Trasplante hepático por metástasis hepáticas irresecables de cáncer colorrectal: revisión de la literatura / Liver transplantation for non-resectable colorectal liver metastases: A review

In Chile, colorectal cancer ranks third in incidence and fifth in mortality. Half of these patients have liver metastases at the diagnosis, and only 30% of them are resectable. Despite the development of many complex hepatobiliary procedures to achieve the total resection of metastases, the long-term survival with these techniques is not good. Liver transplantation is an alternative to treat unresectable liver metastasis from colorectal cancer with a good outcome. Several prognostic scores allow the selection of patients with good tumor biology. These patients have better overall and disease-free survival after liver transplantation. The use of immunosuppressive treatment doesn't increase recurrence, and even the pattern of tumor growth is slower in liver transplant recipients. The purpose of this review is to summarize the current evidence in this topic and to highlight the need for a formal protocol for liver transplantation for unresectable colorectal liver metastases, using living donors or marginal grafts to avoid competition with the rest of the national waiting list.

Hepatitis crónica por virus C: evaluación de los pacientes tratados con antivirales de acción directa en el sistema público de Chile / Evaluation of patients with virus C hepatitis treated with direct-acting antivirals in the Chilean public system

Background Direct-acting antivirals (DAA) allowed a radical change in the treatment of hepatitis C virus (HCV), achieving the elimination of the virus or sustained viral response (SVR) in > 95% of patients, with good tolerance and few adverse effects. Aim To characterize the treated population and evaluate the efficacy of DAA treatment in the Chilean public health system. Material and Methods: Retrospective analysis of data sheets of pa- tients with chronic HCV infection collected by the Ministry of Health of Chile between 2016 and May 2019. Results Two hundred and fifty-five patients with a mean age of 59 years (51% males) were collected. Genotype 1b was predominant, 72% patients had a diagnosis of cirrhosis at the beginning of treatment. Sofosbuvir-Velpatasvir was predominantly used in 56%. SVR was achieved in 92% of cases, only 4% persisted with detectable load at 24 weeks. A significant decrease in alanine aminotransferase values (88 and 31 U/L respectively, p < 0.01) and a significant increase in plasma albumin (3.7 and 3.9 mg/dl respectively, p = 0.02) were observed. The comparative analysis of MELD-Na before and after treatment did not show a signifi- cant variation (10.8 and 10.4 respectively, p = 0.34). Conclusions These patients treated with DAAs presented SVR rates comparable with national and international data.

Resumen ejecutivo: Enfermedad por hígado graso no alcohólico en sujetos con diabetes mellitus tipo 2: Postura conjunta de la Asociación Chilena de Hepatología (ACHHEP) y la Sociedad Chilena de Diabetología (SOCHIDIAB) / Non-alcoholic fatty liver disease in type 2 diabetes: a joint statement of the Chilean Hepatology and Diabetology Societies

Non-alcoholic fatty liver disease (NAFLD) has a high prevalence and risk of progression to cirrhosis and other complications in patients with type 2 diabetes mellitus (T2DM). Likewise, the presence of NAFLD implies a high risk of developing T2DM, determining a bidirectional relationship between them. The diabetology and hepatology societies, developed a joint initiative aiming to unify criteria, reviewing the definitions, diagnostic criteria, risk stratification, treatment, and follow-up of patients with NAFLD and T2DM. The key questions to be discussed were defined by a panel of specialists in diabetology and hepatology. The Delphi methodology was used to reach consensus on the respective recommendations. Based on the discussion generated among the experts, diagnostic and treatment algorithms were proposed, as well as an indication for referral and the role of the different specialists involved in the management of these patients. Strengthening multidisciplinary work with patients with NAFLD and T2DM will allow the early recognition of the disease, the prevention of the progression to cirrhosis, and reducing the associated complications.

