Preliminary Evidence of Efficacy, Safety, and Treatment Satisfaction with Tirbanibulin 1% Ointment: A Clinical Perspective on Actinic Keratoses

background: actinic keratosis is a common precancerous skin lesion that can progress into invasive squamous cell carcinomas. many topical treatments for actinic keratoses often have poor tolerability and prolonged duration. Tirbanibulin is a novel synthetic drug with potent antitumor and antiproliferative activities. methods: we conducted a single-center, prospective and observational study using tirbanibulin ointment on a 25 cm2 area for 5 consecutive days on 30 participants with AKs on the face or scalp. They were followed for at least 57 days to assess the safety profile and efficacy of the drug as well as treatment satisfaction. we evaluated six signs of local skin reaction (LSR): erythema, scaling, crusting, swelling, blisters/pustules, and erosions/ulcerations, grading the severity as mild, moderate, or severe. The effectiveness was evaluated both clinically and dermoscopically. the treatment satisfaction was assessed using the treatment satisfaction questionnaire for medication (TSQM 1.4). results: on day 57, 70% of the patients showed a complete clinical and dermoscopic response. The highest scores obtained from the TSQM 1.4 were more evident in the convenience and side effects domains. most LSRs, including erythema (83.3%), scaling (30%), and swelling (3.3%), occurred on day 8 but resolved spontaneously. Conclusion: Tirbanibulin is a viable therapeutic option with a short regimen treatment and good tolerability, which favors therapy adherence

Idiopathic pulmonary fibrosis is strongly associated with productive infection by herpesvirus saimiri

Idiopathic pulmonary fibrosis is a fatal disease without effective therapy or diagnostic test. To investigate a potential role for c�herpesviruses in this disease, 21 paraffin-embedded lung biopsies from patients diagnosed with idiopathic pulmonary fibrosis and 21 lung biopsies from age-matched controls with pulmonary fibrosis of known etiology were examined for a series of c�herpesviruses’ DNA/RNA and related proteins using in situ hybridization and reverse transcriptase-polymerase chain reaction (RT-PCR)-based methods. We detected four proteins known to be in the genome of several c�herpesviruses (cyclin D, thymidylate synthase, dihydrofolate reductase, and interleukin-17) that were strongly co-expressed in the regenerating epithelial cells of each of the 21 idiopathic pulmonary fibrosis cases and not in the benign epithelia of the controls. Among the c� herpesviruses, only herpesvirus saimiri expresses all four of these ‘pirated’ mammalian proteins. We found herpesvirus saimiri DNA in the regenerating epithelial cells of 21/21 idiopathic pulmonary fibrosis cases using four separate probe sets but not in the 21 controls. RT-PCR showed that the source of the cyclin D RNA in active idiopathic pulmonary fibrosis was herpesvirus saimiri and not human. We cloned and sequenced part of genome corresponding to the DNA polymerase herpesvirus saimiri gene from an idiopathic pulmonary fibrosis sample and it matched 100% with the published viral sequence. These data are consistent with idiopathic pulmonary fibrosis representing herpesvirus saimiri-induced pulmonary fibrosis. Thus, treatment directed against viral proliferation and/or viral-associated proteins may halt disease progression. Further, demonstration of the viral nucleic acids or proteins may help diagnose the disease

Impact of COVID-19 on cardiovascular testing in the United States versus the rest of the world

