ABSTRACT
Gamification is a dynamic tool for educational transformation useful to encourage student interest and enhance learning. Here we present a study conducted to investigate the effectiveness of an educational card game developed by us in veterinary anatomy practicals to reinforce knowledge acquisition in veterinary students. A total of four sets of cards were designed, each one with different anatomical topics (structure identification, articulation and positioning, clinical anatomy, and comparative anatomy); students were arranged in small groups (7-10 students per group) and played the game at the end of each anatomy practical session, discussing the corresponding questions, randomly chosen, as a team. This activity was highly valued by students, most of whom (>80%) expressed that the game was enjoyable, challenging, helpful to improve their knowledge and understanding in clinical anatomy, and effective for anatomy exam preparation. Thus, the use of educational games in practical sessions seems to improve student engagement in the learning process individually and as a team.NEW & NOTEWORTHY The development and implementation of a card game as a training resource that allows learning veterinary anatomy in a motivating and cooperative environment, promoting teamwork, relationships, and trust and communication between colleagues, is described. Stimulating the ability to solve problems as a team has provided help to students preparing for their exams in a more dynamic and enjoyable way.
Subject(s)
Anatomy , Education, Veterinary , Anatomy/education , Anatomy, Veterinary/education , Educational Measurement , Humans , Learning , StudentsABSTRACT
BACKGROUND: Ticagrelor has a bactericidal effect in vitro, and clinical studies suggest a beneficial effect in infections. Our aim was to determine the incidence of infections in patients treated with 3 different P2Y12 receptor inhibitors. METHODS: Retrospective registry in a cardiology department. Patients with coronary artery disease discharged on ticagrelor, prasugrel, or clopidogrel from March 2017 to June 2019 were included. The risk of infection was analyzed during the period of P2Y12 inhibitor treatment (12.4 ± 6.7 months). RESULTS: A total of 250 patients were included (ticagrelor 91 [36.4%], prasugrel 89 [35.6%], clopidogrel 70 [28.0%]). Mean age was 61.0 ± 13.1 years, and 63 (25.2%) were women. The most common reason to use these drugs was ST-segment elevation acute myocardial infarction (STEMI) (152 patients - 60.8%). STEMI was the reason to use prasugrel in 84 patients (94.4%), ticagrelor in 44 (48.4%), and clopidogrel in 24 (34.3%), p < 0.001. An infection during follow-up was seen in 87 patients (34.8%), 23 treated with ticagrelor (25.3%), 30 with prasugrel (33.7%) and 34 with clopidogrel (48.6%), p = 0.009. Ticagrelor was independently associated with a lower likelihood of infection (Hazard Ratio [HR] 0.52, 95% confidence interval [CI] 0.28-0.95; p = 0.035) compared to prasugrel (HR 0.96, 95% CI 0.54-1.73; p = 0.909) and clopidogrel (HR = 1). CONCLUSIONS: In patients admitted with coronary artery disease patients treated with ticagrelor had a lower frequency of infections during follow-up than those treated with other P2Y12 inhibitors. Further studies are necessary to clarify the bactericidal effect of ticagrelor in this context.
Subject(s)
Coronary Artery Disease , Aged , Clopidogrel/therapeutic use , Coronary Artery Disease/drug therapy , Coronary Artery Disease/epidemiology , Female , Humans , Middle Aged , Prasugrel Hydrochloride/therapeutic use , Retrospective Studies , Ticagrelor/therapeutic useABSTRACT
BACKGROUND: Patients with chest pain and persistent ST segment elevation (STE) may not have acute coronary occlusions or serum troponin curves suggestive of acute necrosis. Our objective is the validation and cost-effectiveness analysis of a diagnostic model assisted by artificial intelligence (AI). METHODS: Prospective multicenter registry in two groups of patients with STE: I) coronary arteries without significant lesions and without serum troponin curve suggestive of acute necrosis, II) myocardial infarction with acute coronary occlusion. The inclusion criteria are the following: 1) age ≥ 18 years, 2) chest pain or symptoms suggestive of myocardial ischemia, 3) STE at point J in two contiguous leads ≥0.1 mV, in V2 and V3 ≥ 0,2 mV and 4) signature of informed consent. The exclusion criteria are the following: 1) left bundle branch block, 2) acute cardiac necrosis in the absence of significant epicardial coronary artery stenosis, 3) STE ≤ 0.1 mV with pathologic Q wave, 4) severe anemia (hemoglobin <8.0 g/dl). For each patient without acute cardiac necrosis, the next patient from that center of the same sex and similar age (± 5 years) with myocardial infarction and acute coronary occlusion will be included. A manual centralized electrocardiographic analysis and another by deep learning AI will be performed. CONCLUSIONS: The results of the study will provide new information for the stratification of patients with STE. Our hypothesis is that an AI analysis of the surface electrocardiogram allows a better distinction of patients with STE due to acute myocardial ischemia, from those with another etiology.
