Comparative Efficacy and Safety of Mycophenolate Mofetil and Azathioprine in Combination with Corticosteroids in the Treatment of Lymphocytic Myocarditis.

AIMS: This paper aimed to study the efficacy and safety of mycophenolate mofetil (MM) in combination with corticosteroids in the treatment of lymphocytic myocarditis (LM) when compared to the standard combination of corticosteroids and azathioprine. METHODS: The study included 50 adult patients (47.8 ± 10.8 y.o.) in a NYHA III functional class due to LM who were verified using endomyocardial biopsy. The main group included 29 patients who received MM at 2 g/day. The comparison group comprised 21 patients who received azathioprine at 150 [50; 150] mg/day. Both groups were administered with methylprednisolone. The average follow-up period was 30 [22; 35] months, but no less than 6 months. RESULTS: The groups were comparable in the baseline parameters and standard drug therapy. In both groups, there was a comparable significant increase in the ejection fraction (from 30.6 ± 7.7% to 44.0 ± 9.4% vs. 29.2 ± 7.7% to 46.2 ± 11.8%, p < 0.001), and a decrease in systolic pressure in the pulmonary artery and the dimensions of the left ventricle and atrium. The frequency of death was two (6.9%) and two (9.5%), transplantation was one (3.4%) and one (4.8%) patient and the "death + transplantation" endpoint was three (10.3%) and three (14.3%) without differences between the groups. The presence of the parvovirus B19 in the myocardium in 6/5 patients did not affect the results. The incidence of infectious complications was comparable. The most severe infectious complications were pneumonia and fatal purulent encephalitis (both cases in the azathioprine group), leptospirosis meningitis (in the mycophenolate mofetil group). CONCLUSIONS: In the patients with LM, the combination of corticosteroids with MM at a dose of 2 g/day was at least no less effective than with azathioprine. There was a tendency toward a better tolerance using MM.

Hypertrophic Cardiomyopathy Complicated by Post-COVID-19 Myopericarditis in Patient with ANO5-Related Distal Myopathy.

A 60-year-old male with hypertrophic cardiomyopathy, conduction disorders, post-COVID-19 myopericarditis and heart failure was admitted to the hospital's cardiology department. Blood tests revealed an increase in CPK activity, troponin T elevation and high titers of anticardiac antibodies. Whole exome sequencing showed the presence of the pathogenic variant NM_213599:c.2272C>T of the ANO5 gene. Results of the skeletal muscle biopsy excluded the diagnosis of systemic amyloidosis. Microscopy of the muscle fragment demonstrated sclerosis of the perimysium, moderate lymphoid infiltration, sclerosis of the microvessels, dystrophic changes and a lack of cross striations in the muscle fibers. Hypertrophy of the LV with a low contractile ability, atrial fibrillation, weakness of the distal skeletal muscles and increased plasma CPK activity and the results of the skeletal muscle biopsy suggested a diagnosis of a late form of distal myopathy (Miyoshi-like distal myopathy, MMD3). Post-COVID-19 myopericarditis, for which genetically modified myocardium could serve as a favorable background, caused heart failure decompensation.

Photodynamic therapy of lung cancer with photosensitizers based on polycationic derivatives of synthetic bacteriochlorin (experimental study).

BACKGROUND: One of the tasks of anticancer photodynamic therapy is increasing the efficacy of treatment of cancer nodes with large (clinically relevant) sizes using near-infrared photosensitizers (PS). METHODS: The anticancer efficacy and mechanisms of the photodynamic action of PS based on polycationic derivatives of synthetic bacteriochlorin against Lewis lung carcinoma were studied in vitro and in vivo. RESULTS: It was found that studied PS have high phototoxicity against Lewis lung carcinoma cells: the IC50 values were about 0.8 µM for tetracationic PS and 0.5 µM for octacationic PS. In vivo studies have shown that these PS provide effective inhibition of the tumor growth with an increase in the lifespan of mice in the group by more than 130%, and more than 50% survival of mice in the group. CONCLUSIONS: Photosensitizers based on polycationic derivatives of synthetic bacteriochlorin have high photodynamic efficacy caused by the induction of necrosis and apoptosis of cancer cells, including cancer stem cells, and a sharp decrease of mitotic and proliferative activity. Studied polycationic photosensitizers are much more effective at destroying cancer stem cells and newly formed cancer vessels in comparison with anionic photosensitizers, and ensure the cessation of tumor blood flow without hemorrhages and thrombosis.

