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 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.

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.

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.

Genetic Markers as Predictors for Response to Treatment and Possible Therapeutic Targets in Medulloblastoma.

BACKGROUND: Medulloblastomas (MB) are the most common malignant brain tumors in the pediatric age. In 2021, WHO categorized medulloblastomas into two groups: molecularly defined and histologically defined medulloblastomas. Molecularly defined medulloblastomas are divided into WNTactivated medulloblastoma, SHH-activated and TP53-wildtype medulloblastoma, SHH-activated, and TP53-mutant and non-WNT/non-SHH medulloblastoma, which include Group 3 (MYC) and Group 4 (CDK6 and MYCN). In this paper, we will focus on molecularly defined medulloblastomas. OBJECTIVE: This paper aims to review the literature in order to describe the molecular structure of the medulloblastoma groups and to emphasize the importance of genetic predictors in medulloblastoma that can be used in clinical practice, either as a prognostic tool or as a therapeutic target in the future. RESULTS: Each molecular subtype of medulloblastoma presents a different prognosis, and the molecular subtype with the best prognosis is medulloblastoma-activated WNT. It has even been observed that a reduction in the intensity of the combined treatment does not modify the prognosis of the patients, resulting in even fewer adverse effects due to the treatment. On the other hand, it was observed that the subtypes with the worst prognosis are medulloblastomas with activated MYC and medulloblastomas with activated SHH and mutated TP53, due to their high capacity to metastasize or to their radio-resistance. However, a new target therapy has emerged that could help improve the prognosis in these patients. CONCLUSION: The deeper knowledge of the molecular pathways involved in the appearance and progression of medulloblastomas will allow us to offer a prognosis at the time of diagnosis and more specific treatments through the development of the targeted therapy.

Sex and Age Influence on Association of CYP450 Polymorphism with Midazolam Levels in Critically Ill Children.

Midazolam is a drug that is metabolized by cytochrome P450 (CYP450) enzymes, particularly CYP3A4 and CYP3A5. The present study aimed to determine the sex and age influence on association of CYP450 polymorphism with midazolam levels in critically ill children. Seventy-two DNA samples were genotyped by real-time PCR. Children ≤ five years of age who carry the rs776746 (T) allele in CYP3A5 gene were associated with lower plasma midazolam levels. The concentration median in patients was 0.0 ng/mL, while in patients with the normal (C) allele, it was 438.17 ng/mL (Q25 135.75-Q75 580.24), p = 0.005. The midazolam plasmatic concentration in female patients with the minor (T) allele was 0.0 ng/mL (Q250.00-Q75204.3), while in patients with the normal (C) allele median it was 459.0 ng/mL (Q25296.9-Q75789.7), p = 0.002. Analysis of the dominant model for the rs2740574 variant in CYP3A4 revealed a median of 0.38 L/kg (Q250.02-Q751.5) for the volume of distribution parameter in female patients with the normal T allele, while female patients with the minor C allele showed a median of 18.1 L/kg (Q257.5-Q7528.7) p = 0.02. Our results suggest an altered midazolam metabolism due to the presence the allelic rs2740574 variants of CYP3A4 and rs776746 of CYP3A5, and also the strong influence of age and sex.

Functional Repercussions of Hypoxia-Inducible Factor-2α in Idiopathic Pulmonary Fibrosis.

Hypoxia and hypoxia-inducible factors (HIFs) are essential in regulating several cellular processes, such as survival, differentiation, and the cell cycle; this adaptation is orchestrated in a complex way. In this review, we focused on the impact of hypoxia in the physiopathology of idiopathic pulmonary fibrosis (IPF) related to lung development, regeneration, and repair. There is robust evidence that the responses of HIF-1α and -2α differ; HIF-1α participates mainly in the acute phase of the response to hypoxia, and HIF-2α in the chronic phase. The analysis of their structure and of different studies showed a high specificity according to the tissue and the process involved. We propose that hypoxia-inducible transcription factor 2a (HIF-2α) is part of the persistent aberrant regeneration associated with developing IPF.

Effect of Hypoxia in the Transcriptomic Profile of Lung Fibroblasts from Idiopathic Pulmonary Fibrosis.

