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CASE REPORT: We report the first case of orbital myeloid sarcoma that was successfully treated with a standard venetoclax dose of 25%. A 38-year-old man with acute myeloid leukemia (AML) post-haplo-hematopoietic stem cell transplantation (HSCT) presented with a nine-month history of progressive right proptosis and a visual acuity deficit. The patient was treated with venetoclax (100 mg orally on days 1-28), cytarabine (40 mg subcutaneously, days 1-10), and itraconazole (100 mg twice daily orally on days 1-28). MANAGEMENT AND OUTCOME: The present case report shows that using cytochrome P450 (CYP) inhibitors is a helpful strategy to reduce the cost of expensive treatments. DISCUSSION: There are limited data on the use of CYP inhibitors as a strategy to reduce the costs of expensive drugs (i.e. venetoclax). This approach has some advantages over standard dose venetoclax (400 mg/day) such as significantly reduced costs (which is relevant for patients in low-income countries). In this case, we used itraconazole-a potent CYP3A4 inhibitor-which can theoretically reduce the dose to 100 mg/day without losing serum therapeutic concentrations.

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The inhibition of cytochrome P450 (CYP) enzymes is the most frequent cause of drug-drug interactions. Many safe, inexpensive and widely available therapeutic drugs can inhibit CYP enzymes (e.g., azoles). Also, the specific potency of inhibition and the targeted CYP enzyme have been well described (e.g., itraconazole strongly inhibits CYP enzyme 3A4 and, in turn, CYP3A4 metabolizes venetoclax and ibrutinib). CYP enzyme inhibitors increase the plasma concentration of other drugs via shared metabolic pathways. We herein present the effects of inhibiting CYP enzymes with itraconazole-venetoclax for the treatment of refractory acute myeloid leukaemia, as well as itraconazole-ibrutinib to treat steroid-refractory acute graft vs. host disease in the same patient. Both of the patient's conditions responded completely. This appears to be a feasible strategy that decreases treatment costs by 75%. Previous Food and Drug Administration recommendations and clinical data support these subsequent dose reductions. Eleven months after the transplant, the patient remains in complete response and with no minimal residual disease. Another patient had been effectively treated before with CYP enzyme inhibition prior to venetoclax-itraconazole administration for orbital myeloid sarcoma. Thus, this case study furthers information on the CYP enzyme inhibition strategy when associated with another costly drug, ibrutinib. The CYP enzyme inhibition strategy could be applied to many more anticancer drugs (e.g., ruxolitinib and ponatinib) and facilitate the availability of expensive oncological treatments in low- and middle-income countries. Also, this strategy could be further generalized by using different CYP enzyme inhibitors with varied pharmacokinetic and pharmacodynamic properties (i.e., grapefruit, azoles and clarithromycin).

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OBJECTIVE: To explore the diagnostic utility of 31 electrocardiogram (ECG) criteria for detecting echocardiographic (Echo) left ventricular geometry using accuracy. METHODS: This cross-sectional study included consecutive adults (> 18 years) that were classified by Echo left ventricular geometry as normal (NL), concentric remodeling (CR), concentric hypertrophy (CH), and eccentric hypertrophy (EH). Thirty-one state-of-the-art ECG criteria for Echo left ventricular hypertrophy were calculated. AUC 95%CI, accuracy, sensitivity, specificity, and positive and negative predictive value for detecting Echo left ventricular geometries were compared. Multivariable linear regression models were produced using the ECG criteria as the dependent variable. RESULTS: A total of 672 adults were included in the study. From 31 ECG criteria, Cornell (ECG21, SV3 + RaVL) and modified Cornell (ECG 31, RaVL + deepest S in all leads) criteria have the best overall AUC in differentiating NL versus CH (0.666 and 0.646), NL versus EH (0.686 and 0.656), CR versus CH (0.687 and 0.661), and CR versus EH (0.718 and 0.676). In multivariable linear regression models, CH and EH had the strongest effect on the final voltage in Cor- nell (ECG21) and modified Cornell (ECG31). CONCLUSIONS: From 31 state-of-the-art criteria, Cornell and modified Cornell criteria have the best AUC and accuracy for predicting most left ventricular geometries. CH and EH had the strongest effect on the voltage of Cornell and modified Cornell criteria compared to body mass index, age, diabetes, hypertension, and chronic heart disease. The ECG criteria poorly differentiate NL from CR and CH from EH.