Nuevas terapias orales de acción directa para tratamiento de virus de hepatitis C (VHC) / Direct antivirals for the treatment of chronic hepatitis C virus infection: experience in 106 patients

Background: The availability of direct-acting antivirals (DAA) for the treatment of chronic hepatitis C virus (HCV) infection is just starting to expand in Chile. Aim: To report the initial experience of patients treated with DAA and their evolution after treatment. Material and Methods: Prospective cohort study, from June 2013 to August 2016 of patients treated with DAA for HCV in three clinical centers. The presence of cirrhosis, clinical and laboratory features; adverse events (AE) and post-treatment changes in liver function were evaluated. Sustained viral response at 12 weeks post-treatment (SVR12) was determined. Results: One hundred six patients aged 58 ± 13 years, 54% males, were included. HCV genotype 1b was present in 88% and 47% had cirrhosis. Treatment regimens were asunaprevir + daclatasvir (DCV) in 17% of patients, paritaprevir / ritonavir / ombitasvir + dasabuvir in 33%, sofosbuvir (SOF) + DCV in 19%, and SOF + ledipasvir in 30%. Twenty five percent of patients used generic drugs. SVR12 was 92.1%, with no differences between generic and brand-name drugs. Serious AE were recorded in 22% of patients, being more common in those with cirrhosis (34% vs 11.5%, p < 0.01). At 12 weeks post-treatment follow-up, there was a decrease in aminotransferase values (p < 0.01), improvement in Child-Pugh score (5.9 vs. 5.5, p = 0.03) and decreased presence of ascites (p = 0.02). Conclusions: In our setting, DAA for HCV was highly effective and safe in non-cirrhotic patients. Hepatic function and inflammation improved at 12 weeks of follow-up. AE were common in patients with cirrhosis, suggesting that these patients should be treated by experienced teams. Generic drugs had similar effectiveness compared to originals.

Aumento aislado y sostenido de aspartato aminotransferasa por presencia de macroenzimas: caso clínico / Persistent elevation of aspartate aminotransferase (AST) due to the presence of macro-AST: report of one case

We report an asymptomatic 23-year-old woman with an isolated and persistent increase in serum levels of aspartate aminotransferase (AST). An extensive work up including laboratory and image testing revealed no abnormalities thus suggesting the presence of macro-AST. A polyethylene glycol (PEG) precipitation assay was performed and confirmed the presence of macro-AST.

Evaluación de la carga laboral en residentes Chilenos de especialidades y subespecialidades médicas / Workload assessment in Chilean residents of specialties and medical subspecialties

Introducción: La sobrecarga laboral horaria es un importante problema en los programas de especialización médica. Se asocia a mayor prevalencia de depresión, burnout, deserción, e impacta en la calidad de vida de los residentes. Nuestro objetivo fue cuantificar las horas semanales de carga laboral horaria en residentes de especialidad y subespecialidad de la Pontificia Universidad Católica de Chile (PUC). Métodos: Se realizó una encuesta electrónica a los residentes de especialidad y subespecialidad de la Pontificia Universidad Católica de Chile (2013). Esta incluyó autorreporte de horas semanales trabajadas (jornada habitual, turnos presenciales y turnos de llamada). Para el análisis se consideraron solo las horas presenciales (jornada habitual y turnos presenciales Resultados: se obtuvieron 415 respuestas (tasa de respuesta 86%). Los residentes de especialidad reportaron una jornada de 52,8 ± 20,3 horas semanales más un promedio de 22,6 ± 22,5 horas de turnos presenciales semanales. Los residentes de programas de subespecialidad reportaron una jornada de 55,9 ± 22,2 horas semanales más un promedio de 23 ± 3,9 horas de turnos presenciales semanales. De los 53 programas evaluados, el 22,6 por ciento sobrepasó el límite recomendado por la Dirección de Postgrado PUC (80 horas semanales). Cinco programas reportaron 90-100 horas semanales (todas especialidades o subespecialidades quirúrgicas) y 7 programas reportaron 80-90 horas semanales (3 subespecialidades médicas, 1 subespecialidad quirúrgica, 2 especialidades médicas y 1 especialidad quirúrgica). Conclusión: los residentes de especialidades y subespecialidades médicas en la Pontificia Universidad Católica de Chile están sometidos a una carga horaria significativa. Los programas quirúrgicos presentaron la mayor sobrecarga horaria presencial, con un promedio mayor al recomendado a nivel internacional. (AU)

