005), vitamin B6 (p = 0.034), and vitamin D (p = 0.002). The study showed an association between oxidative stress-related SNVs, BMD, and antioxidant-nutrient intake in Mexican women. Therefore, treatments for low BMD could be developed based on antioxidant supplementation.

Hypoxia Induces Alterations in the Circadian Rhythm in Patients with Chronic Respiratory Diseases.

The function of the circadian cycle is to determine the natural 24 h biological rhythm, which includes physiological, metabolic, and hormonal changes that occur daily in the body. This cycle is controlled by an internal biological clock that is present in the body's tissues and helps regulate various processes such as sleeping, eating, and others. Interestingly, animal models have provided enough evidence to assume that the alteration in the circadian system leads to the appearance of numerous diseases. Alterations in breathing patterns in lung diseases can modify oxygenation and the circadian cycles; however, the response mechanisms to hypoxia and their relationship with the clock genes are not fully understood. Hypoxia is a condition in which the lack of adequate oxygenation promotes adaptation mechanisms and is related to several genes that regulate the circadian cycles, the latter because hypoxia alters the production of melatonin and brain physiology. Additionally, the lack of oxygen alters the expression of clock genes, leading to an alteration in the regularity and precision of the circadian cycle. In this sense, hypoxia is a hallmark of a wide variety of lung diseases. In the present work, we intended to review the functional repercussions of hypoxia in the presence of asthma, chronic obstructive sleep apnea, lung cancer, idiopathic pulmonary fibrosis, obstructive sleep apnea, influenza, and COVID-19 and its repercussions on the circadian cycles.

Adverse Events and Drug Resistance in Critically Ill Patients Treated with Colistimethate Sodium: A Review of the Literature.

The adverse events related to sodium colistimethate have had variability regarding the prevalence of nephrotoxicity, neurotoxicity, and less frequent respiratory depression. In recent years, its use has been relevant due to the increase of multidrug-resistant bacteria since it is considered the last-line drug, being its main adverse event and reason for discrepancies between authors' nephrotoxicity. The indiscriminate use of antibiotic therapy has generated multiple mechanisms of resistance, the most common being related to Colistin, the bactericidal escape effect. Based on the search criteria, no randomized clinical trials were identified showing safety and efficacy with the use of Colistin, inferring that the application of the appropriate dose is governed by expert opinion and retrospective and prospective observational studies, which confounding factors such as the severity of the patient and the predisposition to develop acute renal failure are constant. In this review, we focus on identifying the mechanism of nephrotoxicity and bacterial resistance, where much remains to be known.

Pandemic influenza A/H1N1 virus infection and TNF, LTA, IL1B, IL6, IL8, and CCL polymorphisms in Mexican population: a case-control study.

BACKGROUND: Some patients have a greater response to viral infection than do others having a similar level of viral replication. Hypercytokinemia is the principal immunopathological mechanism that contributes to a severer clinical course in cases of influenza A/H1N1. The benefit produced, or damage caused, by these cytokines in severe disease is not known. The genes that code for these molecules are polymorphic and certain alleles have been associated with susceptibility to various diseases. The objective of the present study was to determine whether there was an association between polymorphisms of TNF, LTA, IL1B, IL6, IL8, and CCL1 and the infection and severity of the illness caused by the pandemic A/H1N1 in Mexico in 2009. METHODS: Case-control study. The cases were patients confirmed with real time PCR with infection by the A/H1N1 pandemic virus. The controls were patients with infection like to influenza and non-familial healthy contacts of the patients with influenza. Medical history and outcome of the disease was registered. The DNA samples were genotyped for polymorphisms TNF rs361525, rs1800629, and rs1800750; LTA rs909253; IL1B rs16944; IL6 rs1818879; IL8 rs4073; and CCL1 rs2282691. Odds ratio (OR) and the 95% confidence interval (95% CI) were calculated. The logistic regression model was adjusted by age and severity of the illness in cases. RESULTS: Infection with the pandemic A/H1N1 virus was associated with the following genotypes: TNF rs361525 AA, OR = 27.00; 95% CI = 3.07-1248.77); LTA rs909253 AG (OR = 4.33, 95% CI = 1.82-10.32); TNF rs1800750 AA (OR = 4.33, 95% CI = 1.48-12.64); additionally, LTA rs909253 AG showed a limited statistically significant association with mortality (p = 0.06, OR = 3.13). Carriers of the TNF rs1800629 GA genotype were associated with high levels of blood urea nitrogen (p = 0.05); those of the TNF rs1800750 AA genotype, with high levels of creatine phosphokinase (p=0.05). The IL1B rs16944 AA genotype was associated with an elevated number of leukocytes (p <0.001) and the IL8 rs4073 AA genotype, with a higher value for PaO2 mm Hg. CONCLUSION: The polymorphisms of genes involved in the inflammatory process contributed to the severity of the clinical behavior of infection by the pandemic influenza A/H1N1 virus.

