Dupilumab in patients with atopic dermatitis: assessing treatment response, clinical features and potential biomarkers in real-life.

Summary: Background. The clinical and pathophysiological heterogeneity of atopic dermatitis (AD) endophenotypes is associated with wide diversity in response to therapy. The aim of this study was to evaluate the response to dupilumab in a group of AD patients and identify clinical/immunological features associated with different patterns of response. Methods. A retrospective observational study was performed, including 30 adults with AD who completed 12 months treatment with dupilumab, in a Portuguese Immunoallergology Department. Demographic, clinical, and immunological data were analyzed, including total serum IgE, sensitization to aeroallergens, peripheral eosinophilia and inflammatory biomarkers (sedimentation rate, C-reactive protein and lactate dehydrogenase-LDH). Patients who achieved EASI-75/EASI ≤ 7, SCORAD-75/SCORAD ≤ 24, NRS-pruritus ≤ 4 or DLQI≤5 at 6 months of treatment were considered responders and those that achieved all these goals at 16 weeks were considered super-responders. Results. Clinical evaluation revealed a significant reduction in median SCORAD, EASI, DLQI, NRS-pruritus and NRS-sleep over 12 months on dupilumab (p less than 0.01), in parallel with decrease in serum Th2 pathway biomarkers and LDH. All patients responded to dupilumab, and 26.7% were super-responders, supporting that dupilumab is highly effective in moderate to severe Th2-high AD. Conclusions. In this cohort, none of the evaluated biomarkers at baseline were associated with a better/earlier clinical response to dupilumab. Dupilumab treatment for 52 weeks resulted in a significant and sustained reduction in blood levels of total IgE and allergen-specific IgE to aeroallergens. The potential long-term clinical benefit of these effects, even after discontinuing dupilumab therapy in patients with AD, should be explored to a greater extent.

A real-world characterization of a cohort with eosinophilic esophagitis: looking for severity biomarkers.

Summary: Background. Eosinophilic esophagitis (EoE) is an immune-mediated chronic esophageal disease, with frequent association with atopy. A validated non/minimally invasive biomarker of disease severity has not been identified. We aimed to determine if sensitization to airborne and food allergens correlates with disease severity, and to evaluate the association between clinical and laboratory characteristics with the severity of EoE. Methods. Retrospective study of EoE patients observed in a differentiated center, 2009-2021. The association between patients' diagnosis age, disease duration before diagnosis, sensitization to airborne/food allergens, serum total IgE and peripheral blood eosinophil values and severe clinical disease (presence of symptoms with a significant impact on quality of life and/or ≥ 1 hospital admission due to EoE complications, namely severe dysphagia, food impaction or esophageal perforation) and histological severe disease (≥ 55 eos/hpf and/or microabscesses in esophageal biopsies) was evaluated. Results. 92 patients were observed, 83% male, 87% atopic. There was a mean delay in diagnosis of 4 years (range 0-31). 84% had aeroallergen sensitization and 71% food sensitization. Food impaction and dysphagia were the most frequent symptoms, and severe clinical disease was observed in 55%. Histologically, 37% had severity criteria. Patients with severe clinical disease had a significantly longer mean disease duration before diagnosis than patients without severe clinical disease (79 vs 15 months, p = 0.021). Patients who described food impaction were significantly older at time of diagnosis than those who have never had impaction (18 vs 9 years, p less than 0.001). There was no significant association (p less than 0.05) between sensitization, serum total IgE and peripheral blood eosinophil values and clinical or histological severity. Conclusions. An older age at diagnosis and a longer disease duration before diagnosis appear to be useful for predicting EoE clinical severity. Despite having been demonstrated a high prevalence of allergic disease, the presence of sensitization to airborne and/or food allergens do not seem to be useful for predicting clinical or histological severity.

Rapid desensitization to acetylsalicylic acid in patients with ischemic heart disease: 10-year experience of a Portuguese Allergy Department.

