1,2,3-Triazoles in Biomolecular Crystallography: A Geometrical Data-Mining Approach.

The 1,2,3-triazole scaffold has become very attractive to identify new chemical entities in drug discovery projects. Despite the widespread use of click chemistry to synthesize numerous 123Ts, there are few drugs on the market that incorporate this scaffold as a substructure. To investigate the true potential of 123Ts in protein-ligand interactions, we examined the noncovalent interactions between the 1,2,3-triazole ring and amino acids in protein-ligand cocrystals using a geometrical approach. For this purpose, we constructed a nonredundant database of 220 PDB IDs from available 123T-protein cocrystal structures. Subsequently, using the Protein Ligand Interaction Profiler web platform (PLIP), we determined whether 1,2,3-triazoles primarily act as linkers or if they can be considered interactive scaffolds. We then manually analyzed the geometrical descriptors from 333 interactions between 1,4-disubstituted 123T rings and amino acid residues in proteins. This study demonstrates that 1,2,3-triazoles exhibit diverse preferred interactions with amino acids, which contribute to protein-ligand binding.

Cogan syndrome: a case report and review of the literature.

Cogan syndrome is a rare disease whose etiology is still undetermined. It typically affects men and women between the second and fourth decade of life. We report a case of Cogan syndrome with ocular and audio-vestibular involvement as a systemic manifestation in a 31-year-old woman.

Taxation of tobacco, alcohol, and sugar-sweetened beverages: reviewing the evidence and dispelling the myths.

The article reviews the large body of evidence on how taxation affects the consumption of tobacco, alcohol, and sugar-sweetened beverages (SSB). There is abundant evidence that demand for tobacco, alcohol, and SSB is price-responsive and that tax changes are quickly passed on to consumers. This suggests that taxes can be highly effective in changing consumption and reducing the burden of diseases associated with consuming these products. Tobacco, alcohol, and SSB industries oppose taxation on similar grounds, mostly on the regressivity of taxes since regressive taxes take a larger percentage of income from low income earners than from middle and high income earners; but also on the effects taxes might have on employment and economic activity; and, in the case of tobacco, the effects taxation has on illicit trade.Contrary to industry arguments, evidence shows that taxation may have short-term negative financial consequences for low-income households. However, medium and long-term financial benefits from reduced healthcare costs, better health, and welfare largely compensate for such consequences. Moreover, taxation does not negatively affect aggregate economic activity or employment, as consumers switch demand to other products that generate employment and may compensate for any employment loss in taxed sectors. Evidence also shows the revenues generated are generally spent on labour-intensive services. In the case of illicit trade in tobacco, evidence shows that illicit trade has not increased globally (rather the opposite) despite increases in tobacco taxes. Profit-maximising smugglers increase illicit cigarette prices along with the increases in licit cigarette prices. This implies that even when increased taxes divert some demand to the illicit market, they push prices up in the illicit market, discouraging consumption.

3D Filaments Based on Polyhydroxy Butyrate-Micronized Bacterial Cellulose for Tissue Engineering Applications.

In this work, scaffolds based on poly(hydroxybutyrate) (PHB) and micronized bacterial cellulose (BC) were produced through 3D printing. Filaments for the printing were obtained by varying the percentage of micronized BC (0.25, 0.50, 1.00, and 2.00%) inserted in relation to the PHB matrix. Despite the varying concentrations of BC, the biocomposite filaments predominantly contained PHB functional groups, as Fourier transform infrared spectroscopy (FTIR) demonstrated. Thermogravimetric analyses (i.e., TG and DTG) of the filaments showed that the peak temperature (Tpeak) of PHB degradation decreased as the concentration of BC increased, with the lowest being 248 °C, referring to the biocomposite filament PHB/2.0% BC, which has the highest concentration of BC. Although there was a variation in the thermal behavior of the filaments, it was not significant enough to make printing impossible, considering that the PHB melting temperature was 170 °C. Biological assays indicated the non-cytotoxicity of scaffolds and the provision of cell anchorage sites. The results obtained in this research open up new paths for the application of this innovation in tissue engineering.

