Cardiac Workup of Ischemic Stroke

Stroke is the leading cause of disability in developed countries and the third cause of mortality. Up to 15-30% of ischemic strokes are caused by cardiac sources of emboli being associated with poor prognosis and high index of fatal recurrence. In order to establish an adequate preventive strategy it is crucial to identify the cause of the embolism. After a complete diagnostic workup up to 30% of strokes remain with an undetermined cause, and most of them are attributed to an embolic mechanism suggesting a cardiac origin

Aberrant Gene Promoter Methylation Associated with Sporadic Multiple Colorectal Cancer

BACKGROUND: Colorectal cancer (CRC) multiplicity has been mainly related to polyposis and non-polyposis hereditary syndromes. In sporadic CRC, aberrant gene promoter methylation has been shown to play a key role in carcinogenesis, although little is known about its involvement in multiplicity. To assess the effect of methylation in tumor multiplicity in sporadic CRC, hypermethylation of key tumor suppressor genes was evaluated in patients with both multiple and solitary tumors, as a proof-of-concept of an underlying epigenetic defect. METHODOLOGY/PRINCIPAL FINDINGS: We examined a total of 47 synchronous/metachronous primary CRC from 41 patients, and 41 gender, age (5-year intervals) and tumor location-paired patients with solitary tumors. Exclusion criteria were polyposis syndromes, Lynch syndrome and inflammatory bowel disease. DNA methylation at the promoter region of the MGMT, CDKN2A, SFRP1, TMEFF2, HS3ST2 (3OST2), RASSF1A and GATA4 genes was evaluated by quantitative methylation specific PCR in both tumor and corresponding normal appearing colorectal mucosa samples. Overall, patients with multiple lesions exhibited a higher degree of methylation in tumor samples than those with solitary tumors regarding all evaluated genes. After adjusting for age and gender, binomial logistic regression analysis identified methylation of MGMT2 (OR, 1.48; 95% CI, 1.10 to 1.97; p = 0.008) and RASSF1A (OR, 2.04; 95% CI, 1.01 to 4.13; p = 0.047) as variables independently associated with tumor multiplicity, being the risk related to methylation of any of these two genes 4.57 (95% CI, 1.53 to 13.61; p = 0.006). Moreover, in six patients in whom both tumors were available, we found a correlation in the methylation levels of MGMT2 (r = 0.64, p = 0.17), SFRP1 (r = 0.83, 0.06), HPP1 (r = 0.64, p = 0.17), 3OST2 (r = 0.83, p = 0.06) and GATA4 (r = 0.6, p = 0.24). Methylation in normal appearing colorectal mucosa from patients with multiple and solitary CRC showed no relevant difference in any evaluated gene. CONCLUSIONS: These results provide a proof-of-concept that gene promoter methylation is associated with tumor multiplicity. This underlying epigenetic defect may have noteworthy implications in the prevention of patients with sporadic CRC

The Influence of Multilevel Spinal Deformity Surgery on the EuroQol 5 Dimensions' (EQ-5D) Questionnaire and Residential Status in the Elderly: A Prospective, Observational, Multicenter Study

STUDY DESIGN: Multicenter, international prospective study. OBJECTIVE: This study investigated the clinical outcome up to 2 years after multi-level spinal deformity surgery in the elderly by reporting the minimal clinically important difference (MCID) of EuroQol 5-dimensions (EQ-5D), EQ-VAS, and residential status. METHODS: As an ancillary study of 219 patients ≥60 years with spinal deformity undergoing primary instrumented fusion surgery of ≥5 levels, this study focuses on EQ-5D (3-L) as the primary outcome and EQ-VAS and residential status as secondary outcomes. Data on EQ-5D were compared between pre-operatively and postoperatively at 10 weeks, 12 months, and 24 months. An anchor-based approach was used to calculate the MCID. RESULTS: The EQ-5D index and EQ-VAS, respectively, improved significantly at each time point compared to pre-operatively (from .53 (SD .21) and 55.6 (SD 23.0) pre-operatively to .64 (SD .18) and 65.8 (SD 18.7) at 10 weeks, .74 (SD .18) and 72.7 (SD 18.1) at 12 months, and .73 (SD .20) and 70.4 (SD 20.4) at 24 months). 217 (99.1%) patients lived at home pre-operatively, while 186 (88.6%), 184 (98.4%), and 172 (100%) did so at 10 weeks, 12 months, and 24 months, respectively. Our calculated MCID for the EQ-5D index at 1 year was .22 (95% CI .15-.29). CONCLUSIONS: The EQ-5D index significantly increased at each time point over 24 months after ≥5 level spinal deformity surgery in elderly patients. The MCID of the EQ-5D-3 L was .22. Patients living at home pre-operatively can expect to be able to live at home 2 years postoperatively

