Mapping early serum proteome signatures of liver regeneration in living donor liver transplant cases.

The liver is the only solid organ capable of regenerating itself to regain 100% of its mass and function after liver injury and/or partial hepatectomy (PH). This exceptional property represents a therapeutic opportunity for severe liver disease patients. However, liver regeneration (LR) might fail due to poorly understood causes. Here, we have investigated the regulation of liver proteome and phosphoproteome at a short time after PH (9 h), to depict a detailed mechanistic background of the early LR phase. Furthermore, we analyzed the dynamic changes of the serum proteome and metabolome of healthy living donor liver transplant (LDLT) donors at different time points after surgery. The molecular profiles from both analyses were then correlated. Insulin and FXR-FGF15/19 signaling were stimulated in mouse liver after PH, leading to the activation of the main intermediary kinases (AKT and ERK). Besides, inhibition of the hippo pathway led to an increased expression of its target genes and of one of its intermediary proteins (14-3-3 protein), contributing to cell proliferation. In association with these processes, metabolic reprogramming coupled to enhanced mitochondrial activity cope for the energy and biosynthetic requirements of LR. In human serum of LDLT donors, we identified 56 proteins and 13 metabolites statistically differential which recapitulate some of the main cellular processes orchestrating LR in its early phase. These results provide mechanisms and protein mediators of LR that might prove useful for the follow-up of the regenerative process in the liver after PH as well as preventing the occurrence of complications associated with liver resection.

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.

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.

Neutrophil Extracellular Traps, Local IL-8 Expression, and Cytotoxic T-Lymphocyte Response in the Lungs of Patients With Fatal COVID-19.

BACKGROUND: Excessive inflammation is pathogenic in the pneumonitis associated with severe COVID-19. Neutrophils are among the most abundantly present leukocytes in the inflammatory infiltrates and may form neutrophil extracellular traps (NETs) under the local influence of cytokines. NETs constitute a defense mechanism against bacteria, but have also been shown to mediate tissue damage in a number of diseases. RESEARCH QUESTION: Could NETs and their tissue-damaging properties inherent to neutrophil-associated functions play a role in the respiratory failure seen in patients with severe COVID-19, and how does this relate to the SARS-CoV-2 viral loads, IL-8 (CXCL8) chemokine expression, and cytotoxic T-lymphocyte infiltrates? STUDY DESIGN AND METHODS: Sixteen lung biopsy samples obtained immediately after death were analyzed methodically as exploratory and validation cohorts. NETs were analyzed quantitatively by multiplexed immunofluorescence and were correlated with local levels of IL-8 messenger RNA (mRNA) and the density of CD8+ T-cell infiltration. SARS-CoV-2 presence in tissue was quantified by reverse-transcriptase polymerase chain reaction and immunohistochemistry analysis. RESULTS: NETs were found in the lung interstitium and surrounding the bronchiolar epithelium with interindividual and spatial heterogeneity. NET density did not correlate with SARS-CoV-2 tissue viral load. NETs were associated with local IL-8 mRNA levels. NETs were also detected in pulmonary thrombi and in only one of eight liver tissues. NET focal presence correlated negatively with CD8+ T-cell infiltration in the lungs. INTERPRETATION: Abundant neutrophils undergoing NETosis are found in the lungs of patients with fatal COVID-19, but no correlation was found with viral loads. The strong association between NETs and IL-8 points to this chemokine as a potentially causative factor. The function of cytotoxic T-lymphocytes in the immune responses against SARS-CoV-2 may be interfered with by the presence of NETs.

Long-Term Outcome of Critically Ill Advanced Cancer Patients Managed in an Intermediate Care Unit.

