Photodynamic Therapy Interventions in Facial Photodamage: A Systematic Review

Publication date: Available online 30 December 2017
Source:Actas Dermo-Sifiliográficas
Author(s): G. Sanclemente, V. Ruiz-Cañas, J.M. Miranda, A.P. Ferrín, P.A. Ramirez, G.N. Hernandez
IntroductionPhotodynamic therapy (PDT) involves the combination of a light source and a photosensitizing agent to induce tissue damage via the generation of singlet oxygen. Although topical PDT has been approved for other indications, its use in facial photodamage is uncertain.AimsTo assess the efficacy and safety of PDT in facial skin photoaging.MethodsAll randomized clinical trials (RCTs) evaluating the efficacy and safety of any form of topical PDT for the treatment of facial photodamage (dermatoheliosis) or photoaging in patients older than 18 years, were included. Photodynamic-therapy using any topical photosensitizing agent at any dose, and with any light-source, were considered. Comparators were chemical exfoliation, intense pulsed light (IPL), light emitting diodes (LED), dermabrasion or microdermabrasion, ablative or non-ablative lasers, injectables, surgery, placebo and/or no treatment.A systematic search in PubMed, Embase, Lilacs, Google Scholar and RCT's registry databases, was performed.ResultsSearch was conducted up to May 4th 2016. Four authors independently selected and assessed methodological quality of each RCT. According to inclusion criteria, twelve studies were included (6 aminolevulinate (ALA) trials and 6 methyl aminolevulinate (MAL) trials), but the majority of them had methodological constraints particularly in randomization description and patients/outcome assessors blindness.Discussion and conclusionsOverall results indicated that PDT either with ALA or with MAL was effective and safe for facial photodamage treatment, but high quality of evidence was found mainly for MAL studies.

Graphical abstract

Mice over-expressing placenta growth factor in the skin exhibit increased vascularization and vessel permeability independently of VEGF-A

Placenta growth factor (PlGF), a member of the vascular endothelial growth factor (VEGF) family, shows strong pro-angiogenic properties in adult pathological angiogenesis [1]. In the skin, where keratinocytes represent the major source of VEGF-A and PlGF, these two factors are contemporaneously induced [2,3]. VEGF-A is also expressed in macrophages, and at minimal levels in dermal fibroblasts and endothelial cells; PlGF is also expressed in endothelial cells, at higher levels than VEGF-A. PlGF binds to tyrosine kinase receptor VEGFR-1 (Flt-1), while VEGF-A also binds to VEGFR-2 (Flk-1), which mediates the strongest angiogenic response.

Virus and Antibody Dynamics in Travelers With Acute Zika Virus Infection

Abstract

Background

To improve our understanding of the natural history of Zika virus (ZIKV) infection in humans, we described the dynamics of ZIKV RNA shedding in different body fluids and antibody responses in patients with acute infection.

Methods

Twenty-nine adults with travel-associated infection and 1 case of sexual transmission were enrolled and followed up with weekly ZIKV RNA testing in blood, urine, saliva, and semen samples and antibody testing.

Results

ZIKV RNA was detected in plasma, urine, and saliva of 57%, 93.1%, and 69.2% of participants, with estimated median times to clearance of 11.5 days (interquartile range [IQR] 6–24 days), 24 days (IQR, 17–34), and 14 days (IQR, 8–31), respectively. In 2 pregnant women, ZIKV RNA persisted in blood until delivery of apparently healthy infants. ZIKV RNA was detected in semen of 5 of 10 tested men; median time to clearance was 25 days (IQR 14–29), and the longest time of shedding in semen was 370 days. In flavivirus-naive patients, the median times to detection of ZIKV nonstructural protein 1 (NS1)–specific immunoglobulin M (IgM) and immunoglobulin G (IgG) antibodies were estimated as 8 days (IQR, 5–15 days) and 17 days (IQR, 12–26 days), respectively. ZIKV NS1 IgM antibodies were undetectable in patients with previous dengue.

Conclusions

Prolonged viremia and ZIKV RNA shedding in urine, saliva, and semen occur frequently in patients with acute ZIKV infection. At the time of diagnosis, about half of patients are ZIKV IgM negative. ZIKV NS1 IgM antibodies remain undetectable in patients with previous dengue. Estimates of the times to viral clearance and seroconversion are useful to optimize diagnostic algorithms.

