Search

Gastrointestinal bleeding (GIB) is a clinical challenge in kidney failure. The INSPIRE group assessed if machine learning could assist with determining a hemodialysis (HD) patient’s 180-day GIB hospitalization risk. Model was developed using adult HD patient data from United States (2017-2020). Patient data was randomly split (50% training, 30% validation, and 20% testing). HD treatments ≤ 180 days before GIB hospitalization were classified as positive observations, and others were negative observations. Datasets were randomly sampled to build an XGBoost model that considered 386 exposures initially and was refined to the top 50 exposures. Unseen testing dataset was used to determine final model performance. Incidence of 180-day GIB hospitalization was 1.18% in the HD population (n=451,579), and 1.16% among patients in the testing dataset (n=27,991). Model showed an area under the curve=0.69, sensitivity=57.9%, specificity=68.9%, accuracy=68.8% and balanced accuracy=63.4%. Exposures with largest effect size per Shapley values were older age (group mean GIB event=68.2 years vs no GIB event=63.4 years), shorter days since last all-cause hospital admission (group mean GIB event=203.2 days vs no GIB event=253.2 days), and higher serum 25-hydroxy (OH) vitamin D levels from most recent lab (group mean GIB event=33.4 ng/mL vs no GIB event=30.5 ng/mL). Other important predictors included lower hemoglobin and iron indices, longer dialysis vintage, and proton pump inhibitor use. Model appears suitable for early detection of GIB event risk in HD, yet prospective testing is needed. The association between higher 25OH vitamin D and GIB events was unexpected and warrants investigation.

Immunoadsorption is well known to selectively remove immunoglobulins and immune complexes from plasma and is applied in a variety of autoimmune diseases and for desensitization before, or at acute rejection after organ transplantation. Performance, safety, and clinical effectiveness of immunoadsorption were the aim of this study. This prospective, noninterventional, multicentre cohort study included patients treated with immunoadsorption (Immunosorba or GLOBAFFIN adsorbers) for any indication. Clinical effectiveness was assessed after termination of the patient's individual treatment schedule. Eighty-one patients were included, 69 were treated with Immunosorba, 11 with GLOBAFFIN, one patient with both adsorbers. A majority of patients was treated for neurological indications, dilated cardiomyopathy, and before or after kidney or heart transplantation. Mean IgG reduction from pre- to post-treatment was 69.9% ± 11.5% for Immunosorba and 74.1% ± 5.0% for GLOBAFFIN, respectively. The overall IgG reduction over a complete treatment block was 68%-93% with Immunosorba and 62%-90% with GLOBAFFIN depending on the duration of the overall treatment. After termination of the immunoadsorption therapy, an improvement of clinical status was observed in 63.0%, stabilization of symptoms in 29.6%, and a deterioration in 4.9% of patients. Changes in fibrinogen, thrombocytes, and albumin were mostly classified as noncritical. Overall, the treatments were well tolerated. Immunoadsorption in routine clinical practice with both GLOBAFFIN and Immunosorba has been safely performed, was well tolerated by patients, and effective in lowering immunoglobulins with an improvement or maintenance of clinical status, thus represents an additional therapeutic option for therapy refractory immune disorders.

Toxin removal capacity (i.e., performance) of a dialyzer is not constant but diminishes during treatment, as the adsorption of proteins to the membrane provides an additional barrier to uremic solutes. We investigated time-resolving molecular weight retention changes among synthetic high-flux dialyzers and compared the results with recent data from a randomized controlled trial.In plasma recirculation experiments over 240 min, sieving coefficients (SC) for β2-microglobulin, myoglobin, and albumin were determined for the FX CorAL (Fresenius Medical Care), ELISIO (Nipro), and xevonta (B. Braun). Molecular weight retention (MWR) curves were generated and the shifts over 120 min were characterized. Effective pore radius was determined, and the predicted albumin loss was compared with clinical data.SC decreased over time for all dialyzers (mean relative decrease across all dialyzers: β2-microglobulin: 8.0% (120 min); myoglobin: 56.6% (240 min); albumin: 94.1% (240 min)). FX CorAL (7.3%, 52.6% and 91.1%) and ELISIO (7.7%, 51.0%, and 93.8%) showed a lower decrease than xevonta (9.0%, 66.2%, and 97.4%). For all dialyzers, MWR curves shifted toward lower molecular weight, with the lowest shift for FX CorAL (by 0.23 nm at SC50%, 120 min) and highest for xevonta (0.50 nm). FX CorAL had the highest slope over time and the smallest decrease in the effective pore radius (2 min: 2.31 nm, 120 min: 2.08 nm). Predicted albumin loss over 4 h was highest for xevonta (609.3 mg) and comparable between ELISIO (283.6 mg) and FX CorAL (313.3 mg).Substantial differences in the temporal performance profile of dialyzers exist. The present approach allows the characterization of dialyzer permeability changes over time using standard, clinically relevant protein markers.

Background The hemocompatibility of dialyzers for extracorporeal kidney replacement therapy (KRT) is of importance to minimize harmful reactions between blood constituents and the membrane. We investigated in these exploratory studies the hemocompatibility profile of several types of polysulfone dialyzers. Methods Hemocompatibility of various high-flux polysulfone dialyzers were compared in two consecutive, prospective, randomized, crossover studies, each including 24 adult patients being at least 3 months on hemodialysis (HD) or on-line hemodiafiltration (HDF). These dialyzers, differing in membrane type, fiber geometry, sterilization method, and production technology, were each applied for 1 week in HD or HDF. Hemocompatibility was assessed through markers of complement activation, cell activation, coagulation, contact activation, and immunologic reactions. Results The patients in the two studies were on average 67±11 and 68±11 years old, 75% and 67% were male, and were on KRT for 5.4±5.0 and 4.4±3.6 years. The complement factors C3a and C5a increased early and transiently during treatment, less so with HDF than with HD, and with dialyzers combining wider inner fiber diameter (210 versus 185 µm) and advanced membrane type (Helixone plus versus Helixone). sC5b-9 increased in all study phases, reaching its highest level after 60 minutes, with lower values over the entire treatment (area under the curve) for HDF than HD, and for wider inner fiber diameter and advanced membrane type. Leukocytes decreased in the first 10 minutes, without significant differences between dialyzers. PMN elastase increased in the first hour, more so with HD than HDF. Thrombocytes decreased slightly in the first 30 minutes, with differences only between HDF and HD mode. IL-8 decreased from pre- to postdialysis, particularly on HDF. No differences were observed for kallikrein, IgE, and hsCRP. Conclusions In these explorative studies we found indications to a comparable hemocompatibility profile of the investigated dialyzers. We observed distinctions in compounds between HDF and HD and for some dialyzer and membrane characteristics.

