The majority of dermal wounds are colonized with aerobic and anaerobic microorganisms that originate predominantly from mucosal surfaces such as those of the oral cavity and gut. The role and significance of microorganisms in wound healing has been debated for many years. While some experts consider the microbial density to be critical in predicting wound healing and infection, others consider the types of microorganisms to be of greater importance. However, these and other factors such as microbial synergy, the host immune response, and the quality of tissue must be considered collectively in assessing the probability of infection. Debate also exists regarding the value of wound sampling, the types of wounds that should be sampled, and the sampling technique required to generate the most meaningful data. In the laboratory, consideration must be given to the relevance of culturing polymicrobial specimens, the value in identifying one or more microorganisms, and the microorganisms that should be assayed for antibiotic susceptibility. Although appropriate systemic antibiotics are essential for the treatment of deteriorating, clinically infected wounds, debate exists regarding the relevance and use of antibiotics (systemic or topical) and antiseptics (topical) in the treatment of nonhealing wounds that have no clinical signs of infection. In providing a detailed analysis of wound microbiology, together with current opinion and controversies regarding wound assessment and treatment, this review has attempted to capture and address microbiological aspects that are critical to the successful management of microorganisms in wounds.

Wound microbiology and associated approaches to wound management.

1 Interventions for cutaneous molluscum contagiosum (Review) Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. Main results We found 11 new studies for this update, resulting in 22 included studies with a total of 1650 participants. The studies examined the effects of topical (20 studies) and systemic interventions (2 studies). Among the new included studies were the full trial reports of three large unpublished studies, brought to our attention by an expert in the field. They all provided moderate-quality evidence for a lack of effect of 5% imiquimod compared to vehicle (placebo) on shortterm clinical cure (4 studies, 850 participants, 12 weeks after start of treatment, risk ratio (RR) 1.33, 95% confidence interval (CI) 0.92 to 1.93), medium-term clinical cure (2 studies, 702 participants, 18 weeks after start of treatment, RR 0.88, 95% CI 0.67 to 1.14), and long-term clinical cure (2 studies, 702 participants, 28 weeks after start of treatment, RR 0.97, 95% CI 0.79 to 1.17). We found similar but more certain results for short-term improvement (4 studies, 850 participants, 12 weeks after start of treatment, RR 1.14, 95% CI 0.89 to 1.47; high-quality evidence). For the outcome ’any adverse effect’, we found high-quality evidence for little or no difference between topical 5% imiquimod and vehicle (3 studies, 827 participants, RR 0.97, 95% CI 0.88 to 1.07), but application site reactions were more frequent in the groups treated with imiquimod (moderate-quality evidence): any application site reaction (3 studies, 827 participants, RR 1.41, 95% CI 1.13 to 1.77, the number needed to treat for an additional harmful outcome (NNTH) was 11); severe application site reaction (3 studies, 827 participants, RR 4.33, 95% CI 1.16 to 16.19, NNTH over 40). For the following 11 comparisons, there was limited evidence to show which treatment was superior in achieving short-term clinical cure (low-quality evidence): 5% imiquimod less effective than cryospray (1 study, 74 participants, RR 0.60, 95% CI 0.46 to 0.78) and 10% potassium hydroxide (2 studies, 67 participants, RR 0.65, 95% CI 0.46 to 0.93); 10% Australian lemon myrtle oil more effective than olive oil (1 study, 31 participants, RR 17.88, 95% CI 1.13 to 282.72); 10% benzoyl peroxide cream more effective than 0.05% tretinoin (1 study, 30 participants, RR 2.20, 95% CI 1.01 to 4.79); 5% sodium nitrite co-applied with 5% salicylic acid more effective than 5% salicylic acid alone (1 study, 30 participants, RR 3.50, 95% CI 1.23 to 9.92); and iodine plus tea tree oil more effective than tea tree oil (1 study, 37 participants, RR 0.20, 95% CI 0.07 to 0.57) or iodine alone (1 study, 37 participants, RR 0.07, 95% CI 0.01 to 0.50). Although there is some uncertainty, 10% potassium hydroxide appears to be more effective than saline (1 study, 20 participants, RR 3.50, 95% CI 0.95 to 12.90); homeopathic calcarea carbonica appears to be more effective than placebo (1 study, 20 participants, RR 5.57, 95% CI 0.93 to 33.54); 2.5% appears to be less effective than 5% solution of potassium hydroxide (1 study, 25 participants, RR 0.35, 95% CI 0.12 to 1.01); and 10% povidone iodine solution plus 50% salicylic acid plaster appears to be more effective than salicylic acid plaster alone (1 study, 30 participants, RR 1.43, 95% CI 0.95 to 2.16). We found no statistically significant differences for other comparisons (most of which addressed two different topical treatments). We found no randomised controlled trial evidence for expressing lesions or topical hydrogen peroxide. Study limitations included no blinding, many dropouts, and no intention-to-treat analysis. Except for the severe application site reactions of imiquimod, none of the evaluated treatments described above were associated with serious adverse effects (low-quality evidence). Among the most common adverse events were pain during application, erythema, and itching. Included studies of the following comparisons did not report adverse effects: calcarea carbonica versus placebo, 10% povidone iodine plus 50% salicylic acid plaster versus salicylic acid plaster, and 10% benzoyl