Association of polymorphous light eruption with NOD-2 and TLR-5 gene polymorphisms.

BACKGROUND: Polymorphous light eruption (PLE) is a common, immunologically mediated, photosensitive skin disease. After ultraviolet-B (UV-B) irradiation, patients with PLE show reduced Langerhans cell (LC) depletion in the epidermis, which results in a non-suppressive microenvironment in the skin. Interestingly, severe acute graft-versus-host disease (aGvHD) occurred in stem cell transplanted patients that showed no or incomplete depletion of LCs after UVB irradiation. Genetic variation in nucleotide-binding oligomerization domain 2 (NOD-2) and toll-like receptor 5 (TLR-5) genes also confers susceptibility to aGvHD. OBJECTIVES: We hypothesized that PLE is associated with genetic variation in the NOD-2 and TLR-5 genes. METHODS: We investigated single-nucleotid polymorphisms (SNPs) of NOD-2 (R702W, G908R, 3020Cins) and TLR-5 (A592S, P616L, N392STOP) in skin biopsies of patients with PLE (n = 143) and in healthy controls (n = 104) using restriction fragment length polymorphism analysis. RESULTS: The frequency of NOD-2 alleles with the SNP R702W was significantly higher in PLE than in controls (31.8% vs. 6.3%; P < 0.0001), and homozygous carriers of this mutation were more common in PLE (27.9% vs. 0%; P < 0.0001). For SNP 3020Cins, the allele frequency (7.3% vs. 0.7%; P = 0.0025) and the number of heterozygotes (14.7% vs. 1.3%; P = 0.0019) were higher in PLE. The frequency of alleles with the N392STOP SNP of the TLR5 gene, which is associated with a truncated, non-functional receptor, was significantly higher in PLE (21% vs. 5%; 7% vs. 1% homozygotes, 28% vs. 8% heterozygotes; P < 0.0001). The other SNPs did not differ significantly. CONCLUSIONS: This study yielded a high frequency of functional SNPs in the NOD-2 and TLR-5 genes in PLE. The same SNPs are associated with aGvHD and there are similarities in the reaction of LCs after UVB irradiation between aGvHD and PLE. This leads to the hypothesis that patients with PLE may be more susceptible to developing GvHD after stem cell transplantation, an assumption that needs to be investigated further.

[Photodynamic therapy-trends and new developments]. / Photodynamische Therapie ­ Trends und neue Entwicklungen.

Photodynamic therapy (PDT) is a licensed and established procedure for the treatment of actinic keratosis, basal cell carcinoma, and Bowen's disease, but there are several new and clinically relevant developments and trends. These concern on the one hand the main components of PDT, which are the photosensitizer and the light source. Furthermore, modifications and therapy combinations have been developed that lead to an improved therapeutic efficacy. An important aspect of field-directed PDT is also skin cancer prevention. Finally, PDT has been used successfully for nonlicensed indications including inflammatory diseases and skin rejuvenation. This article focuses on these new developments and on recent guideline recommendations.

European Dermatology Forum guidelines on topical photodynamic therapy 2019 Part 2: emerging indications - field cancerization, photorejuvenation and inflammatory/infective dermatoses.

In addition to approved indications in non-melanoma skin cancer in immunocompetent patients, topical photodynamic therapy (PDT) has also been studied for its place in the treatment of, as well as its potential to prevent, superficial skin cancers in immune-suppressed patients, although sustained clearance rates are lower than for immune-competent individuals. PDT using a nanoemulsion of ALA in a daylight or conventional PDT protocol has been approved for use in field cancerization, although evidence of the potential of the treatment to prevent new SCC remained limited. High-quality evidence supports a strong recommendation for the use of topical PDT in photorejuvenation as well as for acne, refractory warts, cutaneous leishmaniasis and in onychomycosis, although these indications currently lack approvals for use and protocols remain to be optimized, with more comparative evidence with established therapies required to establish its place in practice. Adverse events across all indications for PDT can be minimized through the use of modified and low-irradiance regimens, with a low risk of contact allergy to photosensitizer prodrugs, and no other significant documented longer-term risks with no current evidence of cumulative toxicity or photocarcinogenic risk. The literature on the pharmacoeconomics for using PDT is also reviewed, although accurate comparisons are difficult to establish in different healthcare settings, comparing hospital/office-based therapies of PDT and surgery with topical ointments, requiring inclusion of number of visits, real-world efficacy as well as considering the value to be placed on cosmetic outcome and patient preference. This guideline, published over two parts, considers all current approved and emerging indications for the use of topical photodynamic therapy in Dermatology prepared by the PDT subgroup of the European Dermatology Forum guidelines committee. It presents consensual expert recommendations reflecting current published evidence.