Introduction: Residents work hours' overload constitutes an important problem in medical postgraduate residency programs. It has been associated to an increased prevalence of depression, burnout, attrition and affects quality of life of residents. The aim of our study was to quantify the duty hours in residents of specialty and subspecialty at the Pontificia Universidad Católica de Chile (PUC). Methods: An electronic survey was performed to residents of specialty and subspecialty at PUC (2013). It included an auto report of the duty hours worked in a week (regular working day, night shifts and on call shifts). We only included for analysis the face hours (regular working day and night shifts). Results: 415 surveys were answered (response rate 86percent). Specialty residents reported 52.8 ± 20.3 regular working hours per week plus an average of 22.6 ± 22.5 hours of night shifts. Subspecialty residents reported 55.9 ± 22.2 regular working hours per week plus an average of 23 ± 3.9 hours of night shifts. From the 53 evaluated programs, 22.6 percent exceeded the limit recommended in the PUC Postgraduate Office (80 hours per week). Five programs reported 90-100 hours per week (all were surgical specialties and subspecialties) and 7 programs reported 80-90 hours per week (3 medical subspecialties, 1 surgical subspecialty, 2 medical specialties and 1 surgical specialty). Conclusion: The residents of specialty and subspecialty from medical postgraduate programs at PUC are subject to a significant workload. The surgical programs present the highest time workload, with a greater average than the internationally recommended.(AU)

Evaluación de docentes clínicos de Postgrado: desarrollo y propiedades psicométricas del instrumento MEDUC-PG14 / Development of MEDUC-PG14 survey to assess postgraduate teaching in medical specialties

Background: Feedback is one of the most important tools to improve teaching in medical education. Aim: To develop an instrument to assess the performance of clinical postgraduate teachers in medical specialties. Material and Methods: A qualitative methodology consisting in interviews and focus-groups followed by a quantitative methodology to generate consensus, was employed. After generating the instrument, psychometric tests were performed to assess the construct validity (factor analysis) and reliability (Cronbach’s alpha). Results: Experts in medical education, teachers and residents of a medical school participated in interviews and focus groups. With this information, 26 categories (79 items) were proposed and reduced to 14 items (Likert scale 1-5) by an expert’s Delphi panel, generating the MEDUC-PG14 survey, which was answered by 123 residents from different programs of medical specialties. Construct validity was carried out. Factor analysis showed three domains: Teaching and evaluation, respectful behavior towards patients and health care team, and providing feedback. The global score was 4.46 ± 0.94 (89% of the maximum). One teachers’ strength, as evaluated by their residents was “respectful behavior” with 4.85 ± 0.42 (97% of the maximum). “Providing feedback” obtained 4.09 ± 1.0 points (81.8% of the maximum). MEDUC-PG14 survey had a Cronbach’s alpha coefficient of 0.947. Conclusions: MEDUC-PG14 survey is a useful and reliable guide for teacher evaluation in medical specialty programs. Also provides feedback to improve educational skills of postgraduate clinical teachers.

Evaluación para el aprendizaje: experiencia en un curso teórico de pregrado en medicina / Assessment for learning: experience in an undergraduate medical theoretical course

