Chronic wounds and novel therapeutic approaches.

In the past decade, the frequency of chronic wounds in older population has increased, and their impact on quality of life is substantial. Chronic wounds are a public health problem associated with very high economic and psychosocial costs. These wounds result from various pathologies and comorbidities, such arterial and venous insufficiency, diabetes mellitus and continuous skin pressure. Recently, the role of infection and biofilms in the healing of chronic wounds has been the subject of considerable research. This paper presents an overview of various methods and products used to manage chronic wounds and discusses recent advances in wound care. To decide on the best treatment for any wound, it is crucial to holistically assess the patient and the wound. Additionally, multiple strategies could be used to prevent or treat chronic wounds.

Hard-to-heal wounds, biofilm and wound healing: an intricate interrelationship.

Hard-to-heal wounds are a major public health problem that incur high economic costs. A major source of morbidity, they can have an overwhelming impact on patients, caregivers and society. In contrast to acute wound healing, which follows an 'orderly and timely reparative process', the healing of hard-to-heal wounds is delayed because the usual biological progression is interrupted. This article discusses hard-to-heal wounds, the impact they have on patients and healthcare systems, and how biofilms and other factors affect the wound-healing process. Controlling and preventing infection is of utmost importance for normal wound healing. Rational use of anti-infectious agents is crucial and is particularly relevant in the context of rising healthcare costs. Knowledge of the complex relationship between hard-to-heal wounds, biofilm formation and wound healing is vital for efficient management of hard-to-heal wounds.

High Prevalence of Human Papillomavirus on Anal and Oral Samples from Men and Women with External Anogenital Warts: The HERCOLES Study.

Human papillomavirus (HPV) infection is highly prevalent in the sexually active population. This study estimates the prevalence of HPV DNA in anal and oral samples from a cohort of men and women with incident anogenital warts. Anal and/or oral samples from 541 patients with anogenital warts were tested for 35 HPV genotypes using a PCR assay. The overall prevalence of anal HPV and oral HPV DNA was 59.9% (n = 305/509; 95% confidence interval (CI) 55.6-64.1%) and 14.5% (n = 78/538; 95% CI 11.8-17.7%), respectively. Among patients with perianal warts, the anal HPV DNA prevalence was 92.3% (95% CI 87.0-95.5%). Anal HPV DNA prevalence in patients with genital warts but no perianal warts was 55.7% (95% CI 50.6-60.7%). Both anal and oral HPV infections were more common in men who have sex with men than in heterosexual men (90.4% versus 38.5% and 20.8% versus 11.8%, respectively). Anal high risk-HPV infection was more common in women (58.8%) and in men who have sex with men (67.7%). We found that anogenital warts represent a clinical marker for both anal and oral HPV infections, including anal high risk-HPV infections, particularly among women and men who have sex with men.

Malassezia interaction with a reconstructed human epidermis: Keratinocyte immune response.

The immediate immune response developed by the keratinocytes against Malassezia yeasts has been addressed yielding conflicting results. This study aims the assessment of cytokines and antimicrobial peptides gene expression elicited by M. sympodialis and M. furfur once in contact with a reconstructed human epidermis. A yeast suspension was prepared in RPMI 1640 medium (Sigma-Aldrich, St. Louis, MO) supplemented with Tween 60 and oleic acid to obtain approximately 1 × 106 cells in a volume of 100 µL. Clinical isolates of M. sympodialis (from pityriasis versicolor) and M. furfur (from seborrhoeic dermatitis) were inoculated, separately, onto a reconstructed human epidermis. A distinct expression pattern was found between the two tested species, with a tendency for overexpression of pro-inflammatory cytokines very soon after infection, whereas no significant expression or gene downregulation was often noticed following 24 and 48 h of incubation. A possible Malassezia species-dependent immune response pattern is highlighted.

Malassezia colonisation on a reconstructed human epidermis: Imaging studies.

