Treatment Access for Gastrointestinal Stromal Tumor in Predominantly Low- and Middle-Income Countries.

Importance: Gastrointestinal stromal tumor (GIST) is a rare cancer treated with the tyrosine kinase inhibitors imatinib mesylate or sunitinib malate. In general, in low- and middle-income countries (LMICs), access to these treatments is limited. Objective: To describe the demographic characteristics, treatment duration, and survival of patients with GIST in LMICs treated with imatinib and sunitinib through The Max Foundation programs. Design, Setting, and Participants: This retrospective database cohort analysis included patients in 2 access programs administered by The Max Foundation: the Glivec International Patient Assistance Program (GIPAP), from January 1, 2001, to December 31, 2016, and the Max Access Solutions (MAS) program, January 1, 2017, to October 12, 2020. Sixty-six countries in which The Max Foundation facilitates access to imatinib and sunitinib were included. Participants consisted of patients with approved indications for imatinib, including adjuvant therapy in high-risk GIST by pathologic evaluation of resected tumor or biopsy-proven unresectable or metastatic GIST. All patients were reported to have tumors positive for CD117(c-kit) by treating physicians. A total of 9866 patients received treatment for metastatic and/or unresectable disease; 2100 received adjuvant imatinib; 49 received imatinib from another source and were only included in the sunitinib analysis; and 53 received both imatinib and sunitinib through The Max Foundation programs. Data were analyzed from October 13, 2020, to January 30, 2024. Main Outcomes and Measures: Demographic and clinical information was reported by treating physicians. Kaplan-Meier analysis was used to estimate time to treatment discontinuation (TTD) and overall survival (OS). An imputation-based informed censoring model estimated events for patients lost to follow-up after treatment with adjuvant imatinib. Patients who were lost to follow-up with metastatic or unresectable disease were presumed deceased. Results: A total of 12 015 unique patients were included in the analysis (6890 male [57.6%]; median age, 54 [range, 0-100] years). Of these, 2100 patients were treated with imatinib in the adjuvant setting (median age, 54 [range 8-88] years) and 9866 were treated with imatinib for metastatic or unresectable disease (median age, 55 [range, 0-100] years). Male patients comprised 5867 of 9866 patients (59.5%) with metastatic or unresectable disease and 1023 of 2100 patients (48.7%) receiving adjuvant therapy. The median OS with imatinib for unresectable or metastatic disease was 5.8 (95% CI, 5.6-6.1) years, and the median TTD was 4.2 (95% CI, 4.1-4.4) years. The median OS with sunitinib for patients with metastatic or unresectable GIST was 2.0 (95% CI, 1.5-2.5) years; the median TTD was 1.5 (95% CI, 1.0-2.1) years. The 10-year OS rate in the adjuvant setting was 73.8% (95% CI, 67.2%-81.1%). Conclusions and Relevance: In this cohort study of patients with GIST who were predominantly from LMICs and received orally administered therapy through the GIPAP or MAS programs, outcomes were similar to those observed in high-resource countries. These findings underscore the feasibility and relevance of administering oral anticancer therapy to a molecularly defined population in LMICs, addressing a critical gap in cancer care.

Craniectomías descompresivas en el traumatismo craneoencefálico: la visión del intensivista / Decompressive craniectomy in traumatic brain injury: the intensivist's point of view

Objetivo Realizar una escala con parámetros clínicos y radiológicos precoces tras un TCE que identifique a los enfermos que en su evolución posterior van a someterse a una CD. Método Estudio observacional de una cohorte retrospectiva de pacientes que tras un TCE ingresan en la Sección de Neurocríticos del Servicio de Medicina Intensiva de nuestro hospital durante un periodo de 5 años (2014-2018). Detección de variables clínicas y radiológicas y creación de todos los modelos posibles con las variables significativas, clínicamente relevantes y de fácil detección precoz. Selección del que presentaba valores más bajos de criterios de información bayesiano y de Akaike para la creación de la escala. Calibración y validación interna mediante la prueba de bondad de ajuste de Hosmer-Lemeshow y análisis bootstrapping con 1.000 re-muestreos. Resultados Se realizaron 37 CD en 153 enfermos que ingresaron tras un TCE. El modelo final resultante incluía desviación de línea media, GCS y colapso ventricular con un área bajo la curva ROC de 0,84 (IC95% 0,78-0,91) y Hosmer-Lemeshow p=0,71. La escala desarrollada detectaba bien a los enfermos que iban a precisar una CD precoz (en las primeras 24horas) tras un TCE (2,5±0,5) pero no a aquellos que la necesitarían en una fase más tardía de su enfermedad (1,7±0,8). Sin embargo, parece prevenirnos sobre los enfermos que si bien no precisan inicialmente una CD sí tienen probabilidades de necesitarla posteriormente en su evolución (CD tardía vs. no precisan CD, 1,7±0,8 vs. 1±0,7; p=0,002). Conclusión Hemos desarrollado una escala pronóstica que permite detectar en nuestro medio, con una buena sensibilidad y especificidad y usando criterios clínico-radiológicos precoces, aquellos pacientes que tras un TCE van a precisar una CD (AU)

