Long-Term Outcomes of Biological Therapy in Crohn's Disease Complicated With Internal Fistulizing Disease: BIOSCOPE Study From GETECCU.

INTRODUCTION: The prevalence of penetrating complications in Crohn's disease (CD) increases progressively over time, but evidence on the medical treatment in this setting is limited. The aim of this study was to evaluate the effectiveness of biologic agents in CD complicated with internal fistulizing disease. METHODS: Adult patients with CD-related fistulae who received at least 1 biologic agent for this condition from the prospectively maintained ENEIDA registry were included. Exclusion criteria involved those receiving biologics for perianal disease, enterocutaneous, rectovaginal, anastomotic, or peristomal fistulae. The primary end point was fistula-related surgery. Predictive factors associated with surgery and fistula closure were evaluated by multivariate logistic regression and survival analyses. RESULTS: A total of 760 patients from 53 hospitals (673 receiving anti-tumor necrosis factors, 69 ustekinumab, and 18 vedolizumab) were included. After a median follow-up of 56 months (interquartile range, 26-102 months), 240 patients required surgery, with surgery rates of 32%, 41%, and 24% among those under anti-tumor necrosis factor, vedolizumab, or ustekinumab, respectively. Fistula closure was observed in 24% of patients. Older patients, ileocolonic disease, entero-urinary fistulae, or an intestinal stricture distal to the origin of the fistula were associated with a higher risk of surgery, whereas nonsmokers and combination therapy with an immunomodulator reduced this risk. DISCUSSION: Biologic therapy is beneficial in approximately three-quarters of patients with fistulizing CD, achieving fistula closure in 24%. However, around one-third still undergo surgery due to refractory disease. Some patient- and lesion-related factors can identify patients who will obtain more benefit from these drugs.

Effectiveness and Safety of Ustekinumab in Elderly Patients with Crohn's Disease: Real World Evidence From the ENEIDA Registry.

BACKGROUND AND AIMS: Clinical trials and real-life studies with ustekinumab in Crohn's disease [CD] have revealed a good efficacy and safety profile. However, these data are scarcely available in elderly patients. Therefore, we aim to assess the effectiveness and safety of ustekinumab in elderly patients with CD. METHODS: Elderly patients [>60 years old] from the prospectively maintained ENEIDA registry treated with ustekinumab due to CD were included. Every patient was matched with two controls under 60 years of age, according to anti-tumour necrosis factor use and smoking habit. Values for the Harvey-Bradshaw Index [HBI], endoscopic activity, C-reactive protein [CRP] and faecal calprotectin [FC] were recorded at baseline and at weeks 16, 32 and 54. RESULTS: In total, 648 patients were included, 212 of whom were elderly. Effectiveness was similar between young and elderly patients during the follow-up. Steroid-free remission was similar at week 16 [54.6 vs 51.4%, p = 0.20], 32 [53.0% vs 54.5%, p = 0.26] and 54 [57.8% vs 51.1%, p = 0.21]. Persistence of ustekinumab as maintenance therapy was similar in both age groups [log-rank test; p = 0.91]. There was no difference in the rate of adverse effects [14.2% vs 11.2%, p = 0.350], including severe infections [7.1% vs 7.3%, p = 1.00], except for the occurrence of de novo neoplasms, which was higher in older patients [0.7% vs 4.3%, p = 0.003]. CONCLUSIONS: Ustekinumab is as effective in elderly patients with CD as it is in non-elderly patients. The safety profile also seems to be similar except for a higher rate of de novo neoplasms, probably related to the age of the elderly patients.

Effect of Consuming Beef with Varying Fatty Acid Compositions as a Major Source of Protein in Volunteers under a Personalized Nutritional Program.

Beef is an excellent source of nutrients; unfortunately, most nutritional recommendations suggest limiting or even avoiding it. Studies have shown that the fatty acid composition of meat influences weight loss. This randomized controlled clinical trial evaluated the anthropometric and serum lipid changes after a food intervention that included frequent beef consumption (120 g consumed four days/week for four weeks). Volunteers were randomly assigned to the commercial or Wagyu-Cross beef groups, with the latter beef possessing higher fat and MUFA contents. Both groups exhibited reductions in body measurements and lipid profiles; however, the Wagyu-Cross group exhibited greater changes in weight (-3.75 vs. -2.90 kg) and BMI (-1.49 vs. -1.03) than the commercial group, without a significant difference between them. No significant group differences in lipid profiles were observed; however, the Wagyu-Cross group exhibited a more favorable change in decreasing the TC concentration (-7.00 mg/dL) and LDL-C concentration (-12.5 mg/dL). We suggest that high MUFA beef could be included in weight-loss programs since it does not affect weight loss and hasn't a negative influence on lipid metabolism.