BACKGROUND: Biofilm formation represents a major microbial virulence attribute especially at epithelial surfaces such as the skin. Malassezia biofilm formation at the skin surface has not yet been addressed. OBJECTIVE: The present study aimed to evaluate Malassezia colonisation pattern on a reconstructed human epidermis (RhE) by imaging techniques. METHODS: Malassezia clinical isolates were previously isolated from volunteers with pityriasis versicolor and seborrhoeic dermatitis. Yeast of two strains of M furfur and M sympodialis were inoculated onto the SkinEthic™ RHE. The tissues were processed for light microscopy, wide-field fluorescence microscopy and scanning electron microscopy. RESULTS: Colonisation of the RhE surface with aggregates of Malassezia yeast entrapped in a multilayer sheet with variable amount of extracellular matrix was unveiled by imaging techniques following 24, 48, 72 and 96 hours of incubation. Whenever yeast were suspended in RPMI medium supplemented with lipids, the biofilm substantially increased with a dense extracellular matrix in which the yeast cells were embedded. Slight differences were found in the biofilm architectural structure between the two tested species with an apparently higher entrapment and viscosity in M furfur biofilm. CONCLUSION: Skin isolates of M furfur and M sympodialis were capable of forming biofilm in vitro at the epidermal surface simulating in vivo conditions. Following 24 hours of incubation, without added lipids, rudimental matrix was barely visible, conversely to the reported at plastic surfaces. The amount of biofilm apparently increased progressively from 48 to 96 hours. A structural heterogeneity of biofilm between species was found.

Anogenital warts in children: Analysis of a cohort of 34 prepubertal children.

Anogenital warts are caused by infection with the human papillomavirus. We reviewed the clinical data of 34 children younger than 13 with anogenital warts referred to the department of dermatovenereology of a tertiary care hospital. Suspicion of sexual abuse was raised in 11 (32.4%). Human papilloma virus testing and genotyping was performed in 19 (55.9%) children, and human papilloma virus type 16 was found in 4, which raises the question regarding what type of follow-up is required for children infected with high-risk oncogenic HPV types. Although the diagnosis of anogenital warts in children raises concerns regarding sexual abuse, our study supports that pediatric anogenital warts can be associated with nonsexual transmission.

Hospitalisations with Hidradenitis Suppurativa: An Increasing Problem That Deserves Closer Attention.

BACKGROUND/AIMS: Hidradenitis suppurativa (HS), a chronic inflammatory skin disease of the hair follicle, can lead to scarring and disability. With an estimated European prevalence of 1%, few epidemiological studies of HS have been performed, and none focused on hospitalisations. We aimed to study the time trends of HS hospitalisations and to evaluate the demographic characteristics, hospital incidence rate, readmissions, length of stay, comorbidities and risk factors of hospitalised HS patients. METHODS: We performed a retrospective observational study using a national administrative database in Portugal, with discharges between 2000 and 2014. All the inpatients aged 5 years or more with a diagnosis of HS were included. Variables analysed were age, sex, admission and discharge date, discharge outcome and diagnoses. RESULTS: A total of 1,177 patients were hospitalised in this time period (48 were aged 18 years or younger) with a male-to-female ratio of 1:1.17. There was a hospital incidence rate of 0.83 patients with HS per 100,000 person-years (95% CI = 0.78-0.88). The age group with the highest incidence rate was 20-29 years among women and 40-49 years among men. We recorded an increasing trend in the number of new hospitalised patients and in the hospital incidence rate of HS. Tobacco was the most common comorbidity/risk factor. Eighty-three percent of our population underwent HS surgery. CONCLUSION: This hospital-based incidence study showed that admission for HS is increasing and that the majority of the HS inpatients were surgical cases. In the future, prospective studies will be important to assess risk factors for hospitalisations and complications.

Occurrence of respiratory symptoms in persons with restrictive ventilatory impairment compared with persons with chronic obstructive pulmonary disease: The PLATINO study.

