Gastrointestinal bleeding in a kidney transplant recipient.

Opportunistic infections are common in transplant recipients, but gastrointestinal bleed is rarely reported to be due to opportunistic fungal infections, and hence could present as a diagnostic challenge. We report a case of disseminated histoplasmosis in a kidney transplant recipient whose initial presentation was acute lower gastrointestinal bleeding with no other symptoms. The colonoscopy showed scattered punchout circular colonic ulcers with biopsy revealing budding yeasts consistent with a diagnosis of histoplasmosis. The patient was successfully treated with a prolonged course of intravenous amphotericin B followed by oral itraconazole.

Pérdida de peso no intencionada, un diagnóstico de patología orgánica con costos a la salud.

No disponible.

Genomic Analysis Enlightens Agaricales Lifestyle Evolution and Increasing Peroxidase Diversity.

As actors of global carbon cycle, Agaricomycetes (Basidiomycota) have developed complex enzymatic machineries that allow them to decompose all plant polymers, including lignin. Among them, saprotrophic Agaricales are characterized by an unparalleled diversity of habitats and lifestyles. Comparative analysis of 52 Agaricomycetes genomes (14 of them sequenced de novo) reveals that Agaricales possess a large diversity of hydrolytic and oxidative enzymes for lignocellulose decay. Based on the gene families with the predicted highest evolutionary rates-namely cellulose-binding CBM1, glycoside hydrolase GH43, lytic polysaccharide monooxygenase AA9, class-II peroxidases, glucose-methanol-choline oxidase/dehydrogenases, laccases, and unspecific peroxygenases-we reconstructed the lifestyles of the ancestors that led to the extant lignocellulose-decomposing Agaricomycetes. The changes in the enzymatic toolkit of ancestral Agaricales are correlated with the evolution of their ability to grow not only on wood but also on leaf litter and decayed wood, with grass-litter decomposers as the most recent eco-physiological group. In this context, the above families were analyzed in detail in connection with lifestyle diversity. Peroxidases appear as a central component of the enzymatic toolkit of saprotrophic Agaricomycetes, consistent with their essential role in lignin degradation and high evolutionary rates. This includes not only expansions/losses in peroxidase genes common to other basidiomycetes but also the widespread presence in Agaricales (and Russulales) of new peroxidases types not found in wood-rotting Polyporales, and other Agaricomycetes orders. Therefore, we analyzed the peroxidase evolution in Agaricomycetes by ancestral-sequence reconstruction revealing several major evolutionary pathways and mapped the appearance of the different enzyme types in a time-calibrated species tree.

Association of neutrophil-to-lymphocyte and lymphocyte-to-C-reactive protein ratios with COVID-19-related mortality.