Background: To analyze the long-term outcomes for advanced cancer patients admitted to an intermediate care unit (ImCU), an analysis of a do not resuscitate orders (DNR) subgroup was made. Methods: A retrospective observational study was conducted from 2006 to January 2019 in a single academic medical center of cancer patients with stage IV disease who suffered acute severe complications. The Simplified Acute Physiology Score 3 (SAPS 3) was used as a prognostic and severity score. In-hospital mortality, 30-day mortality and survival after hospital discharge were calculated. Results: Two hundred and forty patients with stage IV cancer who attended at an ImCU were included. In total, 47.5% of the cohort had DNR orders. The two most frequent reasons for admission were sepsis (32.1%) and acute respiratory failure (excluding sepsis) (38.7%). Mortality in the ImCU was 10.8%. The mean predicted in-hospital mortality according to SAPS 3 was 51.9%. The observed in-hospital mortality was 37.5% (standard mortality ratio of 0.72). Patients discharged from hospital had a median survival of 81 (30.75−391.25) days (patients with DNR orders 46 days (19.5−92.25), patients without DNR orders 162 days (39.5−632)). The observed mortality was higher in patients with DNR orders: 52.6% vs. 23.8%, p 0 < 0.001. By multivariate logistic regression, a worse ECOG performance status (3−4 vs. 0−2), a higher SAPS 3 Score and DNR orders were associated with a higher in-hospital mortality. By multivariate analysis, non-invasive mechanical ventilation, higher bilirubin levels and DNR orders were significantly associated with 30-day mortality. Conclusion: For patients with advanced cancer disease, even those with DNR orders, who suffer from acute complications or require continuous monitoring, an ImCU-centered multidisciplinary management shows encouraging results in terms of observed-to-expected mortality ratios.

Dysautonomia in COVID-19 Patients: A Narrative Review on Clinical Course, Diagnostic and Therapeutic Strategies.

Introduction: On March 11, 2020, the World Health Organization sounded the COVID-19 pandemic alarm. While efforts in the first few months focused on reducing the mortality of infected patients, there is increasing data on the effects of long-term infection (Post-COVID-19 condition). Among the different symptoms described after acute infection, those derived from autonomic dysfunction are especially frequent and limiting. Objective: To conduct a narrative review synthesizing current evidence of the signs and symptoms of dysautonomia in patients diagnosed with COVID-19, together with a compilation of available treatment guidelines. Results: Autonomic dysfunction associated with SARS-CoV-2 infection occurs at different temporal stages. Some of the proposed pathophysiological mechanisms include direct tissue damage, immune dysregulation, hormonal disturbances, elevated cytokine levels, and persistent low-grade infection. Acute autonomic dysfunction has a direct impact on the mortality risk, given its repercussions on the respiratory, cardiovascular, and neurological systems. Iatrogenic autonomic dysfunction is a side effect caused by the drugs used and/or admission to the intensive care unit. Finally, late dysautonomia occurs in 2.5% of patients with Post-COVID-19 condition. While orthostatic hypotension and neurally-mediated syncope should be considered, postural orthostatic tachycardia syndrome (POTS) appears to be the most common autonomic phenotype among these patients. A review of diagnostic and treatment guidelines focused on each type of dysautonomic condition was done. Conclusion: Symptoms deriving from autonomic dysfunction involvement are common in those affected by COVID-19. These symptoms have a great impact on the quality of life both in the short and medium to long term. A better understanding of the pathophysiological mechanisms of Post-COVID manifestations that affect the autonomic nervous system, and targeted therapeutic management could help reduce the sequelae of COVID-19, especially if we act in the earliest phases of the disease.

A new animal model of atrophy-hypertrophy complex and liver damage following Yttrium-90 lobar selective internal radiation therapy in rabbits.