Sebastian Zschätzsch,1 Manuela Stauss-Grabo,2 Adelheid Gauly,2 Jennifer Braun2 1Center for Kidney and Blood Pressure Diseases, Georg-Haas-Dialysis Center, Giessen, Germany; 2Fresenius Medical Care, Global Medical Office, Bad Homburg, GermanyCorrespondence: Adelheid GaulyFresenius Medical Care Deutschland GmbH, Global Medical Office, Else-Kröner-Strasse 3, Bad Homburg, 61352, GermanyTel +49 6172 6092260Email adelheid.gauly@fmc-ag.comPurpose: Volume management in hemodialysis (HD) requires the ability to assess volume status objectively and determine treatment strategies that achieve euvolemia without compromising hemodynamic stability. The aim of this study was to compare dialysis with and without blood volume-controlled ultrafiltration (UF) in combination with body composition monitoring, and to evaluate indicators for adequate dialysis (Kt/V), ultrafiltration volume, fluid status, and the occurrence of intradialytic morbid events (IME).Patients and Methods: Patients undergoing hemodialysis or on-line hemodiafiltration with support of a blood volume monitor (BVM) – a feedback control device integrated into the 5008 and 6008 HD systems – were enrolled. Patients received treatment for four weeks using the 6008 CAREsystem and the BVM (6008+). Data on dialysis dose (Kt/V), UF volume and predialysis fluid status were documented. This data was also documented retrospectively for four weeks with (5008+) and without (5008−) the use of the BVM with the 5008 system. Comparisons were analyzed using linear mixed models.Results: Twenty-four patients were enrolled. Kt/V was unaffected by blood volume-controlled UF (5008− vs 5008+: p=0.230) and was equally achieved with both HD systems (5008+ vs 6008+: p=0.922). The UF volume and fluid status achieved were comparable, independent of the use of UF control with BVM (5008− vs 5008+; UF volume: p=0.166; fluid overload: p=0.390) or the HD system (5008+ vs 6008+: UF volume: p=0.003; fluid overload: p=0.838), except for UF volume being higher in the 6008+ phase. IMEs occurred in less than 3% of treatments, with no difference between study phases.Conclusion: This study demonstrates that a clinical approach to kidney replacement therapy that tracks volume status and manages intradialytic fluid removal by blood volume-controlled UF delivers adequate dialysis without compromising fluid removal. It maintains volume status and ensures low incidence of IMEs.Keywords: fluid status, blood volume monitoring, body composition monitoring, dialysis dose, intradialytic morbid events

Background Dialyzers should be designed to efficiently eliminate uraemic toxins during dialysis treatment, given that the accumulation of small and middle molecular weight uraemic solutes is associated with increased mortality risk of patients with end-stage renal disease. In the present study we investigated the novel FX CorAL dialyzer with a modified membrane surface for performance during online hemodiafiltration (HDF) in a clinical setting. Methods comPERFORM was a prospective, open, controlled, multicentric, interventional, crossover study with randomized treatment sequences. It randomized stable patients receiving regular post-dilution online HDF to FX CorAL 600 (Fresenius Medical Care Deutschland), xevonta Hi 15 (B. Braun) and ELISIO 150H (Nipro) each for 1 week. The primary outcome was β2-m removal rate (β2-m RR) during online HDF. Secondary endpoints were RR and/or clearance of β2-m and other molecules. Albumin removal over time was an exploratory endpoint. Non-inferiority and superiority of FX CorAL 600 versus comparators were tested. Results Fifty-two patients were included and analysed. FX CorAL 600 showed the highest β2-m RR (75.47%), followed by xevonta Hi 15 (74.01%) and ELISIO 150H (72.70%). Superiority to its comparators was statistically significant (P = 0.0216 and P Conclusions FX CorAL 600 efficiently removed middle and small molecules and was superior to the two comparators in β2-m RR. Albumin sieving kinetics point to reduced formation of a secondary membrane.

Background and Aims Hemodialyzers containing membranes made from a blend of polysulfone and polyvinylpyrrolidone (PVP) are widely used. PVP makes the membrane material more hydrophilic to reduce interactions with plasma proteins and platelets. A modified spinning technique has been established to stabilize the PVP on the blood-side surface in the polysulfone dialysis membrane in the new dialyzer FX CorAL 600. The objective of the present study was to prove for this new dialyzer non-inferiority of performance in comparison to established dialyzers. Further, hemocompatibility and safety of the dialyzers were explored. Method In a multicenter, prospective, randomized, crossover study adult patients on online hemodiafiltration (HDF) were enrolled. They were treated for one week each with on-line HDF in post-dilution mode, and in randomized order with the dialyzers FX CorAL 600, FX 600, and FX CorDiax 600 (all Fresenius Medical Care, Bad Homburg, Germany). Blood samples were taken on the midweek session before start, at the end to analyze removal rate and at 60 min to determine clearance of ß2-microglobulin, myoglobin, urea, creatinine and phosphate. Further a pattern of hemocompatibility parameters and safety was evaluated. Assuming no carry over effect, linear mixed models were used for statistical analysis. Results The mean age of the 49 enrolled patients was 66.3±13.6 years, 76% were male. Treatments were performed in post-dilution mode with a mean blood flow > 300 mL/min and a substitution volume >19 L. The removal rate of ß2-microglobulin was 74.4, 70.4, and 73.1% for the FX CorAL 600, FX 600, and FX CorDiax 600 dialyzer, respectively. FX CorAL 600 proved to be statistically significantly non-inferior to FX 600 (p=0.0006) and to FX CorDiax 600 (p=0.036). The removal rate of FX CorAL 600 was by 4.0% (confidence interval 0.4 – 7.5%) significantly higher than with FX 600. The difference to FX CorDiax 600 was not significant. The clearance of ß2-microglobulin and myoglobin and the removal rate of myoglobin were significantly higher with the new dialyzer FX CorAL 600 than with the FX 600, and comparable to the FX CorDiax 600. Performance for small molecules was similar for all dialyzers. The complement factors C3a and C5a increased early in the treatment with a peak at 15 min, without differences between the three dialyzers for C3a, and for C5a with significantly lower increase at 15 min with FX CorAL 600 than for FX 600 (p=0.007); the difference of increase between FX CorAL 600 and FX CorDiax 600 was not significant (p=0.515). The course of sC5b9 was similar for all three dialyzers, with significantly lower increase at 15 min for both FX CorAL 600 (p=0.009) and FX CorDiax 600 (p=0.026) as compared to FX 600 and similar increase at 60 min for both FX CorAL 600 (p=0.573) and FX CorDiax 600 (p=0.386) as compared to FX 600. The area-under-the-curve for the course of sC5b-9 with FX CorAL 600 was significantly lower than with FX 600 (p=0.044) and comparable to FX CorDiax 600 (p=0.092). The leukocyte count showed a decrease in the first 15 min of the treatment, which recovered afterwards, similarly for all treatment phases with the different dialyzers. Further, the dialyzers did not differ with respect to adverse events. Conclusion All three dialyzers showed good performance, with higher removal rates for middle molecules with the new dialyzer FX CorAL 600 compared to the FX 600. Hemocompatibility profiles were mostly similar, with lower activation of C5a and of sC5b9 with FX CorAL 600 compared to FX 600. The new dialyzer provides comparable performance levels capable of delivering adequate treatment and good tolerability for the patient.