European Dermatology Forum guidelines on topical photodynamic therapy 2019 Part 1: treatment delivery and established indications - actinic keratoses, Bowen's disease and basal cell carcinomas.

Topical photodynamic therapy (PDT) is a widely approved therapy for actinic keratoses, Bowen's disease (squamous cell carcinoma in situ), superficial and certain thin basal cell carcinomas. Recurrence rates when standard treatment protocols are used are typically equivalent to existing therapies, although inferior to surgery for nodular basal cell carcinoma. PDT can be used both as lesional and field therapies and has the potential to delay/reduce the development of new lesions. A protocol using daylight to treat actinic keratoses is widely practised, with conventional PDT using a red light after typically a 3-h period of occlusion employed for other superficial skin cancer indications as well as for actinic keratoses when daylight therapy is not feasible. PDT is a well-tolerated therapy although discomfort associated with conventional protocol may require pain-reduction measures. PDT using daylight is associated with no or minimal pain and preferred by patient. There is an emerging literature on enhancing conventional PDT protocols or combined PDT with another treatment to increase response rates. This guideline, published over two parts, considers all current approved and emerging indications for the use of topical PDT in dermatology, prepared by the PDT subgroup of the European Dermatology Forum guidelines committee. It presents consensual expert recommendations reflecting current published evidence.

Methyl aminolevulinate daylight photodynamic therapy applied at home for non-hyperkeratotic actinic keratosis of the face or scalp: an open, interventional study conducted in Germany.

BACKGROUND: The efficacy and safety of methyl aminolevulinate daylight photodynamic therapy (MAL DL-PDT) for actinic keratosis (AK) treatment has previously been demonstrated in several studies. OBJECTIVE: To evaluate patient-reported outcomes, effectiveness and tolerability of patient self-applied MAL DL-PDT. PATIENTS AND METHODS: An open study was conducted in Germany in patients with thin or non-hyperkeratotic and non-pigmented AK. At baseline, the investigator delimited the target anatomical area and skin preparation was discretionary. On day 1, the patient performed MAL DL-PDT at home, in accordance with instructions (after applying sunscreen and skin preparation by abrasive pad). Patient questionnaires were completed on day 1 and 3 months post-treatment. Effectiveness was assessed by investigator at 3 months. Pain and adverse events (AE) were recorded. RESULTS: Patients (n = 50) were mostly elderly (mean age: 73.4 years) men (86%). After treatment on day 1, 94% of patients were overall satisfied or very satisfied with the treatment and 98% found the instructions convenient. At 3 months, most patients were satisfied or very satisfied with treatment effectiveness (88%) and aspect of their skin (80%). At 3 months, 62% of overall lesions were completely clear. The main related AEs were mild and expected (erythema, procedural pain and skin burning sensation). CONCLUSIONS: Patient self-application of MAL DL-PDT resulted in high levels of patient satisfaction, effectiveness and tolerability.

Daylight photodynamic therapy versus cryosurgery for the treatment and prophylaxis of actinic keratoses of the face - protocol of a multicenter, prospective, randomized, controlled, two-armed study.