INTRODUCTION: Neutrophil-to-lymphocyte (NLR) and lymphocyte-to-C-reactive protein (LCR) ratios are used to predict severity and mortality in various infections. OBJECTIVE: To establish the best NLR and LCR cutoff point to predict mortality in patients hospitalized for COVID-19 in Mexico. METHOD: Analytical cross-sectional study of patients hospitalized for severe COVID-19 in a specialty hospital. RESULTS: Out of 242 analyzed patients, 34 % died. The deceased subjects were older (62 vs. 51 years; p < 0.001), had a higher prevalence of > 10 years with systemic arterial hypertension (59.4 vs. 45.1 %, p = 0.022), as well as a higher NLR (17.66 vs. 8.31, p < 0.001) and lower LCR (0.03 vs. 0.06, p < 0.002) with regard to those who survived. The cutoff points to predict mortality were NLR > 12 and LCR < 0.03. The combination of NLR/LCR had a sensitivity of 80 %, specificity of 74 %, positive predictive value of 46.15 %, negative predictive value of 93.02 % and an odds ratio of 11.429 to predict mortality. CONCLUSION: NLR > 12 and LCR < 0.03 are useful biomarkers to evaluate the risk of mortality in Mexican patients with severe COVID- 19. INTRODUCCIÓN: Los índices neutrófilo/linfocito (INL) y linfocito/proteína C reactiva (ILR) se usan para predecir severidad y mortalidad en diversas infecciones. OBJETIVO: Establecer en México el mejor punto de corte de INL e ILR para predecir la mortalidad en pacientes hospitalizados por COVID-19. MÉTODO: Estudio transversal analítico de pacientes hospitalizados por COVID-19 grave en un hospital de especialidades. RESULTADOS: Falleció 34 % de 242 pacientes analizados. Los sujetos fallecidos tenían mayor edad (62 versus 51 años, p < 0.001), mayor prevalencia de hipertensión arterial sistémica > 10 años (59.4 versus 45.1 %, p = 0.022), así como INL más alto (17.66 versus 8.31, p < 0.001) e ILR más bajo (0.03 versus 0.06, p < 0.002) respecto a quienes sobrevivieron. Los puntos de corte para predecir mortalidad fueron INL > 12 e ILR < 0.03. La combinación de INL e ILR tuvo sensibilidad de 80 %, especificidad de 74 %, valor predictivo positivo de 46.15 %, valor predictivo negativo de 93.02 % y razón de momios de 11.429 para predecir la mortalidad. CONCLUSIÓN: INL > 12 e ILR < 0.03 son biomarcadores útiles para evaluar el riesgo de mortalidad en pacientes mexicanos con COVID-19 grave.

5-gene differential expression predicts stability of human intestinal allografts.

In intestinal allografts, endoscopy and histology detect the injury once changes in the bowel wall architecture have occurred. We aimed to identify a molecular signature that could predict early deterioration, within histologically indistinguishable biopsies with "minimal changes" (MC) pathology. Sixty biopsies from 12 adult recipients were longitudinally taken during 8years post-transplant. They were classified as either stable (STA) or non-stable (NSTA) according to the prospectively recorded number, frequency and severity of rejection events of the allograft. In a discovery set of MC samples analyzed by RNA-Seq, 816 genes were differentially expressed in STA vs NSTA biopsies. A group of 5 genes (ADH1C, SLC39A4, CYP4F2, OPTN and PDZK1) correctly classified all NSTA biopsies in the discovery set and all STA biopsies from an independent set. These results were validated by qPCR in a new group of MC biopsies. Based on a logistic regression model, a cutoff of 0.28 predicted the probability of being a NSTA biopsy with 85% sensitivity and 69% specificity. In conclusion, by analyzing MC samples early after transplantation, the expression of a 5-gene set may predict the evolution of the bowel allograft. This prognostic biomarker may be of help to personalize care of the intestinal transplant recipient.

Development of a novel multiplex beads-based assay for autoantibody detection for colorectal cancer diagnosis.

Humoral response in cancer patients can be used for early cancer detection. By screening high-density protein microarrays with sera from colorectal cancer (CRC) patients and controls, we identified 16 tumor-associated antigens (TAAs) exhibiting high diagnostic value. This high number of TAAs requires the development of multiplex assays combining different antigens for a faster and more accurate prediction of CRC. Here, we have developed and optimized a bead-based assay using nine selected TAAs and two controls to provide a multiplex test for early CRC diagnosis. We screened a collection of 307 CRC patients' and control sera with the beads assay to identify and validate the best TAA combination for CRC detection. The multiplex bead-based assay exhibited a similar diagnostic performance to detect the humoral response in comparison to multiple ELISA analyses. After multivariate analysis, a panel composed of GTF2B, EDIL3, HCK, PIM1, STK4, and p53, together with gender and age, was identified as the best combination of TAAs for CRC diagnosis, achieving an AUC of 89.7%, with 66% sensitivity at 90.0% fixed specificity. The model was validated using bootstrapping analysis. In summary, we have developed a novel multiplex bead assay that after validation with a larger independent cohort of sera could be utilized in a high-throughput manner for population screening to facilitate the detection of early CRC patients.

