Urszula Adamska

New directions for pharmacotherapy in the treatment of acute coronary syndrome

ABSTRACT Introduction: Acute coronary syndromes (ACS) are one of the leading causes of death worldwide. Several landmark trials, followed by a widespread introduction of new agents, have significantly improved ACS outcomes in recent years. However, despite the use of contemporary therapy, a substantial number of ACS patients continue to suffer from cardiovascular events. Areas covered: The aim of this review was to summarize available data on innovative drugs and pharmacological strategies that have potential to amend the current ACS therapy. We present the results of recent large clinical trials, as well as insights from ongoing phase III and phase IV studies, exploring the value of new strategies for the improvement of outcomes in ACS. Expert opinion: More potent platelet inhibition, more profound lipid reduction and possibly anti-inflammatory action are considered to have potential to further reduce the rates of adverse cardiovascular and thrombotic events in ACS patients. ‘Hit fast, hit hard’ approach regarding novel antiplatelet and lipid-lowering therapy seems attractive, but it has to be considered that these strategies may be associated with increased adverse events rate. Introduction of cangrelor and ezetimibe, and potentially future recognition of proprotein convertase subtilisin/kexin type 9 antibodies, are likely to alter the landscape of ACS pharmacotherapy.

Comparison of bioavailability and antiplatelet action of ticagrelor in patients with ST-elevation myocardial infarction and non-ST-elevation myocardial infarction: A prospective, observational, single-centre study

Background Data from available studies suggest that the presence of ST-elevation myocardial infarction (STEMI) may be associated with delayed and attenuated ticagrelor bioavailability and effect compared with non-ST-elevation myocardial infarction (NSTEMI). Methods In a single-center, prospective, observational trial 73 patients with myocardial infarction (STEMI n = 49, NSTEMI n = 24) underwent a pharmacokinetic and pharmacodynamic assessment after a 180 mg ticagrelor loading dose (LD). Ticagrelor and its active metabolite (AR-C124910XX) plasma concentrations were determined with liquid chromatography tandem mass spectrometry, and their antiplatelet effect was measured with the VASP assay and multiple electrode aggregometry. Results During the first six hours after ticagrelor LD, STEMI patients had 38% and 34% lower plasma concentration of ticagrelor and AR-C124910XX, respectively, than NSTEMI (ticagrelor AUC(0–6): 2491 [344–5587] vs. 3991 [1406–9284] ng*h/mL; p = 0.038; AR-C124910XX AUC(0–6): 473 [0–924] vs. 712 [346–1616] ng*h/mL; p = 0.027). STEMI patients also required more time to achieve maximal concentration of ticagrelor (tmax: 4.0 [3.0–12.0] vs. 2.5 [2.0–6.0] h; p = 0.012). Impaired bioavailability of ticagrelor and AR-C124910XX seen in STEMI subjects was associated with diminished platelet inhibition in this group, which was most pronounced during the initial hours of treatment. Conclusions Plasma concentrations of ticagrelor and AR-C124910XX during the first hours after ticagrelor LD were one third lower in STEMI than in NSTEMI patients. This reduced and delayed ticagrelor bioavailability was associated with weaker antiplatelet effect in STEMI. Clinical trial registration ClinicalTrials.gov identifier: NCT02602444 (November 09, 2015)

Photosensitive pityriasis rubra pilaris

Pityriasis rubra pilaris (PRP) is a rare, chronic papulosquamous skin disorder. The skin lesions rarely have a predilection to sun-exposed areas although it is known that natural sunlight and phototherapy can exacerbate PRP [1–4]. We present a case of a patient suffering from pityriasis rubra pilaris with photoexposed distribution and photosensitivity exclusively to UVB objectively detected by phototesting, successfully treated with methotrexate.

