Liver transplantation for alpha 1 antitrypsin deficiency (A1ATD) using a heterozygous donor: Outcomes and review of the literature.

INTRODUCTION: Alpha 1 antitrypsin deficiency (A1ATD) accounts for 21% of all pediatric liver transplants due to metabolic disease in the western world. Donor heterozygosity has been evaluated in adults but not to a recipient with A1ATD. METHODS: The data of patient were retrospectively analyzed and a literature review performed. RESULTS: We present a unique case of living related donation from a A1ATD heterozygote female to a child for decompensated cirrhosis due to A1ATD. In the immediate postoperative period, the child had low-alpha 1 antitrypsin levels, but these normalized by 3 months posttransplant. He is currently 19 months post-transplant with no evidence of recurrent disease. CONCLUSION: Our case provides initial evidence that A1ATD heterozygote donors may be safely used for pediatric patients with A1ATD, thus expanding the donor pool.

Fazirsiran for Liver Disease Associated with Alpha1-Antitrypsin Deficiency.

BACKGROUND: Alpha1-antitrypsin (AAT) deficiency results from carriage of a homozygous SERPINA1 "Z" mutation (proteinase inhibitor [PI] ZZ). The Z allele produces a mutant AAT protein called Z-AAT, which accumulates in hepatocytes and can lead to progressive liver disease and fibrosis. This open-label, phase 2 trial investigated the safety and efficacy of fazirsiran, an RNA interference therapeutic, in patients with liver disease associated with AAT deficiency. METHODS: We assigned adults with the PI ZZ genotype and liver fibrosis to receive fazirsiran at a dose of 200 mg (cohorts 1 [4 patients] and 2 [8 patients]) or 100 mg (cohort 1b [4 patients]) subcutaneously on day 1 and week 4 and then every 12 weeks. The primary end point was the change from baseline to week 24 (cohorts 1 and 1b) or week 48 (cohort 2) in liver Z-AAT concentrations, which were measured by means of liquid chromatography-mass spectrometry. RESULTS: All the patients had reduced accumulation of Z-AAT in the liver (median reduction, 83% at week 24 or 48). The nadir in serum was a reduction of approximately 90%, and treatment was also associated with a reduction in histologic globule burden (from a mean score of 7.4 [scores range from 0 to 9, with higher scores indicating a greater globule burden] at baseline to 2.3 at week 24 or 48). All cohorts had reductions in liver enzyme concentrations. Fibrosis regression was observed in 7 of 15 patients and fibrosis progression in 2 of 15 patients after 24 or 48 weeks. There were no adverse events leading to trial or drug discontinuation. Four serious adverse events (viral myocarditis, diverticulitis, dyspnea, and vestibular neuronitis) resolved. CONCLUSIONS: In this small trial, fazirsiran was associated with a strong reduction of Z-AAT concentrations in the serum and liver and concurrent improvements in liver enzyme concentrations. (Funded by Arrowhead Pharmaceuticals; AROAAT-2002 ClinicalTrials.gov number, NCT03946449.).

Integrated weighted gene co-expression network analysis reveals biomarkers associated with prognosis of high-grade serous ovarian cancer.

BACKGROUND: Ovarian cancer is the gynecologic tumor with the highest fatality rate, and high-grade serous ovarian cancer (HGSOC) is the most common and malignant type of ovarian cancer. One important reason for the poor prognosis of HGSOC is the lack of effective diagnostic and prognostic biomarkers. New biomarkers are necessary for the improvement of treatment strategies and to ensure appropriate healthcare decisions. METHODS: To construct the co-expression network of HGSOC samples, we applied weighted gene co-expression network analysis (WGCNA) to assess the proteomic data obtained from the Clinical Proteomic Tumor Analysis Consortium (CPTAC), and module-trait relationship was then analyzed and plotted in a heatmap to choose key module associated with HGSOC. Subsequently, hub genes with high connectivity in key module were identified by Cytoscape software. Furthermore, the biomarkers were selected through survival analysis, followed by evaluation using the relative operating characteristic (ROC) analysis. RESULTS: A total of 9 modules were identified by WGCNA, and module-trait analysis revealed that the brown module was significantly associated with HGSOC (cor = 0.7). Ten hub genes with the highest connectivity were selected by protein-protein interaction analysis. After survival and ROC analysis, ALB, APOB and SERPINA1 were suggested to be the biomarkers, and their protein levels were positively correlated with HGSOC prognosis. CONCLUSION: We conducted the first gene co-expression analysis using proteomic data from HGSOC samples, and found that ALB, APOB and SERPINA1 had prognostic value, which might be applied for the treatment of HGSOC in the future.