Patients with chronic obstructive pulmonary disease (COPD) usually complain of symptoms such as cough, sputum, wheezing, and dyspnea. Little is known about clinical symptoms in individuals with restrictive ventilatory impairment. The aim of this study was to compare the prevalence and type of respiratory symptoms in patients with COPD to those reported by individuals with restrictive ventilatory impairment in the Proyecto Latinoamericano de Investigacion en Obstruccion Pulmonar study. Between 2002 and 2004, individuals ≥40 years of age from five cities in Latin America performed pre and post-bronchodilator spirometry and had their respiratory symptoms recorded in a standardized questionnaire. Among the 5315 individuals evaluated, 260 (5.1%) had a restrictive spirometric diagnosis (forced vital capacity (FVC) < lower limit of normal (LLN) with forced expiratory volume in the first second to forced vital capacity ratio (FEV1/FVC) ≥ LLN; American Thoracic Society (ATS)/European Respiratory Society (ERS) 2005) and 610 (11.9%) were diagnosed with an obstructive pattern (FEV1/FVC < LLN; ATS/ERS 2005). Patients with mild restriction wheezed more ((30.8%) vs. (17.8%); p < 0.028). No difference was seen in dyspnea, cough, and sputum between the two groups after adjusting for severity stage. The health status scores for the short form 12 questionnaire were similar in restricted and obstructed patients for both physical (48.4 ± 9.4 vs. 48.3 ± 9.8) and mental (50.8 ± 10.6 vs. 50.0 ± 11.5) domains. Overall, respiratory symptoms are not frequently reported by patients with restricted and obstructed patterns as defined by spirometry. Wheezing was more frequent in patients with restricted pattern compared with those with obstructive ventilatory defect. However, the prevalence of cough, sputum production, and dyspnea are not different between the two groups when adjusted by the same severity stage.

Malassezia infections: a medical conundrum.

Malassezia yeasts have long been considered commensal fungi, unable to elicit significant damage. However, they have been associated with a diversity of cutaneous diseases, namely pityriasis versicolor, Malassezia folliculitis, seborrheic dermatitis, atopic dermatitis, psoriasis, and confluent and reticulate papillomatosis. Several hypotheses have been proposed to explain the pathogenic mechanisms of these fungi, but none have been confirmed. More recently, such organisms have been increasingly isolated from bloodstream infections raising serious concern about these fungi. Given the difficulty to culture these yeasts to proceed with speciation and antimicrobial susceptibility tests, such procedures are most often not performed and the cutaneous infections are treated empirically. The recurring nature of superficial skin infections and the potential threat of systemic infections raise the need of faster and more sensitive techniques to achieve isolation, identification, and antimicrobial susceptibility profile. This article reviews and discusses the latest available data concerning Malassezia infections and recent developments about diagnostic methods, virulence mechanisms, and susceptibility testing.

Genital Warts in Women Vaccinated against HPV in Childhood: A Systematic Review.

Human papillomavirus (HPV) is the most prevalent sexually transmitted infection among young women. Notably, more than ten years after the introduction of HPV vaccination programs in Europe, it is essential to review the real-world evidence of the incidence of anogenital warts (GWs) among women vaccinated during childhood. In this systematic review, three databases were searched for studies published between January 2008 and September 2023. Nine cohort studies were included. A total of 890,320 HPV-vaccinated women and 1,922,033 unvaccinated women were evaluated. All the studies but one investigated the 4vHPV vaccine. The incidence rate of GWs in vaccinated women ranged from 0.0 to 1650 per 100,000 person-years. The highest incidence rates were found in women vaccinated with one dose at the age of 17-19 years old and in fully vaccinated women only after 19 years of age. Similar incidence values were reported among unvaccinated women. The incidence of GWs was lower when the age at first dose was 9-11 years old. This systematic review reveals that the incidence of GWs among HPV-vaccinated women is related to the age of vaccination and the number of vaccine doses received. In the post-vaccination era, epidemiological surveillance of the incidence of GWs and their genotypes is crucial.