Background: Assessment for learning is a paradigm that is taking shape in the field of medical education. This approach aims to embed the assessment process within the educational and learning process. Aim: To evaluate the impact of curricular changes, from a focus of assessment of learning to one of assessment for learning, in the perception of undergraduate students of medicine and their final grades obtained in a theoretical course (TCG). Material and Methods: In the year 2011 lectures were reduced and intermediate assessments followed by a feedback session were introduced. The activities of each program course, surveys about student perceptions of the course and the final grades of students (assessments with multiple choice questions) were compared between the periods prior and after curricular changes (2005-2010 and 2011-2013). Results: As a consequence of curricular changes, time for lectures was reduced by 19.5%, time for summative assessments was increased by 8.5%, and feedback activity, occupying 7.3% of the course time was added. There were significant improvements in student is perceptions in all areas assessed by surveys, emphasizing feedback and assessments. The overall grade assigned to the course dictated after implementing the changes increased from 6.18 to 6.59 (p < 0.001, 1-7 scale). The grades of students also improved from an average of 5.78 to 6.43 (p < 0.001, 1-7 scale). Conclusions: Assessment for learning achieved the desired educational impact without increasing the assigned curricular time. Programmatic assessment is favorably perceived by students.

Incorporación de paciente virtual en portafolio de estudiantes de medicina de pregrado / Introduction of virtual patients to clinical case portfolios for undergraduate medical students

Background: In 2007, a Clinical-Case-Portfolio (CCP) was introduced as a new assessment instrument for fourth grade undergraduate medical students. Since then, several changes have been implemented such as reduction on the number of clinical cases, peer review and the introduction of virtual patient to the portfolio. Aim: To describe the virtual patient model incorporated to the CCP and assess the perception of this change and its effects on the performance of undergraduate students. Material and Methods: Virtual patients were implemented based on prototype clinical cases with specific syndromes. Students’ perceptions about CCP before and after the introduction of virtual patients were evaluated using a validated questionnaire that was answered voluntarily and anonymously. Results: Overall perception of CCP significantly improved after the incorporation of virtual patients (97.1 ± 24.9 and 111.3 ± 25.7 points; 57.8 and 66.2% respectively). The same improvements were observed for the domains “Student Learning”, “Organization and Evaluation”, “Teaching Methodology” and “Integration”. In both years, students obtained high grades in CCP evaluations. However CCP grades were not significantly correlated with integrated final grades. Conclusions: The incorporation of virtual patients improved undergraduate students’ perception of CCP.

Cetoacidosis diabética: Casuística 2008-2012, epidemiología y fisiopatología / Treatment of diabetic ketoacidosis using 2009 American Diabetes Association guidelines

Background: During 2009, new guidelines for the treatment of diabetic ketoacidosis were published by the American Diabetes Association. Aim: To assess the impact of new treatment guidelines on the evolution of patients treated for diabetic ketoacidosis (KAD). Patients and Methods: Anonymous data was obtained from computational medical records of patients treated for KAD at our institution two years before (“Traditional Protocol”) and TWO years after (“ADA-2009 Protocol”) the publication of the 2009 American Diabetes Association (ADA) KAD guidelines. Results: Twenty three patients aged 36.5 ± 15.1 years were treated with the traditional method and 23 patients aged 44.4 ± 21.1 years were treated following 2009 ADA guidelines. Among patients treated with the traditional protocol and treated following ADA 2009 guidelines, the diabetes type 1/type 2 ratio was18/5 and 19/16 respectively (p = NS), the glycosylated hemoglobin on admission was 12.6 ± 2.5 and 14.3 ± 2.7% respectively (p = 0.03), minimal blood pH was 7.15 ± 0.14 and 7.19 ± 0.09 respectively (p = NS), bicarbonate was required in seven and no patient respectively (p = 0.01), hypokalemia < 3.5 mEq/L occurred in 78.2 and 48.5% of patients (p = 0.03), the lapse until resolution was 28.7 ± 28.0 and 28.8 ± 20.6 hours (p = NS). Only one patient, treated following ADA 2009 guidelines, died. Conclusions: Introduction of the ADA-2009 protocol for the treatment of KAD resulted in decrease in the use of intravenous bicarbonate and a reduction in the incidence of hypokalemia. There was no impact neither in the lapse until resolution or lethality.

