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

Stopping long-acting beta2-agonists (LABA) for adults with asthma well controlled by LABA and inhaled corticosteroids.

BACKGROUND: Poorly controlled asthma often leads to preventable exacerbations that require additional medications, as well as unscheduled hospital and clinic visits.Long-acting beta2-agonists (LABA) are commonly given to adults with asthma whose symptoms are not well controlled by inhaled corticosteroids (ICS). US and UK regulators have issued warnings for LABA in asthma, and now recommend they be used "for the shortest duration of time required to achieve control of asthma symptoms and discontinued, if possible, once asthma control is achieved". OBJECTIVES: To compare cessation of long-acting beta2-agonists (LABA) versus continued use of LABA/inhaled corticosteroids (LABA/ICS) for adults whose asthma is well controlled, and to determine whether stopping LABA:1. results in loss of asthma control or deterioration in quality of life;2. increases the likelihood of asthma attacks or 'exacerbations'; or3. increases or decreases the likelihood of serious adverse events of any cause. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register (CAGR), www.ClinicalTrials.gov, www.who.int/ictrp/en/, reference lists of primary studies and existing reviews and manufacturers' trial registries (GlaxoSmithKline (GSK) and AstraZeneca). We searched all databases from their inception to April 2015, and we imposed no restriction on language of publication. SELECTION CRITERIA: We looked for parallel randomised controlled trials (RCTs) of at least eight weeks' duration, in which adults whose asthma was well controlled by any dose of ICS+LABA combination therapy were randomly assigned to (1) step-down therapy to ICS alone versus (2) continuation of ICS and LABA. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all records identified by the search strategy. We used an Excel extraction tool to manage searches, document reasons for inclusion and exclusion and extract descriptive and numerical data from trials meeting inclusion criteria.Prespecified primary outcomes were (1) exacerbations requiring oral steroids, (2) asthma control and (3) all-cause serious adverse events. MAIN RESULTS: Six randomised, double-blind studies between 12 and 24 weeks' long met the inclusion criteria. Five studies contributed data to the meta-analysis, assigning 2781 people with stable asthma to the comparison of interest. The definition of stable asthma and inclusion criteria varied across studies, and Global Initiative for Asthma (GINA) criteria were not used. Risk of bias across studies was generally low, and most evidence was rated as moderate quality.Stopping LABA might increase the number of people having exacerbations and requiring oral corticosteroids (odds ratio (OR) 1.74, 95% confidence interval (CI) 0.83 to 3.65; participants = 1257; studies = 4), although the confidence intervals did not exclude the possibility that stopping LABA was beneficial; over 17 weeks, 19 people per 1000 who continued their LABA had an exacerbation, compared with 32 per 1000 when LABA were stopped (13 more per 1000, 95% CI 3 fewer to 46 more).People who stopped LABA had worse scores on the Asthma Control Questionnaire (mean difference (MD) 0.24, 95% CI 0.13 to 0.35; participants = 645; studies = 3) and on measures of asthma-related quality of life (standardised mean difference (SMD) 0.36, 95% CI 0.15 to 0.57; participants = 359; studies = 2) than those who continued LABA, but the effects were not clinically relevant.Too few events occurred for investigators to tell whether stopping LABA has a greater effect on serious adverse events compared with continuing LABA+ICS (OR 0.82, 95% CI 0.28 to 2.42; participants = 1342; studies = 5), and no study reported exacerbations requiring an emergency department visit or hospitalisation as a separate outcome. Stopping LABA may result in fewer adverse events of any kind compared with continuing, although the effect was not statistically significant (OR 0.83, 95% CI 0.66 to 1.05; participants = 1339; studies = 5), and stopping LABA made people more likely to withdraw from participation in research studies (OR 1.95, 95% CI 1.47 to 2.58; participants = 1352; studies = 5). AUTHORS' CONCLUSIONS: This review suggests that stopping LABA in adults who have stable asthma while they are taking a combination of LABA and ICS inhalers may increase the likelihood of asthma exacerbations that require treatment with oral corticosteroids, but this is not certain. Stopping LABA may slightly reduce asthma control and quality of life, but evidence was insufficient to show whether this had an effect on important outcomes such as serious adverse events and exacerbations requiring hospital admission, and longer trials are warranted. Trialists should include patient-important outcomes such as asthma control and quality of life and should use validated measurement tools. Definitions of exacerbations should be provided

Stopping long-acting beta2-agonists (LABA) for children with asthma well controlled on LABA and inhaled corticosteroids.