Background and Aims Activation of the complement system may occur during blood-membrane interactions in hemodialysis and contribute to chronic inflammation of patients with end-stage renal disease (ESRD). Hydrophilic modification with polyvinylpyrrolidone (PVP) has been suggested to increase the biocompatibility profile of dialysis membranes. In the present study we compared complement activation of synthetic and cellulose-based membranes, including the polysulfone membrane with α-tocopherol-stabilized, PVP-enriched inner surface of the novel FX CorAL dialyzer, and linked the results to their physical characteristics. Method Eight synthetic and cellulose-based dialyzers (FX CorAL, FX CorDiax [Fresenius Medical Care]; Polyflux, THERANOVA [Baxter]; ELISIO, SUREFLUX [Nipro]; xevonta [B. Braun]; FDX [Nikkisio Medical]) were investigated in the present study. Complement activation (C3a, C5a, sC5b-9) was evaluated in a 3h ex vivo recirculation model with human blood. Albumin sieving coefficients were determined over a 4h ex vivo recirculation model with human plasma as a surrogate of secondary membrane formation. Zeta potential was measured as an indicator for the surface charge of the membranes. Results The FX CorAL dialyzer induced the lowest activation of the three complement factors (C3a: -39.4%; C5a: -57.5%; sC5b-9: -58.9% compared to the reference). Highest complement activation was found for the cellulose-based SUREFLUX (C3a: +154.0%) and the FDX (C5a: +335.0%; sC5b-9: +287.9%) dialyzers. Moreover, the FX CorAL dialyzer had the nearest-to-neutral zeta potential (-2.38 mV) and the lowest albumin sieving coefficient decrease over time. Albumin sieving coefficient decrease was associated with complement activation by the investigated dialyzers. Conclusion Our present results indicate that the surface modification implemented in the FX CorAL dialyzer reduces secondary membrane formation and improves the biocompatibility profile. Further clinical studies are needed to investigate whether these observations will result in a lower inflammatory burden of hemodialysis patients.

Background and Aims Hydrophilic modification with polyvinylpyrrolidone (PVP) increases the biocompatibility profile of synthetic dialysis membranes. However, PVP may be eluted into patient’s blood, which has been discussed as a possible cause for adverse reactions rarely occurring with synthetic membranes. We now investigated the content of PVP and its elution from the blood-side surface from commercially available dialyzers, including the novel FX CorAL with α-tocopherol-stabilized, PVP-enriched membrane, and link the results to the level of platelet loss during dialysis as a maker of biocompatibility. Method Six synthetic, PVP containing, dialyzers (FX CorAL, FX CorDiax [Fresenius Medical Care]; Polyflux, THERANOVA [Baxter]; ELISIO [Nipro]; xevonta [B. Braun]) were investigated in the present study. The content of PVP on blood-side surface was determined with X-ray photoelectron spectroscopy (XPS). The amount of elutable PVP was measured photometrically after 5h recirculation. The level of platelet loss was evaluated in an ex vivo recirculation model with human blood. Results Highest PVP content on the blood-side surface was found for the polysulfone-based FX CorAL (26.3%), while the polyethersulfone-based THERANOVA (15.6%) had the lowest PVP content. Elution of PVP was highest for the autoclave steam sterilized THERANOVA (9.1 mg/1.6m² dialyzer) and Polyflux (9.0 mg/1.6m² dialyzer), while the lowest PVP elution was found for the INLINE steam sterilized FX CorAL and FX CorDiax (< 0.5 mg/1.6m² dialyzer, for both). Highest platelet loss was found for xevonta (+164.4% compared to the reference) and the lowest for the FX CorAL (-225.2%) among the polysulfone-based dialyzers; among the polyethersulfone-based dialyzers, THERANOVA (+95.5%) had the highest and ELISIO (-52.1%) the lowest platelet loss. Conclusion PVP content and elution differs between commercially available dialyzers and was found to be linked to the membrane material and sterilization method. The amount of non-eluted PVP on the blood-side surface may be an important determinant for the hemocompatibility of dialyzers.

INTRODUCTION Hydrophilic modification with polyvinylpyrrolidone (PVP) increases the biocompatibility profile of synthetic dialysis membranes. However, PVP may be eluted into the patient's blood, which has been discussed as a possible cause for adverse reactions rarely occurring with synthetic membranes. We investigated the content of PVP and its elution from the blood-side surface from commercially available dialyzers, including the novel FX CorAL, with PVP-enriched and α-tocopherol-stabilized membrane, and link the results to the level of platelet loss during dialysis as a maker of biocompatibility. METHODS Six synthetic, PVP containing, dialyzers (FX CorAL, FX CorDiax [Fresenius Medical Care]; Polyflux, THERANOVA [Baxter]; ELISIO [Nipro]; xevonta [B. Braun]) were investigated in the present study. The content of PVP on blood-side surface was determined with X-ray photoelectron spectroscopy (XPS). The amount of elutable PVP was measured photometrically after 5 h recirculation. The level of platelet loss was evaluated in an ex vivo recirculation model with human blood. FINDINGS Highest PVP content on the blood-side surface was found for the polysulfone-based FX CorAL (26.3%), while the polyethersulfone-based THERANOVA (15.6%) had the lowest PVP content. Elution of PVP was highest for the autoclave steam-sterilized THERANOVA (9.1 mg/1.6 m2 dialyzer) and Polyflux (9.0 mg/1.6 m2 dialyzer), while the lowest PVP elution was found for the INLINE steam sterilized FX CorAL and FX CorDiax (

Activation of the complement system may occur during blood-membrane interactions in hemodialysis and contribute to chronic inflammation of patients with end-stage renal disease. Hydrophilic modification with polyvinylpyrrolidone (PVP) has been suggested to increase the biocompatibility profile of dialysis membranes. In the present study we compared the complement activation of synthetic and cellulose-based membranes, including the polysulfone membrane with α-tocopherol-stabilized PVP-enriched inner surface of the novel FX CorAL dialyzer, and linked the results to their physical characteristics. Eight synthetic and cellulose-based dialyzers (FX CorAL, FX CorDiax [Fresenius Medical Care]; Polyflux, THERANOVA [Baxter]; ELISIO, SUREFLUX [Nipro]; xevonta [B. Braun]; FDX [Nikkisio Medical]) were investigated in the present study. Complement activation (C3a, C5a, and sC5b-9) was evaluated in a 3 hours ex vivo recirculation model with human blood. Albumin sieving coefficients were determined over a 4 hours ex vivo recirculation model with human plasma as a surrogate of secondary membrane formation. Zeta potential was measured as an indicator for the surface charge of the membranes. The FX CorAL dialyzer induced the lowest activation of the three complement factors (C3a: -39.4%; C5a: -57.5%; and sC5b-9: -58.9% compared to the reference). Highest complement activation was found for the cellulose-based SUREFLUX (C3a: +154.0%) and the FDX (C5a: +335.0% and sC5b-9: +287.9%) dialyzers. Moreover, the FX CorAL dialyzer had the nearest-to-neutral zeta potential (-2.38 mV) and the lowest albumin sieving coefficient decrease over time. Albumin sieving coefficient decrease was associated with complement activation by the investigated dialyzers. Our present results indicate that the surface modification implemented in the FX CorAL dialyzer reduces the secondary membrane formation and improves the biocompatibility profile. Further clinical studies are needed to investigate whether these observations will result in a lower inflammatory burden of hemodialysis patients.