Subject(s)
Coronary Occlusion , Deep Learning , Myocardial Infarction , Adolescent , Artificial Intelligence , Electrocardiography , Humans , Myocardial Infarction/diagnosis , RegistriesABSTRACT
BACKGROUND: Previous studies have described a circadian pattern of death from cardiovascular causes with a morning peak. Our aim is to describe the daytime oscillations in mortality in hospitalized patients with cardiovascular diseases. METHODS: Our retrospective registry including all patients who died in the Cardiology Department, including the cardiac intensive care unit, Madrid, Spain. RESULTS: From a total of 500 patients, time of death was registered in 373 (74.6%), which are the focus of our study; 354 (70.8%) died in the cardiac intensive care unit and 146 (29.2%) in the conventional ward. Mean age was 74.2 ± 13.1 years, and 239 (64.1%) were male. Cardiovascular causes were the leading cause of death (308 patients; 82.6%). Mortality followed a circadian biphasic pattern with a peak at dawn (00.00-05.59 a.m.: 104 patients [27.9%]) and in the afternoon (12.00-17.59 p.m.: 135 patients [36.2%]), irrespective of the cause of death. The peak of mortality occurred in the afternoon (12.00-17.59 p.m.) in the case of cardiovascular mortality (119 deaths [38.6%]) and in the evening (18.00-23.59 p.m.) for non-cardiovascular deaths (21 deaths [32.3%], p = 0.03). This pattern was present regardless from the place of death (conventional ward or cardiac intensive care unit) and also throughout the four seasons. CONCLUSIONS: Mortality in hospitalized patients with cardiovascular diseases follows a circadian biphasic pattern.
Subject(s)
Cardiology , Circadian Rhythm , Aged , Humans , Intensive Care Units , Male , Retrospective Studies , SeasonsABSTRACT
Our aim was to describe the clinical profile of patients presenting sustained ventricular arrhythmias after sacubitril/valsartan (SV) initiation. All cases of sustained ventricular arrhythmias in patients receiving SV were consecutively recorded in two centers. Nineteen patients had sustained ventricular arrhythmias after SV. All were men and were previously receiving angiotensin-converting enzyme inhibitors, or angiotensin II receptor blockers before SV initiation. Fifteen patients (78.9%) had electrical stability in the previous 6 months. Nine patients (47.4%) initiated SV at the lowest available dose (24/26 mg). Globally, in all but five patients alive at discharge, SV was discontinued after the event. Six patients presented new arrhythmic events after discontinuation of SV. Two deaths and three heart transplants occurred (one due to heart failure and the other two due to persistent ventricular arrhythmias). All patients had a high arrhythmic risk, and 17 (89.5%) had an implanted cardioverter defibrillator. No specific triggers for the arrhythmic event were found. Male sex and previous episodes of ventricular arrhythmias could be associated with an increased risk of sustained ventricular tachycardia after SV initiation. Discontinuation of the drug might be an additional approach to enable a better control of ventricular arrhythmias in some patients.
