Pathobiological signatures of dysbiotic lung injury in pediatric patients undergoing stem cell transplantation.

Hematopoietic cell transplantation (HCT) uses cytotoxic chemotherapy and/or radiation followed by intravenous infusion of stem cells to cure malignancies, bone marrow failure and inborn errors of immunity, hemoglobin and metabolism. Lung injury is a known complication of the process, due in part to disruption in the pulmonary microenvironment by insults such as infection, alloreactive inflammation and cellular toxicity. How microorganisms, immunity and the respiratory epithelium interact to contribute to lung injury is uncertain, limiting the development of prevention and treatment strategies. Here we used 278 bronchoalveolar lavage (BAL) fluid samples to study the lung microenvironment in 229 pediatric patients who have undergone HCT treated at 32 children's hospitals between 2014 and 2022. By leveraging paired microbiome and human gene expression data, we identified high-risk BAL compositions associated with in-hospital mortality (P = 0.007). Disadvantageous profiles included bacterial overgrowth with neutrophilic inflammation, microbiome contraction with epithelial fibroproliferation and profound commensal depletion with viral and staphylococcal enrichment, lymphocytic activation and cellular injury, and were replicated in an independent cohort from the Netherlands (P = 0.022). In addition, a broad array of previously occult pathogens was identified, as well as a strong link between antibiotic exposure, commensal bacterial depletion and enrichment of viruses and fungi. Together these lung-immune system-microorganism interactions clarify the important drivers of fatal lung injury in pediatric patients who have undergone HCT. Further investigation is needed to determine how personalized interpretation of heterogeneous pulmonary microenvironments may be used to improve pediatric HCT outcomes.

High-Specificity CRISPR-Mediated Genome Engineering in Anti-BCMA Allogeneic CAR T Cells Suppresses Allograft Rejection in Preclinical Models.

Allogeneic chimeric antigen receptor (CAR) T cell therapies hold the potential to overcome many of the challenges associated with patient-derived (autologous) CAR T cells. Key considerations in the development of allogeneic CAR T cell therapies include prevention of graft-vs-host disease (GvHD) and suppression of allograft rejection. Here, we describe preclinical data supporting the ongoing first-in-human clinical study, the CaMMouflage trial (NCT05722418), evaluating CB-011 in patients with relapsed/refractory multiple myeloma. CB-011 is a hypoimmunogenic, allogeneic anti-B-cell maturation antigen (BCMA) CAR T cell therapy candidate. CB-011 cells feature 4 genomic alterations and were engineered from healthy donor-derived T cells using a Cas12a CRISPR hybrid RNA-DNA (chRDNA) genome-editing technology platform. To address allograft rejection, CAR T cells were engineered to prevent endogenous HLA class I complex expression and overexpress a single-chain polyprotein complex composed of beta-2 microglobulin (B2M) tethered to HLA-E. In addition, T-cell receptor (TCR) expression was disrupted at the TCR alpha constant locus in combination with the site-specific insertion of a humanized BCMA-specific CAR. CB-011 cells exhibited robust plasmablast cytotoxicity in vitro in a mixed lymphocyte reaction in cell cocultures derived from patients with multiple myeloma. In addition, CB-011 cells demonstrated suppressed recognition by and cytotoxicity from HLA-mismatched T cells. CB-011 cells were protected from natural killer cell-mediated cytotoxicity in vitro and in vivo due to endogenous promoter-driven expression of B2M-HLA-E. Potent antitumor efficacy, when combined with an immune-cloaking armoring strategy to dampen allograft rejection, offers optimized therapeutic potential in multiple myeloma. See related Spotlight by Caimi and Melenhorst, p. 385.

Real-world experience of vedolizumab use in Colombian patients with inflammatory bowel disease-EXVEDOCOL.

BACKGROUND: Real-world studies about the effectiveness and safety of vedolizumab (VDZ) in the treatment of inflammatory bowel disease (IBD) in Latin America are scarce. Our study describes the effectiveness and safety of VDZ in Colombian patients with IBD. METHODS: EXVEDOCOL (EXperience of VEDOlizumab in COLombia) was a retrospective, multicenter, observational study. Adults with IBD receiving a first dose of VDZ between July 2016 and October 2018 were included. The co-primary outcomes clinical response, and remission, were determined at week 14 and last visit during the maintenance phase (LVMP). The secondary outcomes, deep remission and loss of response were recorded at LVMP. RESULTS: Thirty-one patients (25 ulcerative colitis (UC), 6 Crohn's disease (CD)) were included. At week 14, clinical response was achieved by 87.1% (27/31) of the patients treated with VDZ, while loss of response was reported in 6.7% (2/30). The remission rate at week 14 was 65.5% (19/29) and 75.9% (22/29) at LVMP. Prior anti-TNF exposure was reported in 61.3% (19 patients) of whom 84.2% (16/19) achieved clinical response at week 14 and 89.5% (17/19) at LVMP. For anti-TNF naïve patients, clinical response was recorded in 91.7% (11/12) at week 14 and 100% (12/12) at LVMP. CONCLUSIONS: High clinical remission rates and safety profile highlight VDZ as a valuable treatment option for IBD patients. Anti-TNF naïve patients may derive greater benefit from therapy. Studies with larger cohorts could confirm these findings.

