A method for determining groups in cumulative incidence curves in competing risk data.

The cumulative incidence function is the standard method for estimating the marginal probability of a given event in the presence of competing risks. One basic but important goal in the analysis of competing risk data is the comparison of these curves, for which limited literature exists. We proposed a new procedure that lets us not only test the equality of these curves but also group them if they are not equal. The proposed method allows determining the composition of the groups as well as an automatic selection of their number. Simulation studies show the good numerical behavior of the proposed methods for finite sample size. The applicability of the proposed method is illustrated using real data.

Arthrospira (Spirulina) platensis feeding reduces the early stage of chemically induced rat colon carcinogenesis.

Colorectal cancer is the third most diagnosed cancer worldwide and linked to dietary/lifestyle factors. Arthrospira (Spirulina) platensis (AP) contains bioactive compounds with beneficial effects in vivo/in vitro. We evaluated the effects of AP feeding against 1,2-dimethylhydrazine (DMH)-induced colon carcinogenesis. Male Sprague Dawley rats were given subcutaneous injections of DMH (4 × 40 mg/kg body weight) (G1-G3) or vehicle (G4-G5) twice a week (weeks 3-4). During weeks 1-4, animals were fed a diet containing 1 % (G2) or 2 % (G3-G4) AP powder (w/w). After this period, all groups received a balanced diet until week 12. Some animals were euthanised after the last DMH injection (week 4) for histological, immunohistochemical (Ki-67, γ-H2AX and caspase-3) and molecular analyses (real time-PCR for 91 genes), while other animals were euthanised at week 12 for preneoplastic aberrant crypt foci (ACF) analysis. Both AP treatments (G2-G3) significantly decreased the DMH-induced increase in γ-H2AX (DNA damage) and caspase 3 (DNA damage-induced cell death) in colonic crypts at week 4. In addition, Cyp2e1 (Drug metabolism), Notch1, Notch2 and Jag1 genes (Notch pathway) and Atm, Wee1, Chek2, Mgmt, Ogg1 and Xrcc6 genes (DNA repair) were also down-regulated by 2 % AP feeding (G3) at week 4. A significant reduction in ACF development was observed in both AP-treated groups (G2-G3) at week 12. In conclusion, findings indicate that AP feeding reduced acute colonic damage after DMH, resulting in fewer preneoplastic lesions. Our study provided mechanistic insights on dietary AP-preventive effects against early colon carcinogenesis.

Osteotomies around the knee are not correlated to substantial post-operative ankle pain.

PURPOSE: The relationship between osteotomies around the knee and ankle alignment has been well established. However, little is known about the incidence of new-onset ankle pain after knee osteotomies in the setting of both varus and valgus lower limb malalignments. The purpose of this study is to determine the incidence and characteristics of ankle pain after knee osteotomies; and to clarify the relationship between knee alignment correction, coronal changes suffered by the ankle joint and the development of new-onset ankle pain. METHODS: Fifty-four lower limbs in 51 consecutive patients, who underwent realignment osteotomies around the knee between April 2013 and October 2020, were retrospectively reviewed. Ultimately, 39 patients (42 knees) were enrolled: 34 had varus deformities and eight had valgus deformities. Ankle pain was assessed according to the Numerical Pain Rating Scale by telephonic interview. The magnitude of alignment correction and the consequent change of both knee and ankle joint lines were analyzed. Correlation between the former and the onset of post-operative ankle pain was evaluated. Patient satisfaction and complications were also noted. RESULTS: The incidence of new-onset ankle pain after knee realignment osteotomy was 14%, at a mean follow-up of 55 ± 26 months (range 12-93 months). The mean time between osteotomy and onset of ankle pain was 21 ± 25 months (range 2-60 months). The degree of coronal correction was significantly correlated with ankle joint obliquity changes. However, a significant correlation with post-operative ankle pain was not found (p > 0.05). CONCLUSION: Fourteen percent of the patients who underwent osteotomies around the knee developed new-onset persistent low-intensity ankle pain. The knee and ankle joint biomechanics are closely related, however, only a small percentage of patients suffer from low-intensity ankle pain which is successfully managed with occasional analgesics. Most osteotomies around the knee seem to require no particular concern for the ipsilateral ankle function.

