Porokeratosis ptychotropica responding to photodynamic therapy: An alternative treatment for a refractory disease.

BACKGROUND: Porokeratosis ptychotropica (PP) is a rare variant of porokeratosis with a special predisposition to affect body folds, particularly the intergluteal cleft. This disease is resistant to most topical and systemic treatments, as shown in the review of the literature we provide here. Itching and discomfort are often a difficult problem to solve. PATIENTS AND METHODS: Two patients with PP that had not responded to multiple topical treatments were treated with photodynamic therapy (PDT). Changes in plaque size, thickness and symptoms were assessed after treatment. RESULTS: Pruritus disappearance was observed in both patients after treatment with PDT. Partial clearance of the plaques was observed in one case. In the other case, a moderate clearance of hyperkeratosis was observed, although the size of the lesions persisted unchanged. CONCLUSIONS: PDT seems to be a good therapeutic alternative in the treatment of PP, as it can provide symptomatic relief and clinical improvement of the lesions. However, it does not appear to be a curative treatment. Moreover, long-term response is still unknown.

Alopecic and aseptic nodule of the scalp in a girl.

Alopecic and aseptic nodule of the scalp is a rare entity characterized by the presence of nodules or cysts with sterile punctured material and negative cultures accompanied by nonscarring alopecia in the scalp of young men. We describe a case in which an 11-year-old girl presented with a nodular, fluctuant, round lesion on the vertex with localized alopecia. High-resolution ultrasound showed a hypoechoic lesion with increased flow on Doppler imaging and culture of the citrine-yellowish material obtained by puncture was negative. The patient showed complete clinical response to treatment with topical indomethacin.

Telaprevir and ribavirin interaction: higher ribavirin levels are not only due to renal dysfunction during triple therapy.

A higher incidence of anemia has been observed during the treatment of hepatitis C virus genotype 1 (HCV-1) infection with pegylated alpha interferon (pegIFN-α), ribavirin, and telaprevir. We assessed the impacts that concomitant administration of telaprevir and changes in the glomerular filtration rate have on ribavirin plasma levels. The minimum concentrations of ribavirin in plasma (ribavirin Cmin) determined during triple therapy including telaprevir were compared with those observed after telaprevir withdrawal and those observed in the same subjects and in a large cohort during a previous course of pegIFN-α plus ribavirin. Intensive pharmacokinetic sampling for ribavirin was performed at steady state during the triple-therapy phase. Ribavirin levels were measured by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Twenty-seven HCV-1/HIV-coinfected patients were enrolled. The median ribavirin Cmin for triple therapy (4.08 µg/ml; range, 2.14 to 5.56 µg/ml) was higher than that observed after telaprevir withdrawal (1.96 µg/ml; range, 0.41 to 3.45 µg/ml) (P < 0.001) and that observed for 125 HCV-1/HIV-coinfected patients treated only with pegIFN-α plus ribavirin (1.65 µg/ml; range, 0.41 to 5.56 µg/ml) (P < 0.001). The estimated glomerular filtration rate (eGFR) decreased >20% from the baseline value in 11 of 27 patients and became normal after telaprevir removal in almost all cases. There was a negative correlation between eGFR and ribavirin clearance (r(2) = 0.257; P = 0.064) but not the ribavirin area under the concentration-time curve from 0 to 12 h (AUC0-12) (r(2) = 0.001; P = 0.455). Thus, there is a significant pharmacokinetic interaction between telaprevir and ribavirin that results in very high ribavirin levels, which explains the excess of toxicity observed with this drug combination. A blockade of the proximal tubular transporters might be implicated in both the increase in plasma creatinine and the high ribavirin levels. (This study has been registered at ClinicalTrials.gov under registration no. NCT01818856.).

Role of ritonavir in the drug interactions between telaprevir and ritonavir-boosted atazanavir.