Development of a protein assay with copper chelator chromeazurol B, based on the biuret reaction.

This study aimed to provide a novel and highly sensitive protein assay based on the biuret reaction and using chromeazurol B, a metal chelate compound. The method consists of two reagents and an automated analyzer. First, a complex of copper and protein (biuret reaction) is formed. Second, a chelating reagent containing chromeazurol B forms a three-dimensional complex of protein, copper, and chromeazurol B at neutral pH, resulting in highly sensitive coloration. The intra-assay (n = 20) variation for the three levels was 3.54 % or lower at each concentration. Each response with α, ß-, and γ-globulin was 103.8 % and 104.3 %, respectively, against albumin. The molar absorption coefficient (ε) of the present method was 2.5 × 105 m2/mol against human albumin, higher than that of the commercially available Lowry method (ε = 8.7 × 104 m2/mol), which is based on the same principle. The correlation test for the pyrogallol method with 30 urine samples showed good performance (r = 0.961). The method described here (the Biuret-based CAB method) is a more sensitive and rapid assay than the Lowry method, and it may also be applied to biological samples because of its similar reactivity towards various proteins.

Correlation of Low Levels of α-1 Antitrypsin and Elevation of Neutrophil to Lymphocyte Ratio with Higher Mortality in Severe COVID-19 Patients.

BACKGROUND: Variations in COVID-19 prevalence, severity, and mortality rate remain ambiguous. Genetic or individual differences in immune response may be an explanation. Moreover, hyperinflammation and dysregulated immune response are involved in the etiology of severe forms of COVID-19. Therefore, the aim of the present study was to analyze serum alpha-1 antitrypsin (AAT) levels, as an acute-phase plasma protein with immunomodulatory effect and neutrophil to lymphocyte ratio (NLR) as a marker of inflammation response in severe COVID-19 illness. METHODS: In this retrospective observational cohort study, 64 polymerase chain reaction (PCR) positive COVID-19 hospitalized patients were studied for AAT, C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), troponin, complete blood count (CBC), random blood sugar, serum glutamate oxaloacetate transaminase (SGOT), serum glutamate pyruvate transaminase (SGPT), and arterial oxygen saturation (O2sat) at admission and during hospitalization. RESULTS: The results showed that hospitalized patients with COVID-19 had low serum levels of AAT and high CRP levels at the first days of hospitalization. In particular, the percentages of individuals with low, normal, and high AAT levels were 7.80%, 82.80%, and 9.40%, respectively, while high and low values of CRP accounted for 86.70% and 13.30% of patients. Most of the patients had an upward neutrophil to lymphocyte ratio (NLR) trend, with a higher mortality rate (p < 0.05) and troponin levels (p < 0.05). However, comorbidities, CRP alterations, ESR alterations, nonfasting blood sugar, SGOT, SGPT, O2sat, RBC, and PLT values were not significantly different between the NLR downward and upward trend groups. CONCLUSIONS: The current study revealed that severe COVID-19 patients had low serum AAT levels related to CRP values. Therefore, AAT response may be considered as a new mechanism by which some COVID-19 patients show immune dysregulation and more severe symptoms.

Effects of a combined water and sanitation intervention on biomarkers of child environmental enteric dysfunction and associations with height-for-age z-score: A matched cohort study in rural Odisha, India.

