Long-term evaluation of climatotherapy for psoriasis.

Climatotherapy (CT) is a treatment with immediate high clearance rate for chronic psoriasis, but evidence of long-term effects is scarce. Assessment of the impact of a single CT treatment on disease activity and quality of life was carried out at 4- to 6-month follow-ups. A prospective study of patients with psoriasis undergoing 4 weeks of CT in Israel describes long-term outcomes of CT. Psoriasis Area Severity Index (PASI) and Dermatology Life Quality Index (DLQI) scores were assessed before CT and at an average of 5 months after return. Assessment of the eligibility for CT takes place twice a year. A total of 49 patients (28/21 M/F) participated. Pretreatment PASI was 2.6 to 18.7 (mean 8.1 ± 3.8) vs control PASI 0 to 16.9 (mean 5 ± 2.8), (P < .0001). Mean ΔPASI was 3.2 (39.5% reduction). PASI 75 was achieved by 11/49 patients; 10/49 had increased PASI. The mean DLQI score was 16.1 (range 2-30); 10.6 at follow-up (range 0-28), and 33 patients achieved DLQI minimal clinically important difference (P < .0001). Age, sex, number of previous CT, and duration of observation period did not affect endpoints. CT and unmonitored self-treatment induces PASI 75 in one-fifth patients at follow-up 4 to 6 months later. Six of 10 patients report a clinically important improvement of patients' quality of life as measured by DLQI.

Uncontrolled gelatin degradation in non-healing chronic wounds.

OBJECTIVE: To compare matrix metalloproteinase (MMP)-9 and the antiproteinase tissue inhibitor of metalloproteinases (TIMP)-1 in wound fluids and sera from patients with chronic non-healing or acute healing wounds. In addition, the functional consequences on MMP-9 activity and general gelatinase activity were assessed. METHOD: In this observational study, samples were collected from patients with venous leg ulcers (VLUs), patients with type 2 diabetes with neuropathic foot ulcers (DFUs), and from another cohort of VLU patients with sterile split-thickness skin graft donor sites after autologous skin grafting, serving as healing control wounds. MMP-9 and TIMP-1 concentrations were determined by enzyme-linked immunosorbent assays. MMP-9 and gelatinase activities were determined in wound fluids in subsets of the patients. RESULTS: A total of 24 patients took part in the study. No significant differences in MMP-9 wound fluid levels were found among the three groups. TIMP-1 levels were markedly and significantly lower in the two chronic wound groups resulting in a severely unbalanced MMP-9/TIMP-1 ratio, especially notable in the VLU group and possibly in the elevated endogenous MMP-9 activity (p<0.01) compared with the acute wound fluids. At least 20% of the chronic wound fluids displayed atypical patterns on gelatin zymography and showed high general gelatinase activity that was not inhibited by either TIMP-1 or by a gelatinase inhibitor (AG3340). MMP-9 levels were higher in the sera of the patients with type 2 diabetes. CONCLUSION: We hypothesise that non-MMP proteinases contribute to matrix destruction in a significant number of chronic wounds. Blocking the excessive MMP-9 activity may be insufficient to normalise wound healing. The reasons and effects of the very low TIMP-1 levels in chronic wounds need further clarification.

Pseudomonas aeruginosa biofilm hampers murine central wound healing by suppression of vascular epithelial growth factor.

