Demographic, clinical and antibody characteristics of patients with digital ulcers in systemic sclerosis: data from the DUO Registry

OBJECTIVES: The Digital Ulcers Outcome (DUO) Registry was designed to describe the clinical and antibody characteristics, disease course and outcomes of patients with digital ulcers associated with systemic sclerosis (SSc). METHODS: The DUO Registry is a European, prospective, multicentre, observational, registry of SSc patients with ongoing digital ulcer disease, irrespective of treatment regimen. Data collected included demographics, SSc duration, SSc subset, internal organ manifestations, autoantibodies, previous and ongoing interventions and complications related to digital ulcers. RESULTS: Up to 19 November 2010 a total of 2439 patients had enrolled into the registry. Most were classified as either limited cutaneous SSc (lcSSc; 52.2%) or diffuse cutaneous SSc (dcSSc; 36.9%). Digital ulcers developed earlier in patients with dcSSc compared with lcSSc. Almost all patients (95.7%) tested positive for antinuclear antibodies, 45.2% for anti-scleroderma-70 and 43.6% for anticentromere antibodies (ACA). The first digital ulcer in the anti-scleroderma-70-positive patient cohort occurred approximately 5 years earlier than the ACA-positive patient group. CONCLUSIONS: This study provides data from a large cohort of SSc patients with a history of digital ulcers. The early occurrence and high frequency of digital ulcer complications are especially seen in patients with dcSSc and/or anti-scleroderma-70 antibodies

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Chromium induced stress conditions in heterotrophic and auxotrophic strains of Euglena gracilis

Oxidative stress parameter and antioxidant defense compound as well as enzyme activity were studied in relation to different Cr(VI) concentrations (0, 10, 20, 40μM) in two strains of Euglena gracilis, one isolated from a polluted river (MAT) and the other acquired from a culture collection (UTEX). Chromium toxicity was measured in the auxotrophic and obligated heterotrophic variants of the two strains. Chromium uptake was higher in auxotrophic cultures, reflected by their higher cell proliferation inhibition and lower IC50 levels compared to heterotrophic ones. In the Cr(VI) treatments a reduction of chlorophyll a and b ratio (Chl a/Chl b) was observed, the ratio of protein to paramylon content was augmented, and total lipid content increased, having the auxotrophic strains the highest values. TBARS content increased significantly only at 40μM Cr(VI) treatment. Unsaturated fatty acids also increased in the Cr(VI) treatments, with the higher storage lipid (saturated acids) content in the heterotrophic cells. The antioxidant response, such as SOD activity and GSH content, increased with chromium concentration, showing the highest GSH values in the heterotrophic cultures and the SOD enzyme participation in chromium toxicity. The MAT strain had higher IC50 values, higher carbohydrate and saturated acid content, and better response of the antioxidant system than the UTEX one. This strain isolated from the polluted place also showed higher GSH content and SOD activity in control cells and in almost all treated cultures. SOD activity reached a 9-fold increase in both MAT strains. These results suggest that tolerance of MAT strain against Cr(VI) stress is not only related to GSH level and/or biosynthesis capacity but is also related to the participation of the SOD antioxidant enzyme.Fil: Rocchetta, Iara. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Mazzuca, Marcia. Universidad Nacional de la Patagonia "San Juan Bosco"; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Conforti, Visitacion Teresa D.. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; ArgentinaFil: Balzaretti, Vilma Teresa. Universidad Nacional de la Patagonia "San Juan Bosco"; ArgentinaFil: de Molina, María del Carmen Ríos. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Ciudad Universitaria. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Instituto de Química Biológica de la Facultad de Ciencias Exactas y Naturales; Argentin

The Role of Gut Bacteriome in Asthma, Chronic Obstructive Pulmonary Disease and Obstructive Sleep Apnoea

The human body contains a very complex and dynamic ecosystem of bacteria. The bacteriome interacts with the host bi-directionally, and changes in either factor impact the entire system. It has long been known that chronic airway diseases are associated with disturbances in the lung bacteriome. However, less is known about the role of gut bacteriome in the most common respiratory diseases. Here, we aim to summarise the evidence concerning the role of the intestinal bacteriome in the pathogenesis and disease course of bronchial asthma, chronic obstructive pulmonary disease, and obstructive sleep apnea. Furthermore, we discuss the consequences of an altered gut bacteriome on the most common comorbidities of these lung diseases. Lastly, we also reflect on the therapeutic potential of influencing the gut microbiome to improve disease outcomes

Effect of chromium on the fatty acid composition of two strains of Euglena gracilis