peroxide versus 0.05% tretinoin. We were unable to judge the risk of bias in most studies due to insufficient information, especially regarding concealment of allocation and possible selective reporting. We considered five studies to be at low risk of bias. Authors’ conclusions No single intervention has been shown to be convincingly effective in the treatment of molluscum contagiosum. We found moderatequality evidence that topical 5% imiquimod was no more effective than vehicle in terms of clinical cure, but led to more application site reactions, and high-quality evidence that there was no difference between the treatments in terms of short-term improvement. However, high-quality evidence showed a similar number of general side effects in both groups. As the evidence found did not favour any one treatment, the natural resolution of molluscum contagiosum remains a strong method for dealing with the condition. P L A I N L A N G U A G E S U M M A R Y Treatments for molluscum contagiosum, a common viral skin infection in children Review question 2 Interventions for cutaneous molluscum contagiosum (Review) Copyright © 2017 The Cochrane Collaboration. Published by John Wiley & Sons, Ltd. We reviewed the evidence for the effect of any treatment on the common viral skin infection molluscum contagiosum. We excluded people with a repressed immune system or sexually transmitted molluscum contagiosum. Background Molluscum contagiosum in healthy people is a self limiting, relatively harmless viral skin infection. It mainly affects children and adolescents and is rare in adults. It occurs worldwide, but seems much more frequent in geographic areas with warm climates. Molluscum contagiosum usually presents as single or multiple pimples filled with an oily substance. People may seek treatment for social and cosmetic reasons and because of concerns about spreading the disease to others. Treatment is intended to speed up the healing process. Study characteristics We searched the literature to July 2016. We included 22 trials (total of 1650 participants). Twenty of the studies evaluated topical treatment, and two studies evaluated treatment taken by mouth (oral). Comparisons included physical therapies, as well as topical and oral treatments. Most studies were set in hospital outpatient or emergency departments, and were performed in North America, the UK, Asia, or South America. Participants were of both sexes and were mainly children or young adults. Follow-up duration varied from 3 to 28 weeks after randomisation. Only five studies had longer than 3 months’ follow-up. Five studies reported commercial funding, three studies obtained medication for free from pharmaceutical companies, 12 studies did not mention the source of funding, one study reported charity funding, and one study reported they had had no financial support. Key results We found that many common treatments for molluscum, such as physical destruction, have not been adequately evaluated. Some of the included treatments are not part of standard practice. We found moderate-quality evidence that topical 5% imiquimod is probably no more effective than vehicle (i.e. the same cream but without imiquimod) in achieving short-, medium-, and long-term clinical cure. High-quality (and thus more certain) evidence showed that topical 5% imiquimod is no better than placebo at improving molluscum up to three months after the start of treatment. High-quality evidence showed that 5% imiquimod differed little or not at all in the number of side effects compared to vehicle. However, moderate-quality evidence suggests that there are probably more application site reactions when using topical 5% imiquimod compared with vehicle. Low-quality evidence, based on one or two mostly small studies, revealed the following results for the outcome short-term clinical cure: 5% imiquimod less effective than cryospray or 10% potassium hydroxide; 10% Australian lemon myrtle oil more effective than olive oil; 10% benzoyl peroxide cream more effective than 0.05% tretinoin; 5% sodium nitrite co-applied with 5% salicylic acid more effective than 5% salicylic acid alone; and iodine plus tea tree oil more effective than tea tree oil or iodine alone. We found more uncertain (low-quality) evidence to suggest that 10% potassium hydroxide is more effective than saline; homeopathic calcarea carbonica is more effective than placebo; 2.5% solution of potassium hydroxide is less effective than 5% solution of potassium hydroxide; and 10% povidone iodine solution and 50% salicylic acid plaster are more effective than salicylic acid plaster alone. Except for the severe application site reactions of imiquimod, none of these treatments led to serious adverse effects (low-quality evidence). Pain during treatment application, redness, and itching were among the most reported adverse effects. We found no differences between the treatments assessed in the other comparisons. We found no randomised trials for several commonly used treatments, such as expressing lesions with an orange stick or topical hydrogen peroxide. Since most lesions resolve within months, unless better evidence for the superiority of active treatments emerges, molluscum contagiosum can be left to heal naturally. Quality of the evidence For topical imiquimod, the quality of the evidence for clinical cure, short-term improvement, and adverse effects was moderate to high. For all other comparisons, the quality of the evidence for short-term clinical cure and adverse effects was low. Common limitations of the included studies were that the numbers of participants were small, the investigators were not blinded, and participants who did not complete the study (numerous in some studies) were not included in the analyses. 3 Interventions for cutaneous molluscum contagiosum (Rev