Objectives: This study sought to quantify and compare the decline in volumes of cardiovascular procedures between the United States and non-US institutions during the early phase of the coronavirus disease-2019 (COVID-19) pandemic. Background: The COVID-19 pandemic has disrupted the care of many non-COVID-19 illnesses. Reductions in diagnostic cardiovascular testing around the world have led to concerns over the implications of reduced testing for cardiovascular disease (CVD) morbidity and mortality. Methods: Data were submitted to the INCAPS-COVID (International Atomic Energy Agency Non-Invasive Cardiology Protocols Study of COVID-19), a multinational registry comprising 909 institutions in 108 countries (including 155 facilities in 40 U.S. states), assessing the impact of the COVID-19 pandemic on volumes of diagnostic cardiovascular procedures. Data were obtained for April 2020 and compared with volumes of baseline procedures from March 2019. We compared laboratory characteristics, practices, and procedure volumes between U.S. and non-U.S. facilities and between U.S. geographic regions and identified factors associated with volume reduction in the United States. Results: Reductions in the volumes of procedures in the United States were similar to those in non-U.S. facilities (68% vs. 63%, respectively; p = 0.237), although U.S. facilities reported greater reductions in invasive coronary angiography (69% vs. 53%, respectively; p < 0.001). Significantly more U.S. facilities reported increased use of telehealth and patient screening measures than non-U.S. facilities, such as temperature checks, symptom screenings, and COVID-19 testing. Reductions in volumes of procedures differed between U.S. regions, with larger declines observed in the Northeast (76%) and Midwest (74%) than in the South (62%) and West (44%). Prevalence of COVID-19, staff redeployments, outpatient centers, and urban centers were associated with greater reductions in volume in U.S. facilities in a multivariable analysis. Conclusions: We observed marked reductions in U.S. cardiovascular testing in the early phase of the pandemic and significant variability between U.S. regions. The association between reductions of volumes and COVID-19 prevalence in the United States highlighted the need for proactive efforts to maintain access to cardiovascular testing in areas most affected by outbreaks of COVID-19 infection

A new therapeutic for the treatment of moderate to severe plaque psoriasis: apremilast

Psoriasis is a common, chronic, inflammatory skin disease. Being a life-long condition, a prolonged and safe control of the disease is needed. Current anti-psoriatic treatments show some limits in terms of tolerability and route of administration. Recently, a new oral small molecule, apremilast, has been approved for the treatment of patients with moderate-to-severe plaque psoriasis. Apremilast is a phosphodiesterase 4 (PDE4) inhibitor that regulates the transduction of intracellular signals, including pro-inflammatory and anti-inflammatory pathways. Because of the favorable safety profile and the oral route of administration, apremilast may represent a promising therapeutic target for moderate-to-severe psoriasis. In this review, we report an updated overview about clinical trials testing apremilast in the treatment of psoriasis and seek to provide comprehensive information about this anti-psoriatic drug and a future perspective of the therapeutic algorithm for psoriasis

Effects of topical piroxicam and sun filters in actinic keratosis evolution and field cancerization: a two-center, assessor-blinded, clinical, confocal microscopy and dermoscopy evaluation trial

Background: Actinic keratosis (AK) is considered an "in situ" non-melanoma skin cancer induced by ultraviolet chronic exposure. Sunscreen and topical anti-inflammatory agents like diclofenac could improve the evolution of this kind of lesions. A topical product containing piroxicam 0.8% and sun filters (50 SPF) (ACTX) has shown to be very effective in reducing AK lesions. So far, no data are available regarding the effects of this product on skin modifications evaluated by reflectance confocal microscopy (RCM) and dermoscopy at the lesions site and on the skin around the lesions (field cancerization). Study aim: To evaluate in a two-center, assessor-blinded, prospective trial the effect of ACTX on AK number, RCM and dermoscopy parameters evolution of a target lesion in subjects with multiple AK lesions. Subjects and methods: A total of 54 subjects (42 men and 12 women; mean age 65 years) with AK lesions grade I-III located on the scalp (n = 36) or face (n = 18) were enrolled after their written informed consent. ACTX was applied twice daily on the face and scalp for 6 consecutive months. AK lesion count was performed at baseline and after 3 and 6 months. Lesion count was assessed in a blind fashion evaluating digital color high definition images performed at each visit and coded in a blinded fashion. An RCM evaluation were performed at the same time-points. A dermoscopy evaluation was performed at baseline and after 6 months. RCM and dermoscopy were assessed on a pre-specified target lesion. The RCM severity score was used evaluating 11-item examining stratum corneum, stratum granulosum, stratum spinous and dermal layers (maximum score 11 points). The dermoscopy score evaluated erythema, scaling and follicular plugs (from 0 to 4 for each item) and pigmentation (from 0 to 5). Results: Forty-nine subjects (90%) concluded the trial. At baseline, the mean(SD) number of AK lesions was 9.6(5.2). AK lesions significantly decreased to 5.9 and to 5.6 after 3 and 6 months of ACTX treatment (P = 0.001; Intention to treat analysis), representing a -42% reduction. A reduction of AK lesion number &gt;50% in comparison with baseline was observed in 51% of subjects at month 6. New AK lesions appeared in 5 subjects (9%). The RCM mean(SD) severity score at baseline was 6.4(2.0). ACTX treatment was associated with a progressive and significant (P = 0.002) reduction to 4.9 after 3 months and to 4.8(2.3) at month 6 (a -25% reduction). The Dermoscopy score at baseline was 5.5(2) and it was reduced significantly (P = 0.007) to 4.5(2) at the end of the study. The product was in general very well tolerated. Conclusion: A 6-month application of ACTX in subjects with AK lesions was associated with an improvement of AK lesion count and with a reduction in the RCM/dermoscopy severity scores of the target lesion. (Trial Registration Number: ISRCTN22070974)