Dietary Capsaicin Reduces Chemically Induced Rat Urinary Bladder Carcinogenesis.

Capsaicin (CAP) is the compound responsible for pungency in chili peppers, presenting several biological properties. But its general safety and effectiveness in the context of carcinogenesis has not been fully clarified. Thus, the present study evaluated whether dietary CAP modifies the development of urothelial lesions induced by the carcinogen N-butyl-N-(4-hydroxybutyl)nitrosamine (BBN) in male Sprague-Dawley rats. Animals were randomly allocated into 6 groups: G1 - treated with 0.05% BBN in drinking water (weeks 1-12) and received a balanced diet (weeks 1-20); G2 and G3-treated with BBN (weeks 1-12) and received a balanced diet with 0.01 or 0.02% CAP (weeks 1-20), respectively; G4 and G5- only received a balanced diet with 0.01 or 0.02% CAP (weeks 1-20), respectively; G6 - only received a balanced diet (weeks 1-20). At the end of week 20, the incidence and types of urothelial lesions, proliferating cell nuclear antigen (PCNA) labeling index, and matrix metalloproteinases (MMP) 2 and 9 activities were analyzed. A significant reduction was observed in the incidence and multiplicity of simple (p = 0.020 and p = 0.011) and nodular/papillary (p = 0.030 and p = 0.003) hyperplasias and papillomas/carcinomas (p = 0.023 and p = 0.020), epithelial proliferation (p = 0.007) and in the activity of the intermediate form of MMP-2 (p < 0.001) and pro-MMP-9 activities (p < 0.002), in BBN + 0.02% CAP (G3) group in comparison to BBN (G1) group. Capsaicin intake per se did not alter body weight, liver and kidney weights, urothelial histology or serum biochemical parameters. Thus, dietary CAP was safe and showed a protective effect against rat BBN-induced urothelial carcinogenesis.

Anxiety and/or depression: which symptoms contribute to adverse clinical outcomes after amputation?

BACKGROUND: One of the most serious complications of diabetes mellitus (DM) is a diabetic foot ulcer (DFU), with lower extremity amputation (LEA). AIMS: This study aims to explore the role of anxiety and depression on mortality, reamputation and healing, after a LEA due to DFU. METHODS: A sample of 149 patients with DFU who underwent LEA answered the Hospital Anxiety and Depression Scale and a sociodemographic and clinical questionnaire. This is a longitudinal and multicenter study with four assessment moments that used Cox proportional hazards models adjusted for demographic and clinical variables. RESULTS: Rate of mortality, reamputation and healing, 10 months after LEA were 9.4%, 27.5% and 61.7%, respectively. Anxiety, at baseline, was negatively associated with healing. However, depression was not an independent predictor of mortality. None of the psychological factors was associated with reamputation. CONCLUSION: Results highlight the significant contribution of anxiety symptoms at pre-surgery, to healing after a LEA. Suggestions for psychological interventions are made.

Systematics, biogeography and evolution of the Saharo-Arabian naked-toed geckos genus Tropiocolotes.