The Cochrane Database of Systematic Reviews

Over 100 years ago, Robert Koch introduced his ideas about how to prove a causal relationship between a microorganism and a disease. Koch9s postulates created a scientific standard for causal evidence that established the credibility of microbes as pathogens and led to the development of modern microbiology. In more recent times, Koch9s postulates have evolved to accommodate a broader understanding of the host-parasite relationship as well as experimental advances. Techniques such as in situ hybridization, PCR, and representational difference analysis reveal previously uncharacterized, fastidious or uncultivated, microbial pathogens that resist the application of Koch9s original postulates, but they also provide new approaches for proving disease causation. In particular, the increasing reliance on sequence-based methods for microbial identification requires a reassessment of the original postulates and the rationale that guided Koch and later revisionists. Recent investigations of Whipple9s disease, human ehrlichiosis, hepatitis C, hantavirus pulmonary syndrome, and Kaposi9s sarcoma illustrate some of these issues. A set of molecular guidelines for establishing disease causation with sequence-based technology is proposed, and the importance of the scientific concordance of evidence in supporting causal associations is emphasized.

/pdf/sequence-based-identification-of-microbial-pathogens-a-1j98d6hs81.pdf

Sequence-based identification of microbial pathogens: a reconsideration of Koch's postulates.

Detection of Kaposi sarcoma associated herpesvirus in peripheral blood of HIV-infected individuals and progression to Kaposi's sarcoma

Striking differences in Kaposi's sarcoma (KS) risk for AIDS patients who acquire HIV via homosexual activity and those whose HIV infections derive from blood product exposure suggest the presence of a sexually transmitted agent other than HIV in the development of KS Using an immunofluorescence assay, we examined serum samples from 913 patients for the presence of antibody specific for infection by human herpesvirus 8 (HHV8), an agent whose genome is regularly found in KS tissue The distribution of HHV8 seropositivity conforms to that expected for a sexually transmitted pathogen and tracks closely with the risk for KS development Our data support the inference that this virus is the etiologic cofactor predicted by the epidemiology of KS

The seroepidemiology of human herpesvirus 8 (kaposi’s sarcoma-associated herpesvirus): distribution of infection in ks risk groups and evidence for sexual transmission

Background Previous studies of the incidence and the most common causes of cutaneous metastasis have not led to a consensus. We compiled data from many retrospective studies and from patient data registries and autopsies to increase the total number of cases available for a larger analysis of this subject. This study was conducted to gain a better understanding of the true incidence of cutaneous metastasis, the tumors most commonly involved in this presentation, and the locations of such lesions. Methods A meta-analysis of cutaneous metastases from patient tumor registries and autopsic studies was performed. Results The overall incidence of cutaneous metastasis is 5.3%. The most common tumor to metastasize to the skin is breast cancer. The chest is the most common site of cutaneous metastasis. Every practitioner should be highly suspicious of acute-onset, persistent, firm papulonodules, especially when they develop on the chest. Conclusion This meta-analysis greatly increases the total number of cases available for the analysis of cutaneous metastases and provides a better overall view of this topic than was previously possible.

Cutaneous metastasis: a meta-analysis of data.

