[Recommendations based on the management of patients with Crohn disease in the Peruvian context. Position paper of the Association for the Study of the Intestine (ASPEIN)]. / Recomendaciones basadas en el manejo de pacientes con diagnóstico de enfermedad de Crohn en el contexto peruano. Documento de posición de la Asociación Peruana para el Estudio del Intestino (ASPEIN).

Crohn's disease is a chronic inflammatory disease of the gastrointestinal tract whose etiology is unknown, which can transmurally affect any segment of the intestine and/or the perineal region. Worldwide, the incidence of inflammatory bowel disease has increased in recent decades, and the same upward trend can be seen in South America. At national level, there are no official data, however, the increase in the number of publications in the last 20 years confirms this upward trend. Crohn's disease is a forgotten disease and does not have implemented clinical guidelines based on evidence that contribute to clinicians in decision making. In this sense, the Peruvian Association for the Study of the Intestine considers the preparation of this document relevant and timely. clinical contextualized for Peru.

Evaluation of the quality of multiple-choice questions according to the students' academic level.

BACKGROUND: One of the most important challenges in medical education is the preparation of multiple-choice questions able to discriminate between students with different academic level. Average questions may be very easy for students with good performance, reducing their discriminant power in this group of students. The aim of this study was to analyze if the discriminative power of multiple-choice questions is different according to the students' academic performance. METHODS: We retrospectively analyzed the difficulty and discrimination indices of 257 multiple-choice questions used for the end of course examination of pathophysiology and analyzed whether the discrimination indices were lower in students with good academic performance (group 1) than in students with moderate/poor academic performance (group 2). We also evaluated whether case-based questions maintained their discriminant power better than factual questions in both groups of students or not. Comparison of the difficulty and discrimination indices between both groups was based on the Wilcoxon test. RESULTS: Difficulty index was significantly higher in group 1 (median: 0.78 versus 0.56; P <  0.001) and discrimination index was significantly higher in group 2 (median: 0.21 versus 0.28; P <  0.001). Factual questions had higher discriminative indices in group 2 than in group 1 (median: 0.28 versus 0.20; P <  0.001), but discriminative indices of case-based questions did not differ significantly between groups (median: 0.30 versus 0.24; P = 0.296). CONCLUSIONS: Multiple-choice question exams have lower discriminative power in the group of students with high scores. The use of clinical vignettes may allow to maintain the discriminative power of multiple-choice questions.

Effects of two personalized dietary strategies during a 2-year intervention in subjects with nonalcoholic fatty liver disease: A randomized trial.

BACKGROUND AND OBJECTIVES: Nonalcoholic fatty liver disease (NAFLD) management is focused on lifestyle modifications, but long-term maintenance is a challenge for many individuals. This study aimed to evaluate the long-term effects of two personalized energy-restricted dietary strategies on weight loss, metabolic and hepatic outcomes in overweight/obese subjects with NAFLD. METHODS: Ninety-eight subjects from the Fatty Liver in Obesity (FLiO) study (NCT03183193) were randomly assigned to the American Heart Association (AHA) or the FLiO dietary group in a 2-year controlled trial. Anthropometry, body composition (DXA), biochemical parameters and hepatic status (ultrasonography, Magnetic Resonance Imaging, and elastography) were assessed at baseline, 6, 12 and 24 months. RESULTS: Both the AHA and FLiO diets significantly reduced body weight at 6 (-9.7% vs -10.1%), 12 (-6.7% vs -9.6%), and 24 months (-4.8% vs -7.6%) with significant improvements in body composition, biochemical and liver determinations throughout the intervention. At the end of the follow-up, the FLiO group showed a greater decrease in ALT, liver stiffness and Fatty Liver Index, among others, compared to AHA group, although these differences were attenuated when the analyses were adjusted by weight loss percentage. The FLiO group also showed a greater increase in adiponectin compared to AHA group. CONCLUSIONS: The AHA and FLiO diets were able to improve body weight and body composition, as well as metabolic and hepatic status of participants with overweight/obesity and NAFLD within a 2-year follow-up. These findings show that both strategies are suitable alternatives for NAFLD management. However, the FLiO strategy may provide more persistent benefits in metabolic and hepatic parameters.