Biofilm-infected wounds are clinically challenging. Vascular endothelial growth factor and host defence S100A8/A9 are crucial for wound healing but may be suppressed by biofilms. The natural course of Pseudomonas aeruginosa biofilm infection was compared in central and peripheral zones of burn-wounded, infection-susceptible BALB/c mice, which display delayed wound closure compared to C3H/HeN mice. Wounds were evaluated histopathologically 4, 7 or 10 days post-infection. Photoplanimetry evaluated necrotic areas. P. aeruginosa biofilm suppressed vascular endothelial growth factor levels centrally in BALB/c wounds but increased peripheral levels 4-7 days post-infection. Central zones of the burn wound displayed lower levels of central vascular endothelial growth factor as observed 4 and 7 days post-infection in BALB/c mice compared to their C3H/HeN counterparts. Biofilm suppressed early, centrally located S100A8/A9 in BALB/c and centrally and peripherally later on in C3H/HeN wounds as compared to uninfected mice. Peripheral polymorphonuclear-dominated inflammation and larger necrosis were observed in BALB/c wounds. In conclusion, P. aeruginosa biofilm modulates wounds by suppressing central, but inducing peripheral, vascular endothelial growth factor levels and reducing host response in wounds of BALB/c mice. This suppression is detrimental to the resolution of biofilm-infected necrosis.

Immune Modulating Topical S100A8/A9 Inhibits Growth of Pseudomonas aeruginosa and Mitigates Biofilm Infection in Chronic Wounds.

Pseudomonas aeruginosa biofilm maintains and perturbs local host defense, hindering timely wound healing. Previously, we showed that P. aeruginosa suppressed S100A8/A9 of the murine innate host defense. We assessed the potential antimicrobial effect of S100A8/A9 on biofilm-infected wounds in a murine model and P. aeruginosa growth in vitro. Seventy-six mice, inflicted with a full-thickness burn wound were challenged subcutaneously (s.c.) by 106 colony-forming units (CFUs) of P. aeruginosa biofilm. Mice were subsequently randomized into two treatment groups, one group receiving recombinant murine S100A8/A9 and a group of vehicle controls (phosphate-buffered saline, PBS) all treated with s.c. injections daily for up to five days. Wounds were analyzed for quantitative bacteriology and contents of key inflammatory markers. Count of blood polymorphonuclear leukocytes was included. S100A8/A9-treatment ameliorated wound infection, as evaluated by quantitative bacteriology (p ≤ 0.05). In vitro, growth of P. aeruginosa was inhibited dose-dependently by S100A8/A9 in concentrations from 5 to 40 µg/mL, as determined by optical density-measurement (OD-measurement) and quantitative bacteriology. Treatment slightly augmented key inflammatory cytokine Tumor Necrosis Factor-α (TNF-α), but dampened interferon-γ (IFN-γ) levels and blood polymorphonuclear count. In conclusion, topical S100A8/A9 displays remarkable novel immune stimulatory and anti-infective properties in vivo and in vitro. Importantly, treatment by S100A8/A9 provides local infection control. Implications for a role as adjunctive treatment in healing of chronic biofilm-infected wounds are discussed.

Polymorphonuclear leukocytes restrict growth of Pseudomonas aeruginosa in the lungs of cystic fibrosis patients.

Cystic fibrosis (CF) patients have increased susceptibility to chronic lung infections by Pseudomonas aeruginosa, but the ecophysiology within the CF lung during infections is poorly understood. The aim of this study was to elucidate the in vivo growth physiology of P. aeruginosa within lungs of chronically infected CF patients. A novel, quantitative peptide nucleic acid (PNA) fluorescence in situ hybridization (PNA-FISH)-based method was used to estimate the in vivo growth rates of P. aeruginosa directly in lung tissue samples from CF patients and the growth rates of P. aeruginosa in infected lungs in a mouse model. The growth rate of P. aeruginosa within CF lungs did not correlate with the dimensions of bacterial aggregates but showed an inverse correlation to the concentration of polymorphonuclear leukocytes (PMNs) surrounding the bacteria. A growth-limiting effect on P. aeruginosa by PMNs was also observed in vitro, where this limitation was alleviated in the presence of the alternative electron acceptor nitrate. The finding that P. aeruginosa growth patterns correlate with the number of surrounding PMNs points to a bacteriostatic effect by PMNs via their strong O2 consumption, which slows the growth of P. aeruginosa in infected CF lungs. In support of this, the growth of P. aeruginosa was significantly higher in the respiratory airways than in the conducting airways of mice. These results indicate a complex host-pathogen interaction in chronic P. aeruginosa infection of the CF lung whereby PMNs slow the growth of the bacteria and render them less susceptible to antibiotic treatment while enabling them to persist by anaerobic respiration.