BACKGROUND: Asthma is the most common chronic medical condition among children and is one of the most common causes of hospitalisation and medical visits. Poorly controlled asthma often leads to preventable exacerbations that require additional medications, hospital stays, or treatment in the emergency department.Long-acting beta2-agonists (LABA) are the preferred add-on treatment for children with asthma whose symptoms are not well controlled on inhaled corticosteroids (ICS). The US Food and Drug Administration has issued a 'black box' warning for LABA in asthma, and now recommends that they be used "for the shortest duration of time required to achieve control of asthma symptoms and discontinued, if possible, once asthma control is achieved". OBJECTIVES: To compare the effect on asthma control and adverse effects of stepping down to inhaled corticosteroids (ICS)-only therapy versus continuing ICS plus LABA in children whose asthma is well controlled on combined ICS and LABA therapy. SEARCH METHODS: We searched the Cochrane Airways Group Specialised Register, and also searched www.ClinicalTrials.gov, www.who.int/ictrp/en/, reference lists of primary studies and existing reviews, and manufacturers' trial registries (GlaxoSmithKline and AstraZeneca). We searched all databases from their inception to the present, and imposed no restriction on language of publication. The most recent search was done in April 2015. SELECTION CRITERIA: We looked for parallel randomised controlled trials of at least eight weeks' duration, available as published full text, abstract only, or unpublished data. We excluded studies including participants with other chronic respiratory comorbidities (for example bronchiectasis).We looked for studies in which children (18 years or younger) whose asthma was well controlled on any dose of ICS and LABA combination therapy were randomised to: a) step-down therapy to ICS alone or b) continued use of ICS and LABA.We included any dose of LABA (formoterol, salmeterol, vilanterol) and any dose of ICS (beclomethasone, budesonide, ciclesonide, mometasone, flunisolide, fluticasone propionate, fluticasone furoate, triamcinolone) delivered in a combination inhaler or in separate inhalers. DATA COLLECTION AND ANALYSIS: Two review authors independently screened all records identified in the searches. We used a data extraction tool in Microsoft Excel to manage searches and document reasons for inclusion and exclusion, and to extract descriptive and numerical data from trials meeting the inclusion criteria.The prespecified primary outcomes were exacerbations requiring oral steroids, asthma control, and all-cause serious adverse events. MAIN RESULTS: Despite conducting extensive searches of electronic databases, trial registries and manufacturers' websites we identified no trials matching the inclusion criteria.After removing duplicates, we screened 1031 abstracts, and assessed 43 full-text articles for inclusion. We identified several adult studies, which will be summarised in a separate review (Ahmad 2014). The most common reasons for exclusion after viewing full texts were 'wrong comparison' (n = 22) and 'adult population' (n = 18).Some adult studies recruited adolescents from age 15, but none reported data separately for those under 18. AUTHORS' CONCLUSIONS: There is currently no evidence from randomised trials to inform the discontinuation of LABAs in children once asthma control is achieved with ICS plus LABA. It is disappointing that such an important issue has not been studied, and a randomised double-blind trial recruiting children who are controlled on ICS plus LABA is warranted. The study should be large enough to assess children of different ages, and to measure the important safety and efficacy outcomes suggested in this review over at least six months.The only randomised evidence for stopping LABA has been conducted in adults; it will be summarised in a separate review

Toward personalization of asthma treatment according to trigger factors

Asthma is a severe and chronic disabling disease affecting more than 300 million people worldwide. Although in the past few drugs for the treatment of asthma were available, new treatment options are currently emerging, which appear to be highly effective in certain subgroups of patients. Accordingly, there is a need for biomarkers that allow selection of patients for refined and personalized treatment strategies. Recently, serological chip tests based on microarrayed allergen molecules and peptides derived from the most common rhinovirus strains have been developed, which may discriminate 2 of the most common forms of asthma, that is, allergen- and virus-triggered asthma. In this perspective, we argue that classification of patients with asthma according to these common trigger factors may open new possibilities for personalized management of asthma.Fil: Niespodziana, Katarzyna. Vienna University of Technology; AustriaFil: Borochova, Kristina. Vienna University of Technology; AustriaFil: Pazderova, Petra. Vienna University of Technology; AustriaFil: Schlederer, Thomas. Vienna University of Technology; AustriaFil: Astafyeva, Natalia. Saratov State Medical University; RusiaFil: Baranovskaya, Tatiana. Belarusian Medical Academy of Post Diploma Studies; BielorrusiaFil: Barbouche, Mohamed Ridha. Institut Pasteur de Tunis; TúnezFil: Beltyukov, Evgeny. Ural State Medical University; RusiaFil: Berger, Angelika. Vienna University of Technology; AustriaFil: Borzova, Elena. Russian Medical Academy of Continuous Professional Education; RusiaFil: Bousquet, Jean. MACVIA; Francia. Humboldt-Universität zu Berlin; AlemaniaFil: Bumbacea, Roxana S.. University of Medicine and Pharmacy "Carol Davila"; RumaniaFil: Bychkovskaya, Snezhana. Krasnoyarsk Medical University; RusiaFil: Caraballo, Luis. Universidad de Cartagena; ColombiaFil: Chung, Kian Fan. Imperial College London; Reino Unido. MRC and Asthma UK Centre in Allergic Mechanisms of Asthma; Reino UnidoFil: Custovic, Adnan. Imperial College London; Reino Unido. MRC and Asthma UK Centre in Allergic Mechanisms of Asthma; Reino UnidoFil: Docena, Guillermo H.. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Instituto de Estudios Inmunológicos y Fisiopatológicos. Universidad Nacional de La Plata. Facultad de Ciencias Exactas. Instituto de Estudios Inmunológicos y Fisiopatológicos; ArgentinaFil: Eiwegger, Thomas. University Of Toronto. Hospital For Sick Children; CanadáFil: Evsegneeva, Irina. Sechenov First Moscow State Medical University; RusiaFil: Emelyanov, Alexander. North-Western Medical University; RusiaFil: Errhalt, Peter. University Hospital Krems and Karl Landsteiner University of Health Sciences; AustriaFil: Fassakhov, Rustem. Kazan Federal University; RusiaFil: Fayzullina, Rezeda. Bashkir State Medical University; RusiaFil: Fedenko, Elena. NRC Institute of Immunology FMBA of Russia; RusiaFil: Fomina, Daria. Sechenov First Moscow State Medical University; RusiaFil: Gao, Zhongshan. Zhejiang University; ChinaFil: Giavina Bianchi, Pedro. Universidade de Sao Paulo; BrasilFil: Gotua, Maia. David Tvildiani Medical University; GeorgiaFil: Greber Platzer, Susanne. Vienna University of Technology; AustriaFil: Hedlin, Gunilla. Karolinska Huddinge Hospital. Karolinska Institutet; Sueci