Clinical Manifestations of Human Exposure to Fungi.

Biological particles, along with inorganic gaseous and particulate pollutants, constitute an ever-present component of the atmosphere and surfaces. Among these particles are fungal species colonizing almost all ecosystems, including the human body. Although inoffensive to most people, fungi can be responsible for several health problems, such as allergic fungal diseases and fungal infections. Worldwide fungal disease incidence is increasing, with new emerging fungal diseases appearing yearly. Reasons for this increase are the expansion of life expectancy, the number of immunocompromised patients (immunosuppressive treatments for transplantation, autoimmune diseases, and immunodeficiency diseases), the number of uncontrolled underlying conditions (e.g., diabetes mellitus), and the misusage of medication (e.g., corticosteroids and broad-spectrum antibiotics). Managing fungal diseases is challenging; only four classes of antifungal drugs are available, resistance to these drugs is increasing, and no vaccines have been approved. The present work reviews the implications of fungal particles in human health from allergic diseases (i.e., allergic bronchopulmonary aspergillosis, severe asthma with fungal sensitization, thunderstorm asthma, allergic fungal rhinosinusitis, and occupational lung diseases) to infections (i.e., superficial, subcutaneous, and systemic infections). Topics such as the etiological agent, risk factors, clinical manifestations, diagnosis, and treatment will be revised to improve the knowledge of this growing health concern.

Impact of Human Papillomavirus Vaccination on Male Disease: A Systematic Review.

Human papillomavirus (HPV)-related diseases are highly prevalent in men worldwide, comprising external anogenital condyloma, anal intraepithelial neoplasia (AIN), penile intraepithelial neoplasia (PIN), and anogenital and oropharyngeal cancers. There is exceptionally low vaccine coverage in the male population. Only 4% of men were fully vaccinated, worldwide, as of 2019. The aim of this review is to assess the impact of HPV vaccination on male disease. Three databases (MEDLINE, Web of Science, Scopus) and Clinical Trials.gov were searched. We included thirteen studies, eight randomized controlled trials (RCTs), and five cohorts, comprising a total of 14,239 participants. Regarding anal disease, seven studies reported HPV vaccine efficacy ranging from 91.1% to 93.1% against AIN1, and ranging from 89.6% to 91.7% against AIN2|3 and anal cancer. Five studies showed an efficacy against genital condyloma of 89.9% in HPV-naïve males, varying between 66.7% and 67.2% in intention-to-treat populations. Studies reporting no efficacy have included older participants. These results support vaccination of young men previously infected, beyond HPV-naïve males. The evidence quality was moderate to low for most outcomes, namely genital diseases. RCTs are needed to assess the efficacy of HPV vaccination on male oropharyngeal cancer.

Mpox Person-to-Person Transmission-Where Have We Got So Far? A Systematic Review.

The recent multi-country outbreak of Mpox (Monkeypox disease) constituted a public health emergency. Although animal-to-human transmission is known to be the primary way of transmission, an increasing number of cases transmitted by person-to-person contact have been reported. During the recent Mpox outbreak sexual or intimate contact has been considered the most important way of transmission. However, other routes of transmission must not be ignored. The knowledge of how the Monkeypox Virus (MPXV) spreads is crucial to implement adequate measures to contain the spread of the disease. Therefore, this systematic review aimed to collect scientific data published concerning other implicated sources of infection beyond sexual interaction, such as the involvement of respiratory particles, contact with contaminated surfaces and skin-to-skin contact. The current study was performed using the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Publications analyzing contacts of Mpox index cases and their outcome after contact were included. A total of 7319 person-to-person contacts were surveyed and 273 of them became positive cases. Positive secondary transmission of MPXV was verified after contact with people cohabiting in the same household, with family members, with healthcare workers, or within healthcare facilities, and sexual contact or contact with contaminated surfaces. Using the same cup, sharing the same dishes, and sleeping in the same room or bed were also positively associated with transmission. Five studies showed no evidence of transmission despite contact with surfaces, skin-to-skin contact, or through airway particles within healthcare facilities where containment measures were taken. These records support the case for person-to-person transmission and suggest that other types of contact beyond sexual contact pose a significant risk of acquiring the infection. Further investigation is crucial to elucidate MPXV transmission dynamics, and to implement adequate measures to contain the spread of the infection.