Management and Long-term Outcomes of Crohn's Disease Complicated with Enterocutaneous Fistula: ECUFIT Study from GETECCU.

BACKGROUND AND AIMS: Crohn's disease [CD] can develop penetrating complications at any time during the disease course. Enterocutaneous fistulae [ECF] are disease-related complications with an important impact on quality of life. Our aim was to describe the outcomes of this complication, including its medical and/or surgical management and their temporal trends. The primary endpoint was fistula closure, defined as the absence of drainage, with no new abscess or surgery, over the preceding 6 months. METHODS: Clinical information from all adult patients with CD and at least one ECF-excluding perianal fistulae-were identified from the prospectively-maintained ENEIDA registry. All additional information regarding treatment for this complication was retrospectively reviewed. RESULTS: A total of 301 ECF in 286 patients [January 1970-September 2020] were analysed out of 30 088 records. These lesions were mostly located in the ileum [67%] and they had a median of one external opening [range 1-10]. After a median follow-up of 146 months (interquartile range [IQR], 69-233), 69% of patients underwent surgery. Fistula closure was achieved in 84%, mostly after surgery, and fistula recurrence was uncommon [13%]. Spontaneous and low-output fistulae were associated with higher closure rates (hazard ratio [HR] 1.51, 95% confidence interval [CI] 1.17-1.93, p = 0.001, and HR 1.49, 95% CI 1.07-2.06, p = 0.03, respectively); this was obtained more frequently with medical therapy since biologics have been available. CONCLUSIONS: ECF complicating CD are rare but entail a high burden of medical and surgical resources. Closure rates are high, usually after surgery, and fistula recurrence is uncommon. A significant proportion of patients receiving medical therapy can achieve fistula closure.

El compostaje de cáscara de Musa paradisiaca L. para la producción de biogás y biometano como estrategia de preservación de la salud ambiental / Musa paradisiaca L. husk composting for biogas and biomethane production as a strategy for preserving environmental health

A medida que a se avanza en el siglo XXI, los sistemas de energía deben alejarse de los combustibles fósiles y aumentar la capacidad de las energías renovables si se quieren cumplir los objetivos de temperaturas máximas del Acuerdo de París. Sin embargo, debido a los desafíos en la adopción de tecnologías bajas en carbono, ciertas áreas de los sistemas energéticos globales son difíciles de controlar y descarburar. Por otra parte, el compostaje es una de las prácticas de gestión de residuos orgánicos más importantes que se puede utilizar para lograr la sostenibilidad del suelo y del medio ambiente. El compost tiene un mínimo impacto en algunas emisiones, y puede ayudar a controlar la huella de carbono y limitar los efectos ambientales negativos de los métodos de eliminación de desechos más deficientes. La investigación tuvo por objetivo determinar la calidad de producir biogás y biometano a partir de la cáscara de plátano (Musa paradisiaca L.). Metodológicamente se desarrolló una investigación aplicada, con nivel de investigación de tipo experimental. Las cáscaras de plátano se colectaron de la planta de compostaje de la Municipalidad Provincial de Leoncio Prado, Perú. De la muestra se prepararon cinco sub muestras para la producción de biogás y cinco muestras adicionales para la producción de biometano. Los sistemas mostraron una producción de 0,067 m3 BG/Kg ST de biogás y 0,059 m3CH4/Kg ST de biometano, que generó subproductos como el biol y biosol. Estos resultados presentaron una baja toxicidad al ser sometidos a pruebas germinativas, concluyéndose que solo el 11,5% de la cáscara introducida al biorreactor se degrado y de esta fracción solo el 2,8% se convirtió en biogás(AU)

As progress is being made in the 21st century, energy systems must move away from fossil fuels and increase the capacity of renewable energies if you want to meet the maximum temperatures objectives of the Paris Agreement. However, due to the challenges in the adoption of low carbon technologies, certain areas of global energy systems are difficult to control and decarbure. On the other hand, composting is one of the most important organic waste management practices that can be used to achieve soil and environmental sustainability. The compost has a minimum impact on some emissions, and can help control the carbon footprint and limit the negative environmental effects of the most deficient waste removal methods. The research aimed to determine the quality of producing biogas and biomethane from the banana peel (Musa paradisiaca L.). Methodologically, an applied investigation was developed, with experimental research level. The banana peels were collected from the composting plant of the Provincial Municipality of Leoncio Prado, Peru. From the sample, five sub samples were prepared for the production of biogas and five additional samples for biomethane production. The systems showed a production of 0.067 m3 bg/kg ST of biogas and 0.059 m3ch4/kg ST of biomethane, which generated by -products such as biol and biosol. These results presented a low toxicity when they were subjected to germinative evidence, concluding that only 11.5% of the shell introduced into the bioreactor was degraded and of this fraction only 2.8% became biogas(AU)