Summary: Background. Managing Acetylsalicylic Acid (ASA) hypersensitivity (HS) in patients with ischemic heart disease (IHD) is a challenge. Data on Rapid Desensitization (RD) to ASA is scarce. We aimed to report the outcomes of our 10-year experience with RD to ASA. Methods. Retrospective, observational, single-center study of patients with ASA HS and suspected IHD who underwent RD to ASA between March 2009 and February 2019. Results. Fifty patients were included. ASA HS presentation ranged from urticaria (56%) to anaphylaxis (32%). Regarding cardiologic diagnoses, 40 patients (80%) had acute coronary syndrome and 10 (20%) stable angina. The majority of patients (N = 36.72%) underwent percutaneous coronary intervention. RD to ASA was successful in all patients. Two patients presented a mild HS reaction during the RD, which was promptly treated, and subsequent daily doses of ASA 100 mg were tolerated. Conclusions. In our cohort, RD to ASA in patients with ASA HS and IHD was very effective and safe.

Caesarean delivery in a pregnant woman with epidermolysis bullosa: anaesthetic challenges.

Epidermolysis bullosa is a heterogeneous group of hereditary diseases characterised by extreme fragility of skin and mucosa, with blister and lesion formation spontaneously or in response to trauma. Anaesthetic management of these patients is challenging with respect to positioning, monitoring, use of medical devices and airway management. These challenges are increased when managing labour. We report an elective caesarean delivery in a nulliparous woman with autosomal recessive dystrophic epidermolysis bullosa, managed successfully with spinal anaesthesia.

Ankle stiffness in postmenopausal women: influence of hormone therapy and menopause nature.

BACKGROUND: Literature suggests that muscle-tendon unit (MTU) stiffness is implicated in human motion performance and injuries. In addition, muscle and joint pains comprise a set of very common climacteric symptoms. Concomitant with such symptoms, physical fragility and mobility limitations are expected, which further affect the functional physical fitness of postmenopausal women. To the authors' knowledge, this is the first study relating MTU stiffness with hormone therapy (HT) and the nature of menopause. The purpose of this study was to investigate the influence of HT and the nature of menopause on triceps-surae MTU stiffness in postmenopausal women. METHODS: Ninety-three women participated in this study. The data concerning menopause were obtained through medical consultation. MTU stiffness was assessed in vivo using a damped oscillation technique and a load equivalent to 30% of maximal voluntary isometric contraction. RESULTS: None of the following pair groups showed statistical differences for MTU stiffness: the HT group (19,426 +/- 4148 N/m) and the without-HT group (20,056 +/- 3579 N/m); the natural menopause group (19,525 +/- 3718 N/m) and the induced menopause group (20,469 +/- 4705 N/m). No significant differences were also found between the following pair groups: the natural menopause with-HT group (19,078 +/- 3910 N/m) and the without-HT group (20,076 +/- 3442 N/m); the induced menopause with-HT group (20,756 +/- 4932 N/m) and the without-HT group (19,942 +/- 4656 N/m). CONCLUSION: The data suggest that MTU stiffness is not related to either the administration of HT in postmenopausal women or to the nature of menopause.

Monoazo and diazo dye decolourisation studies in a methanogenic UASB reactor.

Mixed anaerobic bacterial consortia have been show to reduce azo dyes and batch decolourisation tests have also demonstrated that predominantly methanogenic cultures also perform azo bond cleavage. The anaerobic treatment of wool dyeing effluents, which contain acetic acid, could thus be improved with a better knowledge of methanogenic dye degradation. Therefore, the decolourisation of two azo textile dyes, a monoazo dye (Acid Orange 7, AO7) and a diazo dye (Direct Red 254, DR254), was investigated in a methanogenic laboratory-scale Upflow Anaerobic Sludge Blanket (UASB), fed with acetate as primary carbon source. As dye concentration was increased a decrease in total COD removal was observed, but the acetate load removal (90%) remained almost constant. A colour removal level higher than 88% was achieved for both dyes at a HRT of 24h. The identification by HPLC analysis of sulfanilic acid, a dye reduction metabolite, in the treated effluent, confirmed that the decolourisation process was due mainly to azo bond reduction. Although, HPLC chromatograms showed that 1-amino-2-naphthol, the other AO7 cleavage metabolite, was removed, aeration batch assays demonstrated that this could be due to auto-oxidation and not biological mineralization. At a HRT of 8h, a more extensive reductive biotransformation was observed for DR254 (82%) than for AO7 (56%). In order to explain this behaviour, the influence of the dye aggregation process and chemical structure of the dye molecules are discussed in the present work.