Idiopathic pulmonary fibrosis (IPF) is an aging-associated disease characterized by exacerbated extracellular matrix deposition that disrupts oxygen exchange. Hypoxia and its transcription factors (HIF-1α and 2α) influence numerous circuits that could perpetuate fibrosis by increasing myofibroblasts differentiation and by promoting extracellular matrix accumulation. Therefore, this work aimed to elucidate the signature of hypoxia in the transcriptomic circuitry of IPF-derived fibroblasts. To determine this transcriptomic signature, a gene expression analysis with six lines of lung fibroblasts under normoxia or hypoxia was performed: three cell lines were derived from patients with IPF, and three were from healthy donors, a total of 36 replicates. We used the Clariom D platform, which allows us to evaluate a huge number of transcripts, to analyze the response to hypoxia in both controls and IPF. The control's response is greater by the number of genes and complexity. In the search for specific genes responsible for the IPF fibroblast phenotype, nineteen dysregulated genes were found in lung fibroblasts from IPF patients in hypoxia (nine upregulated and ten downregulated). In this sense, the signaling pathways revealed to be affected in the pulmonary fibroblasts of patients with IPF may represent an adaptation to chronic hypoxia.

Risk of Pulmonary Fibrosis and Persistent Symptoms Post-COVID-19 in a Cohort of Outpatient Health Workers.

Background: Infection by SARS-CoV-2 has been associated with multiple symptoms; however, still, little is known about persistent symptoms and their probable association with the risk of developing pulmonary fibrosis in patients post-COVID-19. Methods: A longitudinal prospective study on health workers infected by SARS-CoV-2 was conducted. In this work, signs and symptoms were recorded of 149 health workers with a positive PCR test for SARS-CoV-2 at the beginning of the diagnosis, during the active infection, and during post-COVID-19 follow-up. The McNemar chi-square test was used to compare the proportions and percentages of symptoms between the baseline and each follow-up period. Results: The signs and symptoms after follow-up were cardiorespiratory, neurological, and inflammatory. Gastrointestinal symptoms were unusual at the disease onset, but unexpectedly, their frequency was higher in the post-infection stage. The multivariate analysis showed that pneumonia (HR 2.4, IC95%: 1.5−3.8, p < 0.001) and positive PCR tests still after four weeks (HR 5.3, IC95%: 2.3-12.3, p < 0.001) were factors associated with the diagnosis of post-COVID-19 pulmonary fibrosis in this study group. Conclusions: Our results showed that pneumonia and virus infection persistence were risk factors for developing pulmonary fibrosis post-COVID-19, after months of initial infection.

Ivermectin: A Controversial Focal Point during the COVID-19 Pandemic.

The SARS-CoV-2 pandemic has confirmed the apocalyptic predictions that virologists have been making for several decades. The challenge the world is facing is that of trying to find a possible treatment, and a viable and expedient option for addressing this challenge is the repurposing of drugs. However, in some cases, although these drugs are approved for use in humans, the mechanisms of action involved are unknown. In this sense, to justify its therapeutic application to a new disease, it is ideal, but not necessary, to know the basic mechanisms of action involved in a drug's biological effects. This review compiled the available information regarding the various effects attributed to Ivermectin. The controversy over its use for the treatment of COVID-19 is demonstrated by this report that considers the proposal unfeasible because the therapeutic doses proposed to achieve this effect cannot be achieved. However, due to the urgent need to find a treatment, an exhaustive and impartial review is necessary in order to integrate the knowledge that exists, to date, of the possible mechanisms through which the treatment may be helpful in defining safe doses and schedules of Ivermectin.

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.

Changes in the neutrophil to lymphocyte ratio as predictors of outcome in pediatric patients with central nervous system tumors undergoing surgical resection.

BACKGROUND: Changes in neutrophil to lymphocyte ratio (ΔNLR) have been used as a clinical tool for stratification and prognosis of patients with solid tumors, there is scarce evidence of their clinical relevance in patients with tumors of the central nervous system who have also undergone surgical resection. OBJECTIVE: Determine if (ΔNLR) are associated with poor response to treatment and worse prognosis in pediatric patients with central nervous system tumors (CNST) who underwent surgical resection. METHODS: We performed a retrospective cohort study; demographic, clinical, and hematological variables were evaluated, Kaplan-Meier survival curves and Cox proportional hazards regression model were performed to evaluate prognosis. RESULTS: The ΔNLR cutoff value obtained through the third interquartile range was 4.30; The probability of survival and complete response to treatment was different between patients with high ΔNLR when compared to patients with low ΔNLR (p= 0.013, p=≪ 0.001, respectively). A high ΔNLR behaved as an independent predictor of worse Overall Survival (HR 2,297; 95% CI: 1,075-4.908, p= 0.032). CONCLUSION: An elevated ΔNLR was a predictor of poor response to treatment and a prognostic factor for worse Overall Survival in pediatric patients with CNST undergoing surgical resection.