Time and temperature abuse of milk in conditions representing a school cafeteria share table does not meaningfully reduce microbial quality.

Share tables (ST) are tables or stations in school cafeterias where students can return unopened foods and beverages, providing an opportunity to access these items at no cost. Currently, research suggests that milk is among the most wasted items in breakfast and lunch programs in the United States. Share tables present a simple solution for reducing milk waste, but research is needed to understand the microbial spoilage potential of milk in ST. To this end, uninoculated milk cartons and milk cartons inoculated with 2 to 3 log10(cfu/mL) Pseudomonas poae, a fast-growing psychrotroph, was exposed to ambient temperature during winter (mean temperature = 20.3°C) and summer (23.1°C) for 125 min, repeated over 5 d (the length of a school week). Microbial counts in the inoculated milk cartons increased linearly, exceeding the spoilage threshold of 6.0 log10(cfu/mL) after d 3 and after d 4 in the winter and summer season trials, respectively. In the winter trial, the microbial counts for uninoculated milk cartons never exceeded the lower limit of detection, 2.31 log10(cfu/mL), and in the summer trials, microbial counts never reached the spoilage threshold, indicating that initial contamination is a driving factor of microbial milk spoilage. Regardless of sharing status or seasonality, the greatest changes in counts for inoculated milk cartons occurred during overnight refrigeration, ranging from 0.56 to 1.4 log10(cfu/mL), while during the share table ranged from no observable change up to 0.29 log10(cfu/mL), emphasizing that school nutrition personnel should focus efforts on tightly controlling refrigeration temperatures and returning milk to refrigeration as soon as possible. A previously developed model for school cafeteria share tables was adapted to understand the typical residence time of milk in a simulated cafeteria with an ambient temperature share table for the summer and winter seasons over 1,000 wk. Milk was predicted to have a very short mean residence time (85 min) regardless of sharing status or season, with 99.8% of milk consumed, discarded, or donated within the first 2 d. As a result, only 3 out of 451,410 and 6 out of 451,410 simulated milks spoiled in the winter and summer seasons, respectively. The data generated here can be used to inform science-based decision-making for including milk in share tables, or applied to any system where one might have to accept short-term unrefrigerated storage of milk to meet a waste reduction or food security goal.

Pulmonary microbiome and transcriptome signatures reveal distinct pathobiologic states associated with mortality in two cohorts of pediatric stem cell transplant patients.

Lung injury is a major determinant of survival after pediatric hematopoietic cell transplantation (HCT). A deeper understanding of the relationship between pulmonary microbes, immunity, and the lung epithelium is needed to improve outcomes. In this multicenter study, we collected 278 bronchoalveolar lavage (BAL) samples from 229 patients treated at 32 children's hospitals between 2014-2022. Using paired metatranscriptomes and human gene expression data, we identified 4 patient clusters with varying BAL composition. Among those requiring respiratory support prior to sampling, in-hospital mortality varied from 22-60% depending on the cluster (p=0.007). The most common patient subtype, Cluster 1, showed a moderate quantity and high diversity of commensal microbes with robust metabolic activity, low rates of infection, gene expression indicating alveolar macrophage predominance, and low mortality. The second most common cluster showed a very high burden of airway microbes, gene expression enriched for neutrophil signaling, frequent bacterial infections, and moderate mortality. Cluster 3 showed significant depletion of commensal microbes, a loss of biodiversity, gene expression indicative of fibroproliferative pathways, increased viral and fungal pathogens, and high mortality. Finally, Cluster 4 showed profound microbiome depletion with enrichment of Staphylococci and viruses, gene expression driven by lymphocyte activation and cellular injury, and the highest mortality. BAL clusters were modeled with a random forest classifier and reproduced in a geographically distinct validation cohort of 57 patients from The Netherlands, recapitulating similar cluster-based mortality differences (p=0.022). Degree of antibiotic exposure was strongly associated with depletion of BAL microbes and enrichment of fungi. Potential pathogens were parsed from all detected microbes by analyzing each BAL microbe relative to the overall microbiome composition, which yielded increased sensitivity for numerous previously occult pathogens. These findings support personalized interpretation of the pulmonary microenvironment in pediatric HCT, which may facilitate biology-targeted interventions to improve outcomes.