Riesgo patogénico por Aspergillus fumigatus en la producción de compost de Musa paradisiaca / Pathogenic risk by Aspergillus fumigatus in the compost production of Musa paradisiaca

Aspergillus fumigatus es un hongo con características de saprofito que crece en las partes muertas y en descomposición de la materia orgánica. La presencia de terapias inmunosupresoras o de antifúngicos pueden convertirlo en un patógeno fúngico oportunista causante de enfermedades como aspergilosis pulmonar crónica (CPA), aspergilosis invasiva aguda y síndrome de alergias. Pacientes que sufren de enfermedad pulmonar severa como la pulmonar obstructiva crónica (EPOC) tienen un mayor riesgo de desarrollar aspergilosis pulmonar crónica y aspergilosis pulmonar necrosante crónica (CNPA) que pueden causar crecimiento de hongos en los tejidos dañados. Por otro lado, una de las fuentes más comunes de estos hongos son la generación de compost. Estos fertilizantes orgánicos no dañan al medio ambiente y podrían resultar una estrategia eficaz para salvaguardar el medio ambiente. El compost orgánico promueve el suelo con mejor capacidad de retención de agua y resistencia a la sequía. Entre los residuos agrícolas postcosecha más comunes utilizados en la formación de compost, se pueden mencionar a las cáscaras de yuca, de maní, de frutas y verduras, desechos de cervecería, cascarilla de cacao, cascarilla de cola, maíz, conchas de plátano (Musa paradisiaca). Esta investigación tuvo por objetivo determinar la calidad del compost producido a partir de la cáscara de plátano con el fin de aprovechar hasta un 70% de su biomasa en la Municipalidad Provincial de Leoncio Prado, Perú. Los resultados mostraron que la la degradación aerobia de la cáscara de M. paradisiaca generó emisiones de CO2 (88,61%), así como compost (6,57 %) y lixiviados (4,82 %). Sin embargo, los efectos fitotóxicos usando el índice de germinación mostraron una inhibición completa de las semillas probadas posiblemente debido al gran contenido de minerales (alto contenido de salinidad del compost y lixiviado), presencia de metales pesados, compuestos orgánicos presentes, o la presencia de hongos tales como el A. fumigatus(AU)

Aspergillus fumigatus is a saprophytic fungus that grows on dead and decomposing parts of organic matter. The presence of immunosuppressive or antifungal therapies can make it an opportunistic fungal pathogen causing diseases such as chronic pulmonary aspergillosis (CPA), acute invasive aspergillosis, and allergy syndrome. Patients suffering from severe lung disease such as chronic obstructive pulmonary disease (COPD) are at increased risk of developing chronic pulmonary aspergillosis and chronic necrotizing pulmonary aspergillosis (CNPA) which can cause fungal growth in damaged tissues. On the other hand, one of the most common sources of these fungi is the generation of compost. These organic fertilizers do not harm the environment and could be an effective strategy to safeguard the environment. Organic compost promotes soil with better water holding capacity and drought resistance. Among the most common postharvest agricultural residues used in the formation of compost, we can mention cassava shells, peanut shells, fruit and vegetable shells, brewery waste, cocoa shells, tail shells, corn, banana shells (Musa paradisiaca). The objective of this research was to determine the quality of the compost produced from the banana peel in order to take advantage of up to 70% of its biomass in the Provincial Municipality of Leoncio Prado, Peru. The results showed that the aerobic degradation of the shell of M. paradisiaca generated CO2 emissions (88.61%), as well as compost (6.57%) and leachates (4.82%). However, the phytotoxic effects using the germination index showed a complete inhibition of the tested seeds, possibly due to the high mineral content (high salinity content of the compost and leachate), the presence of heavy metals, organic compounds present, or the presence of fungi such as A. fumigatus(AU)

Great-tailed Grackles (Quiscalus mexicanus) as Biomonitors of Atmospheric Heavy Metal Pollution in Urban Areas of Monterrey, Mexico.

Heavy metals exposure has been linked to severe health problems. In Mexico, the Monterrey metropolitan area (MMA) is considered one of the most polluted industrial regions. Because birds have been used successfully as environmental biomonitors, the levels of lead, cadmium, and arsenic in feathers of Great-tailed grackles (Quiscalus mexicanus) from two sites within and one site outside the MMA were determined. One hundred birds were captured, samples were analyzed by atomic absorption spectrometry. Ciudad Universitaria had the highest mean values of lead and cadmium, 11.91 ppm d.w. and 1.66 ppm d.w., respectively. This was at least, 10- and 8-times higher than the two other sample sites. We believe that using Great-tailed grackles as bioindicators in conjunction with air pollutants sampling from meteorological stations in Monterrey City could help in making decisions when applying environmental remediation measures as well as in the selection of places for housing, school and work among others.

