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Context.—Several countries of the Central America and Caribbean region have been sharing regional neuroblastoma (NB) treatment guidelines. However, there is no standardization in the diagnosis, subclassification, or tumor biology to aid in the risk stratification of these patients.Objective.—To examine the histology and assess the accuracy of the local pathology reports; to evaluate the usefulness of manual MYCN immunohistochemistry (IHC); and to use NB as a model to identify the needs to establish a central pathology review (CPR) program in this region.Design.—A retrospective CPR of specimens derived from patients with a diagnosis of NB and treated under the regional NB guidelines between 2012 and 2017 was conducted, allowing for a comparison between local diagnoses and the CPR diagnoses. Manual MYCN IHC was performed in the confirmed NB specimens and the results compared with known fluorescence in situ hybridization or automated IHC results, when available.Results.—The 156 specimens reviewed included 460 blocks and 183 original slides. Neuroblastoma was confirmed in 138 samples (88.5%), but low concordance rates for Shimada classification (n = 39; 25.0%), mitotic-karyorrhectic index (n = 4; 2.5%), and International Neuroblastoma Pathology Classification (n = 18; 11.5%) were noted. Manual MYCN IHC performed on 120 specimens showed conclusive results in 89.2% (28 positive, 23.4%; 79 negative, 65.8%) and questionable results in 10.8% (n = 13).Conclusions.—This retrospective CPR highlights the need for a CPR program to serve this region, to ensure correct diagnosis and subclassification of NB, and to provide manual MYCN IHC—with reflexing to fluorescence in situ hybridization, if questionable. This approach can further regional collaboration, enhance test utilization, and ultimately improve patients' outcomes.

Accessibility to immunohistochemistry (IHC) is invaluable to proper diagnosis and treatment of pediatric patients with malignant neoplasms. Whereas IHC is widely available in anatomic pathology laboratories in high-income countries, access to it in anatomic pathology laboratories of low- and middle-income countries remains a struggle, with many limitations. To advance the quality of the pathology service offered to children with cancer in areas with limited resources, a 5-day pathology training workshop was offered to pathologists and histotechnologists from various countries of the Central American and Caribbean region. An initial assessment of the workshop participants’ current laboratory capacities was performed, and a regional training center was selected. Didactic and hands-on activities were offered, and review and evaluation of the IHC slides produced during the training course were compared with original slides from the participants’ sites. This model of intensive 5-day training appears to be effective and can potentially be used in other budget-constrained regions. Moreover, it can serve as a continuing education activity for pathologists and histotechnologists, and as part of validations and quality improvement projects to build capacity and develop IHC assay proficiency in low- and middle-income countries.

Assess the cost-effectiveness of an EGFR-mutation testing strategy for advanced NSCLC in first-line therapy with either gefitinib or carboplatin–paclitaxel in Mexican institutions. Cost-effectiveness analysis using a discrete event simulation (DES) model to simulate two therapeutic strategies in patients with advanced NSCLC. Strategy one included patients tested for EGFR-mutation and therapy given accordingly. Strategy two included chemotherapy for all patients without testing. All results are presented in 2014 US dollars. The analysis was made with data from the Mexican frequency of EGFR-mutation. A univariate sensitivity analysis was conducted on EGFR prevalence. Progression-free survival (PFS) transition probabilities were estimated on data from the IPASS and simulated with a Weibull distribution, run with parallel trials to calculate a probabilistic sensitivity analysis. PFS of patients in the testing strategy was 6.76 months (95 % CI 6.10–7.44) vs 5.85 months (95 % CI 5.43–6.29) in the non-testing group. The one-way sensitivity analysis showed that PFS has a direct relationship with EGFR-mutation prevalence, while the ICER and testing cost have an inverse relationship with EGFR-mutation prevalence. The probabilistic sensitivity analysis showed that all iterations had incremental costs and incremental PFS for strategy 1 in comparison with strategy 2. There is a direct relationship between the ICER and the cost of EGFR testing, with an inverse relationship with the prevalence of EGFR-mutation. When prevalence is >10 % ICER remains constant. This study could impact Mexican and Latin American health policies regarding mutation detection testing and treatment for advanced NSCLC.