Lobar selective internal radiation therapy (SIRT) is widely used to treat liver tumors inducing atrophy of the treated lobe and contralateral hypertrophy. The lack of animal model has precluded further investigations to improve this treatment. We developed an animal model of liver damage and atrophy-hypertrophy complex after SIRT. Three groups of 5-8 rabbits received transportal SIRT with Yttrium 90 resin microspheres of the cranial lobes with different activities (0.3, 0.6 and 1.2 GBq), corresponding to predicted absorbed radiation dose of 200, 400 and 800 Gy, respectively. Another group received non-loaded microspheres (sham group). Cranial and caudal lobes volumes were assessed using CT volumetry before, 15 and 30 days after SIRT. Liver biochemistry, histopathology and gene expression were evaluated. Four untreated rabbits were used as controls for gene expression studies. All animals receiving 1.2 GBq were euthanized due to clinical deterioration. Cranial SIRT with 0.6 GBq induced caudal lobe hypertrophy after 15 days (median increase 34% -ns-) but produced significant toxicity. Cranial SIRT with 0.3 GBq induced caudal lobe hypertrophy after 30 days (median increase 82%, p = 0.04). No volumetric changes were detected in sham group. Transient increase in serum transaminases was detected in all treated groups returning to normal values at 15 days. There was dose-dependent liver dysfunction with bilirubin elevation and albumin decrease. Histologically, 1.2 GBq group developed permanent severe liver damage with massive necrosis, 0.6 and 0.3 GBq groups developed moderate damage with inflammation and portal fibrosis at 15 days, partially recovering at 30 days. There was no difference in the expression of hepatocyte function and differentiation genes between 0.3 GBq and control groups. Cranial SIRT with 0.3 GBq of 90Y resin microspheres in rabbits is a reliable animal model to analyse the atrophy-hypertrophy complex and liver damage without toxicity.

Efficacy and Safety of Endoscopic Submucosal Dissection for Superficial Gastric Neoplasms: A Latin American Cohort Study.

BACKGROUND/AIMS: Endoscopic submucosal dissection (ESD) is the preferred technique for treating early gastric cancer (EGC). However, very few studies have been conducted in South America. This study aimed to assess the efficacy and safety of ESD for EGC. METHODS: We analyzed data from a prospective cohort from 2013 to 2020. A total of 152 superficial gastric neoplasms that fulfilled the absolute or expanded criteria for ESD were included. Outcomes were en bloc, R0, and curative resection rates, incidence of adverse events, and length of procedure. RESULTS: The age of the enrolled patients was 68.4±11.3 years. The number of included patients based on the absolute and expanded indications was 150 and 2, respectively. En bloc, R0, and curative resections were achieved in 98.0%, 96.1%, and 89.5% of the cases, respectively. Bleeding and perforation were reported in 5.9% and 6.6% of the cases, respectively. Histopathological examination revealed lowgrade dysplasia, high-grade dysplasia, well-differentiated adenocarcinoma, and poorly differentiated adenocarcinoma in 13, 20, 117, and 2 cases, respectively. CONCLUSION: Our study shows that ESD performed by properly trained endoscopists in reference centers is safe and effective, with comparable therapeutic outcomes to those reported in the Eastern series.

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.

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.

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.

Acquiring sepsis competencies through simulation-based learning bundle during intermediate care unit internship.

ABSTRACT: Intermediate care units (ImCUs) have been shown as appropriate units for the management of selected septic patients. Developing specific protocols for residents in training may be useful for their medical performance. The objective of this study was to analyze whether a simulation-based learning bundle is useful for residents while acquiring competencies in the management of sepsis during their internship in an ImCU.A prospective study, set in a tertiary-care academic medical center was performed enrolling residents who performed their internship in an ImCU from 2014 to 2017. The pillars of the simulation-based learning bundle were sepsis scenario in the simulation center, instructional material, and sepsis lecture, and management of septic patients admitted in the ImCU. Each resident was evaluated in the beginning and at the end of their internship displaying a sepsis-case scenario in the simulation center. The authors developed a sepsis-checklist that residents must fulfill during their performance which included 5 areas: hemodynamics (0-10), oxygenation (0-5), antibiotic therapy (0-9), organic injury (0-5), and miscellaneous (0-4).Thirty-four residents from different years of residency and specialties were evaluated. The total median score (interquartile range) increased significantly after training: 12 (25) vs 23 (16), P = .001. First-year residents scored significantly lower than older residents at baseline: 10 (14) vs 14.5 (19), P = .024. However, the performance at the end of the training period was similar in both groups: 21.5 (11) vs 23 (16), P = 1.000. Internal Medicine residents scored significantly higher than residents from other specialties: 18 (17) vs 10.5 (21), P = .007. Nonetheless, the performance at the end of the training period was similar in both groups: 24.5 (9) vs 22 (13), P = 1.000.Combining medical simulation with didactic lectures and a rotation in an ImCU staffed by hospitalists seems to be useful in acquiring competencies to manage critically ill patients with sepsis. We designed a checklist to assure an objective evaluation of the performance of the residents and to identify those aspects that could be potentially improved.