Objetive To perform a score with early clinical and radiological findings after a TBI that identifies the patients who in their subsequent evolution are going to undergo DC. Method Observational study of a retrospective cohort of patients who, after a TBI, enter the Neurocritical Section of the Intensive Care Unit of our hospital for a period of 5 years (2014-2018). Detection of clinical and radiological criteria and generation of all possible models with significant, clinically relevant and easy to detect early variables. Selection of the one with the lowest Bayesian Information Criterion and Akaike Information Criterion values for the creation of the score. Calibration and internal validation of the score using the Hosmer-Lemeshow and a bootstrapping analysis with 1,000 re-samples respectively. Results 37 DC were performed in 153 patients who were admitted after a TBI. The resulting final model included Cerebral Midline Deviation, GCS and Ventricular Collapse with an Area under ROC Curve: 0.84 (95% IC 0.78-0.91) and Hosmer-Lemeshow p=0.71. The developed score detected well those patients who were going to need an early DC (first 24hours) after a TBI (2.5±0.5) but not those who would need it in a later stage of their disease (1.7±0.8). However, it seems to advice us about the patients who, although not requiring an early DC are likely to need it later in their evolution (DC after 24hours vs do not require DC, 1.7±0.8 vs 1±0.7; p=0.002). Conclusion We have developed a prognostic score using early clinical-radiological criteria that, in our environment, detects with good sensitivity and specificity those patients who, after a TBI, will require a DC (AU)

Decompressive craniectomy in traumatic brain injury: The intensivist's point of view.

OBJETIVE: To perform a score with early clinical and radiological findings after a TBI that identifies the patients who in their subsequent evolution are going to undergo DC. METHOD: Observational study of a retrospective cohort of patients who, after a TBI, enter the Neurocritical Section of the Intensive Care Unit of our hospital for a period of 5 years (2014-2018). Detection of clinical and radiological criteria and generation of all possible models with significant, clinically relevant and easy to detect early variables. Selection of the one with the lowest Bayesian Information Criterion and Akaike Information Criterion values for the creation of the score. Calibration and internal validation of the score using the Hosmer-Lemeshow and a bootstrapping analysis with 1000 re-samples respectively. RESULTS: 37 DC were performed in 153 patients who were admitted after a TBI. The resulting final model included Cerebral Midline Deviation, GCS and Ventricular Collapse with an Area under ROC Curve: 0.84 (95% IC 0.78-0.91) and Hosmer-Lemeshow p=0.71. The developed score detected well those patients who were going to need an early DC (first 24h) after a TBI (2.5±0.5) but not those who would need it in a later stage of their disease (1.7±0.8). However, it seems to advice us about the patients who, although not requiring an early DC are likely to need it later in their evolution (DC after 24h vs. do not require DC, 1.7±0.8 vs. 1±0.7; p=0.002). CONCLUSION: We have developed a prognostic score using early clinical-radiological criteria that, in our environment, detects with good sensitivity and specificity those patients who, after a TBI, will require a DC.

Incidence, Treatment, and Outcome Trends of Necrotizing Enterocolitis in Preterm Infants: A Multicenter Cohort Study.

Background: Data regarding the incidence and mortality of necrotizing enterocolitis trends are scarce in the literature. Recently, some preventive strategies have been confirmed (probiotics) or increased (breastfeeding rate). This study aims to describe the trends of necrotizing enterocolitis incidence, treatment, and mortality over the last decade in Spain. Methods: Multicenter cohort study with data from the Spanish Neonatal Network-SEN1500 database. The study period comprised from January 2005 to December 2017. Preterm infants <32 weeks of gestational age at birth without major congenital malformations were included for analysis. The main study outcomes were necrotizing enterocolitis incidence, co-morbidity (bronchopulmonary dysplasia, late-onset sepsis, cystic periventricular leukomalacia, retinopathy of prematurity, acute kidney injury), mortality, and surgical/non-surgical treatment. Results: Among the 25,821 included infants, NEC incidence was 8.8% during the whole study period and remained stable when comparing 4-year subperiods. However, more cases were surgically treated (from 48.8% in 2005-2008 to 70.2% in 2015-2017, p < 0.001). Mortality improved from 36.7% in the 2005-2008 to 26.6% in 2015-2017 (p < 0.001). Breastfeeding rates improved over the studied years (24.3% to 40.5%, p < 0.001), while gestational age remained invariable (28.5 weeks, p = 0.20). Prophylactic probiotics were implemented during the study period in some units, reaching 18.6% of the patients in 2015-2017. Conclusions: The incidence of necrotizing enterocolitis remained stable despite the improvement regarding protective factors frequency. Surgical treatment became more frequent over the study period, whereas mortality decreased.