Improvement of serum lipid parameters in consumers of Mexican Wagyu-Cross beef: A randomized controlled trial.

Beef is considered an excellent source of high-quality protein and micronutrients. The high saturated fatty acid (SFA) composition of beef has been associated with cardiovascular diseases; however, this is a controversial issue because at present, no evidence has scientifically proven such an association. Wagyu cattle have been used as an option to generate high-quality fatty acids (FAs) in beef and have been crossed with local beef cattle (Wagyu-Cross). In Mexico, Wagyu-Cross is marketed assuming the same quality as purebred Wagyu meat without scientific support. This study aimed to determine whether the differences in the FA composition of Wagyu-Cross and commercial beef affected lipid metabolism in frequent consumers of beef. The study is a randomized, controlled, double-blinded phase IV clinical trial. Thirty-four volunteers completed treatments in which 120 g ground beef was consumed 3 days per week for 2 weeks. Volunteers were randomized to the "A" (commercial meat) or "B" (Wagyu-Cross meat) groups. The beef fat content was 87% higher, the SFA content was 2.3% lower, and the monounsaturated fatty acid (MUFA) C18:1 n-9 concentrations were higher in Wagyu-Cross beef than in commercial beef. The B group exhibited a significantly larger change from baseline in the serum lipid profile in total cholesterol (TC) (-4.7% versus +6.9%), low-density lipoprotein (LDL) (-4.1% versus +10.0%), nonhigh-density lipoprotein (non-HDL) (-6.1% versus +4.9%), and the ratio of three atherogenic indexes-TC/HDL (-3.5% versus +6.4%), LDL/HDL (-2.8% versus +14.6%), and non-HDL/HDL (-4.7% versus +9.3%)-than the A group. This result confirms that meat FA composition is a key point for redirecting cattle breeding strategies and promotes beef as a healthful protein source. PRACTICAL APPLICATION: Here, we found new evidence based on a clinical trial that beef with a favorable fatty acid composition (i.e., monounsaturated fatty acid and polyunsaturated fatty acid content) is a key factor in improving parameters associated with consumer health. This information will support the design of cattle breeding strategies as an option to promote beef consumption as a healthier protein source and create opportunities for the development of the functional food industry.

Gastroenterologists' attitudes on the detection and management of gastric premalignant conditions: results of a nationwide survey in Spain.

INTRODUCTION: Gastric premalignant conditions (GPC) surveillance has been proposed to improve the prognosis of gastric cancer (GC), but the early GC detection rate remaining low, and missing GC during an esophago-gastro-duodenoscopy is still a problem. We aimed to explore the gastroenterologists' attitudes on the detection and management of GPC. METHODS: A cross-sectional study was designed based on a survey among gastroenterologists from Asociación Española de Gastroenterología. RESULTS: The participation rate was 12% (146/1243). Eighty-one percent worked at secondary or tertiary-care hospitals with the capability to perform mucosectomy (80%), but with a lesser availability of endoscopic submucosal dissection (35%). Most respondents had high-definition endoscopes (88%), and virtual chromoendoscopy (86%), but during performing an upper endoscopy, 34% never or rarely use chromoendoscopy, and 73% apply a biopsy protocol often/very often when atrophy or intestinal metaplasia (IM) is suspected. Half of the respondents self-reported their ability to recognize atrophy or IM ≤7 (on a scale from 0 to 10), whereas ≤6 for dysplasia or early GC. Helicobacter pylori infection is eradicated and verified by ≥90%. Endoscopic surveillance of atrophy/IM is performed by 62%. An immediate endoscopy for dysplasia is not always performed. For low-grade dysplasia, 97.6% consider endoscopic management, but for high-grade dysplasia, 23% regard gastric surgery. CONCLUSION: There is a wide variability in the detection and management of GPC among Spanish gastroenterologists, and compliance with guidelines and biopsy protocols could be improved. Performance of high-quality gastroscopies including use of virtual chromoendoscopy, that might allow an improvement in the GPC detection, needs also to be generalized.