Imaging in a rare case of neuroendocrine tumour with skin metastases

Purpose Disseminated malignancies are a diagnostic and therapeutic challenge that is often encountered in radiology. Finding the primary tumour is crucial for planning proper surgical and oncological treatment. Computed tomography (CT) of the thorax and abdomen is typically the initial examination. However, abdominal magnetic resonance imaging (MRI) or positron emission tomography (PET/CT) or PET/MRI are often subsequently performed. Histopathological examination of metastatic tumours is performed as well, followed by immunohistochemistry. The aim of the report was to present diagnostic workup in a rare case of skin metastases. Case report A 72-year-old patient was admitted to a dermatology ward because of skin lesions – violaceous nodules localised on the hair-covered skin of the head. On abdominal CT, a generalised neoplastic process with metastases in the liver, pancreas, adrenal glands, lymph nodes, bones, thoracic wall, and a suspected metastasis in the right breast was revealed. Histopathology of the skin nodules confirmed a neuroendocrine tumour. Metastases of a pancreatic neuroendocrine tumour or small-cell lung cancer were suspected on immunohistochemistry. The patient died before we were able to localise the primary source of the tumour and provide treatment. Conclusions Skin metastases are relatively rare, aggravate the prognosis, and usually indicate spread of the neoplastic process in the internal organs. It is not always possible to localise the primary tumour using radiological imaging. In such cases, co-operation with the pathologist is crucial as are the results of histopathological and immunohistochemical examinations.

Evaluating current and emerging antithrombotic therapy currently available for the treatment of acute coronary syndrome in geriatric populations

ABSTRACT Introduction: Acute coronary syndromes (ACS) represent one of the most perilous presentations of ischemic heart disease. Temporal trends clearly demonstrate that ACS occur later and later in life. Elderly patients with ACS comprise a populous and growing group, with more than half of individuals presenting with myocardial infarction being 75 years or older. Nevertheless, geriatric patients are greatly underrepresented in the landmark ACS trials evaluating innovative pharmacological strategies. Areas covered: The authors critically summarize recently published research on contemporary and emerging antithrombotic therapy for the treatment of ACS in geriatric patients. Expert opinion: Elderly ACS patients are characterized by simultaneously increased risk of cardiovascular events and bleeding. Very few studies assessing the efficacy and safety of novel ACS pharmacotherapy in geriatric patients are currently available. Guidelines on the treatment of ACS are based on the overall results of major randomized clinical trials (RCTs), and data supporting the recommended therapy in elderly mainly derive from subanalyses of these RCTs. Properly designed and powered RCTs are necessary to properly evaluate the net effect of current and emerging pharmacotherapy in geriatric patients. Until such data are available, elderly ACS patients should receive treatment according to the general recommendations.

Folliculitis decalvans and orofacial granulomatosis

Folliculitis decalvans (FD) is a rare and chronic inflammatory dermatosis which pathogenesis remains unclear. It is classified as primary neutrophilic cicatricial alopecia presented clinically with follicular pustules and papules, hemorrhagic crusts, erosions and scarring within scalp. Orofacial granulomatosis (OFG) is a recurrent or persistent orofacial swelling histopathologically presented with non-caseating granulomas. The etiology of the disease is not fully understood. There are hypotheses concerning pathogenesis of the disease including genetic, allergic, infectious and immunological factors. We report a case of a patient with FD and concomitant orofacial granulomatosis successfully treated with dapsone. A 32-year-old man was admitted to the Department of Dermatology to diagnose follicular pustules, erosions, yellow scales, crusts with scarred areas and focal hair loss within the scalp, especially within vertex and accompanying persistent lip swelling with normal appearance of the tongue and no oral lesions (Figure 1). Moreover, we observed erythrosquamous lesions and papules on the lateral surfaces of the trunk, within groins and armpits. The lesions on the scalp occurred in childhood and the lip swelling persisted for 3 years. Except skin eruptions the patient did not report any other complaints. He was initially treated in another clinic for seborrheic dermatitis and acne inversa topically with antibiotics, glucocorticosteroids, tacrolimus and orally with antibiotics (doxycycline), antihistamines with temporary improvement. The patient suffered from post-traumatic epilepsy and was treated with carbamazepine. He had a craniotomy due to head injury (concussions and subdural hematoma of the left temporo-parietal brain region, basilar skull fracture and squamous part of the right temporal bone fracture) during the traffic accident 20 years earlier. During the hospitalization routine laboratory tests showed an elevated C-reactive protein level and erythrocyturia which occurred to be irrelevant (the patient was consulted by the urologist). Swabs from erosions and pustules were collected and two types of bacteria were cultured – Staphylococcus aureus and Streptococcus agalactiae. To exclude concomitant systemic diseases, we performed additional examinations. There were no abnormalities in abdominal ultrasonography or chest X-ray. Antinuclear antibodies, lupus anticoagulant, cardiolipin antibodies (IgG and IgM), b2-glycoprotein 1 antibodies (IgG and IgM), anti-Borrelia spp. antibodies tests (IgG and IgM), concentration of C1 esterase inhibitor and Quantiferon-TB Gold test in patient’s serum were negative or within normal