Subject(s)
Aminobutyrates/adverse effects , Angiotensin II Type 1 Receptor Blockers/adverse effects , Heart Failure/drug therapy , Heart Rate/drug effects , Protease Inhibitors/adverse effects , Tachycardia, Ventricular/chemically induced , Tetrazoles/adverse effects , Aged , Aged, 80 and over , Biphenyl Compounds , Drug Combinations , Heart Failure/complications , Heart Failure/diagnosis , Heart Failure/physiopathology , Humans , Male , Middle Aged , Neprilysin/antagonists & inhibitors , Risk Assessment , Risk Factors , Spain , Tachycardia, Ventricular/diagnosis , Tachycardia, Ventricular/physiopathology , Time Factors , Treatment Outcome , ValsartanABSTRACT
BACKGROUND: Long-term prognosis of acute coronary syndromes (ACS) in human immunodeficiency virus (HIV)-infected patients is unknown. AIMS: To compare outcomes after ACS in HIV-infected and uninfected patients. METHODS: Retrospective observational study. HIV cases were matched with two HIV-uninfected controls for age, sex and type of ACS. RESULTS: In 92 HIV patients (mean age 51.3 ± 9.0 years, 7.6% women), the prevalence of cardiovascular risk factors was high (smoking 71.7%; hypertension 41.3%; diabetes 14.1%); dyslipidaemia was more frequent (53 (57.6%) vs 79 (42.9%), P = 0.02) and obesity less common (8 (8.7%) vs 41 (22.3%), P = 0.002) than in controls. Eighty-seven (94.6%) HIV patients had undetectable viral load and 85 (92.4%) were under anti-retroviral therapy. Multivessel disease was more common in HIV patients than in controls (44 (47.8%) vs 71 (39.1%); P = 0.05) as was Killip class 3-4 on admission (9 (9.8%) vs 6 (3.3%); P = 0.04). The rate of in-hospital mortality was similar in both groups (2%), and there were no significant differences in 3-year mortality (10.2% vs 5.7%; P = 0.27). Non-cardiovascular readmissions at 3 years were more frequent in HIV patients than in controls (36.5% vs 7.4%; P < 0.001). Multivariate analysis identified previous coronary artery disease as the strongest predictor of mortality in HIV patients (hazard ratio 4.7, 95% confidence interval 1.4-15.7, P = 0.01), whereas HIV infection was not associated with prognosis. CONCLUSION: HIV patients with ACS had more frequent multivessel disease and heart failure than matched controls. However, in-hospital and long-term mortality was similar in both groups. Non-cardiovascular re-hospitalisations were more common in HIV patients.
Subject(s)
Acute Coronary Syndrome , HIV Infections , Acute Coronary Syndrome/diagnosis , Acute Coronary Syndrome/epidemiology , Adult , Female , HIV , HIV Infections/complications , HIV Infections/drug therapy , HIV Infections/epidemiology , Humans , Male , Middle Aged , Prognosis , Retrospective Studies , Risk FactorsABSTRACT
BACKGROUND: Previous studies have indicated that cardiovascular mortality follows a seasonal trend. The aim of this work was to determine the evolution of mortality throughout the year in a cardiology department. METHODS: All admissions and deaths occurring in our Cardiology Department over a 5-year period (2013-2017) were recorded retrospectively. RESULTS: From a total of 17,829 hospital admissions, 500 patients died (2.8%, 0.3 patients/day). The mean age of deceased patients was 74.2 ± 13.1 years, and 186 (37.2%) were women. Mortality ranged from 0.17 deaths/day in August to 0.40 deaths/day in February (p = 0.03), and from 0.20 deaths/day in summer to 0.36 deaths/day in winter (p = 0.001). There was also a trend towards a variation in hospitalizations, with a peak in January (10.5 admissions/day) and the lowest figure in August (7.0 admissions/day), p = 0.047. We found no significant seasonal trend regarding mortality rate with respect to the number of hospital admissions (p = 0.89). The most common cause of death was refractory heart failure (267 patients [65.8%]). A noncardiac cause of death was observed in 134 patients (26.8%). CONCLUSIONS: In a cardiology department, there are twice as many deaths in winter as in summer. Hospitalizations also tend to be more frequent in winter than in summer.
