Evolution of Melanocytic Nevi under Vemurafenib, Followed by Combination Therapy with Dabrafenib and Trametinib for Metastatic Melanoma

ABSTRACT Treatment of advanced melanoma with selective BRAF and MEK inhibitors is associated with a series of mucocutaneous side effects, among which morphological changes in preexisting nevi and the development of new melanocytic lesions, both benign and malignant.Objective was to describe the changes observed in melanocytic nevi under vemurafenib therapy, followed by combination therapy with dabrafenib and trametinib for metastatic melanoma.The melanocytic lesions of a 51-year-old Caucasian male patient diagnosed with stage IV melanoma were monitored both clinically and dermoscopically throughout vemurafenib, followed by combined treatment with dabrafenib and trametinib.The 65 monitored nevi presented different behaviors under vemurafenib treatment: 18 reticular nevi, 9 reticular-homogenous nevi, 3 reticular-globular nevi, and 2 globular nevi showed a diffuse decrease in pigmentation. Ten reticular nevi remained unchanged, while the rest of the nevi, independent of the dermoscopic pattern, presented a gradual increase in pigmentation. On the other hand, under dabrafenib and trametinib treatment 57 of these nevi showed gradual decrease in pigmentation and central involution, while 7 reticular nevi and 1 globular nevus remained unchanged; none of the monitored nevi increased in pigmentation nor presented new globules following this combination therapy.Systematic total body skin examination is mandatory in patients receiving BRAF inhibitors. The divergent course of melanocytic nevi during vemurafenib vs. dabrafenib and trametinib therapy remains to be elucidated by further research. KEY WORDS: melanoma; pigmented nevus; dermoscopy; vemurafenib</p

Evolution of Melanocytic Nevi under Vemurafenib, Followed by Combination Therapy with Dabrafenib and Trametinib for Metastatic Melanoma

ABSTRACT Treatment of advanced melanoma with selective BRAF and MEK inhibitors is associated with a series of mucocutaneous side effects, among which morphological changes in preexisting nevi and the development of new melanocytic lesions, both benign and malignant.Objective was to describe the changes observed in melanocytic nevi under vemurafenib therapy, followed by combination therapy with dabrafenib and trametinib for metastatic melanoma.The melanocytic lesions of a 51-year-old Caucasian male patient diagnosed with stage IV melanoma were monitored both clinically and dermoscopically throughout vemurafenib, followed by combined treatment with dabrafenib and trametinib.The 65 monitored nevi presented different behaviors under vemurafenib treatment: 18 reticular nevi, 9 reticular-homogenous nevi, 3 reticular-globular nevi, and 2 globular nevi showed a diffuse decrease in pigmentation. Ten reticular nevi remained unchanged, while the rest of the nevi, independent of the dermoscopic pattern, presented a gradual increase in pigmentation. On the other hand, under dabrafenib and trametinib treatment 57 of these nevi showed gradual decrease in pigmentation and central involution, while 7 reticular nevi and 1 globular nevus remained unchanged; none of the monitored nevi increased in pigmentation nor presented new globules following this combination therapy.Systematic total body skin examination is mandatory in patients receiving BRAF inhibitors. The divergent course of melanocytic nevi during vemurafenib vs. dabrafenib and trametinib therapy remains to be elucidated by further research. KEY WORDS: melanoma; pigmented nevus; dermoscopy; vemurafenib</p

Familial Case of White Sponge Nevus – Diagnosis and Therapeutical Challenges

Letter to the editor No abstract available</p

Rhinitis associated with asthma is distinct from rhinitis alone: TARIA‐MeDALL hypothesis