Plane warts on the back of the hand successfully treated with oral isotretinoin

Address for correspondence: Agnieszka Białecka MD, Chair of Dermatology, Sexually Transmitted Diseases and Immunodermatology, Faculty of Medicine, Nicolaus Copernicus University, 9 Skłodowskiej-Curie St, 85-094 Bydgoszcz, Poland, phone: +48 696 557 558, +48 535 854 568, e-mail: agnieszka_bialecka@wp.pl Received: 13.07.2017, accepted: 24.08.2017. Plane warts on the back of the hand successfully treated with oral isotretinoin

Low-level laser therapy (LLLT) does not reduce subcutaneous adipose tissue by local adipocyte injury but rather by modulation of systemic lipid metabolism.

Low-level laser (light) therapy (LLLT) has been applied recently to body contouring. However the mechanism of LLLT-induced reduction of subcutaneous adipose tissue thickness has not been elucidated and proposed hypotheses are highly controversial. Non-obese volunteers were subject to 650nm LLLT therapy. Each patient received 6 treatments 2-3 days apart to one side of the abdomen. The contralateral side was left untreated and served as control. Subjects’ abdominal adipose tissue thickness was measured by ultrasound imaging at baseline and 2 weeks post-treatment. Our study is to the best of our knowledge, the largest split-abdomen study employing subcutaneous abdominal fat imaging. We could not show a statistically significant reduction of abdominal subcutaneous adipose tissue by LLLT therapy. Paradoxically when the measurements of the loss of fat thickness on treated side was corrected for change in thickness on non treated side, we have observed that in 8 out of 17 patients LLLT increased adipose tissue thickness. In two patients severe side effect occurred as a result of treatment: one patient developed ulceration within appendectomy scar, the other over the posterior superior iliac spine. The paradoxical net increase in subcutaneous fat thickness observed in some of our patients is a rationale against liquefactive and transitory pore models of LLLT-induced adipose tissue reduction. LLLT devices with laser diode panels applied directly on the skin are not as safe as devices with treatment panels separated from the patient’s skin.

Properties of skin stem cells and their potential clinical applications in modern dermatology

Stem cells play an important role in medical science, and scientists are investing large sums in order to perform sophisticated studies designed to establish potential clinical applications of stem cells. Growing experience has enabled researchers to determine the precise nature of stem cell division. Although the properties of this particular population of cells have been known and used for some time, mainly with regards to bone marrow-derived mesenchymal stem cell transplantation, we now face a significant challenge in implementing the practical use of skin-derived precursors, making it possible to avoid the necessity for patients to undergo invasive procedures in order to obtain stem cells from bone marrow. Multiple trials have so far been performed, bringing hope for the treatment of disorders previously considered untreatable. Patients suffering from a number of dermatological diseases, including malignant melanoma, systemic lupus erythematosus, vitiligo, alopecia or junctional epidermolysis bullosa, may benefit from treatment based on stem cells. The aim of this review is to summarize available data on stem cells and their potential application in the treatment of dermatological disorders. Thework described is based on data published up to the end of September 2016.

Pyoderma gangrenosum mimicking inflammatory breast cancer

Address for correspondence: Agnieszka Białecka MD, Chair of Dermatology, Sexually Transmitted Diseases and Immunodermatology, Faculty of Medicine, Nicolaus Copernicus University, 9 Skłodowskiej-Curie St, 85-094 Bydgoszcz, Poland, phone: +48 696 557 558, +48 535 854 568, fax: +48 52 585 40 18, e-mail: agnieszka_bialecka@wp.pl Received: 2.08.2016, accepted: 5.09.2016. Pyoderma gangrenosum mimicking inflammatory breast cancer