ZusammenfassungVeränderungen in der Mikrozirkulation der Haut sind ein häufig beobachtetes Begleitphänomen vieler Erkrankungen, weit über das Spektrum dermatologischer Krankheiten hinausreichend. Nicht alle dieser Veränderungen haben einen Krankheitswert, viele treten temporär auf, ohne schwerwiegende Folgen zu verursachen. Dies trifft für viele inflammatorische Erkrankungen wie die Psoriasis vulgaris oder das atopische Ekzem zu.Daneben gibt es aber auch Erkrankungen, bei denen funktionell und morphologisch erkennbare Mikroangiopathien zu schwerwiegenden Krankheitsfolgen führen. Eine der wichtigsten Erkrankungen in diesem Zusammenhang ist die systemische Sklerose, eine autoimmune Systemerkrankung mit multiplen Organmanifestationen. Hier sind die Untersuchungen der kutanen Mikrozirkulation sowohl in der Erstdiagnose als auch in der Prognose‐ und Verlaufsbeurteilung von weitreichender Bedeutung.Auch bei Erkrankungen der peripheren Hämodynamik wie der peripheren arteriellen Verschlusskrankheit (pAVK) und der chronisch venösen Insuffizienz (CVI) spielt das Verständnis von Mikrozirkulationsstörungen eine wichtige Rolle für die Therapie und die Erfolgskontrolle therapeutischer Interventionen.

Objective: to study the characteristics of mechanisms of the distant stimulating effect of full-thickness skin autograft (FTSG) on microvascular perfusion in local and systemic microcirculation disorders. Materials and methods. The experiment was carried out on 87 white male rats, divided into 5 groups: 1) control; 2) animals with local microcirculation disorders induced by sciatic nerve transection and neuroraphy; 3) animals with systemic microcirculation disorders caused by alloxan-induced diabetes; 4) animals that underwent FTSG after sciatic nerve transection and neurography; 5) animals that underwent FTSG in alloxan-induced diabetes. Laser Doppler flowmetry (LDF) was used to study microcirculation of the dorsal skin of the rear paw. Serum concentrations of vasoactive substances, including catecholamines (CA), histamine, and vasculoendothelial growth factor (VEGF) in the experimental animals were measured. A morphological study of the tissues of the autograft site was carried out on day 42 of the experiment. Results. On day 42 of the experiment, FTSG normalized perfusion in local and systemic microcirculation disorders. FTSG decreases CA level in nerve injury, and to a greater extent in alloxan-induced diabetes. Serum histamine increase under FTSG was more pronounced in rats with nerve injury. Serum VEGF in rats with nerve injury and FTSG increased, which was not observed in alloxan-induced diabetes. Histological assay of the autograft site revealed degenerative changes in the epidermis and dermis of the autotransplant in both experimental models of microcirculatory disorders. Eosinophilic infiltration of the autograft site was more pronounced in nerve injury than in alloxan-induced diabetes. Conclusion. FTSG has a distant stimulating effect on microcirculation, which manifests itself in the same degree in both local and systemic microcirculation disorders. The distant stimulating effect of FTSG on microcirculation is multicomponent in nature and includes a set of regulatory reactions, whose severity differs in local and systemic microcirculatory disorders.

Background:Intermittent pneumatic compression (IPC) has established itself as a cornerstone in the combined decongestive therapy (CDT) of leg oedema, however, there is little evidence on the degree of volume shifts.Objectives:We performed continuous volume measurements during CDT to quantify volume shifts in a controlled trial. In addition, "wrapping/underpadding" and medical compression stockings were evaluated regarding decongestion and leg oedema, respectively.Materials & Methods:The volume reduction of CDT in patients with lymphoedema of the legs was measured. The additive decongesting effect of a padding surrounding the leg under the lymph cuff (IPC +) was evaluated. The efficacy of compression stockings in the maintenance phase was analysed.Results:Volume reductions were observed on the thigh (2%) and lower leg (5%) utilising IPC. Further significant volume reduction of the thigh (6%, p < 0.001) and lower leg (8%, p = 0.002) was observed with IPC +. Considering the thigh volume, patients with thigh-length compression stockings in the maintenance phase showed a significantly less pronounced increase in volume than patients with below-knee compression stockings (98% vs. 101% after six weeks; p < 0.05).Conclusion:The additional padding of the leg during an IPC session induces significantly more pronounced volume reduction. Medical compression stockings help to prevent volume increase in the maintenance phase.