BACKGROUND: Detrimental bidirectional pharmacokinetic interactions have been observed when telaprevir (TVR) and ritonavir (RTV)-boosted human immunodeficiency virus (HIV) protease inhibitors are coadministered in healthy volunteers. Our aim was to evaluate the role of RTV in the bidirectional TVR and atazanavir (ATV) interactions. METHOD: An open-label, sequential study was carried out in hepatitis C virus (HCV)/HIV-coinfected patients on a RTV-boosted ATV-based (ATVr) antiretroviral regimen (300/100 mg every 24 hours) and triple therapy for chronic C hepatitis genotype 1 (TVR, 1125 mg every 12 hours, pegylated interferon-alpha and ribavirin). Pharmacokinetic profiles were acquired before and after switching from ATVr to unboosted ATV (200 mg every 12 hours). The plasma levels of both drugs were determined by liquid chromatography coupled with mass spectrometry. Pharmacokinetic parameters were calculated by noncompartmental analysis and compared by geometric mean ratios and their 90% confidence intervals. RESULTS: Fourteen white HCV/HIV-coinfected males were enrolled in this study. After RTV was withdrawn, the TVR AUC(0-12) (area under the concentration-time curve), maximum concentration (C(max)), and minimum concentration (C(min)) values increased by 19% (7%-30%), 12% (0.9%-29%), and 18% (2%-34%), respectively, without any changes in the TVR terminal half-life. The ATV AUC(0-12), C(max), and C(min) values were 39% (13%-66%), 19% (8%-59%), and 48% (1%-96%) higher, respectively, with a significantly shorter terminal half-life (22.6 hours vs 10.4 hours). CONCLUSIONS: RTV is responsible for the adverse interactions that occur when TVR and ATVr are administered together, possibly by influencing either the absorption phase or first-pass metabolism of TVR. The boost effect of TVR on ATV exposure is higher than on RTV, despite its shorter terminal half-life. The coadministration of TVR and unboosted ATV results in increased exposure of both drugs compared with their coadministration with RTV. CLINICAL TRIALS REGISTRATION: ClinicalTrials.gov: NCT01818856. European Medicines Agency EudraCT no. 2012-002515-25.

The Alopecia Areata Severity and Morbidity Index (ASAMI) Study: Results From a Global Expert Consensus Exercise on Determinants of Alopecia Areata Severity.

Importance: Current measures of alopecia areata (AA) severity, such as the Severity of Alopecia Tool score, do not adequately capture overall disease impact. Objective: To explore factors associated with AA severity beyond scalp hair loss, and to support the development of the Alopecia Areata Severity and Morbidity Index (ASAMI). Evidence Review: A total of 74 hair and scalp disorder specialists from multiple continents were invited to participate in an eDelphi project consisting of 3 survey rounds. The first 2 sessions took place via a text-based web application following the Delphi study design. The final round took place virtually among participants via video conferencing software on April 30, 2022. Findings: Of all invited experts, 64 completed the first survey round (global representation: Africa [4.7%], Asia [9.4%], Australia [14.1%], Europe [43.8%], North America [23.4%], and South America [4.7%]; health care setting: public [20.3%], private [28.1%], and both [51.6%]). A total of 58 specialists completed the second round, and 42 participated in the final video conference meeting. Overall, consensus was achieved in 96 of 107 questions. Several factors, independent of the Severity of Alopecia Tool score, were identified as potentially worsening AA severity outcomes. These factors included a disease duration of 12 months or more, 3 or more relapses, inadequate response to topical or systemic treatments, rapid disease progression, difficulty in cosmetically concealing hair loss, facial hair involvement (eyebrows, eyelashes, and/or beard), nail involvement, impaired quality of life, and a history of anxiety, depression, or suicidal ideation due to or exacerbated by AA. Consensus was reached that the Alopecia Areata Investigator Global Assessment scale adequately classified the severity of scalp hair loss. Conclusions and Relevance: This eDelphi survey study, with consensus among global experts, identified various determinants of AA severity, encompassing not only scalp hair loss but also other outcomes. These findings are expected to facilitate the development of a multicomponent severity tool that endeavors to competently measure disease impact. The findings are also anticipated to aid in identifying candidates for current and emerging systemic treatments. Future research must incorporate the perspectives of patients and the public to assign weight to the domains recognized in this project as associated with AA severity.