OBJETIVO: Explorar la utilidad diagnóstica de 31 criterios de ECG para detectar la geometría ecocardiográfica del ventrículo izquierdo usando la exactitud, área bajo la curva, sensibilidad, especificidad, y valor predictivo positivo y negativo. ­. MÉTODOS: Este estudio transversal incluyó adultos (> 18 años) que se sometieron a ECG y ecocardiograma transtorácico. Los pacientes fueron clasificados según la geometría del ventrículo izquierdo: normal (NL), remodelado concéntrico (RC), hipertrofia concéntrica (HC) e hipertrofia excéntrica (HE). Se calcularon 31 criterios clásicos de ECG para detectar hipertrofia ventricular izquierda y se comparó el rendimiento diagnóstico en cada geometría. Creamos un modelo de regresión lineal múltiple usando los criterios de ECG como variable dependiente. RESULTADOS: Se incluyeron 672 adultos. Los criterios de Cornell (ECG 21, SV3 + RaVL) y Cornell modificado (ECG31, RaVL + S mas profunda de las 12 derivaciones) tienen el mejor AUC para diferenciar NL versus HC (0.666 y 0.646), NL versus HE (0.686 y 0.656), RC versus HC (0.687 y 0.661) y RC versus HE (0.718 y 0.676). En el análisis multivariado la geometría del ventrículo izquierdo (HC e HE) fue la variable que mas influyó en el resultado final del criterio de Cornell y de Cornell modificado. CONCLUSIÓN: De los 31 criterios clásicos explorados, los criterios de Cornell y Cornell modificado tienen el mejor AUC y exactitud para predecir la mayoría de las geometrías del ventrículo izquierdo. Los criterios del ECG no diferencian bien la geometría NL del RC ni HC de la HE.

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Immune thrombocytopenia (ITP) is an autoimmune disease that results from antibody-mediated platelet destruction and impaired platelet production. Novel therapies have emerged in the last decade, but 15-20% of patients will relapse or fail and require further therapy. We performed a prospective, single-arm intervention study on seven patients with chronic, persistent, or refractory ITP from the Hospital Universitario "Dr. José E González", in Monterrey, Mexico between 2015 and 2019. Eligible patients received oral oseltamivir 75 mg twice daily for 5 days and were followed up for six months. Most patients received a median of three distinct therapies (range 2-6). Four patients (57.1%) received combined therapy. The median time for any response was 55.5 days (range = 14-150). All patients responded at some point in time (ORR = 100%, six had a proportion of loss of response [PR], and one achieved [CR]). Six months after oseltamivir administration, three patients (42.9%) maintained a response, and one patient had a CR (14.3%). Oseltamivir was well tolerated with a good overall response rate and was useful for treating chronic ITP. We observed an initial increase in the number of platelets; however, this response was not maintained.

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BACKGROUND: Left ventricular hypertrophy detected by echocardiography (Echo-LVH) is an independent predictor of mortality. Integration of the Philips DXL-16 algorithm into the electrocardiogram (ECG) extensively analyses the electricity of the heart. Machine learning techniques such as the C5.0 could lead to a new decision tree criterion to detect Echo-LVH. OBJECTIVES: To search for a new combination of ECG parameters predictive of Echo-LVH. The final model is called the Cardiac Hypertrophy Computer-based model (CHCM). METHODS: We extracted the 458 ECG parameters provided by the Philips DXL-16 algorithm in patients with Echo-LVH and controls. We used the C5.0 ML algorithm to train, test, and validate the CHCM. We compared its diagnostic performance to validate state-of-the-art criteria in our patient cohort. RESULTS: We included 439 patients and considered an alpha value of 0.05 and a power of 99%. The CHCM includes T voltage in I (≤0.055 mV), peak-to-peak QRS distance in aVL (>1.235 mV), and peak-to-peak QRS distance in aVF (>0.178 mV). The CHCM had an accuracy of 70.5% (CI95%, 65.2-75.5), a sensitivity of 74.3%, and a specificity of 68.7%. In the external validation cohort (n = 156), the CHCM had an accuracy of 63.5% (CI95%, 55.4-71), a sensitivity of 42%, and a specificity of 82.9%. The accuracies of the most relevant state-of-the-art criteria were: Romhilt-Estes (57.4%, CI95% 49-65.5), VDP Cornell (55.7%, CI95%47.6-63.7), Cornell (59%, CI95%50.8-66.8), Dalfó (62.9%, CI95%54.7-70.6), Sokolow Lyon (53.9%, CI95%45.7-61.9), and Philips DXL-16 algorithm (54.5%, CI95%46.3-62.5). CONCLUSION: ECG computer-based data and the C5.0 determined a new set of ECG parameters to predict Echo-LVH. The CHCM classifies patients as Echo-LVH with repolarization abnormalities or LVH with increased voltage. The CHCM has a similar accuracy, and is slightly more sensitive than the state-of-the-art criteria.