Self-reported systemic symptoms among women with breast implants.

Around 2,500 women receive a breast augmentation with silicone-based implants yearly in Denmark. A number of these women report various uncharacteristic systemic symptoms, which they attribute to the breast implants, including impaired cognition, joint pain, etc. This condition has been termed "breast implant illness" and is currently not a recognised diagnosis. The correlation between the patient's self-reported symptoms and breast implants has not been established and there is limited evidence that surgery has any effect. In this review, the current literature on the topic has been reviewed.

Pseudomonas aeruginosa biofilm aggravates skin inflammatory response in BALB/c mice in a novel chronic wound model.

Chronic wounds are presumed to persist in the inflammatory state, preventing healing. Emerging evidence indicates a clinical impact of bacterial biofilms in soft tissues, including Pseudomonas aeruginosa (PA) biofilms. To further investigate this, we developed a chronic PA biofilm wound infection model in C3H/HeN and BALB/c mice. The chronic wound was established by an injection of seaweed alginate-embedded P. aeruginosa PAO1 beneath a third-degree thermal lesion providing full thickness skin necrosis, as in human chronic wounds. Cultures revealed growth of PA, and both alginate with or without PAO1 generated a polymorphonuclear-dominated inflammation early after infection. However, both at days 4 and 7, there were a more acute polymorphonuclear-dominated and higher degree of inflammation in the PAO1 containing group (p < 0.05). Furthermore, PNA-FISH and supplemented DAPI staining showed bacteria organized in clusters, resembling biofilms, and inflammation located adjacent to the PA. The chronic wound infection showed a higher number of PAO1 in the BALB/c mice at day 4 after infection as compared to C3H/HeN mice (p < 0.006). In addition, a higher concentration of interleukin-1beta in the chronic wounds of BALB/c mice was observed at day 7 (p < 0.02), despite a similar number of bacteria in the two mouse strains. The present study succeeded in establishing a chronic PA biofilm infection in mice. The results showed an aggravating impact of local inflammation induced by PA biofilms. In conclusion, our findings indicate that improved infection control of chronic wounds reduces the inflammatory response and may improve healing.

Cutaneous malakoplakia.

Malakoplakia is a form of chronic, granulomatous, inflammatory condition which usually affects the genitourinary tract or other internal organs of immunocompromised patients. It is usually caused by acquired bactericidal incapacity of macrophages in connection to Eschericia coli infection. This case report presents an extremely rare case of cutaneous malakoplakia in the left axilla of a 48-year-old male patient, who had undergone kidney transplant one year earlier. The clinical presentation of cutaneous malakoplakia varies from nodules to plaques and moist wounds. The primary treatment is long-term antibiotic therapy.

The impact of neoadjuvant chemotherapy on surgical outcomes following autologous and implant-based immediate breast reconstruction: A systematic review and meta-analysis.

BACKGROUND: The impact of neoadjuvant chemotherapy (NACT) on the complication rate after implant-based and autologous breast reconstruction remains unclear. The aim of this study was to systematically review and perform a meta-analysis of previously published studies on immediate breast reconstruction (IBR) in breast cancer patients treated with NACT compared with controls. METHODS: PubMed and EMBASE were searched to identify studies assessing the impact of NACT on major and minor complications after IBR. The primary effect measures were relative risk (RR), 95% confidence interval (95% CI), and p-value. RESULTS: Eight studies comprising 51,731 patients were included in the meta-analysis. Of these, 5161 patients received NACT and 46,570 patients did not receive NACT. In regard to major complications, NACT did not statistically significant increase the rate of reconstructive failure (RR = 1.35, 95% CI = 0.96-1.91, p = 0.09), the rate of mastectomy skin-flap necrosis (RR = 1.39, 95% CI = 0.61-3.17, p = 0.44), or the rate of reoperation (RR = 1.09, 95% CI = 0.87-1.37, p = 0.45). Regarding minor complications, NACT did not significantly increase the rate of wound complications (RR = 1.05, 95% CI = 0.87-1.28, p = 0.62). In a subgroup analysis of implant-based breast reconstruction following NACT, single-stage direct-to-implant (DTI) had a significantly lower implant failure rate compared with two-staged tissue expander/implant (TE/I) (RR = 0.43, 95% CI = 0.26-0.71, p = 0.0011). CONCLUSION: NACT did not increase the major or minor complication rate after IBR with either autologous tissue or implants. Thus, NACT and IBR should be considered safe procedures. The review of studies describing patients undergoing implant-based breast reconstruction following NACT could indicate that single-stage DTI was a safer procedure than two-staged TE/I. However, the association requires further evaluation.