Evidence for Mother-to-Child Transmission of Zika Virus Through Breast Milk

Abstract

Zikavirus (ZIKV) is an emerging viral pathogen that continues to spread throughout different regions of the world. Herein we report a case that provides further evidence that ZIKV transmission can occur through breastfeeding by providing a detailed clinical, genomic, and virological case-based description.

Impact of Dengue Vaccination on Serological Diagnosis: Insights From Phase III Dengue Vaccine Efficacy Trials

Abstract

Background

We previously reported that vaccination with the tetravalent dengue vaccine (CYD-TDV; Dengvaxia) may bias the diagnosis of dengue based on immunoglobulin M (IgM) and immunoglobulin G (IgG) assessments.

Methods

We undertook a post hoc pooled analysis of febrile episodes that occurred during the active surveillance phase (the 25 months after the first study injection) of 2 pivotal phase III, placebo-controlled CYD-TDV efficacy studies that involved ≥31000 children aged 2–16 years across 10 countries in Asia and Latin America. Virologically confirmed dengue (VCD) episode was defined with a positive test for dengue nonstructural protein 1 antigen or dengue polymerase chain reaction. Probable dengue episode was serologically defined as (1) IgM-positive acute- or convalescent-phase sample, or (2) IgG-positive acute-phase sample and ≥4-fold IgG increase between acute- and convalescent-phase samples.

Results

There were 1284 VCD episodes (575 and 709 in the CYD-TDV and placebo groups, respectively) and 17673 other febrile episodes (11668 and 6005, respectively). Compared with VCD, the sensitivity and specificity of probable dengue definition were 93.1% and 77.2%, respectively. Overall positive and negative predictive values were 22.9% and 99.5%, respectively, reflecting the much lower probability of correctly confirming probable dengue in a population including a vaccinated cohort. Vaccination-induced bias toward false-positive diagnosis was more pronounced among individuals seronegative at baseline.

Conclusions

Caution will be required when interpreting IgM and IgG data obtained during routine surveillance in those vaccinated with CYD-TDV. There is an urgent need for new practical, dengue-specific diagnostic algorithms now that CYD-TDV is approved in a number of dengue-endemic countries.

Arbovirus Diagnostics: From Bad to Worse due to Expanding Dengue Virus Vaccination and Zika Virus Epidemics

dengueZikadiagnosticsserologyarbovirus

Improved survival and cure rates with concurrent treatment for MDR-TB/HIV co-infection in South Africa

Abstract

Background

The global epidemic of multidrug-resistant tuberculosis (MDR-TB) threatens gains in TB and HIV outcomes over the past two decades. Mortality in MDR-TB/HIV co-infection has historically been high, but most studies predated the availability of antiretroviral therapy (ART). We prospectively compared survival and treatment outcomes in MDR-TB/HIV co-infected patients on ART to those in patients with MDR-TB alone.

Methods

This prospective, observational study enrolled culture-confirmed MDR-TB patients, with and without HIV co-infection, in South Africa between 2011–2013. Participants received standardized MDR-TB and HIV regimens and were followed monthly for treatment response, adverse events, and adherence. The primary outcome was survival.

Results

Among 206 participants, 150 were HIV-infected, 131 (64%) were female, and the median age was 33 years (IQR 26-41). Of the 191 participants with a final MDR-TB outcome, 130 (73%) were cured or successfully completed treatment, which did not differ by HIV status (p=0.50). After two years, the median CD4 count was 386 cells/mm³ (IQR 219-510), an increase of 140 cells/mm³ from baseline (p=0.005), and 64% had an undetectable HIV viral load. HIV-infected and HIV-uninfected participants had high rates of survival (86% and 94%, respectively; p=0.34). The strongest risk factor for mortality was having a CD4 count ≤100 cells/mm³ (aHR 15.6, 95%CI 4.4-55.6).

Conclusions

Survival and treatment outcomes among MDR-TB/HIV individuals receiving concurrent ART were improved, approaching those of HIV-uninfected MDR-TB patients. The greatest risk of death was among HIV-infected individuals with CD4 counts ≤100 cells/mm³. These findings provide critical evidence to support concurrent treatment of MDR-TB and HIV.