Introduction: The aim of the study was to systematically analyze the influence of extracorporeal photopheresis (ECP) on the quality of life (LQ) and the course of the disease in patients with Mycosis Fungoides ( MF), as well as with Graft-versus-Host Disease (GvHD). Methods: LQ was monitored retrospectively by using the dermatology life quality index (DLQI) and Skindex29 test before ECP onset and after the last ECP. Disease parameters were assessed by objective criteria i.e. number of associated medical drugs taken, intervals between therapeutic cycles, gradual change of the disease, and eventual side-effects and complications of ECP therapy. Results: Fifty-one patients were treated with ECP during 2008-19; 19 out of 51 died, and follow-up was not completed in 13 patients. Finally, treatment protocols of 671 ECP procedures were evaluated in 19 patients (10 MF; 9 GvHD). MF and GvHD subpopulations did not differ in the individual scores of LQ questions, either before the outset or after the last ECP. DLQI and Skindex-29 scores were ameliorated by the ECP therapy (p= 0.001 and p< 0.001, respectively) due to improvement of individual scores of feelings, daily/social activities (p< 0.05), and functionality (p= 0.05). The median interval between ECP cycles was extended from two to eight weeks (p= 0.001). Needs of GvHD patients for drugs being received for the underlying disease were reduced (p= 0.035). Two of the 10 MF patients worsened from stage IIA to IIIA. Severe or minor side effects leading to a therapy interruption were not recorded. Conclusion: Patients with GvHD experienced a notable decrease in the administration of drugs for their underlying condition, and there were no instances of severe side effects that resulted in the discontinuation of treatment. ECP is safe and effective for the treatment of MF and GvHD.

Background While rapid healing of diabetic foot ulcers (DFUs) is highly desirable to avoid infections, amputations and life-threatening complications, DFUs often respond poorly to standard treatment. GMP-manufactured skin-derived ABCB5 + mesenchymal stem cells (MSCs) might provide a new adjunctive DFU treatment, based on their remarkable skin wound homing and engraftment potential, their ability to adaptively respond to inflammatory signals, and their wound healing-promoting efficacy in mouse wound models and human chronic venous ulcers. Methods The angiogenic potential of ABCB5 + MSCs was characterized with respect to angiogenic factor expression at the mRNA and protein level, in vitro endothelial trans-differentiation and tube formation potential, and perfusion-restoring capacity in a mouse hindlimb ischemia model. Finally, the efficacy and safety of ABCB5 + MSCs for topical adjunctive treatment of chronic, standard therapy-refractory, neuropathic plantar DFUs were assessed in an open-label single-arm clinical trial. Results Hypoxic incubation of ABCB5 + MSCs led to posttranslational stabilization of the hypoxia-inducible transcription factor 1 α (HIF-1 α ) and upregulation of HIF-1 α mRNA levels. HIF-1 α pathway activation was accompanied by upregulation of vascular endothelial growth factor (VEGF) transcription and increase in VEGF protein secretion. Upon culture in growth factor-supplemented medium, ABCB5 + MSCs expressed the endothelial-lineage marker CD31, and after seeding on gel matrix, ABCB5 + MSCs demonstrated formation of capillary-like structures comparable with human umbilical vein endothelial cells. Intramuscularly injected ABCB5 + MSCs to mice with surgically induced hindlimb ischemia accelerated perfusion recovery as measured by laser Doppler blood perfusion imaging and enhanced capillary proliferation and vascularization in the ischemic muscles. Adjunctive topical application of ABCB5 + MSCs onto therapy-refractory DFUs elicited median wound surface area reductions from baseline of 59% (full analysis set, n = 23), 64% (per-protocol set, n = 20) and 67% (subgroup of responders, n = 17) at week 12, while no treatment-related adverse events were observed. Conclusions The present observations identify GMP-manufactured ABCB5 + dermal MSCs as a potential, safe candidate for adjunctive therapy of otherwise incurable DFUs and justify the conduct of a larger, randomized controlled trial to validate the clinical efficacy. Trial registration : ClinicalTrials.gov, NCT03267784, Registered 30 August 2017, https://clinicaltrials.gov/ct2/show/NCT03267784