Subject(s)
Coronary Care Units/statistics & numerical data , Heart Failure/mortality , Hospital Mortality/trends , Seasons , Adult , Aged , Aged, 80 and over , Cause of Death , Female , Humans , Male , Middle Aged , Patient Admission/trends , Retrospective Studies , Spain/epidemiologyABSTRACT
OBJECTIVES: Our goal was to determine the presentation and prognosis of influenza in an intensive cardiac care unit and to analyze the impact of an active surveillance program in the diagnosis. METHODS: We performed a prospective registry during the flu season in a coronary unit. In the first phase, no systematic screening was performed. Systematic influenza A and B detection was performed in a second phase for all patients admitted. RESULTS: From 227 patients, we identified 17 (7.5%) with influenza. Influenza patients were more likely to have a non-ischemic cause of admission (14 patients [82.4%] vs. 48 patients [40.3%], p = 0.002), fever (8 patients [47.1%] vs. 3 patients [2.6%], p < 0.001), and respiratory failure (7 patients [41.2%] vs. 8 patients [7%], p = 0.001). Influenza infection was an independent predictor of mortality (odds ratio 12.0, 95% confidence interval 1.9-13.6, p < 0.001). The incidence of influenza was 6.6% (6 patients) when no active screening was performed and 7.9% (11 patients) when systematic detection was performed (p = 0.005). The time to diagnosis was shorter in the systematic screening phase (0.92 ± 1.6 vs. 5.2 ± 3.8 days, p = 0.01). CONCLUSIONS: Influenza affects approximately 8% of patients admitted to an intensive cardiac care unit during the flu season, with a high mortality rate. An active surveillance program improves early detection.
Subject(s)
Coronary Care Units/statistics & numerical data , Influenza, Human/epidemiology , Registries , Aged , Aged, 80 and over , Female , Hospital Mortality , Humans , Incidence , Male , Prospective Studies , Spain/epidemiologyABSTRACT
BACKGROUND: The influence of interatrial block (IAB) in the prognosis after an acute ST-segment elevation myocardial infarction (STEMI) is unknown. OBJECTIVES: To assess the prognostic impact of IAB after an acute STEMI regarding long-term mortality, development of atrial fibrillation, and stroke. METHODS: Registry of 972 consecutive patients with STEMI and sinus rhythm at discharge, with a long-term follow-up (49.6 ± 24.9 months). P wave duration was analyzed using digital calipers, and patients were divided into three groups: normal P wave duration (<120 ms), partial IAB (pIAB) (P wave ≥120 ms and positive in inferior leads), and advanced IAB (aIAB) (P wave ≥120 ms plus biphasic [positive/negative] morphology in inferior leads). RESULTS: Mean age was 62.6 ± 13.5 years. A total of 708 patients had normal P wave (72.8%), 207 pIAB (21.3%), and 57 aIAB (5.9%). Patients with aIAB were older (mean age 73 years) than the rest (62 years in the other two groups, p < 0.001). They also had a higher rate of hypertension (70 vs. 55% in pIAB and 49% in normal P wave, p = 0.006) and higher all-cause mortality (26.3 vs. 12.6% in pIAB and 10.3% in normal P wave, p = 0.001). However, multivariable analysis did not show an independent association between IAB and prognosis. CONCLUSION: About a quarter of patients discharged in sinus rhythm after an acute STEMI have IAB. Patients with aIAB have a poor prognosis, although this is explained mainly by the association of aIAB with age and other variables.
Subject(s)
Hypertension/complications , Interatrial Block/complications , Interatrial Block/epidemiology , ST Elevation Myocardial Infarction/complications , Acute Disease , Aged , Aged, 80 and over , Electrocardiography , Female , Humans , Hypertension/epidemiology , Male , Middle Aged , Mortality , Prognosis , Proportional Hazards Models , Registries , Spain/epidemiologyABSTRACT
BACKGROUND & AIMS: We investigated whether patients with multiple serrated polyps, but not meeting the World Health Organization criteria for serrated polyposis syndrome, and their relatives have similar risks for colorectal cancer (CRC) as those diagnosed with serrated polyposis. METHODS: We collected data from patients with more than 10 colonic polyps, recruited in 2008-2009 from 24 hospitals in Spain for a study of causes of multiple colonic polyps. We analyzed data from 53 patients who met the criteria for serrated polyposis and 145 patients who did not meet these criteria, but who had more than 10 polyps throughout the colon, of which more than 50% were serrated. We calculated age- and sex-adjusted standardized incidence ratios (SIRs) for CRC in both groups, as well as in their first-degree relatives. RESULTS: The prevalence of CRC was similar between patients with confirmed serrated polyposis and multiple serrated polyps (odds ratio, 1.35; 95% confidence interval [CI], 0.64-2.82; P = .40). The SIR for CRC in patients with serrated polyposis (0.51; 95% CI, 0.01-2.82) did not differ significantly from the SIR for CRC in patients with multiple serrated polyps (0.74; 95% CI, 0.20-1.90; P = .70). The SIR for CRC also did not differ significantly between first-degree relatives of these groups (serrated polyposis: 3.28, 95% CI, 2.16-4.77; multiple serrated polyps: 2.79, 95% CI, 2.10-3.63; P = .50). Kaplan-Meier analysis showed no differences in the incidence of CRC between groups during the follow-up period (log-rank, 0.6). CONCLUSIONS: The risk of CRC in patients with multiple serrated polyps who do not meet the criteria for serrated polyposis, and in their first-degree relatives, is similar to that of patients diagnosed with serrated polyposis.