Lipophilic modification of salirasib modulates the antiproliferative and antimigratory activity.

Salirasib, or farnesylthiosalicylic acid (FTS), is a salicylic acid derivative with demonstrated antineoplastic activity. While designed as a competitor of the substrate S-farnesyl cysteine on Ras, it is a potent competitive inhibitor of isoprenylcysteine carboxymethyl transferase. In this study, the antiproliferative activity on six different solid tumor cell lines was evaluated with a series of lipophilic thioether modified salirasib analogues, including those with or without a 1,2,3-triazole linker. A combination of bioassay, cheminformatics, docking, and in silico ADME-Tox was also performed. SAR analysis that analogues with three or more isoprene units or a long aliphatic chain exhibited the most potent activity. Furthermore, three compounds display superior antiproliferative activity than salirasib and similar potency compared to control anticancer drugs across all tested solid tumor cell lines. In addition, the behavior of the collection on migration and invasion, a key process in tumor metastasis, was also studied. Three analogues with specific antimigratory activity were identified with differential structural features being interesting starting points on the development of new antimetastatic agents. The antiproliferative and antimigratory effects observed suggest that modifying the thiol aliphatic/prenyl substituents can modulate the activity.

Garbage in, garbage out: how reliable training data improved a virtual screening approach against SARS-CoV-2 MPro.

Introduction: The identification of chemical compounds that interfere with SARS-CoV-2 replication continues to be a priority in several academic and pharmaceutical laboratories. Computational tools and approaches have the power to integrate, process and analyze multiple data in a short time. However, these initiatives may yield unrealistic results if the applied models are not inferred from reliable data and the resulting predictions are not confirmed by experimental evidence. Methods: We undertook a drug discovery campaign against the essential major protease (MPro) from SARS-CoV-2, which relied on an in silico search strategy -performed in a large and diverse chemolibrary- complemented by experimental validation. The computational method comprises a recently reported ligand-based approach developed upon refinement/learning cycles, and structure-based approximations. Search models were applied to both retrospective (in silico) and prospective (experimentally confirmed) screening. Results: The first generation of ligand-based models were fed by data, which to a great extent, had not been published in peer-reviewed articles. The first screening campaign performed with 188 compounds (46 in silico hits and 100 analogues, and 40 unrelated compounds: flavonols and pyrazoles) yielded three hits against MPro (IC50 ≤ 25 µM): two analogues of in silico hits (one glycoside and one benzo-thiazol) and one flavonol. A second generation of ligand-based models was developed based on this negative information and newly published peer-reviewed data for MPro inhibitors. This led to 43 new hit candidates belonging to different chemical families. From 45 compounds (28 in silico hits and 17 related analogues) tested in the second screening campaign, eight inhibited MPro with IC50 = 0.12-20 µM and five of them also impaired the proliferation of SARS-CoV-2 in Vero cells (EC50 7-45 µM). Discussion: Our study provides an example of a virtuous loop between computational and experimental approaches applied to target-focused drug discovery against a major and global pathogen, reaffirming the well-known "garbage in, garbage out" machine learning principle.

Understanding the Fate of the Banert Cascade of Propargylic Azides: Sigmatropic versus Prototropic Pathway.

The Banert cascade is an efficient synthetic strategy for obtaining 4,5-disubstituted 1,2,3-triazoles. The reaction can proceed via a sigmatropic or prototropic mechanism depending on the substrate and the conditions. In this work, the mechanisms of both pathways from propargylic azides with different electronic features were investigated using density functional theory, quantum theory of atoms in molecules, and natural bond orbital approaches. The calculated energy barriers were consistent with the experimental data. Three patterns of electron density distribution on the transition structures were observed, which reflected the behaviors of the reactants in the Banert cascade. The stronger conjugative effects were associated with lower/higher free activation energies of sigmatropic/prototropic reactions, respectively. A clear relationship between the accumulation of the charge at the C3 atom of propargylic azides with the energy barriers for prototropic reactions was found. Thus, the obtained results would allow the prediction of the reaction's course by evaluating reactants.