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BACKGROUND: Several electrocardiographic (ECG) criteria have been validated for the diagnosis of left ventricular hypertrophy (LVH); the majority in Caucasian subjects from Europe and North America. Diagnostic utility of ECG criteria to detect LVH has never been established in our population; nonetheless they are frequently used. OBJECTIVE: To evaluate the diagnostic utility of different LVH ECG criteria in a Northern Mexican population and to determine the effect of gender, age, body mass index (BMI), hypertension and ischaemic heart disease (IHD) on their performance. METHODS: We conducted an observational, case-control study in patients divided according to the presence of LVH in an echocardiogram (Echo). We calculated the accuracy, sensitivity (Se), specificity (Sp), positive predictive value (PPV) and negative predictive value (NPV) of 22 ECG criteria. RESULTS: Four hundred thirty-two patients were studied (202 had LVH). The Dalfó criterion (ECG18. SV3 + RaVL) had the best diagnostic performance with a Se of 56%, Sp of 71.3%, PPV 62.9%, NPV 65% and a diagnostic accuracy (95%CI) of 64.1% (59.5-68.6). This criterion had the highest accuracy in both genders, in all BMI, in older patients (>60 years) and in those with positive Echo ischaemic heart disease (IHD); it also performed well in patients with history of IHD and in hypertensive patients. VDP Cornell had the best accuracy in patients less than 60 years old, and in patients with non-ischaemic findings by Echo. CONCLUSIONS: The Dalfó criteria had the overall best accuracy in the detection of LVH, and specific populations.

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The electrocardiogram (ECG) is the most common tool used to predict left ventricular hypertrophy (LVH). However, it is limited by its low accuracy (<60%) and sensitivity (30%). We set forth the hypothesis that the Machine Learning (ML) C5.0 algorithm could optimize the ECG in the prediction of LVH by echocardiography (Echo) while also establishing ECG-LVH phenotypes. We used Echo as the standard diagnostic tool to detect LVH and measured the ECG abnormalities found in Echo-LVH. We included 432 patients (power = 99%). Of these, 202 patients (46.7%) had Echo-LVH and 240 (55.6%) were males. We included a wide range of ventricular masses and Echo-LVH severities which were classified as mild (n = 77, 38.1%), moderate (n = 50, 24.7%) and severe (n = 75, 37.1%). Data was divided into a training/testing set (80%/20%) and we applied logistic regression analysis on the ECG measurements. The logistic regression model with the best ability to identify Echo-LVH was introduced into the C5.0 ML algorithm. We created multiple decision trees and selected the tree with the highest performance. The resultant five-level binary decision tree used only six predictive variables and had an accuracy of 71.4% (95%CI, 65.5-80.2), a sensitivity of 79.6%, specificity of 53%, positive predictive value of 66.6% and a negative predictive value of 69.3%. Internal validation reached a mean accuracy of 71.4% (64.4-78.5). Our results were reproduced in a second validation group and a similar diagnostic accuracy was obtained, 73.3% (95%CI, 65.5-80.2), sensitivity (81.6%), specificity (69.3%), positive predictive value (56.3%) and negative predictive value (88.6%). We calculated the Romhilt-Estes multilevel score and compared it to our model. The accuracy of the Romhilt-Estes system had an accuracy of 61.3% (CI95%, 56.5-65.9), a sensitivity of 23.2% and a specificity of 94.8% with similar results in the external validation group. In conclusion, the C5.0 ML algorithm surpassed the accuracy of current ECG criteria in the detection of Echo-LVH. Our new criteria hinge on ECG abnormalities that identify high-risk patients and provide some insight on electrogenesis in Echo-LVH.

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The aim was to analyze the effect of fractional flow reserve (FFR), intravascular ultrasound (IVUS) and optical coherence tomography (OCT) on fluoroscopy time (FT), radiation dose (RD) and contrast volume (CV) in patients undergoing coronary angiography. This case-control study included consecutive patients above the age of 18, who underwent coronary angiography. FT, RD, and CV after each procedure were retrospectively recorded. Multivariate models were used to demonstrate the effect of these complementary studies and other factors, on radiation and contrast exposure. A total of 1047 patients were included, 74.5% were men and the mean (SD) age was 62.4 (12.1) years. Complementary studies performed were: IVUS (n = 237), FFR (n = 56) and OCT (n = 37). FFR and IVUS had a small effect on FT (η = 0.008 B = 2.2, p < 0.001; η = 0.009, B = 2.5, p < 0.001), while OCT had no effect (η = 0.002 B = 2.9, p < 0.183). IVUS, FFR and OCT had no effect on the RD. IVUS did not affect contrast volume (η = 0.002 B = 9.4, p < 0.163) while OCT and FFR had a small effect on CV (η = 0.006 B = 39, p < 0.01; η = 0.008 B = 37, p < 0.003). The number of placed stents had a significant effect on FT (η = 0.192, Β = 4.2, p < 0.001), RD (η = 0.129, Β = 511.8, p < 0.001) and CV (η = 0.177, Β = 40.5, p < 0.001). The use of complementary studies in hemodynamics did not modify the received RD and had a minor effect on FT and the CV used.

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