Background Increased inflammation has been well defined in COVID-19, while definitive pathways driving severe forms of this disease remain uncertain. Neutrophils are known to contribute to immunopathology in infections, inflammatory diseases and acute respiratory distress syndrome (ARDS), a primary cause of morbidity and mortality in COVID-19. Changes in neutrophil function in COVID-19 may give insight into disease pathogenesis and identify therapeutic targets. Methods Blood was obtained serially from critically ill COVID-19 patients for eleven days. Neutrophil extracellular trap formation (NETosis), oxidative burst, phagocytosis and cytokine levels were assessed. Lung tissue was obtained immediately post-mortem for immunostaining. Pubmed searches for neutrophils, lung and COVID-19 yielded ten peer-reviewed research articles in English. Results Elevations in neutrophil-associated cytokines IL-8 and IL-6, and general inflammatory cytokines IP-10, GM-CSF, IL-1b, IL-10 and TNF, were identified both at first measurement and across hospitalization (p<0.0001). COVID neutrophils had exaggerated oxidative burst (p<0.0001), NETosis (p<0.0001) and phagocytosis (p<0.0001) relative to controls. Increased NETosis correlated with leukocytosis and neutrophilia, and neutrophils and NETs were identified within airways and alveoli in lung parenchyma of 40% of SARS-CoV-2 infected lungs available for examination (2 out of 5). While elevations in IL-8 and ANC correlated with disease severity, plasma IL-8 levels alone correlated with death. Conclusions Literature to date demonstrates compelling evidence of increased neutrophils in the circulation and lungs of COVID-19 patients. importantly, neutrophil quantity and activation correlates with severity of disease. Similarly, our data shows that circulating neutrophils in COVID-19 exhibit an activated phenotype with enhanced NETosis and oxidative burst.
Background: Treatment refusal and abandonment are major causes of treatment failure for children with cancer in low-and middle-income countries (LMICs), like Guatemala. This study identified risk factors for and described the intervention that decreased abandonment. younger age (P = 0.017) and earlier year of diagnosis (P < 0.001). Indigenous race/ethnicity (P = 0.002) was associated with increased risk of abandonment alone. Abandonment correlated with decreased overall survival: 0.57 ± 0.02 (survival ± standard error) for those who completed therapy versus 0.06 ± 0.02 for those who abandoned treatment (P < 0.001) at 8.3 years. Methods Conclusion:This study identified distance, age, year of diagnosis and indigenous race/ethnicity as risk factors for abandonment. A multidisciplinary intervention reduced abandonment and can be replicated in other LMICs. K E Y W O R D Sabandonment, global oncology, low-and middle-income country, pediatric oncology, refusal
The prospects for survival of children in low and middle income countries are linked to their families socio-economic status (SES), of which income is only one component. Developing a comprehensive measure of SES is required. Informed by clinical experience, a 15-item instrument was designed in Guatemala to categorize SES by five levels in each item. Almost 75% of families attending the Unidad Nacional de Oncología Pediátrica were in the lowest three of six categories, providing a framework for stratified financial and nutritional support. The measure of SES offers an opportunity for examining associations with health outcomes throughout Latin America.
Background At least 80% of children with cancer live in low‐ and middle‐income countries where the prevalence of malnutrition and socioeconomic disadvantage is high. We examined the relationship between nutritional status (NS), assessed by arm anthropometry, and socioeconomic status (SES) in children diagnosed with cancer at Unidad Nacional de Oncologia Pediatrica (UNOP) in Guatemala over a three‐year period. Method Patients aged 0 to 18 years of age diagnosed between January 2015 and December 2017 were included. NS was evaluated by mid‐upper arm circumference, triceps skin fold thickness, and serum albumin level, and subjects were classified as adequately nourished, moderately depleted, and severely depleted nutritionally. SES was measured by a 15‐item instrument developed at UNOP. Results Of 1365 patients diagnosed in the study period, 1060 (78%) fulfilled the eligibility criteria. Only 6% of patients were classified as medium to high, the remainder as medium–low to extremely low SES. Almost 47% were severely depleted at diagnosis, 19% moderately depleted, and 34% adequately nourished. SES was shown to be a determinant of NS; with progressively lower SES, the probability of a decline in NS increased by a factor of 1.04 points (P < 0.0001). Leukemia and lymphoma were also important predictors of nutritional depletion with odds ratios of 6.08 (95% CI, 1.74–28.28; P = 0.008) for leukemias and 4.83 (95% CI, 1.33–23.03; P = 0.03) for lymphomas. Conclusion Both low SES and a diagnosis of leukemia or lymphoma are strong predictors of poor NS at diagnosis in children with cancer in Guatemala.
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