Clinical features and outcomes of tuberculosis in transplant recipients as compared with the general population: a retrospective matched cohort study

AbstractThere are no previous studies comparing tuberculosis in transplant recipients (TRs) with other hosts. We compared the characteristics and outcomes of tuberculosis in TRs and patients from the general population. Twenty-two TRs who developed tuberculosis from 1996 through 2010 at a tertiary hospital were included. Each TR was matched by age, gender and year of diagnosis with four controls selected from among non-TR non-human immunodeficiency virus patients with tuberculosis. TRs (21 patients, 96%) had more factors predisposing to tuberculosis than non-TRs (33, 38%) (p <0.001). Pulmonary tuberculosis was more common in non-TRs (77 (88%) vs. 12 TRs (55%); p 0.001); disseminated tuberculosis was more frequent in TRs (five (23%) vs. four non-TRs (5%); p 0.005). Time from clinical suspicion of tuberculosis to definitive diagnosis was longer in TRs (median of 14 days) than in non-TRs (median of 0 days) (p <0.001), and invasive procedures were more often required (12 (55%) TRs and 15 (17%) non-TRs, respectively; p 0.001). Tuberculosis was diagnosed post-mortem in three TRs (14%) and in no non-TRs (p <0.001). Rates of toxicity associated with antituberculous therapy were 38% in TRs (six patients) and 10% (seven patients) in non-TRs (p 0.014). Tuberculosis-related mortality rates in TRs and non-TRs were 18% and 6%, respectively (p 0.057). The adjusted Cox regression analysis showed that the only predictor of tuberculosis-related mortality was a higher number of organs with tuberculosis involvement (adjusted hazard ratio 8.6; 95% CI 1.2–63). In conclusion, manifestations of tuberculosis in TRs differ from those in normal hosts. Post-transplant tuberculosis resists timely diagnosis, and is associated with a higher risk of death before a diagnosis can be made

Global mortality and readmission rates following COPD exacerbation-related hospitalisation: a meta-analysis of 65 945 individual patients

\ua9 2024, European Respiratory Society. All rights reserved.Background Exacerbations of COPD (ECOPD) have a major impact on patients and healthcare systems across the world. Precise estimates of the global burden of ECOPD on mortality and hospital readmission are needed to inform policy makers and aid preventive strategies to mitigate this burden. The aims of the present study were to explore global in-hospital mortality, post-discharge mortality and hospital readmission rates after ECOPD-related hospitalisation using an individual patient data meta-analysis (IPDMA) design. Methods A systematic review was performed identifying studies that reported in-hospital mortality, postdischarge mortality and hospital readmission rates following ECOPD-related hospitalisation. Data analyses were conducted using a one-stage random-effects meta-analysis model. This study was conducted and reported in accordance with the PRISMA-IPD statement. Results Data of 65 945 individual patients with COPD were analysed. The pooled in-hospital mortality rate was 6.2%, pooled 30-, 90- and 365-day post-discharge mortality rates were 1.8%, 5.5% and 10.9%, respectively, and pooled 30-, 90- and 365-day hospital readmission rates were 7.1%, 12.6% and 32.1%, respectively, with noticeable variability between studies and countries. Strongest predictors of mortality and hospital readmission included noninvasive mechanical ventilation and a history of two or more ECOPD-related hospitalisation