Background The iron-based phosphate binder (PB), sucroferric oxyhydroxide (SFOH), is indicated to control serum phosphorus levels in patients with chronic kidney disease on dialysis. Methods This non-interventional, prospective, multicentre, cohort study conducted in seven European countries evaluated the safety and effectiveness of SFOH in dialysis patients with hyperphosphataemia in routine practice. Safety outcomes included adverse drug reactions (ADRs) and changes in iron-related parameters. SFOH effectiveness was evaluated by changes-from-baseline (BL) in serum phosphorus and percentage of patients achieving in-target phosphorus levels. Results The safety analysis set included 1365 patients (mean observation: 420.3 ± 239.3 days). Overall, 682 (50.0%) patients discontinued the study. Mean SFOH dose during the observation period was 1172.7 ± 539.9 mg (2.3 pills/day). Overall, 617 (45.2%) patients received concomitant PB(s) during SFOH treatment. ADRs and serious ADRs were observed for 531 (38.9%) and 26 (1.9%) patients. Most frequent ADRs were diarrhoea (194 patients, 14.2%) and discoloured faeces (128 patients, 9.4%). Diarrhoea generally occurred early during SFOH treatment and was mostly mild and transient. Small increases from BL in serum ferritin were observed (ranging from +12 to +75 µg/L). SFOH treatment was associated with serum phosphorus reductions (6.3 ± 1.6 mg/dL at BL versus 5.3 ± 1.8 mg/dL at Month 30; ΔBL: −1.0 mg/dL, P Conclusions SFOH has a favourable safety and tolerability profile in a real-world setting, consistent with results of the Phase 3 study. Moreover, SFOH improved serum phosphorus control with a low daily pill burden.

Background and Aims Vascular calcification as cause of vascular stiffness is a major contributor to the high cardiac burden among stage 5 chronic kidney disease dialysis (CKD5HD) patients. Early identification of patients with high calcification propensity is crucial for proper risk stratification and management of these patients. Recently, a novel in vitro test (T50-test) was developed which determines calcification propensity of human serum and predicts mortality among ND-CKD (non-dialysis chronic kidney disease) patients, kidney transplant recipients and CKD5HD patients suffering from secondary hyperparathyroidism. We now evaluated whether these results can be confirmed in an unselected cohort of CKD5HD patients and can be used in the future for improving care of these patients. Method This prospective clinical study included 776 incident and prevalent hemodialysis patients from 8 Fresenius Medical Care NephroCare centers in Cataluña (Spain). T50 was determined at Calciscon AG, all other clinical data were retrieved from the European Clinical Database (EuCliD®). After their baseline T50 measurement, patients were followed for two years for the occurrence of the primary endpoint all-cause mortality. The association between T50 and all-cause mortality was examined by using proportional subdistribution hazards regression modelling accounting for kidney transplantation as competing event. In sensitivity analyses we adjusted for age, sex, vascular access (fistula/graft, catheter), treatment modality (HD, HDF), Charlson comorbidity index and dialysis vintage. Results Mean age of the study population was 72.2 years and 63.8% were male. 42.5% had diabetes and 55.0% past history of cardiovascular disease. Mean T50 was 283.4 min among the total cohort. During follow-up, 185 (23.8%) patients died. Patients who reached the endpoint had a significantly lower T50 at baseline as compared to those who survived during follow-up (269.6 vs 287.7 min, p = 0.001). A cross-validated model (mean c statistic: 0.5767) identified T50 as a linear predictor of all-cause-mortality (subdistribution hazard ratio (per min): 0.9957, 95% CI [0.9933;0.9981]). T50 remained a significant predictor of all-cause mortality after adjusting for relevant confounding in sensitivity analyses. Conclusion In this prospective study, we confirmed that T50 is an independent predictor of all-cause mortality among a large unselected cohort of hemodialysis patients. T50 may be used to identify patients with high vascular calcification propensity and mortality risks and may help physicians to implement a personalized and more precise renal replacement therapy option.

Background and Aims Chronic kidney diseases disrupt normal bone-mineral axis endocrine functions causing the onset of mineral bone disorders (MBDs). The general and hemodialysis (HD) populations have been found to exhibit diurnal rhythms in phosphate (PO4), calcium (Ca), and parathyroid hormone (PTH) regulation (Trivedi et al. J Nephrol. 2015), but reference values for fluctuations have not been established in HD patients and do not consider PO4 binder use. We profiled the diurnal rhythms of MBD labs overall and stratified by PO4 binder use in a large nationally representative HD population in the United States. Method We used prevalent in-center HD patient (vintage >90 days) data on adults (age ≥18 years) treated at a dialysis organization in 2018. Mean annual pre-HD blood PO4, corrected Ca, and intact PTH levels were computed in 2-hour periods through 24 hours for the population and stratified by binder use. HD initiation time was a varying exposure, allowing patients to switch time groups if blood draws occurred in multiple time periods. Mean MBD lab levels with 95% confidence limits were plotted using nonparametric smoothing spline models to fit data and calculate trajectories throughout the day. Results The population of adult HD patients (n=156,873) was: mean age 62.8±14.3 years, 57.1% male, 58.2% white race, 41.9% with diabetes, 19.6% with congestive heart failure, and HD vintage 1510±1289 days. Mean pre-dialysis albumin=3.8±0.4 g/dL, PO4=5.4±1.5 mg/dL, corrected Ca=9.1±0.6 mg/dL, PTH=468±333 pg/dL for the population. Mean PO4, corrected Ca and PTH levels varied remarkably by 0.9 mg/dL, 0.2 mg/dL, and 186 pg/dL throughout the day. For PO4 and PTH, nadir levels occurred from 0900 to 1100 hours (5.3±1.6 mg/dL and 473±340 pg/dL), followed by a rise to a mid-day peak from 1700 to 1900 hours (5.8±1.8 mg/dL and 562±401 pg/dL), and the highest levels had a peak time from 2300 to 0100 hours (6.2±2.1 mg/dL and 659±389 pg/dL) (Figure 1A & C). Corrected Ca showed relatively inverse fluctuations to PO4 and PTH, with peak levels from 1100 to 1300 hours (9.2±0.7 mg/dL) and nadir levels from 1900 to 2100 hours (9.0±0.7 mg/dL) (Figure 1B). Similar fluctuations and levels were observed for PO4 and PTH among patients using any phosphate binder type (90.7%), however, patients not using a phosphate binder exhibited absolute values that were persistently lower at every timepoint (Figure 1D & F). Corrected Ca levels were similar by any binder use (Figure 1E). Conclusion Our results suggest PO4, Ca, and PTH levels have a diurnal variation of 0.9 mg/dL, 0.2 mg/dL, and 186 pg/dL in hemodialysis patients. PO4 and PTH exhibit a nadir in the morning, a mid-day peak and a larger nocturnal peak. Ca exhibits relatively inverse diurnal fluctuations with PO4 and PTH. Patients using any binder exhibit similar fluctuations and levels of PO4 and PTH; while patients not requiring a binder have similar fluctuations, yet persistently lower levels of PO4 and PTH. Given PO4 binder and calcimimetic therapies are commonly used for treatment of MBDs based on pre-dialysis blood levels, these findings provide insights for further research and pose the question if algorithms are warranted to compute daily time-adjusted levels for MBD laboratories.