Plate tectonics constitute one of the main mechanisms of biological diversification on Earth, often being associated with cladogenetic events at different phylogenetic levels, as well as with exchange of faunas and floras across previously isolated biogeographic regions. North Africa and Arabia share a complex geological history that dates back to the break-up of the Arabian plate from the African plate ~30-25 Mya, followed by various geological events, such as the formation of the Red Sea or the connection between the African, Arabian and Eurasian plates. Species with Saharo-Arabian distributions have shown a close association between their evolutionary history and these geological events. In this study, we investigate the systematics, biogeography and evolution of the genus Tropiocolotes, a group of small ground-dwelling geckos, comprised by 12 species distributed from the Atlantic coast of North Africa to southwestern Iran. Species delimitation analyses uncovered the existence of high levels of undescribed diversity, with forms here considered at the species level including Tropiocolotes tripolitanus (Mauritania and southern Morocco), T. nattereri (southern Israel) and T. scorteccii (Yemen and Oman). Phylogenetic and biogeographic analyses recovered two main clades, an exclusively African clade and a Saharo-Arabian clade, that split ~25 Mya following the vicariant event mediated by the separation of the Arabian and African plates. The complex geological activity around the Red Sea is associated with the diversification within the Saharo-Arabian clade, including the colonization of North Africa from a second Tropiocolotes group. Results also provide new insights into the geographic distribution of Tropiocolotes nubicus, previously considered as exclusively associated to the Nile River valley, extending its known distribution further west, up to the Central Mountains of the Sahara. Accordingly, the Nile River seems to act as a major biogeographic barrier, separating Tropiocolotes nubicus and T. steudneri in their western and eastern margins, respectively.

Protective Effects of Dietary Capsaicin on the Initiation Step of a Two-Stage Hepatocarcinogenesis Rat Model.

Capsaicin (CPS), an ingredient of Capsicum plants, has anti-inflammatory, antioxidant and antitumoral properties. The mechanisms of CPS on hepatocarcinogenesis preclinical bioassays are not described. Thus, the protective effects CPS were evaluated in the early stages of chemically-induced hepatocarcinogenesis. Male Wistar rats received diet containing 0.01% or 0.02% CPS for 3 weeks. Afterwards, animals received a dose of hepatocarcinogen diethylnitrosamine (DEN, 100 mg/kg body weight). From weeks 4-12, groups had their diet replaced by a 0.05% phenobarbital supplemented one to promote DEN-induced preneoplastic lesions. Animals were euthanized 24 h after DEN administration (n = 5/group) or at week 12 (n = 9/group). The estimated CPS intake in rats resembled human consumption. At the end of week 3, dietary 0.02% CPS attenuated DEN-induced oxidative damage and, consequently, hepatocyte necrosis by reducing serum alanine aminotransferase levels, liver CD68-positive macrophages, lipid peroxidation, while increasing antioxidant glutathione system. Additionally, 0.02% CPS upregulated vanilloid Trpv1 receptor and anti-inflammatory epoxygenase Cyp2j4 genes in the liver. Ultimately, previous 0.02% CPS intake decreased the number of GST-P-positive preneoplastic lesions at week 12. Thus, CPS attenuated preneoplastic lesion development, primarily by diminishing DEN-induced oxidative liver injury. Findings indicate that CPS is a promising chemopreventive agent when administered after and during the early stages of hepatocarcinogenesis.

Diagnostic Accuracy of Positive Airway Pressure Device for Sleep Apnea Detection in Acute Stroke Patients.

Background and Purpose- Sleep apnea has been associated with a poor outcome in acute stroke patients. Polysomnography is the gold standard diagnostic method for sleep apnea, but it is not feasible as a routine in the acute stroke setting. The current generation of positive airway pressure (PAP) devices can detect the different types of respiratory events. This study aimed to compare the algorithms used in PAP device to manually scored events on polysomnography in patients with acute stroke. Methods- A sleep study was performed with standard polysomnography and PAP device, simultaneously, within the first 48 hours after acute stroke onset. Results- We prospectively evaluated 29 patients with acute stroke (59.5±12.1 years). The area under the receiver operating characteristic curve for each apnea-hypopnea index value was above 0.90 by PAP device. There was a good correlation of apnea-hypopnea index (rs=0.92; P<0.001), hypopnea index (rs=0.89; P<0.001), and apnea index (rs=0.70; P<0.001) between device-detected events and manually scored polysomnography. Conclusions- Given the high frequency of sleep apnea during the acute phase of stroke and the complexity of a full polysomnography study in this setting, PAP device on diagnostic mode can be used as an alternative tool for sleep apnea detection in acute stroke patients.