Web-based formative assessment through clinical cases: role in pathophysiology teaching.

BACKGROUND: Active learning strategies such as formative assessment through clinical cases may help to get a deeper learning. We have studied the effect of this kind of online formative assessment in pathophysiology teaching. METHODS: Seven brief clinical cases were used to give formative assessment in the first semester of a pathophysiology course. To evaluate its effect on learning, we analyzed the proportion of students that passed the end of semester exam with a score above 60 over 100. We also analyzed the effect of the intervention according to the students' previous academic performance. RESULTS: Ninety-six students participated in the study and sat the exam. Sixty-five of them passed it. Students that passed the exam had a higher previous academic performance and had done a higher number of exercises of formative assessment, both in univariate and multivariate analysis. The participants were divided in three groups, according to their previous academic performance. In the intermediate group, the number of cases done by the students who passed the exam was significantly higher than in those who did not pass it (median: 4 versus 0; P = 0.009). CONCLUSION: Formative assessment through web-based clinical cases was followed by an improvement of the academic results in pathophysiology, mainly in students with intermediate performance.

Peroral endoscopic myotomy in a pediatric patient with refractory achalasia: a case report and review of the literature.

A 15-year-old male patient presented with dysphagia, regurgitation, weight loss and retrosternal pain. The diagnosis of achalasia was made 4 years before. The esophagogram revealed severe esophagus dilatation and the classic "bird-beak" termination. A Heller myotomy plus fundoplication and endoscopic balloon dilatation were conducted four months previously. Nevertheless, the symptoms persisted and the last high-resolution manometry study still showed achalasia type II. The patient underwent a peroral endoscopic esophageal myotomy (POEM). POEM is a feasible and safe procedure for experienced and properly-equipped health care delivery centers and could be used as a rescue treatment in refractory achalasia. We present the youngest patient with achalasia in our region who had a successful response to rescue POEM.

Histopathological findings in fatal COVID-19 severe acute respiratory syndrome: preliminary experience from a series of 10 Spanish patients.

In December 2019, an outbreak of severe acute respiratory syndrome associated to SARS-CoV2 was reported in Wuhan, China. To date, little is known on histopathological findings in patients infected with the new SARS-CoV2. Lung histopathology shows features of acute and organising diffuse alveolar damage. Subtle cellular inflammatory infiltrate has been found in line with the cytokine storm theory. Medium-size vessel thrombi were frequent, but capillary thrombi were not present. Despite the elevation of biochemical markers of cardiac injury, little histopathological damage could be confirmed. Viral RNA from paraffin sections was detected at least in one organ in 90% patients.

Flipped classroom improves results in pathophysiology learning: results of a nonrandomized controlled study.

The flipped classroom has become increasingly popular in health professions education. The aim of this study was to analyze its effect on learning in a pathophysiology course. Flipped classroom was introduced to teach respiratory pathophysiology in 2018. We compared the exam results in respiratory pathophysiology in 2017 and 2018 and the exam results in blood pathophysiology from both years (taught by the same teacher, in a traditional way). Groups were compared with Student's t test. Students answered a survey after finishing the term. Two hundred and one students were examined in 2018 (and 229 in 2017). Gender distribution and the qualifications obtained in general pathology (in the previous year) were comparable in both years. Results in respiratory pathophysiology were significantly better in 2018 than in 2017 (mean: 48 vs. 42 out of 100; P = 0.004), but the results in blood pathophysiology remained similar. The improvement was significant only in students who scored below the median (mean: 40 vs. 33; P = 0.009) and was more evident in male than in female students (mean: 52 vs. 44; P = 0.01) and in those who did not have an academic delay (mean 51 vs. 44; P = 0.002). Most students considered that flipped classroom was more attractive and helped them to learn more and with less effort. Flipped classroom increased medical students' knowledge acquisitions in pathophysiology. It was more beneficial to male students and those with lower qualifications with no academic delay.

Closure of colonic deep mural injury and perforation with endoclips.