Background: Leg discomfort is common in the general population. Volume increase and discomfort in the lower legs especially occur in occupations with long standing or sitting periods and less movement. Are both related to each other? Patients and methods: A time-controlled standing period of 15 min was performed in this nonrandomized controlled study to investigate the change and temporal relationship of volume increase and the occurrence of lower leg discomfort. Sensations of discomfort and the urge to move were queried using a numerical rating scale from 0 to 10 (NRS). Correlation analysis was conducted between the lower leg volume and the data regarding the discomfort and urge to move in each subject. Further, linear mixed effect models were performed to detect a causal relationship between the lower leg volume and the sensations of discomfort/urge to move in the standing period. Results: Lower leg volume increased by an average of 63 ml (p<0.001) during the standing period. The sensations of discomfort increased by a mean of 3.46 points on the NRS (p<0.001) during orthostasis. Participants' urge to move increased by 3.47 points on the NRS (p<0.001) during the standing period. A significant correlation was shown between the increase of lower leg volume and the occurrence of discomfort sensation in 9 out of 15 subjects (p<0.05) and between the increase of lower leg volume and the urge to move in 11 out of 15 subjects (p<0.05). Association was shown between volume increase and symptoms in linear mixed effects models. Conclusions: Prolonged standing with lack of movement leads to an increase in the lower leg volume and a sensation of discomfort in venous healthy subjects. Causal relationships are indicated between these variables by linear mixed effects models.

BACKGROUND: In this paper, the method of steam vein occlusion for the treatment of the great/small saphenous vein (GSV/SSV) was analyzed in terms of a therapeutic influence on the dynamic parameters of global vein function, its effects on subjective symptoms based on chronic venous insufficiency (CVI) and the side effects of the steam vein sclerosis (SVS). It has been questioned whether the effects of this method lead to a recommendation for routine clinical practice. METHODS: The venous drainage and the venous refilling time (T-0) of the leg treated were determined by photoplethysmography (Elcat, Wolfratshausen, Germany) before, six weeks and one year after the intervention to examine the effects on global venous function. Further changes of clinical symptoms and findings were assessed by the Venous Clinical Severity Score (VCSS), preoperatively and after one year, and the complication rate at 6-week follow-up was monitored. RESULTS: The SVS was performed on 167 veins (GSV: 124; SSV: 43) in a total of 156 patients. Eight patients (5.1%) did not attend the 6-week follow-up, while 29 patients (18.6%) were lost in the 1-year follow-up. Patients were suffering from symptoms such as leg pain and leg edema, which resulted in a VCSS of 9.4 (cumulated mean score of all patients) preoperatively. The T-0 was reduced to mean values of 20.6 s (GSV cohort) and 21 s (SSV cohort). The VCSS improved to 6.0 after one year. This correlated with the hemodynamic parameters. The T-0 increased in the GSV cohort after six weeks to 31.8 s, p < 0.001, and showed a nonsignificant improvement to 32.2 s, p = 0.509, in the 1-year check. The T-0 also increased in the SSV cohort significantly after 6 weeks to 30.1 s, p < 0.001, and showed a nonsignificant reduction after one year, p = 0.289. A total of 71% of the GSV and 69.8% of the SSV of the patients involved no complications following the treatment. Light complications (grade 1) occurred (reddening, hematoma, hyperpigmentation) in the majority: 24.2% of the GSV and 18.6% of the SSV. We noticed one grade 3 complication with thrombosis in the SSV cohort, which led to a pulmonary embolism. Forty-seven complete questionnaires were analyzed (responder rate: 28.1%); 40.4% of the patients had light complaints after the treatment, such as pain, warmth or local pressure sensations (Fig. 7); 63% of those patients noticed only slight pain at a maximum of 3 out of 10. The majority (91%) would recommend this procedure. CONCLUSION: The SVS revealed endoluminal catheter-based intervention to abolish venous reflux of the G/SSV as safe. As one therapeutic target is to eliminate venous reflux, effectiveness of a method cannot be based on sonographic data alone; one must further assess patients' symptoms and dynamic venous function. This data shows an improvement of patients' symptoms which correlated well with the improvement of the venous function in digital photoplethysmography. The SVS can be recommended as a catheter-based treatment in the future.