Poor water, sanitation and hygiene (WaSH) conditions are hypothesized to contribute to environmental enteric dysfunction (EED), a subclinical condition that may be associated with chronic undernutrition and impaired linear growth. We evaluated the effect of a combined water and sanitation intervention on biomarkers of EED, and then assessed associations of biomarkers of EED with height-for-age z-scores (HAZ), in children under five. We conducted a sub-study within a matched cohort study of a household-level water and sanitation infrastructure intervention in rural Odisha, India, in which we had observed an effect of the intervention on HAZ. We collected stool samples (N = 471) and anthropometry data (N = 209) for children under age 5. We analyzed stool samples for three biomarkers of EED: myeloperoxidase (MPO), neopterin (NEO), and α1-anti-trypsin (AAT). We used linear mixed models to estimate associations between the intervention and each biomarker of EED and between each biomarker and HAZ. The intervention was inversely associated with AAT (-0.25 log µg/ml, p = 0.025), suggesting a protective effect on EED, but was not associated with MPO or NEO. We observed an inverse association between MPO and HAZ (-0.031 per 1000 ng/ml MPO, p = 0.0090) but no association between either NEO or AAT and HAZ. Our results contribute evidence that a transformative WaSH infrastructure intervention may reduce intestinal permeability, but not intestinal inflammation and immune activation, in young children. Our study also adds to observational evidence of associations between intestinal inflammation and nutritional status, as measured by HAZ, in young children. Trial Registration: ClinicalTrials.gov (NCT02441699).

Multiplexed MRM-Based Proteomics Identified Multiple Biomarkers of Disease Severity in Human Heart Failure.

Heart failure (HF) is a complex disease due to the intricate interplay of several mechanisms, which therefore implies the need for a multimarker strategy to better personalize the care of patients with HF. In this study, we developed a targeted mass spectrometry approach based on multiple reaction monitoring (MRM) to measure multiple circulating protein biomarkers, involved in cardiovascular disease, to address their relevance in the human HF, intending to assess the feasibility of the workflow in the disease monitoring and risk stratification. In this study, we analyzed a total of 60 plasma proteins in 30 plasma samples from eight control subjects and 22 age- and gender- matched HF patients. We identified a panel of four plasma proteins, namely Neuropilin-2, Beta 2 microglobulin, alpha-1-antichymotrypsin, and complement component C9, that were more abundant in HF patients in relation to disease severity and pulmonary dysfunction. Moreover, we showed the ability of the combination of these candidate proteins to discriminate, with sufficient accuracy, HF patients from healthy subjects. In conclusion, we demonstrated the feasibility and potential of a proteomic workflow based on MRM mass spectrometry for the evaluation of multiple proteins in human plasma and the identification of a panel of biomarkers of HF severity.

Fecal host biomarkers predicting severity of Clostridioides difficile infection.

Clostridioides difficile is a major cause of health care-associated diarrhea. Severity ranges from mild to life-threatening, but this variability remains poorly understood. Microbiologic diagnosis of C. difficile infection (CDI) is straightforward but offers little insight into the patient's prognosis or into pathophysiologic determinants of clinical trajectory. The aim of this study was to discover host-derived, CDI-specific fecal biomarkers involved in disease severity. Subjects without and with CDI diarrhea were recruited. CDI severity was based on Infectious Diseases Society of America/Society for Healthcare Epidemiology of America criteria. We developed a liquid chromatography tandem mass spectrometry approach to identify host-derived protein biomarkers from stool and applied it to diagnostic samples for cohort-wise comparison (CDI-negative vs. nonsevere CDI vs. severe CDI). Selected biomarkers were orthogonally confirmed and subsequently verified in a CDI mouse model. We identified a protein signature from stool, consisting of alpha-2-macroglobulin (A2MG), matrix metalloproteinase-7 (MMP-7), and alpha-1-antitrypsin (A1AT), that not only discriminates CDI-positive samples from non-CDI ones but also is potentially associated with disease severity. In the mouse model, this signature with the murine homologs of the corresponding proteins was also identified. A2MG, MMP-7, and A1AT serve as biomarkers in patients with CDI and define novel components of the host response that may determine disease severity.