Microbiota of Urine, Glans and Prostate Biopsies in Patients with Prostate Cancer Reveals a Dysbiosis in the Genitourinary System.

Prostate cancer (PCa) is the most common malignant neoplasm with the highest worldwide incidence in men aged 50 years and older. Emerging evidence suggests that the microbial dysbiosis may promote chronic inflammation linked to the development of PCa. Therefore, this study aims to compare the microbiota composition and diversity in urine, glans swabs, and prostate biopsies between men with PCa and non-PCa men. Microbial communities profiling was assessed through 16S rRNA sequencing. The results indicated that α-diversity (number and abundance of genera) was lower in prostate and glans, and higher in urine from patients with PCa, compared to non-PCa patients. The different genera of the bacterial community found in urine was significantly different in PCa patients compared to non-PCa patients, but they did not differ in glans and prostate. Moreover, comparing the bacterial communities present in the three different samples, urine and glans show a similar genus composition. Linear discriminant analysis (LDA) effect size (LEfSe) analysis revealed significantly higher levels of the genera Streptococcus, Prevotella, Peptoniphilus, Negativicoccus, Actinomyces, Propionimicrobium, and Facklamia in urine of PCa patients, whereas Methylobacterium/Methylorubrum, Faecalibacterium, and Blautia were more abundant in the non-PCa patients. In glans, the genus Stenotrophomonas was enriched in PCa subjects, while Peptococcus was more abundant in non-PCa subjects. In prostate, Alishewanella, Paracoccus, Klebsiella, and Rothia were the overrepresented genera in the PCa group, while Actinomyces, Parabacteroides, Muribaculaceae sp., and Prevotella were overrepresented in the non-PCa group. These findings provide a strong background for the development of potential biomarkers with clinical interest.

Skin disorders in the neonatal intensive care unit of a central hospital.

Cutaneous abnormalities in the newborn are usually benign and transitory. However, they may sometimes be extremely distressing both for parents and the medical staff, presenting with significant morbidity and mortality. The aim of this study was to access the clinical features of different skin disorders in a series of newborns, at a level III neonatal intensive care unit (NICU) in the Northern Region of Portugal, and review some of the most impressive cases. Between January 1997 and December 2010, 27 patients were found to have an important cutaneous condition that required admission to the NICU. The most frequent presentations were vesicles and pustules (n=8; 29.6%), followed by erythroderma (n=7; 25.9%), atrophic (n=5; 18.5%) and vascular lesions (n=4; 14.8%). Four (14.8%) patients died in the neonatal period, and further 4 afterwards. Genetic studies, when available, revealed three chromosomal disorders and 6 gene mutations. Overall, skin disorders were not a leading cause of NICU admission (0.43%), but were associated with significant morbidity and mortality.

Acute generalized exanthematous pustulosis to amoxicillin associated with parvovirus B19 reactivation.

We report the case of a 22-year-old male patient with 2 episodes, 4 months apart, of acute generalized exanthematous pustulosis (AGEP) associated with oral intake of amoxicillin and simultaneous reactivation of parvovirus B19 infection proven by positive polymerase chain reaction test in the skin fragment and blood sample and elevation of the IgG antibodies titer. To our knowledge, this is the first report of AGEP resulting from the interaction between drug hypersensitivity and the reactivation of parvovirus B19. A combination of an immunological reaction to the drug and virus infection could be responsible for the clinical picture.