Immunohistochemical Analysis of Spermatogenesis in Patients with SARS-CoV-2 Invasion in Different Age Groups.

Based on studies that focused on the effect of SARS-CoV-2 on human tissues, not only pulmonary invasion was revealed, but also impaired testicular function. Thus, the study of the mechanisms of influence of SARS-CoV-2 on spermatogenesis is still relevant. Of particular interest is the study of pathomorphological changes in men of different age groups. The purpose of this study was to evaluate immunohistochemical changes in spermatogenesis during SARS-CoV-2 invasion in different age groups. In our study, for the first time, a cohort of COVID-19-positive patients of different age groups was collected, and the following were conducted--confocal microscopy of the testicles and immunohistochemical evaluation of spermatogenesis disorders in SARS-CoV-2 invasion with antibodies to the spike protein, the nucleocapsid protein of the SARS-CoV-2 virus, and angiotensin convertase type 2. An IHC study and confocal microscopy of testicular autopsies from COVID-19-positive patients revealed an increase in the number of S-protein- and nucleocapsid-positively stained spermatogenic cells, which indicates SARS-CoV-2 invasion into them. A correlation was found between the number of ACE2-positive germ cells and the degree of hypospermatogenesis, and in the group of patients with confirmed coronavirus infection older than 45 years, the decrease in spermatogenic function was more pronounced than in the cohort of young people. Thus, our study found a decrease in both spermatogenic and endocrine (Leydig cells) testicular functions in patients with COVID-19 infection. In the elderly, these changes were significantly higher than in the group of young patients.

Antitumor activity of photodynamic therapy with tetracationic derivative of synthetic bacteriochlorin in spheroid culture of liver and colon cancer cells.

Efficient screening of photosensitizers (PS) as well as studying their photodynamic activity, especially PS excited in the near-infrared region, require informative in vitro models to adequately reflect the architecture, thickness, and intercellular interactions in tumors. In our study, we used spheroids formed from human colon cancer HCT-116 cells and liver cancer Huh7 cells to assess the phototoxicity of a new PS based on tetracationic derivative of synthetic bacteriochlorin (BC4). We optimized conditions for the irradiation regime based on the kinetics of BC4 accumulation in spheroids and kinetics of spheroid growth. Although PS accumulated more efficiently in HCT-116 cells, characterized by more aggressive growth and high proliferative potential, they were less susceptible to the photodynamic therapy (PDT) compared to the slower growing Huh7 cells. We also showed that 3D models of spheroids were less sensitive to BC4 than conventional 2D cultures with relatively identical kinetics of drug accumulation. Our findings suggest that BC4 is a perspective agent for photodynamic therapy against cancer cells.

Different Phenotypes of Sarcomeric MyBPC3-Cardiomyopathy in the Same Family: Hypertrophic, Left Ventricular Noncompaction and Restrictive Phenotypes (in Association with Sarcoidosis).

The same variants in sarcomeric genes can lead to different cardiomyopathies within the same family. This gave rise to the concept of a continuum of sarcomeric cardiomyopathies. However, the manifestations and evolution of these cardiomyopathies in pathogenic variant carriers, including members of the same family, remains poorly understood. We present a case of familial sarcomeric cardiomyopathy caused by heterozygous truncating pathogenic variant p.Q1233* in cardiac myosin-binding protein C (MyBPC3) gene. The proband was first diagnosed with restrictive cardiomyopathy combined with left ventricular noncompaction (LVNC) and sarcoidosis at the age of 64. The predominantly restrictive phenotype of cardiomyopathy is considered to be a result of interaction between LVNC and sarcoid myocarditis. His 39-year-old son and 35-year-old daughter have identical non-obstructive asymmetric hypertrophic cardiomyopathy. The risk of sudden cardiac death in the son is high due to myocardial fibrosis, ischemia and nonsustained VT. We assume that both phenotypes in the family may have originally been different or there may have been a gradual transformation of the hypertrophic phenotype into LVNC. Myocarditis is regarded as an important epigenomic modifier of sarcomeric cardiomyopathy. In the proband and his son, cardioverter-defibrillators were implanted, and the proband experienced appropriate shocks due to ventricular tachycardia/fibrillation. The proband was also treated with corticosteroids. His death at the age of 69 years occurred due to acute gastric hemorrhage accompanied by progressive heart failure. This report confirms the concept of the phenotypic continuum of sarcomeric cardiomyopathies and describes possible phenotypic patterns and their transformation over time.