Cerebellar Ataxia in the Setting of Hashimoto's Thyroiditis: A Case Report Update and Review.

Hashimoto's encephalopathy (HE) is a rare diagnosis. Establishing the diagnosis itself is quite challenging, as symptoms vary among cases and there is still no standard confirmatory test. The clinical presentation is heterogeneous; however, patients with HE most commonly experience focal neurological deficits, frequently accompanied by cognitive dysfunction, aphasia, or paresis. The most widely recommended initial treatment for cases of HE is a course of corticosteroids. Nonetheless, their response varies from patient to patient, and some may become resistant to them. There are many proposed second-line treatments; however, there is little data and no consensus on the best alternative treatment when steroid therapy fails. This article provides an update on a case of cerebellar ataxia in a 30-year-old female patient with Hashimoto's thyroiditis. She initially presented with rapid-onset progressive symptoms of cerebellar ataxia (movement incoordination, dysmetria, and balance problems) and had elevated serum anti-thyroid peroxidase antibodies. She was diagnosed with HE and was initially treated with methylprednisolone. However, her symptoms recurred after tapering steroid therapy, and eventually, they ceased to manage her symptoms, plus she developed steroid-induced osteoporosis. She began treatment with intravenous immunoglobulin (IVIG) as an alternative in April 2022. Since then, she has had four infusions of IVIG that have allowed her to remain symptom-free.

Modeling Preharvest Cyclospora cayetanensis Sampling and Testing for Various Water and Produce Sampling Plans.

As of August 2023, the two U.S. Food and Drug Administration (FDA) official detection methods for C. cayetanensis are outlined in the FDA Bacteriological Analytical Manual (BAM) Chapters 19b (produce testing) and 19c (agricultural water testing). These newly developed detection methods have been shown to not always detect contamination when present at low levels. Yet, industry and regulators may choose to use these methods as part of their monitoring and verification activities while detection methods continue to be improved. This study uses simulation to better understand the performance of these methods for various produce and water sampling plans. To do so, we used published FDA test validation data to fit a logistic regression model that predicts the methods' detection rate given the number of oocysts present in a 10-L agricultural water or 25 g produce sample. By doing so, we were able to determine contamination thresholds at which different numbers of samples (n = 1, 2, 4, 8, 16, and 32) would be adequate for detecting contamination. Furthermore, to evaluate sampling plans in use cases, a simulation was developed to represent C. cayetanensis contamination in agricultural water and on cilantro throughout a 45-day growth cycle. The model included uncertainty around the contamination sources, including scenarios of unintentionally contaminated irrigation water or in-field contamination. The results demonstrate that in cases where irrigation water was the contamination source, frequent water testing proved to be more powerful than produce testing. In scenarios where contamination occurred in-field, conducting frequent produce testing or testing produce toward the end of the season more reliably detected contamination. This study models the power of C. cayetanensis detection methods to understand the sampling plan performance and how these methods can be better used to monitor this emerging food safety hazard.

[Health-related quality of life by IBDQ-32 in colombian patients with inflammatory bowel disease in remission: A cross-sectional study]. / Calidad de vida relacionada con la salud por IBDQ-32 en pacientes colombianos con enfermedad inflamatoria intestinal en remisión: Un estudio de corte transversal.

In Colombia there are no data about perception of quality of life (QoL) in inflammatory bowel disease (IBD). The aim of this study was to determine the perception of QoL by means of the IBDQ-32 questionnaire in patients with IBD from a sample of patients from different referral centers. We carried out a cross-sectional study in adults with IBD in clinical remission, in outpatient follow-up, in 3 institutions in different cities, between June 2022 and November 2022, eligible subjects were identified, information was collected on different dates, about socio-demographic and clinical aspects, and the IBDQ-32 questionnaire was evaluated on one occasion. Descriptive and analytical analysis of the variables evaluated was performed. 80 patients, 70% women, mean age 38.5(range 18-72; SD 13.25) years. 67.5% ulcerative colitis (UC), 32.5% Crohn's disease (CD). Moderate QoL involvement (median 150 points, interquartile range118.3-181.5) was found in IBD, in UC median 151 (interquartile range120-174.75) points, while in CD 133 (interquartile range106.25-186.25) points. There was greater involvement in the systemic domain, with median 21 (interquartile range 15.8-27) points, and 18.5 (interquartile range 12.8-25.3) points, for UC and CD, respectively. The least affected corresponded to the digestive domain and social function, in median UC 48.5 (interquartile range 40-58.3), and 27(interquartile range 20.8-33); in median CD 43 (interquartile range 35.5-61.75) and 24.5(interquartile range 18-32.5), respectively. No statistically significant differences were found. This study provides unique information about QoL of patients with IBD in Colombia. It is necessary to continue reinforcing the accompaniment, support, and education of patients with IBD.