Frecuencia y aspectos clínicos del cáncer gástrico precoz en relación con el avanzado en un área sanitaria de España / Frequency and clinical characteristics of early gastric cancer in comparison to advanced gastric cancer in a health area of Spain

INTRODUCCIÓN: En la actualidad, la incidencia del cáncer gástrico (CG) está disminuyendo, sin embargo, la supervivencia continúa siendo baja. El cáncer gástrico precoz (CGP) ofrece un mejor pronóstico y la posibilidad de tratamientos endoscópicos curativos. PACIENTES Y MÉTODOS: Estudio observacional de una cohorte retrospectiva de todos los pacientes con CG en un periodo de 5años en un área sanitaria de España. El CGP incluyó los pacientes con afectación mucosa o submucosa (T1) independientemente de la afectación ganglionar, mientras que el avanzado fueron los T2-T4. RESULTADOS: Se incluyeron 209 pacientes de los cuales 26 (12%) fueron CGP. El CGP no tuvo diferencias en comparación con el avanzado en la edad, sexo, infección por HP, lesiones premalignas ni tipo histológico; sin embargo, tuvo diferencias significativas en la localización (antro e incisura en un 76% vs. 38%, p = 0,01), síntomas de alarma (69% vs. 90%, p < 0,01), tratamiento con intención curativa (100% vs. 30%, p < 0,01), performance status (PS 0-1: 92% vs. 75%, p = 0,03) y supervivencia (85% vs. 20%, p < 0,001). Entre los pacientes tratados con intención curativa, el 98% (79/81) fueron operados y el 2% (2/81) fueron tratados con mucosectomía. Siete (27%) pacientes con CGP se hubiesen podido beneficiar de disección submucosa. DISCUSIÓN: La frecuencia del CGP fue baja en nuestra área sanitaria (12% de los CG). El CGP tuvo síntomas de alarma en un alto porcentaje, se localizó en el tercio distal del estómago (antro e incisura) y tuvo mejor pronóstico en relación con el CG avanzado. Se deben implementar medidas para incrementar la detección y tratamiento endoscópico del CGP

INTRODUCTION: Gastric cancer (GC) incidence is currently decreasing; however, survival is still low. Early GC (EGC) has better prognosis and it could be cured by endoscopic methods. PATIENTS AND METHODS: Observational study of a retrospective cohort of all patients with GC during a five-year period in a health area of Spain. EGC diagnosis was defined as mucosal or submucosal (T1) cancers regardless of lymph node involvement, whereas the advanced GC were T2-T4. RESULTS: 209 patients were included, and 26 (12%) of them were EGC. There was no difference between EGC and advanced GC in age, sex, HP infection, precancerous lesions or histological type. Other characteristics of EGC were different from advanced GC: location (antrum and incisura in 76% vs 38%, p = 0.01), alarm symptoms (69% vs 90%, p < 0.01), curative treatment (100% vs 30%, p < 0.01), performance status (PS 0-1: 92% vs 75%, p = 0.03) and survival (85% vs 20%, p < 0.001). Among patients who received curative treatment, 98% (79/81) underwent surgery and 2% (2/81) were treated by mucosectomy. Seven (27%) patients with EGC could have benefited from treatment by endoscopic submucosal resection. DISCUSSION: EGC frequency was low (12% of GCs) in our health area. EGC had a high percentage of alarm symptoms, and was located in the distal third of the stomach (antrum and incisura) and had better prognosis compared to advanced GC. Strategies to increase detection and endoscopic treatment of EGC should be implemented

Immunotyping of tumor-infiltrating lymphocytes in triple-negative breast cancer and genetic characterization.

Tumor-infiltrating lymphocytes (TILs) reflect the host immune response against cancer cells. Immunomodulators have been recently suggested as a novel therapeutic strategy against triple-negative breast cancer (TNBC). However, the TIL profile in TNBC has not been thoroughly investigated. In the present study, the percentage, immunophenotype and genetic profiles of TILs in pre-surgical tumor samples of patients with TNBC were evaluated prior to neoadjuvant chemotherapy (NAC). Patients diagnosed with breast cancer at Hospital San José TecSalud were consecutively and prospectively enrolled in the present study between August 2011 and August 2015. The pathological response to NAC was evaluated using the de Miller-Payne and MD Anderson Cancer Center system. TIL percentage (low, intermediate, and high) was evaluated using special hematoxylin-eosin staining on the core needle biopsies. The immunophenotype of TILs was assessed by immunohistochemistry (IHC) for CD3+, CD4+ and CD8+. In addition, the gene expression profile of CD3, CD4, CD8, CD20, CD45, forkhead box P3, interleukin 6, programmed cell death 1 and CD274 molecule was assessed in all patients. A total of 26 samples from patients with TNBC prior to NAC were included in the present study. TILs were low in 30.7%, intermediate in 38.4% and elevated in 30.7% of tumors. CD3+ and CD4+ counts were associated with the pathological response to NAC (P=0.04). Finally, an overexpression pattern of CD3, CD4, CD8, CD45 and CD20 genes was observed in patients with a partial or complete pathological response. The present results demonstrated that TILs may predict the pathological response to NAC in patients with TNBC. Furthermore, a more accurate association was identified between the high expression levels of CD3, CD4, CD8, CD45 and CD20 genes and partial and complete pathological response, compared with the association between high expression and IHC alone.

