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The effect of tissue-tolerable plasma (TTP) on inflammatory diseases such as psoriasis was investigated. Three plaques of six psoriatic patients were subjected to different treatments (A: TTP, brine baths (BB)+5% salicylic acid ointment (SAO); B: BB+SAO; C: BB, UV irradiation, SAO+dithranol). While redness and infiltration was reduced in groups A and C, scaling was reduced in group C. TTP temporarily reduced the bacterial colonization on the skin lesions. In summary, the treatment of psoriatic plaques with TTP showed no significant advantage over conventional therapies.

Potential antimicrobial effects of sequential applications of tissue-tolerable plasma (TTP) and the conventional liquid antiseptic octenidine dihydrochloride (ODC) were investigated. 34 patients with chronic leg ulcers were treated with TTP, ODC or a combination of both. The bacterial colonization was measured semi-quantitatively before and immediately after treatment and changes in the microbial strains' compositions before and after antiseptic treatments were analyzed. All antiseptic procedures reduced the bacterial counts significantly. The sequential application of TTP and ODC displayed the highest antimicrobial efficacy. Me combined use of TTP and conventional antiseptics might represent the most efficient strategy for antiseptic treatment of chronic wounds.

Sunscreens are a key pillar of the multimodal protection strategy against short- and long-term impacts of intermittent and continuous UV exposure. Hitherto, an unanswered part of current scientific discourse is the question whether a cosmetic pretreatment has an impact on distribution and adhesiveness of sunscreens on the skin and therefore affects UV protection. In order to evaluate the homogeneity of sunscreen filter distribution, water resistance as a parameter of adhesiveness and effective UV protection of sunscreens after a pretreatment with cream or lotion was investigated in 18 volunteers who were examined before and after swimming, using the established combination of the tape stripping procedure and UV/VIS spectroscopy. It was shown that a cosmetic skin pretreatment affects neither filter homogeneity nor effective UV protection prior to water contact. However, compared to nonpretreated skin, a considerable loss of water resistance is caused. Therefore, using a cream or lotion before application of sunscreens is not to be recommended.

The results of the risk assessment of the tissue-tolerable plasma (TTP) jet kINPen med ® and first results of pilot clinical studies are presented. Producing an atmospheric pressure plasma, this plasma jet entails no risk for humans in terms of temperature increase, UV radiation or free radical formation by the plasma. The antiseptic efficacy in vitro on porcine skin and in vivo on human skin was compared to that of octenidine. TTP could significantly reduce the bacterial load in comparison to untreated skin. However, the slightly reduced antiseptic properties of TTP are attributed to the current parameter set-up and technical limitations.

Palmoplantar erythrodysesthesia (PPE) is one of the most frequent side effects during systemic treatment with pegylated liposomal doxorubicin (PLD, Caelyx®). PPE lesions show a range of symptoms, from numbness to painful erosions, and can have a major impact on the quality of life in affected patients. Previously, a possible pathomechanism of PPE was found in doxorubicin-treated patients based on radical formation in the skin. Here, a preventive strategy using a topically applied ointment with a high radical protection factor was investigated. In this randomized placebo-controlled double-blind study the antioxidant-containing ointment was compared with a placebo ointment regarding PPE grade III occurrence, overall PPE grade I–III occurrence and PPE severity in PLD patients. The verum or placebo cream was topically applied for a period of 16 weeks, starting 3 days prior to the first cycle of chemotherapy. Clinical evaluations were carried out by a dermatologist prior to the first cycle of chemotherapy and every 4 weeks for the duration of 16 weeks. Thirty-two patients were enrolled in total, of which 17 (66%) completed the study. No PPE grade III was found in the verum group, while five out of seven patients (71%) had to be unblinded in the placebo arm due to PPE grade III (p = 0.003). General PPE occurrence of all grades was 60% under verum and 86% under placebo treatment. The preventive application of an antioxidant-containing ointment was shown to be significantly more effective in the prevention of PPE grade III compared to placebo treatment.

Objective: In the age of multiresistant microbes and the increasing lack of efficient antibiotics, conventional antiseptics play a critical role in the prevention and therapy of wound infections. Recent studies have demonstrated the antiseptic effects of cold atmospheric pressure plasma (APP). In this pilot, study we investigate the overall suitability of one of the first APP sources for wound treatment focusing on its potential antimicrobial effects. Method: The wound closure rate and the bacterial colonisation of the wounds were investigated. Patients suffering from chronic leg ulcers were treated in a clinical controlled monocentric trial with either APP or octenidine (OCT). In patients who presented with more than one ulceration in different locations, one was treated with APP and the other one with OCT. Each group was treated three times a week over a period of two weeks. The antimicrobial efficacy was evaluated immediately after and following two weeks of treatment. Results: Wounds treated with OCT showed a significantly higher microbial reduction (64%) compared to wounds treated with APP (47%) immediately after the treatment. Over two weeks of antiseptic treatment the bacterial density was reduced within the OCT group (-35%) compared to a slight increase in bacterial density in the APP-treated group (+12%). Clinically, there were no signs of delayed wound healing observed in either group and both treatments were well tolerated. Conclusion: The immediate antimicrobial effects of the APP prototype source were almost comparable to OCT without any signs of cytotoxicity. This pilot study is limited by current configurations of the plasma source, where the narrow plasma beam made it difficult to cover larger wound surface areas and in order to avoid untreated areas of the wound bed, smaller wounds were assigned to the APP-treatment group. This limits the significance of AAP-related effects on the wound healing dynamics, as smaller wounds tend to heal faster than larger wounds. However, clinical wound healing studies on a larger scale now seem justifiable. A more advanced plasma source prototype allowing the treatment of larger wounds will address APP's influence on healing dynamics, synergetic treatment with current antiseptics and effects on multiresistant bacteria.