Plasma Cytokeratin 18 and fecal Alpha-1 Antitrypsin concentrations in dogs with osteosarcoma receiving carboplatin chemotherapy.

Gastrointestinal (GI) toxicosis is a common side effect of cytotoxic chemotherapy treatment in humans and dogs. Measurement of cytokeratin 18 (CK18), an intracellular structural protein released during epithelial apoptosis, and Alpha1-Antitrypsin (A1AT) in faeces provides a mechanism for evaluating damage to the intestinal mucosa secondary to cytotoxic chemotherapy. Our goal was to evaluate the clinical utility of plasma CK18 and faecal A1-AT levels as non-invasive biomarkers of cytotoxic chemotherapy induced GI toxicity. We conducted a prospective cohort study in dogs (N = 10) with osteosarcoma undergoing amputation followed by carboplatin chemotherapy. We hypothesized that plasma CK18 and faecal A1-AT levels would increase following carboplatin administration due to drug-induced GI epithelial damage/apoptosis, and that plasma CK18 and faecal A1-AT levels would correlate with severity of GI toxicity. Mean baseline plasma CK18 concentration was variable amongst patients; however, CK18 concentration prior to carboplatin chemotherapy treatment was not significantly different from CK18 levels after treatment. There was significant intra and inter-patient variability in mean faecal A1-AT levels at baseline. Mean A1-AT concentration did not change significantly from day 0 to day 21. Gastrointestinal toxicity was minimal; therefore, we were unable to determine the association of plasma CK18 and faecal A1-AT concentrations with development of GI toxicosis. In this study population, plasma CK18 and faecal A1-AT concentration were not clinically useful biomarkers for the detection of GI toxicosis secondary to carboplatin administration. Further prospective evaluation of CK18 and A1-AT as biomarkers of drug-induced GI toxicity is warranted in a larger cohort of dogs receiving cytotoxic chemotherapy. AVMA clinical trial registration number: AAHSD004827.

Mediterranean Diet and Atherothrombosis Biomarkers: A Randomized Controlled Trial.

SCOPE: To assess whether following a Mediterranean diet (MedDiet) improves atherothrombosis biomarkers in high cardiovascular risk individuals. METHODS AND RESULTS: In 358 random volunteers from the PREvención con DIeta MEDiterránea trial, the 1-year effects on atherothrombosis markers of an intervention with MedDiet, enriched with virgin olive oil (MedDiet-VOO; n = 120) or nuts (MedDiet-Nuts; n = 119) versus a low-fat control diet (n = 119), and whether large increments in MedDiet adherence (≥3 score points, versus compliance decreases) and intake changes in key food items are associated with 1-year differences in biomarkers. Differences are observed between 1-year changes in the MedDiet-VOO intervention and control diet on the activity of platelet activating factor acetylhydrolase in high-density lipoproteins (HDLs) (+7.5% [95% confidence interval: 0.17; 14.8]) and HDL-bound α1 -antitrypsin levels (-6.1% [-11.8; -0.29]), and between the MedDiet-Nuts intervention and the control arm on non-esterified fatty acid concentrations (-9.3% [-18.1; -0.53]). Large MedDiet adherence increments are associated with less fibrinogen (-9.5% [-18.3; -0.60]) and non-esterified fatty acid concentrations (-16.7% [-31.7; -1.74]). Increases in nut, fruit, vegetable, and fatty fish consumption, and decreases in processed meat intake are linked to enhancements in biomarkers. CONCLUSION: MedDiet improves atherothrombosis biomarkers in high cardiovascular risk individuals.

[Screening for alpha1-antitrypsin deficiency using dried blood spot: Assessment of the first 20 months]. / Dépistage du déficit en alpha1-antitrypsine sur sang capillaire recueilli sur papier-filtre : bilan des 20 premiers mois.