BACKGROUND: Photodynamic therapy with daylight (DL-PDT) is efficacious in treating actinic keratosis (AK), but the efficacy of field-directed, repetitive DL-PDT for the treatment and prophylaxis of AK in photodamaged facial skin has not yet been investigated. METHODS/DESIGN: In this multicenter, prospective, randomized, controlled, two-armed, observer-blinded trial, patients with a minimum of 5 mild-to-moderate AK lesions on photodamaged facial skin are randomly allocated to two treatment groups: DL-PDT with methyl aminolevulinate (MAL) and cryosurgery. In the DL-PDT group (experimental group), 5 treatments of the entire face are conducted over the course of 18 months. After preparation of the lesion and within 30 min after MAL application, patients expose themselves to daylight for 2 h. In the control group, lesion-directed cryosurgery is conducted at the first visit and, in the case of uncleared or new AK lesions, also at visits 2 to 5. The efficacy of the treatment is evaluated at visits 2 to 6 by documenting all existing and new AK lesions in the face. Cosmetic results and improvement of photoaging parameters are evaluated by means of a modified Dover scale. Primary outcome parameter is the cumulative number of AK lesions observed between visits 2 and 6. Secondary outcome parameters are complete clearance of AK, new AK lesions since the previous visit, cosmetic results independently evaluated by both patient and physician, patient-reported pain (visual analogue scale), patient and physician satisfaction scores with cosmetic results, and patient-reported quality of life (Dermatology Life Quality Index). Safety parameters are also documented (adverse events and serious adverse events). DISCUSSION: This clinical trial will assess the efficacy of repetitive DL-PDT in preventing AK and investigate possible rejuvenating effects of this treatment. (Trial registration: ClinicalTrials.gov Identifier: NCT02736760). TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02736760 . Study Code Daylight_01. EudraCT 2014-005121-13.

Investigation of toxicity and mutagenicity of cold atmospheric argon plasma.

Cold atmospheric argon plasma is recognized as a new contact free approach for the decrease of bacterial load on chronic wounds in patients. So far very limited data are available on its toxicity and mutagenicity on eukaryotic cells. Thus, the toxic/mutagenic potential of cold atmospheric argon plasma using the MicroPlaSter ß® , which has been used efficiently in humans treating chronic and acute wounds, was investigated using the XTT assay in keratinocytes and fibroblasts and the HGPRT (hypoxanthine guanine phosphoribosyl transferase) assay with V79 Chinese hamster cells. The tested clinical parameter of a 2 min cold atmospheric argon plasma treatment revealed no relevant toxicity on keratinocytes (viability: 76% ± 0.17%) and on fibroblasts (viability: 81.8 ± 0.10) after 72 hr as compared to the untreated controls. No mutagenicity was detected in the HGPRT assay with V79 cells even after repetitive CAP treatments of 2-10 min every 24 hr for up to 5 days. In contrast, UV-C irradiation of V79 cells, used as a positive control in the HGPRT test, led to DNA damage and mutagenic effects. Our findings indicate that cold atmospheric plasma using the MicroPlaSter ß® shows negligible effects on keratinocytes and fibroblasts but no mutagenic potential in the HGPRT assay, indicating a new contact free safe technology. Environ. Mol. Mutagen. 58:172-177, 2017. © 2017 Wiley Periodicals, Inc.

Photodynamic therapy using intense pulsed light for treating actinic keratoses and photoaged skin of the dorsal hands: a randomized placebo-controlled study.

BACKGROUND: The efficacy of photodynamic therapy (PDT) with intense pulsed light (IPL) has been shown for treating actinic keratoses (AK) and improving photoaged skin on the face but not yet on the dorsal hands. OBJECTIVES: To evaluate the efficacy of PDT with IPL for treating AK of the dorsal hands, inducing neocollagenesis and improving photoaged skin. METHODS: In this prospective, randomized, placebo-controlled, monocentric, within-patient, observer-blinded trial, patients with one to four mild-to-moderate AK on the dorsal hands were randomly allocated to two different treatment groups: methyl aminolaevulinate (MAL) and IPL (λ ≥ 600 nm, 16·2 J cm-2 , three passes, Ellipse Flex PPT) (MAL-IPL) or placebo and IPL (λ ≥ 600 nm, 16·2 J cm-2 , three passes, Ellipse Flex PPT) (placebo-IPL). Patients received three treatments at 6-week intervals, and follow-up was 10 weeks after the last treatment. Thirty-seven patients aged 68·84 ± 9·28 years were randomized. The primary study end points were complete AK clearance per hand and neocollagenesis of subepidermal collagen 10 weeks after the last treatment. RESULTS: Ten weeks after the last treatment, complete AK clearance rates per hand were 54·5% after MAL-IPL and 3·0% after placebo-IPL (P < 0·0001); complete AK clearance rates per lesion were 69% and 15%, respectively (P < 0·001). The thickness of the subepidermal collagen band had increased by 290·6% (± 327·4%, P < 0·001) after MAL-IPL and by 215·5% (± 215·3%, P < 0·001) after placebo-IPL without any significant difference between the two groups. Ratings regarding mottled pigmentation and overall appearance by the blinded investigator were significantly higher for MAL-IPL than for placebo-IPL. Wrinkle size (MAL-IPL, -23·5%, P = 0·006; placebo-IPL, -17·7%, P = 0·010) and skin roughness (MAL-IPL, -18·3%, P < 0·001; placebo-IPL, -12·4%, P = 0·009) were significantly reduced in both groups without any significant difference between the two groups. CONCLUSIONS: On the dorsal hands, MAL-IPL reduced AK more efficaciously than placebo-IPL; both treatment modalities significantly improved photoaged skin.