Dolutegravir plus lamivudine maintain HIV-1 suppression through week 48 in a pilot randomized trial

Abstract

In this randomized pilot clinical trial, dolutegravir plus lamivudine was non-inferior to continuation of standard three-drug maintenance therapy in virologically-suppressed HIV-1 infected individuals. There was no emergence of drug resistance in the participant with virologic failure on dolutegravir plus lamivudine.

Impact of Culture-Independent Diagnostic Testing on Recovery of Enteric Bacterial Infections

Abstract

Background

Culture-independent diagnostic tests (CIDT) are increasingly used to identify enteric pathogens. However, foodborne illness surveillance systems have relied upon culture confirmation to estimate disease burden and identify outbreaks through molecular subtyping. This study examined the impacts of CIDT and estimated costs for culture verification of Shigella, Salmonella, Shiga-Toxin producing E. coli (STEC), and Campylobacter at the Tennessee Department of Health Public Health Laboratory (PHL).

Methods

This observational study included laboratory and epidemiological surveillance data collected between years 2013-2016 from patients with the reported enteric illness. We calculated pathogen recovery at PHL based on initial diagnostic test type reported at the clinical laboratory. Adjusted prevalence ratios (PR) and 95% confidence intervals (CI) were estimated with Modified Poisson Regression. Estimates of cost were calculated for pathogen recovery from CIDT positive specimens compared to recovery from culture-derived isolates.

Results

During the study period, PHL received 5553 specimens from clinical laboratories from patients with the enteric illness. Pathogen recovery was 57% (984/1713) from referred CIDT positive stool specimens and 95% (3662/3840) from culture-derived isolates (PR=0.61, 95% CI: 0.56-0.66). Pathogen recovery from CIDT-positive specimens varied based on pathogen type: Salmonella (72%), Shigella (64%), STEC (57%) and Campylobacter (26%). Compared to stool culture-derived isolates, the cost to recover pathogens from 100 CIDT positive specimens was higher for Shigella ($6,192), Salmonella ($18,373) and STEC ($27,783).

Conclusions

Pathogen recovery was low from CIDT positive specimens for enteric bacteria. This has important implications for the current enteric disease surveillance system, outbreak detection and costs for public health programs.

Busting the Myth of “Static vs. Cidal”: A Systemic Literature Review

Abstract

We sought to determine if clinical data validate the dogma that bactericidal antibiotics are more clinically effective than bacteriostatic agents. We performed a systematic literature review of published, randomized controlled trials that compared a bacteriostatic agent to a bactericidal agent in the treatment of clinical, bacterial infections. From among a total of 56 identified trials, 49 found no significant difference in efficacy between bacteriostatic and bactericidal agents. Six trials found that the bacteriostatic agent was superior in efficacy to the bactericidal agent. Only one trial found that the bactericidal agent was superior; in this case, the inferiority of the static agent was explainable by under-dosing of the drug based on pharmacokinetic-pharmacodynamic analysis. Thus, virtually all available data from high quality, randomized controlled trials demonstrate no intrinsic superiority of bactericidal compared to bacteriostatic agents. Other drug characteristics, such as optimal dosing, pharmacokinetics, and tissue penetration, may be more important efficacy drivers.

Characteristics and outcomes of influenza-associated encephalopathy cases among children and adults in Japan, 2010-2015

Abstract

Background

Influenza-associated encephalopathy (IAE) can result in severe neurologic disease with high mortality. Most IAE cases have been reported among children worldwide; understanding of IAE among adults is limited.

Methods

Data were collected on IAE cases reported through the National Epidemiological Surveillance of Infectious Diseases database in Japan during 2010 through 2015. IAE cases were stratified by age category and analyzed using descriptive statistics to assess differences in characteristics and outcomes.

Results

Among 385 reported IAE cases, median age at diagnosis was 7 years (range 0-90), and 283 (74%) were children aged <18 years. The mean seasonal incidence of IAE cases among children and adults (≥18 years) was 2.83 and 0.19 cases per 1,000,000 population, respectively. IAE incidence did not vary by predominant influenza A virus subtype. The frequency of IAE was highest in school-aged (5-12 years) children (38%), followed by young children aged 2-4 years (21%) and adults aged 18-49 years (11%). The proportion of cases with seizures was more common in pediatric IAE cases. There were more cases with cerebrospinal fluid pleocytosis among adults than in children (p<0.01), especially among those aged 18-49 (17%) and 50-64 (19%) years. Case fatality proportion was highest in those aged 40-64 (17%) and ≥65 (20%) years.