Murine burn lesion model for studying acute and chronic wound infections.

Acute wounds, such as thermal injury, and chronic wounds are challenging for patients and the healthcare system around the world. Thermal injury of considerable size induces immunosuppression, which renders the patient susceptible to wound infections, but also in other foci like the airways and urinary tract. Infected thermal lesions can progress to chronic wounds with biofilm making them more difficult to treat. While animal models have their limitations, murine wound models are still the best tool at the moment to identify strategies to overcome these challenges. Here, we present a murine burn model, which has been developed to study biofilm formation, the significance of wound healing, and for identifying novel treatment candidates. Investigating the effect of a thermal injury in mice, we observed that 48 h after introduction of the injury, the mice showed a reduction in polymorphonuclear neutrophil granulocytes (PMNs) and a reduced capacity for phagocytosis and oxidative burst. Regarding the chronic wound, Pseudomonas aeruginosa biofilm arrested wound healing and kept the wound in an inflammatory state, but suppressing PMN function by means of the PMN factor S100A8/A9, corresponding to observations in human venous leg ulcers. Monotherapy and dual treatment with S100A8/A9 and ciprofloxacin on P. aeruginosa biofilm-infected murine wounds have been investigated. In combination, S100A8/A9 and ciprofloxacin reduced the bacterial quantity, lowered the proinflammatory response, and increased anti-inflammatory cytokines after 4 days of treatment. When the treatment was prolonged, an additional prevention of resistance development was detected in all the dual-treated mice. In the present review, we provide data on using the murine model for research with the aim of better understanding pathophysiology of wounds and for identifying novel treatments for humans suffering from these lesions.

A Multidisciplinary Approach to Complex Dermal Sarcomas Ensures an Optimal Clinical Outcome.

Primary dermal sarcomas (PDS) belong to a highly clinically, genetically and pathologically heterogeneous group of rare malignant mesenchymal tumours primarily involving the dermis or the subcutaneous tissue. The tumours are classified according to the mesenchymal tissue from which they originate: dermal connective tissue, smooth muscle or vessels. Clinically, PDS may mimic benign soft tissue lesions such as dermatofibromas, hypertrophic scarring, etc. This may cause substantial diagnostic delay. As a group, PDS most commonly comprises the following clinicopathological forms of dermal sarcomas: dermatofibrosarcoma protuberans (DFSP), atypical fibroxanthoma (AFX), dermal undifferentiated pleomorphic sarcoma (DUPS), leiomyosarcoma (LMS), and vascular sarcomas (Kaposi's sarcoma, primary angiosarcoma, and radiation-induced angiosarcoma). This clinical entity has a broad spectrum regarding malignant potential; however, local aggressive behaviour in some forms causes surgical challenges. Preoperative, individualised surgical planning with complete free margins is pivotal along with a multidisciplinary approach and collaboration across highly specialised surgical and medical specialties. The present review gives a structured overview of the most common forms of dermal sarcomas including surgical recommendations and examples for advanced reconstructions as well as the current adjunctive medical treatment strategies. Optimal aesthetic and functional outcomes with low recurrence rates can be achieved by using a multidisciplinary approach to complex dermal sarcomas. In cases of extended local tumour invasion in dermal sarcomas, advanced reconstructive techniques can be applied, and the interdisciplinary microsurgeon should be an integral part of the sarcoma board.