On the mechanisms of photodynamic action of photosensitizers based on polycationic derivatives of synthetic bacteriochlorin against human lung cancer cells A549 (in vitro study).

BACKGROUND: One of the tasks of anticancer photodynamic therapy is increasing the efficacy of treatment of cancer nodes with large (clinically relevant) sizes using near-infrared photosensitizers (PS). We study the photodynamic action against A549 human lung cancer cells using PS based on polycationic derivatives of synthetic bacteriochlorin. METHODS: The efficacy and mechanisms of the photodynamic action of PS based on polycationic derivatives of synthetic bacteriochlorin against A549 lung cancer cells were studied in vitro using immunocytochemical and morphological methods. RESULTS: It was found that PS based on tetracationic and octacationic derivatives of synthetic bacteriochlorin induce necrosis, apoptosis, decreasing of proliferative and mitotic activity, as well as reducing the number of ALDH1-positive cancer cells with signs of stem cells in A549 human lung cancer cell culture. The IC50 values (concentration of a PS that reduces cells survival by 50%) were about 0.69 µM for tetracationic PS and 0.57 µM for octacationic PS under irradiation at 30 J/cm2 while in the "dark" control they were higher than 100 µM for both PSs. CONCLUSIONS: Photosensitizers based on polycationic derivatives of synthetic bacteriochlorin have high phototoxicity against A549 cancer cells caused by the induction of necrosis and apoptosis of cancer cells, including cells with signs of stemness, and a sharp decrease of mitotic and proliferative activity.

Mixed-Etiology Restrictive Cardiomyopathy (Desminopathy and Hemochromatosis) with Complex Liver Lesions.

A 28 year-old male with restrictive cardiomyopathy (RCM) and endocardium thickening, conduction disorders, heart failure, and depressive disorder treated with paroxetine was admitted to the clinic. Blood tests revealed an increase in serum iron level, transferrin saturation percentage, and slightly elevated liver function tests. Sarcoidosis, storage diseases and Loeffler endocarditis were ruled out. Mutations in desmin (DES) and hemochromatosis gene (HFE1) were identified. Liver biopsy was obtained to verify the hemochromatosis, assess its possible contribution to the RCM progression and determine indications for treatment. Biopsy revealed signs of drug-induced injury, subcompensated heart failure, and hemosiderin accumulation. Thus, even if one obvious cause (desmin mutation) of RCM has been identified, other less likely causes should be taken into consideration.

Morphologically, immunohistochemically and PCR proven lymphocytic viral peri-, endo-, myocarditis in patients with fatal COVID-19.

BACKGROUND: Despite a reported cardiac injury in patients with new coronavirus infection, the possibility and specifics of genuine viral myocarditis in COVID-19 remains not fully clear. PURPOSE: To study the presence of SARS-CoV-2 in the myocardium and the morphological properties of myocarditis in patients with severe coronavirus infection (COVID-19). METHODS: Autopsy data of eight elderly patients (75.6 ± 7.4 years), four male and four female, with severe new coronavirus infection were studied. The lifetime diagnosis of COVID-19 is based on a positive result of the PCR study. The inclusion criterion was the presence of morphological signs of myocarditis according to the Dallas criteria. A standard histological examination included staining by hematoxylin and eosin, toluidin blue and Van Gieson. An immunohistochemical study was performed using antibodies to CD3, CD 68, CD20, perforin, toll-like receptor (TLR) types 4 and 9. PCR in real-time was performed to determine the viral RNA in the myocardium. RESULTS: All patients had severe bilateral viral pneumonia. In all cases, myocarditis was not clinically diagnosed. Morphological examination of the heart found signs of active lymphocytic myocarditis. PCR identified the SARS-Cov2 RNA in all cases. There were also signs of destructive coronaritis in all cases, thrombovasculitis, lymphocytic pericarditis (in 3 cases) and endocarditis (in 2 cases). The absence of neutrophils confirms the aseptic nature of inflammation. An immunohistochemical study showed the CD3-positive T lymphocytes in the infiltrates. Increased expression of TLR type 4 and less 9 was also detected. CONCLUSION: Morphological and immunohistochemical evidence of myocarditis in COVID-19 was presented. Lymphocytic infiltrations and positive PCR confirm the viral nature of inflammation. Myocarditis in COVID-19 is also characterized by coronaritis with microvascular thrombosis and associated with lymphocytic endo- and pericarditis.