Dietary Supplementation with Yerba Mate (Ilex paraguariensis) Infusion Increases IRS-1 and PI3K mRNA Levels and Enhances Insulin Sensitivity and Secretion in Rat Pancreatic Islets.

"Yerba mate" (YM), an aqueous extract of Ilex paraguariensis, has antioxidant, diuretic, cardio-protective and hypoglycaemic properties. Since its effect on the pancreatic islets remains unclear, we evaluated insulin sensitivity and glucose-stimulated insulin secretion (GSIS) in rats consuming YM or tap water (C) for 21 days. Glucose tolerance, glycemia, triglyceridemia, insulinemia, TBARS and FRAP serum levels were evaluated. GSIS and mRNA levels of insulin signaling pathway and inflammatory markers were measured in isolated pancreatic islets from both groups. In C rats, islets were incubated with YM extract or its phenolic components to measure GSIS. YM improved glucose tolerance, enhanced GSIS, increased FRAP plasma levels and islet mRNA levels of IRS-1 and PI3K (p110), and decreased TBARS plasma levels and islet gene expression of TNF-α and PAI-1. Islets from C rats incubated with 100 µg/mL dry YM extract, 1 µM chlorogenic acid, 0.1 and 1 µM rutin, 1 µM caffeic acid or 1 µM quercetin showed an increase in GSIS. Our results suggest that YM enhances glucose tolerance because of its positive effects on GSIS, oxidative stress rate and insulin sensitivity in rat islets, suggesting that long-term dietary supplementation with YM may improve glucose homeostasis in pre-diabetes or type 2 diabetes.

Systematic study of 1,2,3-triazolyl sterols for the development of new drugs against parasitic Neglected Tropical Diseases.

A series of thirty 1,2,3-triazolylsterols, inspired by azasterols with proven antiparasitic activity, were prepared by a stereocontrolled synthesis. Ten of these compounds constitute chimeras/hybrids of 22,26-azasterol (AZA) and 1,2,3-triazolyl azasterols. The entire library was assayed against the kinetoplastid parasites Leishmania donovani, Trypanosoma cruzi, and Trypanosoma brucei, the causatives agents for visceral leishmaniasis, Chagas disease, and sleeping sickness, respectively. Most of the compounds were active at submicromolar/nanomolar concentrations with high selectivity index, when compared to their cytotoxicity against mammalian cells. Analysis of in silico physicochemical properties were conducted to rationalize the activities against the neglected tropical disease pathogens. The analogs with selective activity against L. donovani (E4, IC50 0.78 µM), T brucei (E1, IC50 0.12 µM) and T. cruzi (B1- IC50 0.33 µM), and the analogs with broad-spectrum antiparasitic activities against the three kinetoplastid parasites (B1 and B3), may be promising leads for further development as selective or broad-spectrum antiparasitic drugs.

Design, Synthesis, Characterization, and Evaluation of the Anti-HT-29 Colorectal Cell Line Activity of Novel 8-Oxyquinolinate-Platinum(II)-Loaded Nanostructured Lipid Carriers Targeted with Riboflavin.