Comparative Bioavailability and Pharmacokinetics Between the Solid Form of Metformin vs a Novel Liquid Extemporaneous Formulation in Children.

Metformin pharmacokinetics in a liquid extemporaneous formulation from commercial tablets was determined in paediatric patients. A randomized, transversal clinical trial was conducted in 34 children and adolescents between 7 and 17 years of age. 17 children were randomized to take metformin in the liquid formulation and, after a 1-week wash period, a 500 mg metformin tablet was administered to them. Blood samples were obtained in Whatman 903® cards at 0, 1, 2, 4, 8, 12 and 24 hours. Extraction was made by direct precipitation with acetonitrile (ACN) and methanol, detection by UPLC and tandem mass spectrometry. The method was accurate, precise, selective and linear from 50 to 1000 ng/mL (r = .9982). Comparative pharmacokinetics, tablet vs formulation, were as follows: Cmax 1503.2 ng/mL vs 1521.4, Tmax 1.5 h vs 2.3, and half-life 8.2 vs 7.5 h. The liquid formulation of metformin showed similar pharmacokinetics to the tablet, and the ratios (90% CI) of geometric mean for metformin were 100.63% (89.13-113.6), 98.08% (88.04-109.2), and 97.52% (84.9-112.01), for Cmax, AUC0-t, and AUC 0-∞, respectively. Pharmacokinetics was determined using WinNonlin Pro 3.1 software. The liquid formulation of metformin showed similar pharmacokinetics to the tablet, allowing a more precise dose adjustment and ease of administration.

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.

Antitumor Therapy under Hypoxic Microenvironment by the Combination of 2-Methoxyestradiol and Sodium Dichloroacetate on Human Non-Small-Cell Lung Cancer.

A hypoxic microenvironment is a hallmark in different types of tumors; this phenomenon participates in a metabolic alteration that confers resistance to treatments. Because of this, it was proposed that a combination of 2-methoxyestradiol (2-ME) and sodium dichloroacetate (DCA) could reduce this alteration, preventing proliferation through the reactivation of aerobic metabolism in lung adenocarcinoma cell line (A549). A549 cells were cultured in a hypoxic chamber at 1% O2 for 72 hours to determine the effect of this combination on growth, migration, and expression of hypoxia-inducible factors (HIFs) by immunofluorescence. The effect in the metabolism was evaluated by the determination of glucose/glutamine consumption and the lactate/glutamate production. The treatment of 2-ME (10 µM) in combination with DCA (40 mM) under hypoxic conditions showed an inhibitory effect on growth and migration. Notably, this reduction could be attributed to 2-ME, while DCA had a predominant effect on metabolic activity. Moreover, this combination decreases the signaling of HIF-3α and partially HIF-1α but not HIF-2α. The results of this study highlight the antitumor activity of the combination of 2-ME 10 µl/DCA 40 mM, even in hypoxic conditions.

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.

Comorbidity Index as a Predictor of Mortality in Pediatric Patients With Solid Tumors.

Purpose: The objective of this study was to determine whether a comorbidity index could be used to predict mortality in pediatric patients with chemotherapy-treated solid tumors. Methods: Pediatric patients who underwent chemotherapy treatment for solid tumors were included, and demographic, clinical, and comorbidity data were obtained from patient electronic records. Results: A total of 196 pediatric patients with embryonic solid tumors were included. Metastatic tumors were the most frequently observed (n = 103, 52.6%). The most common comorbidities encountered for the Charlson comorbidity index (CCI) were cellulitis (n = 24, 12.2%) and acute renal failure (n = 15, 7.7%). For the Pediatric Comorbidity Index (PCI), the most frequent comorbidities were pneumonia and sepsis, with n = 64 (32.7%) for each. We evaluated established the prognostic values for both indexes using Kaplan-Meier curves, finding that the CCI and PCI could predict mortality with p < 0.0001. Conclusion: Using the PCI, we observed 100% survival in patients without comorbidities, 70% survival in patients with a low degree of comorbidity, and 20% survival in patients with a high degree of comorbidity. Greater discrimination of probability of survival could be achieved using degrees of comorbidity on the PCI than using degrees of comorbidity on the CCI. The application of the PCI for assessing the hospitalized pediatric population may be of importance for improving clinical evaluation.