Risk Stratification of Local Flaps and Skin Grafting in Skin Cancer-Related Facial Reconstruction: A Retrospective Single-Center Study of 607 Patients.

Background: Non-melanoma skin cancer (NMSC) takes up a substantial fraction of dermatological and plastic surgical outpatient visits and surgeries. NMSC develops as an accumulated exposure to UV light with the face most frequently diagnosed. Method: This retrospective study investigated the risk of complications in relation to full-thickness skin grafts (FTSG) or local flaps in 607 patients who underwent facial surgery and reconstruction at a high-volume center for facial cancer surgery at a tertiary university hospital. Results: Between 01.12.2017 and 30.11.2020, 304 patients received reconstructive flap surgery and 303 received FTSG following skin cancer removal in the face. Flap reconstruction was predominantly performed in the nasal region (78%, n = 237), whereas FTSG reconstruction was performed in the nasal (41,6%, n = 126), frontal (19.8%, n = 60), and temporal areas (19.8%, n = 60), respectively. Patients undergoing FTSGs had a significantly higher risk of hematoma (p = 0.003), partial necroses (p < 0.001), and total necroses (p < 0.001) compared to flap reconstruction. Age and sex increased the risk of major complications (hematoma, partial or total necrosis, wound dehiscence, or infection) for FTSG, revealing that men exhibited 3.72 times increased risk of major complications compared to women reconstructed with FTSG. A tumor size above 15 mm increased the risk of hematoma and necrosis significantly. In summary, local flaps for facial reconstruction after skin cancer provide lower complication rate compared with FTSGs, especially in elderly and/or male patients. The indication for FTSG should be considered critically if the patient's tumor size and location allow for both procedures.

Subungual Onycholemmal Cysts: A Case Report.

Subungual onycholemmal cysts (SOCs) are rare nail abnormalities. The clinical findings vary and include onychodystrophy, ridging, nail bed pigmentation, and thickening, but most often SOCs do not cause any symptoms and are accidental findings. In this case report, we present a case of a woman with pigmentation of the toenail, suspect for melanoma. Surprisingly, the histopathological examination showed SOCs. We discuss the histological features of SOCs, etiology, and differential diagnoses.

Adjunctive S100A8/A9 Immunomodulation Hinders Ciprofloxacin Resistance in Pseudomonas aeruginosa in a Murine Biofilm Wound Model.

Objective: Pseudomonas aeruginosa is known to contribute to the pathogenesis of chronic wounds by biofilm-establishment with increased tolerance to host response and antibiotics. The neutrophil-factor S100A8/A9 has a promising adjuvant effect when combined with ciprofloxacin, measured by quantitative bacteriology, and increased anti- and lowered pro-inflammatory proteins. We speculated whether a S100A8/A9 supplement could prevent ciprofloxacin resistance in infected wounds. Method: Full-thickness 2.9cm2-necrosis was inflicted on 32 mice. On day 4, P.aeruginosa in seaweed alginate was injected sub-eschar to mimic a mono-pathogenic biofilm. Mice were randomized to receive ciprofloxacin and S100A8/A9 (n=14), ciprofloxacin (n=12) or saline (n=6). Half of the mice in each group were euthanized day 6 and the remaining day 10 post-infection. Mice were treated until sacrifice. Primary endpoint was the appearance of ciprofloxacin resistant P.aeruginosa. The study was further evaluated by genetic characterization of resistance, means of quantitative bacteriology, wound-size and cytokine-production. Results: Three mice receiving ciprofloxacin monotherapy developed resistance after 14 days. None of the mice receiving combination therapy changed resistance pattern. Sequencing of fluoroquinolone-resistance determining regions in the ciprofloxacin resistant isolates identified two high-resistant strains mutated in gyrA C248T (MIC>32µg/ml) and a gyr B mutation was found in the sample with low level resistance (MIC=3µg/ml). Bacterial densities in wounds were lower in the dual treated group compared to the placebo group on both termination days. Conclusion: This study supports the ciprofloxacin augmenting effect and indicates a protective effect in terms of hindered ciprofloxacin resistance of adjuvant S100A8/A9 in P.aeruginosa biofilm infected chronic wounds.