A Case of Severe Left-Ventricular Noncompaction Associated with Splicing Altering Variant in the FHOD3 Gene.

Left ventricular noncompaction (LVNC) is a highly heterogeneous primary disorder of the myocardium. Its clinical features and genetic spectrum strongly overlap with other types of primary cardiomyopathies, in particular, hypertrophic cardiomyopathy. Study and the accumulation of genotype-phenotype correlations are the way to improve the precision of our diagnostics. We present a familial case of LVNC with arrhythmic and thrombotic complications, myocardial fibrosis and heart failure, cosegregating with the splicing variant in the FHOD3 gene. This is the first description of FHOD3-dependent LVNC to our knowledge. We also revise the assumed mechanism of pathogenesis in the case of FHOD3 splicing alterations.

Progressive chronic SARS-CoV-2-positive giant cell myoendocarditis with atrial standstill and sudden cardiac death.

Giant cell myocarditis (GCM) is a rare condition. Its association with SARS-CoV-2 has not been described before. The 46-year-old female patient was admitted to the clinic on September 2020. She had 7 year adrenal insufficiency history and infarct-like debut of myocardial disease in November 2019. After COVID-19 in April 2020, cardiac disease progressed. The examination showed low QRS voltage, QS complexes in V1 -V5 leads, atrial standstill, left ventricular systolic and restrictive dysfunction, elevated anti-heart antibodies, and subepicardial late gadolinium enhancement by magnetic resonance imaging. Endomyocardial biopsy and pacemaker implantation were performed, but the patient died suddenly due to ventricular tachycardia or ventricular fibrillation (the resuscitation was ineffective). The autopsy revealed GCM, SARS-CoV-2, and Parvovirus B19 were detected in the myocardium. The role of SARS-CoV-2 in the pathogenesis of autoimmune myocarditis is discussed.

Primary Undifferentiated Pericardial Sarcoma after Radiоtherapy for Hodgkin Lymphoma.

Various types of sarcomas arise as a result of postradiation chronic fibrous pericarditis. A primary undifferentiated spindle cell pericardial sarcoma is a rare type of sarcoma after radiotherapy. The risk of sarcoma increases with time after treatment of cancer. A 55-year-old woman underwent successful radiation and chemotherapy for Hodgkin lymphoma 20 years ago. She was hospitalized with typical manifestations of severe heart failure. Echocardiography, сomputed tomography of the chest and magnetic resonance imaging scan of the heart detected neoplastic formations of the pericardium. A biopsy of the pericardium was performed. Histological, immunohistochemical, and genetic studies showed a primary undifferentiated spindle cell pericardial sarcoma (an extremely rare type of sarcoma).

Immunosuppressive therapy of biopsy proved immune-mediated lymphocytic myocarditis in the virus-negative and virus-positive patients.

PURPOSE: to study the effect of immunosupressive therapy (IST) in the virus-negative and virus-positive patients with immune-mediated myocarditis. METHODS: in 60 patients (45 male, 46.7 ± 11.8 years, mean LV EDD, 6.7 ± 0.7 cm, EF 26.2 ± 9.1%) active/borderline myocarditis was verified by endomyocardial biopsy (n = 38), intraoperative biopsy (n = 10), examination of explanted heart (n = 3) and autopsy (n = 9). Indications for IST determined based on histological, immune activity. The follow-up was 19.0 [7.25; 40.25] months. RESULTS: The viral genome in the myocardium was detected in 32 patients (V+ group), incl. parvovirus B19 in 23. The anti-heart antibody level was equally high in the V+ and V- patients. Antiviral therapy was administered in 24 patients. IST (in 22 V+ and 24 V- patients) include steroids (n = 40), hydroxychloroquine (n = 20), azathioprine (n = 21). The significant decrease of LV EDD (6.7 ± 0.7 to 6.4 ± 0.8), PAP (48.9 ± 15.5 to 39.4 ± 11.5 mm Hg, р<0,01), increase of EF (26.5 ± 0.9 to 36.0 ± 10.8), and lower lethality (23.9% and 64.3%; RR 0.37, 95% CI 0.19-0.71), p<0.01, were found only in IST group. Significant improvement due to IST were achieved not only in V-, but also in V+ patients. CONCLUSIONS: IST in patients with immune-mediated lymphocytic myocarditis is effective and is associated with lower lethality both in virus-negative and virus-positive patients.