Colon capsule endoscopy versus CT colonography in FIT-positive colorectal cancer screening subjects: a prospective randomised trial-the VICOCA study

Background: Colon capsule endoscopy (CCE) and CT colonography (CTC) are minimally invasive techniques for colorectal cancer (CRC) screening. Our objective is to compare CCE and CTC for the identification of patients with colorectal neoplasia among participants in a CRC screening programme with positive faecal immunochemical test (FIT). Primary outcome was to compare the performance of CCE and CTC in detecting patients with neoplastic lesions. Methods: The VICOCA study is a prospective, single-centre, randomised trial conducted from March 2014 to May 2016; 662 individuals were invited and 349 were randomised to CCE or CTC before colonoscopy. Endoscopists were blinded to the results of CCE and CTC. Results: Three hundred forty-nine individuals were included: 173 in the CCE group and 176 in the CTC group. Two hundred ninety individuals agreed to participate: 147 in the CCE group and 143 in the CTC group. In the intention-toscreen analysis, sensitivity, specificity and positive and negative predictive values for the identification of individuals with colorectal neoplasia were 98.1%, 76.6%, 93.7% and 92.0% in the CCE group and 64.9%, 95.7%, 96.8% and 57.7% in the CTC group. In terms of detecting significant neoplastic lesions, the sensitivity of CCE and CTC was 96.1% and 79.3%, respectively. Detection rate for advanced colorectal neoplasm was higher in the CCE group than in the CTC group (100% and 93.1%, respectively; RR = 1.07; p = 0.08). Both CCE and CTC identified all patients with cancer. CCE detected more patients with any lesion than CTC (98.6% and 81.0%, respectively; RR = 1.22; p = 0.002). Conclusion: Although both techniques seem to be similar in detecting patients with advanced colorectal neoplasms, CCE is more sensitive for the detection of any neoplastic lesion

Computational model of the fetal cardiovascular system with aortic coarctation

Tutors: Bart Bijnens, Inma Villanueva. Treball de fi de grau en BiomèdicaAortic coarctation (AoC) is a challenging congenital heart disease (CHD) to diagnose prenatally, accounting for 6-8% of all CHDs. It involves the narrowing of a segment of the aortic arch, typically affecting the aortic isthmus. Prenatal diagnosis of AoC is difficult due to the presence of the fetal shunt called ductus arteriosus (DA), which bypasses the defect in fetal circulation. During fetal life, the body adapts to coarctation by establishing mechanisms for adequate oxygen and nutrient delivery as well as pressure regulation to prevent adverse remodelling. However, following birth, a multitude of hemodynamic effects can arise as a result of ductal closure. The primary indicator of AoC is ventricular disproportion, characterized by left-to-right blood flow redistribution resulting in an imbalance with dominant right ventricles. Nonetheless, false-positive diagnoses can occur due to physiological right dominance in the third trimester. The lack of clear prenatal diagnosis criteria for AoC arises from the inconsistency of associated signs. Thus, achieving an accurate prenatal diagnosis of AoC continues to pose a significant challenge. Given the above, this study aimed to develop a closed 0D computational model of the fetal cardiovascular system to improve the understanding of AoC. Particularly, it aimed to simulate the hemodynamic changes in the fetal circulation considering different scenarios of AoC. To that end, we used a closed 0D model that was further extended in order to add more detail and obtain a circuit more consistent with the real anatomical configuration of the fetal system. Then, a thorough parametric analysis was carried out to adjust the parameters of the extended lumped circuit and replicate the behavior of a healthy fetus described in the literature. Finally, multiple scenarios of aortic coaction were simulated considering different degrees of narrowing, ventricular disproportion and increment in the radius of the DA. The obtained results demonstrate the capacity of the extended closed 0D lumped circuit to mimic the hemodynamic behavior of a healthy fetus. Moreover, it has been found that, in the context of AoC, it is imperative for the body to combine the narrowing of aortic segments and the ventricular disproportion, to ensure proper blood delivery, regulate wall stress and wall shear stress in the upper body and most importantly, the brain and the left ventricle. Thus, this study has identified the specific conditions under which physiological ranges are achieved in the context of AoC. Finally, it has been demonstrated that while DA plays a crucial role in blood flow redistribution toward the lower body, it does not experience any increase in its radius