Simulation Evaluation of Power of Sampling Plans to Detect Cronobacter in Powdered Infant Formula Production.

Cronobacteris a hazard in Powdered Infant Formula (PIF) products that is hard to detect due to localized and low-level contamination. We adapted a previously published sampling simulation to PIF sampling and benchmarked industry-relevant sampling plans across different numbers of grabs, total sample mass, and sampling patterns. We evaluated performance to detect published Cronobacter contamination profiles for a recalled PIF batch [42% prevalence, -1.8 ± 0.7 log(CFU/g)] and a reference, nonrecalled, PIF batch [1% prevalence, -2.4 ± 0.8 log(CFU/g)]. Simulating a range of numbers of grabs [n = 1-22,000 (representing testing every finished package)] with 300 g total composite mass showed that taking 30 or more grabs detected contamination reliably (<1% median probability to accept the recalled batch). Benchmarking representative sampling plans ([n = 30, mass grab = 10g], [n = 30, m = 25g], [n = 60, m = 25g], [n = 180, m = 25g]) showed that all plans would reject the recalled batch (<1% median probability to accept) but would rarely reject the reference batch (>50% median probability of acceptance, all plans). Overall, (i) systematic or stratified random sampling patterns are equal to or more powerful than random sampling of the same sample size and total sampled mass, and, (ii) taking more samples, even if smaller, can increase the power to detect contamination.

Leafy Green Farm-to-Customer Process Model Predicts Product Testing Is Most Effective at Detecting Contamination When Conducted Early in the System before Effective Interventions.

Commercial leafy green supply chains often are required to have test and reject (sampling) plans for specific microbial adulterants at primary production or finished product packing for market access. To better understand the impact of this type of sampling, this study simulated the effect of sampling (from preharvest to consumer) and processing interventions (such as produce wash with antimicrobial chemistry) on the microbial adulterant load reaching the system endpoint (customer). This study simulated seven leafy green systems, an optimal system (all interventions), a suboptimal system (no interventions), and five systems where single interventions were removed to represent single process failures, resulting in 147 total scenarios. The all-interventions scenario resulted in a 3.4 log reduction (95% confidence interval [CI], 3.3 to 3.6) of the total adulterant cells that reached the system endpoint (endpoint TACs). The most effective single interventions were washing, prewashing, and preharvest holding, 1.3 (95% CI, 1.2 to 1.5), 1.3 (95% CI, 1.2 to 1.4), and 0.80 (95% CI, 0.73 to 0.90) log reduction to endpoint TACs, respectively. The factor sensitivity analysis suggests that sampling plans that happen before effective processing interventions (preharvest, harvest, and receiving) were most effective at reducing endpoint TACs, ranging between 0.05 and 0.66 log additional reduction compared to systems with no sampling. In contrast, sampling postprocessing (finished product) did not provide meaningful additional reductions to the endpoint TACs (0 to 0.04 log reduction). The model suggests that sampling used to detect contamination was most effective earlier in the system before effective interventions. Effective interventions reduce undetected contamination levels and prevalence, reducing a sampling plan's ability to detect contamination. IMPORTANCE This study addresses the industry and academic need to understand the effect of test-and-reject sampling within a farm-to-customer food safety system. The model developed looks at product sampling beyond the preharvest stage by assessing sampling at multiple stages. This study shows that individual interventions and combined interventions substantially reduce the total adulterant cells reaching the system endpoint. When effective interventions occur during processing, sampling at earlier stages (preharvest, harvest, receiving) has more power to detect incoming contamination than postprocessing sampling, as prevalence and contamination levels are lower. This study reiterates that effective food safety interventions are crucial for food safety. When product sampling is used to test and reject a lot as a preventive control, it may detect critically high incoming contamination. However, if contamination levels and prevalence are low, typical sampling plans will fail to detect contamination.