Background and Aims The patient’s reported perception of their health-related quality of life (HRQOL) are important patient-centered metrics that associate with outcomes in hemodialysis (HD) populations. Patients using an arteriovenous (AV) access (fistula or graft) tend to report better HRQOL compared with those dialyzing via a catheter (Wasse et al. 2007; Moura et al. 2014). However, these differences might be due to distinct characteristics of patients who have an AV access placed, or not. For example, catheter-dependent patients are typically older and have more comorbidities than those with an AV access. We considered a different way to evaluate the impact of vascular access on HRQOL in HD patients by assessing whether a change from a catheter to an AV access, and vice versa, associates with changes in HRQOL. Method We used data from adult in-center HD patients (age ≥18 years) treated at a large dialysis organization in the United States from 2016-2017. Patients who had one vascular access conversion and used the corresponding access for at least 12 months before and after the conversion were included in the analysis. HRQOL was assessed by Kidney Disease Quality of Life (KDQOL-36) surveys (0-100 scale) performed over the 12 months preceding and following the change. We computed the mean score for each of the five KDQOL domains in each time period and compared the score differences between pre- and post-access change using Student’s t-tests for each conversion type. Results A total of 1088 HD patients (mean age 59.2 years, 52.6% male, and 59.3% white race) switched from a catheter to an AV access and 3427 patients (mean age 61.8 years, 47.8% male, and 50.7% white race) switched from an AV access to a catheter over the analysis period. After conversion from a catheter to an AV access, patients reported significantly higher physical component summary (+0.5, p Conclusion Our results suggest switching from a catheter to an AV access may associate with patients perceiving an improved physical and mental HRQOL. In contrast, changing from an AV access to a catheter might associate with a diminished perception of physical HRQOL. Albeit distinctions in HRQOL are statistically significant, absolute differences were below two points and the clinical meaning needs to be assessed in further adjusted analyses considering the underlying reasons for vascular access conversions. Nonetheless, these findings may be of importance to provide more patient focused care.

BACKGROUND: High-flux dialyzers effectively remove uremic toxins, are hemocompatible to minimize intradialytic humoral and cellular stimulation, and have long-term effects on patient outcomes. A new dialyzer with a modified membrane surface has been tested for performance and hemocompatibility. METHODS: This multicenter, prospective, randomized, crossover study involved the application of the new polysulfone-based FX CorAL 600 (Fresenius Medical Care, Bad Homburg, Germany), the polyarylethersulfone-based Polyflux 170H (Baxter Healthcare Corporation, Deerfield, IL), and the cellulose triacetate–based SureFlux 17UX (Nipro Medical Europe, Mechelen, Belgium), for 1 week each, to assess the noninferiority of the FX CorAL 600’s removal rate of β2-microglobulin. Performance was assessed by removal rate and clearance of small- and medium-sized molecules. Hemocompatibility was assessed through markers of complement, cell activation, contact activation, and coagulation. RESULTS: Of 70 patients, 58 composed the intention-to-treat population. The FX CorAL 600’s removal rate of β2-microglobulin was noninferior to both comparators (P

International audience; The hemodialysis (HD) session per se is a catabolic event contributing to protein-energy wasting via several mechanisms including nutrient losses. Amino acids (AAs) losses in the dialysate are estimated from 6 to 10 g per treatment. The HD patient plasma AA concentration is usually lower than in normal subjects. This is even more marked in patients with long dialysis vintage or malnutrition. Methods: The aim of the study was to evaluate the effect on mass balance of a branched-chain AA (BCAA)-enriched (valine, isoleucine, leucine) dialysis fluid in a group of 6 stable HD anuric patients, fasting since 12 hours. The specific choice of BCAA relied on their key role on protein and muscle anabolism and their usual decreased plasma concentration in HD patients. Each patient was prescribed in a cross-over design and random order, either receiving a standard high-flux HD or an HD treatment using a BCAA-enriched acid concentrate designed to achieve a physiological plasma concentration of BCAAs. HD prescription remained unchanged during the 2 phases of study. Dialysate electrolytes prescription was kept constant for each individual patient, as well as dialysate glucose concentration (5.5 mmol/L). Pre- and post-dialysis BCAAs concentrations were measured by Ion-Exchange Liquid Chromatography. Postdialysis concentrations were corrected for hemoconcentration, and net mass transfer was calculated.Results: Six stable prevalent end-stage kidney disease patients were studied. They consisted of 5 men and 1 woman, aged 69.9 years, with body mass index of 25.2 kg/m2. Treatment schedule consisted of treatment time 4 hours, high-flux polysulfone membrane (1.8 m2), blood flow 350 mL/minute, and dialysate/blood flow ratio at 1.5. The average BCAAs concentration in dialysate was targeted to physiological levels and assessed in 6 different samples, respectively for plasma valine, isoleucine, and leucine at 271, 78, and 145 μmol/L. With standard dialysate, plasma valine decreased from 204.5 to 130.8 (P = .0014). Plasma isoleucine and leucine changes were not significant, respectively from 65.7 to 59.3 μmol/L and 110.3 to 113.4 μmol/L. When using the BCAA-enriched dialysis fluid, plasma valine increased from 197.2 to 269.2 μmol/L (P = .0001), plasma isoleucine and leucine respectively from 63.2 to 84.7 (P = .0022) and from 107.2 to 161.6 μmoles/L (P = .0002). Dialysis dose estimated from KT/V did not differ between the sessions. The mass transfer with BCAA-enriched dialysate was +115, +16, and + 83 μmol per session for leucine, isoleucine, and valine, respectively.Conclusion(s): In conclusion, the addition of BCAAs at physiological concentration in the dialysis fluid contributes to restore physiological plasma concentrations for valine, isoleucine, and leucine at the end of a dialysis session. As BCAAs are essential to muscle balance, this could help to limit losses of BCAAs, restore physiological BCAAs concentrations, and decrease muscle catabolism observed during the HD treatment. Further outcome-based studies are needed to confirm this hypothesis on a larger scale and longer treatment time.

Tungiasis (sand flea disease) is a neglected tropical disease. Heavy infestation results in mutilation of the feet and difficulty in walking. We identified eight individuals with extremely severe tungiasis in rural Madagascar. To prevent reinfestation, four individuals received solid shoes and four received a daily application of an herbal repellent effective against Tunga penetrans. Over a period of 10 weeks the feet were examined and the severity of tungiasis- associated morbidity was measured. Within this period, the severity score for acute tungiasis decreased 41% in the shoe group and 89% in the repellent group. The four major inflammation-related symptoms disappeared in the four patients of the repellent group, but only in two patients of the shoe group. Those observations indicate that cases with extremely severe tungiasis, associated morbidity almost totally disappears within 10 weeks if the feet are protected by a repellent. Wearing shoes reduced acute morbidity only marginally.