Analgesia con morfina intratecal en cirugía de las deformidades raquídeas

Introducción: la efectividad y seguridad en el control de la analgesia postoperatoria forman una combinación difícil de alcanzar, especialmente en la población pediátrica. En nuestro estudio pretendemos evaluar la eficacia de la morfina administrada de forma intratecal a pequeñas dosis, la calidad de la analgesia y la aparición de efectos secundarios en pacientes adolescentes, sometidos a cirugía correctora de las deformidades raquídeas. Material y método: estudiamos un total de 36 pacientes (11 V /25 M) que fueron intervenidos de cifoescoliosis desde Febrero hasta Diciembre de 1994. La etiología de la deformidad raquídea era en 26 pacientes idiopática y en 10 pacientes secundaria a una enfermedad neuromuscular. A todos ellos se les practicó el mismo examen preoperatorio según protocolo del Servicio y la misma técnica anestésica. Al finalizar la artrodesis vertebral, bajo visión directa el cirujano realizaba la punción en el espacio vertebral L4/L5, L3/L4 con una aguja n2 25 G de punta de lápiz y, administraba la morfina preparada por el Servicio de Farmacia con solución salina apirógena a concentración de 0,1 mg.ml·1 a dosis de 0,01 mg.kg·1, hasta dosis máximas de 0,5 mg en total. Valorábamos, la hora de aparición del dolor, la necesidad de módicos u otros analgésicos parenterales para el control del dolor, la aparición de electos secundarios y si se precisó de naloxona, y también, recogíamos el grado de confort del paciente mediante una modificación de la escala analógica visual (V AS). Resultados: la edad media de los pacientes fue de 15,36 años (11-19). el peso de 54,58 kg (35-78) y la talla 162 cm (142- 187). El tiempo medio de analgesia mórfico dependiente fue de 24,25 horas (1,30-64). Un total de 23 pacientes (63,8%) no precisaron ningún tipo de analgésicos durante su estancia en la sala de reanimación, en 12 pacientes (33,3%) se administraron analgésicos de tipo AINE y sólo en 1 paciente (2,77%) hubo necesidad de administrar mórlicos parenterales para el control del dolor. En cuanto a los electos secundarios, no se registró ningún caso de depresión respiratoria, somnolencia, cefalea, ni prurito. Aparecieron vómitos en 13 pacientes (36, 1 %) y náuseas en 4 ( 11 , 1 %) que no precisaron de la administración de naloxona para su control. La analgesia fue calificada como excelente en el 69,2% de los pacientes idiopáticos y en el 70% en el caso de los secundarios. Conclusiones: la morfina intratecal a dosis aproximadas de 0,01 mg.kg·1 para el control del dolor postoperatorio en la cirugía de la escoliosis es electiva, segura y confortable. Evitando la administración de mórlicos por vía parenteral, los pacientes son capaces de realizar una fisioterapia respiratoria activa, consiguiendo así una recuperación más temprana