[Plasma medicine in dermatology: Mechanisms of action and clinical applications]. / Plasmamedizin in der Dermatologie : Wirkmechanismen und Anwendungsmöglichkeiten.

Plasma medicine has developed into an innovative field of research showing high potential. Since the establishment of cold atmospheric plasma, new, multifaceted medical treatment opportunities have become available. Within a short time a multidisciplinary special interest group of medical scientists, physicists, and biologists was created, aiming to understand plasma medicine and answer clinical as well as scientific questions. In dermatology, new horizons are being opened for wound healing, tissue regeneration, treatment of skin infections, and tumor therapy. A major task will be the introduction of plasma into clinical medicine and, simultaneously, the further investigation of the mechanisms of action of plasma at the cellular level. Only then can the safety of plasma treatment in patients be assured.

[Quality of life in dermatology. From measurement to practical implementation]. / Lebensqualität in der Dermatologie. Von der Messung zur praktischen Umsetzung.

Health-related quality of life has not only been established as an important patient-reported outcome measure in patient care but has been defined as an evaluation criterion for therapies in the German Code of Social Law as well as in the guidelines of the American Food and Drug Administration and of the European Medicines Agency (EMA). Quality of life can be measured in a standardised manner. Validated questionnaires are available for recording specific problems of patients with, for example, skin diseases. Measuring quality of life has not yet been implemented into daily dermatological routine, although (1) studies have confirmed that the measurement of quality of life offers major benefits for the treatment of skin diseases, and (2) first experiences in implementing quality of life measurement into practice have been positive. The further implementation of systemically measuring quality of life requires advancements in automated measurement and the assumption of cost by social health insurances.

Comparing cold-air analgesia, systemically administered analgesia and scalp nerve blocks for pain management during photodynamic therapy for actinic keratosis of the scalp presenting as field cancerization: a randomized controlled trial.

BACKGROUND: Photodynamic therapy (PDT) using methyl aminolaevulinate (MAL) is an effective treatment for extensive actinic keratosis (AK). However, pain is a major side-effect of this therapy. OBJECTIVES: To investigate whether scalp nerve blocks (group 1) provide adequate pain relief during MAL-PDT of the scalp and forehead in 32 men with baldness. METHODS: The patients received intravenous (IV) analgesia [piritramide 7.5 mg IV, plus oral metamizole (40 drops 30 min prior to PDT)] in combination with cold-air analgesia (group 2; IV analgesia) and cold-air analgesia alone (group 3). Maximum pain was evaluated by means of a visual analogue scale (VAS) during and up to 300 min after PDT. Pain during PDT was further analysed according to a pain perception scale. Furthermore, we measured haemodynamics and investigated stress hormone levels in blood samples at different time points. RESULTS: Maximum pain during PDT (primary end point) was significantly reduced in the treatment group receiving scalp nerve blocks (VAS 2.1 ± 1.3) compared with the treatment groups receiving IV analgesia (VAS 7.3 ± 1.1) and cold-air analgesia (VAS 8.4 ± 2.0; P < 0.05). No significant difference was found between groups 2 and 3 with regard to pain relief (P = 0.32). The increase in systolic blood pressure during the first 3 min of PDT was significantly lower for group 1 than for groups 2 and 3 (P < 0.001). No correlation between stress hormone levels and pain were found. CONCLUSIONS: Scalp nerve blocks provide an effective method for pain management during PDT for patients with extensive AK.

[Current detection rates of multiresistant gram negative bacteria (3MRGN, 4MRGN) in patients with chronic leg ulcers]. / Aktuelle Nachweisraten multiresistenter Gram-negativer Bakterien (3MRGN, 4MRGN) bei Patienten mit chronischem Ulcus cruris.