Ethics competences in the undergraduate medical education curriculum: the Spanish experience.

Aim .To investigate if there are differences in medical ethics education between different schools of medicine in Spain, specifically between private and public schools and between recently founded schools and older ones. METHOD: The curricula of medical degrees from all Spanish faculties were reviewed for the 2014/2015 academic year, identifying subjects concerning bioethics, deontology, and ethics. We identified the type of teaching, format and method of the course, the number of credits and hours, and the school year of each subject. An analysis with descriptive parameters and the Cohen's coefficient (d) was performed. RESULTS: All medical schools in Spain (n=44) were included. A mean of 3.64 European Credit Transfer and Accumulation System (ECTS) credits was specifically devoted to ethical values teaching in Spain. Private medical schools offered more credits than public ones (6.51 ECTS vs 2.88 ECTS, relevant difference: d=2.06>>0.8), and the 10 most recently founded medical schools offered more credits than the 10 oldest (5.86 ECTS vs 2.63 ECTS, relevant difference: d=1.43>0.8). A mean of 36.75 hours was dedicated to ethics education. CONCLUSIONS: Although ethics education is incorporated into the training of future Spanish physicians, there is still notable heterogeneity between different medical schools in the time devoted to this topic.

[Communication skills in the curriculum of Medical students from Spain (1990-2014): From the Primary Health Care to the Bologna Plan. A descriptive study]. / Competencia en comunicación en el currículo del estudiante de Medicina de España (1990-2014): de la Atención Primaria al Plan Bolonia. Un estudio descriptivo.

OBJECTIVES: Analyse the currently situation of teaching in communication skills in the Spanish Medical Schools (MS) and the grade of implementation from the recommended by the National Agency of Evaluation of the Quality and Accreditation. DESIGN: Descriptive-comparative, transversal and quantitative-qualitative study. SITUATION: University teaching field. SAMPLE: The whole population of MS in Spain. INCLUSION CRITERIA: teaching during the academic year 2013-2014 the Degree in Medicine homologated by the National Agency of Evaluation of the Quality and Accreditation and offering information of their educational plans and teaching guides (online, telephonic or e-mail). VARIABLES: 1) Existence of courses about communication skills; 2) type of teaching; 3) format of the course; 4) credits; 5) length, and 6) grade. They were analysed with descriptive parameters and the Cohen's coefficient (d). RESULTS: Forty-two MS: 10 privates and 32 publics. Thirty MS (71.43%) presented at least one course of communication skills. The 78.12% of the public MS contained this kind of teaching as an entire course versus the 50.00% of the private MS. The national average by MS was 2.77 (σ=2.41), lower than the 5.0 credits recommended by the the National Agency of Evaluation of the Quality and Accreditation (relevant difference: d=1.63>>0,8). The 63.63% contained this teaching over the second cycle (mode: second degree). CONCLUSIONS: The course loads in terms of credits destined to this skills has increased considerably from 1990 to 2014 (d= 1,43>>0,8). However, it has not been completely established yet the recommendations about this aspect in most of the Spanish MS. The public universities seem to be more aware of this teaching. Furthermore, it would be interesting strengthen this skills in the sixth grade.

Potential biomarkers for fatal outcome prognosis in a cohort of hospitalized COVID-19 patients with pre-existing comorbidities.