The effect of hexavalent chromium on fatty acid composition was studied in two strains of Euglena gracilis; UTEX 753 (from the Culture Collection of Algae of Texas University, USA) and MAT (isolated from a highly polluted River). Both were grown in photoauxotrophic and photoheterotrophic conditions and exposed to two metal concentrations, one below and one above IC50. The high malondialdehyde (MDA) levels (3 to 7-fold) obtained with chromium concentration above IC50, suggested the existence of metal-induced lipid peroxidation. Total lipid content increased only with concentration below IC50, whereas it was inhibited by higher metal concentration. Photoheterotrophic control strains exhibited a significantly higher proportion of saturated and polyunsaturated fatty acids. Polyunsaturated acids were most affected by chromium, especially those related to chloroplast structures. Ultra-structure studies showed clear thylakoid disorganization in all treated cells. The results indicate that hexavalent chromium affects levels of fatty acids, especially those related to photosynthetic activity.Fil: Rocchetta, Iara. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental; ArgentinaFil: Mazzuca, Marcia. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Comodoro. Departamento de Química; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Conforti, Visitacion Teresa D.. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental; ArgentinaFil: Ruiz, Laura Beatriz. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Biodiversidad y Biología Experimental; ArgentinaFil: Balzaretti, Vilma Teresa. Universidad Nacional de la Patagonia "San Juan Bosco". Facultad de Ciencias Naturales - Sede Comodoro. Departamento de Química; ArgentinaFil: Rios, Maria del Carmen. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales. Departamento de Química Biológica; Argentin

Omalizumab in eosinophilic granulomatosis with polyangiitis: friend or foe? A systematic literature review

OBJECTIVES: To systematically evaluate, through a Medline search, the role of omalizumab in eosinophilic granulomatosis with polyangiitis (EGPA). METHODS: A systematic review was performed with the following inclusion criteria: original articles and case reports written in English and reporting an association between omalizumab and EGPA. RESULTS: We found 18 papers on EGPA (14 case reports, 3 retrospective cohort studies, 1 prospective cohort study). Omalizumab showed to be effective as corticosteroid-sparing agent in EGPA patients with severe asthmatic manifestations. On the contrary, conflicting results concerned its use in refractory forms of EGPA. Plausible is the increased risk of EGPA onset among asthmatic patients treated with omalizumab, probably related to steroid reduction, even if it cannot be excluded that omalizumab might be occasionally directly involved in the pathogenesis. CONCLUSIONS: Our findings support the use of omalizumab in selected forms of EGPA, but caution in the tapering of corticosteroids is also recommended. Quality of evidence is limited, as the source of information was mainly case reports. Clinical trials are required in order to evaluate the role of omalizumab in EGPA and to ascertain the risk of asthmatic patients given omalizumab to develop EGPA

Reactivity to allergenic food contaminants: A study on products on the market

Abstract Background The frequency and severity of reactions in food‐allergic consumers exposed to unintentional food allergen contamination during production is unknown. To warn allergic consumers, it has been suggested for pre‐packaged foods to be precautionary labelled when the food allergen contamination may exceed the amount to which 1%–5% of the population could react (ED01–ED05). ED01 for hazelnut and milk have been estimated at 0.1 and 0.2 mg, respectively, by the Voluntary Incidental Trace Allergen Labelling (VITAL) initiative. The respective reference doses recommended by the FAO/WHO Codex consultation are 3 and 2 mg. We evaluated the reactivity to potential traces of milk and hazelnut allergens in allergen‐free pre‐packaged products by children affected by severe allergies to milk and hazelnuts. Methods Oral Food Challenges with commercially available hazelnut‐free wafer biscuits and milk‐free chocolate pralines were administered to patients with severe food allergies to hazelnut and cow's milk, respectively. Contamination levels of milk or hazelnut allergens were measured using chromatographic separation interfaced with triple quadrupole mass spectrometry. Results No hazelnut allergic patient showed allergic reactions to exposure to biscuits, nor any milk allergic patient displayed allergic reactions to the dark chocolate praline. While no hazelnut trace was detected in biscuits, the praline was found to be contaminated by milk at concentrations ranging between 8 and 35 mg total protein/kg food. In our dose model, these amounts exceeded 1.5–10 times the VITAL ED01 and reached the threshold suggested by the FAO/WHO Codex consultation. Conclusions Upon the consumption of food products available on the market, many patients with severe food allergies tolerate significantly higher doses of allergen than reference doses indicated in the VITAL system used for precautionary allergen labelling. These doses support the safety of the FAO/WHO recommended reference doses