Calidad de vida relacionada con la salud por IBDQ-32 en pacientes colombianos con enfermedad inflamatoria intestinal en remisión: Un estudio de corte transversal

En Colombia no hay datos acerca de la percepción de la calidad de vida (CdV) en enfermedad infamatoria intestinal (EII). Se plantea como objetivo determinar la percepción de la CdV mediante el cuestionario IBDQ-32 en pacientes con EII a partir de una muestra de pacientes de diferentes centros de referencia. Se realizó un estudio de corte transversal en adultos, con EII en remisión clínica, en seguimiento ambulatorio, en 3 instituciones en diferentes ciudades, entre junio 2022 a noviembre 2022, se identificaron sujetos elegibles, se recolectó información en fechas distintas, acerca aspectos sociodemográficos y clínicos, se evaluó el cuestionario IBDQ-32 en una ocasión y se realizó análisis descriptivo y analítico de las variables evaluadas. Como resultado, se obtuvieron 80 pacientes, 70% mujeres, edad media 38,5 (rango18-72; SD 13,25) años. 67,5% colitis ulcerosa (CU), 32,5% enfermedad de Crohn (EC). Se encontró compromiso moderado de la CdV (mediana 150 puntos, rango-intercuartílico 118,3-181,5) en EII, en CU mediana 151 (rango-intercuartílico 120-174,75) puntos, mientras en EC 133(rango-intercuartílico 106,25-186,25) puntos. Hubo mayor afección en dominio sistémico, con medianas 21 (rango-intercuartílico 15,8-27) puntos, y 18,5 (rango-intercuartílico 12,8-25,3) puntos, para CU y EC, respectivamente. Y, los menos afectados correspondieron al dominio digestivo y función social, en CU medianas 48,5 (rango-intercuartílico 40-58,3), y 27 (rango-intercuartílico 20,8-33); en EC medianas 43 (rango-intercuartílico 35,5-61,75) y 24,5 (rango-intercuartílico 18-32,5), respectivamente. No se encontraron diferencias estadísticamente significativas. Este estudio aporta información única acerca CdV de los pacientes con EII en Colombia. Se requiere seguir reforzando el acompañamiento, apoyo, y educación a los pacientes con EII.

In Colombia there are no data about perception of quality of life (QoL) in inflammatory bowel disease (IBD). The aim of this study was to determine the perception of QoL by means of the IBDQ-32 questionnaire in patients with IBD from a sample of patients from different referral centers. We carried out a cross-sectional study in adults with IBD in clinical remission, in outpatient follow-up, in 3 institutions in different cities, between June 2022 and November 2022, eligible subjects were identified, information was collected on different dates, about socio-demographic and clinical aspects, and the IBDQ-32 questionnaire was evaluated on one occasion. Descriptive and analytical analysis of the variables evaluated was performed. 80 patients, 70% women, mean age 38.5(range 18-72; SD 13.25) years. 67.5% ulcerative colitis (UC), 32.5% Crohn´s disease (CD). Moderate QoL involvement (median 150 points, interquartile range118.3-181.5) was found in IBD, in UC median 151 (interquartile range120-174.75) points, while in CD 133 (interquartile range106.25-186.25) points. There was greater involvement in the systemic domain, with median 21 (interquartile range 15.8-27) points, and 18.5 (interquartile range 12.8-25.3) points, for UC and CD, respectively. The least affected corresponded to the digestive domain and social function, in median UC 48.5 (interquartile range 40-58.3), and 27(interquartile range 20.8-33); in median CD 43 (interquartile range 35.5-61.75) and 24.5(interquartile range 18-32.5), respectively. No statistically significant differences were found. This study provides unique information about QoL of patients with IBD in Colombia. It is necessary to continue reinforcing the accompaniment, support, and education of patients with IBD.

Características clínicas y tratamiento de la enfermedad de Crohn perianal fistulizante en Colombia: resultados de un registro multicéntrico / Clinical characteristics and treatment of perianal fistulising Crohn's disease in Colombia: Results of a multicentric registry