Frequency and clinical characteristics of early gastric cancer in comparison to advanced gastric cancer in a health area of Spain. / Frecuencia y aspectos clínicos del cáncer gástrico precoz en relación con el avanzado en un área sanitaria de España.

INTRODUCTION: Gastric cancer (GC) incidence is currently decreasing; however, survival is still low. Early GC (EGC) has better prognosis and it could be cured by endoscopic methods. PATIENTS AND METHODS: Observational study of a retrospective cohort of all patients with GC during a five-year period in a health area of Spain. EGC diagnosis was defined as mucosal or submucosal (T1) cancers regardless of lymph node involvement, whereas the advanced GC were T2-T4. RESULTS: 209 patients were included, and 26 (12%) of them were EGC. There was no difference between EGC and advanced GC in age, sex, HP infection, precancerous lesions or histological type. Other characteristics of EGC were different from advanced GC: location (antrum and incisura in 76% vs 38%, p=0.01), alarm symptoms (69% vs 90%, p<0.01), curative treatment (100% vs 30%, p<0.01), performance status (PS 0-1: 92% vs 75%, p=0.03) and survival (85% vs 20%, p<0.001). Among patients who received curative treatment, 98% (79/81) underwent surgery and 2% (2/81) were treated by mucosectomy. Seven (27%) patients with EGC could have benefited from treatment by endoscopic submucosal resection. DISCUSSION: EGC frequency was low (12% of GCs) in our health area. EGC had a high percentage of alarm symptoms, and was located in the distal third of the stomach (antrum and incisura) and had better prognosis compared to advanced GC. Strategies to increase detection and endoscopic treatment of EGC should be implemented.

Early treatment with anti-tumor necrosis factor agents improves long-term effectiveness in symptomatic stricturing Crohn's disease.

BACKGROUND: There is limited evidence on the effectiveness of biological therapy in stricturing complications in patients with Crohn's disease. AIM: The study aims to determine the effectiveness of anti-tumor necrosis factor (TNF) agents in Crohn's disease complicated with symptomatic strictures. METHODS: In this multicentric and retrospective study, we included adult patients with symptomatic stricturing Crohn's disease receiving their first anti-TNF therapy, with no previous history of biological, endoscopic or surgical therapy. The effectiveness of the anti-TNF agent was defined as a composite outcome combining steroid-free drug persistence with no use of new biologics or immunomodulators, hospital admission, surgery or endoscopic therapy during follow-up. RESULTS: Overall, 262 patients with Crohn's disease were included (53% male; median disease duration, 35 months, 15% active smokers), who received either infliximab (N = 141, 54%) or adalimumab (N = 121, 46%). The treatment was effective in 87% and 73% of patients after 6 and 12 months, respectively, and continued to be effective in 26% after a median follow-up of 40 months (IQR, 19-85). Nonetheless, 15% and 21% of individuals required surgery after 1 and 2 years, respectively, with an overall surgery rate of 32%. Postoperative complications were identified in 15% of patients, with surgical site infection as the most common. Starting anti-TNF therapy in the first 18 months after the diagnosis of Crohn's disease or the identification of stricturing complications was associated with a higher effectiveness (HR 1.62, 95% CI 1.18-2.22; and HR 1.55, 95% CI 1.1-2.23; respectively). Younger age, lower albumin levels, strictures located in the descending colon, concomitant aminosalicylates use or presence of lymphadenopathy were associated with lower effectiveness. CONCLUSIONS: Anti-TNF agents are effective in approximately a quarter of patients with Crohn's disease and symptomatic intestinal strictures, and 68% of patients are free of surgery after a median of 40 months of follow-up. Early treatment and some potential predictors of response were associated with treatment success in this setting.

Gastric cancer missed at esophagogastroduodenoscopy in a well-defined Spanish population.

BACKGROUND: Although esophagogastroduodenoscopy (EGD) is the standard procedure for the diagnosis of gastric cancer (GC), some GCs are missed. There are no published data on the missed rate of GC in Spain. AIMS: To determine the frequency and characteristics of missed GCs and assess the quality of the EGD in a specific population with GC. METHODS: Records of all patients diagnosed with gastric adenocarcinoma between 2012 and 2016 in a defined geographic area were reviewed. Missed GC was defined as a case with a prior negative EGD for cancer. Quality indicators from the prior EGDs were measured. RESULTS: From 212 cases of GC, 25 cases were excluded. Seventeen out of 187 patients had a prior EGD (9.1%). Twelve of those 17 missed GC had a prior EGD with some abnormal findings. In 6 of them, biopsies were taken. Survival was no different between patients with missed and non-missed GC. Quality indicators that failed to meet standards were recording time, image documentation, and a protocol of biopsies. CONCLUSIONS: Missed GC in an EGD in a defined population in Spain is not uncommon (9.1%). The endoscopist is an important factor in missed GC due to lack of adequate detection and sampling error. Compliance with performance of quality indicators could reduce missed GC.