Radiobiological comparison of two radiotherapy treatment techniques for high-risk prostate cancer.

BACKGROUND: To make a radiobiological comparison, for high risk prostate cancer (T3a, PSA > 20 ng/ml or Gleason > 7) of two radiotherapy treatment techniques. One technique consists of a treatment in three phases of the pelvic nodes, vesicles and prostate using a conventional fractionation scheme of 2 Gy/fraction (SIMRT). The other technique consists of a treatment in two phases that gives simultaneously different dose levels in each phase, 2 Gy/fraction, 2.25 Gy/fraction and 2.5 Gy/fraction to the pelvic nodes, vesicles and prostate, respectively (SIBIMRT). MATERIALS AND METHODS: The equivalent dose at fractionation of 2 Gy (EQD2), calculated using the linear quadratic model with α/ß prostate = 1.5 Gy, was the same for both treatment strategies. For comparison the parameters employed were D95, mean dose and Tumour Control Probabilities for prostate PTV and D15, D25, D35, D50, mean dose and Normal Tissue Complication Probabilities for the rectum and bladder, with physical doses converted to EQD2. Parameters were obtained for α/ß prostate = 1.5, 3 and 10 Gy and for α/ß oar = 1, 2, 3, 4, 6 and 8. RESULTS: For prostate PTV, both treatment strategies are equivalent for α/ß prostate = 1.5 Gy but for higher α/ß prostate, EQD2 and TCP, decrease for the SIBIMRT technique. For the rectum and bladder when α/ß oar ≤ 2 Gy, EQD2 and NTCP are lower for the SIMRT technique or equal in both techniques. For α/ß oar ≥ 2-3 Gy, EQD2 and NTCP increase for the SIMRT treatment. CONCLUSIONS: A comparison between two radiotherapy techniques is presented. The SIBIMRT technique reduces EQD2 and NTCP for α/ß oar from 2 to 8 Gy.

Intracellular and plasma pharmacokinetics of 400 mg of etravirine once daily versus 200 mg of etravirine twice daily in HIV-infected patients.

OBJECTIVES: To compare intracellular and plasma etravirine concentrations when etravirine was given at 200 mg/12 h versus 400 mg/24 h and to evaluate whether the results would support once-daily dosing. METHODS: This was an open-label sequential study in which eight patients on protease inhibitor (PI)-sparing regimens containing etravirine were included. Full pharmacokinetic profiles were performed while on 200 mg of etravirine/12 h and after switching to 400 mg of etravirine/24 h. Intracellular and plasma levels were determined by liquid chromatography coupled with mass spectrometry. Pharmacokinetic parameters were calculated by non-compartmental analysis and compared by geometric mean ratios (GMRs) using 200 mg of etravirine/12 h as the reference group. TRIAL REGISTRATION: ClinicalTrials.gov NCT01121809. RESULTS: The geometric mean (GM) for etravirine AUC(0-τ) (5602 versus 5076 ng · h/mL, GMR 0.91), C(max) (403 versus 495 ng/mL, GMR 1.23) and C(min) (139 versus 102 ng/mL, GMR 0.74) were similar with both dosing schedules at the intracellular level. In plasma, the GMRs for AUC(0-τ), C(max) and C(min) were 1.31, 1.76 and 0.99, respectively. The mean intracellular penetration, evaluated as intracellular and plasma AUC(0-τ) ratios, was 81% when etravirine was dosed twice daily and 56% with once-daily dosing. CONCLUSIONS: Our results show that intracellular etravirine levels were similar with both dosing regimens in patients with PI-sparing regimens, while etravirine plasma AUC(0-τ) and C(max) were 30% and 76% higher with the once-daily regimen, respectively. Thus, a once-daily dosing regimen is supported not only by plasma etravirine pharmacokinetic profiles but also by intracellular levels.

Pseudo Green Hair.