Decompressive craniectomy in traumatic brain injury: the intensivist's point of view. / Craniectomías descompresivas en el traumatismo craneoencefálico: la visión del intensivista.

OBJETIVE: To perform a score with early clinical and radiological findings after a TBI that identifies the patients who in their subsequent evolution are going to undergo DC. METHOD: Observational study of a retrospective cohort of patients who, after a TBI, enter the Neurocritical Section of the Intensive Care Unit of our hospital for a period of 5 years (2014-2018). Detection of clinical and radiological criteria and generation of all possible models with significant, clinically relevant and easy to detect early variables. Selection of the one with the lowest Bayesian Information Criterion and Akaike Information Criterion values for the creation of the score. Calibration and internal validation of the score using the Hosmer-Lemeshow and a bootstrapping analysis with 1,000 re-samples respectively. RESULTS: 37 DC were performed in 153 patients who were admitted after a TBI. The resulting final model included Cerebral Midline Deviation, GCS and Ventricular Collapse with an Area under ROC Curve: 0.84 (95% IC 0.78-0.91) and Hosmer-Lemeshow p=0.71. The developed score detected well those patients who were going to need an early DC (first 24hours) after a TBI (2.5±0.5) but not those who would need it in a later stage of their disease (1.7±0.8). However, it seems to advice us about the patients who, although not requiring an early DC are likely to need it later in their evolution (DC after 24hours vs do not require DC, 1.7±0.8 vs 1±0.7; p=0.002). CONCLUSION: We have developed a prognostic score using early clinical-radiological criteria that, in our environment, detects with good sensitivity and specificity those patients who, after a TBI, will require a DC.

Early prognostic value of an Algorithm based on spectral Variables of Ventricular fibrillAtion from the EKG of patients with suddEn cardiac death: A multicentre observational study (AWAKE).

OBJECTIVE: Ventricular fibrillation (VF)-related sudden cardiac death (SCD) is a leading cause of mortality and morbidity. Current biological and imaging parameters show significant limitations on predicting cerebral performance at hospital admission. The AWAKE study (NCT03248557) is a multicentre observational study to validate a model based on spectral ECG analysis to early predict cerebral performance and survival in resuscitated comatose survivors. METHODS: Data from VF ECG tracings of patients resuscitated from SCD will be collected using an electronic Case Report Form. Patients can be either comatose (Glasgow Coma Scale - GCS - ≤8) survivors undergoing temperature control after return of spontaneous circulation (RoSC), or those who regain consciousness (GCS=15) after RoSC; all admitted to Intensive Cardiac Care Units in 4 major university hospitals. VF tracings prior to the first direct current shock will be digitized and analyzed to derive spectral data and feed a predictive model to estimate favorable neurological performance (FNP). The results of the model will be compared to the actual prognosis. RESULTS: The primary clinical outcome is FNP during hospitalization. Patients will be categorized into 4 subsets of neurological prognosis according to the risk score obtained from the predictive model. The secondary clinical outcomes are survival to hospital discharge, and FNP and survival after 6 months of follow-up. The model-derived categorisation will be also compared with clinical variables to assess model sensitivity, specificity, and accuracy. CONCLUSIONS: A model based on spectral analysis of VF tracings is a promising tool to obtain early prognostic data after SCD.

Med-Score 24: A multivariable prediction model for poststernotomy mediastinitis 24 hours after admission to the intensive care unit.