Background: The basis for adequate psycho-oncological care is the identification of patients with psychosocial support needs. The German Working Group for Psychooncology also recommends the Hornheider Screening Instrument (HSI) for this purpose. The question, "Is anyone in your family particularly burdened by the hospital stay?" is intended to capture disease-related family stress. But is this item equally suitable for outpatients and inpatients? The study objective was to examine how replacing the original item affects the test performance of this modified version of the HSI and the frequency of psychosocial stress. Patients and Methods: 92 outpatients and 98 inpatients with skin tumors assessed their psychosocial situation using different questionnaires. Results: Compared to inpatients, less than half as many outpatients answered the item in the affirmative. If the question was replaced by: "Is someone in your family particularly burdened by your disease or the course of the disease?" this setting-related difference did not arise. The "Alternative item" and the "Modified version of the HIS" (HSI-MV) proved to be superior to the original item and the original HSI with regard to all examined criteria. Conclusions: The HSI-MV can be used as a reliable and valid instrument for the systematic assessment of psychosocial care needs in outpatient and inpatient settings. Depending on care capacity, a threshold of >= 5 or >= 4 is appropriate. In addition to screening, the desire for support should be enquired.

Background: Leg discomfort is common in the general population. Volume increase and discomfort in the lower legs especially occur in occupations with long standing or sitting periods and less movement. Are both related to each other? Patients and methods: A time-controlled standing period of 15 min was performed in this nonrandomized controlled study to investigate the change and temporal relationship of volume increase and the occurrence of lower leg discomfort. Sensations of discomfort and the urge to move were queried using a numerical rating scale from 0 to 10 (NRS). Correlation analysis was conducted between the lower leg volume and the data regarding the discomfort and urge to move in each subject. Further, linear mixed effect models were performed to detect a causal relationship between the lower leg volume and the sensations of discomfort/urge to move in the standing period. Results: Lower leg volume increased by an average of 63 ml (p<0.001) during the standing period. The sensations of discomfort increased by a mean of 3.46 points on the NRS (p<0.001) during orthostasis. Participants' urge to move increased by 3.47 points on the NRS (p<0.001) during the standing period. A significant correlation was shown between the increase of lower leg volume and the occurrence of discomfort sensation in 9 out of 15 subjects (p<0.05) and between the increase of lower leg volume and the urge to move in 11 out of 15 subjects (p<0.05). Association was shown between volume increase and symptoms in linear mixed effects models. Conclusions: Prolonged standing with lack of movement leads to an increase in the lower leg volume and a sensation of discomfort in venous healthy subjects. Causal relationships are indicated between these variables by linear mixed effects models.

The central topics of digitalization in dermatology are image analysis supported by artificial intelligence and machine learning as well as teledermatology. Teledermatology has been revealed as an appropriate method to care for dermatologically diseased patients in emergency units of hospitals without dermatologists and for skin patients treated in the family doctor's practice. Dermatopathology deals with the histomorphological analysis of skin samples and holds a key position in dermatological diagnostics. In their daily routine, dermatopathologists analyze and integrate data from various sources, such as clinical information, image data of stained tissue sections, and molecular data. Digital teaching formats have recently become part of everyday university life. One of the reasons is that students use modern media naturally and as a matter of course. Digital courses in particular offer many students the advantage that they are not tied to a specific location and, if they are recorded, also not tied to a specific time.