Subject(s)
Adenoma/diagnosis , Colonic Polyps/genetics , Colonic Polyps/pathology , Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/epidemiology , Population Surveillance , Adenoma/pathology , Adult , Aged , Colonic Polyps/diagnosis , Colonoscopy , Colorectal Neoplasms/pathology , DNA Glycosylases/genetics , DNA Mutational Analysis , Female , Humans , Incidence , Male , Middle Aged , Mutation , Pedigree , Prevalence , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins p21(ras)/genetics , Risk Factors , Syndrome , Tumor BurdenABSTRACT
OBJECTIVES: Sacubitril/valsartan was approved recently for the treatment of patients with heart failure and reduced ejection fraction. We present 6 cases of ventricular arrhythmia, that occurred shortly after sacubitril/valsartan initiation, that required drug withdrawal. Other potential triggering factors of electrical storm were ruled out and, from the arrhythmic perspective, all of the patients were stable in the previous year. Our aim is to describe the possible association of sacubitril/valsartan with arrhythmic storm. METHODS: This was an observational monocentric study performed in the first 7 months of sacubitril/valsartan commercialization in Spain (October 2016). All patients were included in the SUMA (Sacubitril/Varsartan Usado Ambulatoriamente en Madrid [Sacubitril/Valsartan Used in Outpatients in Madrid]) registry. Patients were consecutively enrolled on the day they started the drug. Ventricular arrhythmic storm was defined as ≥2 episodes of sustained ventricular arrhythmia or defibrillator therapy application in 24 h. RESULTS: From 108 patients who received the drug, 6 presented with ventricular arrhythmic storm (5.6%). Baseline characteristics were similar in the patients with and without ventricular arrhythmic storm. The total number of days that sacubitril/valsartan was administered to each patient was 5, 6, 44 (8 since titration), 84, 93, and 136 (105 since titration), respectively. CONCLUSIONS: Our data are not enough to infer a cause-and-effect relationship. Further investigations regarding a potential proarrhythmic effect of sacubitril/valsartan are probably needed.
Subject(s)
Aminobutyrates/adverse effects , Angiotensin Receptor Antagonists/adverse effects , Arrhythmias, Cardiac/chemically induced , Tetrazoles/adverse effects , Aged , Aged, 80 and over , Biphenyl Compounds , Drug Combinations , Heart Diseases/drug therapy , Humans , Male , Middle Aged , ValsartanABSTRACT
Germline mutations in DNA polymerase É (POLE) and δ (POLD1) have been recently identified in families with multiple colorectal adenomas and colorectal cancer (CRC). All reported cases carried POLE c.1270C>G (p.Leu424Val) or POLD1 c.1433G>A (p.Ser478Asn) mutations. Due to the scarcity of cases reported so far, an accurate clinical phenotype has not been defined. We aimed to assess the prevalence of these recurrent mutations in unexplained familial and early-onset CRC and polyposis, and to add additional information to define the clinical characteristics of mutated cases. A total of 858 familial/early onset CRC and polyposis patients were studied: 581 familial and early-onset CRC cases without mismatch repair (MMR) deficiency, 86 cases with MMR deficiency and 191 polyposis cases. Mutation screening was performed by KASPar genotyping assays and/or Sanger sequencing of the involved exons. POLE p.L424V was identified in a 28-year-old polyposis and CRC patient, as a de novo mutation. None of the 858 cases studied carried POLD1 p.S478N. A new mutation, POLD1 c.1421T>C (p.Leu474Pro), was identified in a mismatch repair proficient Amsterdam II family. Its pathogenicity was supported by cosegregation in the family, in silico predictions, and previously published yeast assays. POLE and POLD1 mutations explain a fraction of familial CRC and polyposis. Sequencing the proofreading domains of POLE and POLD1 should be considered in routine genetic diagnostics. Until additional evidence is gathered, POLE and POLD1 genetic testing should not be restricted to polyposis cases, and the presence of de novo mutations, considered.