Sirt1 protects from K-Ras-driven lung carcinogenesis.

The NAD+-dependent deacetylase SIRT1 can be oncogenic or tumor suppressive depending on the tissue. Little is known about the role of SIRT1 in non-small cell lung carcinoma (NSCLC), one of the deadliest cancers, that is frequently associated with mutated K-RAS Therefore, we investigated the effect of SIRT1 on K-RAS-driven lung carcinogenesis. We report that SIRT1 protein levels are downregulated by oncogenic K-RAS in a MEK and PI3K-dependent manner in mouse embryo fibroblasts (MEFs), and in human lung adenocarcinoma cell lines. Furthermore, Sirt1 overexpression in mice delays the appearance of K-RasG12V-driven lung adenocarcinomas, reducing the number and size of carcinomas at the time of death and extending survival. Consistently, lower levels of SIRT1 are associated with worse prognosis in human NSCLCs. Mechanistically, analysis of mouse Sirt1-Tg pneumocytes, isolated shortly after K-RasG12V activation, reveals that Sirt1 overexpression alters pathways involved in tumor development: proliferation, apoptosis, or extracellular matrix organization. Our work demonstrates a tumor suppressive role of SIRT1 in the development of K-RAS-driven lung adenocarcinomas in mice and humans, suggesting that the SIRT1-K-RAS axis could be a therapeutic target for NSCLCs.

A Multistate Model for Analyzing Transitions Between Body Mass Index Categories During Childhood: The Generation XXI Birth Cohort Study.

Prevalences of overweight and obesity in young children have risen dramatically in the last several decades in most developed countries. Childhood overweight and obesity are known to have immediate and long-term health consequences and are now recognized as important public health concerns. We used a Markov 4-state model with states defined by 4 body mass index (BMI; weight (kg)/height (m)2) categories (underweight (<-2 standard deviations (SDs) of BMI z score), normal weight (-2 ≤ SD ≤ 1), overweight (1 < SD ≤ 2), and obese (>2 SDs of BMI z score)) to study the rates of transition to higher or lower BMI categories among children aged 4-10 years. We also used this model to study the relationships between explanatory variables and their transition rates. The participants consisted of 4,887 children from the Generation XXI Birth Cohort Study (Porto, Portugal; 2005-2017) who underwent anthropometric evaluation at age 4 years and in at least 1 of the subsequent follow-up waves (ages 7 and 10 years). Children who were normal weight were more likely to move to higher BMI categories than to lower categories, whereas overweight children had similar rates of transition to the 2 adjacent categories. We evaluated the associations of maternal age and education, type of delivery, sex, and birth weight with childhood overweight and obesity, but we observed statistically significant results only for sex and maternal education with regard to the progressive transitions.

A method for determining groups in multiple survival curves.

Survival analysis includes a wide variety of methods for analyzing time-to-event data. One basic but important goal in survival analysis is the comparison of survival curves between groups. Several nonparametric methods have been proposed in the literature to test for the equality of survival curves for censored data. When the null hypothesis of equality of curves is rejected, leading to the clear conclusion that at least one curve is different, it can be interesting to ascertain whether curves can be grouped or if all these curves are different from each other. A method is proposed that allows determining groups with an automatic selection of their number. The validity and behavior of the proposed method was evaluated through simulation studies. The applicability of the proposed method is illustrated using real data. Software in the form of an R package has been developed implementing the proposed method.

Estimation in the progressive illness-death model: A nonexhaustive review.