Antimikrobielle Peptide (AMPs) sind kleine, kationische, amphiphile Peptide mit breiter mikrobizider Aktivität sowohl gegen Bakterien als auch gegen Pilze. Bei Säugetieren bilden die AMPs die vorderste Verteidigungslinie des Wirts gegen Infektionen und sie spielen allgemein eine wichtige Rolle als Effektoren des angeborenen Immunsystems. Die Ära der AMPs wurde vor mehr als 60 Jahren eingeläutet, als mit den Polymyxinen und Tyrothricin die ersten kationischen zyklischen Peptidantibiotika Eingang in die klinische Anwendung fanden. Die guten klinischen Erfahrungen in der Behandlung von beispielsweise Schleimhautinfektionen und das spätere Verständnis des Wirkmechanismus haben dazu geführt, dass die AMPs heute zur Behandlung entzündlicher Hauterkrankungen und zur Verbesserung der Heilung infizierter Wunden in Betracht gezogen werden. Auf Grundlage der präklinischen Ergebnisse, darunter Pathobiochemie und molekulare Medizin, werden gezielte Therapiestrategien entwickelt, und ersten Ergebnissen zufolge beeinflussen AMPs die Prozesse in der erkrankten Haut. Wichtig ist, dass AMPs im Gegensatz zu anderen Antibiotika offenbar nicht die Entwicklung antibiotikaresistenter Mikroorganismen fördern. Daher sollten AMPs in klinischen Studien auf ihre Wirksamkeit und Verträglichkeit bei entzündlichen Hauterkrankungen und chronischen Wunden untersucht werden. Abgesehen von möglichen Anwendungsfeldern scheinen diese Peptide ein geeignetes Beispiel für das Paradigma der translationalen Medizin für Hautkrankheiten zu sein, das heute als «Straße mit Verkehr in beiden Richtungen» gesehen wird - aus dem Labor ans Krankenbett und umgekehrt vom Krankenbett ins Labor.

Background: Topical preparations are a common treatment for superficial acute wounds, which at the least do not interfere with healing and ideally result in enhanced wound healing irrespective of microbial colonization. Objective: To examine the effects of a topical antimicrobial gel and its vehicle on the wound healing of standardized, superficial abrasions. Methods: Thirty-three healthy volunteers were enrolled in a double-blinded, randomized, intraindividual comparison study. Three standardized, superficial abrasions were induced on their forearms. A tyrothricin 0.1% gel (Tyrosur® gel; Engelhard Arzneimittel GmbH & Co. KG, Niederdorfelden, Germany) and its vehicle were randomly applied to two of the test areas, and one lesion remained untreated. Results: A significant improvement of wound healing was seen with both tyrothricin 0.1% gel and its corresponding vehicle in the clinical assessment. The mean area under the curve (AUC) of wound healing scores was the same for both preparations and the mean reepithelization scores were comparable at all test points over the entire 12 days. A lower mean AUC representing less reepithelization was found for the untreated test fields. Conclusion: The use of tyrothricin 0.1% gel and its corresponding vehicle resulted in statistically significant improved wound healing with an earlier onset of healing in particular. Based on these results obtained using an abrasive wound model, it can be concluded that the addition of tyrothricin 0.1% to the gel vehicle did not interfere with the improved wound healing seen with the vehicle alone.

An acute pharyngitis is characterised by mild to severe sore throat mostly accompanied by inflammation, throat pain, pain on swallowing, and burning. This randomised, double-blind, placebo-controlled phase III study was conducted for comparison of the efficacy and safety of a newly developed lidocaine (2-(diethylamino)-N-(2,6-dimethylphenyl) acetamide, CAS 137-58-6) 8 mg lozenge formulation (Trachisan Halsschmerztabletten) for the treatment of acute sore throat not necessarily to be treated with antibiotics. 240 patients of both genders were enrolled. The study was performed in a single centre setting and consisted of two parts. A 2-h stationary phase (single dose treatment) was directly followed by a 46-h ambulatory phase, where patients were allowed to take up to a maximum of 11 further lozenges (multiple dose treatment). Pain intensity was assessed via Visual Analogue Scale during the course of the study. Moreover, the global efficacy and tolerability of the treatments were assessed. Lidocaine 8 mg sore throat lozenges were found to be superior to placebo for all efficacy parameters investigated. For the primary efficacy parameter, area under the curve of pain intensity from baseline over 2 h (AUC(0-2h)), i.e. after single-dose treatment, a significant treatment difference with a p-value of p < 0.001 in favour of the verum treatment could be demonstrated. Significant superiority could also be demonstrated for the descriptive AUC(0-48h) values, reflecting the treatment effect during the ambulatory multiple dose phase. Pain relief, minimum pain intensity, meaningful pain relief and the time of onset of meaningful pain relief as well as the assessments of global efficacy underlined the superiority of the treatment with lidocaine 8 mg sore throat lozenges. Global tolerability of the verum treatment was rated as "good" or "very good" in the majority of cases, the number of study drug related adverse events was low and evenly distributed to both treatment groups. Therefore, the results of the trial emphasise lidocaine 8 mg sore throat lozenges to be a favourable option in the treatment of pain symptoms of an acute sore throat.

Introduction VERIFIE ( NCT02687594 ) est une etude de securite et d’efficacite de l’oxyhydroxyde sucroferrique (SFOH), un chelateur des phosphates (CP) non calcique a base de fer, chez des patients dialyses dans le cadre de la pratique clinique quotidienne. Patients et methodes VERIFIE est une etude d’incidence europeenne prospective, multicentrique, non interventionnelle. Cette analyse intermediaire de la population de patients francais reprend les resultats de securite et d’efficacite 18 mois apres la premiere visite du premier patient. Resultats Les donnees disponibles concernaient 214 patients traites parmi le groupe d’analyse de securite (âge moyen : 63,4 ans ; 72,9 % de sexe masculin). Parmi ceux-ci, 195 patients ont ete inclus dans le groupe d’analyse complete pour l’evaluation de l’efficacite du SFOH. Lors de leur recrutement dans l’etude, 53,3 % des patients avaient deja utilise precedemment un chelateur des phosphates. La dose journaliere moyenne de SFOH etait de 1035,9 mg (2,1 comprimes/jour) au debut de l’etude et cette dose initiale avait ete portee a 1223,7 mg (2,5 comprimes/jour) pour la derniere dose documentee. Environ la moitie des patients (48,1 %) ont recu un traitement concomitant par un autre chelateur des phosphates au cours de la periode d’observation. Un total de 78 patients (36,5 %) ont rapporte au moins un effet indesirable lie au medicament ; la plupart de ces effets indesirables concernaient le tractus gastro-intestinal (70 patients). Cinquante-neuf patients (27,6 %) ont arrete prematurement l’etude. On n’a constate aucune modification significative des concentrations de ferritine, de TSAT ou d’hemoglobine entre le debut de l’etude et le 3e et le 6e mois. Le traitement par le SFOH a ete associe a une diminution significative des phosphates seriques (sP), de 2,0 mmol/L au debut de l’etude a 1,8 mmol/L au 3e et au 6e mois (Δ par rapport au debut de l’etude pour ces deux points temporels : p Conclusion Le SFOH a ete bien tolere chez les patients francais dialyses et aucun nouveau risque de securite n’a ete identifie. Le SFOH s’est avere efficace pour reduire et maintenir les concentrations de phosphates seriques, avec un nombre limite de comprimes quotidiens.