Green hair is due to insoluble copper deposits in the hair of blonde people. Although it is most frequently due to an increase in the copper content of algaecides in swimming pools, other causes have been recognized. Herewith, we present a case of a blonde girl who had previously commercially highlighted her hair and the hair had turned green following a swim in a pool with excess copper content in the water. Lifeguard swimming pool commented another previously affected blonde female swimmer 2 days ago. To date, <10 cases involving swimming pools with clearly increased copper concentrations have been published, and to the best of our knowledge, no similar case without traces of copper in X-ray microanalysis has been reported in the literature.

Recent Progress Using De Novo Design to Study Protein Structure, Design and Binding Interactions.

De novo protein design is a powerful methodology used to study natural functions in an artificial-protein context. Since its inception, it has been used to reproduce a plethora of reactions and uncover biophysical principles that are often difficult to extract from direct studies of natural proteins. Natural proteins are capable of assuming a variety of different structures and subsequently binding ligands at impressively high levels of both specificity and affinity. Here, we will review recent examples of de novo design studies on binding reactions for small molecules, nucleic acids, and the formation of protein-protein interactions. We will then discuss some new structural advances in the field. Finally, we will discuss some advancements in computational modeling and design approaches and provide an overview of some modern algorithmic tools being used to design these proteins.

Atypical Congenital Triangular Alopecia (Brauer Nevus): Case Report and Review of Literature in Occipital and Mid-Frontal Localizations.

INTRODUCTION: Brauer nevus, also known as congenital triangular alopecia (CTA) is a localized alopecia that rarely affects the occipital or mid-frontal region. CTA is a localized follicular hypoplasia, commonly misdiagnosed as alopecia areata. Although named congenital, onset in adulthood is possible. CASE PRESENTATION: We present a review of literature of eighteen atypical locations, providing 4 new cases to the 9 previously published, with particular attention to trichoscopy and histopathological descriptions in this exceptional presentation forms. DISCUSSION: Occipital and mid-frontal Brauer nevus are unusual findings with very few cases reported so far. Because of its rarity and atypical presentation, it can often lead to a misdiagnosis. A higher incidence in the male sex stands clear in these locations. Detection at birth is slightly more frequent than in the classical CTA. Histopathological and trichoscopy findings do not differ from the classical entity, although white or hypopigmented hairs do not seem to be an item present in the mid-frontal forms.

An Analytic Network Process approach for siting a municipal solid waste plant in the Metropolitan Area of Valencia (Spain).

In this paper the Analytic Network Process (ANP) is applied to select the best location for the construction of a municipal solid waste (MSW) plant in the Metropolitan area of Valencia (Spain). Selection of the appropriate MSW facility location can be viewed as a complex multicriteria decision-making problem that requires an extensive evaluation process of the potential MSW plant locations and other factors as diverse as economic, technical, legal, social or environmental issues. The decision-making process includes the identification of six candidate MSW plant sites and 21 criteria grouped into clusters for the construction of a network. Two technicians of the Metropolitan Waste Disposal Agency acted as decision makers (DMs). The influences between the elements of the network were identified and analyzed using the ANP multicriteria decision method. Two different ANP models were used: one hierarchy model (that considers AHP as a particular case of ANP) and another network-based model. The results obtained in each model were compared and analyzed. The strengths and weaknesses of ANP as a multicriteria decision analysis tool are also described in the paper. The main findings of this research have proved that ANP is a useful tool to help technicians to make their decision process traceable and reliable. Moreover, this approach helps DMs undertake a sound reflection of the siting problem.

A comparative analysis of the pharmacovigilance systems of Brazil, Spain, the European Union and the United States based on the information provided by their regulatory agency websites.

BACKGROUND: Pharmacovigilance (PV) plays an essential role in monitoring and raising awareness of adverse drug reactions (ADRs). Increasingly, ADRs are reported and PV information and activities are circulated via the Internet. PV actions are carried out by the Regulatory Agencies (RAs) responsible for medicinal products in each country. OBJECTIVE: The objective of this study is to ascertain and assess the operation and areas of competence of the PV system in Brazil and to compare them with those of Spain, the European Union (EU) and the United States (USA), through the information available on the websites of the RAs in each country. METHODS: A search of the information provided on the websites of these countries' RAs, establishing indicators to assess how far the information is available and accessible. RESULTS: The RAs we studied are similarly organised and they complied with most of the 38 indicators we defined to obtain and assess the information they provide on PV procedures and their systems for electronic reporting of ADRs. Brazil's RA, ANVISA, complied with 100% of the areas of competence analysed and with 92.11% of the indicators established for the study. CONCLUSIONS: Brazil's PV system, through ANVISA, achieves a good level of performance, both in itself and compared to the other RAs. There is room for improvement in three of the indicators analysed.