Colorectal cancer is occasionally called colon or rectal cancer, depending on where cancer begins to form, and is the second leading cause of cancer death among both men and women. The platinum-based [PtCl(8-O-quinolinate)(dmso)] (8-QO-Pt) compound has demonstrated encouraging anticancer activity. Three different systems of 8-QO-Pt-encapsulated nanostructured lipid carriers (NLCs) with riboflavin (RFV) were investigated. NLCs of myristyl myristate were synthesized by ultrasonication in the presence of RFV. RFV-decorated nanoparticles displayed a spherical shape and a narrow size dispersion in the range of 144-175 nm mean particle diameter. The 8-QO-Pt-loaded formulations of NLC/RFV with more than 70% encapsulation efficiency showed sustained in vitro release for 24 h. Cytotoxicity, cell uptake, and apoptosis were evaluated in the HT-29 human colorectal adenocarcinoma cell line. The results revealed that 8-QO-Pt-loaded formulations of NLC/RFV showed higher cytotoxicity than the free 8-QO-Pt compound at 5.0 µM. All three systems exhibited different levels of cellular internalization. Moreover, the hemotoxicity assay showed the safety profile of the formulations (less than 3.7%). Taken together, RFV-targeted NLC systems for drug delivery have been investigated for the first time in our study and the results are promising for the future of chemotherapy in colon cancer treatment.

Bacterial Cellulose-Based Materials as Dressings for Wound Healing.

Bacterial cellulose (BC) is produced by several microorganisms as extracellular structures and can be modified by various physicochemical and biological strategies to produce different cellulosic formats. The main advantages of BC for biomedical applications can be summarized thus: easy moldability, purification, and scalability; high biocompatibility; and straightforward tailoring. The presence of a high amount of free hydroxyl residues, linked with water and nanoporous morphology, makes BC polymer an ideal candidate for wound healing. In this frame, acute and chronic wounds, associated with prevalent pathologies, were addressed to find adequate therapeutic strategies. Hence, the main characteristics of different BC structures-such as membranes and films, fibrous and spheroidal, nanocrystals and nanofibers, and different BC blends, as well as recent advances in BC composites with alginate, collagen, chitosan, silk sericin, and some miscellaneous blends-are reported in detail. Moreover, the development of novel antimicrobial BC and drug delivery systems are discussed.

Quantitative determination of voriconazole by thionine reduction and its potential application in a pharmaceutical and clinical setting.

Voriconazole (VCZ) is a triazolic drug used to treat serious fungal infections and invasive mycosis and has also been more recently used as a generic antifungal treatment. However, VCZ therapies can cause undesirable side effects and doses must be carefully monitored before administration to avoid or reduce severe toxic effects. Analytical techniques used to quantify VCZ are mostly based on HPLC/UV and often associated with multiple technical steps as well as expensive equipment. The present work aimed to develop an accessible and affordable spectrophotometric technique in the visible range (λ = 514 nm) for the simple quantification of VCZ. The technique was based on VCZ-induced reduction of thionine (TH, red) to leucothionine (LTH, colorless) under alkaline conditions. The reaction showed a linear correlation over the range of 1.00 µg mL-1 to 60.00 µg mL-1 at room temperature, the limits of detection and quantification being 1.93 µg mL-1 and 6.45 µg mL-1, respectively. VCZ degradation products (DPs) according to 1H and 13C-NMR spectrometric determinations not only showed good agreement with the ones previously reported (DP1 and DP2 - T. M. Barbosa, G. A. Morris, M. Nilsson, R. Rittner and C. F. Tormena, RSC Adv., 2017, DOI: 10.1039/c7ra03822d), but also revealed a new degradation product (DP3). Mass spectrometry not only confirmed the presence of LTH as a result of the VCZ DP-induced TH reduction, but also revealed the formation of a novel and stable Schiff base as a reaction product between DP1 and LTH. The latter finding became significant as it stabilizes the reaction for quantification purposes, by hindering LTH ↔TH redox reversibility. This analytical method was then validated according to the ICH Q2 (R1) guidelines, and additionally, it could be demonstrated as applicable for the reliable VCZ quantification in commercially available tablets. Importantly, it also represents a useful tool for detecting toxic threshold concentrations in human plasma from VCZ-treated patients, alerting when these risky limits are exceeded. In this way, this technique independent from sophisticated equipment, highly qualifies as a low-cost, reproducible, trustable, and non-laborious alternative method for VCZ measurements from different matrices.

