Nutritional Status as a Risk Factor for Doxorubicin Cardiotoxicity in Mexican Children with Acute Lymphoblastic Leukemia.

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer in the world. Doxorubicin (Dox) is a very useful drug in these patients, however, one of the main adverse effects caused by the use of Dox is cardiotoxicity (CT). Protein-calorie malnutrition (PCM) is a factor that, among others, can influence the development of CT due to Dox. The aim of our study was to associate PCM as a risk factor for CT induced by Dox in Mexican children with ALL. We included 89 children with ALL who were treated with Dox, from October 2018 to July 2023, and of whom 14 developed some type of CT, 15 were underweight and 3 were overweight. The analysis of the association risk of CT due to PCM shows a statistically significant association of risk of developing CT due to PCM. On the other hand, healthy weight was associated with protection for developing CT due to Dox use. Of the total number of girls who presented CT, all had systolic dysfunction, while 6 of them also had diastolic dysfunction. On the other hand, of the total number of boys who presented CT, all of them had systolic dysfunction and only one of them also had diastolic dysfunction. These results show that in patients in which Dox is being administered, special attention is suggested for girls with PCM, since systolic failure is a precursor and occurs before diastolic failure in girls with PCM.

Evaluation of the Efficacy and Safety of Silver Nanoparticles in the Treatment of Non-Neurological and Neurological Distemper in Dogs: A Randomized Clinical Trial.

Canine distemper is caused by canine distemper virus (CDV), a multisystemic infectious disease with a high morbidity and mortality rate in dogs. Nanotechnology represents a development opportunity for new molecules with antiviral effects that may become effective treatments in veterinary medicine. This study evaluated the efficacy and safety of silver nanoparticles (AgNPs) in 207 CDV, naturally infected, mixed-breed dogs exhibiting clinical signs of the non-neurological and neurological phases of the disease. Group 1a included 52 dogs (experimental group) diagnosed with non-neurologic distemper treated with 3% oral and nasal AgNPs in addition to supportive therapy. Group 1b included 46 dogs (control group) diagnosed with non-neurological distemper treated with supportive therapy only. Group 2a included 58 dogs with clinical signs of neurological distemper treated with 3% oral and nasal AgNPs in addition to supportive therapy. Group 2b included 51 dogs (control group) diagnosed with clinical signs of neurological distemper treated with supportive therapy only. Efficacy was measured by the difference in survival rates: in Group 1a, the survival rate was 44/52 (84.6%), versus 7/46 in Group 1b (15.2%), while both showed clinical signs of non-neurological distemper. The survival rate of dogs with clinical signs of neurological distemper in Group 2a (38/58; 65.6%) was significantly higher than those in Control Group 2b (0/51; 0%). No adverse reactions were detected in experimental groups treated with AgNPs. AgNPs significantly improved survival in dogs with clinical signs of neurological and non-neurological distemper. The use of AgNPs in the treatment of neurological distemper led to a drastic increase in the proportion of dogs recovered without sequels compared to dogs treated without AgNPs. The evidence demonstrates that AgNP therapy can be considered as a targeted treatment in dogs severely affected by canine distemper virus.

Association of genetic polymorphisms NCF4 rs1883112, CBR3 rs1056892, and ABCC1 rs3743527 with the cardiotoxic effects of doxorubicin in children with acute lymphoblastic leukemia.

OBJECTIVES: Cardiotoxicity is a frequent complication secondary to the use of anthracyclines for cancer chemotherapy. Evidence suggests that certain polymorphic genetic variants modify the risk for anthracycline-related cardiotoxicity. Reports documenting the impact of genetic polymorphisms on anthracycline-cardiotoxicity risk in pediatric patients with cancers from Latin American countries are scarce. The objective of this study was to evaluate associations between NCF4 rs1883112, CBR3 rs1056892 and ABCC1 rs3743527 genotype status and echocardiographic parameters indicative of anthracycline-cardiotoxicity in a group of Mexican children with acute lymphoblastic leukemia (ALL). METHODS: Sixty-seven children (2-18 years old) with ALL were treated at the State Cancer Center in Durango, Mexico. NCF4, CBR3, and ABCC1 genotypes were examined by real-time PCR. Left ventricular ejection fraction and diastolic filling ratio were examined as markers of systolic and diastolic anthracycline-toxicity. RESULTS: NCF4 rs1883112 genotype status was significantly associated with the risk of doxorubicin cardiotoxicity [odds ratio (OR) = 10.80, 95% confidence interval (CI) 1.69-68.98, P = 0.01]. There was a significant association between heterozygous CBR3 rs1056892 genotype status and anthracycline-cardiotoxicity risk (OR = 9.91, 95% CI 1.07-91.47, P = 0.04). Heterozygosis for the ABCC1 rs3743527 allele was associated with protection from anthracycline-cardiotoxicity (OR = 0.30, 95% CI 0.09-0.91, P = 0.03). CONCLUSION: This pilot study suggests that selected polymorphic variants may impact the risk for anthracycline-cardiotoxicity in pediatric patients with ALL treated with a contemporary chemotherapeutic regimen in Mexico.

Genotype Analysis of ABCC1, NCF4 and CBR3 Polymorphism and the Association With Childhood Acute Lymphoblastic Leukemia in Mexican Childhood Population.

Background: The identification of genetic risk factors for Acute Lymphoblastic Leukemia (ALL), are increasingly urgent and necessary. Objective: The purpose of this study is to determine the association of the genetic polymorphisms ABCC1 rs3743527, NCF4 rs1883112 and CBR3 rs1056892 with ALL. Methods: DNA samples were obtained in 71 children with ALL (from 2 to 18 years) and in 71 controls without ALL, to determine the polymorphisms by real-time polymerase chain reaction (qPCR), using specific TaqMan probes in a StepOne® thermal cycler (Applied Biosystems, United States). Results: The results of the Odds Ratio analysis show that in the rs1883112 polymorphism of the NCF4 gene, the heterozygous allele has a risk effect for ALL (OR = 3.1870, CI = 1.8880-7.9383 and p = 0.0002), in turn the mutated genotype (AA) is associated with a protective effect (OR = 0.26, 0.1248 to 0.5434 and p = 0.0003). On the other hand, the CBR3 rs1056892 polymorphism shows a significant association of risk to ALL, in the presence of the HT genotype (OR = 2.77, IC = 1.3837 to 5.5651 and p = 0.004) and the mutated genotype of this polymorphism has a significant association with protection to ALL in the HM genotype (OR = 0.52, IC = 0.2639 to 1.0304 and p = 0.05). While the inheritance models of the polymorphisms let us see that of the rs1883112 polymorphism of the NCF4 polymorphism; the HT genotype of the codominant model shows a protective effect against ALL (OR = 0.4117, IC = 0.1718 to 0.9866 and p = 0.04), the recessive model shows us and confirms what we already saw in table number 3, being that there is an association with protective effect in the HM genotype (OR = 0.2604, IC = 0.1248 to 0.5434 and p = 0.0003). In the polymorphism rs1056892 of the CBR3 gene, a protection association was found in the heterozygous allele of the codominant model (OR = 0.3448, IC = 0.1375 to 0.8896 and p = 0.0274). In addition, the recessive inheritance model for the HM genotype shows a protective effect to ALL, (OR = 0.52, CI = 0.9919 to 3.8638 and p = 0.05). Conclusion: There is an evident impact of the NCF4 rs1883112 and CBR3 rs1056892 polymorphisms with an increased risk of susceptibility to ALL; Likewise, through the codominant inheritance model, the effect of the variation of the CBR3 rs1056892 gene as a protective factor against ALL was evaluated.