Introducción: La enfermedad de Crohn (EC) perianal fistulizante es un fenotipo de mal pronóstico. No existen estudios en nuestro medio. Nuestro objetivo es determinar las características clínicas, sociodemográficas y el tratamiento de la EC perianal fistulizante en un registro multicéntrico colombiano. Materiales y métodos: Se realizó un estudio observacional multicéntrico, retrospectivo, con recolección prospectiva de la información, en los principales centros de referencia de enfermedad inflamatoria intestinal (EII) del país. Las variables continuas se expresaron como medianas y rangos intercuartílicos. Las variables de resultado categóricas fueron comparados por la prueba de Chi-cuadrado. Resultados: Se documentaron 65 pacientes con EC perianal fistulizante, con una mediana de edad de aparición de fistula perianal de 31,0 años (rango: 24-42), predominando en hombres (61,5%; razón H:M: 1,4:1). Las fístulas perianales complejas fueron más frecuentes que las simples (75,35 vs. 24,6%). En cuanto al tratamiento médico, el 66,2% de los pacientes recibieron antibióticos, el 64,6% esteroides, el 78,5% terapia biológica, el 47,7% setones no cortantes y el 46,2% requirieron manejo quirúrgico, diferente a la colocación de setones. En solo el 29,2% se logró remisión completa de la fístula, y el 9,2% de los pacientes terminaron en colostomía definitiva. Los pacientes con EC con fístulas complejas recibieron más terapia biológica comparado con pacientes con EC y fístulas simples (84,8 vs. 56,3%; p: 0,038). Conclusiones: La EC perianal fistulizante es de mal pronóstico en nuestro medio, solo 3 de cada 10 pacientes logran la remisión completa a pesar del tratamiento. Un manejo multidisciplinario es fundamental para el manejo integral de esta difícil enfermedad.(AU)

Introduction: Perianal fistulizing Crohn's disease (CD) is a phenotype with a poor prognosis. There are no studies in our country. Our objective is to determine the clinical, sociodemographic and treatment characteristics of perianal fistulizing CD in a Colombian multicenter registry. Materials and methods: A retrospective, multicenter observational study was carried out, with prospective data collection, in the main reference centers for inflammatory Bowel disease (IBD) in the country. Continuous variables were expressed as medians and interquartile ranges. The categorical outcome variables were compared by the Chi-square test. Results: Sixty-five patients with perianal fistulizing CD were documented, with a median age of appearance of perianal fistula of 31.0 years (range: 24-42), predominantly in men (61.5%; H:M ratio: 1.4:1). Complex perianal fistulas were more frequent than simple ones (75.35 vs. 24.6%). Regarding medical treatment, 66.2% of the patients received antibiotics, 64.6% steroids, 78.5% biological therapy, 47.7% non-cutting setons, and 46.2% required surgical management, other than seton placement. Only 29.2% achieved complete remission of the fistula, and 9.2% of the patients ended up in a definitive colostomy. CD patients with complex fistulas received more biological therapy, compared to CD patients with simple fistulas (84.8 vs. 56.3%; P: 0.038). Conclusions: Perianal fistulizing CD has a poor prognosis in our setting, only 3 out of 10 patients achieve complete remission despite treatment. A multidisciplinary management is essential for the comprehensive management of this difficult pathology.(AU)

Clinical characteristics and treatment of perianal fistulising Crohn's disease in Colombia: Results of a multicentric registry. / Características clínicas y tratamiento de la enfermedad de Crohn perianal fistulizante en Colombia: resultados de un registro multicéntrico.

INTRODUCTION: Perianal fistulizing Crohn's disease (CD) is a phenotype with a poor prognosis. There are no studies in our country. Our objective is to determine the clinical, sociodemographic and treatment characteristics of perianal fistulizing CD in a Colombian multicenter registry. MATERIALS AND METHODS: A retrospective, multicenter observational study was carried out, with prospective data collection, in the main reference centers for inflammatory Bowel disease (IBD) in the country. Continuous variables were expressed as medians and interquartile ranges. The categorical outcome variables were compared by the Chi-square test. RESULTS: Sixty-five patients with perianal fistulizing CD were documented, with a median age of appearance of perianal fistula of 31.0 years (range: 24-42), predominantly in men (61.5%; H:M ratio: 1.4:1). Complex perianal fistulas were more frequent than simple ones (75.35 vs. 24.6%). Regarding medical treatment, 66.2% of the patients received antibiotics, 64.6% steroids, 78.5% biological therapy, 47.7% non-cutting setons, and 46.2% required surgical management, other than seton placement. Only 29.2% achieved complete remission of the fistula, and 9.2% of the patients ended up in a definitive colostomy. CD patients with complex fistulas received more biological therapy, compared to CD patients with simple fistulas (84.8 vs. 56.3%; P: 0.038). CONCLUSIONS: Perianal fistulizing CD has a poor prognosis in our setting, only 3 out of 10 patients achieve complete remission despite treatment. A multidisciplinary management is essential for the comprehensive management of this difficult pathology.

Pulmonary microbiome and gene expression signatures differentiate lung function in pediatric hematopoietic cell transplant candidates.