Niveles séricos de alanino-aminotransferasa en población chilena: análisis de los resultados de la encuesta nacional de salud 2009-2010 / Serum levels of alanine aminotransferase in Chilean population: analysis of results of the national health survey 2009-2010

Background: Determination of Alanine aminotransferase serum levels ([ALT]s) is a sensitive ana reliable test for liver diseases. Aim: To report the prevalence of abnormal [ALT]s in Chilean population and to identify associated variables. Methods: We analyzed data from a random sub-sample of 2,794 adults surveyed during the second Chilean National Health Survey. Abnormal [ALT]s were defined by using three different cut-off values (COV), two fixed COV (COV1: > 30 IU/L in men and > 19 IU/L in women and COV2 pre-defined by the performing laboratory) and a COV adjusted by age, weight and sex (COV3 > 31 IU/L for women and > 44 IU/L and men > 42 IU/L and > 66 IU/L with a BMI > 23). Logistic regression analysis was performed to determine risk factors for elevated [ALT]s Results: Mean [ALT]s values were 30.14 I U/L in men and 22.03 IU/L in women. The observed prevalence of abnormal [ALT]s defined by different COV were 38%, 11.5%, and 8.1% for COV1, COV2 and COV3 respectively. Variables independently associated to abnormal [ALT]s in a multivariate analysis were the following: serum gamma-glutamyl-transpeptidase (OR: 1.055 [95% CI 1.033-1.078]) and body mass index (OR:1.13 [95% CI 1.09-1.17]). Variables inversely associated with abnormal [ALT]s (COV1) were mole gender (OR-.0.976 [95% CI 0.96-0.99) and HDL-cholesterol (OR:0979 [95% CI 0.96-0.99]). Conclusions: Independently of the COV used, Chilean population exhibits a high prevalence of abnormal [ALT]s which may reflect a significant burden of liver disease. Non-alcoholic fatty liver disease could be a major contributor to elevated [ALT]s considering the association of abnormal [ALT]s and metabolic variables.

Reanimación cardiopulmonar básica: conocimiento teórico, desempeño práctico y efectividad de las maniobras en médicos generales / Basic cardiopulmonary resuscitation: knowledge, practical skills and effectiveness of maneuvers of general physicians

Background: General physicians should be adequately trained to deliver effective resuscitation during ventricular fibrillation (VF). Aim: To assess the degree of knowledge, skills and practical effectiveness in cardiopulmonary resuscitation (CPR) of Chilean general physicians. Materials and Methods: Forty eight general physicians starting Anesthesiology or Internal Medicine residency programs were evaluated. They answered a modified American Heart Association Basic Life Support Course written test and individually participated in a witnessed VF cardiac arrest simulated scenario. Execution of resuscitation tasks in the correct order, the quality of the maneuvers and the use of defibrillator were registered. Results: All participants acknowledged the importance of uninterrupted CPR and early defibrillation. Seventy five percent knew the correct frequency of chest compressions, but only 6.25% knew all the effective chest compression characteristics. Ninety eight percent knew the recommended number of breaths per cycle. In practice, 58% performed effective ventilations, 33% performed uninterrupted compressions, 14% did them with adequate frequency and only 8% performed chest compressions adequately. Forty four percent requested a defibrillator within 30 seconds and 31% delivered the first defibrillation within 30 seconds of defibrillator arrival. Airway, breathing, circulation and defibrillation sequence was correctly performed by 12% of participants and 80% acknowledged that their medical training was inadequate or insufficient for managing a cardiac arrest. Conclusions: Despite an elevated degree of knowledge about key aspects of CPR, this group of Chilean physicians displayed suboptimal practical skills while performing CPR in a simulated scenario, specially delivering effective chest compressions and promptly asking for and using the defibrillator.

