CCR7-guided neutrophil redirection to skin-draining lymph nodes regulates cutaneous inflammation and infection.

Neutrophils are the first nonresident effector immune cells that migrate to a site of infection or inflammation; however, improper control of neutrophil responses can cause considerable tissue damage. Here, we found that neutrophil responses in inflamed or infected skin were regulated by CCR7-dependent migration and phagocytosis of neutrophils in draining lymph nodes (dLNs). In mouse models of Toll-like receptor-induced skin inflammation and cutaneous Staphylococcus aureus infection, neutrophils migrated from the skin to the dLNs via lymphatic vessels in a CCR7-mediated manner. In the dLNs, these neutrophils were phagocytosed by lymph node-resident type 1 and type 2 conventional dendritic cells. CCR7 up-regulation on neutrophils was a conserved mechanism across different tissues and was induced by a broad range of microbial stimuli. In the context of cutaneous immune responses, disruption of CCR7 interactions by selective CCR7 deficiency of neutrophils resulted in increased antistaphylococcal immunity and aggravated skin inflammation. Thus, neutrophil homing to and clearance in skin-dLNs affects cutaneous immunity versus pathology.

Non-isothermal drying kinetics of human feces.

The non-isothermal drying behavior and kinetics of human feces (HF) were investigated by means of thermogravimetric analysis to provide data for designing a drying unit operation. The effect of heating rate and blending with woody biomass were also evaluated on drying pattern and kinetics. At low heating rate (1 K/min), there is effective transport of moisture, but a higher heating rate would be necessary at low moisture levels to reduce drying time. Blending with wood biomass improves drying characteristics of HF. The results presented in this study are relevant for designing non-sewered sanitary systems with in-situ thermal treatment.

Linkage between patients' characteristics and prescribed systemic treatments for psoriasis: a semantic connectivity map analysis of the Swiss Dermatology Network for Targeted Therapies registry.

BACKGROUND: Several treatment options are currently available for the treatment of psoriasis. OBJECTIVE: To explore the main associations between patients' characteristics and systemic treatments prescribed for psoriasis in a large group of patients observed in real-life clinical practice. METHODS: This was a retrospective analysis of baseline data collected within the Swiss Dermatology Network for Targeted Therapies registry in Switzerland between March 2011 and December 2017. Semantic map analysis was used in order to capture the best associations between variables taking into account other covariates in the system. RESULTS: A total of 549 patients (mean age 46.7 ± 14.7 years) were included in the analysis. Conventional therapies such as retinoids and methotrexate were associated with no previous systemic therapies for psoriasis, a moderate quality of life (QoL) at therapy onset and older age (≥60 years). Fumaric acid derivatives were associated with mild psoriasis (psoriasis area severity index < 10) and long disease duration (≥20 years). On the other side, cyclosporine and psoralen and ultraviolet A/ultraviolet B treatments were linked to a more severe condition, including impaired QoL, hospitalization and inability to work. Regarding biological therapies, both infliximab and adalimumab were connected to the presence of psoriatic arthritis, severe disease condition and other comorbidities, including chronic liver or kidney diseases and tuberculosis. Etanercept, ustekinumab and secukinumab were all connected to a complex history of previous systemic treatments for psoriasis, moderate disease condition, overweight and university education. CONCLUSIONS: The analysis shows multifaceted associations between patients' characteristics, comorbidities, disease severity and systemic treatments prescribed for psoriasis. In particular, our semantic map indicates that comorbidities play a central role in decision-making of systemic treatments usage for psoriasis. Future studies should further investigate specific connections emerging from our data.

Hybrid membrane distillation reverse electrodialysis configuration for water and energy recovery from human urine: An opportunity for off-grid decentralised sanitation.

The integration of membrane distillation with reverse electrodialysis has been investigated as a sustainable sanitation solution to provide clean water and electrical power from urine and waste heat. Reverse electrodialysis was integrated to provide the partial remixing of the concentrate (urine) and diluate (permeate) produced from the membrane distillation of urine. Broadly comparable power densities to those of a model salt solution (sodium chloride) were determined during evaluation of the individual and combined contribution of the various monovalent and multivalent inorganic and organic salt constituents in urine. Power densities were improved through raising feed-side temperature and increasing concentration in the concentrate, without observation of limiting behaviour imposed by non-ideal salt and water transport. A further unique contribution of this application is the limited volume of salt concentrate available, which demanded brine recycling to maximise energy recovery analogous to a battery, operating in a 'state of charge'. During recycle, around 47% of the Gibbs free energy was recoverable with up to 80% of the energy extractable before the concentration difference between the two solutions was halfway towards equilibrium which implies that energy recovery can be optimised with limited effect on permeate quality. This study has provided the first successful demonstration of an integrated MD-RED system for energy recovery from a limited resource, and evidences that the recovered power is sufficient to operate a range of low current fluid pumping technologies that could help deliver off-grid sanitation and clean water recovery at single household scale.