Impaired baseline lung function is associated with mortality after pediatric allogeneic hematopoietic cell transplantation (HCT), yet limited knowledge of the molecular pathways that characterize pretransplant lung function has hindered the development of lung-targeted interventions. In this study, we quantified the association between bronchoalveolar lavage (BAL) metatranscriptomes and paired pulmonary function tests performed a median of 1 to 2 weeks before allogeneic HCT in 104 children in The Netherlands. Abnormal pulmonary function was recorded in more than half the cohort, consisted most commonly of restriction and impaired diffusion, and was associated with both all-cause and lung injury-related mortality after HCT. Depletion of commensal supraglottic taxa, such as Haemophilus, and enrichment of nasal and skin taxa, such as Staphylococcus, in the BAL microbiome were associated with worse measures of lung capacity and gas diffusion. In addition, BAL gene expression signatures of alveolar epithelial activation, epithelial-mesenchymal transition, and down-regulated immunity were associated with impaired lung capacity and diffusion, suggesting a postinjury profibrotic response. Detection of microbial depletion and abnormal epithelial gene expression in BAL enhanced the prognostic utility of pre-HCT pulmonary function tests for the outcome of post-HCT mortality. These findings suggest a potentially actionable connection between microbiome depletion, alveolar injury, and pulmonary fibrosis in the pathogenesis of pre-HCT lung dysfunction.

Hereditary hemorrhagic telangiectasia diagnosed by enteroscopy: a case report.

Hereditary hemorrhagic telangiectasia (HHT) is a very rare autosomal dominant multisystemic disease. Patients with this disease usually present with punctate mucocutaneous telangiectasias and arteriovenous malformations. The diagnostic criteria currently in use are the Curaçao criteria. HHT is considered a clinical diagnosis; thus, no imaging or preclinical laboratory is mandatory, and diagnosis and management are performed according to the experience of the treating team. We herein describe a 58-year-old man with no significant medical history who presented with a 15-day history of intermittent hematochezia. He was admitted to the hospital and underwent a series of laboratory tests, including colonoscopy, which showed normal results. Therefore, the patient was discharged with a diagnosis of gastrointestinal bleeding. During his second visit to the emergency room, the doctors requested video capsule endoscopy because of the patient's history, and a diagnosis of HHT was made. The entire approach and treatment were completed with antegrade double-balloon enteroscopy. This case highlights the importance of endoscopic methods for timely diagnosis and proper management.

Using Qualitative Interviews to Better Understand Differences in How Local Health Departments Inspect School Share Tables.

ABSTRACT: Environmental and health advocates are increasingly promoting food donations to reduce landfilled food waste and feed hungry people. Share tables are locations where students can put unwanted school food or beverage items, allowing their uneaten food items to be "shared" with other students and providing food donation opportunities for the 4.9 billion lunches served annually in the U.S. National School Lunch Program. The purpose of this qualitative study was to identify differences in health inspector interpretations of the Food Code as it relates to share table operations and risk mitigation techniques preferred by inspectors for preventing foodborne illness from recovered food. A snowball sampling technique was used to identify Illinois health inspectors (n = 13) engaged in share table inspections. Telephone interviews were audio recorded and transcribed verbatim. The transcripts were coded using a hybrid process of deductive and inductive content analysis. Participants considered contamination, rather than temperature abuse, to be the primary risk factor for foodborne illness. Those participants with permissive Food Code interpretations considered contamination risk in the context of the overall school environment. Participants had the lowest degree of consensus on whether to allow whole apple recovery via a share table. Participants also lacked consensus on reuse of unclaimed share table items in future meal programs (reservice). This lack of consensus indicates that further research is needed to develop data-driven strategies to assess and manage the microbial risks associated with share tables and ultimately to facilitate increased food recovery.

The pulmonary metatranscriptome prior to pediatric HCT identifies post-HCT lung injury.