OBJECTIVES: Mediastinitis is a serious complication of heart surgery. In this study, we developed a bedside risk score for poststernotomy mediastinitis. METHODS: Data were prospectively collected from 4625 patients admitted to our intensive care unit after heart surgery (January 2005-June 2011). Mediastinitis was defined according to Centers for Disease Control and Prevention criteria. A logistic model was constructed in a randomly selected subgroup of 2618 patients and validated in a second cohort of 1352, as well as in a prospective cohort of 2615 (June 2011-December 2015). Model discriminatory power was assessed according to the area under the receiver operating characteristic curve (AUROC). The ß coefficients of the model were used to define 3 levels of mediastinitis risk as a score designated Med-Score 24. Its performance to predict mediastinitis was compared with that of the logistic EuroSCORE and Society of Thoracic Surgeons score. RESULTS: Ninety-four (2.36%) patients developed mediastinitis. The risk factors identified as predictive of mediastinitis (AUROC 0.80) were 4 preoperative variables (age >70 years, chronic obstructive lung disease, obesity, and antiplatelet therapy) and 3 perioperative variables (prolonged ischemia, emergency reoperation, and prolonged intubation). AUROCs for the Society of Thoracic Surgeons score and logistic EuroSCORE were 0.63 and 0.55, respectively, both differing significantly from the area calculated for Med-Score 24 (P < .001). CONCLUSIONS: The score developed showed excellent predictive power 24 hours after admission to the intensive care unit for mediastinitis risk. This simple tool helps stratify patients according to this risk, thus identifying high-risk patients for preventive measures. In our patient cohort, Med-Score 24 performed better than other scores used for this purpose.

Early prognostic value of an Algorithm based on spectral Variables of Ventricular fibrillAtion from the EKG of patients with suddEn cardiac death: A multicentre observational study (AWAKE) / Valor pronóstico precoz de un algoritmo basado en variables espectrales de la fibrilación ventricular del ECG de pacientes con muerte súbita cardiaca: estudio observacional multicéntrico (AWAKE)

Abstract Objective: Ventricular fibrillation (VF)-related sudden cardiac death (SCD) is a leading cause of mortality and morbidity. Current biological and imaging parameters show significant limitations on predicting cerebral performance at hospital admission. The AWAKE study (NCT03248557) is a multicentre observational study to validate a model based on spectral ECG analysis to early predict cerebral performance and survival in resuscitated comatose survivors. Methods: Data from VF ECG tracings of patients resuscitated from SCD will be collected using an electronic Case Report Form. Patients can be either comatose (Glasgow Coma Scale GCS --- ≤8) survivors undergoing temperature control after return of spontaneous circulation (RoSC), or those who regain consciousness (GCS = 15) after RoSC; all admitted to Intensive Cardiac Care Units in 4 major university hospitals. VF tracings prior to the first direct current shock will be digitized and analyzed to derive spectral data and feed a predictive model to estimate favorable neurological performance (FNP). The results of the model will be compared to the actual prognosis. Results: The primary clinical outcome is FNP during hospitalization. Patients will be categorized into 4 subsets of neurological prognosis according to the risk score obtained from the predictive model. The secondary clinical outcomes are survival to hospital discharge, and FNP and survival after 6 months of follow-up. The model-derived categorisation will be also compared with clinical variables to assess model sensitivity, specificity, and accuracy. Conclusions: A model based on spectral analysis of VF tracings is a promising tool to obtain early prognostic data after SCD.

Resumen Objetivo: La muerte súbita (MS) por fibrilación ventricular (FV) es una importante causa de morbilidad y mortalidad. Los métodos biológicos y de imagen actuales muestran limitaciones para predecir el pronóstico cerebral al ingreso hospitalario. AWAKE es un estudio observacional, multicéntrico, con el objetivo de validar un modelo basado en el análisis espectral del elec- trocardiograma (ECG), que predice precozmente el pronóstico cerebral y la supervivencia en pacientes resucitados y en estado de coma. Métodos: Se recogerán datos de los ECG con FV de pacientes reanimados de MS. Los pacientes pueden ser tanto supervivientes en estado de coma (Glasgow Coma Scale GCS ≤ 8) sometidos a control de temperatura tras la recuperación de circulación espontánea (RCE), como aquellos que recuperan la consciencia (GCS = 15) tras RCE; todos ellos ingresados en unidades de terapia intensiva cardiológica de 4 hospitales de referencia. Los registros de FV previos al primer choque se digitalizarán y analizarán para obtener datos espectrales que se incluirán en un modelo predictivo que estime el pronóstico neurológico favorable (PNF). El resultado del modelo se comparará con el pronóstico real. Resultados: El objetivo principal es el PNF durante la hospitalización. Los pacientes se categorizarán en 4 subgrupos de pronóstico neurológico según la estimación de riesgo obtenida en el modelo predictivo. Los objetivos secundarios son supervivencia al alta hospitalaria, y PNF y supervivencia a los 6 meses. El resultado de este modelo también se comparará con el pronóstico según variables clínicas. Conclusiones: Un modelo basado en el análisis espectral de registros de FV es una herramienta prometedora para obtener datos pronósticos precoces tras MS por FV.