Potential antimicrobial effects of sequential applications of tissue-tolerable plasma (TTP) and the conventional liquid antiseptic octenidine dihydrochloride (ODC) were investigated. 34 patients with chronic leg ulcers were treated with TTP, ODC or a combination of both. The bacterial colonization was measured semi-quantitatively before and immediately after treatment and changes in the microbial strains' compositions before and after antiseptic treatments were analyzed. All antiseptic procedures reduced the bacterial counts significantly. The sequential application of TTP and ODC displayed the highest antimicrobial efficacy. Me combined use of TTP and conventional antiseptics might represent the most efficient strategy for antiseptic treatment of chronic wounds.

Non-melanoma skin cancer (NMSC) belongs to the most frequent human neoplasms. Its exposed location facilitates a fast ambulant treatment. However, in the clinical practice far more lesions are removed than necessary, due to the lack of an efficient pre-operational examination procedure: Standard imaging methods often do not provide a sufficient spatial resolution. The demand for an efficient in vivo imaging technique might be met in the near future by non-linear microscopy. As a first step towards this goal, the appearance of NMSC in various microspectroscopic modalities has to be defined and approaches have to be derived to distinguish healthy skin from NMSC using non-linear optical microscopy. Therefore, in this contribution the appearance of ex vivo NMSC in a combination of coherent anti-Stokes Raman scattering (CARS), second harmonic generation (SHG) and two photon excited fluorescence (TPEF) imaging—referred as multimodal imaging—is described. Analogous to H&E staining, an overview of the distinct appearances and features of basal cell and squamous cell carcinoma in the complementary modalities is derived, and is expected to boost in vivo studies of this promising technological approach.

Background/Aims: The palmoplantar erythrodysaesthesia (PPE) is an inflammatory cutaneous side effect in patients under chemotherapy with pegylated liposomal doxorubicin (PLD), with indications that also other chemotherapeutics induce similar side effects. Recently, it has been demonstrated that PLD escapes with the sweat onto the skin inducing radical-forming processes that damage the skin. The topical application of antioxidants with a high radical protection factor has proven to be a very efficient prevention strategy for PLD-treated patients. Methods: 68 patients, who had been treated with 12 different chemotherapeutics and experienced side effects similar to PPE, were treated with a meanwhile commercially available ointment. Results: At the beginning of the therapy, 46 patients suffered from a PPE of severity grade III, while in 22 patients a PPE of severity grade II was diagnosed. The application of the ointment resulted in a significant improvement of the clinical symptoms and the skin status in all these patients; their chemotherapies could be continued. Conclusion: The obtained results suggest that radical-forming processes play an essential role in a great number of chemotherapeutics which induce dermal side effects. The topical application of the antioxidant-containing ointment proved to be a good therapeutic option which needs further evaluation.

Summary Background The combination of coherent anti-Stokes Raman scattering (CARS), second harmonic generation (SHG) and two-photon excited fluorescence (TPEF) imaging – referred to as multimodal imaging – provides complementary contrast based on molecular vibrations, the structure of various tissue components and endogenous fluorophores, respectively. Objectives To present a comprehensive overview of the appearance of human skin in multimodal imaging. Methods Multimodal imaging of unstained skin cross-sections of 32 individuals was performed using a laser scanning microscope and picosecond laser pulse for excitation. Results The epidermis, dermis and subcutis are distinguishable in all three applied modalities, but are unveiled best in multimodal images. While the subcutis is dominated by the CARS signal, predominately SHG and the secondary TPEF signal detect the dermis. In contrast, no SHG signal is detected in the epidermis, whereas CARS and TPEF show equal contributions. Additionally, the appearance of the major skin appendages is described, i.e. the hair follicle, sebaceous and sweat glands, and blood vessels belonging to the vascular system. All four investigated functional units show a characteristic morphochemistry in TPEF and CARS, allowing identification of further subunits, e.g. the major components of the hair follicle, while the SHG signal delineates the localization of the functional units. Conclusions Multimodal imaging is a powerful tool to investigate human skin by providing high contrast based on the molecular constitution. It is therefore suggested that multimodal imaging has a high potential in application to dermatological research and clinical diagnostics of various skin alterations.