Lung injury after pediatric allogeneic hematopoietic cell transplantation (HCT) is a common and disastrous complication that threatens long-term survival. To develop strategies to prevent lung injury, novel tools are needed to comprehensively assess lung health in HCT candidates. Therefore, this study analyzed biospecimens from 181 pediatric HCT candidates who underwent routine pre-HCT bronchoalveolar lavage (BAL) at the University Medical Center Utrecht between 2005 and 2016. BAL fluid underwent metatranscriptomic sequencing of microbial and human RNA, and unsupervised clustering and generalized linear models were used to associate microbiome gene expression data with the development of post-HCT lung injury. Microbe-gene correlations were validated using a geographically distinct cohort of 18 pediatric HCT candidates. The cumulative incidence of post-HCT lung injury varied significantly according to 4 pre-HCT pulmonary metatranscriptome clusters, with the highest incidence observed in children with pre-HCT viral enrichment and innate immune activation, as well as in children with profound microbial depletion and concomitant natural killer/T-cell activation (P < .001). In contrast, children with pre-HCT pulmonary metatranscriptomes containing diverse oropharyngeal taxa and lacking inflammation rarely developed post-HCT lung injury. In addition, activation of epithelial-epidermal differentiation, mucus production, and cellular adhesion were associated with fatal post-HCT lung injury. In a separate validation cohort, associations among pulmonary respiratory viral load, oropharyngeal taxa, and pulmonary gene expression were recapitulated; the association with post-HCT lung injury needs to be validated in an independent cohort. This analysis suggests that assessment of the pre-HCT BAL fluid may identify high-risk pediatric HCT candidates who may benefit from pathobiology-targeted interventions.

Criptococosis pulmonar en un paciente con colitis ulcerativa tratado con prednisolona y azatioprina / Pulmonary cryptococcosis in a patient with ulcerative colitis treated with prednisolone and azathioprine

Resumen La enfermedad inflamatoria intestinal comprende la enfermedad de Crohn (EC) y la colitis ulcerativa (CU). Esta última es una patología crónica caracterizada por una inflamación difusa de la mucosa colónica, que afecta el recto y se extiende de forma proximal. Su curso clínico es intermitente, con exacerbaciones y remisiones. Su tratamiento, por lo general, es farmacológico, con corticoides, inmunomoduladores e inhibidor del factor de necrosis tumoral (anti tumor necrosis factor, TNF), los cuales causan un estado de inmunosupresión en el paciente, que puede asociarse en algunos casos a infecciones oportunistas. En la literatura se describe la aparición de la criptococosis pulmonar en pacientes con infección por el virus de inmunodeficiencia humana (VIH). En otros casos se asocia al tratamiento farmacológico de pacientes con EC, así como con otras infecciones oportunistas, tales como la tuberculosis y el herpes. Presentamos uno de los primeros casos de criptococosis pulmonar en un paciente con diagnóstico de colitis ulcerativa, quien recibió tratamiento escalonado con salicilatos, inmunomoduladores y terapia biológica. La infección fue documentada clínica, radiológica e histológicamente. El paciente recibió el tratamiento adecuado y presentó una evolución satisfactoria.

Abstract Inflammatory bowel disease comprises Crohn's disease (CD) and ulcerative colitis (UC), the latter being a chronic disease characterized by diffuse inflammation of the colonic mucosa that affects the rectum and extends proximally. Its clinical course is intermittent with exacerbations and remissions and its treatment is generally pharmacological, with steroids, immunomodulators, and anti-tumor necrosis factor inhibitors (TNF), which cause the patient to be in a state of immunosuppression associated, in some cases, with opportunistic infections. The literature describes the occurrence of pulmonary cryptococcosis in patients with human immunodeficiency virus (HIV) infection, in cases associated with drug treatment of patients with CD, as well as with other opportunistic infections such as tuberculosis and herpes. This is one of the first cases of pulmonary cryptococcosis reported in a patient diagnosed with ulcerative colitis, who received step therapy with salicylates, immunomodulators, and biological therapy. The infection was documented clinically, radiologically, and histologically. The patient received the appropriate treatment and had a satisfactory evolution.

Synthesis of UV-11 MOF and Its Characterization by Cyclic Voltammetry.

In this work a Metal-Organic Framework (MOF) was prepared using a solvothermal method, taking as precursors 1. 2-di-(4-pyridyl)-ethylene, 1.2.4.5-benzenetetracarboxylic acid and Co(No3)2-6H2O. This MOF was called UV-11 and was evaluated using microscopic, spectroscopic and electrochemical techniques. According to the obtained results, the melting point of the compound is located in a higher interval than its precursors. Stereoscopic microscopy analysis shows the presence of pink crystals in the form of needles. MEB technique displays a laminar morphology as well as crystals with approximate sizes (36 mm wide and 150 mm long). EDS analysis corroborated the presence of precursor elements such as cobalt, carbon and oxygen. Furthermore, the XRD technique shows the cobalt-related phases in the sample, which is cobalt bis (pyridine-6-carboxylic-2-carboxylate). A modified carbon paste electrode was prepared using MOF UV-11 and by cyclic voltammetry electrochemical technique, semi-reversible redox processes are identified, as well as thermodynamic and kinetic parameters were obtained with the Laviron equation, and electrochemical performance properties from the cyclic voltammetry experimental data.