INTRODUCTION: colorectal perforations are one of the most feared complications after performing an endoscopic resection. The use of endoclips is considered for the management of these complications. OBJECTIVES: to evaluate the efficacy and safety of the use of endoclips in the management of perforations and deep mural injuries that occur after an endoscopic colorectal resection. METHODS: a prospective cohort of consecutively included patients was used with a diagnosis of perforation or deep mural injury after an endoscopic colorectal resection treated with endoclips in our institution. The rates of perforation and deep mural injury were obtained. The factors associated with an unfavorable evolution after the placement of the endoclips were analyzed. RESULTS: after 342 endoscopic mucosal resections (EMR) and 42 endoscopic submucosal dissections (ESD), there were 25 cases with perforation or deep mural injury. The deep mural injury rate was 3.22 % and 7.14 % in the case of EMR and ESD, respectively. The perforation rate was 1.46 % and 14.29 % in the case of EMR and ESD, respectively. Successful closure with endoclips was achieved in 24 cases (96 %). Only one patient presented an unfavorable evolution (10 %) after successful closure. The factors associated with an unfavorable evolution were the presence of diffuse peritoneal symptoms and a perforation size greater than or equal to 10 mm. CONCLUSION: endoscopic closure with endoclips is effective to avoid surgery in cases of deep mural injury or perforation after an endoscopic resection.

[Massive digestive hemorrhage from secondary fistulas of great vessels to the digestive tract]. / Hemorragia digestiva masiva por fístulas secundarias de grandes vasos al tracto digestivo.

The formation of a fistula between large caliber arteries and the digestive tract is an uncommon complication of reconstructive surgery of the large vessels secondary to the use of vascular prostheses, which manifest themselves with massive hemorrhages with high mortality. We report two cases of aorto-enteric fistula and carotid-esophageal fistula that share common characteristics such as the clinical manifestation of massive and fatal gastrointestinal bleeding in patients with a history of vascular prosthesis placement.

Ultrasound/Elastography techniques, lipidomic and blood markers compared to Magnetic Resonance Imaging in non-alcoholic fatty liver disease adults.

INTRODUCTION: Non-alcoholic fatty liver disease (NAFLD) may progress to steatohepatitis, cirrhosis and complicated hepatocellular carcinoma with defined differential symptoms and manifestations. OBJECTIVE: To evaluate the fatty liver status by several validated approaches and to compare imaging techniques, lipidomic and routine blood markers with magnetic resonance imaging in adults subjects with non-alcoholic fatty liver disease. MATERIALS AND METHODS: A total of 127 overweight/obese with NAFLD, were parallelly assessed by Magnetic Resonance Imaging (MRI), ultrasonography, transient elastography and a validated metabolomic designed test to diagnose NAFLD in this cross-sectional study. Body composition (DXA), hepatic related biochemical measurements as well as the Fatty Liver Index (FLI) were evaluated. This study was registered as FLiO: Fatty Liver in Obesity study; NCT03183193. RESULTS: The subjects with more severe liver disease were found to have worse metabolic parameters. Positive associations between MRI with inflammatory and insulin biomarkers were found. A linear regression model including ALT, RBP4 and HOMA-IR was able to explain 40.9% of the variability in fat content by MRI. In ROC analyses a combination panel formed of ALT, HOMA-IR and RBP4 followed by ultrasonography, ALT and metabolomic test showed the major predictive ability (77.3%, 74.6%, 74.3% and 71.1%, respectively) for liver fat content. CONCLUSIONS: A panel combination including routine blood markers linked to insulin resistance showed highest associations with MRI considered as a gold standard for determining liver fat content. This combination of tests can facilitate the diagnosis of early stages of non-alcoholic liver disease thereby avoiding other invasive and expensive methods.

Correction to: Randomized study showing the benefit of medical students writing multiple choice questions on their learning.

Following publication of the original article [1], the author reported an error in the title; the word study should be changed to students as indicated below.

Randomized study showing the benefit of medical study writing multiple choice questions on their learning.