Subject(s)
Adenomatous Polyposis Coli/genetics , Colorectal Neoplasms/genetics , DNA Polymerase III/genetics , DNA Polymerase II/genetics , Germ-Line Mutation/genetics , Adult , Female , Humans , Male , Middle Aged , Poly-ADP-Ribose Binding ProteinsABSTRACT
BACKGROUND AND STUDY AIMS: Endoscopic surveillance in patients with multiple colorectal polyps aims to reduce colorectal cancer (CRC) incidence and mortality, as well as the need for colorectal surgery. The aim of this study was to determine the risk of developing CRC or the need for surgery during endoscopic surveillance in a cohort of patients with multiple (10â-â100) colorectal polyps. PATIENTS AND METHODS: This was a multicentrer, longitudinal, observational study in 15 CRC high risk clinics in Spain, carried out between January 2009 and December 2010.âPatients who were included in the EPIPOLIP trial and had at least 1 year of follow-up were included in the study. The primary outcome of interest was the incidence of CRC at least 1 year following the initial colonoscopy. The secondary outcome was the need for colorectal surgery. RESULTS: A total of 265 patients were followed for a median of 3.8 years. Patients underwent a median of 5 colonoscopies, and 17 patients (6.4â%) were diagnosed with CRC. A total of 32 patients (12.1â%) underwent surgery, including 15 (5.7â%) for prophylaxis without a diagnosis of CRC. The corresponding incidence density rates for CRC and colorectal surgery were 1.4 (95â% confidence interval [CI] 0.7 to 2.1) and 2.7 (95â%CI 1.7 to 3.6) per 100 patient-years, respectively. Only the presence of symptoms at first colonoscopy was independently associated with CRC diagnosis (hazard ratio [HR] 7.7, 95â%CI 1.1 to 59.3) and colorectal surgery (HR 4.6, 95â%CI 1.02 to 20.6). CONCLUSIONS: Patients with more than 10 neoplastic polyps required frequent colonoscopies within a short follow-up period. More than 10â% of patients required colorectal surgery within 4 years, more than half for incident CRC.
Subject(s)
Adenomatous Polyps/pathology , Colonoscopy , Colorectal Neoplasms/pathology , Early Detection of Cancer , Intestinal Polyps/pathology , Precancerous Conditions/pathology , Adolescent , Adult , Aged , Colorectal Neoplasms/epidemiology , Colorectal Neoplasms/surgery , Female , Humans , Incidence , Longitudinal Studies , Male , Middle Aged , Proportional Hazards Models , Retrospective Studies , Spain , Young AdultABSTRACT
BACKGROUND: The prevalence of MLH1 constitutional epimutations in the general population is unknown. We sought to analyse the prevalence of MLH1 constitutional epimutations in unselected and selected series of patients with colorectal cancer (CRC). METHODS: Patients with diagnoses of CRC (n=2123) were included in the unselected group. For comparison, a group of 847 selected patients with CRC who fulfilled the revised Bethesda guidelines (rBG) were also included. Somatic and constitutional MLH1 methylation was assayed via methylation-specific multiplex ligation-dependent probe amplification of cases lacking MLH1 expression. Germline alterations in mismatch-repair (MMR) genes were assessed via Sanger sequencing and methylation-specific multiplex ligation-dependent probe amplification. RESULTS: Loss of MLH1 expression occurred in 5.5% of the unselected series and 12.5% of the selected series (p<0.0001). No constitutional epimutations in MLH1 were detected in the unselected population (0/62); five cases from the selected series were positive for MLH1 epimutations (15.6%, 5/32; p=0.004). CONCLUSIONS: Our results suggest a negligible prevalence of MLH1 constitutional epimutations in unselected cases of CRC. Therefore, MLH1 constitutional epimutation analysis should be conducted only for patients who fulfil the rBG and who lack MLH1 expression with methylated MLH1.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/epidemiology , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , DNA Methylation/genetics , Epigenesis, Genetic/genetics , Mutation/genetics , Nuclear Proteins/genetics , Base Sequence , DNA Mismatch Repair/genetics , Genetic Testing/standards , Humans , Microsatellite Repeats/genetics , Molecular Sequence Data , MutL Protein Homolog 1 , Prevalence , Promoter Regions, Genetic/genetics , Sequence Analysis, DNA , Statistics, NonparametricABSTRACT