Asthma, rhinitis, and atopic dermatitis (AD) are interrelated clinical phenotypes that partly overlap in the human interactome. The concept of “one-airway-one-disease,” coined over 20 years ago, is a simplistic approach of the links between upper- and lower-airway allergic diseases. With new data, it is time to reassess the concept. This article reviews (i) the clinical observations that led to Allergic Rhinitis and its Impact on Asthma (ARIA), (ii) new insights into polysensitization and multimorbidity, (iii) advances in mHealth for novel phenotype definitions, (iv) confirmation in canonical epidemiologic studies, (v) genomic findings, (vi) treatment approaches, and (vii) novel concepts on the onset of rhinitis and multimorbidity. One recent concept, bringing together upper- and lower-airway allergic diseases with skin, gut, and neuropsychiatric multimorbidities, is the “Epithelial Barrier Hypothesis.” This review determined that the “one-airway-one-disease” concept does not always hold true and that several phenotypes of disease can be defined. These phenotypes include an extreme “allergic” (asthma) phenotype combining asthma, rhinitis, and conjunctivitis.info:eu-repo/semantics/publishedVersio

Cabbage and fermented vegetables : From death rate heterogeneity in countries to candidates for mitigation strategies of severe COVID-19

Large differences in COVID-19 death rates exist between countries and between regions of the same country. Some very low death rate countries such as Eastern Asia, Central Europe, or the Balkans have a common feature of eating large quantities of fermented foods. Although biases exist when examining ecological studies, fermented vegetables or cabbage have been associated with low death rates in European countries. SARS-CoV-2 binds to its receptor, the angiotensin-converting enzyme 2 (ACE2). As a result of SARS-CoV-2 binding, ACE2 downregulation enhances the angiotensin II receptor type 1 (AT(1)R) axis associated with oxidative stress. This leads to insulin resistance as well as lung and endothelial damage, two severe outcomes of COVID-19. The nuclear factor (erythroid-derived 2)-like 2 (Nrf2) is the most potent antioxidant in humans and can block in particular the AT(1)R axis. Cabbage contains precursors of sulforaphane, the most active natural activator of Nrf2. Fermented vegetables contain many lactobacilli, which are also potent Nrf2 activators. Three examples are: kimchi in Korea, westernized foods, and the slum paradox. It is proposed that fermented cabbage is a proof-of-concept of dietary manipulations that may enhance Nrf2-associated antioxidant effects, helpful in mitigating COVID-19 severity.Peer reviewe

Nrf2-interacting nutrients and COVID-19 : time for research to develop adaptation strategies

There are large between- and within-country variations in COVID-19 death rates. Some very low death rate settings such as Eastern Asia, Central Europe, the Balkans and Africa have a common feature of eating large quantities of fermented foods whose intake is associated with the activation of the Nrf2 (Nuclear factor (erythroid-derived 2)-like 2) anti-oxidant transcription factor. There are many Nrf2-interacting nutrients (berberine, curcumin, epigallocatechin gallate, genistein, quercetin, resveratrol, sulforaphane) that all act similarly to reduce insulin resistance, endothelial damage, lung injury and cytokine storm. They also act on the same mechanisms (mTOR: Mammalian target of rapamycin, PPAR gamma:Peroxisome proliferator-activated receptor, NF kappa B: Nuclear factor kappa B, ERK: Extracellular signal-regulated kinases and eIF2 alpha:Elongation initiation factor 2 alpha). They may as a result be important in mitigating the severity of COVID-19, acting through the endoplasmic reticulum stress or ACE-Angiotensin-II-AT(1)R axis (AT(1)R) pathway. Many Nrf2-interacting nutrients are also interacting with TRPA1 and/or TRPV1. Interestingly, geographical areas with very low COVID-19 mortality are those with the lowest prevalence of obesity (Sub-Saharan Africa and Asia). It is tempting to propose that Nrf2-interacting foods and nutrients can re-balance insulin resistance and have a significant effect on COVID-19 severity. It is therefore possible that the intake of these foods may restore an optimal natural balance for the Nrf2 pathway and may be of interest in the mitigation of COVID-19 severity

Patient and Physician Perspectives on Asthma and Its Therapy in Romania: Results of a Multicenter Survey