Conclusions

We identified differences in the characteristics of IAE patients between adults and children in Japan. Although IAE cases were more frequently reported among children, mortality was higher in adults. Further efforts are needed to prevent and improve survival of patients with IAE, especially in adults.

The limits of non-standard contingency

Abstract

Gideon Rosen has recently sketched an argument which aims to establish that the notion of metaphysical modality is systematically ambiguous. His argument contains a crucial sub-argument which has been used to argue for Metaphysical Contingentism, the view that some claims of fundamental metaphysics are metaphysically contingent rather than necessary. In this paper, Rosen's argument is explicated in detail and it is argued that the most straight-forward reconstruction fails to support its intended conclusion. Two possible ways to save the argument are rebutted and it is furthermore argued that the crucial sub-argument only supports a rather particular variant of Metaphysical Contingentism.

Evaluation of 1-Nitropyrene as a Surrogate Measure for Diesel Exhaust

Abstract

We investigated the viability of particle bound 1-nitropyrene (1-NP) air concentration measurements as a surrogate of diesel exhaust (DE) exposure, as compared with industry-standard elemental carbon (EC) and total carbon (TC) measurements. Personal exposures are reported for 18 employees at a large underground metal mine during four different monitoring campaigns. Full-shift personal air exposure sampling was conducted using a Mine Safety and Health Administration (MSHA) compliant diesel particulate matter (DPM) impactor cassette downstream of a GS-1 cyclone pre-selector. Each DPM filter element was analyzed for EC and organic carbon (OC) using NIOSH Method 5040. After EC and OC analysis, the remaining portion of each DPM filter was analyzed for 1-NP using liquid chromatography tandem mass spectrometry (LC/MS/MS). We observed high correlations between the quantiles of 1-NP and EC exposures across 10 different work shift task groups (r = 0.87 to 0.96), and a linear relationship with a slope between 6.0 to 6.9 pg 1-NP per µg EC. However, correlation between 1-NP and EC was weak (r =0.34) for the 91 individual sample pairs due to low EC concentrations and possible heterogeneity of DE composition. While both 1-NP and EC differentiated between high and low exposure groups categorized by job location, measurements of 1-NP, but not EC further differentiated between specific job activities. Repeated measurements on individual subjects verified the relationship between 1-NP and EC and demonstrated substantial within-subject variability in exposure. The detection limit of TC air concentration ranged between 18 and 28 µg m⁻³ and was limited by OC contamination of the quartz filters in the MSHA compliant DPM samplers.

Molecular signature of nitric oxide on major cancer hallmarks of colorectal carcinoma

Abstract

Colorectal cancer (CRC) is the one of the most important diseases throughout the world. Several aetiological risk factors, viz. sedentary life style, smoking, alcohol intake, less physical activity, red meat, and microbiota, are associated with the development of CRC. Molecular pathophysiology of CRC implies inflammation, metastasis, apotosis and angiogenesis. Inflammation involves interaction between various immune cells, inflammatory cells, chemokines, cytokines, and pro-inflammatory mediators, such as cyclooxygenase (COX) and lipoxygenase (LOX) pathways, which may lead to signalling towards, tumour cell proliferation, growth, and invasion whereas nitric oxide (NO) has been associated with metastasis, apoptosis, and angiogenesis. Therefore, this review emphasises on the potential molecular mechanisms associated with NO with alteration of cancer biomarkers during development of colorectal carcinogenesis.

Pili torti, pale and elastic skin, and severe neurological impairment

Localized subepidermal blistering: not always bullous pemphigoid but a diagnostic challenge

Leukemia cutis in a patient with chronic myelomonocytic leukemia

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Introduction: Antibody-Mediated Therapy Special Issue Part 2

Antibodies have been used therapeutically for well over a century but the breadth and depth of their applications are increasing so rapidly and successfully that clinical studies are informing mechanistic questions while basic research continues to interrogate how antibodies are made and function, so their properties can be further refined. The first part of this Special Issue comprised five review articles (1); this second part includes four more reviews. Once again, we thank the authors for their excellent contributions. This issue also includes an original research article that builds on observations from patients with hyper-IgM syndrome to further define the mechanism for antibody class-switch recombination (CSR).

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