It is estimated that half of all Americans will be bitten by an animal or another human being during their lifetimes. The vast majority of the estimated 2 million annual mammalian bite wounds are minor, and the victims never seek medical attention. Nonetheless, bite wounds account for approximately 1% of all emergency department visits and more than $30 million in annual health care costs. Infection is the most common bite-associated complication; the relative risk is determined by the species of the inflicting animal, bite location, host factors, and local wound care. Most infections caused by mammalian bites are polymicrobial, with mixed aerobic and anaerobic species. The clinical presentation and appropriate treatment of infected bite wounds vary according to the causative organisms. Human bite wounds have long had a bad reputation for severe infection and frequent complication. However, recent data demonstrate that human bites occurring anywhere other than the hand present no more of a risk for infection than any other type of mammalian bite. The increased incidence of serious infections and complications associated with human bites to the hand warrants their consideration and management in three different categories: occlusional/simple, clenched fist injuries, and occlusional bites to the hand. This article reviews dogs, cat, and human bite wounds, risk factors for complications, evaluation components, bacteriology, antimicrobial susceptibility patterns, and recommended treatments. Epidemiology, clinical presentation, and treatment of infections caused by Pasteurella multocida, Capnocytophaga canimorsus, Eikenella corrodens, and rhabdovirus (rabies only) receive particular emphasis.

https://www.jaad.org/article/0190-9622(95)90296-1/pdf

Dog, cat, and human bites: A review

Herpesvirus-like DNA sequences in non-Kaposi's sarcoma skin lesions of transplant patients

Objective To assess the preventive effect of a cyclooxygenase 2 inhibitor, celecoxib (Celebrex; G.D. Searle & Co, Skokie, Ill), in UV-induced skin cancer in hairless mice. Design Randomized dose-response study. A total of 75 SKH-HR-1 female hairless mice, aged 2 months, were randomized into control, low-dose (200 mg twice daily human dose equivalent), and high-dose (400 mg twice daily human dose equivalent) celecoxib treatment groups. Animals received 1 J/cm 2 daily (5 d/wk) total irradiation. The animals were evaluated weekly for appearance of tumors, and the data were analyzed with respect to tumor latency period and tumor multiplicity using statistical software and Wilcoxon rank sum analyses, respectively. Prostaglandin E 2 levels in the blood and skin were assessed in each group. Setting Veterans Affairs Medical Center, Research and Dermatology Services. Intervention Animals received restricted diets containing the Food and Drug Administration–approved human equivalent doses of 200 mg (low dose) and 400 mg (high dose) of celecoxib twice daily. Controls received no drug. Tumors were induced in all animals with an equivalent UV dose. Main Outcome Measures Animals were evaluated weekly for the appearance of tumors, and data were analyzed with regard to tumor latency period and tumor multiplicity. Constitutive prostaglandin E 2 levels in blood and epidermis were assessed in each group. Results Low doses and high doses of celecoxib significantly lengthened the tumor latency period ( P P P P 2 in the low- or high-dose treated animals compared with controls when analyzed at study termination. Conclusions Celecoxib is an effective and safe chemopreventive agent in UV carcinogenesis. The epidemiologic, laboratory, and animal studies of the influence of celecoxib on cancer incidence and its low association with systemic adverse effects have led to a potentially new therapeutic approach for the prevention of skin cancer.

https://jamanetwork.com/journals/jamadermatology/articlepdf/478864/dst10097.pdf

Celecoxib, a cyclooxygenase 2 inhibitor as a potential chemopreventive to UV-induced skin cancer: a study in the hairless mouse model.

Multiple advances in the field of transplantation over the last several decades have resulted in a significant increase in the number of surgeries performed and in years of life extended. However, with the success of transplant comes the dilemma of potential complications of lifelong immunosuppressive therapy. An enormous increase in skin cancer, especially highly-aggressive squamous cell carcinoma, may affect this special population of patients. This review article discusses the main etiologic theories of squamous cell carcinoma, characteristics of skin cancer in the immunosuppressed patient, differences in skin cancer amongst three types of solid-organ transplantation (kidney, heart, and liver), and established and new treatments.

Ida Orengo

Papers

Cutaneous metastasis: a meta-analysis of data.

Dog, cat, and human bites: A review

Herpesvirus-like DNA sequences in non-Kaposi's sarcoma skin lesions of transplant patients

Celecoxib, a cyclooxygenase 2 inhibitor as a potential chemopreventive to UV-induced skin cancer: a study in the hairless mouse model.

Squamous cell carcinoma in solid-organ transplantation.