The difficulty in predicting fatal outcomes in patients with coronavirus disease 2019 (COVID-19) impacts the general morbidity and mortality due to severe acute respiratory syndrome-coronavirus 2 infection, as it wears out the hospital services that care for these patients. Unfortunately, in several of the candidates for prognostic biomarkers proposed, the predictive power is compromised when patients have pre-existing comorbidities. A cohort of 147 patients hospitalized for severe COVID-19 was included in a descriptive, observational, single-center, and prospective study. Patients were recruited during the first COVID-19 pandemic wave (April-November 2020). Data were collected from the clinical history whereas immunophenotyping by multiparameter flow cytometry analysis allowed us to assess the expression of surface markers on peripheral leucocyte. Patients were grouped according to the outcome in survivors or non-survivors. The prognostic value of leucocyte, cytokines or HLA-DR, CD39, and CD73 was calculated. Hypertension and chronic renal failure but not obesity and diabetes were conditions more frequent among the deceased patient group. Mixed hypercytokinemia, including inflammatory (IL-6) and anti-inflammatory (IL-10) cytokines, was more evident in deceased patients. In the deceased patient group, lymphopenia with a higher neutrophil-lymphocyte ratio (NLR) value was present. HLA-DR expression and the percentage of CD39+ cells were higher than non-COVID-19 patients but remained similar despite the outcome. Receiver operating characteristic analysis and cutoff value of NLR (69.6%, 9.4), percentage NLR (pNLR; 71.1%, 13.6), and IL-6 (79.7%, 135.2 pg/mL). The expression of HLA-DR, CD39, and CD73, as many serum cytokines (other than IL-6) and chemokines levels do not show prognostic potential, were compared to NLR and pNLR values.

Health coaching to improve hypertension treatment in a low-income, minority population.

PURPOSE: Poor blood pressure control is common in the United States. We conducted a study to determine whether health coaching with home titration of antihypertensive medications can improve blood pressure control compared with health coaching alone in a low-income, predominantly minority population. METHODS: We randomized 237 patients with poorly controlled hypertension at a primary care clinic to receive either home blood pressure monitoring, weekly health coaching, and home titration of blood pressure medications if blood pressures were elevated (n = 129) vs home blood pressure monitoring and health coaching but no home titration (n = 108). The primary outcome was change in systolic blood pressure from baseline to 6 months. RESULTS: Both the home-titration arm and the no-home-titration arm had a reduction in systolic blood pressure, with no significant difference between them. When both arms were combined and analyzed as a before-after study, there was a mean decrease in systolic blood pressure of 21.8 mm Hg (P <.001) as well as a decrease in the number of primary care visits from 3.5 in the 6 months before the study to 2.6 during the 6-month study period (P <.001) and 2.4 in the 6 months after the study (P <.001). The more coaching encounters patients had, the greater their reduction in blood pressure. CONCLUSIONS: Blood pressure control in a low-income, minority population can be improved by teaching patients to monitor their blood pressure at home and having nonprofessional health coaches assist patients, in particular, by counseling them on medication adherence. The improved blood pressure control can be achieved while reducing the time spent by physicians.

Differences in mortality rate among patients hospitalized with severe COVID-19 according to their body mass index.

Background: Obesity has been described as a risk factor for COVID-19 severity and mortality. Previous studies report a linear association between BMI and adverse outcomes, meanwhile in other critical illness, excessive fat tissue is related to improved survival. Whether different BMI is related with the survival of patients with severe COVID-19 deserves further analysis. Objective: To determine the mortality rate among hospitalized patients with severe COVID-19 stratified according to BMI. Methods: The clinical files of all patients hospitalized from March to December 2020 with a positive PCR test for SARS-CoV-2 discharged due to improvement or death, were analyzed. A mixed effects logistic regression was carried out to determine which clinical and biochemical characteristics and comorbidities were associated with in-hospital mortality. Results: The cohort consisted of 608 patients with a median age of 59 years (interquartile ranges, IQR 46-69 years), median BMI of 28.7 kg/m2 (IQR 25.4-32.4 kg/m2), 65.5% were male. In-hospital mortality rate was 43.4%. Of the cohort 0.8% had low weight, 20.9% normal weight, 36.0% overweight, 26.5% obesity grade I, 10.2% obesity grade II and 5.6% obesity grade III. Mortality rate was highest in patients with low weight (80%), followed by patients with obesity grade III (58.8%) and grade II (50.0%). Overweight and underweight/obesity grade III were associated with higher mortality (OR of 9.75 [1.01-1.10] and OR 4.08 [1.64-10.14]), after adjusting by sex and age. Conclusions: The patients in the underweight/overweight and grade 3 obesity categories are at higher risk of COVID-19 related mortality, compared to those with grade I or II obesity.