Epidemiology of Aspergillus species causing keratitis in Mexico.

BACKGROUND: The incidence of fungal keratitis has increased in recent years. While the epidemiology and clinical roles of various Candida and Fusarium species have been relatively well-identified in infections of the eye, data regarding keratitis caused by Aspergillus species are scant. Accurate and rapid diagnosis is important for successful management of this infection. OBJECTIVES: To present the first molecular epidemiological data from Mexico during a 4-year period of cases admitted with Aspergillus keratitis to a tertiary care eye institution in Mexico City. PATIENTS/METHODS: A total of 25 cases of keratitis were included in the study. Aspergillus isolates were identified by sequencing the calmodulin gene. Antifungal susceptibility was tested according to CLSI. RESULTS: The aetiological agents belonged to Aspergillus flavus (n = 13), Aspergillus effusus (n = 1), Aspergillus tamarii (n = 4), Aspergillus sydowii (n = 1), Aspergillus protuberus (n = 3) and Aspergillus terreus (n = 3). All strains had low minimum inhibitory concentrations (MICs) of itraconazole and voriconazole (VCZ). Amphotericin B and natamycin showed moderate elevated MICs. CONCLUSIONS: Early diagnosis and application of topical VCZ 1% were associated with good outcome. Monitoring of local epidemiological data plays an important role in clinical practice.

Acanthamoeba keratitis in Mexico: Report of a clinical case and importance of sensitivity assays for a better outcome.

Acanthamoeba keratitis (AK) is a sight-threatening corneal infection. The early symptoms include redness, pain, photophobia and intense tearing. Chronic infection usually progresses to stromal inflammation, ring ulcers, corneal opacification and hypopyon. Here we document an AK case in a high myopic 38-year-old woman from Mexico City, with a history of wearing contact lenses while swimming. Corneal scrapes cultures were positive only for amoebae, consequently a treatment including netilmicin 0.3% and oral itraconazole 100 mg/12 h was prescribed. The infection was resolved after 8 months, leaving a slight leucoma outside the visual axis, with a visual acuity of 20/150. In the laboratory, the amoebic isolate was axenized in PYG medium, with an optimal growth at 30 °C, and was identified morphologically as Acanthamoeba polyphaga according to the taxonomic criteria of Page (1988) and placed in the T4 group by genotyping. The virulence of this strain (40%) was determined by intranasal inoculation of 1 × 106/20 µl trophozoites in BALB/c mice recovering from brain, proving their invasion ability and by the interaction with monolayers of epithelial cells of the established MDCK line of canine kidney origin (1:2 ratio of interaction), at 1, 3, 6, 8 and 24 h; trophozoites migrated to cell junctions inducing few lytic zones. In addition to the biological characterization, in vitro drug sensitivity tests were performed using chlorhexidine, itraconazole, netilmicin and voriconazole. Results revealed that voriconazole was the most effective compound. A. polyphaga remains as one of the most frequently isolated species producing AK. The treatment of AK case using netilmicin and oral itraconazole solved the disease, but the healing process was wide-ranging (8 months). The use of voriconazole and chlorhexidine may be an alternative treatment of future AK cases in Mexico.

Profiles of Amino Acids and Acylcarnitines Related with Insecticide Exposure in Culex quinquefasciatus (Say).

Culex quinquefasciatus Say is a vector of many pathogens of humans, and both domestic and wild animals. Personal protection, reduction of larval habitats, and chemical control are the best ways to reduce mosquito bites and, therefore, the transmission of mosquito-borne pathogens. Currently, to reduce the risk of transmission, the pyrethroids, and other insecticide groups have been extensively used to control both larvae and adult mosquitoes. In this context, amino acids and acylcarnitines have never been associated with insecticide exposure and or insecticide resistance. It has been suggested that changes in acylcarnitines and amino acids profiles could be a powerful diagnostic tool for metabolic alterations. Monitoring these changes could help to better understand the mechanisms involved in insecticide resistance, complementing the strategies for managing this phenomenon in the integrated resistance management. The purpose of the study was to determine the amino acids and acylcarnitines profiles in larvae of Cx. quinquefasciatus after the exposure to different insecticides. Bioassays were performed on Cx. quinquefasciatus larvae exposed to the diagnostic doses (DD) of the insecticides chlorpyrifos (0.001 µg/mL), temephos (0.002 µg/mL) and permethrin (0.01 µg/mL). In each sample, we analyzed the profile of 12 amino acids and 31 acylcarnitines by LC-MS/MS. A t-test was used to determine statistically significant differences between groups and corrections of q-values. Results indicates three changes, the amino acids arginine (ARG), free carnitine (C0) and acetyl-carnitine (C2) that could be involved in energy production and insecticide detoxification. We confirmed that concentrations of amino acids and acylcarnitines in Cx. quinquefasciatus vary with respect to different insecticides. The information generated contributes to understand the possible mechanisms and metabolic changes occurring during insecticide exposure.