We have evaluated the efficacy of dapagliflozin in patients with type 1 diabetes mellitus (DM1) without adequate control. We expected that adding dapagliflozin to this population on top of their base treatment would lower their HbA1c levels.We conducted a pragmatic, open, 24-week study of treatment with 10 mg of oral dapagliflozin in patients with DM1 and chronic hyperglycemia. We evaluated glycemic control, lipid profile, weight, and insulin dose. Safety was assessed by adverse event reporting.Fasting glucose levels decreased from 176.42 ± 45.33 mg/dL to 139.67 ± 44.42 mg/dL (p = 0.05); although no significant valued was reached, postprandial glucose showed a decreased tendency from 230.25 ± 52.06 mg/dL to 193.83 ± 45.43 mg/dL (p = 0.08). The hemoglobin A1C (HbA1C) level decreased from 9.18 ± 1.02 (77 ± 11.1 mmol/mol) to 8.05 ± 1.09 % (64 ± 11.9 mmol/mol) (p = 0.0156); total cholesterol decreased from 299 ± 12 to 199 ± 7 mg/dL (p = 0.02); triglycerides decreased from 184 ± 15 to 160 ± 11 mg/dL (p = 0.0002), HDL-C decreased from 40 ± 17 to 42 ± 9 mg/dL (p = 0.54); and LDL-C decreased from 187 ± 19 to 170 ± 21 mg/dL (p = 0.049). No adverse events were reported.The beneficial effects of SGLT2 inhibitors on metabolic control and their safety after a 24-week open study demonstrate their potential indication as an adjunctive treatment with insulin in patients with DM1; however, long-term clinical trials should be considered.

Diabetic animals have contributed to the understanding of the causes, consequences and treatment of diabetes. There are different ways to induce experimental diabetes, chemically induced experimental diabetes has been widely used. Alloxan and streptozotocin are the chemicals most used. A comparative study of these two agents was performed in order to determine their effectiveness. Twenty−seven Sprague−Dawley male adult rats were intraperitoneally(i.p.) injected with 120mg/kg BW of alloxan(AL) and 27 with 60mg/kg BW of streptozotocin(STZ). Levels of glucose, insulin, triglycerides and total cholesterol were determined at different times after the i.p. injection. The effect of the two chemicals on the Langerhans’ islets was histochemically demonstrated. The reversibility of the diabetic state, 20 days after the i.p. injection of AL, was demonstrated by the recovery of insulin levels, reduction of the glucose and triglycerides concentration and by positive anti−insulin antibodies reaction in the pancreatic tissue. STZ proved to induce a more stable and permanent diabetic state.

The most prevalent dyslipidemias in Mexico are low high-density lipoprotein (HDL) and high triglyceride (TG) levels. Hypertriglyceridemia (HTG) has been considered an independent risk factor for cardiovascular disease (CVD). The aim of this study was to evaluate the efficacy of rosuvastatin (RSV) in reducing TG levels in Mexican patients.A randomized, double-blind, double-dummy, parallel-group, placebo-controlled, multicenter, phase IV study was conducted. Patients were of both genders, ≥ 18 years old, with basal TG levels between 200 and 800 mg/dl, LDL levels ≤ 190 mg/dl. Patients were randomized to receive rosuvastatin 10 mg (Group 1), 20 mg (Group 2) or placebo (Group 3) once daily for 8 weeks. Primary efficacy was TG level; secondary efficacy was non-HDL; HDL, low-density lipoprotein (LDL), total cholesterol (TC), Apo (apolipoprotein) A1, and ApoB. Safety data were evaluated up to 30 days after the last dose of medication. The Mann-Whitney U-test was performed to contrast each RSV groups against placebo; p0.05 was considered significant. Trial registry number is NCT00473655.A total of 334 patients were randomized: Group 1 = 111, Group 2 = 112, and Group 3 = 111. Basal TG median value levels were 278 mg/dl, 266 mg/dl, 279 mg/dl with median reduction (MdR) at 8 weeks of 26.6%, 32.19% and 7.58%, respectively, (Group 1 vs. Group 3 p = 0.002, and Group 2 vs. Group 3 p0.0001). Basal non-HDL values were 179 mg/dl, 180 mg/dl and 179 mg/dl with a MdR of 27%, 32% and 8%, respectively (Group 1 vs. Group 3 p0.0001, and Group 2 vs. Group 3 p0.0001); basal LDL vales were 130 mg/dl, 130 mg/dl and 127 mg/dl with MdR 35%, 44% and -4% (Group 1 vs. Group 3 p0.0001, Group 2 vs. Group 3 p0.0001); basal ApoB values were 114 mg/dl, 115 mg/dl and 110.5 mg/dl with MdR 25%, 33% and -0.5% (Group 1 vs. Group 3 p0.0001, Group 2 vs. Group 3 p0.001).Rosuvastatin 10 and 20 mg/day significantly reduced triglycerides and improved atherogenic lipid profile in HTG Mexican patients. The main limitation was the short follow-up time period.

e12624 Background: With progress made towards meeting the Millennium Development Goals, cancer is now an important contributor to childhood mortality in CA. Hospital-based data suggests regional di...