Batch tests for assessing decolourisation of azo dyes by methanogenic and mixed cultures.

Most of the published studies on azo dye colour removal involve anaerobic mixed cultures and there is some interest in the knowledge of how dye reduction occurs, if by facultative, strictly anaerobic or both bacterial trophic groups present in classic anaerobic digestors. This paper describes the behaviour of methanogenic and mixed bacteria cultures on the colour removal in batch systems, of a commercial azo dye, C.I. Acid Orange 7, used in paper and textile industries. The aim of this study is to demonstrate, by analysing dye decolourisation, that it occurs with mixed cultures as well as with strictly anaerobic (methanogenic) cultures. Tests were performed with a range of dye concentrations between 60 and 300 mg x l(-1). The influence of dye concentration on the carbon source removal and decolourisation processes was studied. The effect of carbon source concentration on colour removal was also analysed for both cultures. The degradation rates in mixed and methanogenic cultures were compared. The consumption of carbon source was monitored by COD analysis and dye degradation by ultraviolet-visible spectrophotometry and thin layer chromatography.

Workshop 3 (synthesis): innovative processes in small scale agricultural production using water more effectively.

The workshop discussed the possibilities of innovative technologies to increase food production. Most of the concepts discussed are based on rainfall management, conservation and recycling. Simple technologies, adopted to local circumstances, can increase farm yields in small-scale agriculture. Small-scale rainfed agriculture is viable with intelligent utilisation of harvested rainfall. These small-scale technologies need however to be complemented with educational programs, incentives and trade to be broadly adopted and effective. The need for better documentation of results was also raised in the discussion.

Glycated haemoglobin: comparison between methods based upon 5-hydroxymethylfurfural determination (colorimetric or HPLC) and ion exchange chromatography (HbA1).

A comparison of methods, two based upon 5-hydroxymethylfurfural determination (colorimetric using a semi-automated procedure and HPLC) and ion exchange chromatography (HbA1 using BioRad method) was performed. The influence of variables on 5-hydroxymethylfurfural determination is reported. The dialysis step appears to be essential for an accurate determination of 5-hydroxymethylfurfural released from glycated haemoglobin. The adjustment of haemoglobin concentration to an accurately known level is required for the colorimetric method, in order to achieve the same background colour absorbance. For the HPLC method this step is not necessary as 5-hydroxymethylfurfural liberation was proved to be stoichiometric. The Sep Pak C-18 cartridge purification appears to be an improvement for the accurate determination of 5-hydroxymethylfurfural using HPLC. When the three methods were compared the overlap between normals and diabetics was found to be less, using the 5-hydroxymethylfurfural HPLC method, suggesting that this procedure, although more time consuming, seems to be more useful in the management of diabetes mellitus.

Glycosylated haemoglobin: high-performance liquid chromatographic determination of 5-(hydroxymethyl)-2-furfuraldehyde after haemoglobin hydrolysis.

A specific and accurate method for the quantitation of the azomethine linkage present in non-enzymatically glycosylated haemoglobin is described. This protein is hydrolysed for 5 h in 1 M oxalic acid at 100 degrees C to yield 5-(hydroxymethyl)-2-furfur-aldehyde (5-HMF), known as a specific degradation product of hexoses linked to the protein. 5-HMF is then purified through a Sep-Pak C18 cartridge and measured by its absorption at 280 nm after separation on a C18 reversed-phase silica column. Quantitation is made accurate by using 1-methylxanthine as internal standard throughout the whole procedure. The identity and the purity of the 5-HMF chromatographic peak was ascertained by UV spectroscopy, gas chromatography on a glass capillary column and mass spectrometry. The method has been successfully used for 5-HMF determinations in monitoring diabetes mellitus patients. The mean values, expressed as nmol of 5-HMF per mg of haemoglobin were 0.64 +/- 0.13 (S.D.) for 27 controls and 1.32 +/- 0.39 for 78 diabetic patients. Unlike the usually employed thiobarbituric acid assay, the present procedure is truly specific for the 5-HMF determination.