Multistate models can be successfully used for describing complex event history data, for example, describing stages in the disease progression of a patient. The so-called "illness-death" model plays a central role in the theory and practice of these models. Many time-to-event datasets from medical studies with multiple end points can be reduced to this generic structure. In these models one important goal is the modeling of transition rates but biomedical researchers are also interested in reporting interpretable results in a simple and summarized manner. These include estimates of predictive probabilities, such as the transition probabilities, occupation probabilities, cumulative incidence functions, and the sojourn time distributions. We will give a review of some of the available methods for estimating such quantities in the progressive illness-death model conditionally (or not) on covariate measures. For some of these quantities estimators based on subsampling are employed. Subsampling, also referred to as landmarking, leads to small sample sizes and usually to heavily censored data leading to estimators with higher variability. To overcome this issue estimators based on a preliminary estimation (presmoothing) of the probability of censoring may be used. Among these, the presmoothed estimators for the cumulative incidences are new. We also introduce feasible estimation methods for the cumulative incidence function conditionally on covariate measures. The proposed methods are illustrated using real data. A comparative simulation study of several estimation approaches is performed and existing software in the form of R packages is discussed.

Functional Popliteal Artery Entrapment Syndrome.

INTRODUCTION: Popliteal artery entrapment is an uncommon syndrome, caused by extrinsic compression of the popliteal artery by muscular or tendinous structures. It occurs mainly in young individuals, with no atherosclerostic risk factors, and a mean age of presentation of 20 to 40 years, and has higher prevalence in males (83% of patients). Clinical presentation depends on the degree of arterial lesion, the most common being intermittent claudication, with critical ischemia being frequent. Occasionally, it may present as acute ischaemia. METHODS: A 40-year-old female patient, physical education teacher, presented with a history of left foot paresthesia and left calf muscle pain during jogging for one year. The patient used to previously run 10 kilometers, currently mentioning claudication at 500 meters. No other medical conditions were mentioned. Lower extremity arterial duplex ultrasound revealed left popliteal artery compression and occlusion during active plantar flexion and passive dorsal flexion. The patient was referred to a vascular surgery center. Physical examination revealed palpable bilateral lower extremity pulses, with left asymmetry. Lower limb angiography and magnetic resonance imaging (MRI) were performed which demonstrated left popliteal artery compression and occlusion during a resisted plantar flexion. MRI revealed no anatomic anomalies, pointing to a probable functional entrapment caused by calf muscle hypertrophy (typo VI). RESULTS: Entrapment correction surgery was performed through a posterior approach and exposure. During the procedure, the artery showed no signs of significant fibrosis. Since compression by the medial head of the gastrocnemius muscle was observed, myotomy of its lateral fibers was performed. The patient was discharged on the second day post-surgery. After three months, the patient remained free of symptoms, having taken up sports practice with no limitations. CONCLUSION: Continuous popliteal artery compression leads to its progressive fibrosis, which may cause thrombosis or post-stenotic aneurysmal dilation. Treatment should be performed as soon as possible as to avoid this course and the eventual necessity of interposition or bypass grafting. Futhermore, late intervention worsens the interposition/ bypass grafting prognosis5. In this sense, the possibility of this diagnosis should be considered in a young patient presenting with intermittent claudication. Diagnostic tests are often decisive for differential diagnosis and to establish the disease subtype and intervention strategy. In most patients, a culprit muscular or tendinous anomaly is detected before surgery, however, in some individuals, especially physically active ones, compression results from muscular hypertrophy.

The taxonomy of the Tarentola mauritanica species complex (Gekkota: Phyllodactylidae): Bayesian species delimitation supports six candidate species.

The lack of morphological diagnosable characters typical of cryptic species, poses a particular problem to taxonomists. This is especially true when taxa are closely related, sharing considerable amounts of ancestral polymorphism. Phylogenetic studies on the Moorish gecko species-complex, Tarentola mauritanica, uncovered extremely high levels of mtDNA diversity with six identified clades, including one from the Canary Islands identified as T. angustimentalis. Because of the conserved morphology of this species and its paraphyletic status with respect to T. angustimentalis, it was suggested that T. mauritanica is a cryptic species complex. Nevertheless, none of the nuclear loci used were reciprocally monophyletic regarding the mitochondrial lineages due to retention of ancestral polymorphism. In this study, we added three new intron markers to the already available dataset and used additional tools, namely phylogenetic gene trees, species tree and species limits within a Bayesian coalescent framework to confirm the support of the main lineages. Bayesian clustering analysis supports all six mtDNA lineages as independent groups, despite showing signs of ancestral polymorphism or possibly gene flow between the Maghreb/South Iberia and Central Morocco clades. The species tree recovered two major groups; one clustering taxa from Europe and Northern Maghreb and another one encompassing the lineages from Central/Southern Morocco, Central Morocco and Canary Islands, indicating that the ancestor of T. angustimentalis came from the Central/Southern Morocco region. Finally, Bayesian coalescent species delimitation analysis supports all six mitochondrial clades as "unconfirmed candidate species", pending morphological data to define them.