BACKGROUND: Due to the increasing problem of antibiotic resistance in gram-negative pathogens, the Commission for Hospital Hygiene and Infection Prevention (KRINKO) decided to establish a new clinically oriented definition of multi-resistance. Gram-negative pathogens with a multidrug-resistance (MRGN) are divided into those with resistance to three (3MRGN) or four (4MRGN) antibiotic groups. PATIENTS AND METHODS: In this multicenter study which was done in ten dermatological wound clinics, the bacteriological swabs from up to 100 patients with chronic leg ulcers per center were analyzed according to the current classification KRINKO and evaluated. RESULTS: Overall, the results of 970 patients (553 women, 417 men) could be evaluated. We found 681 gram-positive and 1155 gram-negative bacteria. Pseudomonas aeruginosa was with a detection-rate of 31.1% the most frequent gram-negative pathogen, followed by Proteus mirabilis with 13.7% and various enterobacteria with 28.6%. According to the current KRINKO classification,eight patients with 4MRGN and 34 patients with 3MRGN could be identified. CONCLUSIONS: Our results demonstrate the current spectrum of bacteria in patients with chronic leg ulcers with a variety of gram-negative pathogens, some of which are classified as multi-drug resistant. As a clinical consequence some of the patients require individualized preventive measures and therapy.

W.A.R. scores in patients with chronic leg ulcers: results of a multicentre study.

OBJECTIVE: To assess the individual patient's risk of wound infection using the wounds-at-risk (W.A.R.) score developed by a group of interdisciplinary experts. METHOD: The W.A.R. score is a clinical test in which, based on anamnestic and clinical criteria, wound patients are assigned point values, where a score of less than or equal to 3 indicates a need for antimicrobial treatment. RESULTS: The data of 970 patients (553 women, 417 men) with chronic leg ulcers were evaluated at 10 dermatological wound clinics in different regions within Germany. The age of the patients was between 10 and 100 years (mean of 69.8 years); the duration of the wounds was between 2 months and 68 years (mean of 41.1 months). Wound sizes were between 1 and 736 cm² (mean of 42.8 cm²). Overall, W.A.R. scores of <3 points were found in 73.1% of patients and scores of greater than or equal to 3 were found in 26.9% [corrected] of patients. There were significant differences in W.A.R. scores by regions with respect to the bacterial species detected and the aetiologies of the wounds. CONCLUSION: Our multicentre study is the first evaluation of clinical data using the newly established W.A.R. scores. We were able to show that the W.A.R. scores are able to identify a segment of the patient population for whom it can be assumed that they are prone to an increased risk of wound infections unless appropriate antimicrobial action is taken. The W.A.R. score is a simple clinical score that identifies patients with an increased risk of wound infection.

[New developments in photodynamic therapy]. / Neue entwicklungen in der photodynamischen therapie.

We review new developments in recent years in photodynamic therapy. Since 2009 two new photosensitizers, a self-adhesive 5-aminolevulinic acid (ALA) patch and a nanoemulsion formulation of 5-aminolevulinic acid have been approved for the treatment of actinic keratoses. Pretreatment with ablative fractional lasers enhances penetration of the photosensitizer and enables intensified PDT in acral lesions and in field-cancerized skin. Several clinical trials have demonstrated the skin-rejuvenating effects of photodynamic therapy, while the underlying mechanisms of action have been clarified. The efficacy of photodynamic therapy has been shown in the treatment and prophylaxis of actinic keratoses in organ transplant recipients at high risk for developing skin cancer. We also summarize the results of available studies on daylight-mediated photodynamic therapy.

A randomized two-sided placebo-controlled study on the efficacy and safety of atmospheric non-thermal argon plasma for pruritus.

BACKGROUND: To look into new potential indications for physical plasma and because some reports suggest plasma having antipruritic effects, we investigated the treatment of pruritus that often represents a therapeutic challenge. OBJECTIVES: To assess the efficacy and safety of cold atmospheric argon plasma as add-on-therapy in pruritic diseases. METHODS: We treated 46 patients with various pruritic diseases with cold plasma for 2 min daily in addition to standard treatment. All patients served as their own control, when their pruritic disease was treated with argon gas (placebo). The outcome measure was a long-term and short-term reduction in itching measured by means of a visual analogue score (VAS). RESULTS: The VAS scores at baseline were comparable (plasma 4.57, SD 2.38, argon 4.34, SD 2.35). We did not find any significant differences in VAS reduction between plasma and argon: long-term VAS difference of 1.97 (SD 1.33) for plasma and 1.74 (SD 2.37) for argon [P = 0.224, 95% CI: (-0.15; 0.60)], short-term VAS difference of 1.92 (SD 1.33) for plasma and 1.97 (SD 1.29) for argon [P = 0.544, 95% CI: (-0.21; 0.11)]. In both groups, patients experienced a significant reduction of pruritus at the end of therapy compared to baseline [plasma 1.97 (P < 0.0001), placebo 1.74 [P < 0.0001)]. No relevant side effects occurred, and treatment was well tolerated. CONCLUSIONS: Treatment with cold plasma did not result in higher pruritus reduction than treatment with placebo. A significant reduction of pruritus compared to no effect was found at the end of therapy in both groups. Both treatment options had similar safety profiles.