BACKGROUND: Writing multiple choice questions may be a valuable tool for medical education. We asked medical students to generate multiple choice questions and studied its effect on their exams. We hypothesized that students generating questions would improve their learning. METHODS: We randomized students in their second and third years at the School of Medicine to write four multiple choice questions on two different sections of General Pathology (Immunopathology and Electrolyte and acid-base status; second year) and Pathophysiology (Blood and Respiratory system; third year). We analyzed whether students writing questions on a section had better results in the exam test in that section than the rest of the students. RESULTS: Seventy-five (38.2%) students wrote questions for General Pathology and 109 (47.6%) for Pathophysiology. Students that wrote questions obtained significantly better results in the exam than those who did not. In General Pathology, students who wrote questions about Immunopathology obtained better results in that section than those who wrote questions about the other section (5.13 versus 3.86 over 10; P = 0.03). In Pathophysiology, the differences between both groups were not significant, but students who wrote good questions about Respiratory system obtained better results in that section than those who wrote good questions about Blood (6.07 versus 4.28 over 10; P = 0.015). Male students wrote good questions in Pathophysiology more frequently than female students (28.1% versus 10.4%; P = 0.02). CONCLUSIONS: The writing of multiple choice questions by medical students may improve their learning. A gender effect may also influence this intervention. Future investigations should refine its potential role in teaching.

[Clinical practice guideline for the evaluation and management of upper gastrointestinal bleeding for the Peruvian Social Security (EsSalud)]. / Guía de práctica clínica para la evaluación y el manejo de la hemorragia digestiva alta en el Seguro Social del Perú (EsSalud).

OBJECTIVE: To provide evidence-based clinical recommendations for the evaluation and management of patients with upper gastrointestinal bleeding (UGB) in the Peruvian Social Security (EsSalud). MATERIALS AND METHODS: A local guideline development group (local GDG) was established, including specialists in gastroenterology and methodologists. The local GDG formulated 11 clinical questions to be answered by this clinical practice guide (CPG). We searched and selected CPG of UGB published from 2012, which answered the posed questions and obtained a score higher than 60% in domains 1 and 3 of the Appraisal of Guidelines for Research and Evaluation II (AGREE-II) tool. During September 2017, bibliographic searches were conducted in Pubmed, to update 9 clinical questions of the preselected CPGs, and to answer 2 de novo questions. The quality of the evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology. In periodic work meetings, the local GDG reviewed the evidence and formulated the recommendations, points of good clinical practice and the flowchart of evaluation and management, using the GRADE methodology Lastly, the CPG was approved with Resolución N° 80-IETSI-ESSALUD-2017. RESULTS: This CPG addressed 11 clinical questions, divided into four themes: risk assessment, initial management, management of non-variceal UGB, and management of variceal UGB. Based on these questions, 10 recommendations (7 strong recommendations and 3 weak recommendations), 24 points of good clinical practice, and 2 flow charts were formulated. CONCLUSION: This article is the summary of the EsSalud' CPG, where the available scientific evidence on evaluation and management of UGB was evaluated.

Radioembolization of hepatocellular carcinoma activates liver regeneration, induces inflammation and endothelial stress and activates coagulation.

BACKGROUND & AIMS: Radioembolization may rarely induce liver disease resulting in a syndrome that is similar to veno-occlusive disease complicating bone marrow transplantation where inflammation, endothelial cell activation and thrombosis are likely involved. We hypothesized that similar mechanisms could be implicated in radioembolization-induced liver disease (REILD). Moreover, lobar radioembolization may induce hypertrophy of the non-treated hemiliver most probably by inducing liver regeneration. METHODS: In patients with hepatocellular carcinoma, we prospectively studied serum levels of markers of liver regeneration, oxidative stress, pro-inflammatory pathways, endothelial activation and coagulation parameters over 2 months after radioembolization. RESULTS: Although REILD did not occur among 14 treated patients, a decrease in effective liver blood flow was observed. Radioembolization was followed by a persistent increase in pro-inflammatory (interleukin 6 and 8) and oxidative stress (malondyaldehide) markers, an induction of endothelial injury markers (vW factor and PAI-1) and an activation of the coagulation cascade (factor VIII, PAI-1, D-Dimer) as well as a significant increase in factors related to liver regeneration (FGF-19 and HGF). CONCLUSION: Radioembolization activates liver regeneration, produces oxidative stress, activates inflammatory cytokines and induces endothelial injury with partial activation of the coagulation cascade. These findings may have implications in the pathogenesis, prevention and therapy of REILD and in the development of new therapies to enhance hypertrophy with a surgical perspective.

Prognostic factors and prevention of radioembolization-induced liver disease.