Nonparametric estimation of time-dependent ROC curves conditional on a continuous covariate.

The receiver-operating characteristic (ROC) curve is the most widely used measure for evaluating the performance of a diagnostic biomarker when predicting a binary disease outcome. The ROC curve displays the true positive rate (or sensitivity) and the false positive rate (or 1-specificity) for different cut-off values used to classify an individual as healthy or diseased. In time-to-event studies, however, the disease status (e.g. death or alive) of an individual is not a fixed characteristic, and it varies along the study. In such cases, when evaluating the performance of the biomarker, several issues should be taken into account: first, the time-dependent nature of the disease status; and second, the presence of incomplete data (e.g. censored data typically present in survival studies). Accordingly, to assess the discrimination power of continuous biomarkers for time-dependent disease outcomes, time-dependent extensions of true positive rate, false positive rate, and ROC curve have been recently proposed. In this work, we present new nonparametric estimators of the cumulative/dynamic time-dependent ROC curve that allow accounting for the possible modifying effect of current or past covariate measures on the discriminatory power of the biomarker. The proposed estimators can accommodate right-censored data, as well as covariate-dependent censoring. The behavior of the estimators proposed in this study will be explored through simulations and illustrated using data from a cohort of patients who suffered from acute coronary syndrome.

Nonparametric estimation of the survival function for ordered multivariate failure time data: A comparative study.

In longitudinal studies of disease, patients may experience several events through a follow-up period. In these studies, the sequentially ordered events are often of interest and lead to problems that have received much attention recently. Issues of interest include the estimation of bivariate survival, marginal distributions, and the conditional distribution of gap times. In this work, we consider the estimation of the survival function conditional to a previous event. Different nonparametric approaches will be considered for estimating these quantities, all based on the Kaplan-Meier estimator of the survival function. We explore the finite sample behavior of the estimators through simulations. The different methods proposed in this article are applied to a dataset from a German Breast Cancer Study. The methods are used to obtain predictors for the conditional survival probabilities as well as to study the influence of recurrence in overall survival.

Nonparametric estimation of transition probabilities in the non-Markov illness-death model: A comparative study.

Multi-state models are often used for modeling complex event history data. In these models the estimation of the transition probabilities is of particular interest, since they allow for long-term predictions of the process. These quantities have been traditionally estimated by the Aalen-Johansen estimator, which is consistent if the process is Markov. Several non-Markov estimators have been proposed in the recent literature, and their superiority with respect to the Aalen-Johansen estimator has been proved in situations in which the Markov condition is strongly violated. However, the existing estimators have the drawback of requiring that the support of the censoring distribution contains the support of the lifetime distribution, which is not often the case. In this article, we propose two new methods for estimating the transition probabilities in the progressive illness-death model. Some asymptotic results are derived. The proposed estimators are consistent regardless the Markov condition and the referred assumption about the censoring support. We explore the finite sample behavior of the estimators through simulations. The main conclusion of this piece of research is that the proposed estimators are much more efficient than the existing non-Markov estimators in most cases. An application to a clinical trial on colon cancer is included. Extensions to progressive processes beyond the three-state illness-death model are discussed.

[Early type I Endoleak after Endovascular Management of an Aorto-esophageal Fistula]. / Endoleak Tipo I Precoce no Tratamento Endovascular de Fístula Aorto-Esofágica.