Qualitative and biochemical characteristics of pomegranate fruit grown using reclaimed water and low input fertigation treatments at harvest and during storage

In recent years, severe climate change leading to by water scarcity reduced water quality has increased the need for effective irrigation strategies for agricultural production. Among these, the reuse of reclaimed water represents a non-expensive and reliable solution. The effect of conventional or reclaimed water, applying convention or smart fertigation system, were investigated during two irrigation seasons on yield, qualitative and biochemical traits of pomegranates fruit (cv Wonderful One) at harvest, and after storage at 7 °C. The results of this study showed that using reclaimed waters with different fertigation systems did not affect the pH values, total soluble solids, and titratable acidity on pomegranates fruit showing slight decrease changes only during postharvest storage. On the other hand, the respiration rate was not affected by water quality. Furthermore, the antioxidant activity was also preserved during storage in pomegranates fruit from plants irrigated with reclaimed water by applying conventional or smart fertigation. The analysis also identified 52 compounds by UHPLC-MSn and HPLC-UV-Vis analyses. A slight decrease (about 17 %) at harvest and during storage in polyphenols content was shown in fruit grown using reclaimed water. The study demonstrates that using reclaimed water is a sustainable and effective way to limit the use of conventional water for irrigating pomegranate crops without significant reduction in yield, or in qualitative and nutritional values of the fruit at harvest and during storage

Latest evidence regarding the effects of photosensitive drugs on the skin: pathogenetic mechanisms and clinical manifestations

Photosensitivity induced by drugs is a widely experienced problem, concerning both molecule design and clinical practice. Indeed, photo-induced cutaneous eruptions represent one of the most common drug adverse events and are frequently an important issue to consider in the therapeutic management of patients. Phototoxicity and photoallergy are the two different pathogenic mechanisms involved in photosensitization. Related cutaneous manifestations are heterogeneous, depending on the culprit drug and subject susceptibility. Here we report an updated review of the literature with respect to pathogenic mechanisms of photosensitivity, clinical manifestations, patient management, and prediction and evaluation of drug-induced photosensitivity. We present and discuss principal groups of photosensitizing drugs (antimicrobials, nonsteroidal anti-inflammatory drugs, anti-hypertensives, anti-arrhythmics, cholesterol, and glycemia-lowering agents, psychotropic drugs, chemotherapeutics, etc.) and their main damage mechanisms according to recent evidence. The link between the drug and the cutaneous manifestation is not always clear; more investigations would be helpful to better predict drug photosensitizing potential, prevent and manage cutaneous adverse events and find the most appropriate alternative therapeutic strategy