Non-isothermal thermogravimetric kinetic analysis of the thermochemical conversion of human faeces.

The "Reinvent the Toilet Challenge" set by the Bill & Melinda Gates Foundation aims to bring access to adequate sanitary systems to billions of people. In response to this challenge, on-site sanitation systems are proposed and being developed globally. These systems require in-situ thermal treatment, processes that are not well understood for human faeces (HF). Thermogravimetric analysis has been used to investigate the pyrolysis, gasification and combustion of HF. The results are compared to the thermal behaviour of simulant faeces (SF) and woody biomass (WB), along with the blends of HF and WB. Kinetic analysis was conducted using non-isothermal kinetics model-free methods, and the thermogravimetric data obtained for the combustion of HF, SS and WB. The results show that the devolatilisation of HF requires higher temperatures and rates are slower those of WB. Minimum temperatures of 475 K are required for fuel ignition. HF and SF showed similar thermal behaviour under pyrolysis, but not under combustion conditions. The activation energy for HF is 157.4 kJ/mol, relatively higher than SS and WB. Reaction order for HF is lower (n = 0.4) to WB (n = 0.6). In-situ treatment of HF in on-site sanitary systems can be designed for slow progressive burn.

ALIGNed on adherence: subanalysis of adherence in immune-mediated inflammatory diseases in the DACH region of the global ALIGN study.

BACKGROUND: Non-adherence to medication is a challenging problem in daily clinical practice. OBJECTIVE: To assess reasons for non-adherence in patients with chronic immune-mediated inflammatory diseases (IMIDs) in a direct comparison including evaluation of treatment necessity and concerns. METHODS: ALIGN was a non-interventional, multicountry, multicentre, self-administered, cross-sectional, epidemiologic survey study. Here, we investigate the German, Austrian and Swiss (DACH) cohort. Six hundred thirty-one patients with different IMIDs (rheumatoid arthritis, ankylosing spondylitis, psoriatic arthritis, plaque psoriasis, Crohn's disease and ulcerative colitis) under systemic therapies were evaluated concerning adherence, beliefs of necessity and concerns towards treatment in patients with IMIDs. RESULTS: The DACH cohort had significantly different levels of adherence depending on the IMID (P < 0.05) and the type of therapy (P < 0.05). Based on the significant influence of concerns on treatment adherence (P < 0.05) and the high belief of treatment necessity, patients could be classified in four attitudinal segments, which were unequally distributed throughout various IMIDs. High concerns had a significant influence on non-adherence, whereas necessity did not. Older age, female sex, TNFi mono-, conventional combination and TNFi combination therapy are positively associated with adherence. CONCLUSIONS: In the DACH region, patients are less concerned about medication and believe in the necessity of treatment. Therefore, we suggest adapting the communication in the various patient groups.

Impact of fouling, cleaning and faecal contamination on the separation of water from urine using thermally driven membrane separation.

In this study, membrane distillation is evaluated as a technology for non-sewered sanitation, using waste heat to enable separation of clean water from urine. Whilst membrane fouling was observed for urine, wetting was not evident and product water quality met the proposed discharge standard, despite concentration of the feed. Fouling was reversible using physical cleaning, which is similar to previous membrane studies operating without pressure as the driving force. High COD reduction was achieved following faecal contamination, but mass transfer was impeded and wetting occurred which compromised permeate quality, suggesting upstream intervention is demanded to limit the extent of faecal contamination. (100 words).

Successful treatment of SAPHO syndrome with apremilast.

SAPHO (synovitis, acne, pustulosis, hyperostosis and osteitis) syndrome is a rare disease with inflammatory osteoarticular and skin involvement. The pathogenesis of SAPHO syndrome remains unclear, but evidence suggests it may be an autoinflammatory disease triggered upon exposure to infectious agents in genetically predisposed individuals. Induction of the interleukin (IL)-23/T helper 17 axis in addition to neutrophil activation seem to play a key role, and therapies targeting these immunological pathways, including tumour necrosis factor (TNF) inhibitors, ustekinumab, secukinumab and the IL-1 inhibitor anakinra, are potential treatment options that need further investigation. Here we report a case of a 24-year-old woman with SAPHO syndrome who presented at our clinic with palmoplantar pustulosis and sternoclavicular joint involvement. Previous treatments with topical steroids and keratolytics combined with nonsteroidal anti-inflammatory drugs, intravenous methylprednisolone, methotrexate and sulfasalazine had all failed to improve symptoms. Therapy with etanercept was not tolerated, and because of a previous demyelinating peripheral neuropathy, further treatment with TNF inhibitors was avoided. We initiated ustekinumab 45 mg, which improved skin manifestations but not joint pain. Dose escalation to 90 mg initially improved joint pain, but the dose had to be reduced to 45 mg again because of increased infections. During subsequent 45-mg ustekinumab treatment, joint pain exacerbated so we switched to adalimumab which caused an exacerbation of the disease, so we switched to secukinumab, which improved skin and joint symptoms significantly but was associated with a pustular hypersensitivity reaction. Finally, we began treatment with apremilast, a pan-cytokine approach, resulting in stabilization of the skin and joint symptoms without side-effects. To our knowledge, this is the first case report of apremilast as a treatment for SAPHO syndrome.