Background and Objectives: Patient’s behaviours, attitudes and beliefs related to asthma and its treatment were shown to influence the adherence to therapy and the level of asthma control. This survey aimed to assess the level of asthma control and patient-reported behaviours, attitudes and expectations related to their disease in Romanian patients. Materials and Methods: This cross-sectional quantitative survey was performed in February-March 2019 and enrolled 70 specialist physicians experienced in asthma management and 433 asthma patients under their care. Results: Of the 433 patients enrolled, 19.4% had mild asthma, 60.5% moderate asthma and 20.1% severe asthma. For the previous 12 months, asthma symptoms, exacerbations and emergency room visits were common in the sample analysed, with significantly higher figures in severe asthma patients (p &lt; 0.001). The most important treatment goal for asthma patients was participation in all activities of daily living, while for physicians this was preventing asthma exacerbations. The valuation of the treatment goals was different between patients with severe asthma and those with mild and moderate forms. Based on the patients’ responses, 3 attitude clusters were identified: empowered savvy (36.5% of the patients), pessimistic non-compliers (43.2%), and anxious strugglers (20.3%). “Empowered savvy” had the lowest frequency of severe asthma, the highest adherence to maintenance therapy and the highest level of confidence in the effectiveness of asthma medication. The opposite of this attitude cluster is the “anxious strugglers”, containing more patients with severe asthma, a higher score for worries about asthma therapy and better self-reported knowledge of their treatment, contrasting with a proportion of 25% taking maintenance therapy only when having breathing difficulties. Conclusion: Asthma control in Romania remains poor, with frequent exacerbations and hospitalizations. The differences in treatment goals found between patients and physicians and between different asthma severity groups suggest the need for more patient-centred approaches

Esophageal Pressure Measurement in Acute Hypercapnic Respiratory Failure Due to Severe COPD Exacerbation Requiring NIV&mdash;A Pilot Safety Study

Esophageal pressure (Pes) measurements could optimise ventilator parameters in acute respiratory failure (ARF) patients requiring noninvasive ventilation (NIV). Consequently, the objectives of our study were to evaluate the safety and accuracy of applying a Pes measuring protocol in ARF patients with AECOPD under NIV in our respiratory intermediate care unit (RICU). An observational cohort study was undertaken. The negative inspiratory swing of Pes (&Delta;Pes) was measured: in an upright/supine position in the presence/absence of NIV at D1 (day of admission), D3 (3rd day of NIV), and DoD (day of discharge). A digital filter for artefact removal was developed. We included 15 patients. The maximum values for &#8710;Pes were recorded at admission (mean &#8710;Pes 23.2 cm H2O) in the supine position. &#8710;Pes decreased from D1 to D3 (p &lt; 0.05), the change being BMI-dependent (p &lt; 0.01). The addition of NIV decreased &#8710;Pes at D1 and D3 (p &lt; 0.01). The reduction of &#8710;Pes was more significant in the supine position at D1 (8.8 cm H2O, p &lt; 0.01). Under NIV, &#8710;Pes values remained higher in the supine versus upright position. Therefore, the measurement of Pes in AECOPD patients requiring NIV can be safely done in an RICU. Under NIV, &#8710;Pes reduction is most significant within the first 24 h of admission

Contact Allergy Induced by Mango (Mangifera indica): A Relevant Topic?

Introduction: The most common clinical manifestation of mango allergy is contact dermatitis, which can be localized or systemic. The sensitising substances that have long been suspected are alk(en)yl catechols and/or alk(en)yl resorcinols. Methods: We reviewed the original articles published on Pubmed, Embase and Cochrane Library before 15 September 2021, on the topic of contact allergy induced by mango and we synthesized the key data. Results: We found 12 case reports and four case series, with a total of 37 patients. Only seven of these cases were reported in patients from mango-cultivating countries, the other 30 were from countries where mango cultivation does not occur, and 26 were also from countries where poison ivy/oak are commonly found. We found that contact dermatitis may occur on the first exposure to mango due to previous sensitisation to urushiol-containing plants. The diagnosis was confirmed by patch testing in some of the cases. There was great heterogeneity between the reagents used. Conclusion: Mango fruit is frequently consumed, but mango induced contact dermatitis, the main hypersensitivity reaction induced by mango, is rare. Further data is necessary for a better understanding of sensitising substances and, consecutively, standardization of patch test reagents