Immune Responses to Pseudomonas aeruginosa Biofilm Infections.

Pseudomonas aeruginosa is a key pathogen of chronic infections in the lungs of cystic fibrosis patients and in patients suffering from chronic wounds of diverse etiology. In these infections the bacteria congregate in biofilms and cannot be eradicated by standard antibiotic treatment or host immune responses. The persistent biofilms induce a hyper inflammatory state that results in collateral damage of the adjacent host tissue. The host fails to eradicate the biofilm infection, resulting in hindered remodeling and healing. In the present review we describe our current understanding of innate and adaptive immune responses elicited by P. aeruginosa biofilms in cystic fibrosis lung infections and chronic wounds. This includes the mechanisms that are involved in the activation of the immune responses, as well as the effector functions, the antimicrobial components and the associated tissue destruction. The mechanisms by which the biofilms evade immune responses, and potential treatment targets of the immune response are also discussed.

Insights into Host-Pathogen Interactions in Biofilm-Infected Wounds Reveal Possibilities for New Treatment Strategies.

Normal wound healing occurs in three phases-the inflammatory, the proliferative, and the remodeling phase. Chronic wounds are, for unknown reasons, arrested in the inflammatory phase. Bacterial biofilms may cause chronicity by arresting healing in the inflammatory state by mechanisms not fully understood. Pseudomonas aeruginosa, a common wound pathogen with remarkable abilities in avoiding host defense and developing microbial resistance by biofilm formation, is detrimental to wound healing in clinical studies. The host response towards P. aeruginosa biofilm-infection in chronic wounds and impact on wound healing is discussed and compared to our own results in a chronic murine wound model. The impact of P. aeruginosa biofilms can be described by determining alterations in the inflammatory response, growth factor profile, and count of leukocytes in blood. P. aeruginosa biofilms are capable of reducing the host response to the infection, despite a continuously sustained inflammatory reaction and resulting local tissue damage. A recent observation of in vivo synergism between immunomodulatory and antimicrobial S100A8/A9 and ciprofloxacin suggests its possible future therapeutic potential.

Unusual Presentation of Cutaneous Spindle Cell Squamous Cell Carcinoma: A Case Report.

Cutaneous spindle cell squamous cell carcinoma (SpSCC) is a rare and often aggressive subtype of squamous cell carcinoma (SCC), which usually appears in sun-exposed areas, in areas that have received prior ionizing radiation, or in immunosuppressed individuals. SpSCCs are histologically characterized by keratinocytes infiltrating the dermis as single cells with elongated nuclei rather than as cohesive nests or islands and, in contrast to conventional SCC, are lacking features of keratinization. Immunohistochemical studies are useful to distinguish SpSCC from other spindle cell neoplasms, such as spindle cell/desmoplastic melanoma, cutaneous leiomyosarcoma, and atypical fibroxanthoma. We present a rare case of a patient with SpSCC in the gluteal region with regional lymph node metastasis. The patient was treated with wide excision of the tumor, inguinal lymph node dissection, and adjuvant radiotherapy. Cutaneous SpSCC is clinically similar to conventional SCC but can demonstrate more aggressive behavior. This case is rare since it was localized in the gluteal region of an otherwise healthy man.

Renal cell carcinoma presenting as a tumor on the scalp: A case report.