Background Tungiasis, a parasitic skin disease caused by the female sand flea Tunga penetrans, is a prevalent condition in impoverished communities in the tropics. In this setting, the ectoparasitosis is associated with important morbidity. It causes disfigurement and mutilation of the feet. Feasible and effective treatment is not available. So far prevention is the only means to control tungiasis-associated morbidity. Methodology In two villages in Central Madagascar, we assessed the efficacy of the availability of closed shoes and the twice-daily application of a plant-based repellent active against sand fleas (Zanzarin) in comparison to a control group without intervention. The study population was randomized into three groups: shoe group, repellent group and control group and monitored for ten weeks. The intensity of infestation, the attack rate and the severity of tungiasis-associated morbidity were assessed every two weeks. Findings In the repellent group, the median attack rate became zero already after two weeks. The intensity of the infestation decreased constantly during the observation period and tungiasis-associated morbidity was lowered to an insignificant level. In the shoe group, only a marginal decrease in the intensity of infestation and in the attack rate was observed. At week 10, the intensity of infestation, the attack rate and the severity score for acute tungiasis remained significantly higher in the shoe group than in the repellent group. Per protocol analysis showed that the protective effect of shoes was closely related to the regularity with which shoes were worn. Conclusions Although shoes were requested by the villagers and wearing shoes was encouraged by the investigators at the beginning of the study, the availability of shoes only marginally influenced the attack rate of female sand fleas. The twice-daily application of a plant-based repellent active against sand fleas reduced the attack to zero and lowered tungiasis-associated morbidity to an insignificant level., Author Summary Tungiasis (sand flea disease) is a parasitic skin disease present in many resource-poor communities in South America, the Caribbean and sub-Saharan Africa. In this setting tungiasis is associated with important morbidity. Hitherto, the only effective treatment is the surgical extraction of embedded sand fleas. In the endemic areas this is done using inappropriate sharp instruments and causes more harm than good. The prevention of the infestation is the only option to control morbidity. In this study we show that the twice daily application of a herbal repellent based on coconut-oil (Zanzarin), is highly effective in preventing sand flea disease in a heavily affected community in Madagascar. The attack rate became zero immediately after starting the application of the repellent. The degree of tungiasis associated morbidity approached zero within 10 weeks. In contrast, the availability of closed solid shoes had only a marginal protective effect; although shoes were requested by the villagers and wearing shoes was encouraged by the investigators at the beginning of the study. In a control group from the same village the attack rate, the intensity of infestation and of tungiasis-associated morbidity remained unchanged. Our study in rural Madagascar shows that effective und sustainable morbidity control is possible using a repellent derived from coconut oil.

Antimicrobial peptides (AMPs) are small, cationic, amphiphilic peptides with broad-spectrum microbicidal activity against both bacteria and fungi. In mammals, AMPs form the first line of host defense against infections and generally play an important role as effector agents of the innate immune system. The AMP era was born more than 6 decades ago when the first cationic cyclic peptide antibiotics, namely polymyxins and tyrothricin, found their way into clinical use. Due to the good clinical experience in the treatment of, for example, infections of mucus membranes as well as the subsequent understanding of mode of action, AMPs are now considered for treatment of inflammatory skin diseases and for improving healing of infected wounds. Based on the preclinical findings, including pathobiochemistry and molecular medicine, targeted therapy strategies are developed and first results indicate that AMPs influence processes of diseased skin. Importantly, in contrast to other antibiotics, AMPs do not seem to propagate the development of antibiotic-resistant micro-organisms. Therefore, AMPs should be tested in clinical trials for their efficacy and tolerability in inflammatory skin diseases and chronic wounds. Apart from possible fields of application, these peptides appear suited as an example of the paradigm of translational medicine for skin diseases which is today seen as a ‘two-way road’ – from bench to bedside and backwards from bedside to bench.

omega-6 and omega-3 polyunsaturated fatty acids (PUFAs) play a central role in the normal development and functioning of the brain and central nervous system. Long-chain PUFAs (LC-PUFAs) such as eicosapentaenoic acid (EPA, C20:5omega-3), docosahexaenoic acid (DHA, C22:6omega-3) and arachidonic acid (AA, C20:4omega-6), in particular, are involved in numerous neuronal processes, ranging from effects on membrane fluidity to gene expression regulation. Deficiencies and imbalances of these nutrients, not only during the developmental phase but throughout the whole life span, have significant effects on brain function. Numerous observational studies have shown a link between childhood developmental disorders and omega-6:omega-3 fatty acid imbalances. For instance, neurocognitive disorders such as attention-deficit hyperactivity disorder (ADHD), dyslexia, dyspraxia and autism spectrum disorders are often associated with a relative lack of omega-3 fatty acids. In addition to a high omega-6 fatty acid intake and, in many cases, an insufficient supply of omega-3 fatty acids among the population, evidence is increasing to suggest that PUFA metabolism can be impaired in individuals with ADHD. In this context, PUFA imbalances are being discussed as potential risk factors for neurodevelopmental disorders. Another focus is whether the nutritive PUFA requirements-especially long-chain omega-3 fatty acid requirements-are higher among some individuals. Meanwhile, several controlled studies investigated the clinical benefits of LC-PUFA supplementation in affected children and adolescents, with occasionally conflicting results.

An acute pharyngitis is characterised by mild to severe sore throat mostly accompanied by inflammation, throat pain, pain on swallowing, and burning. This randomised, double-blind, placebo-controlled phase III study was conducted for comparison of the efficacy and safety of a newly developed lidocaine (2-(diethylamino)-N-(2,6-dimethylphenyl) acetamide, CAS 137-58-6) 8 mg lozenge formulation (Trachisan Halsschmerztabletten) for the treatment of acute sore throat not necessarily to be treated with antibiotics. 240 patients of both genders were enrolled. The study was performed in a single centre setting and consisted of two parts. A 2-h stationary phase (single dose treatment) was directly followed by a 46-h ambulatory phase, where patients were allowed to take up to a maximum of 11 further lozenges (multiple dose treatment). Pain intensity was assessed via Visual Analogue Scale during the course of the study. Moreover, the global efficacy and tolerability of the treatments were assessed. Lidocaine 8 mg sore throat lozenges were found to be superior to placebo for all efficacy parameters investigated. For the primary efficacy parameter, area under the curve of pain intensity from baseline over 2 h (AUC(0-2h)), i.e. after single-dose treatment, a significant treatment difference with a p-value of p0.001 in favour of the verum treatment could be demonstrated. Significant superiority could also be demonstrated for the descriptive AUC(0-48h) values, reflecting the treatment effect during the ambulatory multiple dose phase. Pain relief, minimum pain intensity, meaningful pain relief and the time of onset of meaningful pain relief as well as the assessments of global efficacy underlined the superiority of the treatment with lidocaine 8 mg sore throat lozenges. Global tolerability of the verum treatment was rated as "good" or "very good" in the majority of cases, the number of study drug related adverse events was low and evenly distributed to both treatment groups. Therefore, the results of the trial emphasise lidocaine 8 mg sore throat lozenges to be a favourable option in the treatment of pain symptoms of an acute sore throat.