BACKGROUND & AIMS: Colorectal cancers (CRCs) with microsatellite instability (MSI) and a mismatch repair (MMR) immunohistochemical deficit without hypermethylation of the MLH1 promoter are likely to be caused by Lynch syndrome. Some patients with these cancers have not been found to have pathogenic germline mutations and are considered to have Lynch-like syndrome (LLS). The aim of this study was to determine the risk of cancer in families of patients with LLS. METHODS: We studied a population-based cohort of 1705 consecutive patients, performing MSI tests and immunohistochemical analyses of MMR proteins. Patients were diagnosed with Lynch syndrome when they were found to have pathogenic germline mutations. Patients with MSI and loss of MSH2 and/or MSH6 expression, isolated loss of PMS2 or loss of MLH1 without MLH1 promoter hypermethylation, and no pathogenic mutation were considered to have LLS. The clinical characteristics of patients and the age- and sex-adjusted standardized incidence ratios (SIRs) of cancer in families were compared between groups. RESULTS: The incidence of CRC was significantly lower in families of patients with LLS than in families with confirmed cases of Lynch syndrome (SIR for Lynch syndrome, 6.04; 95% confidence interval [CI], 3.58-9.54; SIR for LLS, 2.12; 95% CI, 1.16-3.56; P < .001). However, the incidence of CRC was higher in families of patients with LLS than in families with sporadic CRC (SIR for sporadic CRC, 0.48; 95% CI, 0.27-0.79; P < .001). CONCLUSIONS: The risk of cancer in families with LLS is lower that of families with Lynch syndrome but higher than that of families with sporadic CRC. These results confirm the need for special screening and surveillance strategies for these patients and their relatives.
Subject(s)
Adaptor Proteins, Signal Transducing/genetics , Colorectal Neoplasms, Hereditary Nonpolyposis/epidemiology , DNA, Neoplasm/genetics , Nuclear Proteins/genetics , Population Surveillance , Adaptor Proteins, Signal Transducing/metabolism , Adult , Aged , Aged, 80 and over , Colorectal Neoplasms, Hereditary Nonpolyposis/diagnosis , Colorectal Neoplasms, Hereditary Nonpolyposis/genetics , DNA Mismatch Repair , DNA Repair , Female , Germ-Line Mutation , Humans , Immunohistochemistry , Incidence , Male , Microsatellite Instability , Middle Aged , MutL Protein Homolog 1 , Nuclear Proteins/metabolism , Risk Factors , Spain/epidemiologySubject(s)
Aminobutyrates , Tetrazoles , Arrhythmias, Cardiac , Biphenyl Compounds , Drug Combinations , Humans , ValsartanABSTRACT
INTRODUCTION AND OBJECTIVES: In the setting of ST-segment elevation myocardial infarction (STEMI), imaging-based biomarkers could be useful for guiding oral anticoagulation to prevent cardioembolism. Our objective was to test the efficacy of intraventricular blood stasis imaging for predicting a composite primary endpoint of cardioembolic risk during the first 6 months after STEMI. METHODS: We designed a prospective clinical study, Imaging Silent Brain Infarct in Acute Myocardial Infarction (ISBITAMI), including patients with a first STEMI, an ejection fraction ≤ 45% and without atrial fibrillation to assess the performance of stasis metrics to predict cardioembolism. Patients underwent ultrasound-based stasis imaging at enrollment followed by heart and brain magnetic resonance at 1-week and 6-month visits. From the stasis maps, we calculated the average residence time, RT, of blood inside the left ventricle and assessed its performance to predict the primary endpoint. The longitudinal strain of the 4 apical segments was quantified by speckle tracking. RESULTS: A total of 66 patients were assigned to the primary endpoint. Of them, 17 patients had 1 or more events: 3 strokes, 5 silent brain infarctions, and 13 mural thromboses. No systemic embolisms were observed. RT (OR, 3.73; 95%CI, 1.75-7.9; P<.001) and apical strain (OR, 1.47; 95%CI, 1.13-1.92; P=.004) showed complementary prognostic value. The bivariate model showed a c-index=0.86 (95%CI, 0.73-0.95), a negative predictive value of 1.00 (95%CI, 0.94-1.00), and positive predictive value of 0.45 (95%CI, 0.37-0.77). The results were confirmed in a multiple imputation sensitivity analysis. Conventional ultrasound-based metrics were of limited predictive value. CONCLUSIONS: In patients with STEMI and left ventricular systolic dysfunction in sinus rhythm, the risk of cardioembolism may be assessed by echocardiography by combining stasis and strain imaging. Registered at ClinicalTrials.gov (NCT02917213).