INTRODUCTION: Renal cell carcinoma (RCC) is often diagnosed as an incidental finding on imaging studies and about a fourth of patients have metastases by the time of diagnosis. RCC is known to metastasize widely but cutaneous metastases are considered uncommon and are rarely the presenting symptom of RCC. We present a case of RCC presenting with a tumor on the scalp. CASE: A 65-year-old healthy man presented with a 9-month history of a growing mass on the scalp. Clinical examination revealed a pulsating, highly vascularized tumor that was excised. Histopathological findings were consistent with a metastasis from a renal cell carcinoma. Further investigations revealed a 13 cm kidney tumor with metastases to the lungs and mediastinum. DISCUSSION: Cutaneous metastasis from RCC is uncommon and is rarely the initial symptom of RCC. The lesions often have a vascularized appearance and may be clinically confused with other vascular tumors. Skin metastasis is a sign of advanced disease and prognosis is poor. CONCLUSION: An occult RCC may present with a skin lesion. Skin metastasis from RCC is an important differential diagnosis in tumors with a vascular appearance, especially in patients with a previous history of RCC.

Don't Judge a Tumor by Its Biopsy!

Trichoblastomas (TBs) are extremely rare, benign hair germ tumors that can mimic basal cell carcinoma (BCC). They usually arise on the head or neck and have a potential for malignant transformation, albeit it is rare. We report a case of giant TB on the forehead of a 75-year-old otherwise healthy woman. Since the age of 20 she reported a bulge on her forehead, in which a superficial-looking wound had now developed. Initially a dermatologist biopsied the tumor suspecting a BCC, which the histological analyses confirmed. The patient was then referred to the Department of Plastic Surgery for complete excision of the carcinoma, including the large frontal bulge. Surprisingly, the concluding pathology report changed the diagnosis from a BCC to a TB. Current management of most skin lesions relies on the histopathological subtype of a single punch biopsy. Many benign and malignant dermatological entities may mimic BCC, and therefore misdiagnosis can lead to either unnecessary excision or delayed treatment of metastatic disease. Mimics may include various types of nonneoplastic processes, benign adnexal tumors, including TB, or cutaneous carcinomas with basaloid features. A single punch biopsy is not always adequate in making the correct diagnosis. Although it is considered the gold standard, the clinical assessment is just as important. Due to its potential for malignant transformation, it is recommended to excise TB with negative margins.

Synergistic effect of immunomodulatory S100A8/A9 and ciprofloxacin against Pseudomonas aeruginosa biofilm in a murine chronic wound model.

The majority of chronic wounds are associated with bacterial biofilms recalcitrant to antibiotics and host responses. Immunomodulatory S100A8/A9 is suppressed in Pseudomonas aeruginosa biofilm infected wounds. We aimed at investigating a possible additive effect between S100A8/A9 and ciprofloxacin against biofilms. MATERIALS/METHODS: Thirty-two mice were injected with alginate-embedded P. aeruginosa following a third-degree burn. The mice were randomized into four groups receiving combination ciprofloxacin and S100A8/A9 or monotherapy ciprofloxacin, S100A8/A9 or a placebo and evaluated by host responses and quantitative bacteriology in wounds. In addition, in vitro checkerboard analysis was performed, with P. aeruginosa and ascending S100A8/A9 and ciprofloxacin concentrations. RESULTS: S100A8/A9 augmented the effect of ciprofloxacin in vivo by lowering the bacterial quantity compared to the placebo arm and the two monointervention groups (P < 0.0001). S100A8 and 100A9 were increased in the double-treated group as compared to the monointervention groups (P = 0.032, P = 0.0023). Tissue inhibitor of metalloproteinases-1 and keratinocyte\chemokine chemoattractant-1 were increased in the double-intervention group compared to the S100A8/A9 group (P = 0.050, P = 0.050). No in vitro synergism was detected. CONCLUSION: The observed ciprofloxacin-augmenting effect of S100A8/A9 in vivo was not confirmed by checkerboard analysis, indicating dependence on host cells for the S100A8/A9 effect. S100A8/A9 and ciprofloxacin is a promising therapy for optimizing chronic wound treatment.