UNLABELLED: Radioembolization (RE)-induced liver disease (REILD) has been defined as jaundice and ascites appearing 1 to 2 months after RE in the absence of tumor progression or bile duct occlusion. Our aims were to study the incidence of REILD in a large cohort of patients and the impact of a series of changes introduced in the processes of treatment design, activity calculation, and the routine use of ursodeoxycholic acid and low-dose steroids (modified protocol). Between 2003 and 2011, 260 patients with liver tumors treated by RE were studied (standard protocol: 75, modified protocol: 185). REILD appeared only in patients with cirrhosis or in noncirrhosis patients exposed to systemic chemotherapy prior to RE. Globally, the incidence of REILD was reduced in the modified protocol group from 22.7% to 5.4% and the incidence of severe REILD from 13.3% to 2.2% (P<0.0001). Treatment efficacy was not jeopardized since 3-month disease control rates were virtually identical in both groups (66.7% and 67.2%, P=0.93). Exposure to chemotherapy in the 2-month period following RE and being treated by the standard protocol were independent predictors of REILD among noncirrhosis patients. In cirrhosis, the presence of a small liver (total volume<1.5 L), an abnormal bilirubin (>1.2 mg/dL), and treatment in a selective fashion were independently associated with REILD. CONCLUSION: REILD is an uncommon but relevant complication that appears when liver tissue primed by cirrhosis or prior and subsequent chemotherapy is exposed to the radiation delivered by radioactive microspheres. We designed a comprehensive treatment protocol that reduces the frequency and the severity of REILD.

[Comparison of the M and XL FibroScan(®) probes to estimate liver stiffness by transient elastography]. / Comparación de las sondas M y XL para estimar la rigidez hepática por medio de elastografía de transición.

The FibroScan(®) XL probe has been specifically designed for obese patients to measure liver stiffness by transient elastography, but it has not been well tested in non-obese patients. The aim of this study was to compare the M and XL FibroScan(®) probes in a series of unselected obese (body mass index above 30 kg/m(2)) and non-obese patients with chronic liver disease. Two hundred and fifty-four patients underwent a transient elastography examination with both the M and XL probes. The results obtained with the two probes were compared in the whole series and in obese (n=82) and non-obese (n=167) patients separately. The reliability of the examinations was assessed using the criteria defined by Castéra et al. The proportion of reliable exams was significantly higher when the XL probe was used (83% versus 73%; P=.001). This significance was maintained in the group of obese patients (82% versus 55%; P<.001), but not in the non-obese patients (84% versus 83%). Despite a high correlation between the stiffness values obtained with the two probes (R=.897; P<.001), and a high concordance in the estimation of fibrosis obtained with the two probes (Cronbach's alpha value: 0.932), the liver stiffness values obtained with the XL probe were significantly lower than those obtained with the M probe, both in the whole series (9.5 ± 9.1 kPa versus 11.3 ± 12.6 kPa; P<0.001) and in the obese and non-obese groups. In conclusion, transient elastography with the XL probe allows a higher proportion of reliable examinations in obese patients but not in non-obese patients. Stiffness values were lower with the XL probe than with the M probe.

[Readability of surgical informed consent in Spain]. / Legibilidad del consentimiento informado quirúrgico en España.

INTRODUCTION: To assess the readability of informed consent documents (IC) of the different national surgical societies. METHODS: During January 2012 we collected 504 IC protocols of different specialties. To calculate readability parameters the following criteria were assessed: number of words, syllables and phrases, syllables/word and word/phrase averages, Word correlation index, Flesch-Szigriszt index, Huerta Fernández index, Inflesz scale degree and the Gunning-Fog index. RESULTS: The mean Flesch-Szigriszt index was 50.65 ± 6,72, so readability is considered normal. There are significant differences between specialties such as Urology (43.00 ± 4.17) and Angiology and Vascular Surgery (63.00 ± 3.26, P<.001). No IC would be appropriate for adult readability according to the Fernández-Huerta index (total mean 55.77 ± 6.57); the IC of Angiology and Vascular Surgery were the closest ones (67.85 ± 3.20). Considering the Inflesz scale degree (total mean of 2.84 ± 3,23), IC can be described as «somewhat difficult¼. There are significant differences between the IC of Angiology and Vascular Surgery (3.23 ± 0.47) that could be qualified as normal, or Cardiovascular Surgery (2.79 ± 0.43) as «nearly normal readability¼; and others such as Urology (1, 70 ± 0.46, P<.001) and Thoracic Surgery (1.90 ± 0.30, P<.001), with a readability between «very¼ and «somewhat¼ difficult. The Gunning-Fog indexes are far from the readability for a general audience (total mean of 26.29 ± 10,89). CONCLUSIONS: IC developed by scientific societies of different surgical specialties do not have an adequate readability for patients. We recommend the use of readability indexes during the writing of these consent forms.