INTRODUCTION: Alpha1-antitrypsin deficiency is a predisposing factor for pulmonary disease and under-diagnosis is a significant problem. The results of a targeted screening in patients with respiratory symptoms possibly indicative of severe deficiency are reported here. METHODS: Data were collected from March 2016 to October 2017 on patients who had a capillary blood sample collected during a consultation with a pulmonologist and sent to the laboratory for processing to determine alpha1-antitrypsin concentration, phenotype and possibly genotype. RESULTS: In 20 months, 3728 test kits were requested by 566 pulmonologists and 718 (19 %) specimens sent: among these, 708 were analyzable and 613 were accompanied by clinical information. Of the 708 samples, 70 % had no phenotype associated with quantitative alpha1- antitrypsin deficiency, 7 % had a phenotype associated with a severe deficiency and 23 % had a phenotype associated with an intermediate deficiency. One hundred and eight patients carried at least one PI*Z allele which is considered to be a risk factor for liver disease. CONCLUSIONS: The results of this targeted screening program for alpha1- antitrypsin deficiency using a dried capillary blood sample reflect improvement in early diagnosis of this deficiency in lung disease with good adherence of the pulmonologists to this awareness campaign.

Effects of Probiotic Strains on Disease Activity and Enteric Permeability in Psoriatic Arthritis-A Pilot Open-Label Study.

(1) Background: Psoriatic Arthritis (PsA) is a painful disease of the joints and spine. Recent reports observed distinct enteric dysbiosis in PsA; intake of probiotic strains is considered to ameliorate enteric dysbiosis. If probiotics are effective in PsA is elusive. (2) Methods: In this pilot open-label study we enrolled 10 PsA patients with low to medium disease activity who received probiotics for 12 weeks. Analysis of faecal zonulin, α1-antitrypsin and calprotectin, as well as peripheral immune phenotyping was performed at baseline, after 12 weeks and 12 weeks after termination of probiotic intake. (3) Results: All patients showed increased levels of the enteric permeability marker zonulin which correlated with the frequency of peripheral Th17 cells. Calprotectin, a marker for intestinal inflammation was elevated in 6 out of 10 patients. Probiotic intake resulted in a reduction of disease activity and gut permeability. These effects, however, were not sustained beyond termination of probiotic intake. (4) Conclusions: PsA patients suffer from enhanced enteric permeability and inflammation. Probiotics may ameliorate disease activity in PsA by targeting these alterations.

Performance evaluation of 14 specific proteins measurement checked by an External Quality Assessment Scheme.

AIMS OF THE STUDY: To evaluate the state-of-the-art of 14 specific proteins measurement; to evaluate the laboratories' performance and the degree of harmonization in reporting results of participants in the External Quality Assessment Program of the Centre of Biomedical Research (CRB). METHODS: Overall and system-related inter-laboratory analytical variability (mean CVs%) and between-system differences (mean bias%) were evaluated from data of six EQA cycles 2013-2018. Moreover, we evaluated the analytical performance of participants as well as the units used to express proteins results. RESULTS: Overall inter-laboratory variability ranged from 3.8% for haptoglobin (HPT) to 12.5% for α1-antitrypsin (AAT) and decreased for IgA, α2-macroglobulin (A2M) and transferrin (TRF). Mean CVs% were generally higher for Siemens BN and Beckman Immage immunonephelometric systems, but <7.0% for all proteins. Mean bias > 7.0% was observed for BN (IgA, C4, AAT, transthyretin TTR), Siemens Vista (IgA, C4) and Immage (C4), whereas mean bias < -7.0% was found for Immage (AAT), Beckman AU (IgM) and Roche Cobas (C4, TTR, C-reactive protein). The laboratories' performance within the limits ranged from 85.1% of albumin (ALB) to 97.2% of HPT. The census of units employed in 2018, demonstrated that ~ 70% of laboratories still express the results in mg/dL. CONCLUSIONS: Despite a reduction in inter-laboratory variability for some proteins, different analytical systems showed both proportional and constant bias between methods. Units used by participants have not been substantially changed and dL is still largely used. The CRB EQA Program, with its performance data sets, is a valuable resource for laboratories and IVD manufacturers and support the goals of harmonization.