Multidrug-resistant bacteria in travellers hospitalized abroad: prevalence, characteristics, and influence on clinical outcome.

BACKGROUND: Worldwide, the burden of multidrug-resistant bacteria (MDR) is increasing, especially in the hospital setting. AIM: To explore characteristics and clinical relevance of MDR obtained from travellers transferred from hospitals abroad. METHODS: This retrospective study included patients transferred from hospitals abroad to the University Hospital Zurich, Switzerland, who routinely underwent admission screening for possible colonization with meticillin-resistant Staphylococcus aureus (MRSA), extended-spectrum beta-lactamase-producing bacteria (ESBL) and multidrug-resistant Gram-negative bacteria (MR Gram negative). FINDINGS: Forty-six (17%) of 259 subjects were found to be colonized with MDR and nine (3.5%) patients to be infected. Thirty-three (12%) patients were colonized with one bacterial species, 12 (4.6%) with two, and three (1.2%) were colonized with three different bacterial species. In total, 36 ESBL, 21 MR Gram-negative and three MRSA isolates were detected. Escherichia coli (N = 18, 30%), Klebsiella pneumoniae (N = 14, 23%) and Acinetobacter baumannii (N = 14, 23%) were most frequently isolated. The most common sites of detection were skin (97%) and respiratory tract (41%). Being colonized contributed to an increased length of ICU stay [median (range): 8 (1-35) vs 3.5 (1-78) days; P = 0.011]. In-hospital mortality in patients colonized with MDR (10.9%) was higher than in uncolonized patients (2.3%, P = 0.018). Being colonized with MDR was associated with death (adjusted odds ratio: 5.176; 95% confidence interval: 1.325-20.218). CONCLUSIONS: A substantial proportion of patients transferred from abroad are colonized with MDR, a fact which is associated with poor clinical outcome.

Successful and safe use of 2 min cold atmospheric argon plasma in chronic wounds: results of a randomized controlled trial.

BACKGROUND: The development of antibiotic resistance by microorganisms is an increasing problem in medicine. In chronic wounds, bacterial colonization is associated with impaired healing. Cold atmospheric plasma is an innovative promising tool to deal with these problems. OBJECTIVES: The 5-min argon plasma treatment has already demonstrated efficacy in reducing bacterial numbers in chronic infected wounds in vivo. In this study we investigated a 2-min plasma treatment with the same device and the next-generation device, to assess safety and reduction in bacterial load, regardless of the kind of bacteria and their resistance level in chronic wounds. METHODS: Twenty-four patients with chronic infected wounds were treated in a prospective randomized controlled phase II study with 2 min of cold atmospheric argon plasma every day: 14 with MicroPlaSter alpha device, 10 with MicroPlaSter beta device (next-generation device) in addition to standard wound care. The patient acted as his/her own control. Bacterial species were detected by standard bacterial swabs and bacterial load by semiquantitative count on nitrocellulose filters. The plasma settings were the same as in the previous phase II study in which wounds were exposed for 5 min to argon plasma. RESULTS: Analysis of 70 treatments in 14 patients with the MicroPlaSter alpha device revealed a significant (40%, P<0.016) reduction in bacterial load in plasma-treated wounds, regardless of the species of bacteria. Analysis of 137 treatments in 10 patients with the MicroPlaSter beta device showed a highly significant reduction (23.5%, P<0.008) in bacterial load. No side-effects occurred and the treatment was well tolerated. CONCLUSIONS: A 2-min treatment with either of two cold atmospheric argon plasma devices is a safe, painless and effective technique to decrease the bacterial load in chronic wounds.