Background: Pegylated liposomal doxorubicin (PLD) is a highly efficient chemotherapeutic; however, it induces dermal side effects such as palmar-plantar erythrodysesthesia (PPE) in up to 80% of cases, probably by being emitted with the sweat onto the skin surface. Aim: The aim of the present study was to examine whether a topically applied ointment containing antioxidants with a high radical protection factor is able to prevent the formation of PPE. Methods: Twenty patients suffering from ovarian carcinoma and treated with PLD were observed. Results: 60% of the patients tolerated the regular application of the cream and developed no PPE. The remaining 40% interrupted the application. Six of them developed PPE and resumed ointment application thereafter. In these cases the PPE disappeared or was strongly reduced. Conclusion: The results of the observation clearly demonstrate that topical application of the ointment is an efficient strategy against the development of PPE during chemotherapy with PLD.

We present a case of a ruptured abdominal aortic aneurysm (AAA) with ambiguous accessory findings on post-mortem computed-tomography (PMCT), post-mortem magnetic resonance (PMMR) imaging, and PMCT-angiography (PMCTA) suggestive of thoracic aortic dissection. The diagnosis of ruptured AAA was confirmed by autopsy; however, there was no aortic dissection. The imaging findings that mimicked the presence of aortic dissection might have been an atypical presentation of post-mortem clotting or sedimentation. This case is an ideal example to illustrate benefits, limitations, and challenges of post-mortem cross-sectional imaging. It serves as a reminder that both, training as well as correlation of imaging findings with autopsy are fundamental to improve our understanding of radiologic findings on post-mortem cross-sectional imaging.

Optical microspectroscopic tools reveal great potential for dermatologic diagnostics in the clinical day-to-day routine. To enhance the diagnostic value of individual nonlinear optical imaging modalities such as coherent anti-Stokes Raman scattering (CARS), second harmonic generation (SHG) or two-photon excited fluorescence (TPF), the approach of multimodal imaging has recently been developed. Here, we present an application of nonlinear optical multimodal imaging with Raman-scattering microscopy to study sizable human-tissue cross-sections. The samples investigated contain both healthy tissue and various skin tumors. This contribution details the rich information content, which can be obtained from the multimodal approach: While CARS microscopy, which - in contrast to spontaneous Raman-scattering microscopy - is not hampered by single-photon excited fluorescence, is used to monitor the lipid and protein distribution in the samples, SHG imaging selectively highlights the distribution of collagen structures within the tissue. This is due to the fact, that SHG is only generated in structures which lack inversion geometry. Finally, TPF reveals the distribution of autofluorophores in tissue. The combination of these techniques, i.e. multimodal imaging, allows for recording chemical images of large area samples and is - as this contribution will highlight - of high clinically diagnostic value.

e20679 Background: Hand foot syndrome (HFS) or palmoplantar erythrodysesthesia (PPE) is a dose-limiting cutaneous side effect with an incidence of up to 78% in patients treated with pegylated lipos...

5064 Background: Pegylated liposomal doxorubicin has proved to be highly efficient in the treatment of various tumors. Depending on the application protocol, up to 80% of patients develop palmar-plantar erythrodysesthesia (PPE). So far, a prevention strategy is still unknown. Recently, it was shown that parts of the chemotherapeutics were excreted with the sweat onto the skin surface, spreading there homogeneously and penetrating into the stratum corneum. The formation of free radicals in the tissue results in PPE. The aim of the study was to investigate if a topically applied ointment containing antioxidants with high radical protection factor (RPF) can be a PPE prevention strategy. Methods: 20 patients with ovarian carcinoma, who had been treated with pegylated liposomal doxorubicin (40 mg/m2), were investigated. They applied the ointment at least twice daily, 2 days before and during 3 cycles of chemotherapy. Their skin condition was examined by a trained dermatologist. Results: From 20 patients enrolled in the study, only 12 (60%) met the conditions by applying the cream at least twice daily in the palmar and plantar regions. These patients did not develop PPE. One patient died in the 2nd cycle of therapy. 7 patients (35%) did not follow the ointment application protocol for various reasons; 6 of them developed PPE and resumed ointment application thereafter. As a result, PPE disappeared or was strongly reduced in these patients so that chemotherapy could be continued. Due to the small group of patients, the fact that PPE was not induced in patients who had applied the ointment regularly can be generalized only restrictedly. Far more interesting are the findings in those patients, who had stopped ointment application during chemotherapy and developed PPE, which disappeared after they resumed applying the ointment. The regression or distinct reduction of PPE after re-application of the ointment clearly proves the efficacy of this strategy. Conclusions: The topical application of an ointment containing antioxidants with high radical protection factor (RPF) could be an efficient strategy against the development of PPE during chemotherapy.