Identification of Salivary Biomarkers for Oral Cancer Detection with Untargeted and Targeted Quantitative Proteomics Approaches.

Oral cavity squamous cell carcinoma (OSCC) is one of the most common cancers worldwide. In Taiwan, OSCC is the fifth leading cause of cancer-related mortality and leads to 2800 deaths per year. The poor outcome of OSCC patients is principally ascribed to the fact that this disease is often advanced at the time of diagnosis, suggesting that early detection of OSCC is urgently needed. Analysis of cancer-related body fluids is one promising approach to identify biomarker candidates of cancers. To identify OSCC biomarkers, salivary proteomes of OSCC patients, individuals with oral potentially malignant disorders (OPMDs), and healthy volunteers were comparatively profiled with isobaric tags for relative and absolute quantitation (iTRAQ)-based mass spectrometry (MS). The salivary levels of 67 and 18 proteins in the OSCC group are elevated and decreased compared with that in the noncancerous group (OPMD and healthy groups), respectively. The candidate biomarkers were further selected using the multiple reaction monitoring (MRM)-MS and validated with the immunoassays. More importantly, the higher salivary level of three proteins, complement factor H (CFH), fibrinogen alpha chain (FGA), and alpha-1-antitrypsin (SERPINA1) was correlated with advanced stages of OSCC. Our results indicate that analysis of salivary proteome is a feasible strategy for biomarker discovery, and the three proteins are potential salivary markers for OSCC diagnosis.

Ratiometric Nanoparticle Array-Based Near-Infrared Fluorescent Probes for Quantitative Protein Sensing.

Quantitative detection of protein biomarkers is crucial to medical diagnosis. Fluorescent probes have been frequently used for protein detection, but they suffered from various weaknesses such as lack of versatility. In particular, most of the reported probes were not capable of simultaneous qualitative and quantitative detection for various proteins. In this paper, we developed novel nanoparticle array-based near-infrared (NIR) ratiometric probes for potent protein analysis, in which the specific protein was able to be distinguished and quantitated within a group of 11 common proteins. The activity of ß-galactosidases (ß-gal) was temporarily inhibited by the adsorption to magnetic nanoparticles and restored to certain content by replacement with detected proteins, leading to distinctive readout of the enzyme-activatable NIR probe (DCM-ß-gal). The readout of the sensor array against 11 proteins, as verified by isothermal titration calorimetry, was processed and transformed into canonical factors with the help of linear discrimination analysis. Moreover, the ratiometric signals of DCM-ß-gal were translated to quantitatively detect proteins within the concentration range of 0-100 µg/mL. Based on clear differentiation within both two-dimensional and three-dimensional plots, different proteins could be detected with 100% accuracy with their concentration simultaneously determined, which endowed the sensing system with great potential in clinical diagnosis.

Alpha 1-antitrypsin deficiency in patients with chronic obstructive pulmonary disease patients: is systematic screening necessary?

OBJECTIVE: Alpha-1-antitrypsin deficiency is a relatively prevalent, but under-diagnosed, genetic disease. The objective of this study was to assess whether the systematic screening for alpha-1-antitrypsin deficiency in all patients with chronic obstructive pulmonary disease from a tertiary service has an impact on the number of patients being diagnosed with this condition. RESULTS: Chronic obstructive pulmonary disease patients were screened for alpha-1-antitrypsin deficiency using immunonephelometry. The presence of a mutation was confirmed by molecular study of the SERPINA1 gene or by genetic sequencing, as needed. A total of 551 patients with chronic obstructive pulmonary disease were analyzed. Among these, 40 (7.2%) had some genetic mutation, while 11 (2%) had a Pi*ZZ genotype, resulting in severe respiratory illness. The systematic evaluation of chronic obstructive pulmonary disease patients revealed that screening is an effective method to diagnose alpha-1-antitrypsin deficiency. Early diagnosis may facilitate smoking cessation and initiation of treatment to maintain lung function.