Does Domestication Affect Structural and Functional Leaf Epidermal Traits? A Comparison between Wild and Cultivated Mexican Chili Peppers (Capsicum annuum).

During domestication, lineages diverge phenotypically and genetically from wild relatives, particularly in preferred traits. In addition to evolutionary divergence in selected traits, other fitness-related traits that are unselected may change in concert. For instance, the selection of chili pepper fruits was not intended to change the structure and function of the leaf epidermis. Leaf stomata and trichome densities play a prominent role in regulating stomatal conductance and resistance to herbivores. Here, we assessed whether domestication affected leaf epidermis structure and function in Capsicum annuum. To do this, we compared leaf stomata and trichome densities in six cultivated varieties of Mexican Capsicum annuum and their wild relative. We measured stomatal conductance and resistance to herbivores. Resistance to (defense against) herbivores was measured as variation in the herbivory rate and larvae mortality of Spodoptera frugiperda fed with leaves of wild and cultivated plants. As expected, the different varieties displayed low divergence in stomatal density and conductance. Leaf trichome density was higher in the wild relative, but variation was not correlated with the herbivory rate. In contrast, a higher mortality rate of S. frugiperda larvae was recorded when fed with the wild relative and two varieties than larvae fed with four other varieties. Overall, although domestication did not aim at resistance to herbivores, this evolutionary process produced concerted changes in defensive traits.

Colloidal delivery of vitamin E into solid lipid nanoparticles as a potential complement for the adverse effects of anemia treatment.

Vitamin E (VitE) is one of the most important antioxidants and plays a key role in decreasing the inflammatory effects of oxidative stress caused by recurrent doses of iron administration in anemia treatment. However, VitE is poorly soluble in aqueous environments. Here, VitE encapsulation into solid lipid nanoparticles (SLN) composed of myristil myristate to improve its bioavailability was proposed. A 99.9 ± 0.1% encapsulation efficiency with a drug/lipid ratio of 500 µg/mg and 478 higher VitE solubility was obtained. The antioxidant properties of VitE after encapsulation were maintained. SLN-VitE showed a 228.2 nm mean diameter with low polidispersitivity (0.335), and negative Z potential (ζ ≈ -9.0 mV). The SLN were well-dispersed, displayed spherical and homogeneous morphology by TEM. A controlled release of VitE from SLN was found. The XRD and FTIR analyses revealed the presence of a nanostructured architecture of SLN after VitE incorporation. We probed the safety of SLN-VitE after contact with three in vitro cell models: erythrocytes, lymphocytes and HepG2 cells. The cell viability in presence of SLN, SLN-VitE, and their combinations with iron was not affected. The comet assay demonstrated that the DNA damage caused by iron administration was decrease in presence of SLN-VitE.

Estudio de prevalencia de lesiones laríngeas y disfagia en pacientes críticos traqueostomizados por COVID-19 / A Study on the Prevalence of Laryngeal Injuries and Dysphagia in Critically Ill Tracheostomized Patients due to COVID-19

Introducción: Los pacientes con neumonía grave por COVID-19 pueden requerir intubación orotraqueal, ventilación mecánica prolongada y traqueostomía. La presencia de la vía aérea artificial puede generar lesiones laríngeas y estar asociada a disfunción deglutoria con aumento del riesgo de aspiración. Objetivo: Describir la prevalencia de lesiones laríngeas y disfagia orofaríngea en los pacientes críticos traqueostomizados por COVID-19. Como objetivo secundario, evaluar la asociación entre la presencia de lesión laríngea y disfagia y de cada una de ellas con antecedentes del paciente, duración de la vía aérea artificial y maniobra de decúbito prono. Material y métodos: Estudio observacional, longitudinal y retrospectivo, realizado en el hospital Juan A. Fernández, CABA, Argentina. Se incluyeron de manera consecutiva pacientes con diagnóstico de COVID-19 traqueostomizados. La presencia de lesiones laríngeas y disfagia se valoró mediante estudio endoscópico de la deglución al momento de la decanulación. Resultados: Se analizaron 32 pacientes, de los cuales, 28 (87,5%) evidenciaron al menos una lesión laríngea, principalmente en la región glótica. La prevalencia de disfagia fue de 65,6% (21/32). No se encontró asociación significativa entre lesiones laríngeas y disfagia (p = 0,70). Conclusión: En esta cohorte de pacientes, las lesiones laríngeas y la disfagia fueron altamente prevalentes. La evaluación precoz mediante endoscopia de la deglución nos ha facilitado un diagnóstico oportuno para guiar el tratamiento de manera individual hasta la decanulación y resolución de la disfagia encontrada.