Hintergrund: Es wurde gezeigt, dass niederfrequenter Ultraschall eine Alternative zum chirurgischen Wunddebridement (WD) ist und die Wundheilung stimuliert; allerdings liegen hierzu nur wenige Daten vor. Ziel: Vergleich von Wirksamkeit, Vertraglichkeit und Nutzen der beiden Wundbehandlungsmethoden. Methoden: Monozentrische, prospektive, randomisierte, kontrollierte klinische Studie zur Beurteilung der von den Patienten berichteten Behandlungsergebnisse und der klinischen Wirksamkeit der ultraschallgestutzten Wundreinigung (UAW) im Vergleich zum WD. Ergebnisse: Insgesamt wurden 67 Patienten behandelt. Beide Behandlungen zeigten gute Wirksamkeit und Vertraglichkeit: 88% der UAW-Patienten und 85,2% der WD-Patienten berichteten einen mehr als geringfugigen Nutzen. Die Lebensqualitat besserte sich signifikant. In beiden Gruppen kam es zu einer Besserung des Wundstatus und zu einem Ruckgang der Schmerzen. Schlussfolgerung: Im Vergleich zum Goldstandard (WD) zeigt die UAW die gleiche hohe Wirksamkeit, einen ahnlichen Patientennutzen und eine verbesserte Lebensqualitat. Beide Verfahren sind fur die auserst nutzbringende leitlinienbasierte Behandlung chronischer Wunden gleichermasen geeignet.

Hintergrund: Psoriasis vulgaris (PV) ist mit einer niedriggradigen systemischen Entzündung verbunden. Ziel: Die Serummuster von Zytokinen und Wachstumsfaktoren wurden bei Patienten mit PV und allergischer Kontaktdermatitis (ACD) sowie bei gesunden Probanden untersucht, um systemische Entzündungsreaktionen bei diesen Erkrankungen zu beschreiben und zu vergleichen. Methoden: Insgesamt 12 entzündungssensitive Biomarker wurden mit Hilfe der Evidence Investigator™ Biochip-Technologie gleichzeitig analysiert. Ergebnisse: Bei PV waren der proinflammatorische Tumornekrosefaktor-α (TNF-α), Interferon-γ (IFN-γ), die Interleukine IL-1β, -2, -6, -8 und das Monozyten-Chemotaktische Protein-1 (MCP-1) erhöht. Bei ACD waren 2 Marker (TNF-α und MCP-1) erhöht und das regulatorische Zytokin IL-10 wies einen niedrigeren Wert auf. Das proinflammatorische IL-2 hatte bei PV und ACD die stärksten Korrelationen mit anderen pro- bzw. antiinflammatorischen Zytokinen, während IL-6 positiv mit dem Psoriasis Area and Severity Index korrelierte. Die Konzentrationen der Wachstumsfaktoren korrelierten mit MCP-1, jedoch nur bei PV. Schlussfolgerung: Obwohl PV eine vielfältigere proinflammatorische systemische Reaktion induziert, ist auch ACD mit einem systemischen Anstieg von Entzündungsmediatoren verbunden.

Hintergrund: Zur Wirksamkeit der Corticosteroid-Pulstherapie bei Alopecia areata (AA) liegen nur wenige Daten vor. Ziel: Mit

Hintergrund: Die photodynamische Therapie (PDT) stellt eine optimale Behandlung fur das Basalzellkarzinom (BCC) dar. Die konfokale Reflexionsmikroskopie (RCM; ref

Hintergrund: Demodex-Milben sind an verschiedenen Hautkrankheiten beteiligt und werden im Allgemeinen mittels Schabetest oder oberflachlichen Hautbiopsien nachgewiesen. Eine neue hochauflosende optische Koharenztomographie (HD-OCT) mit hoher lateraler und axialer Auflosung in einem horizontalen (en-face) und vertikalen (slice) Bildgebungsmodus konnte die Moglichkeit einer nichtinvasiven und schnellen In-vivo-Untersuchung auf Demodex-Milben bieten. Methoden: 20 Patienten mit Demodex-bedingten Hautkrankheiten und 20 nach Alter und Geschlecht vergleichbare Kontrollen wurden mittels HD-OCT untersucht. Die Milben pro Haarfollikel und Haarfollikel pro Gesichtsfeld wurden gezahlt und mit den Ergebnissen des Schabetests verglichen. Ergebnisse: In den HD-OCT-Bildern erschienen die Milben als helle runde Flecken, die in Gruppen von 3-5 Milben pro Haarfollikel angeordnet waren. Bei den Patienten mit Demodex-bedingter Hauterkrankung war eine mittlere Anzahl von 3,4 Milben pro Follikel nachweisbar bei einer mittleren Anzahl von 2,9 befallenen Follikeln pro Gesichtsfeld gegenuber einer mittleren Anzahl von 0,6 Milben in 0,4 befallenen Follikeln bei den Kontrollen. Der Schabetest war bei 21% der Patienten negativ. Schlussfolgerung: Die innovative HD-OCT ermoglicht einen schnellen und nichtinvasiven In-vivo-Nachweis von Demodex-Milben und konnte zu einem wichtigen Hilfsmittel in der Diagnose und Behandlungskontrolle von Demodex-bedingten Hauterkrankungen werden.

Hintergrund: Condylomata acuminata (CA) wird vom humanen Papillomavirus verursacht. Die meisten herkommlichen Therapien fur CA sind mit einer hohen Rezidivrate ve

Hintergrund: Im Jahr 2008 wurde in Deutschland das Hautkrebs-Screening in die gesetzlichen Gesundheitsleistungen fur Personen ≥35 Jahre aufgenommen. Bisher nehmen

Background Polyunsaturated fatty acids are essential nutrients for humans. They are structural and functional components of cell membranes and pre-stages of the hormonally and immunologically active eicosanoids. Recent discoveries have shown that the long-chained omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) also play an important role in the central nervous system. They are essential for normal brain functioning including attention and other neuropsychological skills. Materials and methods In our large observational study we monitored 810 children from 5 to 12 years of age referred for medical help and recommended for consuming polyunsaturated fatty acids (PUFA) in combination with zinc and magnesium by a physician over a period of at least 3 months. The food supplement ESPRICO® (further on referred to as the food supplement) is developed on the basis of current nutritional science and containing a combination of omega-3 and omega-6 fatty acids as well as magnesium and zinc. Study objective was to evaluate the nutritional effects of the PUFA-zinc-magnesium combination on symptoms of attention deficit, impulsivity, and hyperactivity as well as on emotional problems and sleep related parameters. Assessment was performed by internationally standardised evaluation scales, i.e. SNAP-IV and SDQ. Tolerance (adverse events) and acceptance (compliance) of the dietary therapy were documented. Results After 12 weeks of consumption of a combination of omega-3 and omega-6 fatty acids as well as magnesium and zinc most subjects showed a considerable reduction in symptoms of attention deficit and hyperactivity/impulsivity assessed by SNAP-IV. Further, the assessment by SDQ revealed fewer emotional problems at the end of the study period compared to baseline and also sleeping disorders. Mainly problems to fall asleep, decreased during the 12 week nutritional therapy. Regarding safety, no serious adverse events occurred. A total of 16 adverse events with a possible causal relationship to the study medication were reported by 14 children (1.7%) and only 5.2% of the children discontinued the study due to acceptance problems. Continuation of consumption of the food supplement was recommended by the paediatricians for 61.1% of the children. Conclusion Our results suggest a beneficial effect of a combination of omega-3 and omega-6 fatty acids as well as magnesium and zinc consumption on attentional, behavioural, and emotional problems of children and adolescents. Thus, considering the behavioural benefit in combination with the low risk due to a good safety profile, the dietary supplementation with PUFA in combination with zinc and magnesium can be recommended.