High mortality associated with hyperglycemia, neutrophilia, and lymphopenia in critically ill patients.

A common finding in patients admitted to an Intensive Care Unit (ICU) is hyperglycemia without prior history of diabetes. This increase in blood glucose is considered a negative prognostic factor for patients in the ICU. Hence, we performed a retrospective cohort study in patients admitted at the ICU of the National Institute of Respiratory Diseases (INER) in a 7-month period; we collected data about their blood glucose concentration during their stay at the ICU. We gathered the available medical records of 30 patients out of 58 admitted to the ICU. Among the 30 patients, 21 patients survived (70%) and 9 patients with community-acquired pneumonia (CAP) died (30%). The 21 surviving patients included 17 patients with acute respiratory distress secondary to CAP and 4 patients with asthmatic crisis upon admission to the ICU. After admission, all patients progressed to sepsis and showed an increase in blood glucose. We detected higher glucose concentrations in deceased patients (147 mg/dl ± 4.23), as compared to surviving patients (129 mg/dl ± 2.17) (P < 0.001). In addition, the percentage of lymphocytes was lower in deceased patients than that in surviving patients (5.7 vs. 11.8%, P < 0.001), whereas percentage of neutrophils was elevated in the deceased patients (90.7 vs. 80.9%, P < 0.001). It is therefore important to measure continuously glucose concentrations, as well as the numbers of neutrophils and lymphocytes in critically ill patients with hyperglycemia. Such a simple monitoring plan may prevent fatal complications in patients admitted to ICU.

Clinical characteristics and mortality predictors of patients with cancer hospitalized by COVID-19 in a pediatric third-level referral center.

Background: More than 135 million COVID-19 cases (coronavirus disease 2019) have been reported worldwide until today, with over 2.9 million deaths. Several studies have demonstrated that disease severity is lower in the pediatric population than in adults; however, differences are described in patients with chronic diseases, including oncological patients. Current world literature suggests patients with comorbidities, including cancer, have an increased risk of unfortunate outcomes. Therefore, our objective was to describe the clinical characteristics and epidemiological factors associated with mortality in a cohort of pediatric cancer patients hospitalized for COVID-19. Methods: This is a retrospective, descriptive study of the cases of patients with cancer hospitalized for COVID-19. A total of 40 pediatrics were included in the analysis. Data from pediatric patients with COVID-19 included clinical and epidemiological records, laboratory, imaging studies, COVID-19 diagnostic methods, and medical treatment. Results: Of the 40 pediatric patients admitted with cancer with a confirmed diagnosis of COVID-19, 42.5% were solid tumors, 40% leukemias, and 17.5% lymphomas. The clinical parameters associated with mortality were stage IV tumor (p = 0.029) and intubation (p < 0.001). The biochemical factors associated with lower survival were thrombocytopenia under 25,000 cells/mm3 (p < 0.001), D-dimer over 1 µg/ml (p = 0.003), clinical malnutrition (p = 0.023), and disseminated intravascular coagulation (p = 0.03). Conclusion: Our findings showed that the fever was the most frequent symptom, and the clinical parameters associated with mortality were stage IV tumor, intubation, saturation percentage, RDW, platelets, creatinine, ALT, D-dimer, ferritin, and FiO2 percentage. The thrombocytopenia, D-dimer, nutritional status, and disseminated intravascular coagulation were significantly associated with lower survival.