ZusammenfassungHintergrundDie Basis für adäquate psychoonkologische Betreuung ist die Identifikation von Patienten mit psychosozialem Unterstützungsbedarf. Die Deutsche Arbeitsgemeinschaft für Psychoonkologie empfiehlt hierfür das Hornheider Screening‐Instrument (HSI). Die Frage: „Ist jemand in Ihrer Familie durch den Krankenhausaufenthalt besonders belastet?“ soll die krankheitsbedingte familiäre Belastung erfassen. Doch ist dieses Item für ambulante und stationäre Patienten gleichermaßen geeignet? Studienziel war zu überprüfen, wie sich das Ersetzen des Originalitems auf die Testgüte dieser modifizierten Version des HSI und die Häufigkeit psychosozialer Belastungen auswirkt.Patienten und Methodik92 ambulante und 98 stationäre Hauttumorpatienten schätzten ihre psychosoziale Situation mittels verschiedener Fragebögen ein.ErgebnisseIm Vergleich zu stationären Patienten bejahten weniger als halb so viele ambulante Patienten das Item. Wurde die Frage ersetzt durch: „Ist jemand in Ihrer Familie durch Ihre Erkrankung beziehungsweise den Krankheitsverlauf besonders belastet?“ zeigte sich dieser Setting‐bedingte Unterschied nicht. Das „Alternativ‐Item“ und die „Modifizierte Version des HSI“ (HSI‐MV) erwiesen sich dem Originalitem und dem Original‐HSI hinsichtlich aller untersuchten Kriterien überlegen.SchlussfolgerungenDie HSI‐MV kann als reliables und valides Instrument für die systematische Erhebung des psychosozialen Betreuungsbedarfes im ambulanten und stationären Setting eingesetzt werden. Je nach Versorgungskapazität ist ein Schwellenwert von ≥ 5 oder ≥ 4 geeignet. Zusätzlich zum Screening sollte der Unterstützungswunsch erfragt werden.

A significant number of chronic venous ulcers (CVUs) fail to heal despite of guideline-conform standard of care. Skin-derived ABCB5+ mesenchymal stem cells (MSCs) can dampen the sustained IL-1β-driven inflammation present in chronic wounds. Based on their wound healing-facilitating effects in a mouse CVU model and an autologous first-in-human study, ABCB5+ MSCs have emerged as a potential candidate for cell-based advanced therapy of non-healing CVUs. In the present interventional, multicenter, single-arm, phase I/IIa clinical trial, subjects whose CVU had emerged as standard therapy-resistant received one or two topical applications of 1×106 allogeneic ABCB5+ MSCs/cm2 wound area in addition to standard treatment. Out of 83 treatment-emergent adverse events, only three were judged related to the cell product; they were mild or moderate and recovered without sequelae. Wound size markedly decreased from baseline to week 12, resulting in a median wound size reduction of 76% (full analysis set, N=31), 78% (per-protocol set, N=27) and 87% (subset of responders; n=21). In conclusion, the study treatment was well tolerated and safe. The treatment elicited a profound wound size reduction within 12 weeks, identifying ABCB5+ MSCs as a potential candidate for adjunctive therapy of otherwise incurable CVUs. These results justify the conduct of a larger, randomized, controlled trial to confirm clinical efficacy.

The steady development of the antiretroviral therapy (ART) has led to a significant change in the demands on the quality of care. There are different regional challenges. It is a non-interventional, bicentric correlation study in the form of a retrospective data analysis including data of 43 HIV-positive patients in Greifswald and 1669 in Berlin. All variables were evaluated with R. Statistical significance was assumed at a p-value of ≤ 0.05. The immunological parameters showed a significantly lower CD4+ T-lymphocyte cell count in patients from Greifswald compared to those from Berlin (B: 516/μl blood; G: 266/μl blood; p < 0.001). The supply of ART was > 80% (B: 153/184 [83.15%]; G: 36/41 [87.8%]; p = 0.64) in both cohorts and led to a permanent (> than 4 quarters) drop of the viral load below the detection limit in 115/184 [62.25%] patients in Berlin and 23/41 [56.09%] patients in Greifswald (p = 0.008). This study has shown that the quality of care for HIV-infected patients in both urban and rural areas is of a high standard and carried out in accordance with the guidelines.