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.

Un paciente varón de 15 años, con el diagnóstico de acalasia realizado 4 años antes, acudió a evaluación por presentar disfagia, regurgitación, pérdida de peso y dolor restroesternal. El esofagograma baritado evidenció una dilatación severa del esófago y la terminación clásica en "pico de pájaro". El paciente había sido sometido a una miotomía de Heller más fundoplicatura y posteriormente a una dilatación esofágica con balón 4 meses atrás. Sin embargo, los síntomas persistían y la última manometría de alta resolución reveló acalasia tipo II. Finalmente, se realizó una miotomía endoscópica por vía oral (POEM); el cual es un procedimiento seguro y accesible en centros experimentados y debidamente equipados, pudiendo ser una adecuada opción de tratamiento en casos de acalasia refractaria. Presentamos el caso del paciente más joven en nuestra región con acalasia con una respuesta exitosa a un POEM de rescate.

NEUROPATHY, ATAXIA, AND RETINITIS PIGMENTOSA SYNDROME: A MULTIDISCIPLINARY DIAGNOSIS.

PURPOSE: To report a case of neuropathy, ataxia, and retinitis pigmentosa syndrome, a rare and undiagnosed disease in ophthalmology due to the need for multidisciplinary evaluation. METHODS: Multimodal testing was performed, including neurologic, ophthalmologic, and genetic assessments. The neurologic tests comprised electromyogram and muscle biopsy; the ophthalmologic examination consisted of slit-lamp and fundus examinations, optical coherence tomography, visual field testing, and electrophysiology tests such as a full-field electroretinogram and multifocal electroretinogram; and genetic tests were performed for spinocerebellar ataxia. In addition, the patient underwent magnetic resonance imaging, an electrocardiogram, cerebrospinal fluid analysis with lactate levels, and a blood workup including antineuronal, antithyroid peroxidase, antinuclear, antimitochondrial, and antitransglutaminase antibodies and fat-soluble vitamins (A, D, E, K). RESULTS: The ocular fundus examination showed bone spicules with retinal pigment epithelium alteration, optic nerve pallor, and arterial attenuation. Optical coherence tomography demonstrated macular atrophy. Visual field testing revealed concentric reduction. Electrophysiology examinations showed involvement of rods and cones in both eyes. The muscle biopsy was compatible with mitochondrial disease, and electromyogram demonstrated sensory axonal damage. However, genetic tests for spinocerebellar ataxia were negative. Magnetic resonance imaging showed cerebellar atrophy, whereas the electrocardiogram did not detect any abnormalities. Cerebrospinal fluid lactate levels were above normal but antibody levels in blood were normal. CONCLUSION: This is the first report of macular atrophy demonstrated by optical coherence tomography in a patient with neuropathy, ataxia, and retinitis pigmentosa syndrome. For the diagnosis, a multidisciplinary team including a neurologist, a geneticist, and an ophthalmologist was essential. Patients with suspected mitochondrial disease could greatly benefit from an ophthalmology examination like that conducted in this case because it was the key factor that led to the suspicion of syndromic disease, and ultimately the diagnosis.

[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.

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

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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.

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.