Increased expression of hypoxia-induced factor 1α mRNA and its related genes in myeloid blood cells from critically ill COVID-19 patients.

BACKGROUND: COVID-19 counts 46 million people infected and killed more than 1.2 million. Hypoxaemia is one of the main clinical manifestations, especially in severe cases. HIF1α is a master transcription factor involved in the cellular response to oxygen levels. The immunopathogenesis of this severe form of COVID-19 is poorly understood. METHODS: We performed scRNAseq from leukocytes from five critically ill COVID-19 patients and characterized the expression of hypoxia-inducible factor1α and its transcriptionally regulated genes. Also performed metanalysis from the publicly available RNAseq data from COVID-19 bronchoalveolar cells. RESULTS: Critically-ill COVID-19 patients show a shift towards an immature myeloid profile in peripheral blood cells, including band neutrophils, immature monocytes, metamyelocytes, monocyte-macrophages, monocytoid precursors, and promyelocytes-myelocytes, together with mature monocytes and segmented neutrophils. May be the result of a physiological response known as emergency myelopoiesis. These cellular subsets and bronchoalveolar cells express HIF1α and their transcriptional targets related to inflammation (CXCL8, CXCR1, CXCR2, and CXCR4); virus sensing, (TLR2 and TLR4); and metabolism (SLC2A3, PFKFB3, PGK1, GAPDH and SOD2). CONCLUSIONS: The up-regulation and participation of HIF1α in events such as inflammation, immunometabolism, and TLR make it a potential molecular marker for COVID-19 severity and, interestingly, could represent a potential target for molecular therapy. Key messages Critically ill COVID-19 patients show emergency myelopoiesis. HIF1α and its transcriptionally regulated genes are expressed in immature myeloid cells which could serve as molecular targets. HIF1α and its transcriptionally regulated genes is also expressed in lung cells from critically ill COVID-19 patients which may partially explain the hypoxia related events.

A Shift Towards an Immature Myeloid Profile in Peripheral Blood of Critically Ill COVID-19 Patients.

BACKGROUND: SARS-CoV-2, the etiological agent causing COVID-19, has infected more than 27 million people with over 894000 deaths worldwide since its emergence in December 2019. Factors for severe diseases, such as diabetes, hypertension, and obesity have been identified however, the precise pathogenesis is poorly understood. To understand its pathophysiology and to develop effective therapeutic strategies, it is essential to define the prevailing immune cellular subsets. METHODS: We performed whole circulating immune cells scRNAseq from five critically ill COVID-19 patients, trajectory and gene ontology analysis. RESULTS: Immature myeloid populations, such as promyelocytes-myelocytes, metamyelocytes, band neutrophils, monocytoid precursors, and activated monocytes predominated. The trajectory with pseudotime analysis supported the finding of immature cell states. While the gene ontology showed myeloid cell activation in immune response, DNA and RNA processing, defense response to the virus, and response to type 1 interferon. Lymphoid lineage was scarce. Expression of genes such as C/EBPß, IRF1and FOSL2 potentially suggests the induction of trained immunity. CONCLUSIONS: Our results uncover transcriptomic profiles related to immature myeloid lineages and suggest the potential induction of trained immunity.

Sacroilitis paraneoplásica: presentación inusual de leucemia linfoblástica aguda.