ABSTRACT
BACKGROUND & AIMS: We investigated clinical and molecular differences between the different phenotypes of serrated polyposis syndrome (SPS) and the frequency of mutations in BRAF or KRAS in polyps from patients with SPS. METHODS: We collected data on clinical and demographic characteristics of 50 patients who fulfilled the criteria for SPS. Polymerase chain reaction and sequence analysis were used to identify BRAF and KRAS mutations in 432 polyps collected from 37 patients; we analyzed CpG island methylator phenotypes in 272 of these polyps. RESULTS: Fifteen patients (30%) had type 1 SPS and 35 had type 2 SPS. There were no significant differences in age at diagnosis, sex, smoking frequency, body mass index, or colorectal cancer predisposition between groups of patients, or in the pathologic or molecular characteristics of their polyps. A familial history of colorectal cancer or colonic polyps was reported more frequently by patients with type 2 SPS. BRAF mutations were found in 63% of polyps and KRAS mutations were found in 9.9%; 43.4% of polyps had the CpG island methylator phenotype-high phenotype. A per-patient analysis revealed that all patients had a BRAF or KRAS mutation in more than 25% of their polyps; 84.8% of patients had a mutation in BRAF or KRAS in more than 50% of their polyps. CONCLUSIONS: Except for a greater likelihood of familial history of colorectal cancer or colonic polyps in patients with type 2 SPS, we found no significant demographic, pathologic, or molecular differences between types 1 and 2 SPS. All patients had a BRAF or KRAS mutation in at least 25% of their polyps.
Subject(s)
Adenomatous Polyposis Coli/genetics , Adenomatous Polyposis Coli/pathology , Polymorphism, Genetic , Proto-Oncogene Proteins B-raf/genetics , Proto-Oncogene Proteins/genetics , ras Proteins/genetics , Adult , Aged , CpG Islands , DNA Methylation , Female , Humans , Male , Middle Aged , Mutation , Polymerase Chain Reaction , Proto-Oncogene Proteins p21(ras) , Sequence Analysis, DNAABSTRACT
The use of blended learning strategies is increasingly common in health sciences, including veterinary medicine; however, there are very few descriptions of these methods being applied to practicals. We describe here the application of blended learning based on the implementation of flipped classrooms with collaborative learning and gamification to the 2020-2021 veterinary medicine gross anatomy practicals at CEU Cardenal Herrera University (Spain). Students prepared for the sessions by pre-viewing videos and taking a quiz before the start. The sessions were conducted in small groups where students learned through collaborative work and reviewed their learning with a card game. A small but significant increase was observed when comparing the scores of practical exams of the locomotor apparatus with those of 2018-2019 (6.79 ± 2.22 vs. 6.38 ± 2.24, p < 0.05), while the scores were similar (7.76 ± 1.99 vs. 7.64 ± 1.92) for the organ system exams. Students' responses in a satisfaction survey were mostly positive (>80%) regarding the motivating and learning-facilitating effect of this educational method. Our work shows that the application of blended learning in anatomy practicals based on a flipped classroom and with elements of gamification and collaborative work can be an effective way to improve the learning experience of students.