Multiple primary melanoma with the Meyerson phenomenon in a young patient.

Meyerson phenomenon (MP), also called halo eczema or halo dermatitis, was first described in 1971 as a symmetric eczematous halo around acquired melanocytic nevi. Since then, cases of MP have been described in any kind of melanocytic nevi and also in non-melanocytic tumors. To the best of our knowledge, only four cases of melanoma associated with MP have been reported. We report the singular case of a young adult diagnosed with two primary melanomas in the context of dysplastic nevi syndrome who presented several flares-up associated with MP in both benign and malignant melanocytic tumors. MP usually manifests as a halo of erythema and scaling similar to plaques of eczema symmetrically surrounding a central cutaneous tumor. Dermoscopic findings of MP show it as similar to other forms of dermatitis. Histopathology usually shows epidermal changes compatible with subacute eczematous dermatitis. Immunohistochemical studies have shown inflammatory infiltrate composed mainly of CD4+ lymphocytes, which supports the suggested pathogenesis of an immune-mediated reaction. It usually resolves spontaneously, and the use of topical corticosteroids has a good response. In conclusion, MP is not specific for benignity, even when multiple simultaneous lesions are affected. Inflammatory changes can make melanocytic lesions difficult to interpret, both on dermoscopic regression features and on histopathologic examination. Therefore, it is recommended to consider the complete excision of melanocytic lesions with atypical vessels and/or extensive regression phenomena more than 50%. Further studies are needed to know whether the presence of a melanoma could induce a remote immune response in other benign melanocytic lesions.

Sclerodermiform linear lupus erythematosus: A distinct entity or coexistence of two autoimmune diseases?

The coexistence of features of chronic cutaneous lupus erythematosus and scleroderma in the same skin lesions is very infrequent and has only been reported in 3 patients. This exceedingly rare condition has been named "sclerodermiform linear lupus erythematosus." We describe a new case of this dermatosis. Although the cause remains obscure, possible explanations include mosaicism following Blaschko's lines or the transfer of microchimerisms that mount a chronic graft-versus-host-like reaction. We suggest that these features may be a distinct clinicopathologic disorder characterized by an initial lichenoid reaction followed by the production of excessive, abnormal connective tissue.

Nuchal Nevus Flammeus and Alopecia Areata: When Size Matters.

INTRODUCTION: Alopecia areata (AA) is a high-prevalence immuno-mediated hair loss disorder. Extra follicular affections, including nail and ocular abnormalities, are classically related to a worse prognosis of the disease, and previous studies have suggested that the presence of a persistent nuchal nevus flammeus (NNF) also indicates a greater severity and duration of the disease. The association between AA and persistent NNF was first described by Hatzis et al in 1988, who demonstrated that the relation was statistically evident and not due to a simple observer bias. OBJECTIVES: To determine and compare the presence/absence and size of the NNF in 80 individuals (40 patients diagnosed with AA and 40 controls). RESULTS: We found a statistically significant association not only between AA and the presence of NNF, but also with its size. Moreover, we found that the size of the NNF was also associated with the severity of AA. CONCLUSION: The size of the NNF in AA patients might be a useful marker of widespread and chronic disease.

Prostate planning treatment volume margin calculation based on the ExacTrac X-Ray 6D image-guided system: margins for various clinical implementations.