Immunomorphological Features of the Placenta in Allogeneic Pregnancy as the Background for the Development of Obstetric Complications.

OBJECTIVE: To study the structural and immunohistochemical features of placentas in women after assisted reproductive technology (ART) with allogeneic eggs (oocyte donation and surrogate motherhood). STUDY DESIGN: The study involved 89 women whose pregnancy occurred as a result of in vitro fertilization (IVF) with a donor egg in a surrogate motherhood program (IVF-SM, n = 47 patients) or oocyte donation (IVF-DO, n = 42). The comparison group consisted of 21 patients in whom pregnancy occurred as a result of IVF with their own egg (IVF-OE). A clinical and anamnestic analysis of the pregnant women was carried out. Morphological and immunohistochemical studies were performed on placental material. Immunohistochemical analysis of CD8, CD56, CD138, and CD25/CD4 markers indicating the processes of impaired tolerance in placenta was carried out. -Results: We observed a predominance of women aged >40 (range 42.7-3.91) years with a burdened somatic and obstetric-gynecological history and a high incidence of hypertensive pregnancy complications, such as gestational arterial hypertension (27.4%) and preeclampsia (28.5%), in the IVF-DO group. The IVF-SM group included mainly somatically healthy women aged <30 (29.4-3.19) years with a high risk of termination of pregnancy in the third trimester (49.6%) and premature birth (21.6%). Placentas taken from women after allogeneic pregnancy had pronounced signs of immune alteration, such as chronic histiocytic intervillositis, lymphoplasmacytic deciduitis, chronic chorioamnionitis, chronic villitis, and perivillous fibrinoid with lymphocytes (p [F] < 0.05). Immunohistochemical study of the placentas showed accumulation of CD138+ plasma cells, CD8+ T lymphocytes, and uterine natural killer cells, and a decrease in the number of CD25/CD4+ regulatory T cells (Tregs) in the structures of the uteroplacental region (Kruskal-Wallis test, p < 0.05). CONCLUSION: Placentas after IVF with oocyte donation and surrogate motherhood programs are characterized by similar changes, associated with the development of chronic inflammation in the structures of the placenta and immunohistochemical signs of impaired immunological tolerance at the maternal-fetal interface. The data we obtained allow us to classify pregnancies under surrogate motherhood programs as a risk factor for the development of pregnancy complications with immune pathogenesis.

Combination of Calcium Hydroxylapatite Diluted With Normal Saline and Microfocused Ultrasound With Visualization for Skin Tightening.

Background/Objectives: Treatment options for the correction of age-related changes in skin include the use of energy-based devices and dermal fillers. In this study, we evaluate the clinical efficacy and tolerability of microfocused ultrasound with visualization (MFU-V) and injectable calcium hydroxylapatite (CaHA) filler diluted with normal saline, for the correction of age-related changes and to assess patients' satisfaction with this combination therapy. Methods: This was a randomized, split-face, comparative clinical study and immunohistochemical analysis in 20 subjects with indications for lower face, neck and décolleté lifting. Over five visits, CaHA diluted with normal saline (1:2) was injected subdermally in the lower third of the face, neck and décolleté, and lower abdominal quadrant. MFU-V was performed on the lower third of the face, neck, and décolleté, and the right lower abdominal quadrant. Results: Upon baseline examination, the age-related changes were quantified as follows: marionette lines score 2.47 ± 0.8, jawline contour score 2.2 ± 0.7 and neck score 2.1 ± 0.7 points; and after 15 months, they changed to 1.8 ± 0.7 (P≤0.00003), 1.89 ± 0.56 (P≤0.005), and 1.7 ± 0.6 (P≤0.005) points, respectively. The procedures were well tolerated, and subject satisfaction was high. Conclusions: The injections of CaHA in combination with MFU-V treatment stimulated neoangiogenesis, led to the increased synthetic activity of cells, a marked increase in collagen and elastin fibers, and remodeling of both the superficial and deep layers of the dermis. An improvement in the severity of age-related changes was observed in all areas studied. J Drugs Dermatol. 2020;19(4):405-411. doi:10.36849/JDD.2020.4625.