Síndrome de DRESS: eritema cutáneo, fiebre y hepatitis asociado a lamotrigina: reporte de dos casos y revisión de la literatura / DRESS syndrome: skin rash, fever and acute hepatitis associated to lamotrigine: report of two cases and review of the literature

DRESS syndrome is an infrequent adverse drug reaction but in some cases may be life-threatening. It is characterized by cutaneous rash, systemic symptoms and eosinophilia. It is usually caused by aromatic anticonvulsants, sulfonamides and some antiviral drugs, among others. In this article we present two cases of drug induced hypersensitivity syndrome with rash, systemic symptoms (DRESS) associated to lamotrigine therapy with hepatic involvement and a review of the literature. The first case is a 78 year-old woman, presenting with myalgia, fever, abdominal pain and skin rash on her face and extremities. Labora¬tory tests revealed alteration of hepatic profile with hepatocellular pattern. After ruling out other causes, she recognized recent use of lamotrigine. The drug was withdrawn and she had a favourable evolution. The second case is a 30 year-old woman being treated for depression who presented with rash, adenopathies, fever and alteration of hepatic profile twenty four days after starting lamotrigine. Infectious causes were ruled out and she had a good response to corticosteroid treatment.

El síndrome de DRESS es una reacción adversa a medicamentos, poco frecuente pero potencialmente letal. Se caracteriza por eritema cutáneo, síntomas sistémicos y eosinofilia. Suele ser producido por los anticonvulsivantes aromáticos, sulfonamidas y algunos fármacos antivirales, entre otros. En este artículo presentamos dos casos de DRESS secundario a lamotrigina con compromiso hepático y revisión de la literatura. El primero de ellos, una mujer de 78 años, consulta por mialgias, fiebre, dolor abdominal y eritema maculopapular en cara y extremidades. Los exámenes de laboratorio revelaron alteración de pruebas de función hepática con patrón hepatocelular. Luego de descartar otras causas, la paciente reconoció uso reciente de lamotrigina. Se suspendió la droga y evolucionó favorablemente. El segundo caso es una mujer de 30 años en tratamiento por trastorno depresivo quien, veinticuatro días post-inicio de lamotrigina, comienza con eritema, adenopatías, fiebre y alteración de pruebas de función hepática, excluyéndose etiologías infecciosas; se inicia tratamiento corticoesteroidal con buena respuesta.

Bacteriemia por Streptococcus pyogenes: Presentación de un caso clínico con aparición tardía de neumonía / Pneumonia caused by Streptococcus pyogenes: Report of one case

We report a 58-year-old female presenting with fever and vomiting. The initial laboratory examination disclosed two blood cultures that were positive for Streptococcus Pyogenes. An abdominal CAT scan showed a right basal pneumonia. The patient was treated with antimicrobials and discharged with oral cefadroxil for 21 days. One month after discharge she was asymptomatic and with a normal C reactive protein. Pneumonia is an important differential diagnosis in unknown origin bacteremia caused by Streptococcus Pyogenes. It may have a fulminant evolution and may complicate with abscess and empyema.

Hepatitis colestásica por Mycoplasma pneumoniae sin compromiso pulmonar: caso clínico y revisión de la literatura / Cholestatic hepatitis due to mycoplasma pneumoniae without lung involvement: case report and review

El compromiso hepático es una rara manifestación de la infección por Mycoplasma pneumoniae. Casos de hepatitis colestásica sin compromiso pulmonar han sido descritos en niños con infección por M. pneumoniae, pero en adultos sólo unos pocos casos han sido reportados. En este artículo, presentamos el caso de un hombre de 21 años que consultó por un cuadro de fiebre, ictericia y dolor epigástrico asociado con alteración de los exámenes de laboratorio hepático. Los estudios serológicos de M. penumoniae fueron positivos para IgM e IgG. Los síntomas y exámenes de laboratorio mejoraron completamente luego del tratamiento con claritromicina y ácido ursodeoxicólico.

Liver dysfunction is an unusual manifestation of Mycoplasma pneumoniae infection. Cases of cholestatic hepatitis without pulmonary involvement have been described in children with M. pneumoniae infection,but only a few cases have been reported in adults. In this article, we report the case of a 21-year-old man who presented fever, jaundice and epigastric pain associated with altered liver function tests. Serological tests for M. pneumoniae were positive for IgG and IgM. Clinical symptoms and laboratory tests resolved completely after treatment with clarithromycin and ursodeoxicolic acid. A review of reported cases of liver involvement in M. pneumoniae infection is presented.