PURPOSE: To assess the prostate motion from day-to-day setup, as well as during irradiation time, to calculate planning target volume (PTV) margins. PTV margins differ depending on the clinical implementation of an image-guided system. Three cases were considered in this study: daily bony anatomy match, center of gravity of the implanted marker seeds calculated with a limited number of imaged days, and daily online correction based on implanted marker seeds. METHODS AND MATERIALS: A cohort of 30 nonrandomized patients and 1,330 pairs of stereoscopic kV images have been used to determine the prostate movement. The commercial image guided positioning tool employed was ExacTrac X-Ray 6D (BrainLAB AG, Feldkirchen, Germany). RESULTS: Planning target volume margins such that a minimum of 95% of the prescribed dose covers the clinical target volume for 90% of the population are presented. PTV margins based on daily bony anatomy match, including intrafraction correction, would be 11.5, 13.5, and 4.5 mm in the anterior-posterior, superior-inferior, and right-left directions, respectively. This margin can be further reduced to 8.1, 8.6, and 4.8 mm (including intrafraction motion) if implanted marker seeds are used. Finally, daily on line correction based on marker seeds would result in the smallest of the studied margins: 4.7, 6.2, and 1.9 mm. CONCLUSION: Planning target volume margins are dependent on the local clinical use of the image-guided RT system available in any radiotherapy department.

Scanning Electron Microscopy and X-ray Microanalysis of Reconstructive Hair Fibers.

BACKGROUND: Reconstructive hair fibers are an innovative tool in cosmetic dermatology based on electrostatic adherent powder which bonds to the hair shaft and can disguise hair loss in men and women. AIM: This study aims to analyze and compare five different brands of organic hair fibers. MATERIALS AND METHODS: A scanning electron microscope (SEM) was used to obtain amplified images of samples to study their shape and morphological structure. X-ray microanalysis was performed to study the chemical composition of reconstructive hair fibers. The five samples were tested in patients attending a trichology unit of a tertiary hospital. RESULTS: The main component in hair fibers products 1 (Blum Secret™) and 3 (Keratin™) was cotton (cellulose of vegetal origin), while product 2 (Viviscal™) was made of a vegetal keratin. All three samples appeared as parallel-arranged fibres on the scanning electron microscope. The X-ray microanalysis showed an organic polymer mainly composed of C, O, and Si. Hair fibers 4 (Toppik™) and 5 (Nanogen™) were similar. Sample 4 derived from a keratin organic fiber and sample 5 from pure, positively charged keratin. In both cases, SEM revealed microfibers covered by a fine squamous. The X-ray microanalysis in both cases revealed a high presence of S. CONCLUSION: There was no discrepancy among the cosmetic results of the five samples, providing a successful esthetic effect in all of our patients despite the chemical differences found in the X-ray microanalysis.

Primary Scarring Alopecia: Clinical-Pathological Review of 72 Cases and Review of the Literature.

PURPOSE OF THE STUDY: To analyze the epidemiologic, demographic, clinical, and histological characteristics of primary scarring alopecia (PSA) cases diagnosed over a 7-year period at the Department of Dermatology, Hospital Clinic, Barcelona, Spain. PROCEDURES: Seventy-two patients diagnosed with PSA between 2006 and 2012 were included. Age, sex, ethnic group, clinical pattern, predominant histological infiltrate, final clinical diagnosis, time of onset, treatments used, and clinical evolution were evaluated and correlated. RESULTS: The ethnic groups were distributed as follows: 93% European-Caucasian, 5% Mestizo-American, 1% oriental, and 1% Afro-American. Most cases were females (71%), and mean age was 51 ± 6 years. The follicular pattern was the most common, and the predominant inflammatory infiltrate was lymphocytic. Lichen planopilaris and frontal fibrosing alopecia were the main diagnoses. When correlating clinical aspects and histopathology, lymphocytic PSAs had a subacute onset and resulted in a nonchanging, more stable form, while neutrophilic PSAs had a more acute onset with an evolution of acute outbreaks. PSAs in a late stage with an absent/mild infiltrate had a subclinical onset and a slowly progressive or stable evolution. CONCLUSIONS: The PSAs are severe trichological conditions. Their high clinical and histopathological variability make them a diagnostic and therapeutic challenge. MESSAGE OF THE PAPER: Knowing the clinical and histopathological aspects of PSAs should be of crucial importance to the dermatologist.