La sacroilitis es una manifestación poco común de neoplasias hematológicas. Reportamos el caso de una mujer de 40 años que presentó un cuadro de 1 mes de evolución con fiebre y sacroilitis simulando espondiloartritis, acompañado de anemia, hepatomegalia y elevación de marcadores inflamatorios. El abordaje descartó infecciones y causas inflamatorias de dolor sacroilíaco. Los hallazgos en la médula ósea llevaron al diagnóstico de leucemia linfoblástica aguda (LLA) de células B. Hasta donde sabemos, el presente es uno de los pocos casos publicados de LLA que se manifiesta con sacroilitis. La sacroilitis como manifestación inicial de LLA puede resultar en un diagnóstico erróneo, por lo que el diagnóstico diferencial es esencial cuando se encuentran presentes características atípicas.Sacroiliitis is an uncommon manifestation of hematological malignancies. We herein report the case of a 40-year-old female that presented with a one-month-old history of fever and sacroiliitis mimicking spondylarthritis, accompanied by anemia, hepatomegaly, and elevated inflammatory markers. Work-up ruled out infectious and inflammatory causes of sacroiliac pain. Bone marrow findings led to the diagnosis B-cell acute lymphoblastic leukemia (ALL). To the best of our knowledge, the current study represents one of the few published cases of ALL presenting with sacroiliitis. Sacroiliitis as an onset manifestation of ALL may result in misdiagnosis, therefore, a differential diagnosis is essential when atypical features are present.

Communication skills training in undergraduate nursing programs in Spain.

OBJECTIVES: of the present cross sectional study were to analyze the offer of subjects with communication skills in the nursing degree in Spain and to describe the distribution of these subjects. Documentary, systematic and independent search of web pages from Spanish universities was carried out to collect the following variables: subjects with communication skills, course in which the subject is taught, type of teaching (exclusive or combined), type of subject (compulsory or optional) and number of credits on communication skills. Although an average of 3.6 subjects per center was offered, most of the subjects were combined and with little communication content load. In one third of the centers, the offer was below 2.3 credits. Only 1 in 6 centers had exclusive communication skills subjects, and a quarter of them were optional. The teaching load of communication contents was highest in optional subjects. The offer of communication skills contents in Spanish Nursing Schools was scarce and very heterogeneous between centers and between courses in a center, with excessive presence of combined and optional subjects. Our results may be useful when developing the teaching guides for subjects with communication skills, as well as when defining communication competencies in the different Nursing Schools.

Prone position in non-intubated patient with COVID-19 as a maneuver to avoid intubation. / Posición prono en paciente no intubado con COVID-19 como maniobra para evitar la intubación.

BACKGROUND: The COVID-19 (from Coronavirus Disease 2019) is a disease that has generated a pandemic that has affected the world, Mexico included. The spectrum of the disease ranges from asymptomatic infection to severe acute respiratory distress syndrome (ARDS). The objective of the case is to demonstrate the usefulness of the prone position in non-intubated patients. CLINICAL CASE: We present the case of a woman without comorbidities with COVID-19 and moderate ARDS, in whom intubation was avoided after improvement with the prone position, as determined by arterial oxygen saturation by pulse oximetry and by the relationship of arterial oxygen pressure and the fraction of inspired oxygen (PaO2/FiO2). CONCLUSION: There is scarce evidence of this therapeutic maneuver in awake patients. However, it can help to improve oxygenation and to avoid intubation in these patients.

INTRODUCCIÓN: la COVID-19 (del inglés Coronavirus Disease 2019) es una enfermedad que ha generado una pandemia, la cual ha afectado a todo el mundo, incluido México. Esta enfermedad puede presentarse desde una infección asintomática hasta síndrome de distrés respiratorio agudo (SDRA) grave. El objetivo del reporte de caso es mostrar la utilidad de la posición prono en pacientes no intubados. CASO CLÍNICO: presentamos el caso de una mujer sin comorbilidades con COVID-19 y SDRA moderado, en quien se evitó la intubación tras la mejoría con la posición prono, evaluada por la saturación arterial de oxígeno por pulsioximetría y por la relación de la presión arterial de oxígeno y la fracción inspirada de oxígeno (PaO2/FiO2). CONCLUSIÓN: existe poca evidencia sobre esta maniobra terapéutica en pacientes despiertos. Sin embargo, puede ser de ayuda para mejorar la oxigenación y evitar la intubación en estos pacientes.