[C-Reactive protein levels in patients with chronic obstructive pulmonary disease]. / Proteína C Reactiva en la EPOC y su relación con la gravedad de la enfermedad, las exacerbaciones y las comorbilidades.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) have elevated serum levels of ultrasensitive C reactive protein (CRPus). This raise may be related directly to COPD and its associated systemic inflammation or secondary to other factors such as smoking status, disease severity, acute exacerbations, or associated complications. AIM: To evaluate the potential causes of raised levels of CRPus in stable COPD patients. PATIENTS AND METHODS: Cohorts of 133 mild-to-very severe COPD patients (41 current smokers), 31 never-smokers, and 33 current smoker controls were compared. Clinical assessments included body mass index (BMI), fat (FM) and fat-free mass (FFM) measurement by DEXA, forced expiratory volume in one second (FEV1), arterial oxygen tension (PaO2), six-minute walking test (SMWT), emphysema (EMPH) and right thigh muscle cross-sectional area (TMCSA), both quantified by high resolution computed tomography. RESULTS: Serum CRPus levels were significantly higher in COPD patients than in controls (7 ± 4.2 and 3.7 ± 2.7 mg/L respectively; p < 0.0001). Being smoker did not influence CRPus levels. These levels were significantly correlated with FM (r = 0.30), BMI (r = 0.21), FEV1 (r = -0.21), number of acute exacerbations of the disease in the last year (r = 0.28), and PaO2 (r = -0.27). Using multivariate analysis FM, PaO2, and number of acute exacerbations of the disease in the last year had the strongest association with CRPus levels. CONCLUSIONS: CRPus is elevated in COPD patients, independent of smoking status. It is weakly associated with fat mass, arterial oxygen tension and frequency of exacerbations.

Microbiome in Male Genital Mucosa (Prepuce, Glans, and Coronal Sulcus): A Systematic Review.

The human body represents a complex and diverse reservoir of microorganisms. Although the human microbiome remains poorly characterized and understood, it should not be underestimated, since recent studies have highlighted its importance in health. This is especially evident when considering microbiota in the male reproductive system, responsible for men's fertility and sexual behavior. Therefore, the aim of this systematic review is to provide an overview of the microbial communities of the healthy male genital mucosa and its role in disease. This study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The search was limited to the English language and studies published until August 2022 that included culture-independent techniques for microbiome characterization in male genital mucosa. Ten articles were included. The bacterial composition of the male genital mucosa consists of several genera including Prevotella, Finegoldia, Peptoniphilus, Staphylococcus, Corynebacterium, and Anaerococcus, suggesting that the male genital microbiome composition shows similarities with the adjacent anatomical sites and is related with sexual intercourse. Moreover, male circumcision appears to influence the penile microbiome. Despite the lack of knowledge on the male genital mucosa microbiome in disease, it was reported that Staphylococcus warneri and Prevotella bivia were associated with balanoposthitis, whereas Enterobacteriaceae, Prevotella, and Fusobacterium were more abundant in male genital lichen sclerosus. The limited data and paucity of prospective controlled studies highlight the need for additional studies and established criteria for sampling methods and the microbiome assay procedure. Such a consensus would foster the knowledge about the composition of the genital microbiome of healthy males and its role in disease.

Granuloma faciale with subglottic eosinophilic angiocentric fibrosis: case report and review of the literature.

Granuloma faciale (GF) is an uncommon inflammatory dermatosis that usually presents on the face as reddish brown or violaceous papules and nodules that may coalesce into plaques. Eosinophilic angiocentric fibrosis (EAF) is a rare fibrosing condition that shares many histologic characteristics with GF and is regarded by some authors as a mucosal counterpart of GF. We present a case of GF with concurrent EAF in a subglottic location with excellent response to an intralesional corticosteroid on the GF lesion, CO2 laser on the EAF lesion, and oral dapsone treatment.