Trial of complete weaning from immunosuppression for liver transplant recipients: factors predictive of tolerance.

Recipients of liver transplantation (LT) may develop immunological tolerance. Factors predictive of tolerance are not clearly understood. Transplant recipients with normal liver function tests and without active viral hepatitis or autoimmune disease who presented with side effects of immunosuppression or a high risk of de novo malignancies were selected to participate in this prospective study. Twenty-four patients fulfilled the inclusion criteria and, therefore, underwent a gradual reduction of immunosuppression. Tolerance was defined as normal liver function tests after immunosuppression withdrawal. Basal clinical and immunological characteristics, including lymphocyte counts and subpopulations (T, B, natural killer, CD4(+) , CD8(+) , and regulatory T cells) and the phytohemagglutinin stimulation index (SI), were compared for tolerant and nontolerant patients. Fifteen of the 24 patients (62.5%) were tolerant at a median of 14 months (interquartile range = 8.5-22.5 months) after complete immunosuppression withdrawal. Tolerant patients had a longer median interval between transplantation and inclusion in the study (156 for tolerant patients versus 71 months for nontolerant patients, P = 0.003) and a lower median SI (7.49 for tolerant patients versus 41.73 for nontolerant patients, P = 0.01). We identified 3 groups of patients with different probabilities of tolerance: in the first group (n = 7 for an interval > 10 years and an SI < 20), 100% reached tolerance; in the second group (n = 10 for an interval > 10 years and an SI > 20 or an interval < 10 years and an SI < 20), 60% reached tolerance; and in the third group (n = 7 for an interval < 10 years and an SI > 20), 29% reached tolerance. In conclusion, a high proportion of select LT recipients can reach tolerance over the long term. Two simple basal variables-the time from transplantation and the SI-may help to identify these patients.

Photodynamic nasal SARS-CoV-2 decolonization shortens infectivity and influences specific T-Cell responses.

Background: The main objective was to evaluate the efficacy of intranasal photodynamic therapy (PDT) in SARS-CoV-2 mildly symptomatic carriers on decreasing the infectivity period. SARS-CoV-2-specific immune-stimulating effects and safety were also analysed. Methods: We performed a randomized, placebo-controlled, clinical trial in a tertiary hospital (NCT05184205). Patients with a positive SARS-CoV-2 PCR in the last 48 hours were recruited and aleatorily assigned to PDT or placebo. Patients with pneumonia were excluded. Participants and investigators were masked to group assignment. The primary outcome was the reduction in in vitro infectivity of nasopharyngeal samples at days 3 and 7. Additional outcomes included safety assessment and quantification of humoral and T-cell immune-responses. Findings: Patients were recruited between December 2021 and February 2022. Most were previously healthy adults vaccinated against COVID-19 and most carried Omicron variant. 38 patients were assigned to placebo and 37 to PDT. Intranasal PDT reduced infectivity at day 3 post-treatment when compared to placebo with a ß-coefficient of -812.2 (CI95%= -478660 - -1.3, p<0.05) infectivity arbitrary units. The probability of becoming PCR negative (ct>34) at day 7 was higher on the PDT-group, with an OR of 0.15 (CI95%=0.04-0.58). There was a decay in anti-Spike titre and specific SARS-CoV-2 T cell immunity in the placebo group 10 and 20 weeks after infection, but not in the PDT-group. No serious adverse events were reported. Interpretation: Intranasal-PDT is safe in pauci-symptomatic COVID-19 patients, it reduces SARS-CoV-2 infectivity and decelerates the decline SARS-CoV-2 specific immune-responses.