Diagnostic Value of Different Noninvasive Criteria of Latent Myocarditis in Comparison with Myocardial Biopsy.

PURPOSE: The aim of this study was to quantify the value of various clinical, laboratory, and instrumental signs in the diagnosis of myocarditis in comparison with morphological studies of the myocardium. METHODS: In 100 patients (65 men, 44.7 ± 12.5 years old) with "idiopathic" arrhythmias (n = 20) and dilated cardiomyopathy (DCM; n = 80), we performed the following: 71 endomyocardial biopsies (EMB), 13 intraoperative biopsies, 5 studies of explanted hearts, and 11 autopsies with virus investigation (real-time PCR) of the blood and myocardium. Antiheart antibodies (AHA) were also measured as well as cardiac CT (n = 45), MRI (n = 25), and coronary angiography (n = 47). The comparison group included 50 patients (25 men, 53.7 ± 11.7 years old) with noninflammatory heart diseases who underwent open heart surgery. RESULTS: Active/borderline myocarditis was diagnosed in 76.0% of the study group and in 21.6% of patients in the comparison group (p < 0.001). The myocardial viral genome was observed more frequently in patients in the comparison group than in the study group (65.0 and 40.2%; p < 0.01). We evaluated the diagnostic value of noninvasive markers of myocarditis. The panel of AHA had the greatest importance in the identification of myocarditis: sensitivity was 81.5%, and the positive and negative predictive values were 75.0 and 60.5%. This defined the diagnostic value of noninvasive markers of myocarditis and established a diagnostic algorithm providing an individual assessment of the likelihood of myocarditis development. CONCLUSION: AHA have the greatest significance in the diagnosis of latent myocarditis in patients with "idiopathic" arrhythmias and DCM. The use of a complex of noninvasive criteria allows the probability of myocarditis to be estimated and the indications for EMB to be determined.

Improved Neocollagenesis and Skin Mechanical Properties After Injection of Diluted Calcium Hydroxylapatite in the Neck and Décolletage:A Pilot Study.

BACKGROUND: Calcium hydroxylapatite (CaHA; Radiesse (R)) provides safe and effective correction of moderate-to-deep lines, volume replacement, lift and contour, and induction of neocollagenesis and neoelastogenesis for improved skin quality. CaHA hyperdilution takes advantage of its skin-tightening properties without a volumizing effect. OBJECTIVE: To evaluate the collagen- and elastin-stimulating effects of diluted CaHA in subjects with skin laxity in the neck and décolletage. METHODS: Twenty subjects with skin laxity in the neck and décolletage received multiple, linear, subdermal injections of CaHA diluted with preserved saline at baseline and 4 months: 1:2 dilution (normal skin), 1:4 dilution (thin skin), and 1:6 dilution (atrophic skin). Subjects also received deep subdermal injection of CaHA (~0.1 ml) of the same dilution in the peri-auricular area for skin biopsy. Biopsy tissue was obtained at baseline, 4 months, and 7 months for immunohistochemical evaluation of neocollagenesis. Changes to skin mechanical properties were measured by ultrasound scanning and cutometry. Subject and investigator satisfaction was evaluated using the Global Aesthetic Improvement Scale. RESULTS: Immunohistochemical analysis of biopsy tissue demonstrated signi cant increases in collagen I expression at 4 months (P less than 0.05) and 7 months (P less than 0.00001) compared with baseline. Increases in collagen III levels were also significant at 4 months (P less than 0.00001); they declined by 7 months but remained above baseline. Staining for elastin and angiogenesis signi cantly increased at 4 months (P less than 0.05 and P less than 0.01, respectively) and 7 months (P less than 0.00001 for both) compared with baseline. Immunohistochemical data correlated with improvements in skin elasticity and pliability evaluated by cutometry, and with ultrasound-assessed increases in dermal thickness. Subject and investigator satisfaction was high, and the procedure was well tolerated. CONCLUSIONS: Injection of diluted CaHA is very effective for skin tightening of the neck and décolletage. J Drugs Dermatol. 2017;16(1):68-74..