Introduction: Patients with severe pneumonia due to COVID-19 may require orotracheal intubation, prolonged mechanical ventilation and tracheostomy. The presence of an artificial airway can generate laryngeal lesions and it is associated with swallowing dysfunction and increased risk of aspiration. Objective: The main objective of this study is to describe the prevalence of laryngeal lesions and oropharyngeal dysphagia in critically ill tracheostomized patients due to COVID-19. As a secondary objective, is to evaluate the association between the presence of laryngeal injury and dysphagia and each of them with other variables related to the patient's history, duration of the artificial airway and the prone position maneuver. Methods: This is an observational, longitudinal and retrospective study, conducted at the Juan A Fernández Hospital, CABA, Argentina. Tracheostomized patients diagnosed with COVID-19 were consecutively included. The presence of laryngeal lesions and dysphagia was recorded by fibroscopic evaluation of swallowing at the time of decannulation. Results: 32 patients were analyzed, of which 28 (87.5%) showed at least one laryngeal lesion, mainly in the glottic region. The prevalence of dysphagia was 65.6% (21/32). No significant association was found between laryngeal injuries and dysphagia (p = 0.70). Conclusion: laryngeal injuries and dysphagia were highly prevalent in this cohort of patients. The early evaluation through fibroscopic evaluation of swallowing for the protocolized follow-up of these patients, has provided us a timely diagnosis to guide treatment individually until decannulation and resolution of the dysphagia found.

Enzymatic Active Release of Violacein Present in Nanostructured Lipid Carrier by Lipase Encapsulated in 3D-Bioprinted Chitosan-Hydroxypropyl Methylcellulose Matrix With Anticancer Activity.

Violacein (Viol) is a bacterial purple water-insoluble pigment synthesized by Chromobacterium violaceum and other microorganisms that display many beneficial therapeutic properties including anticancer activity. Viol was produced, purified in our laboratory, and encapsulated in a nanostructured lipid carrier (NLC). The NLC is composed of the solid lipid myristyl myristate, an oily lipid mixture composed of capric and caprylic acids, and the surfactant poloxamer P188. Dormant lipase from Rhizomucor miehei was incorporated into the NLC-Viol to develop an active release system. The NLC particle size determined by dynamic light scattering brings around 150 nm particle size and ζ≈ -9.0 mV with or without lipase, but the incorporation of lipase increase the PdI from 0.241 to 0.319 (≈32%). For scaffold development, a 2.5 hydroxypropyl methylcellulose/chitosan ratio was obtained after optimization of a composite for extrusion in a 3D-bioprinter developed and constructed in our laboratory. Final Viol encapsulation efficiency in the printings was over 90%. Kinetic release of the biodye at pH = 7.4 from the mesh containing NLC-lipase showed roughly 20% Viol fast release than without the enzyme. However, both Viol kinetic releases displayed similar profiles at pH = 5.0, where the lipase is inactive. The kinetic release of Viol from the NLC-matrices was modeled and the best correlation was found with the Korsmeyer-Peppas model (R2 = 0.95) with n < 0.5 suggesting a Fickian release of Viol from the matrices. Scanning Electron Microscope (SEM) images of the NLC-meshes showed significant differences before and after Viol's release. Also, the presence of lipase dramatically increased the gaps in the interchain mesh. XRD and Fourier Transform Infrared (FTIR) analyses of the NLC-meshes showed a decrease in the crystalline structure of the composites with the incorporation of the NLC, and the decrease of myristyl myristate in the mesh can be attributed to the lipase activity. TGA profiles of the NLC-meshes showed high thermal stability than the individual components. Cytotoxic studies in A549 and HCT-116 cancer cell lines revealed high anticancer activity of the matrix mediated by mucoadhesive chitosan, plus the biological synergistic activities of violacein and lipase.