Paradoxical ulcerative colitis during adalimumab treatment of psoriasis resolved by switch to ustekinumab.

Here we report the case of a patient with psoriasis who developed ulcerative colitis most likely caused by adalimumab. After cessation of adalimumab, colitis improved significantly. However, as psoriasis worsened, the patient was switched to ustekinumab, which resulted in complete cessation of colitis. During the 2-year follow-up under ustekinumab therapy, no further gastrointestinal complaints occurred. Paradoxical psoriasis manifestations in inflammatory bowel disease (IBD) under tumour necrosis factor (TNF)-inhibitor therapy have been reported and paradoxical IBD occurred rarely (mostly Crohn disease) in patients with rheumatological conditions treated with infliximab or etanercept. Due to the highly probable association of adalimumab with the onset of colitis in this case, we would like to suggest the term 'paradoxical ulcerative colitis' (PUC) for this as yet extremely rarely reported phenomenon. To the best of our knowledge this is the first description of PUC in a patient with psoriasis and in adalimumab treatment. Our observation suggests that ustekinumab is an effective treatment option in patients with paradoxical anti-TNF-driven inflammatory reactions like psoriasis or IBD.

Tube-side mass transfer for hollow fibre membrane contactors operated in the low Graetz range.

Transformation of the tube-side mass transfer coefficient derived in hollow fibre membrane contactors (HFMC) of different characteristic length scales (equivalent diameter and fibre length) has been studied when operated in the low Graetz range (Gz<10). Within the low Gz range, mass transfer is generally described by the Graetz problem (Sh=3.67) which assumes that the concentration profile comprises a constant shape over the fibre radius. In this study, it is experimentally evidenced that this assumption over predicts mass transfer within the low Graetz range. Furthermore, within the low Gz range (below 2), a proportional relationship between the experimentally determined mass transfer coefficient (Kov ) and the Graetz number has been identified. For Gz numbers below 2, the experimental Sh number approached unity, which suggests that mass transfer is strongly dependent upon diffusion. However, within this diffusion controlled region of mass transfer, tube-side fluid velocity remained important. For Gz numbers above 2, Sh could be satisfactorily described by extension to the Lévêque solution, which can be ascribed to the constrained growth of the concentration boundary layer adjacent to the fibre wall. Importantly this study demonstrates that whilst mass transfer in the low Graetz range does not explicitly conform to either the Graetz problem or classical Lévêque solution, it is possible to transform the experimentally derived overall mass transfer coefficient (Kov ) between characteristic length scales (dh and L). T h is was corroborated by comparison of the empirical relationship determined in this study (Sh=0.36Gz) with previously published studies operated in the low Gz range. This analysis provides important insight for process design when slow tube-side flows, or low Schmidt numbers (coincident with gases) constrain operation of hollow fibre membrane contactors to the low Gz range.

Energy recovery from human faeces via gasification: A thermodynamic equilibrium modelling approach.

Non-sewered sanitary systems (NSS) are emerging as one of the solutions to poor sanitation because of the limitations of the conventional flush toilet. These new sanitary systems are expected to safely treat faecal waste and operate without external connections to a sewer, water supply or energy source. The Nano Membrane Toilet (NMT) is a unique domestic-scale sanitary solution currently being developed to treat human waste on-site. This toilet will employ a small-scale gasifier to convert human faeces into products of high energy value. This study investigated the suitability of human faeces as a feedstock for gasification. It quantified the recoverable exergy potential from human faeces and explored the optimal routes for thermal conversion, using a thermodynamic equilibrium model. Fresh human faeces were found to have approximately 70-82 wt.% moisture and 3-6 wt.% ash. Product gas resulting from a typical dry human faeces (0 wt.% moisture) had LHV and exergy values of 17.2 MJ/kg and 24 MJ/kg respectively at optimum equivalence ratio of 0.31, values that are comparable to wood biomass. For suitable conversion of moist faecal samples, near combustion operating conditions are required, if an external energy source is not supplied. This is however at 5% loss in the exergy value of the gas, provided both thermal heat and energy of the gas are recovered. This study shows that the maximum recoverable exergy potential from an average adult moist human faeces can be up to 15 MJ/kg, when the gasifier is operated at optimum equivalence ratio of 0.57, excluding heat losses, distribution or other losses that result from operational activities.