Circulating microRNA expression profile in B-cell acute lymphoblastic leukemia.

BACKGROUND: Acute lymphoblastic leukemia (ALL) is a highly diverse disease characterized by cytogenetic and molecular abnormalities, including altered microRNA (miRNA) expression signatures. AIM: We perform and validate a plasma miRNA expression profiling to identify potential miRNA involved in leukemogenesis METHODS: MiRNA expression profiling assay was realized in 39 B-ALL and 7 normal control plasma samples using TaqMan Low Density Array (TLDA) plates on Applied Biosystems 7900 HT Fast Real-Time PCR System. MiRNA validation was done for six miRNA differentially expressed by quantitative real-time PCR. RESULTS: Seventy-seven circulating miRNA differentially expressed: hsa-miR-511, -222, and -34a were overexpressed, whereas hsa-miR-199a-3p, -223, -221, and -26a were underexpressed (p values < 0.005 for both sets). According to operating characteristic curve analysis, hsa-miR-511 was the most valuable biomarker for distinguishing B-ALL from normal controls, with an area under curve value of 1 and 100% for sensitivity, and specificity respectively. CONCLUSIONS: Measuring circulating levels of specific miRNA implicated in regulation of cell differentiation and/or cell proliferation such as hsa-miRNA-511, offers high sensitivity and specificity in B-ALL detection and may be potentially useful for detection of disease progression, as indicator of therapeutic response, and in the assessment of biological and/or therapeutic targets for patients with B-ALL.

Reference values for amino acids and acylcarnitines in peripheral blood in Quarter horses and American Miniature horses.

BACKGROUND: Free amino acids and acylcarnitines circulating in the blood can be used for diagnosis for metabolic illness and imbalances. To date, the normal reference ranges of amino acids and acylcarnitines in horse peripheral blood have not been established. In this study, the concentrations of 12 amino acids and 26 acylcarnitines were determined by tandem mass spectrometry in complete blood from 100 healthy horses (50 Quarter horses (QH) [23 males and 27 females] and 50 American Miniature horses (AMH) [15 males and 35 females]) with no signs of metabolic disease. The means and standard deviations were determined and data statistically analyzed. FINDINGS: Concentrations of short, medium, and long chain acylcarnitines were significantly higher in male AMH than in male QH. The concentrations of the amino acids alanine, arginine, glycine, proline (glycogenic), and leucine (ketogenic) were higher in the QH than in the AMH. Female AMH had higher concentrations of propionylcarnitine, leucine, proline, arginine, and ornithine than female QH. CONCLUSIONS: Normal reference ranges of amino acids and acylcarnitines were established for AMH and QH. Significant differences were found in concentration of these compounds between breeds and gender.

Molecular evolution and expression profile of the chemerine encoding gene RARRES2 in baboon and chimpanzee.

BACKGROUND: Chemerin, encoded by the retinoic acid receptor responder 2 (RARRES2) gene is an adipocytesecreted protein with autocrine/paracrine functions in adipose tissue, metabolism and inflammation with a recently described function in vascular tone regulation, liver, steatosis, etc. This molecule is believed to represent a critical endocrine signal linking obesity to diabetes. There are no data available regarding evolution of RARRES2 in non-human primates and great apes. Expression profile and orthology in RARRES2 genes are unknown aspects in the biology of this multigene family in primates. Thus; we attempt to describe expression profile and phylogenetic relationship as complementary knowledge in the function of this gene in primates. To do that, we performed A RT-PCR from different tissues obtained during necropsies. Also we tested the hypotheses of positive evolution, purifying selection, and neutrality. And finally a phylogenetic analysis was made between primates RARRES2 protein. RESULTS: RARRES2 transcripts were present in liver, lung, adipose tissue, ovary, pancreas, heart, hypothalamus and pituitary tissues. Expression in kidney and leukocytes were not detectable in either species. It was determined that the studied genes are orthologous. CONCLUSIONS: RARRES2 evolution fits the hypothesis of purifying selection. Expression profiles of the RARRES2 gene are similar in baboons and chimpanzees and are also phylogenetically related.