Intestinal Inflammation in Chilean Infants Fed With Bovine Formula vs. Breast Milk and Its Association With Their Gut Microbiota.

Introduction: Compared to bovine formula (BF), breast milk (BM) has unique properties. In the newborn intestine, there is a homeostatic balance between the counterparts of the immune system, which allows a physiological inflammation, modulated by the gut microbiota. Many studies have attempted to understand the effect of BF vs. BM, and the changes in the gut microbiota, but few also focus on intestinal inflammation. Methods: We conducted a cohort study of newborn infants during their first 3 months. In stool samples taken at 1 and 3 months (timepoints T1 and T3), we quantified calprotectin, IL-8 and α1-antitrypsin by ELISA and we evaluated the expression of IL8 and IL1ß genes by RT-qPCR. To determine the microbiota composition, the 16S rRNA gene was amplified and sequenced using 454 pyrosequencing. Sequences were clustered into operational taxonomic units (OTUs). Results: In total 15 BM and 10 BF infants were enrolled. In the BM group, we found calprotectin and α1-antitrypsin levels were significantly elevated at T3 compared to T1; no differences were found between T1 and T3 in the BF group. A comparison between the BM and BF groups showed that calprotectin levels at T1 were lower in the BM than the BF group; this difference was not observed at T3. For IL-8 levels, we found no differences between groups. A gene expression analysis of the IL8 and IL1ß genes showed that infants from the BF group at T1 have a significantly increased expression of these markers compared to the BM group. Gut microbiota analyses revealed that the phylum Bacteroidetes was higher in BM than BF, whereas Firmicutes were higher in BF. A redundancy analysis and ANOVA showed BM has a community structure statistically different to BF at T1 but not at T3. Compared to BF, BM at T1 showed a higher representation of Enterococcus, Streptococcus, Enterobacter, Lactococcus, and Propionibacterium. Conclusions: We found a basal state of inflammation in the infants' intestine based on inflammation markers. One month after birth, infants receiving BF exhibited higher levels of inflammation compared to BM.

Enfisema pulmonar severo en un paciente joven con una vasculitis asociada a anticuerpos anticitoplasma de neutrófilo tipo proteinasa-3 (ANCA-PR3) / Severe pulmonary emphysema in a young patient with vasculitis associated with proteinase-3 anti-neutrophil cytoplasmic antibodies (PR3-ANCA)

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Characterisation of environmental enteropathy biomarkers and associated risk factors in children in the context of a WASH trial in Timor-Leste.

Environmental enteropathy (EE) is characterised by subclinical inflammation and hyperpermeability of the small intestine, hypothesised to be caused by recurrent ingestion of faecal bacteria. It has been suggested that EE may be a contributor to malnutrition and growth delays seen in children living in unsanitary conditions. We measured putative faecal EE markers myeloperoxidase (MPO) (ng/mL) and alpha-1-antitrypsin (AAT) (mg/g) in stool samples collected from 133 children aged 1-5 years in 16 communities enrolled in the WASH for WORMS randomised controlled trial in Timor-Leste. Samples were collected two years after a community-wide water, sanitation and hygiene (WASH) intervention that was integrated with regular deworming. Mixed effects multivariable linear regression models were used to examine the impact of the study intervention and of various WASH and infection-related factors on EE biomarkers. Children who lived in communities that received both the WASH intervention and deworming had similar AAT values as those who lived in communities that received only deworming (regression coefficient -0.14, p = 0.583), but they had a trend towards lower MPO values (coeff -0.51, p = 0.055). Younger children showed significantly higher MPO levels (coeff: -0.29, p = 0.002). No WASH variables or parasitic infections were associated with AAT levels. Household water being stored in covered containers was associated with lower MPO levels (coeff -1.75, p = 0.046). We found little evidence that a community-based WASH intervention had an impact on EE over a two-year period.