Canakinumab in adults with steroid-refractory pyoderma gangrenosum.

BACKGROUND: Pyoderma gangrenosum (PG) is a rare, neutrophilic, ulcerative skin disease that is difficult to treat, especially when unresponsive to steroids. OBJECTIVES: To determine whether canakinumab is an effective and safe treatment in PG. METHODS: Five adult patients with clinically and histologically confirmed steroid-refractory PG were enrolled in this prospective open-label study. They received canakinumab 150 mg subcutaneously at week 0 with an optional 150 mg at week 2 in case of an inadequate response [Physician's Global Assessment (PGA) ≥ 2], and an optional 150-300 mg at week 8 depending on PGA. The primary clinical end point was clinical improvement (PGA at least -1 from baseline) and/or complete remission (PGA 0 or 1) at week 16. Real-time quantitative polymerase chain reaction was performed on skin samples to quantify cytokine mRNA levels. RESULTS: Interleukin (IL)-1ß and its known target genes IL6, CXCL8 and IL36A were significantly increased in lesional skin of PG. Under canakinumab therapy, four of five patients showed a decrease in target-lesion size, PGA and Dermatology Life Quality Index (DLQI), and three of five achieved complete remission. The mean diameter of target lesions decreased from 4·32 ± 2·6 cm at visit 1 to 0·78 ± 1·3 cm at visit 7 (P = 0·03). Mean DLQI decreased from 15 ± 5 at visit 1 to 8 ± 4 by visit 7 (P = 0·01). Adverse effects were reported in two patients: fatigue in one and worsening of disease at a nontarget lesion in the other. CONCLUSIONS: Our data indicate that IL-1ß plays a key pathogenic role in PG and canakinumab may represent a therapeutic option for steroid-refractory PG.

[Scleromyxedema. A chronic progressive systemic disease]. / Skleromyxödem. Eine chronisch progressive Systemerkrankung.

BACKGROUND: Scleromyxedema is a rare connective tissue disease that may affect numerous internal organs in addition to the skin. The disease is almost exclusively associated with monoclonal gammopathy. MATERIAL AND METHODS: This retrospective study summarizes the clinical characteristics of four patients with scleromyxedema. In all of the patients a systematic serological and apparative check-up was performed. RESULTS: The mean age of the four patients (three women and one man) was 51 years. In all cases, monoclonal gammopathy (3 cases of IgG lambda and 1 case of IgG kappa) was involved. In one patient, skin lesions were restricted to the upper part of the body and three patients had generalized disease. The internal organs of all patients were affected with fibrosis of the lungs, myositis and arthritis, peripheral polyneuropathy and hypomotility of the esophagus. The most effective forms of treatment in this patient collective were dexamethasone-pulse therapy, intravenous immunoglobulins and bortezomib. All patients had recurrences after finishing therapy. The mean observation period after the initial diagnosis of scleromyxedena was 6.25 years (range 2-11 years). CONCLUSION: Scleromyxedema is a rare multisystemic disease. The heterogeneous affection of internal organs necessitates a comprehensive check-up. The response to recently published treatment strategies is low and recurrences after finishing therapy are frequent.

Topical treatment habits in psoriasis patients receiving adalimumab.

BACKGROUND: Biologics are used increasingly to treat moderate-to-severe psoriasis. Here the topical treatment habits (corticosteroids and vitamin D derivates) and moisturizer use of 97 Swiss patients (male 65, female 32) receiving adalimumab have been evaluated. METHODS: Using a short cross-sectional survey the pharmacist asked patients during telephone contact about their topical treatment habits and psoriasis activity. RESULTS: 47 patients with adalimumab monotherapy were still free of psoriatic lesions after a longer follow-up of 13 months of therapy; 8 of them still used topical treatment. In contrast, 38 of 50 patients with remaining lesions used topicals. More than 75% of patients indicated that the perceived efficacy of additional topical therapy was ≥5 on a visual analog scale (0-10). The use of moisturizers did not correlate with disease activity. CONCLUSION: Topical treatment use by adalimumab patients is associated with remaining disease activity. 83% of patients without residual plaques (40% of all adalimumab patients) are able to stop topical treatment completely.

Thyrolymphography.

The present investigation shows that the capacity of thyrolymphography for demonstrating the morphologic features of various thyroid lesions is not inferior to that of isotope scanning. On the contrary, lymphography is an effective procedure for detecting small nodules that remain undetected by other methods. Contrast medium is more rapidly distributed to lymph nodes in patients with diffuse goiter and also in patients pretreated with Lugol's solution. Finally, it is shown that the contrast medium employed (Lipiodol Ultra Fluid) remains in the lymph nodes for a period of several months.