Prodigiosin: a promising biomolecule with many potential biomedical applications.

Pigments are among the most fascinating molecules found in nature and used by human civilizations since the prehistoric ages. Although most of the bio-dyes reported in the literature were discovered around the eighties, the necessity to explore novel compounds for new biological applications has made them resurface as potential alternatives. Prodigiosin (PG) is an alkaloid red bio-dye produced by diverse microorganisms and composed of a linear tripyrrole chemical structure. PG emerges as a really interesting tool since it shows a wide spectrum of biological activities, such as antibacterial, antifungal, algicidal, anti-Chagas, anti-amoebic, antimalarial, anticancer, antiparasitic, antiviral, and/or immunosuppressive. However, PG vehiculation into different delivery systems has been proposed since possesses low bioavailability because of its high hydrophobic character (XLogP3-AA = 4.5). In the present review, the general aspects of the PG correlated with synthesis, production process, and biological activities are reported. Besides, some of the most relevant PG delivery systems described in the literature, as well as novel unexplored applications to potentiate its biological activity in biomedical applications, are proposed.

Microfluidics Approach to the Mechanical Properties of Red Blood Cell Membrane and Their Effect on Blood Rheology.

In this article, we describe the general features of red blood cell membranes and their effect on blood flow and blood rheology. We first present a basic description of membranes and move forward to red blood cell membranes' characteristics and modeling. We later review the specific properties of red blood cells, presenting recent numerical and experimental microfluidics studies that elucidate the effect of the elastic properties of the red blood cell membrane on blood flow and hemorheology. Finally, we describe specific hemorheological pathologies directly related to the mechanical properties of red blood cells and their effect on microcirculation, reviewing microfluidic applications for the diagnosis and treatment of these diseases.

Clinical differentiation of inflammatory bowel disease (IBD) in Latin America and the Caribbean.

ABSTRACT: The aim of the present study was to describe the epidemiological and clinical characteristics of inflammatory bowel disease (IBD), including medical and surgical treatments, in several countries in Latin America and the Caribbean.IBD is recognized as a global health problem because its incidence and prevalence have increased significantly over the last few years.This multicenter retrospective cohort study included 4714 patients with IBD diagnosed from 9 countries in Latin America and the Caribbean: Colombia, Cuba, Dominican Republic, Ecuador, Mexico, Peru, Puerto Rico, Uruguay, and Venezuela.Crohn disease (CD) was more frequent in Puerto Rico (71.9%), the Dominican Republic (61.0%), and Peru (53.1%). Ulcerative colitis was more frequent in Colombia (78.6%), Venezuela (78.2%), Mexico (75.5%), Cuba (69.9%), Ecuador (64.1%), and Uruguay (60.9%). The following clinical characteristics were more frequent in the Caribbean: penetrating behavior in CD, steroid dependence, steroid resistance, intolerance to thiopurines, extraintestinal manifestations, surgeries, hospitalizations due to IBD, and family history of IBD. The factors associated with the use of biological therapy were pancolitis in ulcerative colitis, penetrating behavior in CD, steroid resistance and dependence, presence of extraintestinal manifestations, and the need for surgery.This study from Latin America and the Caribbean demonstrated the different epidemiological and clinical characteristics of IBD.