OBJECTIVE: Presentation of a clinical case of an aorto-esophageal fistula secondary to thoracic aorta pseudoaneurysm, complicated by early type Ia endoleak after endovascular repair. CLINICAL CASE: A 64 years old male patient, with a history of arterial hypertension, smoking, alcohol abuse and ischemic heart disease with previous coronary revascularization was observed because of chest pain and abundant hematemesis, with Angio-CT revealing a 77mm pseudoaneurysm of the descending thoracic aorta, close to the left subclavian artery, with mass effect on the esophagus and trachea and signs of fistulization. He was proposed to endovascular repair with sealing in zone 2 of the aortic arch after building a left carotid-subclavian bypass. In the first 24 hours there were two episodes of massive hematemesis, with new Angio-CT revealing a early distal migration of the prosthesis, conditioning a type Ia endoleak. A carotid-carotid right-left bypass with left carotid ligation was performed and a new endoprosthesis was implanted in the origin of the brachycephalic trunk (zone 1). The final angiography showed aneurysm exclusion with permeability of the supra-aortic trunks. Later contrasted esophageal examination and endoscopy revealed an ulcer of the posterior left lateral wall with clot suggestive of fistula, and an esophageal prosthesis was successfully implanted. It held seven days of antibiotic therapy with ceftriaxone and metronidazole with no evidence of mediastinal infection and with aneurysm exclusion in the CT follow-up. CONCLUSION: The recognized biomechanical and anatomical complexity of the aneurysmatic thoracic aorta represents a considerable challenge to the endovascular treatment of aorto-esophageal fistulas, especially in aneurysmatic sealing of the aortic arch, with significant rates of type Ia and III endoleaks.

[Endovascular management of iatrogenic renal arteriovenous fistulas]. / TRATAMENTO ENDOVASCULAR DE FÍSTULAS ARTERIOVENOSAS RENAIS IATROGÉNICAS.

Renal arteriovenous fistulas are uncommon in clinical practice, however the higher frequency of percutaneous renal procedures led to an increase of iatrogenic renal vascular lesions and associated fistulas. Many of these lesions are asymptomatic, however in case of symptoms they can be indicated for treatment. With the emergence of new techniques and materials for embolization, this therapeutic option has been increasingly used to treat this type of injury. The authors present two clinical cases of iatrogenic renal arteriovenous fistulas successfully treated using percutaneous embolization. The percutaneous management of iatrogenic renal vascular lesions is a safe and effective procedure and should be considered as the first-line treatment.

An overview of chemically induced rodent models for sporadic colorectal cancer: Histopathological and translational perspectives.

Globally, colorectal cancer (CRC) is one of the most frequently diagnosed human gastrointestinal neoplasia and the second leading cause of cancer-related death in both men and women. Despite considerable efforts currently devoted to the study of the biology and treatment of CRC, patient prognosis and survival are still poor. Sporadic CRC is a complex multistep disease and usually emerges in the setting of lifestyle and dietary changes mainly observed in industrialized countries with high human development index (HDI) (westernized style). The molecular pathogenesis of sporadic CRC presents genetic heterogeneity with APC, RAS, PIK3CA, TGFBR, SMAD4, and TP53 mutations usually detected during the progression of this malignancy. The establishment of sporadic CRC models has become essential for both basic and translational research to improve our understanding of the pathophysiology, unravel new molecular drivers, and preventive/therapeutic improvement of this malignancy. Chemically induced rodent models of sporadic CRC recapitulate most key morphological and genetic/epigenetic events observed during the promotion and progression of this malignancy, establishing effective diagnostic and prevention strategies to be translated into clinical practice. The present review gathers the main features of the state-of-the-art evidence on chemically induced rodent models, widely applied for translational modelling of sporadic CRC with a specific focus on histopathology and prevention perspectives. Our narrative review reinforces the persistent value of these bioassays and encourages the use of multimodel strategies for further investigations.